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http://www.ncbi.nlm.nih.gov/pubmed/21685517
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1. Georgian Med News. 2011 May;(194):24-8.
The psychological aspects of burning mouth syndrome.
Kenchadze R(1), Iverieli M, Okribelashvili N, Geladze N, Khachapuridze N.
Author information:
(1)Tbilisi State Medical University, Department of Therapeutic Stomatology,
Georgia.
It should be emphasized that at the present stage there is no consensus achieved
regarding the etiopathogenesis of BMS. Almost all researchers point to lots of
factors, simultaneously participating in genesis and development of BMS and at
the same time most of them agreed on one - psychological factors play a crucial
role in formation and maintenance of painful sensations. The aim of the study
was the identification of psychological or psychiatric deviations (changes)
among the patients with BMS to perform an adequate differentiated therapy.
Clinico-psychological examination (dentist, neurologist, psychiatrist) was
carried out in 39 patients from 46 to 70 years of age. Among them women - 36 and
men - 3. To identify clinical types of BMS a classification of P.J. Lamey (1996)
was used and as a result, depression, insomnia, cancerophobia, severe neurologic
disorders, phobic syndrome were revealed. Three main categories - a chronic
somatoform dysfunction (23 cases), chronic vegetative disorders (8), and chronic
pain phenomenon (12) were identified. Only in one case was revealed a paranoid
syndrome. Alongside with the well-known scheme of treatment (antidepressants,
anticonvulsants, or neuroleptics) Psychotherapy was conducted, while EEG-feed
back (Biofeed back, Neurofeed back) method was used for the first time. A number
of important decisions were made the most important of which are the following:
BMS - must be regarded as a psychosomatic problem rather than a psychiatric
disorder. In addition to psychotherapy, using of EEG - feedback method greatly
improved patients' condition and in 4 cases BMS clinical manifestations were
evened-out completely.
PMID: 21685517 [Indexed for MEDLINE]
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http://www.ncbi.nlm.nih.gov/pubmed/11441716
|
1. Ned Tijdschr Tandheelkd. 2001 Jun;108(6):237-41.
[Burning mouth syndrome].
[Article in Dutch]
van der Waal I(1).
Author information:
(1)Uit de afdeling Mondziekten en kaakchirurgie/Orale pathologie/Algemene
ziekteleer van het Vrije Universiteit Medisch Centrum, Amsterdam/Academisch
Centrum Tandheelkunde Amsterdam (ACTA).
Symptoms of a burning sensation of the oral mucosa mainly occur in the elderly,
more often in women than in men. Often accompanying symptoms are complaints of a
dry mouth and taste disturbances, all together referred to as the burning mouth
syndrome. In the majority of cases there is no detectable cause. Although a
psychogenic aetiology has often been put forward, no scientific evidence has
ever been provided on this matter. In the majority of patients the burning mouth
syndrome will disappear spontaneously, although this may take many years.
PMID: 11441716 [Indexed for MEDLINE]
|
http://www.ncbi.nlm.nih.gov/pubmed/17849966
|
1. J Calif Dent Assoc. 2007 Jun;35(6):397-404.
The burning mouth.
McDonald JS(1).
Author information:
(1)University of Oral Pathology Service, Cincinnati, Ohio 45219, USA.
Burning in the mouth in and of itself is not all that uncommon. It may result
from a variety of local or generalized oral mucosal disorders, or may be
secondary to referred phenomena from other locations. Primary burning mouth
syndrome, on the other hand, is relatively uncommon. Burning mouth syndrome is
an idiopathic pain disorder, which appears to be neuropathic in origin. Thoughts
on management of secondary and particularly primary burning mouth syndrome are
discussed.
PMID: 17849966 [Indexed for MEDLINE]
|
http://www.ncbi.nlm.nih.gov/pubmed/7838464
|
1. Oral Surg Oral Med Oral Pathol. 1994 Nov;78(5):590-3. doi:
10.1016/0030-4220(94)90169-4.
Lip component of burning mouth syndrome.
Lamey PJ(1), Lamb AB.
Author information:
(1)Pain Relief Foundation, School of Clinical Dentistry, Queen's University of
Belfast, Royal Victoria Hospital, U.K.
To our knowledge there has been no previous study of factors specifically
involved in the pathogenesis of patients who complain of burning sensation of
the lips when the lips appear clinically normal. The complaint is akin to
patients who complain of a burning sensation of the mouth when it appears
clinically normal, a condition known as burning mouth syndrome. This study
therefore studied precipitating factors in patients with burning mouth syndrome
who reported lip involvement. Previous studies have shown that the lips are the
third most common site reported as involved in patients who have burning mouth
syndrome. Indeed patients with burning mouth syndrome often report multiple oral
site involvement. To investigate the precipitating factors involved in the lip
component of burning mouth syndrome, we studied 104 patients who reported the
lips as a site affected by the condition from a total population of 312 patients
with burning mouth syndrome. Hematologic, biochemical, and microbiologic
parameters were studied in these patients. Sialometry, patch testing,
psychological testing, and examination of denture status as well as questioning
of parafunctional habits were also undertaken. No clear differences were noted
in relationship to the frequency of abnormalities in burning mouth syndrome
alone or burning mouth syndrome with lip involvement suggesting that similar
precipitating factors apply. The precipitating factors in patients with lip
involvement were found to be the same as burning mouth syndrome in general.
Treatment of patients with lip involvement alone in burning mouth syndrome or
lip involvement in burning mouth syndrome in conjunction with other intraoral
sites gave an equally good response.(ABSTRACT TRUNCATED AT 250 WORDS)
DOI: 10.1016/0030-4220(94)90169-4
PMID: 7838464 [Indexed for MEDLINE]
|
http://www.ncbi.nlm.nih.gov/pubmed/15024358
|
1. Oral Surg Oral Med Oral Pathol Oral Radiol Endod. 2004 Mar;97(3):339-44. doi:
10.1016/j.tripleo.2003.09.017.
Psychological profile in burning mouth syndrome.
Al Quran FA(1).
Author information:
(1)Department of Restorative Dentistry, Faculty of Dentistry, Jordan University
of Science and Technology, Irbid, Jordan. firasquran@hotmail.com
Thirty-two patients with burning mouth syndrome and 32 matched control subjects
were evaluated for their personality profile using a comprehensive, reliable,
and validated inventory. All subjects were requested to complete the Neo PI-R
questionnaire that measures the 5 dimensions of personality and their facets. A
t-test and univariate correlations (Pearson's correlation coefficient) were used
to compare the 2 groups. Results show high significant differences in some
personality factors. Neuroticism and all its facets, which include anxiety,
angry hostility, depression, self-consciousness, impulsiveness and
vulnerability, were significant at P<.001. Other domains like extraversion,
openness, and conscientiousness showed significant differences also (P<.05).
Many personality characteristics differentiate burning mouth syndrome patients
from controllers according to the Neo PI-R and this should affect the treatment
plan according to the identified characteristics.
DOI: 10.1016/j.tripleo.2003.09.017
PMID: 15024358 [Indexed for MEDLINE]
|
http://www.ncbi.nlm.nih.gov/pubmed/21903545
|
1. Gen Dent. 2011 May-Jun;59(3):210-20; quiz 221-2.
Burning mouth syndrome: a challenge for dental practitioners and patients.
Klasser GD(1), Epstein JB, Villines D, Utsman R.
Author information:
(1)Department of Oral Medicine and Diagnostic Sciences, Universitry of Illinois,
Chicago College of Dentistry, USA.
A retrospective study was conducted on patients with burning mouth syndrome
(BMS) to assess demographics, onset characteristics, temporal behavior
(frequency), duration, and progression of oral burning symptoms. Additionally,
treatments provided by health practitioners prior to a definitive diagnosis of
BMS were analyzed with an overview of current management strategies. The records
of 49 adult patients diagnosed with BMS were reviewed. Descriptive statistics
and a Pearson correlation with a statistical significance at p < 0.05 were
utilized to analyze the data. The majority of patients were mid-life white women
who reported a sudden onset of constant oral burning symptoms that increased in
intensity. On average, patients reported oral burning symptoms for 41 months
(standard deviation = 73.5, range = 2-360 months, median = 20 months), and 38 of
the patients received/trialed 71 various interventions (mean = 1.9) prior to
receiving a definitive diagnosis for their oral burning symptoms. This study
sample shared many characteristics with those reported previously in the
literature. The authors found that patients frequently reported delays in
receiving a definitive diagnosis with an array of various trialed interventions.
For this reason, the authors provide this overview of current management
strategies in order to assist dental practitioners in providing appropriate
interventions for patients with BMS.
PMID: 21903545 [Indexed for MEDLINE]
|
http://www.ncbi.nlm.nih.gov/pubmed/19658340
|
1. Lijec Vjesn. 2002 Jun-Jul;124(6-7):220-4.
[Burning mouth syndrome--etiologic, diagnostic and therapeutic considerations].
[Article in Croatian]
Alajbeg I(1), Vucićević-Boras V.
Author information:
(1)Zavod za oralnu medicinu Stomatoloskog fakulteta u Zagrebu.
Burning mouth syndrome represents a chronic orofacial pain disorder without an
apparent lesion of oral mucosa. It affects 0.71-3.4% of general population.
Although a lot of scientific and clinical effort has been undertaken, its
genesis still remains an enigma. Potential etiologic roles of various oral and
systemic factors have been implicated, such as oral candidiasis, hormonal,
neurological, nutritive and psychiatric disorders. In spite of different
treatment approaches and medications, therapeutic success is limited. Although
in our country most of the patients are treated by dentists specialized in oral
medicine, medical doctors should be more involved in diagnosis and treatment of
the disease. Article describes etiologic factors, diagnostic and therapeutic
means in the burning mouth syndrome.
PMID: 19658340 [Indexed for MEDLINE]
|
http://www.ncbi.nlm.nih.gov/pubmed/23713105
|
1. Pediatrics. 2013 Jun;131(6):e1996-2001. doi: 10.1542/peds.2012-0749. Epub 2013
May 27.
Complex chromosome rearrangement of 6p25.3->p23 and 12q24.32->qter in a child
with moyamoya.
Rosenberg RE(1), Egan M, Rodgers S, Harter D, Burnside RD, Milla S, Pappas J.
Author information:
(1)Department of Pediatrics, New York University School of Medicine, New York,
NY, USA. rebecca.rosenberg@nyumc.org
A 7-year-old white girl presented with left hemiparesis and ischemic stroke
secondary to moyamoya syndrome, a progressive cerebrovascular occlusive disorder
of uncertain but likely multifactorial etiology. Past medical history revealed
hearing loss and developmental delay/intellectual disability. Routine karyotype
demonstrated extra chromosomal material on 6p. Single nucleotide polymorphism
microarray revealed a previously unreported complex de novo genetic
rearrangement involving subtelomeric segments on chromosomes 6p and 12q. The
duplicated/deleted regions included several known OMIM-annotated genes. This
novel phenotype and genotype provides information about a possible association
of genomic copy number variation and moyamoya syndrome. Dosage-sensitive genes
in the deleted and duplicated segments may be involved in aberrant vascular
proliferation. Our case also emphasizes the importance of comprehensive
evaluation of both developmental delay and congenital anomalies such as
moyamoya.
DOI: 10.1542/peds.2012-0749
PMID: 23713105 [Indexed for MEDLINE]
|
http://www.ncbi.nlm.nih.gov/pubmed/20068102
|
1. Clin Cancer Res. 2010 Jan 15;16(2):681-90. doi: 10.1158/1078-0432.CCR-09-1091.
Epub 2010 Jan 12.
Identification of markers of taxane sensitivity using proteomic and genomic
analyses of breast tumors from patients receiving neoadjuvant paclitaxel and
radiation.
Bauer JA(1), Chakravarthy AB, Rosenbluth JM, Mi D, Seeley EH, De Matos
Granja-Ingram N, Olivares MG, Kelley MC, Mayer IA, Meszoely IM, Means-Powell JA,
Johnson KN, Tsai CJ, Ayers GD, Sanders ME, Schneider RJ, Formenti SC, Caprioli
RM, Pietenpol JA.
Author information:
(1)Departments of Biochemistry, Vanderbilt-Ingram Cancer Center, Vanderbilt
University Medical Center, Nashville, Tennessee 37232, USA.
PURPOSE: To identify molecular markers of pathologic response to neoadjuvant
paclitaxel/radiation treatment, protein and gene expression profiling were done
on pretreatment biopsies.
EXPERIMENTAL DESIGN: Patients with high-risk, operable breast cancer were
treated with three cycles of paclitaxel followed by concurrent
paclitaxel/radiation. Tumor tissue from pretreatment biopsies was obtained from
19 of the 38 patients enrolled in the study. Protein and gene expression
profiling were done on serial sections of the biopsies from patients that
achieved a pathologic complete response (pCR) and compared to those with
residual disease, non-pCR (NR).
RESULTS: Proteomic and validation immunohistochemical analyses revealed that
alpha-defensins (DEFA) were overexpressed in tumors from patients with a pCR.
Gene expression analysis revealed that MAP2, a microtubule-associated protein,
had significantly higher levels of expression in patients achieving a pCR.
Elevation of MAP2 in breast cancer cell lines led to increased paclitaxel
sensitivity. Furthermore, expression of genes that are associated with the
basal-like, triple-negative phenotype were enriched in tumors from patients with
a pCR. Analysis of a larger panel of tumors from patients receiving presurgical
taxane-based treatment showed that DEFA and MAP2 expression as well as
histologic features of inflammation were all statistically associated with
response to therapy at the time of surgery.
CONCLUSION: We show the utility of molecular profiling of pretreatment biopsies
to discover markers of response. Our results suggest the potential use of immune
signaling molecules such as DEFA as well as MAP2, a microtubule-associated
protein, as tumor markers that associate with response to neoadjuvant
taxane-based therapy.
DOI: 10.1158/1078-0432.CCR-09-1091
PMCID: PMC2892225
PMID: 20068102 [Indexed for MEDLINE]
Conflict of interest statement: Disclosure of Potential Conflicts of Interest
A.B. Chakravarthy: commercial research grants for the support of the clinical
trials from Aventis and BMS. The other authors disclosed no potential conflicts
of interest.
|
http://www.ncbi.nlm.nih.gov/pubmed/19485423
|
1. J Proteome Res. 2009 Jul;8(7):3430-8. doi: 10.1021/pr900071h.
Identification of differentially expressed proteins in triple-negative breast
carcinomas using DIGE and mass spectrometry.
Schulz DM(1), Böllner C, Thomas G, Atkinson M, Esposito I, Höfler H, Aubele M.
Author information:
(1)Institute of Pathology, Helmholtz Zentrum München, German Research Center for
Environmental Health, Ingolstadter Landstrasse 1, 85764 Neuherberg, Germany.
We compared the protein expression pattern of triple-negative breast carcinomas
(HER2-, ER-, PR-) versus those being positive for HER2 and negative for the
hormone receptors (HER2+, ER-, PR-) by 2-D DIGE and mass spectrometry. We
obtained differential expression patterns for several glycolytic enzymes (as for
example MDH2, PGK1, TKT, Aldolase1), cytokeratins (CK7, 8, 9, 14, 17, 19),
further structure proteins (vimentin, fibronectin, L-plastin), for NME1-NME2,
lactoferrin, and members of the Annexin family. Western blot analysis and
immunohistochemistry were conducted to verify the results. The identified marker
proteins may advance a more detailed characterization of triple-negative breast
cancers and may contribute to the development of better treatment strategies.
DOI: 10.1021/pr900071h
PMID: 19485423 [Indexed for MEDLINE]
|
http://www.ncbi.nlm.nih.gov/pubmed/21418666
|
1. BMJ Clin Evid. 2010 Jul 19;2010:1301.
Burning mouth syndrome.
Buchanan JA(1), Zakrzewska JM.
Author information:
(1)Barts and The London School of Medicine and Dentistry, Dental Institute,
Royal London Hospital, London, UK.
INTRODUCTION: Burning mouth syndrome mainly affects women, particularly after
the menopause, when its prevalence may be 18% to 33%.
METHODS AND OUTCOMES: We conducted a systematic review and aimed to answer the
following clinical question: What are the effects of treatments for burning
mouth syndrome? We searched: Medline, Embase, The Cochrane Library, and other
important databases up to November 2009 (Clinical Evidence reviews are updated
periodically, please check our website for the most up-to-date version of this
review). We included harms alerts from relevant organisations such as the US
Food and Drug Administration (FDA) and the UK Medicines and Healthcare products
Regulatory Agency (MHRA).
RESULTS: We found 15 systematic reviews, RCTs, or observational studies that met
our inclusion criteria. We performed a GRADE evaluation of the quality of
evidence for interventions.
CONCLUSIONS: In this systematic review we present information relating to the
effectiveness and safety of the following interventions: anaesthetics (local),
antidepressants, benzodiazepines (topical clonazepam), benzydamine
hydrochloride, cognitive behavioural therapy (CBT), dietary supplements, and
hormone replacement therapy (HRT) in postmenopausal women.
PMCID: PMC3217740
PMID: 21418666 [Indexed for MEDLINE]
|
http://www.ncbi.nlm.nih.gov/pubmed/10478959
|
1. J Oral Pathol Med. 1999 Sep;28(8):350-4. doi:
10.1111/j.1600-0714.1999.tb02052.x.
Burning mouth syndrome: prevalence and associated factors.
Bergdahl M(1), Bergdahl J.
Author information:
(1)Department of Odontology, Umeå University, Sweden.
Burning mouth syndrome (BMS) is characterized by a burning sensation in the oral
cavity although the oral mucosa is clinically normal. The syndrome mostly
affects middle-aged women. Various local, systemic and psychological factors
have been found to be associated with BMS, but its etiology is not fully
understood. Oral complaints and salivary flow were surveyed in 669 men and 758
women randomly selected from 48,500 individuals between the ages 20 and 69
years. Fifty-three individuals (3.7%), 11 men (1.6%) and 42 women (5.5%), were
classified as having BMS. In men, no BMS was found before the age group 40 to 49
years where the prevalence was 0.7%, which increased to 3.6% in the oldest age
group. In women, no BMS was found in the youngest age group, but in the age
group 30 to 39 years the prevalence was 0.6% and increased to 12.2% in the
oldest age group. Subjective oral dryness, age, medication, taste disturbances,
intake of L-thyroxines, illness, stimulated salivary flow rate, depression and
anxiety were factors associated with BMS. In individuals with BMS, the most
prevalent site with burning sensations was the tongue (67.9%). The intensity of
the burning sensation was estimated to be 4.6 on a visual analogue scale. There
were no increased levels of depression, anxiety or stress among individuals with
more pain compared to those with less pain. It was concluded that BMS should be
seen as a marker of illness and/or distress, and the complex etiology of BMS
demands specialist treatment.
DOI: 10.1111/j.1600-0714.1999.tb02052.x
PMID: 10478959 [Indexed for MEDLINE]
|
http://www.ncbi.nlm.nih.gov/pubmed/22934887
|
1. J Proteome Res. 2012 Oct 5;11(10):5034-45. doi: 10.1021/pr300606e. Epub 2012
Sep 20.
Mass spectrometry (LC-MS/MS) identified proteomic biosignatures of breast cancer
in proximal fluid.
Whelan SA(1), He J, Lu M, Souda P, Saxton RE, Faull KF, Whitelegge JP, Chang HR.
Author information:
(1)Department of Biochemistry, School of Medicine, Boston University, Boston,
Massachusetts, USA.
We have begun an early phase of biomarker discovery in three clinically
important types of breast cancer using a panel of human cell lines: HER2
positive, hormone receptor positive and HER2 negative, and triple negative
(HER2-, ER-, PR-). We identified and characterized the most abundant secreted,
sloughed, or leaked proteins released into serum free media from these breast
cancer cell lines using a combination of protein fractionation methods before
LC-MS/MS mass spectrometry analysis. A total of 249 proteins were detected in
the proximal fluid of 7 breast cancer cell lines. The expression of a selected
group of high abundance and/or breast cancer-specific potential biomarkers
including thromobospondin 1, galectin-3 binding protein, cathepsin D, vimentin,
zinc-α2-glycoprotein, CD44, and EGFR from the breast cancer cell lines and in
their culture media were further validated by Western blot analysis.
Interestingly, mass spectrometry identified a cathepsin D protein
single-nucleotide polymorphism (SNP) by alanine to valine replacement from the
MCF-7 breast cancer cell line. Comparison of each cell line media proteome
displayed unique and consistent biosignatures regardless of the individual group
classifications, demonstrating the potential for stratification of breast
cancer. On the basis of the cell line media proteome, predictive Tree software
was able to categorize each cell line as HER2 positive, HER2 negative, and
hormone receptor positive and triple negative based on only two proteins, muscle
fructose 1,6-bisphosphate aldolase and keratin 19. In addition, the predictive
Tree software clearly identified MCF-7 cell line overexpresing the HER2 receptor
with the SNP cathepsin D biomarker.
DOI: 10.1021/pr300606e
PMCID: PMC3521600
PMID: 22934887 [Indexed for MEDLINE]
|
http://www.ncbi.nlm.nih.gov/pubmed/12766776
|
1. Nat Cell Biol. 2003 Jun;5(6):566-71. doi: 10.1038/ncb996.
Rheb promotes cell growth as a component of the insulin/TOR signalling network.
Saucedo LJ(1), Gao X, Chiarelli DA, Li L, Pan D, Edgar BA.
Author information:
(1)Division of Basic Sciences, Fred Hutchinson Cancer Research Center, 1100
Fairview Avenue North, Seattle, WA 98109, USA.
Erratum in
Nat Cell Biol. 2003 Jul;5(7):680.
Insulin signalling is a potent stimulator of cell growth and has been proposed
to function, at least in part, through the conserved protein kinase TOR (target
of rapamycin) [corrected]. Recent studies suggest that the tuberous sclerosis
complex Tsc1-Tsc2 may couple insulin signalling to Tor activity [corrected].
However, the regulatory mechanism involved remains unclear, and additional
components are most probably involved. In a screen for novel regulators of
growth, we identified Rheb (Ras homologue enriched in brain), a member of the
Ras superfamily of GTP-binding proteins. Increased levels of Rheb in Drosophila
melanogaster promote cell growth and alter cell cycle kinetics in multiple
tissues. In mitotic tissues, overexpression of Rheb accelerates passage through
G1-S phase without affecting rates of cell division, whereas in endoreplicating
tissues, Rheb increases DNA ploidy. Mutation of Rheb suspends larval growth and
prevents progression from first to second instar. Genetic and biochemical tests
indicate that Rheb functions in the insulin signalling pathway downstream of
Tsc1-Tsc2 and upstream of TOR. Levels of rheb mRNA are rapidly induced in
response to protein starvation, and overexpressed Rheb can drive cell growth in
starved animals, suggesting a role for Rheb in the nutritional control of cell
growth.
