title stringlengths 0 1.13k | abstract stringlengths 1 15.7k | PMID int64 22 36.5M |
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Presumed primary muscular lymphoma in a dog. | A case of presumed primary muscular lymphoma in an 8-year-old, intact, male Newfoundland dog is reported. The dog was presented for evaluation of an infiltrating ventral cervical mass, respiratory distress, and anorexia of 1-month duration. Fine-needle aspiration of the mass revealed anaplastic large cell lymphoma. Despite chemotherapy, health status declined and the animal was euthanized a few weeks later. At necropsy, the mass infiltrated the cervical muscles and extended ventrally to the left forelimb and cranially to the tongue and laryngeal musculature. Other muscles were infiltrated by the same neoplasm (diaphragm and intercostal, abdominal, and gluteal muscles) indicating a probable multicentric origin. Histological examination confirmed the diagnosis of anaplastic large cell lymphoma, which showed a strong muscular tropism. Immunohistochemical staining revealed neoplastic cell reactivity for cluster of differentiation 3 (CD3) and Ki-67 antigens (70% and 90%, respectively). The neoplastic cells were negative for CD79a. The presumed histological diagnosis in this dog was primary muscular anaplastic large T-cell lymphoma. | 18,987,239 |
Effect of interleukin-15 on depressed splenic dendritic cell functions following trauma-hemorrhage. | Although trauma-hemorrhage (T-H) induces suppressed splenic dendritic cell (DC) maturation and antigen presentation capacity, it remains unclear whether IL-15 modulates splenic DC functions. The aim of this study therefore was to investigate the effect of IL-15 on splenic DC functions after T-H. Male C3H/HeN mice (6-8 wk old) were randomly assigned to T-H or sham operation. T-H was induced by midline laparotomy and approximately 90 min of hemorrhagic shock (blood pressure 35 mmHg), followed by fluid resuscitation (4x the shed blood volume in the form of Ringer lactate). Two hours later, mice were killed, splenic DCs were isolated, and the effects of exogenous IL-15 on their costimulatory factors, major histocompatibility class II expression, ability to produce cytokines, and antigen presentation were measured. The results indicate that IL-15 production capacity of splenic DCs was reduced following T-H. Ex vivo exposure to IL-15 attenuated the suppressed production of TNF-alpha, IL-6, and IFN-gamma from splenic DCs following T-H. In addition, expression of surface antigen studies demonstrate that exogenous IL-15 attenuated T-H-induced downregulation of the activation of DC. The suppressed splenic DC antigen presentation function following T-H was also attenuated by IL-15 treatment. Moreover, IL-15 enhanced IL-12-induced IFN-gamma production and antigen presentation by splenic DCs. These data suggest that ex vivo treatment with IL-15 following T-H provides beneficial effects on splenic DCs. The depression in IL-15 production by splenic DCs could contribute to the host's enhanced susceptibility to infections following T-H. | 18,987,248 |
Unveiling the bovine embryo transcriptome during the maternal-to-embryonic transition. | Bovine early embryos are transcriptionally inactive and subsist through the initial developmental stages by the consumption of the maternal supplies provided by the oocyte until its own genome activation. In bovine, the activation of transcription occurs during the 8- to 16-cell stages and is associated with a phase called the maternal-to-embryonic transition (MET) where maternal mRNA are replaced by embryonic ones. Although the importance of the MET is well accepted, since its inhibition blocks embryonic development, very little is known about the transcripts expressed at this crucial step in embryogenesis. In this study, we generated and characterized a cDNA library enriched in embryonic transcripts expressed at the MET in bovine. Suppression subtractive hybridization followed by microarray hybridization was used to isolate more than 300 different transcripts overexpressed in untreated late eight-cell embryos compared with those treated with the transcriptional inhibitor, alpha-amanitin. Validation by quantitative RT-PCR of 15 genes from this library revealed that they had remarkable consistency with the microarray data. The transcripts isolated in this cDNA library have an interesting composition in terms of molecular functions; the majority is involved in gene transcription, RNA processing, or protein biosynthesis, and some are potentially involved in the maintenance of pluripotency observed in embryos. This collection of genes associated with the MET is a novel and potent tool that will be helpful in the understanding of particular events such as the reprogramming of somatic cells by nuclear transfer or for the improvement of embryonic culture conditions. | 18,987,256 |
Malignant familial hypertrophic cardiomyopathy D166V mutation in the ventricular myosin regulatory light chain causes profound effects in skinned and intact papillary muscle fibers from transgenic mice. | Transgenic (Tg) mice expressing approximately 95% of the D166V (aspartic acid to valine) mutation in the ventricular myosin regulatory light chain (RLC) shown to cause a malignant familial hypertrophic cardiomyopathy (FHC) phenotype were generated, and the skinned and intact papillary muscle fibers from the Tg-D166V mice were examined using a Guth muscle research system. A large increase in the Ca(2+) sensitivity of force and ATPase (Delta pCa(50)>0.25) and a significant decrease in maximal force and ATPase were observed in skinned muscle fibers from Tg-D166V mice compared with control mice. The cross-bridge dissociation rate g was dramatically decreased, whereas the energy cost (ATPase/force) was slightly increased in Tg-D166V fibers compared with controls. The calculated average force per D166V cross-bridge was also reduced. Intact papillary muscle data demonstrated prolonged force transients with no change in calcium transients in Tg-D166V fibers compared with control fibers. Histopathological examination revealed fibrotic lesions in the hearts of the older D166V mice. Our results suggest that a charge effect of the D166V mutation and/or a mutation-dependent decrease in RLC phosphorylation could initiate the slower kinetics of the D166V cross-bridges and ultimately affect the regulation of cardiac muscle contraction. Profound cellular changes observed in Tg-D166V myocardium when placed in vivo could trigger a series of pathological responses and result in poor prognosis for D166V-positive patients. | 18,987,303 |
Transformation mechanism of amorphous calcium carbonate into calcite in the sea urchin larval spicule. | Sea urchin larval spicules transform amorphous calcium carbonate (ACC) into calcite single crystals. The mechanism of transformation is enigmatic: the transforming spicule displays both amorphous and crystalline properties, with no defined crystallization front. Here, we use X-ray photoelectron emission spectromicroscopy with probing size of 40-200 nm. We resolve 3 distinct mineral phases: An initial short-lived, presumably hydrated ACC phase, followed by an intermediate transient form of ACC, and finally the biogenic crystalline calcite phase. The amorphous and crystalline phases are juxtaposed, often appearing in adjacent sites at a scale of tens of nanometers. We propose that the amorphous-crystal transformation propagates in a tortuous path through preexisting 40- to 100-nm amorphous units, via a secondary nucleation mechanism. | 18,987,314 |
Direct demonstration of the cross-bridge recovery stroke in muscle thick filaments in aqueous solution by using the hydration chamber. | Despite >50 years of research work since the discovery of sliding filament mechanism in muscle contraction, structural details of the coupling of cyclic cross-bridge movement to ATP hydrolysis are not yet fully understood. An example would be whether lever arm tilting on the myosin filament backbone will occur in the absence of actin. The most direct way to elucidate such movement is to record ATP-induced cross-bridge movement in hydrated thick filaments. Using the hydration chamber, with which biological specimens can be kept in an aqueous environment in an electron microscope, we have succeeded in recording ATP-induced cross-bridge movement in hydrated thick filaments consisting of rabbit skeletal muscle myosin, with gold position markers attached to the cross-bridges. The position of individual cross-bridges did not change appreciably with time in the absence of ATP, indicating stability of time-averaged cross-bridge mean position. On application of ATP, individual cross-bridges moved nearly parallel to the filament long axis. The amplitude of the ATP-induced cross-bridge movement showed a peak at 5-7.5 nm. At both sides of the filament bare region, across which the cross-bridge polarity was reversed, the cross-bridges were found to move away from, but not toward, the bare region. Application of ADP produced no appreciable cross-bridge movement. Because ATP reacts rapidly with the cross-bridges (M) to form complex (M x ADP x Pi) with an average lifetime >10 s, the observed cross-bridge movement is associated with reaction, M + ATP --> M x ADP x Pi. The cross-bridges were observed to return to their initial position after exhaustion of ATP. These results constitute direct demonstration of the cross-bridge recovery stroke. | 18,987,316 |
Cloning and characterization of new glycopeptide gene clusters found in an environmental DNA megalibrary. | Glycopeptide antibiotics have long served as drugs of last resort for the treatment of antibiotic-resistant gram-positive bacterial infections. Resistance to the clinically relevant glycopeptides, vancomycin and teicoplanin, threatens to undermine the usefulness of this important class of antibiotics. DNA extracted from a geographically diverse collection of soil samples was screened by PCR for the presence of sequences related to OxyC, an oxidative coupling enzyme found in glycopeptide biosynthetic gene clusters. Every soil sample examined contained at least 1 unique OxyC gene sequence. In an attempt to access the biosynthetic gene clusters associated with these OxyC sequences, a 10,000,000-membered environmental DNA (eDNA) megalibrary was created from a single soil sample. Two unique glycopeptide gene clusters were recovered from this eDNA megalibrary. Using the teicoplanin aglycone and the 3 sulfotransferases found in one of these gene clusters, mono-, di-, and trisulfated glycopeptide congeners were produced. The high frequency with which OxyC genes were found in environmental samples indicates that soil eDNA libraries are likely to be a rewarding source of glycopeptide gene clusters. Enzymes found in these gene clusters should be useful for generating new glycopeptides analogs. Environmental DNA megalibraries, like the one constructed for this study, can provide access to many of the natural product biosynthetic gene clusters that are predicted to be present in soil microbiomes. | 18,987,322 |
A CSF biomarker panel for identification of patients with amyotrophic lateral sclerosis. | Amyotrophic lateral sclerosis (ALS) is a progressive neurodegenerative disease with complicated pathogenesis that poses challenges with respect to diagnosis and monitoring of disease progression. To identify a biomarker panel that elucidates ALS disease pathogenesis, distinguishes patients with ALS from neurologic disease controls, and correlates with ALS disease characteristics, and to determine the effect of HFE gene variants, a potential risk factor for sporadic ALS, on the biomarker profile. We obtained CSF samples by lumbar puncture from 41 patients with ALS and 33 neurologic disease controls. All patients were genotyped for HFE polymorphisms. We performed a multiplex cytokine and growth factor analysis and immunoassays for iron-related analytes. Classification statistics were generated using a support vector machine algorithm. The groups of patients with ALS and neurologic disease controls were each associated with distinct profiles of biomarkers. Fourteen biomarkers differed between patients with ALS and the control group. The five proteins with the lowest p values differentiated patients with ALS from controls with 89.2% accuracy, 87.5% sensitivity, and 91.2% specificity. Expression of IL-8 was higher in those patients with lower levels of physical function. Expression of beta2-microglobulin was higher in subjects carrying an H63D HFE allele, while expression of several markers was higher in subjects carrying a C282Y HFE allele. A CSF inflammatory profile associated with amyotrophic lateral sclerosis (ALS) pathogenesis may distinguish patients with ALS from neurologic disease controls, and may serve as a biomarker panel to aid in the diagnosis of ALS pending further validation. Some of these biomarkers differ by HFE genotype. | 18,987,350 |
Novel functions of the CD34 family. | For almost 30 years, the cell-surface protein CD34 has been widely used as a marker to assist in the identification and Summary isolation of hematopoietic stem cells (HSCs) and progenitors in preparation for bone-marrow transplantation. In addition, it has increasingly been used as a marker to help identify other tissue-specific stem cells, including muscle satellite cells and epidermal precursors. Despite its utility as a stem-cell marker, however, the function of CD34 has remained remarkably elusive. This is probably because: (1) it is subject to a range of tissue-specific post-transcriptional and post-translational modifications that are expected to alter its function dramatically; (2) the simple interpretation of CD34 gain- and loss-of-function experiments has been confounded by the overlapping expression of the two recently discovered CD34-related proteins podocalyxin and endoglycan; and (3) there has been a glaring lack of robust in vitro and in vivo functional assays that permit the structural and functional analysis of CD34 and its relatives. Here, we provide a brief review of the domain structure, genomic organization, and tissue distribution of the CD34 family. We also describe recent insights from gain- and loss-of-function experiments and improved assays, which are elucidating a fascinating role for these molecules in cell morphogenesis and migration. | 18,987,355 |
Fast repair activities towards dGMP hydroxyl radical adducts by silybin and its analogues. | The repair activities of silybin (SLB) and its analogues towards the oxidizing deoxyguanosine monophosphate (dGMP) hydroxyl radical adducts are investigated by pulse radiolytic techniques. On pulse irradiation of nitrous oxide saturated 2.0 mM dGMP aqueous solution containing 0.1 mM silybin at neutral pH, the transient absorption spectrum of the dGMP hydroxyl radical adducts decreases with the formation of the phenoxyl radical of silybin within tens of microseconds, indicating that there is a repair reaction between the dGMP hydroxyl radical adduct and silybin. The rate constant of the repair reaction is calculated to be 1.0 x 10(9) M(-1)s(-1) for silybin. The repair activity of hesperetin (HESP), naringin (NAN) and naringenin (NAR) towards hydroxyl radical adducts of dGMP are also studied. | 18,987,437 |