DOI: 10.1038/ncb996
PMID: 12766776 [Indexed for MEDLINE]
|
http://www.ncbi.nlm.nih.gov/pubmed/22178447
|
1. J Proteomics. 2012 Jun 6;75(10):3031-40. doi: 10.1016/j.jprot.2011.11.033.
Epub 2011 Dec 8.
Stat1 and CD74 overexpression is co-dependent and linked to increased invasion
and lymph node metastasis in triple-negative breast cancer.
Greenwood C(1), Metodieva G, Al-Janabi K, Lausen B, Alldridge L, Leng L, Bucala
R, Fernandez N, Metodiev MV.
Author information:
(1)The Helen Rollason Research Laboratory, Anglia Ruskin University, Chelmsford,
Essex, CM1 1SQ, United Kingdom.
Triple-negative breast cancer is difficult to treat because of the lack of
rationale-based therapies. There are no established markers and targets that can
be used for stratification of patients and targeted therapy. Here we report the
identification of novel molecular features, which appear to augment metastasis
of triple negative breast tumors. We found that triple-negative breast tumors
can be segregated into 2 phenotypes based on their genome-wide protein abundance
profiles. The first is characterized by high expression of Stat1, Mx1, and CD74.
Seven out of 9 tumors from this group had invaded at least 2 lymph nodes while
only 1 out of 10 tumors in group 2 was lymph node positive. In vitro experiments
showed that the interferon-induced increase in Stat1 abundance correlates with
increased migration and invasion in cultured cells. When CD74 was overexpressed,
it increased cell adhesion on matrigel. This effect was accompanied with a
marked increase in the membrane expression of beta-catenin, MUC18, plexins,
integrins, and other proteins involved in cell adhesion and cancer metastasis.
Taken together, our results show that Stat1/CD74 positive triple-negative tumors
are more aggressive and suggest an approach for development of better
diagnostics and more targeted therapies for triple negative breast cancer. This
article is part of a Special Issue entitled: Proteomics: The clinical link.
Copyright © 2011 Elsevier B.V. All rights reserved.
DOI: 10.1016/j.jprot.2011.11.033
PMID: 22178447 [Indexed for MEDLINE]
|
http://www.ncbi.nlm.nih.gov/pubmed/23436753
|
1. Proteomics Clin Appl. 2013 Apr;7(3-4):283-91. doi: 10.1002/prca.201200048.
Epub 2013 Mar 6.
Shotgun proteomics of archival triple-negative breast cancer samples.
Gámez-Pozo A(1), Ferrer NI, Ciruelos E, López-Vacas R, Martínez FG, Espinosa E,
Vara JÁ.
Author information:
(1)Laboratorio de Oncología y Patología Molecular, Instituto de Genética Médica
y Molecular-INGEMM, Instituto de Investigación Hospital Universitario La
Paz-IdiPAZ, Madrid, Spain.
PURPOSE: Triple-negative breast cancer (TNBC) accounts for 15-20% of all breast
cancers, and has a worse prognosis compared with hormone receptor-positive
disease. Its unfavorable outcome and the lack of hormonal receptors determine
the use of adjuvant chemotherapy as part of the standard treatment for these
tumors, although several studies have documented that the current standard
combination chemotherapy is suboptimal. Therefore, a new functional taxonomy of
breast cancer and new targets for therapeutic development are urgently needed.
EXPERIMENTAL DESIGN: In this study, we have analyzed the proteome of TNBC
applying a high-throughput proteomics approach to routinely archived
formalin-fixed, paraffin-embedded tumor tissues.
RESULTS: We have been able to identify and quantify more than 1000 protein
groups. Some of these proteins are of outstanding interest in the biology and
clinical management of this disease, such as CD44 and PARP1. Moreover, we have
characterized some signaling pathways that could be related to TNBC genesis and
development.
CONCLUSION AND CLINICAL RELEVANCE: Our results open up new avenues for the use
of proteomics technologies in clinically relevant studies using archival
samples. Shotgun LC-MS/MS studies could serve to discover new biomarkers and may
provide clues to the genesis of TNBC and underlying molecular alterations.
© 2013 WILEY-VCH Verlag GmbH & Co. KGaA, Weinheim.
DOI: 10.1002/prca.201200048
PMID: 23436753 [Indexed for MEDLINE]
|
http://www.ncbi.nlm.nih.gov/pubmed/22692575
|
1. Mol Med. 2012 Sep 25;18(1):1109-21. doi: 10.2119/molmed.2012.00091.
Functional heterogeneity within the CD44 high human breast cancer stem cell-like
compartment reveals a gene signature predictive of distant metastasis.
Leth-Larsen R(1), Terp MG, Christensen AG, Elias D, Kühlwein T, Jensen ON,
Petersen OW, Ditzel HJ.
Author information:
(1)Department of Cancer and Inflammation Research, Institute of Molecular
Medicine, University of Southern Denmark, Odense, Denmark.
The CD44(hi) compartment in human breast cancer is enriched in tumor-initiating
cells; however, the functional heterogeneity within this subpopulation remains
poorly defined. We used a triple-negative breast cancer cell line with a known
bilineage phenotype to isolate and clone CD44(hi) single cells that exhibited
mesenchymal/basal B and luminal/basal A features, respectively. Herein, we
demonstrate in this and other triple-negative breast cancer cell lines that,
rather than CD44(hi)/CD24(-) mesenchymal-like basal B cells, the
CD44(hi)/CD24(lo) epithelioid basal A cells retained classic cancer stem cell
features, such as tumor-initiating capacity in vivo, mammosphere formation and
resistance to standard chemotherapy. These results complement previous findings
using oncogene-transformed normal mammary cells showing that only cell clones
with a mesenchymal phenotype exhibit cancer stem cell features. Further, we
performed comparative quantitative proteomic and gene array analyses of these
cells and identified potential novel markers of breast cancer cells with
tumor-initiating features, such as lipolysis-stimulated lipoprotein receptor
(LSR), RAB25, S100A14 and mucin 1 (MUC1), as well as a novel 31-gene signature
capable of predicting distant metastasis in cohorts of estrogen
receptor-negative human breast cancers. These findings strongly favor functional
heterogeneity in the breast cancer cell compartment and hold promise for further
refinements of prognostic marker profiling. Our work confirms that, in addition
to cancer stem cells with mesenchymal-like morphology, those tumor-initiating
cells with epithelial-like morphology should also be the focus of drug
development.
DOI: 10.2119/molmed.2012.00091
PMCID: PMC3474436
PMID: 22692575 [Indexed for MEDLINE]
|
http://www.ncbi.nlm.nih.gov/pubmed/21630460
|
1. Proteomics. 2011 Jul;11(13):2683-92. doi: 10.1002/pmic.201000801. Epub 2011
May 31.
Quantitative chemical proteomics in small-scale culture of phorbol ester
stimulated basal breast cancer cells.
Dolai S(1), Xu Q, Liu F, Molloy MP.
Author information:
(1)Department of Chemistry and Biomolecular Sciences, Faculty of Science,
Macquarie University, Sydney, Australia.
Basal-like breast cancers are commonly negative for expression of estrogen and
progesterone receptors and HER-2 (triple-negative breast cancer), which makes
this subtype of breast cancers more aggressive and less responsive to standard
treatment. We have applied a small-scale chemical proteomics method using
bisindolylmaleimide (Bis) class of protein kinase C inhibitors to study the
Bis-binding proteome in a cell culture model of basal breast carcinoma
(MDA-MB-231). Using MS, we identified 174 proteins captured by the Bis-probe in
phorbol ester (PMA) stimulated cells. Gene ontology analysis broadly categorised
these proteins as ATP binding (42%), GTP binding (6%) and having
nucleoside-triphosphatase activity (21%). Of the 64 enzymes captured by the
Bis-probe, the majority had either ATP and/or nucleotide binding functions. Two
previously unreported Bis binding protein kinases, serine/arginine-rich
protein-specific kinase 1 (SRPK1) and interferon-induced RNA-dependent protein
kinase (PKR) were observed. We then incorporated SILAC for quantitation to
examine the proteins that were differentially captured by the Bis-probe
following 30 and 60 min PMA stimulation. This provided novel evidence for PMA
regulation of the enzymes glyceraldehyde-3-phosphate dehydrogenase, nucleolar
RNA helicase 2 and Heterogeneous nuclear ribonucleoprotein M.
Copyright © 2011 WILEY-VCH Verlag GmbH & Co. KGaA, Weinheim.
DOI: 10.1002/pmic.201000801
PMID: 21630460 [Indexed for MEDLINE]
|
http://www.ncbi.nlm.nih.gov/pubmed/23185200
|
1. Arch Med Sci. 2012 Nov 9;8(5):886-91. doi: 10.5114/aoms.2012.31620. Epub 2012
Nov 7.
Lipid and protein oxidation in female patients with chronic fatigue syndrome.
Tomic S(1), Brkic S, Maric D, Mikic AN.
Author information:
(1)Clinic for Infectious Diseases, Clinical Center Vojvodina, Novi Sad, Serbia.
INTRODUCTION: Chronic fatigue syndrome (CFS) is a widely recognized problem,
characterized by prolonged, debilitating fatigue and a characteristic group of
accompanying symptoms, that occurs four times more frequently in women than in
men. The aim of the study was to determine the existence of oxidative stress and
its possible consequences in female patients with CFS.
MATERIAL AND METHODS: Twenty-four women aged 15-45 who fulfilled the diagnostic
criteria for CFS with no comorbidities were recruited and were age matched to a
control group of 19 healthy women. After conducting the routine laboratory
tests, levels of the lipid oxidation product malondialdehyde (MDA) and protein
oxidation protein carbonyl (CO) were determined.
RESULTS: The CFS group had higher levels of triglycerides (p = 0.03), MDA (p =
0.03) and CO (p = 0.002) and lower levels of HDL cholesterol (p = 0.001) than
the control group. There were no significant differences in the levels of total
protein, total cholesterol or LDL cholesterol.
CONCLUSIONS: The CFS group had an unfavorable lipid profile and signs of
oxidative stress induced damage to lipids and proteins. These results might be
indicative of early proatherogenic processes in this group of patients who are
otherwise at low risk for atherosclerosis. Antioxidant treatment and life style
changes are indicated for women with CFS, as well as closer observation in order
to assess the degree of atherosclerosis.
DOI: 10.5114/aoms.2012.31620
PMCID: PMC3506242
PMID: 23185200
|
http://www.ncbi.nlm.nih.gov/pubmed/20597947
|
1. Dermatol Ther. 2010 May-Jun;23(3):291-8. doi:
10.1111/j.1529-8019.2010.01325.x.
Burning mouth syndrome.
Torgerson RR(1).
Author information:
(1)Department of Dermatology, Mayo Clinic, Rochester, MN 55905, USA.
torgerson.rochelle@mayo.edu
Burning mouth syndrome (BMS) is a chronic condition characterized by burning of
the oral mucosa, with or without dysgeusia and xerostomia, in the setting of no
underlying systemic disease or identifiable abnormalities on physical
examination or laboratory testing. BMS disproportionately affects postmenopausal
women. The pathophysiology of the disease is unknown; no single treatment has
proven universally successful. In light of these shortcomings, having a
practical approach to the evaluation and management of patients with BMS can
improve both patient quality of life and physician satisfaction.
DOI: 10.1111/j.1529-8019.2010.01325.x
PMID: 20597947 [Indexed for MEDLINE]
|
http://www.ncbi.nlm.nih.gov/pubmed/9844361
|
1. Mt Sinai J Med. 1998 Oct-Nov;65(5-6):343-7.
Burning mouth syndrome.
Miyamoto SA(1), Ziccardi VB.
Author information:
(1)Department of Oral and Maxillofacial Surgery, New Jersey Dental School,
University of Medicine and Dentistry of New Jersey, Newark 07103-2400, USA.
Complaint of a burning mouth is an increasingly common problem in the aging
population. This has remained an enigma for the treating clinician, because
visible pathologic lesions or processes are usually not evident. Local, systemic
and environmental causes must be assessed to elicit the predisposing factors.
Some suggestions for managing burning mouth syndrome are offered.
PMID: 9844361 [Indexed for MEDLINE]
|
http://www.ncbi.nlm.nih.gov/pubmed/11603307
|
1. J Dent Hyg. 2001 Summer;75(3):245-52; quiz 252-3, 255.
Burning mouth syndrome.
Perno M.
A critical component of the dental hygiene process of care is assessment of the
oral and general health conditions of clients. Some clients present with burning
and painful sensations in the oral cavity in the absence of any noticeable
disease. This condition has been referred to as burning mouth syndrome (BMS), an
often complicated condition. Various local, systemic, and psychological factors
have been linked with BMS, but its etiology is not fully understood. Yet as many
as one million people are affected by it in the United States, and it is an
increasingly-common problem in the aging population. Middle-aged women, mostly
postmenopausal, are diagnosed with symptoms seven times more frequently than
men. Careful diagnosis and treatment are necessary to alleviate the symptoms of
this condition. Referral to a physician is warranted in some cases. The purposes
of this course are to review the etiologic factors and clinical implications
related to this condition and to discuss appropriate dental hygiene
interventions. Collaboration among the client, dental hygienist, dentist, and
physician provides for interdisciplinary actions that can lead to palliation of
symptoms and evaluation of the possible underlying factors contributing to the
condition.
PMID: 11603307 [Indexed for MEDLINE]
|
http://www.ncbi.nlm.nih.gov/pubmed/18305436
|
1. Med Oral Patol Oral Cir Bucal. 2008 Mar 1;13(3):E167-70.
Drug-induced burning mouth syndrome: a new etiological diagnosis.
Salort-Llorca C(1), Mínguez-Serra MP, Silvestre FJ.
Author information:
(1)Service of Pharmacy, Mútua de Terrassa Hospital, Barcelona, Spain.
Burning mouth syndrome (BMS) is defined as a burning sensation of the oral
mucosa, in the absence of specific oral lesions. The underlying etiology remains
unclear. Peripheral alterations may be related to the density or reactive
capacity of the oral mucosal membrane receptors - these being largely influenced
by BMS-related risk factors such as stress, anxiety, the female gender,
climacterium and advanced age. The present study compiles the cases of BMS
induced by drugs reported in the literature, and attempts to draw a series of
conclusions. A search was conducted in the PubMed database using the following
key words: burning mouth syndrome, drug-induced, antihypertensive and
chemically-induced. The search was carried out in April 2007. The literature
yielded clinical cases in which oral burning sensation is described after the
administration of drugs belonging to different therapeutic groups:
antiretrovirals, antiseizure drugs, hormones and particularly antihypertensive
medication. Curiously, among the different types of antihypertensive drugs, BMS
was only associated with those compounds that act upon the angiotensin-renin
system.
PMID: 18305436 [Indexed for MEDLINE]
|
http://www.ncbi.nlm.nih.gov/pubmed/15388940
|
1. Acta Crystallogr D Biol Crystallogr. 2004 Oct;60(Pt 10):1883-7. doi:
10.1107/S0907444904018232. Epub 2004 Sep 23.
Expression, purification, crystallization and preliminary structural
characterization of the GTPase domain of human Rheb.
Yu Y(1), Chang Y, Li S, Hu H, Huang Q, Ding J.
Author information:
(1)Key Laboratory of Proteomics, Institute of Biochemistry and Cell Biology,
Shanghai Institutes for Biological Sciences, Chinese Academy of Sciences, 320
Yue-Yang Road, Shanghai 200031, People's Republic of China.
Ras homologue enriched in brain (Rheb) represents a unique group of small
GTPases and shares moderate sequence identity with the Ras/Rap subfamily. It
acts downstream of nutrient signalling as the direct target of the tuberous
sclerosis complex (TSC) and upstream of mTOR/S6K1/4EBP in the insulin-signalling
pathway. The GTPase domain of human Rheb (hRheb) has been recombinantly
expressed in Escherichia coli, purified and cocrystallized in complexes with
GDP, GTP and GppNHp using the hanging-drop vapour-diffusion method. Crystals of
the hRheb-GDP complex belong to space group P2(1)2(1)2(1), with unit-cell
parameters a = 44.5, b = 52.3, c = 70.6 A. The hRheb-GppNHp complex crystallized
in two crystal forms: one has the same space group and unit-cell parameters as
the hRheb-GDP complex and the other belongs to space group C222(1), with
unit-cell parameters a = 102.9, b = 99.2, c = 48.0 A. The hRheb-GTP complex also
crystallized in two crystal forms: one belongs to space group C222(1), with
unit-cell parameters a = 102.4, b = 98.3, c = 47.9 A, and the other belongs to
space group P2(1), with unit-cell parameters a = 77.3, b = 47.9, c = 71.9 A,
beta = 89.0 degrees. All these crystals diffract X-rays to better than 2.8 A
resolution and at least one diffraction data set has been collected for each
crystal form using an in-house R-AXIS IV++ diffractometer. Structural studies of
hRheb in complexes with various substrates may provide insights into the
recognition and specificity of substrate and the catalytic mechanism of
mammalian Rhebs and shed light on the biological functions of Rhebs in the mTOR
signalling pathway.
DOI: 10.1107/S0907444904018232
PMID: 15388940 [Indexed for MEDLINE]
|
http://www.ncbi.nlm.nih.gov/pubmed/20457704
|
1. Arch Dis Child. 2010 May;95(5):391-2. doi: 10.1136/adc.2009.159210.
Sirolimus and tuberous sclerosis-associated renal angiomyolipomas.
Krischock L(1), Beach R, Taylor J.
Author information:
(1)Department of Paediatric Nephrology, Evelina Children's Hospital, Guy's and
St Thomas' Hospitals NHS Trust, London, UK.
Tuberous sclerosis, caused by germline mutations in the TSC1 or TSC2 genes, is
associated with aberrant upregulation of the mammalian target of rapamycin
(mTOR) signalling pathway, resulting in growth of tumours, including renal
angiomyolipomas (AMLs). AMLs may cause hypertension, renal failure and
spontaneous life-threatening haemorrhage. Previously, invasive interventions
were required to treat AMLs. More recently, mTOR inhibitors have been used as
molecularly targeted treatment to treat AMLs. We present here the case of a
paediatric patient with TSC in whom sirolimus has been used successfully to halt
growth of renal AMLs.
DOI: 10.1136/adc.2009.159210
PMID: 20457704 [Indexed for MEDLINE]
|
http://www.ncbi.nlm.nih.gov/pubmed/12172555
|
1. Nat Cell Biol. 2002 Sep;4(9):699-704. doi: 10.1038/ncb847.
Tsc tumour suppressor proteins antagonize amino-acid-TOR signalling.
Gao X(1), Zhang Y, Arrazola P, Hino O, Kobayashi T, Yeung RS, Ru B, Pan D.
Author information:
(1)Department of Physiology, University of Texas Southwestern Medical Center at
Dallas, 5323 Harry Hines Blvd., Dallas, TX 75390-9040, USA.
Comment in
Nat Cell Biol. 2002 Sep;4(9):E214-6. doi: 10.1038/ncb0902-e214.
Target of Rapamycin (TOR) mediates a signalling pathway that couples amino acid
availability to S6 kinase (S6K) activation, translational initiation and cell
growth. Here, we show that tuberous sclerosis 1 (Tsc1) and Tsc2, tumour
suppressors that are responsible for the tuberous sclerosis syndrome, antagonize
this amino acid-TOR signalling pathway. We show that Tsc1 and Tsc2 can
physically associate with TOR and function upstream of TOR genetically. In
Drosophila melanogaster and mammalian cells, loss of Tsc1 and Tsc2 results in a
TOR-dependent increase of S6K activity. Furthermore, although S6K is normally
inactivated in animal cells in response to amino acid starvation, loss of
Tsc1-Tsc2 renders cells resistant to amino acid starvation. We propose that the
Tsc1-Tsc2 complex antagonizes the TOR-mediated response to amino acid
availability. Our studies identify Tsc1 and Tsc2 as regulators of the amino
acid-TOR pathway and provide a new paradigm for how proteins involved in
nutrient sensing function as tumour suppressors.
DOI: 10.1038/ncb847
PMID: 12172555 [Indexed for MEDLINE]
|
http://www.ncbi.nlm.nih.gov/pubmed/23159330
|
1. Neuropharmacology. 2013 Apr;67:1-7. doi: 10.1016/j.neuropharm.2012.11.003.
Epub 2012 Nov 14.
Behavioural and EEG effects of chronic rapamycin treatment in a mouse model of
tuberous sclerosis complex.
Cambiaghi M(1), Cursi M, Magri L, Castoldi V, Comi G, Minicucci F, Galli R,
Leocani L.
Author information:
(1)San Raffaele Scientific Institute, Milan, Italy. cambiaghi.marco@hsr.it
Tuberous Sclerosis Complex (TSC) is a multisystem genetic disorder caused by
mutation in either Tsc1 or Tsc2 genes that leads to the hyper activation of the
mTOR pathway, a key signalling pathway for synaptic plasticity. TSC is
characterized by benign tumors arising in different organs and severe
neuropsychiatric symptoms, such as epilepsy, intellectual disability, autism,
anxiety and depressive behaviour. Rapamycin is a potent inhibitor of mTOR and
its efficacy in treating epilepsy and neurological symptoms remains elusive. In
a mouse model in which Tsc1 has been deleted in embryonic telencephalic neural
stem cells, we analyzed anxiety- and depression-like behaviour by elevated-plus
maze (EPM), open-field test (OFT), forced-swim test (FST) and tail-suspension
test (TST), after chronic administration of rapamycin. In addition, spectral
analysis of background EEG was performed. Rapamycin-treated mutant mice
displayed a reduction in anxiety- and depression-like phenotype, as shown by the
EPM/OFT and FST, respectively. These results were inline with EEG power spectra
outcomes. The same effects of rapamycin were observed in wild-type mice.
Notably, in heterozygous animals we did not observe any EEG and/or behavioural
variation after rapamycin treatment. Together these results suggest that both
TSC1 deletion and chronic rapamycin treatment might have a role in modulating
behaviour and brain activity, and point out to the potential usefulness of
background EEG analysis in tracking brain dysfunction in parallel with
behavioural testing.
Copyright © 2012 Elsevier Ltd. All rights reserved.
DOI: 10.1016/j.neuropharm.2012.11.003
PMID: 23159330 [Indexed for MEDLINE]
|
http://www.ncbi.nlm.nih.gov/pubmed/19506736
|
1. Curr Genomics. 2008 Nov;9(7):475-87. doi: 10.2174/138920208786241243.
Genetics and molecular biology of tuberous sclerosis complex.
Napolioni V(1), Curatolo P.
Author information:
(1)Laboratory of Human Genetics, Department of Molecular, Cellular and Animal
Biology, University of Camerino, Camerino, Italy.
Tuberous Sclerosis Complex is a multisystem disorder exhibiting a wide range of
manifestations characterized by tumour-like lesions called hamartomas in the
brain, skin, eyes, heart, lungs and kidneys. Tuberous Sclerosis Complex is
genetically determined with an autosomal dominant inheritance and is caused by
inactivating mutations in either the TSC1 or TSC2 genes. TSC1/2 genes play a
fundamental role in the regulation of phosphoinositide 3-kinase (PI3K)
signalling pathway, inhibiting the mammalian target of rapamycin (mTOR) through
activation of the GTPase activity of Rheb. Mutations in TSC1/2 genes impair the
inhibitory function of the hamartin/tuberin complex, leading to phosphorylation
of the downstream effectors of mTOR, p70 S6 kinase (S6K), ribosomal protein S6
and the elongation factor binding protein 4E-BP1, resulting in uncontrolled cell
growth and tumourigenesis.Despite recent promising genetic, diagnostic, and
therapeutic advances in Tuberous Sclerosis Complex, continuing research in all
aspects of this complex disease will be pivotal to decrease its associated
morbidity and mortality. In this review we will discuss and analyse all the
important findings in the molecular pathogenesis of Tuberous Sclerosis Complex,
focusing on genetics and the molecular mechanisms that define this multisystemic
disorder.
DOI: 10.2174/138920208786241243
PMCID: PMC2691673
PMID: 19506736
|
http://www.ncbi.nlm.nih.gov/pubmed/12556239
|
1. Ann Hum Genet. 2003 Jan;67(Pt 1):87-96. doi: 10.1046/j.1469-1809.2003.00012.x.
Tuberous sclerosis: from tubers to mTOR.
Kwiatkowski DJ(1).
Author information:
(1)Hematology Division, Department of Medicine, Brigham and Women's Hospital,
Harvard Medical School, Boston, MA 02115, USA. dk@rics.bwh.harvard.edu
Tuberous sclerosis (TSC) is an autosomal dominant hamartoma syndrome whose
causative genes (TSC1 and TSC2) were identified 5 and 9 years ago respectively.
Their encoded proteins are large, and apart from a strong binding interaction
with each other, relatively little was known about their biochemical function.
Recent studies in Drosophila have pinpointed a critical function for the
DrosophilaTSC1/TSC2 homologues in the regulation of cell size. Epistasis
experiments and a variety of biochemical studies that followed have indicated a
critical function for these proteins in the highly conserved
PI-3-kinase-Akt-mTOR signalling pathway.
DOI: 10.1046/j.1469-1809.2003.00012.x
PMID: 12556239 [Indexed for MEDLINE]
|
http://www.ncbi.nlm.nih.gov/pubmed/12937031
|
1. J Appl Physiol (1985). 2003 Dec;95(6):2355-60. doi:
10.1152/japplphysiol.00651.2003. Epub 2003 Aug 22.
Effect of exercise intensity on the postexercise sweating threshold.
Kenny GP(1), Periard J, Journeay WS, Sigal RJ, Reardon FD.
Author information:
(1)Human Performance and Environmental Physiology Research Laboratory, School of
Human Kinetics, Faculty of Health Sciences, University of Ottawa, Ottawa,
Ontario, Canada K1N 6N5. gkenny@uottawa.ca
The hypothesis that the magnitude of the postexercise onset threshold for
sweating is increased by the intensity of exercise was tested in eight subjects.
Esophageal temperature was monitored as an index of core temperature while sweat
rate was measured by using a ventilated capsule placed on the upper back.
Subjects remained seated resting for 15 min (no exercise) or performed 15 min of
treadmill running at either 55, 70, or 85% of peak oxygen consumption (V(o2
peak)) followed by a 20-min seated recovery. Subjects then donned a
liquid-conditioned suit used to regulate mean skin temperature. The suit was
first perfused with 20 degrees C water to control and stabilize skin and core
temperature before whole body heating. Subsequently, the skin was heated (
approximately 4.0 degrees C/h) until sweating occurred. Exercise resulted in an
increase in the onset threshold for sweating of 0.11 +/- 0.02, 0.23 +/- 0.01,
and 0.33 +/- 0.02 degrees C above that measured for the no-exercise resting
values (P < 0.05) for the 55, 70, and 85% of V(o2 peak) exercise conditions,
respectively. We did note that there was a greater postexercise hypotension as a
function of exercise intensity as measured at the end of the 20-min exercise
recovery. Thus it is plausible that the increase in postexercise threshold may
be related to postexercise hypotension. It is concluded that the sweating
response during upright recovery is significantly modified by exercise intensity
and may likely be influenced by the nonthermal baroreceptor reflex adjustments
postexercise.
DOI: 10.1152/japplphysiol.00651.2003
PMID: 12937031 [Indexed for MEDLINE]
|
http://www.ncbi.nlm.nih.gov/pubmed/2703281
|
1. Int J Sports Med. 1989 Feb;10(1):25-9. doi: 10.1055/s-2007-1024868.
Effect of active warming-up on thermoregulatory, circulatory, and metabolic
responses to incremental exercise in endurance-trained athletes.
Chwalbińska-Moneta J(1), Hänninen O.
Author information:
(1)Department of Applied Physiology, Medical Research Center, Polish Academy of
Sciences, Warsaw.
The influence of 10 min warming-up at 40% VO2 max on thermal, circulatory, and
metabolic responses to an incremental exercise to exhaustion as well as on the
anaerobic threshold at the blood lactate level of 4 mmol.l-1 (AT) and the
individual anaerobic threshold (IAT) was investigated in eight cross-country
skiers. During exercise preceded by warming-up, the mean skin temperature (T sk)
and external auditory canal temperature (Tac) did not change significantly in
contrast to exercise without warming-up, producing a rise in both T sk and Tac
(by approx. 1.2 degrees C and 1.1 degrees C, respectively). Warming-up did not
alter the course of the rectal temperature changes during exercise. With
warming-up skin humidity rose immediately after the beginning of exercise,
whereas the onset of sweating without warming-up appeared much later at higher
work intensities. Warming-up did not change the circulatory and ventilatory
responses to incremental exercise and the oxygen uptake (VO2) either at
submaximal or maximal work loads. With warming-up a significant increase was
found in the threshold work load both at the AT and the IAT. The data
demonstrated that warming-up has an advantageous effect on the efficiency of
thermoregulation in endurance-trained athletes producing an early sweating
response to the incremental exercise that results in attenuation of
hyperthermia. An increase in the anaerobic threshold during incremental exercise
preceded by warming-up may indicate an enhancement of the endurance capacity
subsequent to warming-up.
DOI: 10.1055/s-2007-1024868
PMID: 2703281 [Indexed for MEDLINE]
|
http://www.ncbi.nlm.nih.gov/pubmed/21623345
|
1. EMBO J. 2011 May 27;30(13):2596-609. doi: 10.1038/emboj.2011.166.
The DNA-binding domain of the Chd1 chromatin-remodelling enzyme contains SANT
and SLIDE domains.
Ryan DP(1), Sundaramoorthy R, Martin D, Singh V, Owen-Hughes T.
Author information:
(1)Wellcome Trust Centre for Gene Regulation and Expression, College of Life
Sciences, University of Dundee, Dundee, UK.
The ATP-dependent chromatin-remodelling enzyme Chd1 is a 168-kDa protein
consisting of a double chromodomain, Snf2-related ATPase domain, and a
C-terminal DNA-binding domain. Here, we show the DNA-binding domain is required
for Saccharomyces cerevisiae Chd1 to bind and remodel nucleosomes. The crystal
structure of this domain reveals the presence of structural homology to SANT and
SLIDE domains previously identified in ISWI remodelling enzymes. The presence of
these domains in ISWI and Chd1 chromatin-remodelling enzymes may provide a means
of efficiently harnessing the action of the Snf2-related ATPase domain for the
purpose of nucleosome spacing and provide an explanation for partial redundancy
between these proteins. Site directed mutagenesis was used to identify residues
important for DNA binding and generate a model describing the interaction of
this domain with DNA. Through inclusion of Chd1 sequences in homology searches
SLIDE domains were identified in CHD6-9 proteins. Point mutations to conserved
amino acids within the human CHD7 SLIDE domain have been identified in patients
with CHARGE syndrome.
DOI: 10.1038/emboj.2011.166
PMCID: PMC3155300
PMID: 21623345 [Indexed for MEDLINE]
Conflict of interest statement: The authors declare that they have no conflict
of interest.
|
http://www.ncbi.nlm.nih.gov/pubmed/24173008
|
1. Am J Health Syst Pharm. 2013 Nov 15;70(22):1984-94. doi: 10.2146/ajhp130199.
A review of tuberculosis: Focus on bedaquiline.
Chan B(1), Khadem TM, Brown J.
Author information:
(1)Bonnie Chan, Pharm.D., is Assistant Professor of Pharmacy, School of
Pharmacy, Philadelphia College of Osteopathic Medicine, Suwanee, GA; at the time
of writing she was Postgraduate Year 2 Infectious Diseases Pharmacy Resident,
Department of Pharmacy, University of Rochester Medical Center (URMC),
Rochester, NY. Tina M. Khadem, Pharm.D., is Postdoctoral Research Fellow,
Department of Pharmacy Practice, Wegmans School of Pharmacy, St. John Fisher
College, Rochester, and Postdoctoral Research Fellow, Department of Pharmacy,
URMC. Jack Brown, Pharm.D., M.S., is Associate Professor and Chair, Department
of Pharmacy Practice and Administration, Wegmans School of Pharmacy, St. John
Fisher College, and Adjunct Research Assistant Professor, Department of Social
and Preventative Medicine, URMC.
PURPOSE: The history and prevalence of tuberculosis and the role of bedaquiline
in multidrug-resistant (MDR) tuberculosis are reviewed.
SUMMARY: Tuberculosis continues to cause significant morbidity and mortality
worldwide. Increasing rates of drug-resistant tuberculosis are a significant
concern and pose serious implications for current and future treatment of the
disease. In December 2012, the Food and Drug Administration approved bedaquiline
as part of the treatment regimen for pulmonary MDR tuberculosis. Bedaquiline's
unique mechanism of action presents an alternative approach to current
antimycobacterial killing. By directly inhibiting adenosine triphosphate (ATP)
synthase, bedaquiline is effective against both replicating and dormant
mycobacteria. Pulmonary cavitary lesions can contain heterogeneous populations.
This potential mix of semireplicating and hypometabolic mycobacteria is more
difficult to eliminate with conventional antitubercular drugs, thus increasing
the risk of resistance. No in vitro cross-resistance between bedaquiline and
currently available antitubercular agents has been observed thus far. Because
bedaquiline targets a completely different enzyme, cross-resistance with other
conventional agents remains unlikely. Enhanced sterilizing capacity via
synergistic depletion of ATP further exhibits the promising potential of
bedaquiline with pyrazinamide. A course of bedaquiline requires 24 weeks of
therapy in combination with other antitubercular drugs.
CONCLUSION: The approval of bedaquiline represents a major milestone in MDR
tuberculosis therapy. Bedaquiline should be considered in patients who have not
responded to a regimen containing four second-line drugs and pyrazinamide and
patients with documented evidence of MDR tuberculosis resistant to
fluoroquinolones. The exact role of bedaquiline cannot be determined until
further efficacy and safety data are obtained through ongoing Phase III trials.
DOI: 10.2146/ajhp130199
PMID: 24173008 [Indexed for MEDLINE]
|
http://www.ncbi.nlm.nih.gov/pubmed/19031760
|
1. Zhonghua Liu Xing Bing Xue Za Zhi. 2008 Jul;29(7):683-4.
[Molecular epidemiological study on oxidative DNA damage among Hasake ethnic
migrants in Shenzhen].
[Article in Chinese]
Ke YB(1), Cheng JQ, Shuai ZH, Zhang RL, Jiang GF, Tan CR, Zhang ZZ.
Author information:
(1)Department of Genetic Toxicology, Shenzhen Center for Disease Control and
Prevention, Shenzhen 518020, China.
OBJECTIVE: To explore the relationship of migration and oxidative DNA damage by
comparative study of oxidative DNA damage effects on people with different years
of migration among Xinjiang Hasake ethnicity in Shenzhen.
METHODS: Sixty Hasake residents in Shenzhen were selected, and were divided into
three groups (n=20) according to the years of migration. Major changes of their
life style were investigated. 8-hydroxy-2'-deoxyguanosine (8-OH-dG) levels in
urine were analyzed, and comet assay of peripheral blood lymphocytes conducted.
RESULTS: When comparing with the group having a shorter than 1 year of stay,a
significant decrease of oliveira tail moment and tail/head length in comet assay
in the >3 years group (P < 0.05) was observed 8-OH-dG level decreased
significantly in 1-3 years group (P < 0.05) and >3 years group (P < 0.01).
CONCLUSION: Our results suggested that life style changes which related to
migration might reduce DNA damage in Hasake nationalities.
PMID: 19031760 [Indexed for MEDLINE]
|
http://www.ncbi.nlm.nih.gov/pubmed/23105513
|
1. Indian J Clin Biochem. 2005 Jan;20(1):145-9. doi: 10.1007/BF02893061.
Oxidative stress in metabolic syndrome.
Sharma P(1), Mishra S, Ajmera P, Mathur S.
Author information:
(1)Department of Biochemistry, S.M.S. Medical College, 302 004 Jaipur, India.
As antioxidants play a protective role in the pathophysiology of diabetes and
cardiovascular diseases, understanding the physiological status of antioxidant
concentration among people at high risk for developing these conditions, such as
Metabolic Syndrome, is of interest. In present study out of 187 first degree
non-diabetic relatives and 192 non-diabetic spouses, 33.1% and 19.7% were found
to have metabolic syndrome respectively. Subjects with metabolic syndrome (≥3
risk factors) had poor antioxidants status as reflected by significantly low
levels of vitamin A, C & E and significantly increased (p<0.01) oxidative stress
as compared to those without metabolic syndrome. At the same time serum insulin
levels and insulin resistance were found to be significantly high (p<0.001) in
metabolic syndrome. A strong positive correlation (r=0.946; p<0.001) between
oxidative stress and insulin resistance was observed in metabolic syndrome. Low
levels of antioxidants and increased oxidative stress with insulin resistance in
metabolic syndrome suggests that besides therapeutic life style changes (TLC) as
suggested in ATP III guidelines inclusion of antioxidant vitamins, fruits and
vegetable could be beneficial to ward off the consequences of metabolic
syndrome.
DOI: 10.1007/BF02893061
PMCID: PMC3454143
PMID: 23105513
|
http://www.ncbi.nlm.nih.gov/pubmed/7588694
|
1. Eur J Appl Physiol Occup Physiol. 1995;71(2-3):235-9. doi: 10.1007/BF00854984.
Effect of aerobic capacity on sweat rate and fluid intake during outdoor
exercise in the heat.
Yoshida T(1), Nakai S, Yorimoto A, Kawabata T, Morimoto T.
Author information:
(1)Department of Physiology, Kyoto Prefectural University of Medicine, Japan.
We measured the aerobic capacity, sweat rate and fluid intake of trained
athletes during outdoor exercise and examined the relationship between aerobic
capacity and thermoregulatory responses at high ambient temperatures. The
maximal aerobic capacity (VO2max) of the subjects, nine male baseball players of
college age, was determined by maximal exercise tests on a cycle ergometer. The
subjects practised baseball regularly without drinking fluids from 1330 to 1530
hours. After 30 min rest, they played a baseball game with free access to a
sports drink at 15 degrees C from 1600 to 1830 hours. At a mean ambient
temperature of 36.7 (SEM 0.2) degree C, the mean percentage of body mass loss
(delta mb) and increase of oral temperature (delta To) from 1330 to 1530 hours
was 3.47 (SEM 0.12)% and 0.81 (SEM 0.14) degree C, respectively. The sweat loss
from 1330 to 1830 hours was 56.53 (SEM 1.56)ml.kg-1 of body mass (mb) while the
mean fluid consumption was 44.78 (SEM 2.39)ml.kg-1 of mb, with recovery of 76.08
(SEM 2.81)% of sweat loss. The VO2max was significantly inversely correlated
with delta mb, fluid intake and rehydration amount, but showed no correlation
with delta To. These results would suggest that at a given exercise intensity in
subjects with a higher aerobic capacity body temperature is maintained with a
lower sweating rate than that in subjects with a lower aerobic capacity.
DOI: 10.1007/BF00854984
PMID: 7588694 [Indexed for MEDLINE]
|
http://www.ncbi.nlm.nih.gov/pubmed/20005186
|
1. Mol Oncol. 2010 Feb;4(1):65-89. doi: 10.1016/j.molonc.2009.11.003. Epub 2009
Nov 23.
Up-regulated proteins in the fluid bathing the tumour cell microenvironment as
potential serological markers for early detection of cancer of the breast.
Gromov P(1), Gromova I, Bunkenborg J, Cabezon T, Moreira JM, Timmermans-Wielenga
V, Roepstorff P, Rank F, Celis JE.
Author information:
(1)Institute of Cancer Biology, Danish Cancer Society, DK-2100 Copenhagen,
Denmark. psg@cancer.dk <psg@cancer.dk>
Breast cancer is by far the most common diagnosed form of cancer and the leading
cause of cancer death in women today. Clinically useful biomarkers for early
detection of breast cancer could lead to a significant reduction in mortality.
Here we describe a detailed analysis using gel-based proteomics in combination
with mass spectrometry and immunohistochemistry (IHC) of the tumour interstitial
fluids (TIF) and normal interstitial fluids (NIF) collected from 69 prospective
breast cancer patients. The goal of this study was to identify abundant cancer
up-regulated proteins that are externalised by cells in the tumour
microenvironment of most if not all these lesions. To this end, we applied a
phased biomarker discovery research strategy to the analysis of these samples
rather than comparing all samples among each other, with inherent inter and
intra-sample variability problems. To this end, we chose to use samples derived
from a single tumour/benign tissue pair (patient 46, triple negative tumour),
for which we had well-matched samples in terms of epithelial cell numbers, to
generate the initial dataset. In this first phase we found 110 proteins that
were up-regulated by a factor of 2 or more in the TIF, some of which were
confirmed by IHC. In the second phase, we carried out a systematic computer
assisted analysis of the 2D gels of the remaining 68 TIF samples in order to
identify TIF 46 up-regulated proteins that were deregulated in 90% or more of
all the available TIFs, thus representing common breast cancer markers. This
second phase singled out a set of 26 breast cancer markers, most of which were
also identified by a complementary analysis using LC-MS/MS. The expression of
calreticulin, cellular retinoic acid-binding protein II, chloride intracellular
channel protein 1, EF-1-beta, galectin 1, peroxiredoxin-2, platelet-derived
endothelial cell growth factor, protein disulfide isomerase and ubiquitin
carboxyl-terminal hydrolase 5 were further validated using a tissue microarray
containing 70 malignant breast carcinomas of various grades of atypia. A
significant number of these proteins have already been detected in the
blood/plasma/secretome by others. The next steps, which include biomarker
prioritization based on the hierarchal evaluation of these markers, antibody and
antigen development, assay development, analytical validation, and preliminary
testing in the blood of healthy and breast cancer patients, are discussed.
DOI: 10.1016/j.molonc.2009.11.003
PMCID: PMC5527961
PMID: 20005186 [Indexed for MEDLINE]
|
http://www.ncbi.nlm.nih.gov/pubmed/9694410
|
1. Int J Sports Med. 1998 Jun;19 Suppl 2:S103-5. doi: 10.1055/s-2007-971969.
Effects of training, environment, and host factors on the sweating response to
exercise.
Armstrong LE(1), Maresh CM.
Author information:
(1)University of Connecticut, Dept. of Physiology & Neurobiology, Storrs
06269-1110, USA. Armstron@uconnvm.uconn.edu
Because metabolic heat production is proportional to the amount of work
performed, the differences in core body temperature (Tcore) of humans exercising
at similar absolute exercise intensities are due to differences in their
efficiency of heat dissipation. The purpose of this paper is to delineate the
effects of training status, heat acclimation, environmental conditions and host
factors on the sweating response to exercise. These factors are reviewed in
light of their effects on the biophysical enhancement or suppression of
sweating, and modifications of the relationship between local sweat rate and
Tcore (degrees C). Athletes are advised to optimize those factors that enhance,
and eliminate those factors that diminish, the onset and responsiveness of
sweating.
DOI: 10.1055/s-2007-971969
PMID: 9694410 [Indexed for MEDLINE]
|
http://www.ncbi.nlm.nih.gov/pubmed/21669114
|
1. Neurol Res. 2011 Jun;33(5):467-72. doi: 10.1179/016164111X13007856083963.
Chronic Helicobacter pylori infection and ischemic stroke subtypes.
Yang X(1), Gao Y, Zhao X, Tang Y, Su Y.
Author information:
(1)Department of Neurology of Aerospace Central Hospital (Aerospace Clinical
Medical College Affiliated to Peking University), Beijing 100049, China.
OBJECTIVE: Chronic infection by Helicobacter pylori is regarded as an
etiological factor for vascular diseases. However, there are conflicting results
on the relevance of chronic infection by Helicobacter pylori as a risk factor
for ischemic stroke. The aim of our study was to investigate the association
between Helicobacter pylori infection and ischemic stroke subtypes in Chinese.
METHOD: A total of 150 patients with ischemic stroke were enrolled in the
patient group. Analyses were stratified for etiologic stroke subtypes according
to 2007 modified Trial of Org 10172 in Acute Stroke Treatment criteria: 119
patients with atherothrombosis, 15 patients with cardioembolism, and 12 patients
with small artery disease. One hundred and thirty-one control subjects without
clinical and instrumental evidence of atherosclerotic diseases were randomly
selected from health check-up center. The potential risk factors for
Helicobacter pylori infection and traditional risk factors for ischemic stroke
of all subjects were analyzed. The serum specific antibody IgG of Helicobacter
pylori was detected by enzyme-linked immunosorbent assay. Conditional logistic
regression was used to analyze the data.
RESULTS: The Helicobacter pylori/IgG-positive rate in the patient group was
higher than that in the healthy control group, but the difference was not
statistically significant [67.3% versus 61.8%; odds ratio (OR) = 1.272; P =
0.336]. This result remained non-significant after adjustment for other
established risk factors [OR = 1.222; 95% confidence interval (CI): 0.688-2.171;
P = 0.494]. Subgroup analysis using univariate and multivariate analyses yielded
similar results in all etiologic stroke subtypes (univariate analysis,
atherothrombosis: OR = 1.368, 95%CI: 0.810-2.311, P = 0.241; cardioembolism: OR
= 0.926, 95%CI:0.311-2.758, P = 0.890; small artery disease: OR = 1.852, 95%CI:
0.478-7.167, P = 0.366; multivariate analysis, atherothrombosis: OR = 1.385,
95%CI: 0.726-2.639, P = 0.323; cardioembolism: OR = 0.832, 95%CI: 0.236-2.932, P
= 0.775; small artery disease: OR = 1.836, 95%CI: 0.396-8.503, P = 0.437).