DNA damage recognition proteins localize along heavy ion induced tracks in the cell nucleus. | To identify the repair dynamics involved in high linear energy transfer (LET) radiation-induced DNA damage, phospho-H2AX (gammaH2AX) foci formation was analyzed after cellular exposure to iron ions (Fe-ions, 500 MeV u(-1), 200 KeV microm(-1)). The foci located at DNA damage sites were visualized using immunocytochemical methods. Since H2AX is phosphorylated at sites of radiation-induced double strand breaks (DSB), gammaH2AX foci were used to detect or illuminate tracks formed by DSB after exposure to various doses of ionizing radiation. Additional DSB-recognition proteins such as ATM phospho-serine 1981, DNA-PKcs phospho-threonine 2609, NBS1 phospho-serine 343 and CHK2 phospho-threonine 68 all co-localized with gammaH2AX at high LET radiation induced DSB. In addition, Fe-ion induced foci remained for longer times than X-radiation induced foci. These findings suggest that Fe-ion induced damage is repaired more slowly than X-radiation induced damage, possibly because Fe-ion induced damage or lesions are more complex or extensive. Antibodies for all these phosphorylated DNA DSB recognition proteins appear to be very effective for the detection and localization of DSB. | 18,987,440 |
Hepatitis B virus genotype-associated variability in antiviral response to adefovir dipivoxil therapy in Chinese Han population. | It is well known that different genotypes of hepatitis B virus (HBV) have a different sensitivity to interferon-alpha or lamivudine (nucleoside analogue) antiviral therapy. However, for adefovir dipivoxil (ADV, a nucleotide analogue), the antiviral response of the different genotypes remains to be clarified. In order to evaluate the response of HBV genotypes to ADV therapy and to identify factors that might affect initial virological response, we performed a retrospective analysis on patients with chronic hepatitis B (CHB) in Chinese Han population. The study included 183 patients, who had been tested positive for hepatitis B e antigen (HBeAg) and had been treated with ADV (10 mg/day) for 48 weeks. The numbers of patients infected with HBV genotype B and genotype C were 98 and 75 cases, respectively, and the remaining 10 patients were mixture infection of genotypes B plus C or genotypes B plus D. The mean HBV-DNA reduction and HBV-DNA seroclearance of genotypes B and C at 48 weeks were 3.6 log(10) and 3.1 log(10) copies/ml (p < 0.05) and 41.8% and 34.6% (p < 0.05), respectively. There were no statistically significant differences between genotypes B and C in terms of HBeAg loss, anti-HBe seroconversion and normalization of serum alanine aminotransferase (ALT). Multivariate analysis showed that young age, low pretreatment HBV-DNA and/or elevated ALT level might be independent predictive factors associated with initial virological response. Thus, in Han CHB patients who are HBeAg-positive, HBV genotype B shows a better virological response to ADV therapy than does genotype C. | 18,987,454 |
Improvement in medication compliance and glycemic control with voglibose oral disintegrating tablet. | Good compliance with hypoglycemic therapy is important for diabetes treatment, since positive relationship between medication compliance and glycemic control has been reported. To improve medication compliance, the oral disintegrating tablet technology that facilitates drug administration without water has been employed in various drugs, including voglibose, an alpha glucosidase inhibitor. In the present survey, we investigated safety profile of voglibose oral disintegrating tablet (VODT), and whether treatment with VODT results in improvement of medication compliance and glycemic control. Patients with diabetes received VODT 0.6 or 0.9 mg/day for 12 weeks. Among 2,930 eligible patients, adverse drug reactions were observed in 3.6%, with the most common being abdominal distension, flatulence, diarrhea, and increased alanine aminotransferase levels. In 1,067 patients who received conventional voglibose tablet (CVT) prior to VODT, 53.1% reported that taking VODT was easier than taking CVT. Medication compliance was improved after switching to VODT in 28.4% of patients who missed taking tablets more than one time a week during CVT treatment. A significant decrease in HbA(1C) levels was observed in patients whose medication compliance was improved after switching to VODT (P = 0.033), but there was no significant reduction in HbA(1C) levels in patients whose medication compliance did not change. In conclusion, the present survey suggests that the safety profile of VODT is comparable with that of CVT, and switching from CVT to VODT has positive impact on medication compliance which may lead to an improvement in glycemic control. | 18,987,459 |
Anti-inflammatory action of a phosphatidylcholine, phosphatidylethanolamine and N-acylphosphatidylethanolamine-enriched diet in carrageenan-induced pleurisy. | Phosphatidylcholine (PC)-derived choline exhibits anti-inflammatory properties in stress conditions. Phosphatidylethanolamine (PE) and N-acylphosphatidylethanolamines (NAPEs) are endogenous bioactive phospholipids linked to the PC and endocannabinoid metabolisms. We hypothesized that an increased dietary input of PC, PE and NAPE may interfere with leukocyte reactions and thus decreases the inflammatory activation. CFLP mice were fed with a control diet or with a diet supplemented with 1% PC, 0.4% PE and 0.1% NAPE for 7 days before the induction of pleurisy with carrageenan. Pleural leukocyte migration, pulmonary mast cell degranulation (Alcian blue-safranin O staining), and the activities of inducible nitric oxide synthase, xanthine oxidoreductase and myeloperoxidase were determined in lung tissue biopsies. The carrageenan-induced inflammatory response was characterized by pulmonary leukocyte infiltration, mast cell degranulation and significantly increased inducible nitric oxide synthase and xanthine oxidoreductase activities (by 82 and 60%, respectively). Treatment of mice with acetylsalicylic acid or with dietary PC + PE + NAPE supplementation significantly decreased the leukocyte reaction, and suppressed the activity of the pulmonary proinflammatory enzymes. This study confirms a potential for dietary PC + PE + NAPE supplementation to influence events crucial for the remission of acute inflammation. PC + PE + NAPE administration could possibly be a novel preventive or pharmacotherapeutic option in inflammatory pathologies. | 18,987,473 |
Design and fabrication of three-dimensional scaffolds for tissue engineering of human heart valves. | We developed a new fabrication technique for 3-dimensional scaffolds for tissue engineering of human heart valve tissue. A human aortic homograft was scanned with an X-ray computer tomograph. The data derived from the X-ray computed tomogram were processed by a computer-aided design program to reconstruct a human heart valve 3-dimensionally. Based on this stereolithographic model, a silicone valve model resembling a human aortic valve was generated. By taking advantage of the thermoplastic properties of polyglycolic acid as scaffold material, we molded a 3-dimensional scaffold for tissue engineering of human heart valves. The valve scaffold showed a deviation of only +/-3-4% in height, length and inner diameter compared with the homograft. The newly developed technique allows fabricating custom-made, patient-specific polymeric cardiovascular scaffolds for tissue engineering without requiring any suture materials. | 18,987,474 |
Prenatal diagnosis of thanatophoric dysplasia by 3-D helical computed tomography and genetic analysis. | We report the first case of thanatophoric dysplasia (TD) successfully diagnosed in utero by a combination of 2-D ultrasound, computed tomography (CT) 3-D imaging and genetic analysis at 26 weeks' gestation. Prenatal sonographic examinations performed at 23 weeks' gestation revealed micromelic shortening of the limbs, reduced thoracic cavity and a presence of cloverleaf skull deformity. Based on these findings, a lethal form of skeletal dysplasia was suspected and a helical CT imaging with 3-D reconstruction depicted skeletal abnormalities which suggested TD. The prenatal diagnosis was affirmed on amniotic fluid cells by DNA mutation analysis of the fibroblast growth factor receptor 3 gene. A missense mutation (tyrosine 373 to cysteine) was detected, and was diagnosed as TD type I. Helical CT imaging with 3-D reconstruction and molecular testing are useful adjuncts to 2-D ultrasonography in the diagnosis of lethal skeletal dysplasias, allowing for appropriate perinatal support including genetic counseling. | 18,987,480 |
The complex genetics of Kallmann syndrome: KAL1, FGFR1, FGF8, PROKR2, PROK2, et al. | Kallmann syndrome (KS) combines hypogonadotropic hypogonadism and anosmia. Anosmia is related to the absence or hypoplasia of the olfactory bulbs and tracts. Hypogonadism is due to gonadotropin-releasing hormone (GnRH) deficiency, which presumably results from a failure of the embryonic migration of neuroendocrine GnRH cells from the olfactory epithelium to the forebrain. This failure could be a consequence of the early degeneration of olfactory nerve and terminal nerve fibres, because the latter normally act as guiding cues for the migration of GnRH cells. Defects in GnRH cell fate specification, differentiation, axon elongation or axon targeting to the hypothalamus median eminence may, however, also contribute to GnRH deficiency, at least in some genetic forms of the disease. To date, five KS genes have been identified, namely, FGFR1, FGF8, PROKR2, PROK2, and KAL1. Mutations in these genes, however, account for barely 30% of all KS cases. Mutations in FGFR1, encoding fibroblast growth factor receptor 1, underlie an autosomal dominant form of the disease. Mutations in PROKR2 and PROK2, encoding prokineticin receptor-2 and prokineticin-2, have been found in heterozygous, homozygous or compound heterozygous states. These two genes are likely to be involved both in monogenic recessive and digenic or oligogenic KS transmission modes. Finally, KAL1, encoding the extracellular glycoprotein anosmin-1, is responsible for the X chromosome-linked form of the disease. It is believed that anosmin-1 acts as an enhancer of FGF signalling and perhaps of prokineticin signalling too. | 18,987,492 |
Genetics of spermatogenic failure. | Spermatogenesis is an ongoing developmental process in adult testes that requires the coordinated expression of many genes. The genetic causes of spermatogenic failure in men remain largely unknown, though abnormalities in the sex chromosomes constitute a significant portion of them. In this review, we focus on 3 disorders that involve the sex chromosomes and are often screened in infertility clinics. These are Klinefelter syndrome, Y chromosome microdeletion, and XX male syndrome. We describe their prevalence, the associated phenotypes, and the molecular mechanisms underlying the disorders and discuss the difficulties in identifying the causal genes contributing to the spermatogenic defects. Currently, there are no effective therapies for the spermatogenic failure in the patients, and conception through assisted reproductive technology bears the risk of passing genetic abnormalities to the next generation. | 18,987,499 |
The value of a breast care nurse in supporting rural and remote cancer patients in Queensland. | The role of the breast care nurse (BCN) in the Queensland's Supporting Rural Women With Breast Cancer Project was evaluated by mixed methodology. Through questionnaire and interview, patients provided views about the nurse's role under the categories of awareness, access, coordination, information, and psychosocial, emotional, and practical support. Of the 51 participants, 37 resided in rural and remote areas. Eighteen lived between 100 and 500 miles from specialized breast care services. The BCN met patients at their regular hospital visits and was available by telephone at any time. There was overwhelming agreement among the participants that the timing of contact, ease of accessibility, information provided, and support offered were extremely valuable in making their treatment and recovery easier. Most participants would recommend hospitals with a BCN to their friends. Members of the multidisciplinary care team provided views on awareness of the BCN, influence on care management, communication, and patient outcomes. They recognized the benefits of the BCN to patients and to coordination and liaison of the team. The findings concur with unpublished Australian reports that demonstrate the success of BCNs. The BCN model of care could be used to support other medical conditions in rural and remote Australia. | 18,987,503 |
Young female breast cancer survivors: their sexual function and interest in sexual enhancement products and services. | Although American women are living longer after a breast cancer diagnosis, they may experience significant alterations in sexual function. However, little is known about the types of strategies that women are interested in using to address these sexual issues. This study used a reliable and valid instrument, the Sexual Function Questionnaire, to assess survivors' sexual function. Data were collected from 115 women who were younger than 50 years at diagnosis. Compared to normative controls, survivors scored significantly lower, indicating lower functioning, on most subscales of the Sexual Function Questionnaire and the overall measure, with the exception of the masturbation subscale on which they scored significantly higher. Most participants indicated moderate or strong interest in sexual enhancement products and comfort purchasing sexual enhancement products through various venues. Nurses and other health professionals might consider collaborations with entities of the adult retail industry to provide survivors with information about sexual enhancement products and their therapeutic potential. | 18,987,508 |
Managing distress in oncology patients: description of an innovative online educational program for nurses. | The American Psychosocial Oncology Society and the Individual Cancer Assistance Network have launched the online continuing education accredited program "ICAN: Distress Management for Oncology Nursing" to address the ability of oncology nurses to assess, treat, and refer patients with a range of psychosocial problems. An important goal of the program is to reduce traditional barriers to psychosocial oncology education by providing the oncology nursing community with easy access to information from experts in the field. There are 4 Internet webcasts: Nurse's Role in Recognizing Distress in Patients and Caregivers; Assessment Recommendations; Treatment Strategies; and Principles and Guidelines for Psychotherapy and Referral. The program examines the prevalence and dimensions of patient distress and offers instruction on how to effectively integrate screening tools, such as the Distress Thermometer and Problem Check List, into clinical practice. It provides details on relevant interventions and referral algorithms based on the National Comprehensive Cancer Network Guidelines for Distress Management. It explores the devastating impact of psychological distress on quality of life, and the unique position of nurses in busy inpatient settings, outpatient clinics, and offices to detect, intervene, and refer to appropriate services. Providing information over the Internet addresses common barriers to learning, including schedule and time constraints. | 18,987,517 |