CONCLUSIONS: This case-control study does not reveal any strong association
between chronic Helicobacter pylori infection and ischemic stroke. Large
case-control prospective studies are required for further investigation of the
potential association between Helicobacter pylori infection and ischemic stroke
risk, particularly in certain subgroups.
DOI: 10.1179/016164111X13007856083963
PMID: 21669114 [Indexed for MEDLINE]
|
http://www.ncbi.nlm.nih.gov/pubmed/15694938
|
1. Atherosclerosis. 2005 Feb;178(2):303-9. doi:
10.1016/j.atherosclerosis.2004.08.025.
Association between chronic Helicobacter pylori infection and acute ischemic
stroke: Fukuoka Harasanshin Atherosclerosis Trial (FHAT).
Sawayama Y(1), Ariyama I, Hamada M, Otaguro S, Machi T, Taira Y, Hayashi J.
Author information:
(1)Division of General Medicine, Harasanshin General Hospital 1-8, Taihaku-cho,
Hakata-ku, Fukuoka 812-0033, Japan. genmedpr@hrasanshin.or.jp
Helicobacter pylori (H. pylori) have been associated both epidemiologically and
pathogenetically with coronary atherosclerosis, but data on the relationship
between chronic H. pylori infection and stroke are lacking. Therefore, we
investigated the relationship between H. pylori infection and acute ischemic
stroke in 62 patients with their first stroke and 143 controls. The stroke
patients were all admitted to Harasanshin General Hospital (Fukuoka, Japan) and
the controls were asymptomatic age-matched outpatients with hyperlipidemia who
did not have cardiac disease or infections. All patients underwent cranial CT
scanning and/or brain magnetic resonance imaging, duplex ultrasonography of the
extracranial carotid arteries, and transthoracic echocardiography. H. pylori
infection was diagnosed by detection of anti-H. pylori IgG antibodies, the
13C-urea breath test, and histology. Conditional logistic regression analysis
was performed to analyze the data. The 62 stroke patients and 143 controls were
aged from 41 to 92 years. Chronic H. pylori infection was associated with a
higher risk of stroke due to small artery occlusion (odds ratio: 9.68; 95% CI:
3.56-33.08, P <0.001) and a lower risk of cardioembolic stroke (odds ratio:
0.27; 95% CI: 0.03-1.53). Chronic H. pylori infection still showed an overall
association with ischemic stroke (odds ratio for all subtypes combined: 2.57;
95% CI: 1.09-6.08) after adjusting for major cardiovascular risk factors. These
results suggest that chronic H. pylori infection may be a triggering factor that
increases the risk of acute ischemic stroke.
DOI: 10.1016/j.atherosclerosis.2004.08.025
PMID: 15694938 [Indexed for MEDLINE]
|
http://www.ncbi.nlm.nih.gov/pubmed/22713083
|
1. J Dig Dis. 2012 Jul;13(7):342-9. doi: 10.1111/j.1751-2980.2012.00599.x.
Extragastrointestinal manifestations of Helicobacter pylori infection: facts or
myth? A critical review.
Tan HJ(1), Goh KL.
Author information:
(1)Department of Gastroenterology, Sunway Medical Centre, Selangor Department of
Gastroenterology, University of Malaya, Kuala Lumpur, Malaysia.
hucktan@hotmail.com
Helicobacter pylori (H. pylori) infection is reported to be associated with many
extragastrointestinal manifestations, such as hematological diseases [idiopathic
thrombocytopenic purpura (ITP) and unexplained iron deficiency anemia (IDA)],
cardiovascular diseases (ischemic heart diseases), neurological disorders
(stroke, Parkinson's disease, Alzheimer's disease), obesity and skin disorders.
Among these, the best evidence so far is in ITP and unexplained IDA, with
high-quality studies showing the improvement of IDA and ITP after H. pylori
eradication. The evidence of its association with coronary artery disease is
weak and many of the results may be erroneous. The role of H. pylori infection
in affecting serum leptin and ghrelin levels has attracted a lot of attention
recently and available data to date have been conflicting. There have also been
many uncontrolled, small sample studies suggesting an association between H.
pylori infection and neurological disorders or chronic urticaria. However, more
studies are required to clarify such proposed causal links.
© 2012 The Authors. Journal of Digestive Diseases © 2012 Chinese Medical
Association Shanghai Branch, Chinese Society of Gastroenterology, Renji Hospital
Affiliated to Shanghai Jiaotong University School of Medicine and Blackwell
Publishing Asia Pty Ltd.
DOI: 10.1111/j.1751-2980.2012.00599.x
PMID: 22713083 [Indexed for MEDLINE]
|
http://www.ncbi.nlm.nih.gov/pubmed/21060340
|
1. Nat Rev Neurol. 2010 Dec;6(12):681-94. doi: 10.1038/nrneurol.2010.163. Epub
2010 Nov 9.
Common infections and the risk of stroke.
Grau AJ(1), Urbanek C, Palm F.
Author information:
(1)Neurology Department, Klinikum Ludwigshafen am Rhein, Bremserstrasse 79,
Ludwigshafen am Rhein, Germany. graua@klilu.de
The occurrence of stroke in populations is incompletely explained by traditional
vascular risk factors. Data from several case-control studies and one large
study using case series methodology indicate that recent infection is a
temporarily acting, independent trigger factor for ischemic stroke. Both
bacterial and viral infections, particularly respiratory tract infections,
contribute to this association. A causal role for infection in stroke is
supported by a graded temporal relationship between these conditions, and by
multiple pathophysiological pathways linking infection and inflammation,
thrombosis, and stroke. Furthermore, observational studies suggest that
influenza vaccination confers a preventive effect against stroke. Case-control
and prospective studies indicate that chronic infections, such as periodontitis,
chronic bronchitis and infection with Helicobacter pylori, Chlamydia pneumoniae
or Cytomegalovirus, might increase stroke risk, although considerable variation
exists in the results of these studies, and methodological issues regarding
serological results remain unresolved. Increasing evidence indicates that the
aggregate burden of chronic and/or past infections rather than any one single
infectious disease is associated with the risk of stroke. Furthermore, genetic
predispositions relating to infection susceptibility and the strength of the
inflammatory response seem to co-determine this risk. Here, we summarize and
analyze the evidence for common acute and chronic infectious diseases as stroke
risk factors.
DOI: 10.1038/nrneurol.2010.163
PMID: 21060340 [Indexed for MEDLINE]
|
http://www.ncbi.nlm.nih.gov/pubmed/22012946
|
1. Pediatr Blood Cancer. 2012 Aug;59(2):246-53. doi: 10.1002/pbc.23357. Epub 2011
Oct 19.
Initial testing of the investigational NEDD8-activating enzyme inhibitor MLN4924
by the pediatric preclinical testing program.
Smith MA(1), Maris JM, Gorlick R, Kolb EA, Lock R, Carol H, Keir ST, Reynolds
CP, Kang MH, Morton CL, Wu J, Smith PG, Yu J, Houghton PJ.
Author information:
(1)Cancer Therapy Evaluation Program, NCI, Bethesda, Maryland 20892, USA.
smithm@ctep.nci.nih.gov
Erratum in
Pediatr Blood Cancer. 2012 Oct;59(4):772.
BACKGROUND: MLN4924 is an investigational first-in-class small molecule
inhibitor of NEDD8-activating enzyme (NAE). NAE is an essential component of the
NEDD8 conjugation pathway, controlling the activity of a subset of
ubiquitin-proteasome system (UPS) E3 ligases, multiprotein complexes that
transfer ubiquitin molecules to substrate proteins.
PROCEDURES: MLN4924 was tested against the PPTP in vitro panel using 96-hour
exposure time at concentrations ranging from 1.0 nM to 10 µM. It was tested in
vivo at a dose of 100 mg/kg [66 mg/kg for the acute lymphoblastic leukemia (ALL)
xenografts] administered orally twice daily × 5 days. Treatment duration was 3
weeks.
RESULTS: The median relative IC(50) for MLN4924 against the PPTP cell lines was
143 nM, (range: 15-678 nM) with that for the Ewing panel being significantly
lower (31 nM). MLN4924 induced significant differences in EFS distribution
compared to control in 20 of 34 (59%) evaluable solid tumor xenografts. MLN4924
induced intermediate activity (EFS T/C values >2) in 9 of the 33 evaluable
xenografts (27%), including 4 of 4 glioblastoma xenografts, 2 of 3 Wilm's tumor
xenografts, 2 of 5 rhabdomyosarcoma xenografts, and 1 of 4 neuroblastoma
xenografts. For the ALL panel, 5 of 8 evaluable xenografts showed intermediate
activity for the EFS T/C measure. MLN4924 did not induce objective responses in
the PPTP solid tumor or ALL panels.
CONCLUSIONS: MLN4924 showed potent activity in vitro and in vivo showed tumor
growth inhibitory activity against a subset of the PPTP solid tumor and ALL
xenografts.
Copyright © 2011 Wiley Periodicals, Inc.
DOI: 10.1002/pbc.23357
PMCID: PMC3823062
PMID: 22012946 [Indexed for MEDLINE]
Conflict of interest statement: CONFLICT OF INTEREST STATEMENT: Peter G Smith,
and Jie Yu are employees of Millennium Pharmaceuticals, the other authors
consider that there are no actual or perceived conflicts of interest.
|
http://www.ncbi.nlm.nih.gov/pubmed/19355997
|
1. Curr Vasc Pharmacol. 2009 Apr;7(2):146-52. doi: 10.2174/157016109787455707.
Infection, its treatment and the risk for stroke.
Palm F(1), Urbanek C, Grau A.
Author information:
(1)Department of Neurology, Städtisches Klinikum Ludwigshafen, Germany.
Stroke is among the most common causes of death and persisting disability and
therefore represents a great social and economic burden worldwide. In order to
lower this burden it is essential to identify risk factors and respective
preventive strategies. Besides the established stroke risk factors (e.g.
hypertension, diabetes, hypercholesterolemia, atrial fibrillation) both acute
and chronic infectious diseases have emerged as risk factors for stroke. Mainly
acute respiratory tract infection but also urinary tract infections
independently increase the risk of ischemic stroke. Such additional risk was
shown to be highest for infection within 3 days before ischemia and the risk
steadily declines with increasing time intervals between infection and stroke.
Associations between stroke incidence and mortality and influenza epidemics have
been demonstrated. Observational studies showed an inverse association between
influenza vaccination and stroke risk; however, interventional studies in this
field have not been performed so far. Chronic infections, presently discussed as
stroke risk factors mainly include periodontitis and infections with
Helicobacter pylori (Hp) and Chlamydia pneumoniae (Cp). Although most respective
studies identified these infectious diseases as independent stroke risk factors
interventional trials have not been performed so far and causality is not
proven, yet. There is preliminary evidence that the number of pathogens to which
a subject had been exposed to rather than single pathogens are associated with
the risk of stroke or other cardiovascular diseases. Chronic infectious diseases
are treatable conditions and their identification as causal contributors to
stroke risk could offer new avenues in stroke prevention.
DOI: 10.2174/157016109787455707
PMID: 19355997 [Indexed for MEDLINE]
|
http://www.ncbi.nlm.nih.gov/pubmed/12147540
|
1. Circulation. 2002 Jul 30;106(5):580-4. doi:
10.1161/01.cir.0000023894.10871.2f.
Cytotoxin-associated gene-A--positive Helicobacter pylori strains are associated
with atherosclerotic stroke.
Pietroiusti A(1), Diomedi M, Silvestrini M, Cupini LM, Luzzi I, Gomez-Miguel MJ,
Bergamaschi A, Magrini A, Carrabs T, Vellini M, Galante A.
Author information:
(1)Medical Semiology and Methodology, Dipartimento di Medicina Interna, Tor
Vergata University, Rome, Italy. pietroiusti@med.uniroma2.it
BACKGROUND: It is uncertain whether Helicobacter pylori is associated with
ischemic syndromes and whether this association is mediated by the induction of
atherosclerosis. In this study, we tested the hypothesis that atherosclerotic
stroke shows a selective association with virulent H pylori strains.
METHODS AND RESULTS: The seroprevalence of infection by H pylori and by strains
bearing the cytotoxin-associated gene-A (CagA), a strong virulence factor, was
assessed by ELISA in 138 patients with large-vessel stroke (group A), in 61
patients with cardioembolic stroke (group B), and in 151 healthy control
subjects. The 3 groups had a similar socioeconomic status. Serum levels of
C-reactive protein were also measured by ELISA. The prevalence of infection was
71% in group A, 63.9% in group B, and 70.2% in the control group (P=NS), whereas
the prevalence of CagA-positive strains was higher in group A than in group B
(42.8% versus 19.7%, respectively; odds ratio 3.04, 95% CI 1.43 to 6.49;
P<0.001) and higher in group A than in the control group (42.8% versus 17.9%,
respectively; odds ratio 4.3, 95% CI 2.12 to 8.64; P<0.001), after adjusting for
main cardiovascular risk factors and social class. A trend toward a difference
in C-reactive protein was observed between CagA-positive (2.00+/-3.43
[mean+/-SD] mg/dL) and CagA-negative (1.31+/-1.72 [mean+/-SD] mg/dL) patients
(P=0.072, Mann-Whitney U test).
CONCLUSIONS: The association between H pylori and acute cerebrovascular disease
seems to be due to a higher prevalence of more virulent H pylori strains in
patients with atherosclerotic stroke.
DOI: 10.1161/01.cir.0000023894.10871.2f
PMID: 12147540 [Indexed for MEDLINE]
|
http://www.ncbi.nlm.nih.gov/pubmed/24259600
|
1. Ann Pharmacother. 2014 Jan;48(1):107-15. doi: 10.1177/1060028013504087. Epub
2013 Nov 1.
Bedaquiline: a novel diarylquinoline for multidrug-resistant tuberculosis.
Chahine EB(1), Karaoui LR, Mansour H.
Author information:
(1)Palm Beach Atlantic University, West Palm Beach, FL, USA.
Comment in
Ann Pharmacother. 2014 May;48(5):666. doi: 10.1177/1060028014521589.
Ann Pharmacother. 2014 May;48(5):667. doi: 10.1177/1060028014521590.
OBJECTIVE: To review the chemistry, pharmacology, microbiology,
pharmacokinetics, pharmacodynamics, clinical efficacy, safety, dosage, and
administration of bedaquiline, a novel oral diarylquinoline antimycobacterial
agent approved by the Food and Drug Administration for the treatment of adults
with pulmonary multidrug-resistant tuberculosis (MDR-TB).
DATA SOURCES: A search of PubMed (January 2004-May 2013) and International
Pharmaceutical Abstracts (January 2004-May 2013) using the search terms
bedaquiline, diarylquinoline, R207910, and TMC207 was performed. Supplementary
sources included proceedings of the Union World Conference on Lung Health.
STUDY SELECTION AND DATA EXTRACTION: Preclinical data as well as Phase 1 and 2
studies published in English were evaluated.
DATA SYNTHESIS: Bedaquiline possesses a unique mechanism of action that disrupts
the activity of the mycobacterial adenosine triphosphate synthase. Clinical
trials have been conducted evaluating the use of bedaquiline in combination with
a background regimen for the treatment of adults with pulmonary MDR-TB.
Bedaquiline has an excellent in vitro activity against Mycobacterium
tuberculosis, including multidrug resistant M tuberculosis; however, its side
effect profile limits its use against MDR-TB when no other effective regimen can
be provided. Bedaquiline carries Black Box warnings for increased risk of
unexplained mortality and QT prolongation. Bedaquiline is metabolized via the
CYP3A4 isoenzyme and thus interacts with rifamycins and several antiretrovirals.
CONCLUSIONS: In an era of emerging resistance and given the suboptimal efficacy
and toxicity of currently available regimens for MDR-TB, bedaquiline represents
a great addition to the existing armamentarium of anti-TB agents particularly in
areas of the world where the disease is endemic.
DOI: 10.1177/1060028013504087
PMID: 24259600 [Indexed for MEDLINE]
|
http://www.ncbi.nlm.nih.gov/pubmed/12388919
|
1. Med Sci Monit. 2002 Oct;8(10):CR675-84.
Influence of chronic Helicobacter pylori infection on ischemic cerebral stroke
risk factors.
Majka J(1), Róg T, Konturek PC, Konturek SJ, Bielański W, Kowalsky M, Szczudlik
A.
Author information:
(1)Jagiellonian University, College of Medicine, Cracow, Poland.
Comment in
Med Sci Monit. 2002 Dec;8(12):LE52-3; author reply LE53.
BACKGROUND: Infection by Helicobacter pylori (Hp) has been linked to
extradigestive pathologies including ischemic cerebral disease. The aim of our
study was to assess the relationship between chronic Hp infection and ischemic
stroke risk factors.
MATERIAL/METHODS: 80 patients (pts) aged 60-75 years with ischemic stroke
confirmed by CT scans (group I) and 80 age- and gender-matched healthy controls
(group II) were included into trial. Atherosclerotic plaques from 20 Hp positive
pts were obtained at carotid endarterectomy for Hp DNA assessment by PCR. In all
groups following parameters were determined; 1) the prevalence of Hp infection
using (13)C-Urea Breath Test (UBT), 2) plasma anti-Hp and anti-CagA IgG and
interleukin-8 (IL-8), and 3) plasma lipids and fibrinogen. Hp positive pts and
controls received one-week anti-Hp therapy and after six months total
cholesterol, low-density lipoprotein (LDL)-cholesterol, fibrinogen and IL-8
levels were re-examined.
RESULTS: Hp infection was detected by UBT in 83.75% of stroke pts but only in
65% of controls. CagA seropositivity was also significantly higher in stroke pts
(57.5%) than in controls (33.75%). Plasma levels of cholesterol, LDL-cholesterol
and fibrinogen as well as IL-8 were significantly higher in Hp positive
subjects, especially in pts with ischemic stroke. Six months following
successful anti-Hp therapy, the plasma levels of total cholesterol,
LDL-cholesterol, fibrinogen and IL-8 were significantly lower than those in Hp
positive stroke pts and controls.
CONCLUSIONS: Hp infection represents risk factor of ischemic stoke via an
interaction of Hp cytotoxins or cytokines with atherosclerotic plaques in
carotic arteries.
PMID: 12388919 [Indexed for MEDLINE]
|
http://www.ncbi.nlm.nih.gov/pubmed/18665936
|
1. Helicobacter. 2008 Aug;13(4):274-7. doi: 10.1111/j.1523-5378.2008.00610.x.
High prevalence of Cag-A positive H. pylori strains in ischemic stroke: a
primary care multicenter study.
De Bastiani R(1), Gabrielli M, Ubaldi E, Benedetto E, Sanna G, Cottone C,
Candelli M, Zocco MA, Saulnier N, Santoliquido A, Papaleo P, Gasbarrini G,
Gasbarrini A.
Author information:
(1)GIGA-CP (Italian Group for Primary Care Gastroenterology), Feltre (BL) Italy.
Erratum in
Helicobacter. 2013 Dec;18(6):473. Zocco Maria, Assunta [corrected to Zocco,
Maria Assunta].
BACKGROUND: Previous studies suggested an association between CagA-positive H.
pylori strains and ischemic stroke. The aim of the present study was to assess
the prevalence of Helicobacter pylori infection and CagA status in patients with
atherosclerotic stroke in the primary care setting.
MATERIALS AND METHODS: A total of 106 consecutive patients (age 76.6 +/- 8
years; males 52%) with well-documented history of atherosclerotic stroke and 106
sex-age- (age 76.5 +/- 9 years; males 52%) and social background-matched
controls without relevant vascular diseases. Risk factors for ischemic stroke
were recorded in all subjects. H. pylori infection was assessed by[13]C-urea
breath test. A serologic assay for specific IgG against CagA was performed in
infected subjects.
RESULTS: A trend toward a higher prevalence of H. pylori was observed in cases
(63%) with respect to controls (54%) without reaching a statistical
significance. CagA positivity was associated to a higher risk of atherosclerotic
stroke (adjusted odds ratio 2.69, 95% confidence interval 1.37-5.30).
CONCLUSIONS: Our findings suggest that CagA-positive strains of H. pylori are
significantly associated to atherosclerotic stroke. This is not a merely
confirmative study since it has been performed for the first time in the primary
care setting and included only subjects with an active infection.
DOI: 10.1111/j.1523-5378.2008.00610.x
PMID: 18665936 [Indexed for MEDLINE]
|
http://www.ncbi.nlm.nih.gov/pubmed/16709600
|
1. Mol Endocrinol. 2006 Oct;20(10):2444-55. doi: 10.1210/me.2006-0118. Epub 2006
May 18.
Differential expression of FOXO1 and FOXO3a confers resistance to oxidative cell
death upon endometrial decidualization.
Kajihara T(1), Jones M, Fusi L, Takano M, Feroze-Zaidi F, Pirianov G, Mehmet H,
Ishihara O, Higham JM, Lam EW, Brosens JJ.
Author information:
(1)Institute of Reproductive and Developmental Biology, Imperial College London,
Hammersmith Hospital, London W12 0NN, United Kingdom.
The integrity of the feto-maternal interface is critical for survival of the
conceptus. This interface, consisting of the maternal decidua and the invading
placental trophoblast, is exposed to profound changes in oxygen tension during
pregnancy. We demonstrate that human endometrial stromal cells become
extraordinarily resistant to oxidative stress-induced apoptosis upon
decidualization in response to cAMP and progesterone signaling. This
differentiation process is associated with the induction of the forkhead
transcription factor FOXO1, which in turn increases the expression of the
mitochondrial antioxidant manganese superoxide dismutase. However, silencing of
FOXO1 did not increase the susceptibility of decidualized cells to oxidative
cell death. Comparative analysis demonstrated that hydrogen peroxide, a source
of free radicals, strongly induces FOXO3a mRNA and protein expression in
undifferentiated human endometrial stromal cells but not in decidualized cells.
Expression of a constitutively active FOXO3a mutant elicited apoptosis in
decidualized cells. Furthermore, silencing of endogenous FOXO3a in
undifferentiated cells abrogated apoptosis induced by hydrogen peroxide. These
results suggest that the induction of FOXO1 may enhance the ability of
decidualized cells to prevent oxidative damage while the simultaneous repression
of FOXO3a expression disables the signaling pathway responsible for oxidative
cell death. The differential regulation of FOXO expression provides the decidua
with a robust system capable of coping with prolonged episodes of oxidative
stress during pregnancy.
DOI: 10.1210/me.2006-0118
PMID: 16709600 [Indexed for MEDLINE]
|
http://www.ncbi.nlm.nih.gov/pubmed/20184513
|
1. Amyotroph Lateral Scler. 2010;11(1-2):4-15. doi: 10.3109/17482960802379004.
Dysarthria in amyotrophic lateral sclerosis: A review.
Tomik B(1), Guiloff RJ.