Polymorphisms in interleukin 1 beta and interleukin 1 receptor antagonist associated with tumor recurrence in stage II colon cancer. | Identifying molecular markers for tumor recurrence is critical in successfully selecting patients with stage II colon cancer who are more likely to benefit from adjuvant chemotherapy. Interleukin 1 beta (IL1B) and interleukin 1 receptor antagonist (IL1RN) have been shown to play a critical role in the early onset of tumor-associated angiogenesis. In this study, we tested whether eight functionally significant polymorphisms within six genes of the angiogenesis pathway [IL1B, IL1RN, vascular endothelial growth factor A (VEGFA), VEGF receptor 2, interleukin-8, cyclooxygenase-2] will predict the risk of tumor recurrence in stage II colon cancer patients treated with 5-fluorouracil based adjuvant chemotherapy. Blood samples were obtained from 109 patients with stage II colon cancer at the University of Southern California medical facilities. DNA was extracted from peripheral blood and the genotypes were analyzed using PCR-restriction fragment length polymorphism protocols. Patients harboring the IL1RN/IL1B 1-T-C (IL-1RN variable number tandem repeats (VNTR)/IL1B C+3954T/C-511T) haplotype were at greatest risk of developing tumor recurrence [relative risk (RR): 2.72, 95% confidence interval (CI): 1.22-6.08] (adjusted P=0.015). In addition, IL1B +3954 any T (RR: 2.78, 95% CI: 0.99-7.83) (adjusted P=0.043), IL1RN VNTR (RR: 6.09, 95% CI: 1.11-33.4) (adjusted P=0.038), and VEGFA -634 any C (RR: 2.91, 95% CI: 1.13-7.48) (adjusted P=0.026) were shown to be adverse prognostic markers, in both univariate and multivariable analyses. Polymorphisms in IL1B, IL1RN, and VEGFA as well as IL1B/IL1RN haplotype analysis may serve as molecular markers for tumor recurrence in stage II colon cancer, indicating that the analysis of angiogenesis-related gene polymorphisms may help to identify patient subgroups at high risk for tumor recurrence. | 18,987,561 |
A comparison of functional assessment instruments and work status in chronic back pain. | The aim of this cross sectional study was to analyse whether low back pain (LBP) functional assessment instruments correlate well with work status measures. This study was a cross sectional study that enrolled 375 patients with chronic LBP attending back pain outpatient clinics of a University Hospital and a specialist rehabilitation centre over a period of one year. The outcome scores measured were Oswestry Disability Index, Roland Morris Disability Questionnaire and Orebro Musculoskeletal Pain Questionnaire. The effect of back pain on their work status was also recorded and correlated to the above instrument values. There was a only a modest correlation between work status and the three measured outcome scores, with the Spearman rank correlation being 0.47 for OMPQ, 0.43 for ODI and 0.39 for RMQ. The studied standard LBP outcome measures and work status are not interchangeable. The impact on work status should not be assumed based on the severity of these outcome measures and should be recorded as a separate outcome measure in chronic low back pain. | 18,987,564 |
Cardiac protection by volatile anesthetics. A review. | All volatile anesthetics have cardiac depressant effects that decrease myocardial oxygen demand and may thus improve the myocardial oxygen balance during ischemia. Recent experimental evidence has clearly demonstrated that, in addition to these indirect effects, volatile anesthetic agents also directly protect from ischemic myocardial damage. Implementation of these effects during clinical anesthesia can provide an additional tool for treatment or prevention of ischemic cardiac dysfunction during the perioperative period. A recent meta-analysis showed that desflurane and sevoflurane reduce postoperative mortality and the incidence of myocardial infarction following cardiac surgery, with significant advantages in terms of postoperative cardiac troponin release, need for inotropic support, and time on mechanical ventilation, as well as in time spent in the intensive care unit and overall hospital stay. Multicenter, randomized clinical trials previously demonstrated that desflurane could reduce the postoperative release of cardiac troponin I, the need for inotropic support, and the number of patients requiring prolonged hospitalization following coronary artery bypass graft surgery, either with or without cardiopulmonary bypass. However, evidence in non-coronary surgical settings is contradictory and will be reviewed in this paper, together with the mechanism of cardiac protection by volatile agents. | 18,987,572 |
The effect of HI-6 on cholinesterases and on the cholinergic system of the rat bladder. | The current standard treatment of organophosphate poisoning consists of an administration of anticholinergic drugs and cholinesterase reactivators (oximes). Oximes can react - except their reactivating effect on cholinesterases - directly with cholinoreceptors. HI-6 is an oxime that may have an inhibitory effect on the muscarinic receptors, too. In our work, we have investigated an influence of HI-6 on the acetylcholinesterase (AChE), butyrylcholinesterase (BChE) and on the muscarinic receptors in vitro. The study was conducted using biosensor technique and on the rat bladder using in vitro test (tissue bath; methacholine as muscarinic agonist). IC50 for BChE from human serum was determined to be 1.01x10-6 M and for human erythrocytes AChE 3.31x10-6 M, respectively. We assume that the demonstrated contractile response can be attributed to the inhibition of the AChE at the lower concentration and to a predominant inhibition of muscarinic receptor at higher concentration of compound tested. | 18,987,577 |
Structure-efficiency relationship in derivatives of stilbene. Comparison of resveratrol, pinosylvin and pterostilbene. | Oxidative stress is related to a number of autoimmune diseases, e.g. rheumatoid arthritis, cancer, etc. The main source of pathologically working reactive oxygen species (ROS) are activated polymorphonuclear leukocytes (PMNL). There are some papers comparing structure - pharmacological efficiency relationship of vegetal substances from the stilbenoid group. We compared the effect of trans-resveratrol, which is well-known by its antioxidative activity, with the effect of pinosylvin and pterostilbene. Luminol-enhanced chemiluminescence (CL) was used to study the antioxidative action. The effect was observed in whole blood and in isolated PMNL. The concentrations of substances tested were 0.01-100 microM. Due to the different abilities of luminol and isoluminol to pass through the cell membrane, we studied the effect of the substances tested on intracellular and extracellular ROS. To stimulate the production of ROS we used phorbol-myristate-acetate (PMA), which activates PMNL via protein kinase C. Resveratrol, pinosylvin and pterostilbene inhibited significantly the CL of whole blood and extra- and intracellular CL of isolated PMNL in a dosedependent manner. Depending on different functional groups of the stilbene molecule, resveratrol inhibited CL of whole blood and isolated PMNL, whereas pinosylvin influenced mainly intracellular CL and pterostilbene extracellular CL. The presence of different functional groups in the molecules of stilbenoids influence their antioxidative effect. Modification of these functional groups may result in derivatives with required antioxidative properties, targeting mainly extracellular ROS which are responsible for tissue damage during chronic inflammation. | 18,987,580 |
Perfluorinated compounds: occurrence and risk profile. | Perfluorinated compounds (PFCs) such as perfluoro-octane sulphonate (PFOS) and perfluorooctanoic acid (PFOA) are emerging environmental pollutants, arising mainly from their use as surface treatment chemicals, polymerization aids and surfactants. They are ubiquitous, persistent and bioaccumulative in the environment. Perfluorinated compounds are being proposed as a new class of POPs. Although tests in rodents have demonstrated numerous negative effects of PFCs, it is unclear if exposure to perfluorinated compounds may affect human health. This review provides an overview of the recent toxicology and toxicokinetics, monitoring data now available for the environment, wildlife, and humans and attempts to explain the mechanisms of action of PFCs. | 18,987,583 |
Mercury in human hair as an indicator of the fish consumption. | Mercury and most of its compounds are extremely toxic and should be handled with care. It can be inhaled and absorbed through the skin and mucous membranes. The most toxic forms of mercury are its organic compounds such as dimethylmercury and methylmercury. Fish have a natural tendency to accumulate mercury. Methylmercury is produced by microbial methylation of inorganic mercury in water sediment then it infiltrates the food chain and it consequently accumulates in fish. Fish are the main source of methylmercury in human food. Mercury is transferred into a hair; and this can be than used to monitor the long-term exposure to mercury. The content of mercury in hair depends on the frequency of fish consumption. The aim of our study was to compare mercury content in the hair of children that had various amounts of fish consumption (increased or reduced). Total mercury content in hair was determined by direct method of cold vapors using an AMA 245 analyzer. A total of 174 hair samples from the children (9-17 years old) were analyzed. In this study, the following localities were compared: Neratovice (n=42), Jeseníky (n=44), Prague (n=59) in Czech Republic and Olsztyn in Poland (n=29). Every sample was accompanied with questionnaire about age, gender, regions, amalgam fillings and fish consumption. We did not find a correlation between the content of mercury in hair with age, gender or amalgam fillings. We did find a correlation between fish consumption and the amount of mercury found in the hair samples. The amount of mercury in hair increases with more frequent consumption of freshwater and marine fish. | 18,987,591 |
Hyaluronan influence on the onset of chondrogenic differentiation of mesenchymal stem cells. | Hyaluronan (HA) is an abundant component of chondrogenic tissue hence it is often used as a fundamental constituent in cartilage tissue substitutes. However, effects of different molecular weight HA on chondrogenic differentiation are not clear. The aim was to evaluate modulation of mesenchymal stem cell (MSC) early chondrogenesis by HA of molecular weights 100, 600 and 1 500 kDa. HA was applied on MSCs cultured in a pellet system for one, two and three weeks. Chondrogenesis was evaluated by determinations of gene expression of transcription factor Sox-9 and extracellular matrix proteins collagen type II and XI, aggrecan, and COMP by Real-Time PCR and completed with histological analysis. Upon chondrogenic induction, the respective pellets revealed active transcription of the chondrogenic genes together with proceeding accumulation of glycosaminoglycan (GAG) rich extracellular matrix. Sox-9 was also expressed in non-chondrogenic MSC controls. HA treated pellets were not significantly influenced on day 7 of culture. However, on day 14, lowered expression in some of the extracellular matrix proteins appeared together with a moderately smaller amount of GAG content in pellet sections. Nevertheless, the analysis on day 21 has demonstrated that HA did not affect the outcome of the differentiation by the end of the culture. Any difference regarding the molecular weight of the HA was not found. It could be speculated that HA induced a time shift in the phase of the dominant matrix protein onset which was in full compensated by the end of the evaluated time period. Thus, data suggest that HA of any tested molecular weight does not significantly modulate chondrogenesis of MSCs in pellet system. | 18,987,597 |
WNT11 acts as a directional cue to organize the elongation of early muscle fibres. | The early vertebrate skeletal muscle is a well-organized tissue in which the primitive muscle fibres, the myocytes, are all parallel and aligned along the antero-posterior axis of the embryo. How myofibres acquire their orientation during development is unknown. Here we show that during early chick myogenesis WNT11 has an essential role in the oriented elongation of the myocytes. We find that the neural tube, known to drive WNT11 expression in the medial border of somites, is necessary and sufficient to orient myocyte elongation. We then show that the specific inhibition of WNT11 function in somites leads to the disorganization of myocytes. We establish that WNT11 mediates this effect through the evolutionary conserved planar cell polarity (PCP) pathway, downstream of the WNT/beta-catenin-dependent pathway, required to initiate the myogenic program of myocytes and WNT11 expression. Finally, we demonstrate that a localized ectopic source of WNT11 can markedly change the orientation of myocytes, indicating that WNT11 acts as a directional cue in this process. All together, these data show that the sequential action of the WNT/PCP and the WNT/beta-catenin pathways is necessary for the formation of fully functional embryonic muscle fibres. This study also provides evidence that WNTs can act as instructive cues to regulate the PCP pathway in vertebrates. | 18,987,628 |
Structure of a potentially open state of a proton-activated pentameric ligand-gated ion channel. | The X-ray structure of a pentameric ligand-gated ion channel from Erwinia chrysanthemi (ELIC) has recently provided structural insight into this family of ion channels at high resolution. The structure shows a homo-pentameric protein with a barrel-stave architecture that defines an ion-conduction pore located on the fivefold axis of symmetry. In this structure, the wide aqueous vestibule that is encircled by the extracellular ligand-binding domains of the five subunits narrows to a discontinuous pore that spans the lipid bilayer. The pore is constricted by bulky hydrophobic residues towards the extracellular side, which probably serve as barriers that prevent the diffusion of ions. This interrupted pore architecture in ELIC thus depicts a non-conducting conformation of a pentameric ligand-gated ion channel, the thermodynamically stable state in the absence of bound ligand. As ligand binding promotes pore opening in these ion channels and the specific ligand for ELIC has not yet been identified, we have turned our attention towards a homologous protein from the cyanobacterium Gloebacter violaceus (GLIC). GLIC was shown to form proton-gated channels that are activated by a pH decrease on the extracellular side and that do not desensitize after activation. Both prokaryotic proteins, ELIC and GLIC form ion channels that are selective for cations over anions with poor discrimination among monovalent cations, characteristics that resemble the conduction properties of the cation-selective branch of the family that includes acetylcholine and serotonin receptors. Here we present the X-ray structure of GLIC at 3.1 A resolution. The structure reveals a conformation of the channel that is distinct from ELIC and that probably resembles the open state. In combination, both structures suggest a novel gating mechanism for pentameric ligand-gated ion channels where channel opening proceeds by a change in the tilt of the pore-forming helices. | 18,987,630 |
The impact of O2 availability on human cancer. | During the past century it has been established that regions within solid tumours experience mild to severe O(2) deprivation owing to aberrant vascular function. These hypoxic regions are associated with altered cellular metabolism, as well as increased resistance to radiation and chemotherapy. As discussed in this Timeline, over the past decade work from many laboratories has elucidated the mechanisms by which hypoxia-inducible factors (HIFs) modulate tumour cell metabolism, angiogenesis, growth and metastasis. The central role played by intra-tumoural hypoxia and HIF in these processes has made them attractive therapeutic targets in the treatment of multiple human malignancies. | 18,987,634 |
Genetic variants of the HLA-A, HLA-B and AIF1 loci show independent associations with type 1 diabetes in Norwegian families. | The main genetic predisposition to type 1 diabetes (T1D) is known to be conferred by the HLA-DRB1, -DQA1 and -DQB1 genes in the major histocompatibility complex (MHC). Other genetic factors within this complex are known to contribute, but their identity has often been controversial. This picture is shared with several other autoimmune diseases (AIDs). Moreover, as common genetic factors are known to exist between AIDs, associations reported with other AIDs may also be involved in T1D. In this study, we have used these observations in a candidate gene approach to look for additional MHC risk factors in T1D. Using complementary conditional methods (involving conditional logistic regression and family-based haplotype tests) and analyses of linkage disequilibrium (LD) patterns, we confirmed association for alleles of the HLA-A and HLA-B genes and found preliminary evidence for a novel association of a single-nucleotide polymorphism (rs2259571) in the AIF1 gene, independent of the DRB1-DQA1-DQB1 genes and of each other. However, no evidence of independent associations for a number of previously suggested candidate polymorphisms was detected. Our results illustrate the importance of a comprehensive adjustment for LD effects when performing association studies in this complex. | 18,987,644 |
The expanding genetic overlap between multiple sclerosis and type I diabetes. | Familial clustering of autoimmune disease is well recognized and raises the possibility that some susceptibility genes may predispose to autoimmunity in general. In light of this observation, it might be expected that some of the variants of established relevance in one autoimmune disease may also be relevant in other related conditions. On the basis of this hypothesis, we tested seven single nucleotide polymorphisms (SNPs) that are known to be associated with type I diabetes in a large multiple sclerosis data set consisting of 2369 trio families, 5737 cases and 10,296 unrelated controls. Two of these seven SNPs showed evidence of association with multiple sclerosis; that is rs12708716 from the CLEC16A gene (P=1.6 x 10(-16)) and rs763361 from the CD226 gene (P=5.4 x 10(-8)). These findings thereby identify two additional multiple sclerosis susceptibility genes and lend support to the notion of autoimmune susceptibility genes. | 18,987,646 |
Unusual echocardiographic features seen in a case of giant cell myocarditis. | The case of an 18-year-old college football player with a recent history of streptococcal pharyngitis who was experiencing progressive disabling dyspnea on exertion with easy fatigability and lack of stamina, and was taken to the hospital after a syncopal episode is described. The patient was initially diagnosed with heart failure and treated accordingly. However, because of a fulminant clinical deterioration, an endomyocardial biopsy was recommended, which showed focal giant cell transformation consistent with giant cell myocarditis. Treatment with methylprednisolone and cyclosporine was promptly initiated. Several apical clots were noted during treatment, but the patient attained full recovery with treatment. | 18,987,760 |
Antiphospholipid antibodies and atherosclerosis: insights from systemic lupus erythematosus and primary antiphospholipid syndrome. | The issue of atherosclerosis in the antiphospholipid syndrome (APS) is receiving considerable attention within and without the autoimmune setting. Measurement of arterial intima media thickness (IMT) of is an easy and surrogate means of detecting subclinical atherosclerosis. This technique has been applied to patients with systemic lupus erythematosus (SLE) nand primary APS in the attempt to unravel a possible association between antiphospholipid antibodies and premature atherosclerosis. The available data is reviewed in the light of the most recent atherogenic pathways that may differentially account for premature vascular disease in SLE and primary APS. | 18,987,784 |
The HELP assay. | Genomic representations using ligation-mediated PCR have been used successfully as the foundation for a number of high-throughput assays. HpaII tiny fragment enrichment by ligation-mediated PCR (HELP) is an example of the use of such representations to study cytosine methylation in the genome. The HELP assay differs from most other assays testing cytosine methylation because of its positive representation of hypomethylated DNA in the genome, whereas other assays infer the presence of hypomethylated sequences by the absence of signal, for which there can be confounding technical reasons. Hypomethylated sequences represent the minority of the genome and tend to be located at unique sequences with functionally interesting properties such as transcription start sites. By performing a comparative genomic hybridization using an MspI representation from the same DNA sample, we represent all potential loci that could be generated by HpaII in the situation of global hypomethylation; in practice, HpaII generates a subset of loci from this population, allowing us to discriminate hypomethylated loci (represented by both HpaII and MspI) from methylated loci (represented by MspI only). | 18,987,808 |
Restriction landmark genomic scanning: analysis of CpG islands in genomes by 2D gel electrophoresis. | Restriction landmark genomic scanning (RLGS) is a method that provides a quantitative genetic and epigenetic (cytosine methylation) assessment of thousands of CpG islands in a single gel without prior knowledge of gene sequence. The method is based on two-dimensional separation of radiolabeled genomic DNA into nearly 2,000 discrete fragments that have a high probability of containing gene sequences. Genomic DNA is digested with an infrequently cutting restriction enzyme, such as NotI or AscI, radiolabeled at the cleaved ends, digested with a second restriction enzyme, and then electrophoresed through a narrow, 60-cm-long agarose tube-shaped gel. The DNA in the tube gel is then digested by a third, more frequently cutting restriction enzyme and electrophoresed, in a direction perpendicular to the first separation, through a 5% nondenaturing polyacrylamide gel, and the gel is autoradiographed. Radiolabeled NotI or AscI sites are frequently used as "landmarks" because NotI or AscI cannot cleave methylated sites and since an estimated 89% and 83% of the recognition sites, respectively, are found within CpG islands. Using a methylation-sensitive enzyme, the technique has been termed RLGS-M. The resulting RLGS profile displays both the copy number and methylation status of the CpG islands. Integrated with high-resolution gene copy-number analyses, RLGS enables one to define genetic or epigenetic alteration in cells. These profiles are highly reproducible and are therefore amenable to inter- and intraindividual DNA sample comparisons. RLGS was the first of many technologies to allow large-scale DNA methylation analysis of CpG islands. | 18,987,812 |
Profiling DNA methylation from small amounts of genomic DNA starting material: efficient sodium bisulfite conversion and subsequent whole-genome amplification. | noindent Sodium bisulfite modification-based fine mapping of methylated cytosines represents the gold standard technique for DNA methylation studies. A major problem with this approach, however, is that it results in considerable DNA degradation, and large quantities of genomic DNA material are needed if numerous genomic regions are to be profiled. This chapter describes a method for profiling DNA methylation from small amounts of genomic-DNA starting material utilizing an efficient sodium bisulfite conversion method followed by whole-genome amplification (WGA). WGA is a useful method to overcome the problem of low initial amount of DNA and/or severe DNA degradation during conventional sodium bisulfite treatment in studies investigating DNA methylation. WGA is a relatively inexpensive process that can be optimized for high-throughput application and enables the thorough investigation of methylation at numerous genomic locations on samples for which DNA availability is low. Data from our lab has demonstrated that bisulfite-treated DNA amplified using WGA can be used for a range of downstream DNA methylation mapping procedures, including bisulfite-primer optimization, the sequencing of cloned PCR products, MS-SNuPE, and Pyrosequencing. | 18,987,828 |
Visualizing dendritic cell migration within the skin. | Dendritic cells (DCs) within the skin are a heterogeneous population of cells, including Langerhans cells of the epidermis and at least three subsets of dermal DCs. Collectively, these DCs play important roles in the initiation of adaptive immune responses following antigen challenge of the skin as well as being mediators of tolerance to self-antigen. A key functional aspect of cutaneous DCs is their migration both within the skin and into lymphatic vessels, resulting in their emigration to draining lymph nodes. Here, we discuss our current understanding of the requirements for successful DC migration in and from the skin, and introduce some of the microscopic techniques developed in our laboratory to facilitate a better understanding of this process. In particular, we detail our current use of multi-photon excitation (MPE) microscopy of murine skin to dissect the migratory behavior of DCs in vivo. | 18,987,873 |
Hamartomas of the oro- and nasopharyngeal cavity in infancy: two cases and a short review. | Oro- and nasopharyngeal masses are rare in infancy and consist of developmental anomalies and, mostly benign, neoplasms. We report two infants with a tumour in the ear-nose-throat region. As shown by our cases, the clinical presentation of an oropharyngeal mass in infancy varies from respiratory insufficiency at birth to incidental finding by the parents a few months after birth. | 18,987,884 |
Functional genes and proteins of Trichinella spp. | Research of Trichinella proteins has been conducted with emphasis on excretory-secretory (E-S) products of muscle larvae because of two reasons. The first is that it has prominent and narrow specific antigenicity, and the second is that it may play some role in nurse cell formation after being secreted into host muscle cells. Proteomic analysis of E-S proteins was further advanced by the aid of new analytical methods such as gene cloning, matrix-assisted laser desorption-ionization time-of-flight mass spectrometry, and expressed sequence tags database analysis. As the research progressed, the interest of researchers moved to identification of function of E-S products, which has shed further light on the intriguing relationships between parasites and hosts. Major constituents of the E-S products include 43-, 53-, and 45-kDa glycoprotein derived from the stichosome. Many proteins were discovered in E-S products after the 43-, 53-, and 45-kDa proteins although the relationships among them remain unclear. Some of the new proteins were partially defined in terms of their function including nuclear antigens, MyoD-like protein, TsJ5 protein, etc. There are better-characterized proteins based on the gene molecular method, which allow easier identification of the function of proteins of interest. Such examples were demonstrated by proteinases, proteinase inhibitors, heat shock proteins, glycosidases, etc. | 18,987,885 |
A proposed staging system for intrahepatic cholangiocarcinoma. | The American Joint Committee on Cancer (AJCC)/International Union Against Cancer (UICC) staging system for liver cancer is based on data exclusively derived from hepatocellular carcinoma (HCC) patients and thus may be inappropriate for patients with intrahepatic cholangiocarcinoma (ICC). We sought to empirically derive an ICC staging system from population-based data on patients with ICC. The Surveillance, Epidemiology, and End Results (SEER) database was used to identify 598 patients who underwent surgery for ICC between 1988 and 2004. The discriminative abilities of the AJCC/UICC liver cancer and two Japanese ICC staging systems were evaluated. Independent predictors of survival were identified using Cox proportional hazards models. A staging system for ICC was then derived based on these analyses. The AJCC/UICC T classification system failed to adequately stratify the T2 and T3 cohorts due to tumor size >5 cm not being a relevant prognostic factor [hazard ratio (HR) 0.97, 95% confidence interval (CI) 0.72-1.30]. In contrast, presence of multiple lesions (HR 1.42, 95% CI 1.01-2.01) or vascular invasion (HR 1.53, 95% CI 1.10-2.12) predicted adverse prognosis. Based on these findings, an ICC staging system was developed that omits tumor size. This system showed no loss of prognostic discrimination compared with the AJCC/UICC system and significant superiority over the Japanese systems. We conclude that the AJCC/UICC liver cancer staging system fails to stratify ICC patients adequately and inappropriately includes tumor size. We propose a staging system specifically developed for ICC based on number of tumors, vascular invasion, lymph node status, and presence of metastatic disease. | 18,987,916 |
Total laparoscopic resection of the gallbladder together with the gallbladder bed. | Patients with carcinoma of the gallbladder that is preoperatively diagnosed by radiology do not undergo laparoscopic resection, because such surgery is thought to worsen the prognosis of gallbladder carcinoma. However, the prognosis for patients with incidental T2 gallbladder carcinoma who are treated laparoscopically is reportedly no worse than that for patients undergoing conventional surgery. We successfully performed total laparoscopic resection of the gallbladder together with the gallbladder bed without any complications. We believe that this procedure represents a valid therapeutic option for carefully selected patients with T2 carcinoma of the gallbladder. | 18,987,927 |