Author information:
(1)Department of Neurology, Jagiellonian University, Krakow, Poland.
tomik@neuro.cm-uj.krakow.pl <tomik@neuro.cm-uj.krakow.pl>
Dysarthria is a motor disorder of speech characterized by abnormalities of the
articulation and intelligibility of speech. Phonation and the rate of facial
movements may also be affected. Understanding the nature and course of
dysarthria in amyotrophic lateral sclerosis (ALS) is important because loss of
communication prevents patients from participating in many activities, may lead
to social isolation, and reduces the quality of life. The goal of management of
dysarthria in ALS patients is to optimize communication effectiveness for as
long as possible. The information about dysarthria in ALS is dispersed in
physiological, pathological, speech therapy, otorhinolaringological and
neurological publications. This review summarizes the current state of knowledge
on the clinical features, differential diagnosis, pathophysiology,
investigations and management of dysarthria in ALS patients. There is a need to
compare the different methods used to assess dysarthria and for controlled
clinical trials to assess therapeutic strategies.
DOI: 10.3109/17482960802379004
PMID: 20184513 [Indexed for MEDLINE]
|
http://www.ncbi.nlm.nih.gov/pubmed/23033442
|
1. J Speech Lang Hear Res. 2012 Oct;55(5):1472-84. doi:
10.1044/1092-4388(2012/11-0263).
Characterizing intonation deficit in motor speech disorders: an
autosegmental-metrical analysis of spontaneous speech in hypokinetic dysarthria,
ataxic dysarthria, and foreign accent syndrome.
Lowit A(1), Kuschmann A.
Author information:
(1)University of Strathclyde, Glasgow, Scotland. a.lowit@strath.ac.uk
PURPOSE: The autosegmental-metrical (AM) framework represents an established
methodology for intonational analysis in unimpaired speaker populations but has
found little application in describing intonation in motor speech disorders
(MSDs). This study compared the intonation patterns of unimpaired participants
(CON) and those with Parkinson's disease (PD), ataxic dysarthria (AT), and
foreign accent syndrome (FAS) to evaluate the approach's potential for
distinguishing types of MSDs from each other and from unimpaired speech.
METHOD: Spontaneous speech from 8 PD, 8 AT, 4 FAS, and 10 CON speakers were
analyzed in relation to inventory and prevalence of pitch patterns,
accentuation, and phrasing. Acoustic-phonetic baseline measures
(maximum-phonation-duration, speech rate, and F0-variability) were also
performed.
RESULTS: The analyses yielded differences between MSD and CON groups and between
the clinical groups in regard to prevalence, accentuation, and phrasing. AT and
FAS speakers used more rising and high pitch accents than PD and CON speakers.
The AT group used the highest number of pitch accents per phrase, and all 3 MSD
groups produced significantly shorter phrases than the CON group.
CONCLUSIONS: The study succeeded in differentiating MSDs on the basis of
intonational performances by using the AM approach, thus, demonstrating its
potential for charting intonational profiles in clinical populations.
DOI: 10.1044/1092-4388(2012/11-0263)
PMID: 23033442 [Indexed for MEDLINE]
|
http://www.ncbi.nlm.nih.gov/pubmed/23312647
|
1. Handb Clin Neurol. 2013;110:273-81. doi: 10.1016/B978-0-444-52901-5.00022-8.
Disorders of communication: dysarthria.
Enderby P(1).
Author information:
(1)Department of Rehabilitation and Assistive Technology, University of
Sheffield, Sheffield, UK. p.m.enderby@sheffield.ac.uk
Dysarthria is a motor speech disorder which can be classified according to the
underlying neuropathology and is associated with disturbances of respiration,
laryngeal function, airflow direction, and articulation resulting in
difficulties of speech quality and intelligibility. There are six major types of
dysarthria: flaccid dysarthria associated with lower motor neuron impairment,
spastic dysarthria associated with damaged upper motor neurons linked to the
motor areas of the cerebral cortex, ataxic dysarthria primarily caused by
cerebellar dysfunction, and hyperkinetic dysarthria and hypokinetic dysarthria,
which are related to a disorder of the extrapyramidal system. The sixth is
generally termed a mixed dysarthria and is associated with damage in more than
one area, resulting in speech characteristics of at least two groups. The
features of the speech disturbance of these six major types of dysarthria are
distinctive and can assist with diagnosis. Dysarthria is a frequent symptom of
many neurological conditions and is commonly associated with progressive
neurological disease. It has a profound effect upon the patient and their
families as communication is integrally related with expressing personality and
social relationships. Speech and language therapy can be used to encourage the
person to use the speech that is already available to them more effectively, can
increase the range and consistency of sound production, can teach strategies for
improving intelligibility and communicative effectiveness, can guide the
individual to use methods that are less tiring and more successful, and can
introduce the appropriate Augmentative and Alternative Communication approaches
as and when required.
Copyright © 2013 Elsevier B.V. All rights reserved.
DOI: 10.1016/B978-0-444-52901-5.00022-8
PMID: 23312647 [Indexed for MEDLINE]
|
http://www.ncbi.nlm.nih.gov/pubmed/9197089
|
1. Folia Phoniatr Logop. 1997;49(2):63-82. doi: 10.1159/000266440.
A speaking task analysis of the dysarthria in cerebellar disease.
Kent RD(1), Kent JF, Rosenbek JC, Vorperian HK, Weismer G.
Author information:
(1)Waisman Center, University of Wisconsin-Medison 53705-2280, USA.
Cerebellar disease affects a number of skilled movements, including those in
speech. Ataxic dysarthria, the speech disorder that typically accompanies
cerebellar disease, was studied by acoustic methods. Control subjects and
subjects with ataxic dysarthria were recorded while performing a number of
speaking tasks, including sustained vowel phonation, syllable repetition,
monosyllabic word production (intelligibility test), sentence recitation, and
conversation. Acoustic data derived from the speech samples confirmed the
hypothesis that temporal dysregulation is a primary component of the speech
disorder. The data also show that the nature of the disorder varies with the
speaking task. This result agrees with observations on other motor systems in
subjects with cerebellar disease and may be evidence of a dissociation of
impairments. Suggestions are offered on the selection of measures for a given
task and on the role of the cerebellum in the regulation of speaking.
DOI: 10.1159/000266440
PMID: 9197089 [Indexed for MEDLINE]
|
http://www.ncbi.nlm.nih.gov/pubmed/20882349
|
1. J Inherit Metab Dis. 2011 Apr;34(2):377-85. doi: 10.1007/s10545-010-9213-4.
Epub 2010 Sep 30.
Voice disorders in children with classic galactosemia.
Potter NL(1).
Author information:
(1)Department of Speech and Hearing Sciences, Washington State
University-Spokane, Spokane, WA 99210-1495, USA. nlpotter@wsu.edu
Children with classic galactosemia are at risk for motor speech disorders
resulting from disruptions in motor planning and programming (childhood apraxia
of speech or CAS) or motor execution (dysarthria). In the present study of 33
children with classic galactosemia, 21% were diagnosed with CAS, 3% with ataxic
dysarthria, and 3% with mixed CAS-dysarthria. Voice disorders due to laryngeal
insufficiency were common in children with dysarthria and co-occurred with CAS.
Most (58%) of the children with classic galactosemia had decreased
respiratory-phonatory support for speech, and 33% had disturbed vocal quality
that was indicative of cerebellar dysfunction. Three children, two diagnosed
with CAS and one not diagnosed with a motor speech disorder, had vocal tremors.
Treatment of voice dysfunction in neurogenic speech disorders is discussed.
DOI: 10.1007/s10545-010-9213-4
PMCID: PMC3063853
PMID: 20882349 [Indexed for MEDLINE]
Conflict of interest statement: Competing interest: None declared
|
http://www.ncbi.nlm.nih.gov/pubmed/18249521
|
1. Presse Med. 2008 Mar;37(3 Pt 2):525-34. doi: 10.1016/j.lpm.2007.07.029. Epub
2008 Feb 4.
[Does Helicobacter pylori infection play a role in extragastric diseases?].
[Article in French]
de Korwin JD(1).
Author information:
(1)Service de médecine interne H, Université Henri Poincaré, CHU de
Nancy-Hôpital Central, F-54035 Nancy Cedex, France. jd.dekorwin@chu-nancy.fr
Since the discovery of Helicobacter pylori (H. pylori), numerous studies have
considered the possibility that it plays a role in different extragastric
diseases. Most of these studies may be classified as epidemiological studies or
investigations of H. pylori eradication, but there are also case reports and in
vitro studies. This review reveals the limitations common to most of them.
Idiopathic thrombocytopenic purpura is the disease for which the strongest
association with H. pylori infection has been shown. Data are also accumulating
about the role of H. pylori infection in idiopathic iron deficiency anemia and
chronic idiopathic urticaria. Interesting results show that H. pylori infection
affects atherosclerosis and is weakly associated with ischemic heart disease and
stroke. Moreover, CagA-positive H. pylori strains may play a role in the natural
history of atherosclerotic stroke. Recent studies suggest a link between H.
pylori and Parkinson's disease. Preliminary data indicate that H. pylori
infection impairs gastric ghrelin production and may influence nutritional
status. The association between H. pylori infection and other extragastric
diseases remains controversial. H. pylori infection may cause extragastric
manifestations directly or indirectly, by various mechanisms including atrophic
gastritis, the release of inflammatory mediators, molecular mimicry, and
systemic immune response. Evidence suggests that anti-H. pylori therapy improves
idiopathic thrombocytopenic purpura (significant increase of platelet count in
half of the cases), iron-deficiency anemia, and chronic urticaria (30% remission
rate), but the data from randomized controlled trials are insufficient to
confirm these positive effects.
DOI: 10.1016/j.lpm.2007.07.029
PMID: 18249521 [Indexed for MEDLINE]
|
http://www.ncbi.nlm.nih.gov/pubmed/9436737
|
1. J Neurol Neurosurg Psychiatry. 1998 Jan;64(1):104-7. doi:
10.1136/jnnp.64.1.104.
Helicobacter pylori infection: a risk factor for ischaemic cerebrovascular
disease and carotid atheroma.
Markus HS(1), Mendall MA.
Author information:
(1)Department of Clinical Neuroscience, King's College School of Medicine and
Dentistry and the Institute of Psychiatry, London, UK. h.markus@iop.bpmf.ac.uk
OBJECTIVES: Chronic Helicobacter pylori infection has been associated with
ischaemic heart disease although the mechanism by which it mediates this effect
remains unclear. The objective was to determine whether it is also a risk factor
for ischaemic cerebrovascular disease
METHODS: A total of 238 patients and 119 controls were studied. Patients were
characterised into stroke subtypes based on pathogenic mechanisms and carotid
atheroma load was estimated using duplex ultrasound. H pylori seropositivity was
determined on serum samples.
RESULTS: H pylori seropositivity was more common in cases (58.8% v 44.5%,
p=0.01). The odds ratio for cerebrovascular disease associated with
seropositivity was 1.78 (95% confidence interval (95% CI) 1.14-2.77), and this
remained significant after controlling for other risk factors including
socioeconomic status (1.63 (95% CI 1.02-2.60). H pylori seropositivity was
associated with large vessel disease (odds ratio 2.58 (95% CI 1.44-4.63),
p=0.001) and lacunar stroke (odds ratio 2.21 (95% CI 1.12-4.38), p=0.02) but not
stroke due to cardioembolism or unknown aetiology (odds ratio 1.16 (95% CI
0.66-2.02), p=0.5). Mean (SD) carotid stenosis was greater in patients
seropositive for H pylori (37.3 (29.7) v 27.9 (26.2)%, p=0.01). There was no
difference in the prevalence of seropositivity between patients with stroke and
transient ischaemic attack (59.6% v 58.6%, p=0.9)
CONCLUSION: Chronic H pylori infection is an independent risk factor for
ischaemic cerebrovascular disease and may act, at least in part, by increasing
atherosclerosis.
DOI: 10.1136/jnnp.64.1.104
PMCID: PMC2169914
PMID: 9436737 [Indexed for MEDLINE]
|
http://www.ncbi.nlm.nih.gov/pubmed/12725602
|
1. Dig Liver Dis. 2003 Jan;35(1):16-9. doi: 10.1016/s1590-8658(02)00005-1.
Helicobacter pylori infection in subjects with acute ischaemic stroke.
Moayyedi P(1), Carter AM, Braunholtz D, Catto AJ.
Author information:
(1)Unit of Molecular Vascular Medicine, Research School of Medicine, University
of Leeds, General Infirmary at Leeds, Leeds LS1 3EX, UK. p.moayyedi@bham.ac.uk
AIMS: To determine whether infection with Helicobacter pylori is a significant
risk factor for stroke.
SUBJECTS: A total 467 in-patients with clinical evidence of acute ischaemic
stroke and 388 healthy controls with no evidence of cerebrovascular disease.
METHODS: This was a case control study. The prevalence of Helicobacter pylori
was measured by enzyme-linked immunosorbent assay in stroke patients and
controls. A positive titre was defined as >15 U/ml and relationship with
circulating plasma fibrinogen and social depravation was expressed using the
Townsend Index.
RESULTS: There were significantly more Helicobacter pylori positive individuals
(274/398 (69%)) in the cases compared to the controls (206/352 (58.5%)).
Fibrinogen levels were also significantly higher in Helicobacter pylori positive
(mean 4.14, standard deviation 1.33) than negative individuals (mean 3.78,
standard deviation 1.28). The association between Helicobacter pylori and stroke
was lost in a logistic model controlling for socio-economic status. Furthermore,
fibrinogen levels were not associated with Helicobacter pylori status in a
linear regression model controlling for socio-economic status.
CONCLUSIONS: Infection with Helicobacter pylori is associated with an increased
risk of stroke and increased fibrinogen levels but these findings can be
attributed to a confounding effect of socio-economic status.
DOI: 10.1016/s1590-8658(02)00005-1
PMID: 12725602 [Indexed for MEDLINE]
|
http://www.ncbi.nlm.nih.gov/pubmed/14500942
|
1. Stroke. 2003 Oct;34(10):2518-32. doi: 10.1161/01.STR.0000089015.51603.CC. Epub
2003 Sep 18.
Inflammation and infections as risk factors for ischemic stroke.
Lindsberg PJ(1), Grau AJ.
Author information:
(1)Department of Neurology, Helsinki University Central Hospital and Biomedicum
Helsinki, Helsinki, Finland. perttu.lindsberg@hus.fi
BACKGROUND: Inflammatory processes have fundamental roles in stroke in both the
etiology of ischemic cerebrovascular disease and the pathophysiology of cerebral
ischemia. We summarize clinical data on infection and inflammation as risk or
trigger factors for human stroke and investigate current evidence for the
hypothesis of a functional interrelation between traditional risk factors,
genetic predisposition, and infection/inflammation in stroke pathogenesis.
SUMMARY OF REVIEW: Several traditional vascular risk factors are associated with
proinflammatory alterations, including leukocyte activation, and predispose
cerebral vasculature to thrombogenesis on inflammatory stimulation. Furthermore,
accumulation of inflammatory cells, mainly monocytes/macrophages, within the
vascular wall starts early during atherogenesis. During later disease stages,
their activation can lead to plaque rupture and thrombus formation, increasing
stroke risk. Inflammatory markers (eg, leukocytes, fibrinogen, C-reactive
protein) are independent predictors of ischemic stroke. Chronic infections (eg,
infection with Chlamydia pneumoniae or Helicobacter pylori) were found to
increase the risk of stroke; however, study results are at variance, residual
confounding is not excluded, and causality is not established at present. In
case-control studies, acute infection within the preceding week was a trigger
factor for ischemic stroke. Acute and exacerbating chronic infection may act by
activating coagulation and chronic infections and may contribute to
atherogenesis. Genetic predisposition of the inflammatory host response may be
an important codeterminant for atherogenesis and stroke risk.
CONCLUSIONS: Inflammation contributes to stroke risk via various interrelated
mechanisms. Infectious diseases, traditional risk factors, and genetic
susceptibility may cooperate in stimulating inflammatory pathways. Final proof
of a causal role of infectious/inflammatory mechanisms in stroke pathogenesis is
still lacking and will require interventional studies.
DOI: 10.1161/01.STR.0000089015.51603.CC
PMID: 14500942 [Indexed for MEDLINE]
|
http://www.ncbi.nlm.nih.gov/pubmed/11412864
|
1. J Neurol Sci. 2001 May 1;186(1-2):1-5. doi: 10.1016/s0022-510x(01)00507-x.
Helicobacter pylori infection as an independent risk factor for cerebral
ischemia of atherothrombotic origin.
Grau AJ(1), Buggle F, Lichy C, Brandt T, Becher H, Rudi J.
Author information:
(1)Department of Neurology, University of Heidelberg, Im Neuenheimer Feld 400,
69120 Heidelberg, Germany. Armin_Grau@med.uni-heidelberg.de
Chronic infection may increase the risk for ischemic stroke. Presently, it is
insufficiently established whether Helicobacter pylori infection represents a
risk factor for ischemic stroke. We analyzed IgG antibodies against H. pylori in
109 patients with acute cerebral ischemia and 82 age- and sex-matched control
patients with non-vascular and non-inflammatory neurological diseases. Antibody
titers were significantly higher in patients than in control subjects (p=0.007).
H. pylori seropositivity tended to be more common in patients (odds ratio (OR)
1.55, 95% confidence interval (ci) 0.87-2.76), but this trend was further
attenuated in multivariate analysis (OR 1.42; 95% 0.75-2.67) with hypertension,
diabetes mellitus, current or previous smoking, previous cerebral ischemia and
low socioeconomic status. H. pylori seropositivity increased the odds for
cerebral ischemia of atherothrombotic origin in univariate (OR 3.63; 95% ci
1.37-9.65) and multivariate analysis (OR 3.53; 95% ci 1.09-11.4). H. pylori
seropositivity may be an independent risk factor for stroke of atherothrombotic
origin.
DOI: 10.1016/s0022-510x(01)00507-x
PMID: 11412864 [Indexed for MEDLINE]
|
http://www.ncbi.nlm.nih.gov/pubmed/16466297
|
1. Expert Rev Neurother. 2006 Feb;6(2):175-83. doi: 10.1586/14737175.6.2.175.
The effect of infections and vaccinations on stroke risk.
Grau AJ(1), Marquardt L, Lichy C.
Author information:
(1)Department of Neurology, Klinikum der Stadt Ludwigshafen, Bremserstr. 79,
67063 Ludwigshafen a. Rh., Germany. graua@klilu.de
There is increasing evidence that, in addition to conventional risk factors,
acute and chronic infectious diseases increase the risk of stroke. Acute
infection, mainly respiratory, and both bacterial and viral infection, represent
temporarily active trigger factors for cerebral ischemia. Chronic infectious
diseases that may increase the risk of stroke include periodontitis, chronic
bronchitis and infections with microbial antigens, such as Helicobacter pylori
and Chlamydia pneumoniae. From observational studies, there is evidence that
vaccination against influenza is associated with a reduced risk of stroke,
myocardial infarction and all-cause mortality. This report provides an overview
on the influence of infection on stroke risk and potential anti-infective
strategies that may play a future role in stroke prevention.
DOI: 10.1586/14737175.6.2.175
PMID: 16466297 [Indexed for MEDLINE]
|
http://www.ncbi.nlm.nih.gov/pubmed/23237251
|
1. Expert Rev Gastroenterol Hepatol. 2012 Dec;6(6):667-74. doi:
10.1586/egh.12.47.
LINX(™) Reflux Management System: magnetic sphincter augmentation in the
treatment of gastroesophageal reflux disease.
Bonavina L(1), DeMeester TR, Ganz RA.
Author information:
(1)Department of Biomedical Sciences for Health, University of Milano Medical
School, Division of General Surgery, IRCCS Policlinico San Donato, Via Morandi
30 20097, San Donato Milanese, Milan, Italy. luigi.bonavina@unimi.it
Gastroesophageal reflux disease (GERD), commonly manifested by heartburn or
regurgitation, is a chronic, progressive condition in which failed sphincter
function allows the contents of the stomach to reflux into the esophagus, the
airways and the mouth. Chronic GERD affects 10% of Western society. The majority
of patients receive adequate relief from proton pump inhibitors, but up to 40%
have incomplete relief of symptoms that cannot be addressed by increasing the
dose of medications. The laparoscopic Nissen fundoplication is the surgical gold
standard; however, the level of technical difficulty and its side effects have
limited its use to less than 1% of the GERD population. These factors have
contributed to the propensity of patients to persist with medical therapy, even
when inadequate to control symptoms and complications of the disease.
Consequently, a significant gap in the treatment continuum for GERD remains
evident in current clinical practice. The LINX(™) Reflux Management System
(Torax Medical) is designed to provide a permanent solution to GERD by
augmenting the physiologic function of the sphincter barrier with a simple and
reproducible laparoscopic procedure that does not alter gastric anatomy and can
be easily reversed if necessary.
DOI: 10.1586/egh.12.47
PMID: 23237251 [Indexed for MEDLINE]
|
http://www.ncbi.nlm.nih.gov/pubmed/18706211
|
1. Chin Med J (Engl). 2008 May 20;121(10):946-51.
Cytotoxin-associated gene-A-seropositive virulent strains of Helicobacter pylori
and atherosclerotic diseases: a systematic review.
Zhang S(1), Guo Y, Ma Y, Teng Y.
Author information:
(1)Department of Neurology, Shengjing Hospital, China Medical University,
Shenyang, Liaoning 110004, China.
OBJECTIVE: A systematic meta-analysis was performed to explore the role of
cytotoxin-associated gene-A (CagA) seropositive strains of Helicobacter pylori
(H. pylori) in the pathogenesis of atherosclerotic diseases. Data sources Data
from Medline, EMBASE, CBMdisc, CNKI and the Cochrane Collaboration database were
searched. Similar search strategies were applied to each of these databases.
Study selection The review was restricted to the case-control studies on
infective, chronic virulent CagA strains of H. pylori, involving the risk of
ischemic stroke and coronary heart disease, ineligible studies were excluded.
Two reviewers independently extracted the data and assessed study quality.
RESULTS: Totally 26 case-control studies (11 studies on ischemic stroke and 15
studies on coronary heart disease) were retrieved and considered. The combined
data revealed that the chronic seropositive virulent strains of H. pylori
infection had a trend of increasing the risk of ischemic strokes and coronary
heart diseases, yielding pooled ORs of 2.68 (95% CI: 2.20, 3.27) and 2.11 (95%
CI: 1.70, 2.62), respectively. We also performed subgroup analyses, dividing the
total population into Caucasian and Chinese subgroups. Through the subgroup
analysis, no significant difference was found between the subgroups.
CONCLUSIONS: Our results support the hypothesis that CagA-seropositive strains
infection is significantly associated with susceptibility to ischemic strokes
and coronary heart diseases. The magnitude of the association with
atherosclerotic diseases needs to be confirmed by prospective studies and the
studies on CagA-seropositive strains eradication are more important.