Assessment of liver function for successful hepatectomy in patients with hepatocellular carcinoma with impaired hepatic function. | This study aimed to construct a formula for assessing liver function in order to prevent post-hepatectomy liver failure. A formula was constructed by analyzing data from 28 patients with hepatocellular carcinoma (HCC) with liver cirrhosis operated on between 1981 and 1984. Next, we evaluated the validity of this formula in 207 hepatectomy patients operated on from 1985 to 1999. For 145 hepatectomy patients operated on from 2000 to 2006, this formula was calculated before surgery in order to assess their risk of hepatectomy. The formula for liver functional evaluation, constructed from preoperative hepatic function parameters, was: liver failure score = 164.8 - 0.58 x Alb - 1.07 x HPT + 0.062 x GOT - 685 x K. ICG - 3.57 x OGTT. LI + 0.074 x RW, where Alb is albumin (g/dl); HPT, hepaplastin test (%); GOT, glutamate oxaloacetate transaminase (U/l); K. ICG, K value of indocyanine green clearance test; OGTT. LI, 60-min/120-min glucose level in 75-g oral glucose tolerance test. linearity index of OGTT; and RW, weight of resected liver (g). We decided that a score below 25 would be safe for hepatectomy. The mortality rate decreased from 3.9% in 1985--1999 to 1.3% in 2000--2006. This finding allows us to conclude that the formula is valid for assessing the risk of post-hepatectomy liver failure. | 18,987,929 |
A patient with gallbladder cancer with paraaortic lymph node and hepatic metastases who has survived for more than 13 years after the primary extended radical operation. | Gallbladder cancer is a disease with poor prognosis, especially when it is associated with distant metastasis. Here we report a rare case of a patient with gallbladder cancer with extensive local and distant lymph node metastases and multiple liver metastases who has survived for more than 13 years through aggressive treatments. A 54-year-old woman developed right upper quadrant pain. Computed tomography (CT) revealed a papillary tumor in the gallbladder. Low-density tumors in segments 4, 5, and 8 of the liver and extensive paraaortic lymph node swelling were observed. She underwent central hepatic bisectionectomy and paraaortic lymphadenectomy. Two months later, hepatic metastases were found in segments 2, 3, 6, and 7, and percutaneous ethanol injection and transcatheter arterial chemoembolization were performed. Twelve months after the first surgery, CT revealed lymph node swelling around the right external iliac artery and behind the left renal vein. Metastatic lymph node dissection and resection and reconstruction of the right external iliac artery and vein with artificial graft replacements were performed. Two months later, CT revealed a paraesophageal lymph node swelling, which was treated by radiotherapy. At present, 13 years after the first surgery, and 11 years after the last radiotherapy, she is alive without any sign of recurrence. | 18,987,937 |
Influence of L-rhamnosyl-D-glucosyl derivatives on properties and biological interaction of flavonoids. | The anti-proliferative activity of hesperetin, hesperidin, neohesperidin and rutin was evaluated on human hepatoma cell lines (Hep G2) and correlated to their antioxidant activity. The results obtained showed strong anti-proliferative effects of hesperidin and neohesperidin, considerably higher than the other two additives. Hesperetin induced caspase-3 activation, release of LDH and endogenous accumulation of putrescine. Cell cycle distribution seems to indicate that the inhibitory effects of polyphenols on cell growth could be due to G0/G1 block, and activation of apoptotic pathway in the presence of hesperetin. Our results underline also that the glycone forms show reduced scavenging activity against DPPH, but present a remarkable inhibition of cell proliferation and low cytotoxicity. | 18,987,944 |
Improving nerve regeneration of acellular nerve allografts seeded with SCs bridging the sciatic nerve defects of rat. | The objective of the paper is to evaluate the effect of acellular nerve allografts (ANA) seeded with Schwann cells to promote nerve regeneration after bridging the sciatic nerve defects of rats and to discuss its acting mechanisms. Schwann cells were isolated from neonatal Wistar rats. In vitro Schwann cells were microinjected into acellular nerve allografts and co-cultured. Twenty-four Wistar rats weighing 180-220 g were randomly divided into three groups with eight rats in each group: ANA seeded with Schwann cells (ANA + SCs), ANA group and autografts group. All the grafts were, respectively, served for bridging a 10-mm long surgically created sciatic nerve gap. Examinations of regeneration nerve were performed after 12 weeks by transmission electron microscope (TEM), scanning electron microscope (SEM), and electrophysiological methods, and then analyzed statistically. The results obtained indicated that in vitro Schwann cells displayed the feature of bipolar morphology with oval nuclei. Compared with ANA group, the conduction velocity of ANA + SCs group and autograft group was faster after 12 weeks, latent period was shorter, and wave amplitude was higher (P < 0.05). The difference between ANA + SCs group and autograft group is not significant (P > 0.05). Regeneration nerve myelinated fiber number, myelin sheath thickness, and myelinated fibers/total nerves (%) in both ANA + SCs group and autograft group are higher than that in ANA group; the difference is significant (P < 0.05). The difference between the former two is not significant (P > 0.05). In conclusion, ANA seeded with SCs could improve nerve regeneration and functional recovery after bridging the sciatic nerve gap of rats, which offers a novel approach for the repair peripheral nerve defect. | 18,987,968 |
The biochemistry, metabolism and inherited defects of the pentose phosphate pathway: a review. | The recent discovery of two defects (ribose-5-phosphate isomerase deficiency and transaldolase deficiency) in the reversible part of the pentose phosphate pathway (PPP) has stimulated interest in this pathway. In this review we describe the functions of the PPP, its relation to other pathways of carbohydrate metabolism and an overview of the metabolic defects in the reversible part of the PPP. | 18,987,987 |
[Lipid profiles and therapy status in the secondary prevention of high risk patients with cardiovascular disease and/or diabetes mellitus: the Austrian Hospital Screening Project (HSP)]. | Cardiovascular disease is the major cause of morbidity and premature death in most European populations. Due to its prominent role as a risk factor for cardiovascular mortality, lowering of low density lipoprotein cholesterol (LDL-C) levels is the main goal for management of dyslipidemia. To evaluate lipid profiles and management of high risk patients with hyperlipidemia, we performed an observational study in 20 Austrian Departments of Medicine specialized in cardiology, diabetes and/or metabolism from July 2006 to February 2007. Out of 9152 patients [age (mean +/- SD): women 69 +/- 13, men 65 +/- 12 years) 6838 were considered at "very high risk" (group 1; LDL-C: 99 +/- 38 mg/dl) and 2314 at "high risk" (group 2; LDL-C: 108 +/- 39 mg/dl), respectively. Of 4886 patients on statins, 48% of did not reach their LDL-C goals (<70 mg/dl and <100 mg/dl for group 1 and 2, respectively). In 68% of these patients statin therapy was not intensified subsequently. Among patients without lipid-lowering drugs at study entry, 62% did not meet their targets, and despite treatment in the center 1555 of these patients (58%) remained without medication. With regard to national and international guidelines, there is still a need to improve the clinical practice of lowering LDL-C for secondary prevention in high risk patients in Austria. | 18,988,009 |
Systematic review of controlled clinical trials of gastric lavage in acute organophosphorus pesticide poisoning. | Organophosphorus pesticide (OP) self-poisoning is a major problem in the developing rural world. There is little clinical trial data to guide therapy, hindering the identification of best therapy. Despite the recognition of adverse effects, gastric lavage is commonly done in Asia. We aimed to identify studies assessing its effectiveness. We systematically searched the literature for controlled clinical studies that assessed the effect of gastric lavage in OP pesticide self-poisoning. All 56 studies identified were Chinese and reported benefit from the intervention studied, including multiple gastric lavages, use of norepinephrine or pralidoxime in the lavage fluid, concurrent treatment with naloxone or scopolamine, insertion of the gastric tube via a laparotomy incision, and lavage later than 12 h post-ingestion. However, only 23 were RCTs and none presented adequate methodology for their quality to be assessed. The patient population and study treatment protocol were not defined - large variation in case fatality in the control arm of the studies (from 4.5 to 93%) suggests marked variation between studies and likely between study arms. No study compared an intervention against a control group receiving no gastric lavage or provided any data to indicate whether a significant quantity of poison was removed. Despite widespread use of multiple gastric lavages for OP pesticide poisoning across Asia, there is currently no high-quality evidence to support its clinical effectiveness. There is a need for studies to identify in which patients and for what duration gastric lavage is able to remove significant quantities of poison. Following these studies, large clinical trials will be required to address the effectiveness and safety of gastric lavage (either single or multiple) in acute OP pesticide poisoning. | 18,988,062 |
Long-term trend in patch test reactions: a 32-year statistical overview (1970-2002), part II. | Allergic contact dermatitis remains an important problem worldwide. The objective of this study was to analyze patch test positivity trends of the North American Contact Dermatitis Group. Publications from 1970 to 2002 were reviewed and re-analyzed. Statistical significance was determined with a Cochran-Armitage trend test. We observed a significant increase in positive reactions with carbamates, balsam of Peru, thimerosal, formaldehyde, imidazolidinyl urea, and methyldibromoglutaronitrile. The rates of positive reactions to Dimethylol dimethyl (DMDM) hydantoin, diazolidinyl urea, and methylchloroisothiazolone/methylisothiazolone remained unchanged. We showed a significant decrease in positive reactions for all other allergens. These data provide challenges in public health--for industry, government, and medicine--to decrease the frequency of allergic contact dermatitis. However, the complexities of evaluating a 32-year analysis are numerous, so the data should be interpreted with caution and within the context of this work. | 18,988,088 |
UV inactivation of adenovirus type 4 measured by integrated cell culture qPCR. | Recent changes to water quality regulations may increase the prevalence of ultraviolet (UV) disinfection in water treatment applications. Adenoviruses currently pose a tremendous challenge to UV disinfection due to the high dose requirements for inactivation. This study validates a strategy combining cell culture and quantitative polymerase chain reaction (qPCR) for direct quantification of infectious adenoviruses in disinfection studies. Using primary liver carcinoma cell monolayers grown in well trays or flasks, post-infection washing, and a 24-hr incubation period, the time and material requirements for the infectivity assays were reduced significantly in comparison to traditional assays based on cytopathogenic effects. With this integrated cell culture quantitative PCR (ICC-qPCR) strategy, a standard curve was used to quantify infectious adenoviruses and ultimately determine relative inactivation for a disinfection study. Using ICC-qPCR, UV doses of approximately 10, 34, 69, and 116 mJ/cm(2) corresponded to 1, 2, 3, and 4-log inactivation of adenovirus 4 in water, respectively. The results indicate that the new ICC-qPCR strategy represents a practical alternative for the quantification of adenoviruses in disinfection studies. | 18,988,100 |
Total and methyl mercury in wetland soils and sediments of Louisiana's Pontchartrain Basin (USA). | Accumulation of methylmercury (MeHg) in aquatic biota is a primary toxicological concern associated with Hg contamination in the environment. This study reports total mercury (THg) and MeHg measurements in 11 swamp and 24 marsh soils/sediments in wetlands surrounding Lake Pontchartrain and Lake Maurepas located in Louisiana's Pontchartrain Basin. The salinity level ranged from fresh, brackish to salt water. Average THg content in the swamp soils/sediments (112.3 microg kg(-1), n = 10) was significantly higher (P = 0.04) than in the marsh soils/sediments (56.5 microg kg(-1), n = 24). The THg content in the marsh soils/sediments tended to decrease with salinity increase, probably due to geographical locations of the sampling sites with less Hg input in more saline regions. Average MeHg content in the soils/sediments was 1.3 microg kg(-1) (n = 34), higher than reported values in the bottom sediments of Lake Maurepas (0.8 microg kg(-1), n = 27) and Lake Pontchartrain (0.6 microg kg(-1), n = 147). Average MeHg/THg ratio in the marsh soils/sediments (0.022) was considerably higher than in the swamp soils/sediments (0.012). Analysis of MeHg/THg ratio along the salinity gradient at the marsh soils/sediments show that the highest MeHg/THg ratio (up to 0.040, n = 5) was found at the fresh/brackish water sites, and the lowest (0.002, n = 1) at the salt water site. Results suggest that there was a greater potential for MeHg formation in wetland soils/sediments than in bottom sediments of adjacent lakes. Results suggest that wetland surrounding the lakes may be a potential source of MeHg to the aquatic food chain and significance is governed by area of the adjacent wetland. | 18,988,103 |
Assessment of Pb, Cd, Cr and Ag leaching from electronics waste using four extraction methods. | Heavy metals present in electronic components may leach upon disposal and therefore pose significant environmental hazards. The potential leaching of Pb, Cd, Cr and Ag from PC cathode ray tubes, printed circuit boards (PCBs), PC mice, TV remote controls, and mobile phones was assessed. After controlled crushing, each component was extracted using the Toxicity Characteristic Leaching Procedure (TCLP), EPA Method 1312 (SPLP), NEN 7371 (Dutch Environmental Agency), and DIN S4 (Germany). The TCLP consistently leached the greatest amounts of Pb from all components. The SPLP, NEN 7371 and DIN S4 extracted relatively small amounts of metals compared with the TCLP and were not considered effective as leaching tests for e-waste. The smallest size fraction (< 2 mm) of CRT glass and PCBs leached significantly (p < 0.05) highest Pb via the TCLP. A modified TCLP removed 50.9% more extractable Pb compared with the conventional procedure. | 18,988,110 |
Conducting pharmaceutical R&D in India - Critical components of entry strategies. | In the face of challenges associated with expiring patents, the rising cost of R&D and pressure on pricing, most major pharmaceutical companies are seeking ways to enhance productivity, reduce costs and augment the late-stage new-product pipeline. Exploiting the R&D capabilities in India is one option that can be helpful in achieving these goals. However, considering the challenges involved, important considerations must be incorporated to ensure that an appropriate R&D strategy is meticulously implemented. In creating suitable strategies, it is important to understand the historical perspective that provides insight into the relative strengths of companies in India across the R&D value chain. In addition, the ability of a company to take risks and commit to a long-term investment will largely determine the model that is selected. To implement a given model, an understanding of cultural differences and infrastructural challenges that must be overcome is extremely important. The ultimate factor that determines success or failure, however, lies within the organization. Preparing an organization by establishing appropriate structures and processes is imperative. | 18,988,126 |
Management of postkeratoplasty ametropia: IntraLASIK after penetrating keratoplasty. | The authors describe a technique of laser in situ keratomileusis (LASIK) for the management of postkeratoplasty ametropia using a femtosecond laser for flap creation. The first step was the placement of a disposable suction fixation ring to ensure that it was well-centered on the graft. The applanation cone was applied; the border of the flap was adjusted according to the edge of the graft. The hinge was at the 12 o'clock position; the mean flap diameter was 7.93 mm and the flap depth was 113.33 microm. The flap creation was made with the IntraLase femtosecond laser in a raster pattern. Twenty minutes after the flap creation, it was lifted and the treatment was completed with the Allegretto Wavelight excimer laser. Three patients were treated with this technique and no significant intraoperative or postoperative complications were observed. IntraLASIK is a promising and accurate procedure for the correction of postkeratoplasty ametropia and astigmatism. | 18,988,156 |
Nonvisible subthreshold micropulse diode laser (810 nm) treatment of central serous chorioretinopathy. A pilot study. | To verify the efficacy of nonvisible micropulse diode laser irradiation in the treatment of central serous chorioretinopathy (CSC). Twenty-two patients with CSC for a total of 24 eyes with a disease duration longer than 3 months were included in a prospective study. Patients underwent Early Treatment Diabetic Retinopathy Study visual acuity (VA) examination, dilated ophthalmoscopy, fluorescein angiography, and optical coherence tomography before treatment and during follow- up. Treatment with a micropulse diode laser was given with a duty cycle of 15%. Multiple spots were placed over and adjacent to the area of retinal pigment epithelium leak or decompensation. Mean follow-up was 14 months (range 3-36 months). Powers used ranged from 1 to 2 W (mean 1.35 W). Mean number of spots was 215 (range 90-400). Fourteen eyes were treated once, nine eyes received two to three treatments, and one eye had five treatments during a follow-up of 3 years. Subretinal fluid was resolved or improved in two third of cases 1 month after laser treatment, and in three-quarters at the end of follow-up. Mean retinal thickness was 328 microm, 197 microm, and 168 microm before, 1 month after irradiation, and at the end of follow-up, respectively. No evidence of RPE or retinal changes due to laser treatment were discernible in most of the eyes. Median VA was 20/32 (range 20/100-20/20) before treatment and 20/25 (range 20/200-20/20) at the end of the follow-up. Nonvisible micropulse diode laser may have efficacy in the treatment of CSC. A randomized study with larger series is needed. | 18,988,165 |
Inferior sclerotomies without subretinal fluid drainage for exudative retinal detachment in diffuse retinal pigment epitheliopathy. | To evaluate the efficacy of inferior sutureless sclerotomies without subretinal fluid drainage for the treatment of bullous exudative retinal detachment secondary to diffuse retinal pigment epitheliopathy. A retrospective interventional case series of eyes treated with two inferior postequatorial full-thickness sclerotomies without subretinal fluid drainage. Patients were placed in an upright position 24 hours after surgery. Main outcomes were visual acuity and retinal reattachment rate. Three eyes with recent diagnoses of diffuse retinal pigment epitheliopathy and bullous inferior retinal detachment were included in the study. In all cases, a very thick sclera was evident during surgery. The day after surgery the retina was completely attached in the three eyes. Preoperative visual acuity was light perception, 20/200, and counting fingers. After surgery, visual acuity improved to 20/200, 20/70, and 20/50, respectively. No intra- or postoperative complications occurred. The performance of inferior sutureless sclerotomies without a draining procedure in cases of diffuse retinal pigment epitheliopathy with inferior bullous retinal detachment is a simple and effective technique. It achieves retinal reattachment the day after surgery, allowing laser photocoagulation of the leaking lesions disclosed in fluorescein angiography. | 18,988,170 |
Triamcinolone-assisted vitreous imaging using B-scan ultrasonography. | To evaluate the echographic vitreoretinal patterns before and after intravitreal injection of triamcinolone (IVTA) in eyes with opaque media and several pathologies. One eye with pseudophakic cystoid macular edema and two eyes with postoperative endophthalmitis and opaque media were examined using B-scan ultrasonography, before and after 0.1 mL ITVA (4 mg Kenacort). The obtained images were compared and the two eyes with endophthalmitis underwent pars plana vitrectomy (PPV) the same day. The relationship between intraoperative and echographic findings was evaluated. Vitreous was relatively anechoic in all three cases before ITVA. Postinjection examination improved visualization of vitreous and posterior hyaloid face (PHF) and revealed vitreoretinal adhesions. The echographic findings confirmed intraoperatively in the two vitrectomized eyes. Triamcinolone-assisted ultrasonography enhances imaging of the PHF. This method might be useful in cases with opaque media regarding PPV planning and prognosis. It is suggested to be applied in selected cases taking into account the beneficial diagnosis information versus the risks to IVTA application. | 18,988,184 |
Kinetic modeling of a bi-enzymatic system for efficient conversion of lactose to lactobionic acid. | A model has been developed to describe the interaction between two enzymes and an intermediary redox mediator. In this bi-enzymatic process, the enzyme cellobiose dehydrogenase oxidizes lactose at the C-1 position of the reducing sugar moiety to lactobionolactone, which spontaneously hydrolyzes to lactobionic acid. 2,2'-Azino-bis(3-ethylbenzothiazoline-6-sulfonic acid) diammonium salt is used as electron acceptor and is continuously regenerated by laccase. Oxygen is the terminal electron acceptor and is fully reduced to water by laccase, a copper-containing oxidase. Oxygen is added to the system by means of bubble-free oxygenation. Using the model, the productivity of the process is investigated by simultaneous solution of the rate equations for varying enzyme quantities and redox mediator concentrations, solved with the aid of a numerical solution. The isocharts developed in this work provide an easy-to-use graphical tool to determine optimal process conditions. The model allows the optimization of the employed activities of the two enzymes and the redox mediator concentration for a given overall oxygen mass transfer coefficient by using the isocharts. Model predictions are well in agreement with the experimental data. | 18,988,269 |
Investigations of an O-H...S hydrogen bond via Car-Parrinello and path integral molecular dynamics. | The presence of intramolecular hydrogen bonds influences the binding energy, tautomeric equilibrium, and spectroscopic properties of various classes of organic molecules. This article discusses the O-H...S bridge, one of the less commonly investigated types of intramolecular interactions. 3-mercapto-1,3-diphenylprop-2-en-1-one was considered as the model structure. This compound exhibits photochromic properties. Car-Parrinello molecular dynamics (CPMD) was applied to investigate the spectroscopic and molecular properties of this compound in the gas phase and in the solid state. The second part of the study is devoted to the effects of the quantization of nuclear motions, with special attention to the O-H...S moiety. Path integral molecular dynamics (PIMD) of the molecular crystal of 3-mercapto-1,3-diphenylprop-2-en-1-one was carried out for this purpose. The employment of this fully quantum mechanical technique enables one to study, in a time-averaged sense, the zero-point motion important for flat potential energy surfaces. Finally, the potentials of mean force (Pmfs) were calculated from the CPMD and PIMD data obtained for the solid-state calculations. The effect of including quantum nuclear motion was investigated. In the studied compound, quantum effects shortened the H-bridge and provided a better description of the free energy minimum. The computational results place this uncommon intramolecular H-bonding among the class of strong hydrogen bonds with large red shifts of O-H stretching modes, which correspond well with previously presented experimental data in the literature concerning this structure. | 18,988,272 |
Thin core needle biopsy crush preparations in conjunction with fine-needle aspiration for the evaluation of thyroid nodules: a complementary approach. | Fine-needle aspiration (FNA) is widely accepted as the initial test to evaluate thyroid nodules; however, inadequate and suboptimal specimens have been 1 of its limitations. Unsatisfactory rates of 4.1% to 43% have been reported, but suboptimal specimens with adequate epithelial cells and other limiting factors, such as clotting, often are not addressed. The authors' institution has a low unsatisfactory rate, especially for thyroid biopsies performed under ultrasound in the Interventional Radiology (IR) Department. In addition to on-site evaluation for all cases, they concomitantly use thin, 22/20-gauge core needle biopsy (CB) crush preparations (CP) for unsatisfactory/suboptimal FNAs. The CB usually is done after 2 FNA passes and, in most cases, is exhausted by making an air-dried CP, which is evaluated on site for adequacy; any residual tissue is processed for tissue sections. Experience is required to interpret CP on air-dried smears. In this report, the authors describe a complementary approach to thyroid biopsy that has worked well. All thyroid FNA and CB/CP that were performed in the IR Department during the year 2005 were reviewed. Follow-up histology and records of all procedural complications were retrieved. Seven hundred thirteen thyroid biopsies qualified, 225 biopsies (31%) had FNA with CB/CP (85% had only CP for evaluation), and 488 biopsies (69%) had only FNA. The final unsatisfactory rate in IR for FNA was 8.7%; this was reduced to 3.4% with the use of CB/CP. The addition of CB also helped to obtain a more definitive diagnosis in suboptimal FNA specimens. Cytologic-histologic correlation was comparable for FNA only cases and FNA/CB cases. There were no significant procedural complications in CB cases. FNA in conjunction with a thin CB/CP performed during the same procedure is a safe technique that can reduce the rate of unsatisfactory and suboptimal thyroid biopsy. | 18,988,285 |
Investigation of stressful life events in patients with systemic sclerosis. | To assess the occurrence of stressful life events in the year before the initiation of systemic sclerosis. A consecutive series of 40 patients with systemic sclerosis (mean age (56.3+/-11.9) years, mean disease duration (4.3+/-3.1) years; 32 females and 8 males), including 28 with diffuse cutaneous scleroderma and 12 with limited cutaneous scleroderma, were evaluated. A control group of 40 healthy subjects free of systemic sclerosis also was included. Socioeconomic status was investigated and Paykel's interview for recent life events (a semi-structured research interview covering 64 life events) was conducted. Patients with systemic sclerosis showed higher percentages of lower education (72.5%) and working class (82.5%), and reported more stressful life events (P<0.05), such as exits (P<0.05), undesirable events (P<0.01), and uncontrolled events (P<0.001), when compared with the control. More events that had an objective negative impact (P<0.001) were also reported in systemic sclerosis patients than in the control. These results are in accordance with a multifactorial model of pathogenesis in systemic sclerosis. We reported a strong relationship between stressful life events and the initiation of systemic sclerosis. Our findings are consistent with current understanding of the extensive links of behavioral responses to stress with neurophysiological and biochemical processes. | 18,988,303 |
Free soluble receptor activator of nuclear factor-kappab ligand in gingival crevicular fluid correlates with distinct pathogens in periodontitis patients. | The aim of the experiment was to investigate the levels of free soluble receptor activator of nuclear factor-kb ligand (sRANKL) in periodontal health and disease and their correlations to clinical parameters and important periodontal pathogens. Chronic periodontitis (n=35) and periodontally healthy (n=38) subjects participated in the present study. Pocket depth, recession and bleeding index were recorded at a total of 221 sites. Subgingival plaque samples from these sites were analysed for the levels of Porphyromonas gingivalis, Aggregatibacter actinomycetemcomitans, Tannerella forsythia and Treponema denticola. Gingival crevicular fluid samples were analysed with ELISA for levels of free sRANKL. Comparisons between groups were performed by applying non-parametric tests (Mann-Whitney) and correlations among parameters were sought for with Spearman's r coefficient. Mean levels of free sRANKL were higher in periodontitis subjects and correlated significantly with mean counts of T. denticola on the subject level and P. gingivalis, T. denticola on the site level (Spearman's r coefficient, p<0.05), but not with clinical parameters. No correlations were found between the levels of free sRANKL and investigated parameters in periodontally healthy individuals. No effect of smoking was found on investigated parameters and correlations (univariate analysis of variance and pairwise comparisons). Findings from the present study suggest a correlation of levels of sRANKL with important pathogens in periodontitis patients. | 18,988,315 |
[Weight history of patients with newly diagnosed type 2 diabetes--secondary publication]. | The aim was to estimate and illustrate the weight history of 1,320 newly diagnosed diabetic patients according to patient characteristics at diagnosis. The median recalled weight gain from age 20 to diabetes diagnosis at a median age of 65.3 years was 14.7 kg. The average weight gain from 10 years prior to diabetes diagnosis until diagnosis, however, was only 1 kg and varied with e.g. age, sex, diagnostic plasma glucose, and presence of diabetic retinopathy. The findings contribute to the evidence basis of general practitioners' weight advice both before and after diabetes diagnosis. | 18,988,367 |