PMID: 18706211 [Indexed for MEDLINE]
|
http://www.ncbi.nlm.nih.gov/pubmed/8068159
|
1. Pediatr Neurol. 1994 Jun;10(4):317-9. doi: 10.1016/0887-8994(94)90129-5.
Normal serum beta-galactosidase in juvenile GM1 gangliosidosis.
Ishii N(1), Oshima A, Sakuraba H, Fukuyama Y, Suzuki Y.
Author information:
(1)Department of Clinical Genetics, Tokyo Metropolitan Institute of Medical
Science, Japan.
GM1 gangliosidosis is a genetic disease with lysosomal beta-galactosidase
deficiency caused by mutations of the gene coding for this enzyme. However,
apparently normal enzyme activity was found in plasma or serum from juvenile GM1
gangliosidosis patients homozygous for a mutation, R201C (201Arg-->Cys), after
clotting for 30 min. This extracellular fluid finding is unusual in patients
with primary and genetic deficiency of beta-galactosidase. The serum enzyme
activity became relatively low only after 3 1/2-hour clotting because its
increase in normal controls was not observed in these patients.
beta-Galactosidase assay is not always reliable, particularly with serum or
plasma as an enzyme source, for the diagnosis of hereditary beta-galactosidase
deficiency, unless it is conducted under well-controlled conditions.
DOI: 10.1016/0887-8994(94)90129-5
PMID: 8068159 [Indexed for MEDLINE]
|
http://www.ncbi.nlm.nih.gov/pubmed/15166387
|
1. Stroke. 2004 Aug;35(8):1800-4. doi: 10.1161/01.STR.0000131751.35926.48. Epub
2004 May 27.
Association between cerebral ischemia and cytotoxin-associated gene-A-bearing
strains of Helicobacter pylori.
Preusch MR(1), Grau AJ, Buggle F, Lichy C, Bartel J, Black C, Rudi J.
Author information:
(1)Department of Neurology, University of Heidelberg, Germany.
BACKGROUND AND PURPOSE: Studies on Helicobacter pylori infection and risk of
ischemic stroke yielded variable results. Infection with more virulent H. pylori
strains, such as cytotoxin-associated gene-A (CagA)-bearing strains, may be of
particular relevance for ischemic diseases. We investigated whether H. pylori
and CagA seropositivity are independent risk factors for cerebral ischemia or
its etiologic subtypes.
METHODS: We determined IgG antibodies against H. pylori and CagA protein (enzyme
immunoassays) in 190 patients with acute cerebral ischemia and in 229 age- and
sex-matched control subjects selected randomly from the general population.
RESULTS: CagA seropositivity was more common in patients (114/190; 60.0%) than
in control subjects (99/229; 43.2%; odds ratio, 1.97; 95% CI, 1.33 to 2.91;
P<0.001). This result remained significant after adjustment for age, sex,
vascular risk factors and diseases, and childhood and adult social status (odds
ratio, 1.84; 95% CI, 1.13 to 3.00; P=0.015). Subgroup analyses yielded similar
results in all etiologic stroke subtypes. In contrast, H. pylori seropositivity
in general was not associated with increased risk of stroke or its etiologic
subtypes.
CONCLUSIONS: Our results support the hypothesis of an association between
infection with CagA-positive H. pylori strains and acute cerebral ischemia.
DOI: 10.1161/01.STR.0000131751.35926.48
PMID: 15166387 [Indexed for MEDLINE]
|
http://www.ncbi.nlm.nih.gov/pubmed/10571006
|
1. Biochim Biophys Acta. 1999 Oct 8;1455(2-3):85-103. doi:
10.1016/s0925-4439(99)00075-7.
Molecular basis of GM1 gangliosidosis and Morquio disease, type B.
Structure-function studies of lysosomal beta-galactosidase and the non-lysosomal
beta-galactosidase-like protein.
Callahan JW(1).
Author information:
(1)Department of Pediatric Laboratory Medicine, The Hospital for Sick Children,
University of Toronto, ON, Canada. jwc@sickkids.on.ca
GM1 gangliosidosis and Morquio B disease are distinct disorders both clinically
and biochemically yet they arise from the same beta-galactosidase enzyme
deficiency. On the other hand, galactosialidosis and sialidosis share common
clinical and biochemical features, yet they arise from two separate enzyme
deficiencies, namely, protective protein/cathepsin A and neuraminidase,
respectively. However distinct, in practice these disorders overlap both
clinically and biochemically so that easy discrimination between them is
sometimes difficult. The principle reason for this may be found in the fact that
these three enzymes form a unique complex in lysosomes that is required for
their stability and posttranslational processing. In this review, I focus mainly
on the primary and secondary beta-galactosidase deficiency states and offer some
hypotheses to account for differences between GM1 gangliosidosis and Morquio B
disease.
DOI: 10.1016/s0925-4439(99)00075-7
PMID: 10571006 [Indexed for MEDLINE]
|
http://www.ncbi.nlm.nih.gov/pubmed/19842039
|
1. Apoptosis. 2010 Jan;15(1):83-93. doi: 10.1007/s10495-009-0415-x.
Mouse 3T3-L1 cells acquire resistance against oxidative stress as the adipocytes
differentiate via the transcription factor FoxO.
Kojima T(1), Norose T, Tsuchiya K, Sakamoto K.
Author information:
(1)Graduate School of Life and Environmental Sciences, University of Tsukuba,
Tsukuba, Ibaraki 305-8572, Japan.
Repression of excessive increase and enlargement of adipocytes that is closely
associated with obesity is effective in the prevention and treatment of
metabolic syndrome. Generally, apoptosis is induced in cells via a wide variety
of intracellular or extracellular substances, and recently, it has been
suggested that the FoxO subfamily is involved in the induction of apoptosis. We
aimed to elucidate the mechanism of FoxO-mediated apoptosis-induction in the
adipocytes under the reactive oxygen species (ROS) stimulus. The treatment of
differentiated and undifferentiated 3T3-L1 cells with glucose oxidase (GOD), an
enzyme that generates H(2)O(2), induced apoptosis and led to the accumulation of
8-OHdG. Apoptosis analysis revealed that GOD treatment induced apoptosis in
differentiated 3T3-L1 cells less efficiently than in undifferentiated
preadipocytes. GOD remarkably increased the levels of Bad, Bax, and Bim-the
genes that are actively involved in cell apoptosis. GOD treatment also increased
the expression of FoxO3a mRNA and protein. The introduction of FoxO3a-siRNA into
3T3-L1 cells suppressed the oxidative stress-induced expression of Bim mRNA, as
well as the GOD-induced apoptosis. Furthermore, the expression of MnSOD,
Cu/ZnSOD, and catalase, as well as of FoxO, increased significantly along with
the progression of adipocyte differentiation. These results indicated that
ROS-induced apoptosis in undifferentiated 3T3-L1 cells via the expression of
FoxO3a, whereas FoxO expression suppressed the ROS-induced apoptosis in
differentiated 3T3-L1 cells via the expression of ROS-scavenging enzymes.
DOI: 10.1007/s10495-009-0415-x
PMID: 19842039 [Indexed for MEDLINE]
|
http://www.ncbi.nlm.nih.gov/pubmed/1809779
|
1. J Commun Disord. 1991 Oct-Dec;24(5-6):393-409. doi:
10.1016/0021-9924(91)90011-7.
Dysarthria of motor neuron disease: longitudinal measures of segmental
durations.
Seikel JA(1), Wilcox KA, Davis J.
Author information:
(1)Department of Speech and Hearing Sciences, Washington State University,
Pullman 99164-2420.
Erratum in
J Commun Disord 1992 Apr-Jun;25(2-3):201-3.
Motor neuron disease encompasses a group of terminal, demyelinating diseases
affecting upper- and lower-motor neurons and producing muscular weakness
resulting in a flaccid, spastic, or spastic-flaccid dysarthria of speech. The
present study presents measurements of the temporal-acoustic characteristics of
dysarthria in three subjects with Motor Neuron Disease over a two-year recording
period. Changes seen over the course of the disease varied by type of motor
neuron disease, though all types demonstrated some degree of neutralization of
the prevocalic VOT, target vowel duration, and postvocalic closure duration.
These changes are discussed with relation to physical manifestation and
progression of the disease.
DOI: 10.1016/0021-9924(91)90011-7
PMID: 1809779 [Indexed for MEDLINE]
|
http://www.ncbi.nlm.nih.gov/pubmed/22774423
|
1. Span J Psychol. 2012 Jul;15(2):495-504. doi:
10.5209/rev_sjop.2012.v15.n2.38860.
Differential diagnosis between apraxia and dysarthria based on acoustic
analysis.
Melle N(1), Gallego C.
Author information:
(1)Departamento Psicología Básica II, Facultad de Psicología, Universidad
Complutense Madrid, Spain. nmelle@psi.ucm.es
Acoustic analysis provides objective quantitative measures of speech that enable
a comprehensive and accurate understanding of motor disorders and complement the
traditional measures. This paper aims to distinguish between normal and
pathological speech, more specifically between apraxia of speech and spastic
dysarthria in native Spanish speaking patients using acoustic parameters.
Participants (4 aphasic with apraxia of speech, 4 with spastic dysarthria, and
15 without speech disorders) performed three different tasks: repeating the
syllable sequence [pa-ta-ka], repeating the isolated syllable [pa] and repeating
the vowel sequence [i-u]. The results showed that the normative values of motor
control, in general, coincide with those obtained in previous research on native
English speakers. They also show that damage to motor control processes results
in a decrease in the rate of alternating and sequential movements and an
increase in the inter-syllabic time for both types of movements. A subset of the
acoustic parameters analyzed, those that measure motor planning processes,
enable differentiation between normal population and apraxic and dysarthric
patients, and between the latter. The differences between the pathological
groups support the distinction between motor planning and motor programming as
described by van der Merwe's model of sensorimotor processing (1997).
DOI: 10.5209/rev_sjop.2012.v15.n2.38860
PMID: 22774423 [Indexed for MEDLINE]
|
http://www.ncbi.nlm.nih.gov/pubmed/23155537
|
1. Zhonghua Wei Chang Wai Ke Za Zhi. 2012 Sep;15(9):889-92.
[Treatment of gastroesophageal reflux disease: comments from thoracic surgeon].
[Article in Chinese]
Li ZG(1).
Author information:
(1)Department of ThorocicSurgery, Changhai Hospital, Shanghai, China.
dr_lizhigang@hotmail.com
Gastroesophageal reflux disease (GERD) is the most common gastrointestinal
diagnosis recorded during visits to outpatient clinics in west countries. The
prevalence of symptom-defined GERD in China is as high as 3% to 5%. Asa
dysfunction, GERD is characterized by reflux and heartburn. The pathophysiologic
process of GERD is very complicated and subtle. The spectrum of injury from
long-term reflux of acid or bile includes damage mucosa, Barrett's esophagus,
dysplasia, and esophageal cancer. Therefore, the therapies of GERD should focus
on controlling symptom,treating complications, and surveillance the possibility
of oncologic transform. As with therapy with proton-pump inhibitors (PPI),
modifying lifestyle is another most important modality for most GERD. The window
of surgical treatment for GERD is narrow. Surgical therapy is alternative
management approach to the patients with PPI failure, complications, or huge
hernia. The laparoscopic minimally invasive procedure improves the acceptance of
patients to surgical therapy, but the long-term complication and drawbacks of
anti-reflux surgery cannot be ignored, and which is even more common than open
procedures. The limitations of current therapy for GERD have encouraged a search
for more effective treatment.The Linx sphincter augmentation device has been
developed to address this gap with improvement of the barrier function of LES
and reversible design if necessary.
PMID: 23155537 [Indexed for MEDLINE]
|
http://www.ncbi.nlm.nih.gov/pubmed/8112731
|
1. Hum Genet. 1994 Feb;93(2):109-14. doi: 10.1007/BF00210592.
Intracellular processing and maturation of mutant gene products in hereditary
beta-galactosidase deficiency (beta-galactosidosis).
Oshima A(1), Yoshida K, Itoh K, Kase R, Sakuraba H, Suzuki Y.
Author information:
(1)Department of Clinical Genetics, Tokyo Metropolitan Institute of Medical
Science, Japan.
Heterogeneous patterns of biosynthesis, posttranslational processing, and
degradation were demonstrated for mutant enzymes in three clinical forms of
beta-galactosidase deficiency (beta-galactosidosis): juvenile
GM1-gangliosidosis, adult GM1-gangliosidosis, and Morquio B disease. The
precursor of the mutant enzyme in adult GM1-gangliosidosis was not
phosphorylated, and only a small portion of the gene product reached the
lysosomes. The enzyme in Morquio B disease was normally processed and
transported to lysosomes, but its catalytic activity was low. A common gene
mutation in juvenile GM1-gangliosidosis (R201C) produced an enzyme protein that
did not aggregate with protective protein in the lysosome, and was rapidly
degraded by thiol proteases. This abnormal turnover was similar to that for the
normal but dissociated beta-galactosidase in galactosialidosis. Protease
inhibitors restored the enzyme activity in fibroblasts of this clinical form. A
possible therapeutic approach is discussed for this specific type of enzyme
deficiency.
DOI: 10.1007/BF00210592
PMID: 8112731 [Indexed for MEDLINE]
|
http://www.ncbi.nlm.nih.gov/pubmed/17442056
|
1. J Neurochem. 2007 Jun;101(5):1294-302. doi: 10.1111/j.1471-4159.2007.04525.x.
Epub 2007 Apr 17.
Neurochemical, morphological, and neurophysiological abnormalities in retinas of
Sandhoff and GM1 gangliosidosis mice.
Denny CA(1), Alroy J, Pawlyk BS, Sandberg MA, d'Azzo A, Seyfried TN.
Author information:
(1)Biology Department, Boston College, Chestnut Hill, Massachusetts 02467, USA.
Retinal abnormalities are well documented in patients with ganglioside storage
diseases. The total content and distribution of retinal glycosphingolipids was
studied for the first time in control mice and in Sandhoff disease (SD) and GM1
gangliosidosis mice. Light and electron microscopy of the SD and the GM1 retinas
revealed storage in ganglion cells. Similar to previous findings in rat retina,
GD3 was the major ganglioside in mouse retina, while GM2 and GM1 were minor
species. Total ganglioside content was 44% and 40% higher in the SD and the GM1
retinas, respectively, than in the control retinas. Furthermore, GM2 and GM1
content were 11-fold and 51-fold higher in the SD and the GM1 retinas than in
the control retinas, respectively. High concentrations of asialo-GM2 and
asialo-GM1 were found in the SD and the GM1 retinas, respectively, but were
undetectable in the control retinas. The GSL abnormalities in the SD and the GM1
retinas reflect significant reductions in beta-hexosaminidase and
beta-galactosidase enzyme activities, respectively. Although electroretinograms
appeared normal in the SD and the GM1 mice, visual evoked potentials were
subnormal in both mutants, indicating visual impairments. Our findings present a
model system for assessing retinal pathobiology and therapies for the
gangliosidoses.
DOI: 10.1111/j.1471-4159.2007.04525.x
PMID: 17442056 [Indexed for MEDLINE]
|
http://www.ncbi.nlm.nih.gov/pubmed/1909089
|
1. Am J Hum Genet. 1991 Sep;49(3):566-74.
GM1-gangliosidosis (genetic beta-galactosidase deficiency): identification of
four mutations in different clinical phenotypes among Japanese patients.
Nishimoto J(1), Nanba E, Inui K, Okada S, Suzuki K.
Author information:
(1)Department of Neurology, University of North Carolina School of Medicine,
Chapel Hill 27599-7250.
GM1-gangliosidosis is a genetic neurological disorder caused by mutations in the
lysosomal acid beta-galactosidase gene. While its phenotypic expression is
complex, it is usually classified as being of infantile, juvenile, or adult
form, on the basis of age at onset, the rate of symptomatic progression, and
severity of central nervous system involvement. We have analyzed the acid
beta-galactosidase gene in 12 Japanese patients from nine families. The aim was
to identify mutations in individual patients and then to examine possible
correlation between the mutations and the clinical phenotypes. Northern blotting
studies with a full-length human beta-galactosidase cDNA showed that the mRNA
ranged from undetectable to substantially decreased in the infantile patients
but was normal in quantity and size in all juvenile and adult patients. Four
distinct missense mutations have been identified, each limited to the respective
clinical forms within our small-size samples. In the infantile patient with
decreased but detectable mRNA, a point mutation was found resulting in
Arg49----Cys. In the infantile patient with nearly undetectable mRNA, mutation
Arg457----Ter was identified. The mutation Arg201----Cys was found in all four
of the juvenile patients, while all six adult patients were homozygous for the
point mutation Ile51----Thr. The mutations found in the juvenile and adult
patients alter restriction sites in the normal gene and thus are amendable to
quick screening. The prediction that these mutations are responsible for the
clinical disease was confirmed by no expression of the catalytic activity of the
mutant proteins in the COS-I cell expression system.(ABSTRACT TRUNCATED AT 250
WORDS)
PMCID: PMC1683129
PMID: 1909089 [Indexed for MEDLINE]
|
http://www.ncbi.nlm.nih.gov/pubmed/22967682
|
1. BMJ Case Rep. 2012 Sep 11;2012:bcr2012006669. doi: 10.1136/bcr-2012-006669.
Dyke-Davidoff-Masson syndrome-like picture in a case of Takayasu arteritis: an
enigma.
Roy K(1), Talukdar A, Ray S, Pal P.
Author information:
(1)Department of General Medicine, Medical College, Kolkata, India.
Authors describe the case of a 16-year-old girl who presented with fever,
tonic-clonic seizures, unequal arm blood pressures and pulselessness in the left
upper limb. On examination, there was a systolic bruit over umbilical region, a
pansystolic murmur of mitral regurgitation was found. Neurological examination
was normal except for an asymmetry in brain hemicircumference one side compared
with the other. She has borderline intelligence (IQ 70) according to Wechsler
Adult Performance Intelligence Scale. Magnetic resonance imaging (MRI) of brain
revealed atrophic of left cerebral hemisphere with mildly ventricular
dilatation, prominent paranasal and mastoid air cells, suggestive of
Dyke-Davidoff-Masson syndrome (DDMS). Conventional angiography showed narrowed
left internal carotid artery. There was also stenosed brachial artery, absent
left renal artery with narrowed infrarenal abdominal aorta. The patient was put
on antihypertensive drugs. We hypothesise that Takayasu arteritis and related
vascular occlusion is the cause of her acquired cerebral changes.
DOI: 10.1136/bcr-2012-006669
PMCID: PMC4543674
PMID: 22967682 [Indexed for MEDLINE]
|
http://www.ncbi.nlm.nih.gov/pubmed/22538694
|
1. Surg Endosc. 2012 Oct;26(10):2944-9. doi: 10.1007/s00464-012-2289-1. Epub 2012
Apr 27.
The LINX® reflux management system: confirmed safety and efficacy now at 4
years.
Lipham JC(1), DeMeester TR, Ganz RA, Bonavina L, Saino G, Dunn DH, Fockens P,
Bemelman W.
Author information:
(1)Department of Surgery, University of Southern California, 1510 San Pablo
Street, HCC-514, Los Angeles, CA 90033, USA. jlipham@surgery.usc.edu
BACKGROUND: Sphincter augmentation with the LINX® Reflux Management System is a
surgical option for patients with chronic gastroesophageal disease (GERD) and an
inadequate response to proton pump inhibitors (PPIs). Clinical experience with
sphincter augmentation is now available out to 4 years.
METHODS: In a multicenter, prospective, single-arm study, 44 patients underwent
a laparoscopic surgical procedure for placement of the LINX System around the
gastroesophageal junction (GEJ). Each patient's baseline GERD status served as
the control for evaluations post implant. Long-term efficacy measures included
esophageal acid exposure, GERD quality-of-life measures, and use of PPIs.
Adverse events and long-term complications were closely monitored.
RESULTS: For esophageal acid exposure, the mean total % time pH < 4 was reduced
from 11.9 % at baseline to 3.8 % at 3 years (p < 0.001), with 80 % (18/20) of
patients achieving pH normalization (≤ 5.3 %). At ≥ 4 years, 100 % (23/23) of
the patients had improved quality-of-life measures for GERD, and 80 % (20/25)
had complete cessation of the use of PPIs. There have been no reports of death
or long-term device-related complications such as migration or erosion.
CONCLUSIONS: Sphincter augmentation with the LINX Reflux Management System
provided long-term clinical benefits with no safety issues, as demonstrated by
reduced esophageal acid exposure, improved GERD-related quality of life, and
cessation of dependence on PPIs, with minimal side effects and no safety issues.
Patients with inadequate symptom control with acid suppression therapy may
benefit from treatment with sphincter augmentation.
DOI: 10.1007/s00464-012-2289-1
PMID: 22538694 [Indexed for MEDLINE]
|
http://www.ncbi.nlm.nih.gov/pubmed/10757351
|
1. Hum Gene Ther. 2000 Mar 20;11(5):715-27. doi: 10.1089/10430340050015617.
Correction of acid beta-galactosidase deficiency in GM1 gangliosidosis human
fibroblasts by retrovirus vector-mediated gene transfer: higher efficiency of
release and cross-correction by the murine enzyme.
Sena-Esteves M(1), Camp SM, Alroy J, Breakefield XO, Kaye EM.
Author information:
(1)Molecular Neurogenetics Unit, Massachusetts General Hospital, Harvard Medical
School, Boston 02129, USA.
Mutations in the lysosomal acid beta-galactosidase (EC 3.2.1.23) underlie two
different disorders: GM1 gangliosidosis, which involves the nervous system and
visceral organs to varying extents, and Morquio's syndrome type B (Morquio B
disease), which is a skeletal-connective tissue disease without any CNS
symptoms. This article shows that transduction of human GM1 gangliosidosis
fibroblasts with retrovirus vectors encoding the human acid beta-galactosidase
cDNA leads to complete correction of the enzymatic deficiency. The newly
synthesized enzyme is correctly processed and targeted to the lysosomes in
transduced cells. Cross-correction experiments using retrovirus-modified cells
as enzyme donors showed, however, that the human enzyme is transferred at low
efficiencies. Experiments using a different retrovirus vector carrying the human
cDNA confirmed this observation. Transduction of human GM1 fibroblasts and mouse
NIH 3T3 cells with a retrovirus vector encoding the mouse beta-galactosidase
cDNA resulted in high levels of enzymatic activity. Furthermore, the mouse
enzyme was found to be transferred to human cells at high efficiency. Enzyme
activity measurements in medium conditioned by genetically modified cells
suggest that the human beta-galactosidase enzyme is less efficiently released to
the extracellular space than its mouse counterpart. This study suggests that
lysosomal enzymes, contrary to the generalized perception in the field of gene
therapy, may differ significantly in their properties and provides insights for
design of future gene therapy interventions in acid beta-galactosidase
deficiency.