Stroke in Pakistan. | Stroke is the most common cause of disability and a leading cause of mortality world wide. Though the incidence is falling in West but probably is rising in Asia. The burden of stroke risk factors in Pakistan is enormous e.g. by 2020 Pakistan will be 4th most populous country in terms of diabetic patients. Similarly every 3rd person above age of 45 years has hypertension. Ironically a great majority of these patients are unaware of their diagnosis. This is further complicated by the fact that most of diagnosed patients have uncontrolled hypertension, as a result of poor compliance on patients part and poor updated knowledge on physicians part. Data on stroke incidence and prevalence from Pakistan is scarce, however, there are several reported case series in literature highlighting significant differences in terms of stroke epidemiology, risk factors and stroke subtypes/patterns. Considering a high population, absolute number of stroke in our country would be in millions. Its consequences are myriad ranging form physical disability to death, to psychologic, social and economic consequences. These consequences do not only affect the individual or his/her family but also society as a whole. We reviewed available literature on stroke and its risk factors from Pakistan. | 18,988,415 |
Salvage decompressive craniectomy in malignant MCA infarcts--results of local experience at Shifa International Hospital, Islamabad, Pakistan. | Malignant infarctions of the middle cerebral artery (MCA) have high mortality. Recent studies showed decreased mortality with good functional outcome in young people with decompressive surgery. We report prospective, non-randomized case series of live patients in whom successful life saving decompressive craniectomy was performed. All five were males. Mean age was 59.2 +/- 13 years. Four had right MCA infarction while I had left MCA infarction. Ipsilateral temporoparietal craniectomy with duraplasty was performed in mean time of 76 +/- 27 hours after onset of symptoms. Four (80%) patients were discharged to home in awake, alert, conversant, hemiparetic state. One patient developed status epilepticus, and was transferred to another facility in intubated. sedated state. Three month follow-up on three patients showed moderate improvement in neurological status. Early craniectomy was life saving in all of our patients. Neurosurgical intervention should be considered early in large MCA infarcts, especially in young patients. | 18,988,416 |
Variables that predict academic achievement in the Spanish compulsory secondary educational system: a longitudinal, multi-level analysis. | This article presents a study whose objective was to identify certain personal and institutional variables that are associated with academic achievement among Spanish, secondary school students, and to analyze their influence on the progress of those students over the course of that stage of their education. In order to do this, a longitudinal, multi-level study was conducted in which a total of 965 students and 27 different schools were evaluated in Language, Math and Social Science at three different times (beginning, middle and end of the period). The results show progress in all the schools and in all areas. As for the personal, student variables, the longitudinal, HLM analyses confirmed the importance of sex and sociocultural background and, distinguishing it from other studies, also the predictive capacity of meta-cognitive abilities and learning strategies on success in school. On the institutional level, the school climate and teachers' expectations of their students were the most relevant of the variables studied. The size of the school, the percentage of students who repeat grades, and the leadership of the administration also explained a portion of the variance in some areas. | 18,988,427 |
Traumatic events and tonic immobility. | Tonic immobility is a basic defense strategy which has not been studied in depth in humans. Data suggest that it may be a relatively frequent phenomenon in victims of rape and sexual abuse, but its occurrence has not been systematically explored in other types of trauma. We carried out a retrospective study in a sample of 100 university students to establish whether tonic immobility varies depending on the nature of the worst trauma experienced, defined subjectively by each participant. Immobility was assessed using the Tonic Immobility Scale and traumas were assessed using the modified Traumatic Events Questionnaire. Seventy percent of the sample had experienced trauma of some kind. There were no significant differences in tonic immobility between different types of trauma (e.g., physical abuse, assault or aggression, serious accident), except that the mean tonic immobility score was significantly higher in the group with trauma due to physical/psychological or sexual abuse than in the group with trauma due to receiving news of the mutilation, serious injury, or violent or sudden death of a loved one. We conclude tentatively that tonic immobility may be typical not only of sexual traumas, but of other kinds of directly experienced traumas as well. | 18,988,436 |
[Serum proteome profiling for ovarion cancer diagnosis using ClinProt magnetic bead technique and MALDI-TOF-mass-spectrometry]. | Using reverse-phase (MB-HIC 8 and HB-HIC 18) weak cation exchange (MB-WCX) and metal affinity ClinProt magnetoc beads peptides and protein factions were obtained from human sera for their profiling by MALDI-TOF mass spectrometry. Proteome profiling of sera from I-IV stage ovarian cancer patients (47 women, average age 51) and from healthy women (47 subjects, average age 49) using MB-WCX beads allowed calculation of the best diagnostic models based on the Genetic Algorithm and Supervised Neural Network classifiers; these model generated 100% sensitivity and specificity when the test set of subjects was analyzed. Introduction of additional sera from patients with colorectal cancer (19) and ulcerous colitis (5) to the statistical model confirmed 100% ovarian cancer recognition. Statistical mass-spectrometry analysis of mass-spectrometry peak areas included to the diagnostic classifiers showed 3 peaks distinctive for ovarian cancer and 4 peaks distinctive for ovarian and colorectal cancer. | 18,988,457 |
[Lentiviral vectors]. | The delivery of genetic material to mammalian cells has a great importance for modern fundamental biology, biomedicine, biotechnology, agriculture and veterinary medicine. The development of new efficient techniques of gene transfer to human cells has led to the establishment of gene therapy, a novel type of treatment targeting severe metabolic disorders, some viral infections, including HIV, autoimmune diseases and genetic defects causing cancer. This review summarizes the achievements in lentiviral-mediated gene transfer, a powerful tool for use in human gene therapy and transgenic research, with a special focus on the genome structure and life cycle of lentiviruses, as well as on the design and safety aspects of lentiviral vector systems. | 18,988,539 |
The evolving process of European combination product review, Part I. | A new European guideline on drug-eluting stents (DES) introduces for the first time detailed information that European drug authorities should review concerning the medicinal substance that is incorporated into this type of drug-device combination product. Part I of this article discusses European requirements that apply to DES. Part II will discuss the new guideline, other stent guidelines and evolving process of drug-device regulatory review in Europe. | 18,988,546 |
Improving biosensors at the nanoscale. | This, the second in the series on the impact of nanotechnology on different types of medical devices, looks again at the field of medical and biological diagnosis and detection. It examines how knowledge at the nanoscale is also helping to develop new generations of miniature devices that are capable of detecting, in vivo, minute levels of analytes or even individual pathogens. | 18,988,548 |
When nurses do the unthinkable. | This series explores the reasons why some nurses abuse or even kill the patients in their care and asks why such unthinkable behaviour is so difficult to understand. | 18,988,562 |
An overview of topical negative pressure therapy in wound care. | This article examines the historical development of topical negative pressure (TNP) therapy, the growing range of devices available and future possibilities for this treatment. The use of vacuum-assisted closure (VAC), different negative pressure settings and alternative TNP devices are discussed. Further guidance and robust clinical evidence are required to support the use of TNP in practice. | 18,988,585 |
Cold-induced modulation and functional analyses of the DRE-binding transcription factor gene, GmDREB3, in soybean (Glycine max L.). | DREB (dehydration-responsive element-binding protein) transcription factors have important roles in the stress-related regulation network in plants. A DREB orthologue, GmDREB3, belonging to the A-5 subgroup of the DREB subfamily, was isolated from soybean using the RACE (rapid amplification of cDNA ends) method. Northern blot analysis showed that expression of GmDREB3 in soybean seedlings was induced following cold stress treatment for 0.5 h and was not detected after 3 h. However, it was not induced by drought and high salt stresses or by abscisic acid (ABA) treatment. This response was similar to those of members in the A-1 subgroup and different from those of other members in the A-5 subgroup, suggesting that the GmDREB3 gene was involved in an ABA-independent cold stress-responsive signal pathway. Furthermore, analysis of the GmDREB3 promoter elucidated its cold-induced modulation. A promoter fragment containing bases -1058 to -664 was involved in response to cold stress, and its effect was detected for 1 h after treatment, but a transcriptional repressor appeared to impair this response by binding to a cis-element in the region -1403 to -1058 at 24 h after the beginning of cold stress. Moreover, the GmDREB3 protein could specifically bind to the DRE element in vitro, and activated expression of downstream reporter genes in yeast cells. In addition, overexpression of GmDREB3 enhanced tolerance to cold, drought, and high salt stresses in transgenic Arabidopsis. Physiological analyses indicated that the fresh weight and osmolality of GmDREB3 transgenic Arabidopsis under cold stress were higher than those of wild-type controls. GmDREB3 transgenic tobacco accumulated higher levels of free proline under drought stress and retained higher leaf chlorophyll levels under high salt stress than wild-type tobacco. In addition, constitutive expression of GmDREB3 in transgenic Arabidopsis caused growth retardation, whereas its expression under control of the stress-inducible Rd29A promoter minimized negative effects on plant growth under normal growth conditions, indicating that a combination of the Rd29A promoter and GmDREB3 might be useful for improving tolerance to environmental stresses in crop plants. | 18,988,621 |
Relation of mechanical dyssynchrony with underlying cardiac structure and performance in chronic systolic heart failure: implications on clinical response to cardiac resynchronization. | The aim of this study is to describe the relationship between ventricular mechanical dyssynchrony (VMD) and echocardiographic indices of cardiac remodelling. We evaluated 219 ambulatory patients with chronic systolic heart failure [left ventricular ejection fraction (LVEF) <or= 35%, New York Heart Association functional classes II-IV] who underwent echocardiographic evaluation. The presence of dyssynchrony was defined by Bader criteria (intra-VMD > 40 ms and/or inter-VMD > 38 ms). In our study cohort, 59% of patients had evidence of dyssynchrony (including 44% with intra-VMD and 38% with inter-VMD, and 20% with both). Inter-VMD correlated with QRS width (r = 0.48, P < 0.0001) better than intra-VMD (r = 0.24, P < 0.001). Higher inter-VMD was associated with less restrictive filling patterns (rank sums P = 0.012) and larger left ventricular end-diastolic dimension (LVEDD, rank sums P = 0.020), but intra-VMD values were similar across diastolic stages and LVEDD tertiles. In chronic systolic heart failure, evidence of mechanical dyssynchrony is prevalent but the underlying cardiac structure and performance may influence the degree of inter-VMD more so than intra-VMD. Our data suggest that the extent of inter-VMD is directly related to the degree of dilatation of the heart but inversely to diastolic dysfunction. | 18,988,651 |
Comparison between colour-coded and spectral tissue Doppler measurements of systolic and diastolic myocardial velocities: effect of temporal filtering and offline gain setting. | Colour tissue Doppler (TD) has been reported to underestimate the longitudinal myocardial motion velocities measured with spectral TD. This study evaluates the effect of temporal smoothing and offline gain settings on the results of velocity measurements with these two methods and the difference between them. In 57 patients, 2D data and left ventricular velocity profiles were acquired using spectral and colour TD for a subsequent offline analysis. Longitudinal myocardial velocities were measured at unsaturated, 50%-saturated and fully saturated gain, and before and after temporal smoothing using 30, 50, and 70 ms filters, respectively. Gain level and filter width altered significantly the measured velocities. Peak systolic and early diastolic velocities were significantly higher (P < 0.001) and E/E' ratio was significantly lower (P < 0.001) with spectral TD than with colour TD, although there was a good correlation between the results of both TD modalities. The differences between the methods increased at increasing filter width and gain level. Despite good correlation of the results, spectral TD produces significantly higher myocardial velocity values and lower E/E' ratio than colour TD modality. Increasing gain and temporal smoothing alter significantly the results of velocity measurements and accentuate the difference between the two TD methods. | 18,988,658 |
Effects of early progressive eccentric exercise on muscle size and function after anterior cruciate ligament reconstruction: a 1-year follow-up study of a randomized clinical trial. | The authors previously reported that focused eccentric resistance training during the first 15 weeks following anterior cruciate ligament reconstruction (ACL-R) induced greater short-term increases in muscle volume, strength, and measures of function relative to standard rehabilitation. The purpose of this study was to evaluate the effects of early progressive eccentric exercise on muscle volume and function at 1 year after ACL-R. Forty patients who had undergone an ACL-R were randomly assigned to 1 of 2 groups: a group that received early progressive eccentric exercise (n=20) and a group that received standard rehabilitation (n=20). Seventeen participants in the eccentric exercise group and 15 participants in the standard rehabilitation group completed a 1-year follow-up. Magnetic resonance images of the thighs were acquired 1 year after ACL-R and compared with images acquired 3 weeks after surgery. Likewise, routine knee examinations, self-report assessments, and strength and functional testing were completed 1 year after surgery and compared with previous evaluations. A 2-factor analysis of variance for repeated measures (group x time) was used to analyze the data. Compared with the standard rehabilitation group, improvements in quadriceps femoris and gluteus maximus muscle volume in the involved lower extremity from 3 weeks to 1 year following ACL-R were significantly greater in the eccentric exercise group. Improvements in quadriceps femoris and gluteus maximus muscle volume were 23.3% (SD=14.1%) and 20.6% (SD=12.9%), respectively, in the eccentric exercise group and 13.4% (SD=10.3%) and 11.6% (SD=10.4%), respectively, in the standard rehabilitation group. Improvements in quadriceps femoris muscle strength and hopping distance also were significantly greater in the eccentric exercise group 1 year postsurgery. A 12-week focused eccentric resistance training program, implemented 3 weeks after ACL-R, resulted in greater increases in quadriceps femoris and gluteus maximus muscle volume and function compared with standard rehabilitation at 1 year following ACL-R. | 18,988,664 |