DOI: 10.1089/10430340050015617
PMID: 10757351 [Indexed for MEDLINE]
|
http://www.ncbi.nlm.nih.gov/pubmed/2837434
|
1. Hum Hered. 1988;38(2):76-82. doi: 10.1159/000153762.
Lysosomal enzyme activities among Chinese: leukocyte alpha-galactosidase and
beta-galactosidase.
Xu YK(1), Ng WG.
Author information:
(1)Department of Pediatrics, University of Southern California School of
Medicine, Los Angeles.
alpha-Galactosidase and beta-galactosidase activities have been determined in
leukocyte preparations from 100 randomly selected Chinese adults. For
alpha-galactosidase, two groups with low activities were identified: group I
consisted of 3 females having activities below 40% of normal, and group II
consisted of 5 males and 1 female with activities about 60% of normal. Family
studies suggested that these low alpha-galactosidase activities are genetically
determined. Only 1 individual was found to have about 50% of normal
beta-galactosidase activity; presumably he is a carrier for beta-galactosidase
deficiency (GM1 gangliosidosis).
DOI: 10.1159/000153762
PMID: 2837434 [Indexed for MEDLINE]
|
http://www.ncbi.nlm.nih.gov/pubmed/25264655
|
1. Am Surg. 2014 Oct;80(10):1034-8.
Magnetic sphincter augmentation with the LINX device for gastroesophageal reflux
disease after U.S. Food and Drug Administration approval.
Reynolds JL(1), Zehetner J, Bildzukewicz N, Katkhouda N, Dandekar G, Lipham JC.
Author information:
(1)Keck Medical Center of the University of Southern California, Los Angeles,
California, USA.
Magnetic sphincter augmentation (MSA) of the gastroesophageal junction with the
LINX Reflux Management System is an alternative to fundoplication for
gastroesophageal reflux disease (GERD) that was approved by the U.S. Food and
Drug Administration (FDA) in March 2012. This is a prospective observational
study of all patients who underwent placement of the LINX at two institutions
from April 2012 to December 2013 to evaluate our clinical experience with the
LINX device after FDA approval. There were no intraoperative complications and
only four mild postoperative morbidities: three urinary retentions and one
readmission for dehydration. The mean operative time was 60 minutes (range, 31
to 159 minutes) and mean length of stay was 11 hours (range, 5 to 35 hours).
GERD health-related quality-of-life scores were available for 83 per cent of
patients with a median follow-up of five months (range, 3 to 14 months) and a
median score of four (range, 0 to 26). A total of 76.9 per cent of patients were
no longer taking proton pump inhibitors. The most common postoperative complaint
was dysphagia, which resolved in 79.1 per cent of patients with a median time to
resolution of eight weeks. There were eight patients with persistent dysphagia
that required balloon dilation with improvement in symptoms. MSA with LINX is a
safe and effective alternative to fundoplication for treatment of GERD. The most
common postoperative complaint is mild to moderate dysphagia, which usually
resolves within 12 weeks.
PMID: 25264655 [Indexed for MEDLINE]
|
http://www.ncbi.nlm.nih.gov/pubmed/3088302
|
1. Jpn J Exp Med. 1986 Feb;56(1):1-11.
Abnormalities of cerebral lipids in GM1-gangliosidoses, infantile, juvenile, and
chronic type.
Kasama T, Taketomi T.
Cerebral lipids of patients with GM1-gangliosidoses, infantile, juvenile, and
chronic type which are caused by deficiency of beta-galactosidase, were examined
and compared to each other. The infantile type demonstrated abnormal
accumulation of GM1 and asialo-GM1 in contrast with marked decrease in such
major cerebral lipids as cholesterol, phospholipids, cerebroside, and sulfatide.
It was also noted that significant amounts of such unusual lipids as free fatty
acids, GlcCer, LacCer, GbOse3Cer, and GbOse-4Cer plus nLcOse4Cer were found in
the brain. These findings pointed out that this infantile type might accompany a
severe cerebral dysgenesis with poor myelination. The juvenile type also showed
marked increase in GM1 and asialo-GM1, but the decrease in cholesterol,
phospholipids, cerebroside, and sulfatide was not so much as the infantile type.
These findings along with the occurrence of cholesterol ester suggested that the
brain caused progressive demyelination after the immature myelin appeared. An
autopsized brain tissue of a male patient who was eventually diagnosed as a case
of GM1-gangliosidosis chronic type after his death, showed some accumulation of
GM1 and asialo-GM1 particularly in the caudate nucleus and putamen, whereas it
showed moderate amounts of GM1 in apparently normal gray and white matters. It
seemed that there are no abnormal cerebral lipids except for gangliosides and
some neutral glycosphingolipids in the chronic type.
PMID: 3088302 [Indexed for MEDLINE]
|
http://www.ncbi.nlm.nih.gov/pubmed/23622392
|
1. Handb Clin Neurol. 2013;113:1707-8. doi: 10.1016/B978-0-444-59565-2.00039-3.
Gangliosidoses.
Patterson MC(1).
Author information:
(1)Division of Child and Adolescent Neurology, Mayo Clinic, Rochester, MN, USA.
Electronic address: patterson.marc@mayo.edu.
The gangliosidoses comprise a family of lysosomal storage diseases characterized
by the accumulation of complex glycosphingolipids in the nervous system and
other tissues, secondary to the deficient activity of lysosomal hydrolases or
their associated activator proteins. GM1 and GM2 gangliosidosis are associated
with deficiency of β-galactosidase and β-hexosaminidase respectively. All
gangliosidoses are characterized by progressive neurodegeneration, the severity
of which is proportional to the residual enzyme activity. The GM1 gangliosidoses
are characterized by dysostosis, organomegaly and coarsening in their most
severe forms, whereas children with classic infantile GM2 gangliosidosis
(Tay-Sachs disease) are usually spared systemic involvement, except in the case
of the Sandhoff variant, in which organomegaly may occur. Cherry-red macular
spots occur in the early onset forms of the gangliosidoses, but are less
frequently seen in the less severe, later onset phenotypes. Macrocephaly, an
exaggerated startle response, cognitive decline, seizures, ataxia, and
progressive muscular atrophy may occur in different forms of gangliosidosis. The
diagnosis is made by assay of enzyme activity, and can be confirmed by mutation
analysis. Carrier screening for Tay-Sachs disease has been remarkably successful
in reducing the incidence of this disease in the at-risk Ashkenazi population.
There are no proven disease-modifying therapies for the gangliosidoses.
Copyright © 2013 Elsevier B.V. All rights reserved.
DOI: 10.1016/B978-0-444-59565-2.00039-3
PMID: 23622392 [Indexed for MEDLINE]
|
http://www.ncbi.nlm.nih.gov/pubmed/17250509
|
1. Pediatr Int. 2007 Feb;49(1):70-5. doi: 10.1111/j.1442-200X.2007.02299.x.
Cerebral hemiatrophy (Dyke-Davidoff-Masson syndrome) in childhood:
clinicoradiological analysis of 19 cases.
Atalar MH(1), Icagasioglu D, Tas F.
Author information:
(1)Department of Radiology, Division of Pediatric Neurology, Cumhuriyet
University, Faculty of Medicine, Sivas, Turkey. mehmet5896@yahoo.com
BACKGROUND: The purpose of this study was to emphasize the clinical and imaging
findings of 19 child cases of cerebral hemiatrophy.
METHODS: A total of 11 male and eight female patients underwent assessment with
computed tomography and magnetic resonance imaging. The patients ranged from 1
to 17 years in age. The evaluated parameters were: location of the lesions,
midline structural shift effect, ipsilateral calvarial and parenchymal changes.
RESULTS: Left cerebral hemiatrophy was seen in 14 of the cases while right
cerebral hemiatrophy was observed in five cases. Unilateral calvarial thickening
was seen in 11 cases, hyperpneumatization of paranasal sinuses in five, and
hypoplasia of the middle frontal cranial fossa in three patients. Cerebral
peduncle atrophy was noted in seven cases. In total, 11 patients had thalamic
atrophy and lentiform nucleus hypoplasia. In one case, cerebral hemiatrophy was
associated with ipsilateral large schizencephalic cleft and absence of the
septum pellucidum, whereas in another case, there was diffuse cerebellar atrophy
associated with cerebral hemiatrophy.
CONCLUSION: Computed tomography and, in particular, magnetic resonance imaging
are the procedures of choice with respect to assessment of the etiology and
extent of cerebral parenchymal involvement in cerebral hemiatrophy.
DOI: 10.1111/j.1442-200X.2007.02299.x
PMID: 17250509 [Indexed for MEDLINE]
|
http://www.ncbi.nlm.nih.gov/pubmed/23672850
|
1. Ital J Pediatr. 2013 May 14;39:32. doi: 10.1186/1824-7288-39-32.
Dyke-Davidoff-Masson syndrome: case report of fetal unilateral ventriculomegaly
and hypoplastic left middle cerebral artery.
Piro E(1), Piccione M, Marrone G, Giuffrè M, Corsello G.
Author information:
(1)Department of Sciences for Health Promotion and Mother and Child Care
"Giuseppe D'Alessandro", University of Palermo, Palermo, Italy.
ettore.piro@unipa.it
Prenatal ultrasonographic detection of unilateral cerebral ventriculomegaly
arises suspicion of pathological condition related to cerebrospinal fluid flow
obstruction or cerebral parenchimal pathology. Dyke-Davidoff-Masson syndrome is
a rare condition characterized by cerebral hemiatrophy, calvarial thickening,
skull and facial asymmetry, contralateral hemiparesis, cognitive impairment and
seizures. Congenital and acquired types are recognized and have been described,
mainly in late childhood, adolescence and adult ages. We describe a female
infant with prenatal diagnosis of unilateral left ventriculomegaly in which
early brain MRI and contrast enhanced-MRI angiography, showed cerebral left
hemiatrophy associated with reduced caliber of the left middle cerebral artery
revealing the characteristic findings of the Dyke-Davidoff-Masson syndrome.
Prenatal imaging, cerebral vascular anomaly responsible for the cerebral
hemiatrophy and the early clinical evolution have never been described before in
such a young child and complete the acquired clinical descriptions in older
children. Differential diagnosis, genetic investigations, neurophysiologic
assessments, short term clinical and developmental follow up are described.
Dyke-Davidoff-Masson syndrome must be ruled out in differential diagnosis of
fetal unilateral ventriculomegaly. Early clinical assessment, differential
diagnosis and cerebral imaging including cerebral MRI angiography allow the
clinicians to diagnose also in early infancy this rare condition.
DOI: 10.1186/1824-7288-39-32
PMCID: PMC3666998
PMID: 23672850 [Indexed for MEDLINE]
|
http://www.ncbi.nlm.nih.gov/pubmed/1588015
|
1. J Child Neurol. 1992 Apr;7 Suppl:S41-50. doi: 10.1177/08830738920070010711.
GM1 gangliosidosis type 2 in two siblings.
Gascon GG(1), Ozand PT, Erwin RE.
Author information:
(1)Department of Pediatrics, King Faisal Specialist Hospital and Research
Centre, Riyadh, Saudi Arabia.
A sister and brother, now aged 7 and 9 years, presented with developmental
arrest, gait disturbance, dementia, and a progressive myoclonic epilepsy
syndrome with hyperacusis in the second year of life. Then, spastic
quadriparesis led to a decerebrate state. In the absence of macular or retinal
degeneration, organomegaly, and somatic-facial features suggesting
mucopolysaccharidosis, the presence of hyperacusis together with sea-blue
histiocytes in bone marrow biopsies and deficient beta-galactosidase activity
but normal glucosidase, hexosaminidase, and neuraminidase activity on lysosomal
enzyme assays constitutes the clinical-pathologic-biochemical profile of GM1
gangliosidosis type 2. This is a rare, late infantile onset, progressive
gray-matter disease in which beta-galactosidase deficiency is largely localized
to the brain, though it can be demonstrated in leukocytes and cultured skin
fibroblasts. It must be distinguished from the Jansky-Bielschowsky presentation
of neuronal ceroid lipofuscinosis, mitochondrial encephalopathy, lactic
acidosis, strokelike episodes (MELAS) and myoclonic epilepsy with ragged-red
fibers (MERRF) syndromes, atypical presentations of GM2 gangliosidoses
(Tay-Sachs and Sandhoff's diseases), primary sialidosis (neuraminidase
deficiency), galactosialidosis, and Alpers' disease.
DOI: 10.1177/08830738920070010711
PMID: 1588015 [Indexed for MEDLINE]
|
http://www.ncbi.nlm.nih.gov/pubmed/3084261
|
1. Eur J Cell Biol. 1986 Mar;40(1):9-15.
Immunoelectron microscopical localization of lysosomal beta-galactosidase and
its precursor forms in normal and mutant human fibroblasts.
Willemsen R, Hoogeveen AT, Sips HJ, van Dongen JM, Galjaard H.
Immunoelectron microscopy was performed to study the biosynthesis of lysosomal
beta-galactosidase (beta-gal) in normal and mutant human fibroblasts. Using
polyclonal and monoclonal antibodies we show in normal cells precursor forms of
beta-gal in the rough endoplasmic reticulum (RER) and in the Golgi apparatus
throughout the stack of cisternae. In the lysosomes virtually all beta-gal
exists as a high molecular weight multimer of mature enzyme. In the autosomal
recessive disease GM1-gangliosidosis caused by a beta-gal deficiency and in
galactosialidosis, associated with a combined deficiency of lysosomal
neuraminidase and beta-gal, precursor forms of the latter enzyme are found in
RER, Golgi and some labeling is present at the cell surface. The lysosomes
remain unlabeled, indicative for the absence of enzyme molecules in this
organelle. In galactosialidosis fibroblasts also no mature beta-gal is found in
the lysosomes but in these cells the presence of the monomeric form can be
increased by leupeptin (inhibition of proteolysis) whereas addition of a partly
purified 32 kDa "protective protein" results in the restoration of high
molecular weight beta-gal multimers in the lysosomes.
PMID: 3084261 [Indexed for MEDLINE]
|
http://www.ncbi.nlm.nih.gov/pubmed/23189018
|
1. J Neurosci Rural Pract. 2012 Sep;3(3):411-3. doi: 10.4103/0976-3147.102646.
Dyke-Davidoff-Masson syndrome.
Behera MR(1), Patnaik S, Mohanty AK.
Author information:
(1)Department of Paediatrics, Kalinga Institute of Medical Sciences (KIMS), KIIT
University, Patia, Bhubaneswar, Orissa, India.
A 14-month-old male child presented with recurrent generalized seizures, spastic
hemiplegia, microcephaly and had developmental delay in motor and speech
domains. CT of the brain revealed characteristic features diagnostic of
infantile type of cerebral hemiatrophy or Dyke-Davidoff-Masson syndrome.
DOI: 10.4103/0976-3147.102646
PMCID: PMC3505357
PMID: 23189018
Conflict of interest statement: Conflict of Interest: None declared
|
http://www.ncbi.nlm.nih.gov/pubmed/19097769
|
1. Ann Anat. 2009 Apr;191(2):225-7. doi: 10.1016/j.aanat.2008.09.007. Epub 2008
Nov 13.
Postmortal diagnosis of a Dyke-Davidoff-Masson syndrome in a 75-year-old
woman---a case report.
Stoevesandt D(1), Stock K, Spielmann RP, Heine HJ, Paulsen F, Bräuer L.
Author information:
(1)Department of Radiology, Martin Luther-University Halle-Wittenberg, 06120
Halle/Saale, Germany. dietrich.stoevesandt@medizin.uni-halle.de
The Dyke-Davidoff-Masson syndrome is characterized by various symptoms related
to hemiatrophy of the cerebrum and hypertrophy of the ipsilateral calvarium and
paranasal sinuses. Clinical findings include hemiparesis or hemiplegia, seizures
and/or mental retardation. The present report discusses the very unusual case of
a late-diagnosed Dyke-Davidoff-Masson syndrome in a 75-year-old body donor who
had suffered a left-sided stroke associated with the internal carotid artery in
the course of tonsillitis at the age of 5.
DOI: 10.1016/j.aanat.2008.09.007
PMID: 19097769 [Indexed for MEDLINE]
|
http://www.ncbi.nlm.nih.gov/pubmed/20236868
|
1. Epilepsy Behav. 2010 Apr;17(4):536-40. doi: 10.1016/j.yebeh.2010.02.006. Epub
2010 Mar 16.
Right cerebral hemiatrophy: neurocognitive and electroclinical features.
Demirtas-Tatlidede A(1), Yalcin AD, Uysal E, Forta H.
Author information:
(1)Department of Neurology, Sisli Etfal Research and Training Hospital,
Istanbul, Turkey. aslidemirtas@yahoo.com
The purpose of this study was to retrospectively evaluate the cognitive and
electroclinical characteristics of right cerebral hemiatrophy
(Dyke-Davidoff-Masson syndrome [DDMS]). Cognitive assessments with a particular
emphasis on visuospatial functions, electroclinical features, and neuroimaging
characteristics were analyzed for five patients with a clinically and
neuroradiologically confirmed diagnosis of right-sided DDMS. Intelligence tests
revealed mental retardation in all but one. Neuropsychological assessments
demonstrated consistent impairments in tasks that have a spatial component
(spatial processing and orientation discrimination), whereas attention,
executive functions and verbal memory domains were variably impaired.
Electroclinically, the main seizure types were simple partial motor, complex
partial, and secondarily generalized seizures. Interictal EEG delineated lower
amplitudes and slow background activity in the affected hemisphere. Overall, the
cognitive performance of patients with DDMS encompasses a broad spectrum of
impairments affecting multiple domains. Our findings support the concept that
dorsal visual pathways responsible for spatial processing may be lateralized to
the right hemisphere.
Copyright (c) 2010 Elsevier Inc. All rights reserved.
DOI: 10.1016/j.yebeh.2010.02.006
PMID: 20236868 [Indexed for MEDLINE]
|
http://www.ncbi.nlm.nih.gov/pubmed/15086521
|
1. J Neurochem. 2004 May;89(3):645-53. doi: 10.1046/j.1471-4159.2004.02381.x.
N-butyldeoxygalactonojirimycin reduces neonatal brain ganglioside content in a
mouse model of GM1 gangliosidosis.
Kasperzyk JL(1), El-Abbadi MM, Hauser EC, D'Azzo A, Platt FM, Seyfried TN.
Author information:
(1)Department of Biology, Boston College, Chestnut Hill, Massachussetts, USA.
GM1 gangliosidosis is a glycosphingolipid (GSL) lysosomal storage disease caused
by a genetic deficiency of acid beta-galactosidase (beta-gal), the enzyme that
catabolyzes GM1 within lysosomes. Accumulation of GM1 and its asialo form (GA1)
occurs primarily in the brain, leading to progressive neurodegeneration and
brain dysfunction. Substrate reduction therapy aims to decrease the rate of GSL
biosynthesis to counterbalance the impaired rate of catabolism. The imino sugar
N-butyldeoxygalactonojirimycin (NB-DGJ) is a competitive inhibitor of the
ceramide-specific glucosyltransferase that catalyzes the first step in GSL
biosynthesis. Neonatal C57BL/6J (B6) and beta-gal knockout (-/-) mice were
injected daily from post-natal day 2 (p-2) to p-5 with either vehicle or NB-DGJ
at 600 mg or 1200 mg/kg body weight. These drug concentrations significantly
reduced total brain ganglioside and GM1 content in the B6 and the beta-gal (-/-)
mice. Drug treatment had no significant effect on viability, body weight, brain
weight, or brain water content in the B6 and beta-gal (-/-) mice. Significant
elevations in neutral lipids (GA1, ceramide, and sphingomyelin) were observed in
the NB-DGJ-treated beta-gal (-/-) mice, but were not associated with adverse
effects. Also, NB-DGJ treatment of B6 and beta-gal (-/-) mice from p-2 to p-5
had no subsequent effect on brain ganglioside content at p-21. Our results show
that NB-DGJ is effective in reducing total brain ganglioside and GM1 content at
early neonatal ages. These findings suggest that substrate reduction therapy
using NB-DGJ may be an effective early intervention for GM1 gangliosidosis and
possibly other GSL lysosomal storage diseases.
DOI: 10.1046/j.1471-4159.2004.02381.x
PMID: 15086521 [Indexed for MEDLINE]
|
http://www.ncbi.nlm.nih.gov/pubmed/21559157
|
1. J Pediatr Neurosci. 2010 Jul;5(2):124-5. doi: 10.4103/1817-1745.76108.
Dyke-Davidoff-Masson syndrome: Classical imaging findings.
Singh P(1), Saggar K, Ahluwalia A.
Author information:
(1)Department of Radiodiagnosis, Dayanand Medical College & Hospital, Ludhiana,
Punjab, India.
A 15-year-old female presented with seizures, right-sided hemiparesis,
hemiatrophy of the right side of the body and mental retardation. MRI brain
revealed characteristic features diagnostic of congenital type of cerebral
hemiatrophy or Dyke-Davidoff-Masson syndrome.
DOI: 10.4103/1817-1745.76108
PMCID: PMC3087988
PMID: 21559157
Conflict of interest statement: Conflict of Interest: None declared.
|
http://www.ncbi.nlm.nih.gov/pubmed/23523468
|
1. Biochim Biophys Acta. 2013 Aug;1832(8):1194-206. doi:
10.1016/j.bbadis.2013.03.005. Epub 2013 Mar 20.
Barth syndrome: cellular compensation of mitochondrial dysfunction and apoptosis
inhibition due to changes in cardiolipin remodeling linked to tafazzin (TAZ)
gene mutation.
Gonzalvez F(1), D'Aurelio M, Boutant M, Moustapha A, Puech JP, Landes T,
Arnauné-Pelloquin L, Vial G, Taleux N, Slomianny C, Wanders RJ, Houtkooper RH,
Bellenguer P, Møller IM, Gottlieb E, Vaz FM, Manfredi G, Petit PX.
Author information:
(1)INSERM U-747 et Université Paris V-Descartes, Centre de Recherche des
Saint-Pères, 45 Rue des Saint-Pères, 75006 Paris, France.
Cardiolipin is a mitochondrion-specific phospholipid that stabilizes the
assembly of respiratory chain complexes, favoring full-yield operation. It also
mediates key steps in apoptosis. In Barth syndrome, an X chromosome-linked
cardiomyopathy caused by tafazzin mutations, cardiolipins display acyl chain
modifications and are present at abnormally low concentrations, whereas
monolysocardiolipin accumulates. Using immortalized lymphoblasts from Barth
syndrome patients, we showed that the production of abnormal cardiolipin led to
mitochondrial alterations. Indeed, the lack of normal cardiolipin led to changes
in electron transport chain stability, resulting in cellular defects. We found a
destabilization of the supercomplex (respirasome) I+III2+IVn but also decreased
amounts of individual complexes I and IV and supercomplexes I+III and III+IV. No
changes were observed in the amounts of individual complex III and complex II.
We also found decreased levels of complex V. This complex is not part of the
supercomplex suggesting that cardiolipin is required not only for the
association/stabilization of the complexes into supercomplexes but also for the
modulation of the amount of individual respiratory chain complexes. However,
these alterations were compensated by an increase in mitochondrial mass, as
demonstrated by electron microscopy and measurements of citrate synthase
activity. We suggest that this compensatory increase in mitochondrial content
prevents a decrease in mitochondrial respiration and ATP synthesis in the cells.
We also show, by extensive flow cytometry analysis, that the type II apoptosis
pathway was blocked at the mitochondrial level and that the mitochondria of
patients with Barth syndrome cannot bind active caspase-8. Signal transduction
is thus blocked before any mitochondrial event can occur. Remarkably, basal
levels of superoxide anion production were slightly higher in patients' cells
than in control cells as previously evidenced via an increased protein
carbonylation in the taz1Δ mutant in the yeast. This may be deleterious to cells
in the long term. The consequences of mitochondrial dysfunction and alterations
to apoptosis signal transduction are considered in light of the potential for
the development of future treatments.
Copyright © 2013 Elsevier B.V. All rights reserved.
DOI: 10.1016/j.bbadis.2013.03.005
PMID: 23523468 [Indexed for MEDLINE]
|
http://www.ncbi.nlm.nih.gov/pubmed/24342716
|
1. Mol Genet Metab. 2014 Jan;111(1):26-32. doi: 10.1016/j.ymgme.2013.11.006. Epub
2013 Nov 19.
Tafazzin splice variants and mutations in Barth syndrome.
Kirwin SM(1), Manolakos A(2), Barnett SS(2), Gonzalez IL(2).
Author information:
(1)Molecular Diagnostics Laboratory, Nemours/Alfred I. duPont Hospital for
Children, Wilmington, DE, USA. Electronic address: susan.kirwin@nemours.org.
(2)Molecular Diagnostics Laboratory, Nemours/Alfred I. duPont Hospital for
Children, Wilmington, DE, USA.
Barth syndrome is caused by mutations in the TAZ (tafazzin) gene on human
chromosome Xq28. The human tafazzin gene produces four major mRNA splice
variants; two of which have been shown to be functional (TAZ lacking exon 5 and
full-length) in complementation studies with yeast and Drosophila. This study
characterizes the multiple alternative splice variants of TAZ mRNA and their
proportions in blood samples from a cohort of individuals with Barth syndrome
(BTHS). Because it has been reported that collection and processing methods can
affect the expression of various genes, we tested and chose a stabilizing medium
for collecting, shipping and processing of the blood samples of these
individuals. In both healthy controls and in BTHS individuals, we found a
greater variety of alternatively spliced forms than previously described, with a
sizeable proportion of minor splice variants besides the four dominant isoforms.
Individuals with certain exonic and intronic splice mutations produce additional
mutant mRNAs that could be translated into two or more proteins with different
amino acid substitutions in a single individual. A fraction of the minor splice
variants is predicted to be non-productive.
Copyright © 2013 Elsevier Inc. All rights reserved.
DOI: 10.1016/j.ymgme.2013.11.006
PMID: 24342716 [Indexed for MEDLINE]
|
http://www.ncbi.nlm.nih.gov/pubmed/24481314
|
1. Aging (Albany NY). 2014 Jan;6(1):48-57. doi: 10.18632/aging.100633.
BMAL1-dependent regulation of the mTOR signaling pathway delays aging.
Khapre RV(1), Kondratova AA, Patel S, Dubrovsky Y, Wrobel M, Antoch MP,
Kondratov RV.
Author information:
(1)Center for Gene Regulation in Health and Diseases, BGES, Cleveland State
University, Cleveland, OH.
The circadian clock, an internal time-keeping system, has been linked with
control of aging, but molecular mechanisms of regulation are not known. BMAL1 is
a transcriptional factor and core component of the circadian clock; BMAL1
deficiency is associated with premature aging and reduced lifespan. Here we
report that activity of mammalian Target of Rapamycin Complex 1 (mTORC1) is
increased upon BMAL1 deficiency both in vivo and in cell culture. Increased mTOR
signaling is associated with accelerated aging; in accordance with that,
treatment with the mTORC1 inhibitor rapamycin increased lifespan of Bmal1-/-
mice by 50%. Our data suggest that BMAL1 is a negative regulator of mTORC1
signaling. We propose that the circadian clock controls the activity of the mTOR
pathway through BMAL1-dependent mechanisms and this regulation is important for
control of aging and metabolism.
DOI: 10.18632/aging.100633
PMCID: PMC3927809
PMID: 24481314 [Indexed for MEDLINE]
Conflict of interest statement: The authors of this paper declare no conflict of
interests.
|
http://www.ncbi.nlm.nih.gov/pubmed/20519775
|
1. Aging (Albany NY). 2010 May;2(5):285-97. doi: 10.18632/aging.100142.
Circadian clock proteins control adaptation to novel environment and memory
formation.
Kondratova AA(1), Dubrovsky YV, Antoch MP, Kondratov RV.
Author information:
(1)Lerner Research Institute, Cleveland Clinic, OH 44195, USA.
Comment in
Aging (Albany NY). 2010 May;2(5):251-4. doi: 10.18632/aging.100144.
Aging (Albany NY). 2010 May;2(5):259-60. doi: 10.18632/aging.100148.
Aging (Albany NY). 2010 Jun;2(6):320-1. doi: 10.18632/aging.100154.
Deficiency of the transcription factor BMAL1, a core component of the circadian
clock, results in an accelerated aging phenotype in mice. The circadian clock
regulates many physiological processes and was recently implicated in control of
brain-based activities, such as memory formation and the regulation of emotions.
Aging is accompanied by the decline in brain physiology, particularly decline in
the response and adaptation to novelty. We investigated the role of the
circadian clock in exploratory behavior and habituation to novelty using the
open field paradigm. We found that mice with a deficiency of the circadian
transcription factor BMAL1 display hyperactivity in novel environments and
impaired intra- and intersession habituation, indicative of defects in short-
and long-term memory formation. In contrast, mice double-deficient for the
circadian proteins CRY1 and CRY2 (repressors of the BMAL1-mediated
transcription) demonstrate reduced activity and accelerated habituation when
compared to wild type mice. Mice with mutation in theClock gene (encoding the
BMAL1 transcription partner) show normal locomotion, but increased rearing
activity and impaired intersession habituation. BMAL1 is highly expressed in the
neurons of the hippocampus - a brain region associated with spatial memory
formation; BMAL1 deficiency disrupts circadian oscillation in gene expression
and reactive oxygen species homeostasis in the brain, which may be among the
possible mechanisms involved. Thus, we suggest that the BMAL1:CLOCK activity is
critical for the proper exploratory and habituation behavior, and that the
circadian clock prepares organism for a new round of everyday activities through
optimization of behavioral learning.
DOI: 10.18632/aging.100142
PMCID: PMC2898019
PMID: 20519775 [Indexed for MEDLINE]
Conflict of interest statement: The authors of this manuscript have no conflict
of interests to declare.
|
http://www.ncbi.nlm.nih.gov/pubmed/21149897
|
1. Aging (Albany NY). 2010 Dec;2(12):936-44. doi: 10.18632/aging.100241.
Deficiency of circadian protein CLOCK reduces lifespan and increases age-related
cataract development in mice.
Dubrovsky YV(1), Samsa WE, Kondratov RV.
Author information:
(1)Department of Biological, Geological and Environmental Sciences and Center
for Gene Regulation in Health and Disease, Cleveland State University,
Cleveland, OH 44115, USA.
Circadian clock is implicated in the regulation of aging. The transcription
factor CLOCK, a core component of the circadian system, operates in complex with
another circadian clock protein BMAL1. Recently it was demonstrated that BMAL1
deficiency results in premature aging in mice. Here we investigate the aging of
mice deficient for CLOCK protein. Deficiency of the CLOCK protein significantly
affects longevity: the average lifespan of Clock-/- mice is reduced by 15%
compared with wild type mice, while maximum lifespan is reduced by more than
20%. CLOCK deficiency also results in the development of two age-specific
pathologies in these mice, cataracts and dermatitis, at a much higher rate than
in wild type mice. In contrast to BMAL1 deficient animals, Clock-/- mice do not
develop a premature aging phenotype and do not develop the multiple
age-associated pathologies characteristic of BMAL1 deficiency. Thus, although
CLOCK and BMAL1 form a transcriptional complex, the physiological result of
their deficiency is different. Our results suggest that CLOCK plays an important
role in aging, specifically; CLOCK activity is critical for the regulation of
normal physiology and aging of the lens and skin.
DOI: 10.18632/aging.100241
PMCID: PMC3034182
PMID: 21149897 [Indexed for MEDLINE]
Conflict of interest statement: The authors of this paper declare no conflict of
interests.
|
http://www.ncbi.nlm.nih.gov/pubmed/23104054
|
1. Nat Struct Mol Biol. 2012 Dec;19(12):1257-65. doi: 10.1038/nsmb.2434. Epub
2012 Oct 28.
Phf19 links methylated Lys36 of histone H3 to regulation of Polycomb activity.
Ballaré C(1), Lange M, Lapinaite A, Martin GM, Morey L, Pascual G, Liefke R,
Simon B, Shi Y, Gozani O, Carlomagno T, Benitah SA, Di Croce L.
Author information:
(1)Department of Gene Regulation and Stem Cells, Centre for Genomic Regulation
(CRG), Barcelona, Spain.
Comment in
Nat Struct Mol Biol. 2012 Dec;19(12):1214-5. doi: 10.1038/nsmb.2458.
Polycomb-group proteins are transcriptional repressors with essential roles in
embryonic development. Polycomb repressive complex 2 (PRC2) contains the
methyltransferase activity for Lys27. However, the role of other histone
modifications in regulating PRC2 activity is just beginning to be understood.
Here we show that direct recognition of methylated histone H3 Lys36 (H3K36me), a
mark associated with activation, by the PRC2 subunit Phf19 is required for the
full enzymatic activity of the PRC2 complex. Using NMR spectroscopy, we provide
structural evidence for this interaction. Furthermore, we show that Phf19 binds
to a subset of PRC2 targets in mouse embryonic stem cells and that this is
required for their repression and for H3K27me3 deposition. These findings show
that the interaction of Phf19 with H3K36me2 and H3K36me3 is essential for PRC2
complex activity and for proper regulation of gene repression in embryonic stem
cells.
DOI: 10.1038/nsmb.2434
PMCID: PMC3926938
PMID: 23104054 [Indexed for MEDLINE]
|
http://www.ncbi.nlm.nih.gov/pubmed/22101268
|
1. Cell Cycle. 2011 Dec 1;10(23):4162-9. doi: 10.4161/cc.10.23.18381. Epub 2011
Dec 1.
Circadian clock protein BMAL1 regulates cellular senescence in vivo.
Khapre RV(1), Kondratova AA, Susova O, Kondratov RV.
Author information:
(1)Center for Gene Regulation in Health and Disease, BGES Department, Cleveland
State University, Cleveland, OH, USA.
Comment in
Cell Cycle. 2012 Jan 15;11(2):213-4. doi: 10.4161/cc.11.2.18786.
Deficiency of the circadian clock transcriptional factor BMAL1 results in the
development of premature aging in mice. In agreement with the accelerated aging
phenotype, we observed an increase in the number of senescent cells in different
tissues (lungs, liver and spleen) of Bmal1(-/-) mice, which suggests the
important role of BMAL1 in the control of senescence in vivo. However, no
difference in the rate of proliferation and senescence between primary
fibroblasts isolated from wild-type and Bmal1(-/-) mice has been detected,
suggesting that BMAL1 does not play a significant role in replicative senescence
in vitro. BMAL1 deficient fibroblasts had an increased sensitivity to hydrogen
peroxide treatment, and reduced sensitivity to DNA damaging anticancer drugs
etoposide and daunorubicin. Increased sensitivity of Bmal1(-/-) cells to
oxidative stress was p53 independent and correlated with the disrupted
regulation of reactive oxygen species (ROS) homeostasis in BMAL1 deficient
cells: indeed, circadian oscillations of ROS level can be induced in wild-type
but not in Bmal1(-/-) cells. We propose that BMAL1 is important for the
regulation of oxidative stress and DNA damage responses, while deregulation of
these processes upon BMAL1 deficiency leads to development of stress induced
senescence in vivo.
DOI: 10.4161/cc.10.23.18381
PMCID: PMC3272294
PMID: 22101268 [Indexed for MEDLINE]
|
http://www.ncbi.nlm.nih.gov/pubmed/24801725
|
1. Cardiovasc Hematol Disord Drug Targets. 2014;14(2):98-106. doi:
10.2174/1871529x14666140505123753.
Cardiolipin metabolism and the role it plays in heart failure and mitochondrial
supercomplex formation.
Mejia EM, Cole LK, Hatch GM(1).
Author information:
(1)Department of Pharmacology & Therapeutics, University of Manitoba, Manitoba
Institute of Child Health, 501C-715 McDermot Avenue, Winnipeg, Manitoba, Canada,
R3E 3P4. ghatch@mich.ca.
Cardiolipin is a major membrane phospholipid in the mitochondria and is
essential for cellular energy metabolism mediated through mitochondrial
oxidative phosphorylation. Recent studies indicate that it plays a diverse role
in cellular metabolism. Eukaryotic cardiolipin is synthesized de novo from
phosphatidic acid via the cytidine-5'-diphosphate-1,2-diacyl-sn-glycerol pathway
and is deacylated to monolysocardiolipin in order for it to be remodelled into
the form that is observed in mitochondrial membranes. This resynthesis of
deacylated cardiolipin from monolysocardiolipin occurs via the Barth Syndrome
gene product tafazzin and acyllysocardiolipin acyltransferase-1,
monolysocardiolipin acyltransferase-1 and the alpha subunit of trifunctional
protein. Heart failure is a disease condition in which the amount and type of
cardiolipin is altered. Several animal models have been generated to study the
role of altered cardiolipin in heart failure. In many of these models loss of
the tetralinoleoyl-cardiolipin species is observed during the development of the
heart failure. In the doxycycline inducible short hairpin RNA tafazzin knock
down mouse, loss of tetralinoleoyl-cardiolipin is associated with a
mitochondrial bioenergetic disruption. Reduction in mitochondrial supercomplex
formation and NADH dehydrogenase activity within these supercomplexes is
observed. Modulation of CL fatty acyl composition may serve as a therapeutic
strategy for the treatment of several pathologies including cardiac
dysfunction.We propose that increasing cardiolipin may improve mitochondrial
function and potentially serve as a therapy for diseases which exhibit
mitochondrial dysfunction involving reduced cardiolipin.
DOI: 10.2174/1871529x14666140505123753
PMID: 24801725 [Indexed for MEDLINE]
|
http://www.ncbi.nlm.nih.gov/pubmed/24093814
|
1. Prague Med Rep. 2013;114(3):139-53. doi: 10.14712/23362936.2014.16.
Novel mutations in the TAZ gene in patients with Barth syndrome.
Mazurová S(1), Tesařová M, Magner M, Houšťková H, Hansíková H, Augustínová J,
Tomek V, Vondráčková A, Zeman J, Honzík T.
Author information:
(1)Department of Pediatrics and Adolescent Medicine, First Faculty of Medicine,
Charles University in Prague and General University Hospital in Prague, Prague,
Czech Republic.
Barth syndrome is an X-linked recessive disorder that is caused by mutations in
Taffazin gene (TAZ), leading to severe cardiolipin deficiency which results in
respiratory chain dysfunction. Barth syndrome is characterized by
cardiomyopathy, neutropenia, skeletal myopathy, growth deficiency and
3-methylglutaconic aciduria. In this paper, we present clinical, biochemical and
molecular data of the first four Czech patients from four unrelated families
diagnosed with this rare disease. The mean age of onset was 5.5 ± 3.8 months.
One child suffered from sudden cardiac death at the age of 2 years, the age of
living patients is between 3 and 13 years. Muscle hypotonia was present in all
four patients; cardiomyopathy and growth retardation in three and neutropenia in
two of them. Two patients manifested a dilated and one patient a hypertrophic
cardiomyopathy. A characteristic laboratory abnormality was the intermittently
increased excretion of 3-methylglutaconic acid. Three novel hemizygous mutations
in the TAZ gene were found (c.584G>T; c.109+6T>C; c.86G>A). We conclude that
Barth syndrome should be included in differential diagnosis of cardiomyopathy in
childhood, especially in the cooccurrence of dilated cardiomyopathy and
3-methylglutaconic aciduria.
DOI: 10.14712/23362936.2014.16
PMID: 24093814 [Indexed for MEDLINE]
|
http://www.ncbi.nlm.nih.gov/pubmed/24977128
|
1. J Epilepsy Res. 2014 Jun 30;4(1):24-7. doi: 10.14581/jer.14006. eCollection
2014 Jun.
Dyke-davidoff-masson syndrome: cases of two brothers and literature review.
Park KI(1), Chung JM(1), Kim JY(1).
Author information:
(1)Department of Neurology, Inje University College of Medicine, Seoul Paik
Hospital, Seoul, Korea.
Dyke-Davidoff-Masson syndrome (DDMS) has cerebral hemiatrophy and compensatory
ipsilateral skull thickening, and is manifested by recurrent seizures and
hemiparesis. We present one case with typical DDMS, who had a brother suffering
from epilepsy with mild imaging abnormality relevant to DDMS and similar seizure
semiology. A 26-year-old man had a history of developmental delay, mental
retardation, hemiparesis and recurrent seizures. His brother, 23-year-old man
had also experienced recurrent seizures, but he had no neurological deficits.
Older brother experienced focal motor seizures with/without secondary
generalization. Sometimes, he noted an auditory aura. MRI demonstrated the
hemispheric atrophy with the adjacent bony hypertrophy. The seizures of younger
brother were mainly of the auditory type and the MRI showed mild hemispheric
atrophy with hippocampal sclerosis without any bony change. Our sibling cases
might have a familial predisposition and support the idea that clinical courses
and radiological findings of DDMS are varied even within one family.
DOI: 10.14581/jer.14006
PMCID: PMC4066624
PMID: 24977128
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http://www.ncbi.nlm.nih.gov/pubmed/22023389
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1. Eur J Haematol. 2012 Mar;88(3):195-209. doi: 10.1111/j.1600-0609.2011.01725.x.
Epub 2011 Dec 4.
The cellular and molecular mechanisms for neutropenia in Barth syndrome.
Makaryan V(1), Kulik W, Vaz FM, Allen C, Dror Y, Dale DC, Aprikyan AA.
Author information:
(1)Department of Medicine, University of Washington, Seattle, WA, USA.
Barth syndrome (BTHS), a rare, X-linked, recessive disease, is characterized by
neutropenia and cardiomyopathy. BTHS is caused by loss-of-function mutations of
the tafazzin (TAZ) gene. We developed a model of BTHS by transfecting human HL60
myeloid progenitor cells with TAZ-specific shRNAs. Results demonstrate a
significant downregulation in TAZ expression, mimicking the effects of naturally
occurring truncation mutations in TAZ. Flow cytometry analyses of cells with
TAZ-specific, but not scrambled, shRNAs demonstrate nearly twofold increase in
the proportion of annexin V-positive cells and significantly increased
dissipation of mitochondrial membrane potential as determined by DIOC6 staining.
Transfection of TAZ-specific shRNA had similar effects in U937 myeloid cells but
not in lymphoid cell lines. Further studies in HL60 myeloid progenitor cells
revealed aberrant release of cytochrome c from mitochondria and significantly
elevated levels of activated caspase-3 in response to TAZ knockdown. Treatment
with caspase-specific inhibitor zVAD-fmk resulted in substantially reduced
apoptosis to near-normal levels. These data suggest that neutropenia in BTHS is
attributable to increased dissipation of mitochondrial membrane potential,
aberrant release of cytochrome c, activation of caspase-3, and accelerated
apoptosis of myeloid progenitor cells, and that this defect can be partially
restored in vitro by treatment with caspase-specific inhibitors.
© 2011 John Wiley & Sons A/S.
DOI: 10.1111/j.1600-0609.2011.01725.x
PMCID: PMC4445723
PMID: 22023389 [Indexed for MEDLINE]
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http://www.ncbi.nlm.nih.gov/pubmed/25941633
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1. Meta Gene. 2015 Apr 22;4:92-106. doi: 10.1016/j.mgene.2015.04.001. eCollection
2015 Jun.
Structural and functional analyses of Barth syndrome-causing mutations and
alternative splicing in the tafazzin acyltransferase domain.
Hijikata A(1), Yura K(2), Ohara O(3), Go M(4).
Author information:
(1)Nagahama Institute of Bio-Science and Technology, 1266 Tamura-cho, Nagahama,
Shiga 526-0829, Japan.
(2)Graduate School of Humanities and Sciences, Ochanomizu University, 2-1-1
Otsuka, Bunkyo-ku, Tokyo 112-8610, Japan.
(3)Laboratory for Integrative Genomics, RIKEN Center for Integrative Medical
Sciences, 1-7-22 Suehiro-cho, Tsurumi-ku, Yokohama, Kanagawa 230-0045, Japan ;
Department of Technology Development, Kazusa DNA Research Institute, 2-6-7
Kazusa-Kamatari, Kisarazu, Chiba 292-0818, Japan.
(4)Nagahama Institute of Bio-Science and Technology, 1266 Tamura-cho, Nagahama,
Shiga 526-0829, Japan ; Research Organization of Information and Systems,
4-3-13, Toranomon, Minatoku, Tokyo 105-0001, Japan.
Tafazzin is a mitochondrial phospholipid transacylase, and its mutations cause
Barth syndrome (BTHS). Human tafazzin gene produces four distinct alternatively
spliced transcripts. To understand the molecular mechanisms of tafazzin
deficiency, we performed an atomic resolution analysis of the influence of the
BTHS mutations and of alternative splicing on the structure and function of
tafazzin. From the three-dimensional (3D) homology modeling of tafazzin, we
identified candidate amino acid residues that contribute to cardiolipin binding
and to mitochondrial membrane associations that facilitate acyl-transfer
reactions. Primate specific exon 5, which is alternatively spliced, is predicted
to correspond to an intrinsically unstructured region in the protein. We
proposed that this region should change the substrate-binding affinity and/or
contribute to primate-specific molecular interactions. Exon 7, another
alternatively spliced exon, encodes a region forming a part of the putative
substrate-binding cleft, suggesting that the gene products lacking exon 7 will
lose their substrate-binding ability. We demonstrate a clear localization of the
BTHS mutations at residues responsible for membrane association, substrate
binding, and the conformational stability of tafazzin. These findings provide
new insights into the function of defective tafazzin and the pathogenesis of
BTHS at the level of protein 3D structure and the evolution of alternatively
spliced exons in primates.
DOI: 10.1016/j.mgene.2015.04.001
PMCID: PMC4412953
PMID: 25941633
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