Lower-extremity strength differences predict activity limitations in people with chronic stroke. | Body system impairments following stroke have a complex relationship with functional activities. Although gait and balance deficits are well-documented in people after stroke, the overlapping influence of body impairments makes it difficult to prioritize interventions. This study examined the relationship between prospectively selected measures of body function and structure (body mass index, muscle strength, sensation, and cognition) and activity (gait speed, gait endurance, and functional balance) in people with chronic stroke. This was a cross-sectional, observational study. Twenty-six individuals with mean (SD) age of 57.6 (11) years and time after stroke of 45.4 (43) months participated. Four variables (body mass index, muscle strength difference between the lower extremities, sensation difference between the lower extremities, and Mini-Mental Status Exam score) were entered into linear regression models for gait speed, Six-Minute Walk Test distance, and Berg Balance Scale score. Lower-extremity strength difference was a significant individual predictor for gait speed, gait endurance, and functional balance. Cognition significantly predicted only gait speed. The authors did not include all possible factors in the model that may have influenced gait and balance in these individuals. Strength deficits in the hemiparetic lower extremity should be an important target for clinical interventions to improve function in people with chronic stroke. | 18,988,665 |
Expression of immunoregulatory molecules by thyrocytes protects nonobese diabetic-H2h4 mice from developing autoimmune thyroiditis. | One approach to prevent tissue destruction by autoimmune attack in organ-specific autoimmune diseases is to protect the target tissue from autoimmune reaction, regardless of its persistent activity. To provide proof-of-principle for the feasibility of this approach, the immunoregulatory molecules, TNF-related apoptosis-inducing ligand (TRAIL) and indoleamine 2, 3-dioxygenase, were expressed in the thyroid glands using adenovirus vector in nonobese diabetic-H2(h4) mice that spontaneously develop thyroiditis. Mice were anesthetized, and the thyroid glands were exposed by neck dissection, followed by in situ infection with adenovirus vector (5 x 10(10) particles per mouse) twice or thrice, starting 1 d or 4 wk before mice were supplied with sodium iodine (NaI) water. After 8 wk NaI provision, the extent of thyroiditis, serum titers of antithyroglobulin antibodies, and cytokine expression in the spleen were examined. In situ infection of adenovirus expressing TRAIL or indoleamine 2, 3-dioxygenase, but not green fluorescent protein, significantly suppressed thyroiditis scores. However, antithyroglobulin antibody titers and expression levels of cytokines (interferon-gamma and IL-4) in the spleen remained unaltered. Importantly, adenovirus infection 4 wk after NaI provision was also effective at suppressing thyroiditis. The suppressive effect of TRAIL appears to be mediated at least partly by accumulation of CD4(+)Foxp3(+) regulatory T cells into the thyroid glands. Thus, localized expression of immunoregulatory molecules efficiently protected the thyroid glands from autoimmune attack without changing the systemic autoimmunity in nonobese diabetic-H2(h4) mice. This kind of immunological intervention, although it does not suppress autoimmune reactivity, may have a potential for treating organ-specific autoimmune diseases. | 18,988,676 |
An ancient horizontal gene transfer between mosquito and the endosymbiotic bacterium Wolbachia pipientis. | The extent and biological relevance of horizontal gene transfer (HGT) in eukaryotic evolution remain highly controversial. Recent studies have demonstrated frequent and large-scale HGT from endosymbiotic bacteria to their hosts, but the great majority of these transferred genes rapidly become nonfunctional in the recipient genome. Here, we investigate an ancient HGT between a host metazoan and an endosymbiotic bacterium, Wolbachia pipientis. The transferred gene has so far been found only in mosquitoes and Wolbachia. In mosquitoes, it is a member of a gene family encoding candidate receptors required for malaria sporozoite invasion of the mosquito salivary gland. The gene copy in Wolbachia has substantially diverged in sequence from the mosquito homolog, is evolving under purifying selection, and is expressed, suggesting that this gene is also functional in the bacterial genome. Several lines of evidence indicate that the gene may have been transferred from eukaryotic host to bacterial endosymbiont. Regardless of the direction of transfer, however, these results demonstrate that interdomain HGT may give rise to functional, persistent, and possibly evolutionarily significant new genes. | 18,988,686 |
Exposure of alpha2,6-sialylated lactosaminic chains marks apoptotic and necrotic death in different cell types. | Many observations have reported glycosylation changes associated with apoptosis in different biological systems, although none of these has shown any general significance. In this work, we show that in cell lines from different histological origin, (colon, breast, pancreas, and bladder cancer) as well as in normal human and mice neutrophils, apoptosis is accompanied by the exposure of sugar chains recognized by the lectin from Sambucus nigra (SNA), specific for Sia alpha 2,6Gal/GalNAc structures. Also, cells undergoing primary necrosis induced by heat treatment (56 degrees C, 30 min) expose specifically binding sites for SNA. While this modification is recognized also by the lectin from the mushroom Polyporus squamosus, which is highly specific for alpha2,6-sialylated lactosamine, no significant changes were detected in the binding of lectins specific for other carbohydrate structures, such as those from Phaseolus vulgaris, Arachis hypogea, and Maackia amurensis. The binding of SNA to apoptotic/necrotic cells is inhibited by neuraminidase treatment and by alpha2,6-sialylated compounds. In apoptotic, but not in necrotic SW948 cells, SNA reactivity is specifically associated with 65, 69, and 87 kDa glycoproteins. The exposure of SNA-reactive chains by apoptotic/necrotic cells occurs also in cells not expressing sialyltransferases ST6Gal.1 or ST6Gal.2 and is largely independent of the presence of alpha2,6-sialylated lactosaminic chains on the surface of preapoptotic cells. In neutrophils from ST6Gal.1 knock-out mice, the apoptosis-related increase in SNA reactivity is reduced but not abolished. These data demonstrate that apoptosis and primary necrosis induce a specific glycosylation change independent of the cell type and nature of the stimulus. | 18,988,689 |
Gut peristalsis is governed by a multitude of cooperating mechanisms. | Peristaltic motor activity of the gut is an essential activity to sustain life. In each gut organ, a multitude of overlapping mechanisms has developed to acquire the ability of coordinated contractile activity under a variety of circumstances and in response to a variety of stimuli. The presence of several simultaneously operating control systems is a challenge for investigators who focus on the role of one particular control activity since it is often not possible to decipher which control systems are operating or dominant in a particular situation. A crucial advantage of multiple control systems is that gut motility control can withstand injury to one or more of its components. Our efforts to increase understanding of control mechanism are not helped by recent attempts to eliminate proven control systems such as interstitial cells of Cajal (ICC) as pacemaker cells, or intrinsic sensory neurons, nor does it help to view peristalsis as a simple reflex. This review focuses on the role of ICC as slow-wave pacemaker cells and places ICC into the context of other control mechanisms, including control systems intrinsic to smooth muscle cells. It also addresses some areas of controversy related to the origin and propagation of pacemaker activity. The urge to simplify may have its roots in the wish to see the gut as a consequence of a single perfect design experiment whereas in reality the control mechanisms of the gut are the messy result of adaptive changes over millions of years that have created complementary and overlapping control systems. All these systems together reliably perform the task of moving and mixing gut content to provide us with essential nutrients. | 18,988,693 |
Effects of treatment of renal osteodystrophy on bone histology. | Renal osteodystrophy is characterized by abnormalities in bone turnover, mineralization, and bone volume. The effects of treatment modalities for renal osteodystrophy on bone should be analyzed with respect to these abnormalities. The major treatment modalities for renal osteodystrophy include phosphate binders, vitamin D compounds, and calcimimetics. Aluminum-containing phosphate binders have been shown to be toxic to bone secondary to their effects on bone turnover, mineralization, and bone volume. The use of calcium-based phosphate binders has been associated with the development of adynamic bone disease (low bone turnover), bone loss, and worsening of vascular calcifications. New nonaluminum, noncalcium phosphate binders have been developed (sevelamer hydrochloride and lanthanum carbonate). These agents show a potential for improvement in bone turnover and bone volume. Patients with renal osteodystrophy are deficient in calcitriol and often in calcidiol. Calcidiol deficiency has been underappreciated and deserves to be addressed in the treatment of patients with renal osteodystrophy. Calcitriol replacement therapy by daily oral administration is associated with frequent episodes of hypercalcemia and suppression of bone turnover in patients with stages 3 to 5 chronic kidney disease. Pulse oral or intravenous calcitriol administration induces frequent episodes of hypercalcemia or hyperphosphatemia, respectively, and achieves the same degree of correction of bone abnormalities. There are no data on the effects of paricalcitol or doxercalciferol on human bone. Experimental data, however, show that these two analogues and maxacalcitol may control serum parathyroid hormone levels without suppressing bone turnover. Calcimimetics lower parathyroid hormone levels and bone turnover. | 18,988,701 |
Structure of SF-1 bound by different phospholipids: evidence for regulatory ligands. | Despite the fact that many nuclear receptors are ligand dependent, the existence of obligate regulatory ligands is debated for some receptors, including steroidogenic factor 1 (SF-1). Although fortuitously bound bacterial phospholipids were discovered in the structures of the SF-1 ligand-binding domain (LBD), these lipids might serve merely as structural ligands. Thus, we examined whether exogenously added phospholipids would exchange for these bacterial lipids and bind to SF-1. Here, we report the first crystal structure of the SF-1 LBD bound by the exchanged phosphatidylcholine. Although the bound phosphatidylcholine phospholipid mimics the conformation of bound bacterial phosphoplipids, two surface loops, L2-3 and L11-12, surrounding the entrance to the pocket vary significantly between different SF-1 LBD structures. Based on this observation, we hypothesized that a bound ligand might control the conformations of loops L2-3 and L11-12, and that conserved residues in these dynamic loops could influence ligand binding and the receptor function. Consistent with this hypothesis, impaired phospholipid exchange and diminished transcriptional activity were observed for loop L11-12 SF-1 mutants and for the loop L2-3 human mutant R255L. The endocrine disease associated with this L2-3 mutation coupled with our cellular and biochemical data suggest that critical residues at the mouth of the ligand-binding pocket have evolved for efficient binding of phospholipid ligands and for achieving optimal SF-1 activity. | 18,988,706 |
Blood pressure control and pharmacotherapy patterns in the United States before and after the release of the Joint National Committee on the Prevention, Detection, Evaluation, and Treatment of High Blood Pressure (JNC 7) guidelines. | Despite recommendations from the Joint National Committee on the Prevention, Detection, Evaluation, and Treatment of High Blood Pressure (JNC 7), only 36.8% of patients were at target blood pressure (BP) in 2003 and 2004. The objective of this study was to assess improvements in BP control and treatment patterns before and after the publication of JNC 7. This was a retrospective, time series analysis of 27 provider groups and managed care organizations from 1998 through 2006. Patients with hypertension were identified from more than 4000 physicians. Medical charts were collected and clinical data were evaluated using prevailing JNC criteria during the time period before and after JNC 7. A total of 19,258 patients were identified with hypertension: 15,258 included in the before-JNC 7 cohort and 4,000 in the after-JNC 7 cohort. BP control in the before-JNC 7 cohort was 40.8% compared with 49.3% in the after-JNC 7 cohort (P < .0001). After controlling for demographic and clinical covariates, patients in the before-JNC 7 cohort were 45% less likely to achieve BP control compared with the after-JNC 7 cohort (odds ratio, 0.551; P < .0001). Although findings indicate BP control is improving, a significant need for further improvement remains. | 18,988,718 |
Interferon-gamma and interleukin-4 reciprocally regulate CD8 expression in CD8+ T cells. | The CD8 co-receptor can modulate CD8(+) T cell function through its contributions to T cell receptor (TCR) binding and signaling. Here we show that IFN-gamma and IL-4 exert opposing effects on the expression of CD8alpha mRNA and surface CD8 protein during CD8(+) T cell activation. IL-4 caused down-regulation of surface CD8 on ovalbumin (OVA)(257-264)-specific TCR-transgenic OT-I CD8(+) T cells activated with OVA(257-264)-coated antigen presenting cells or polyclonal stimuli, and on wild type CD8(+) T cells activated with polyclonal stimuli. This effect was enhanced in each case when the cells lacked a functional IFN-gamma or IFN-gamma R gene. When WT or IFN-gamma-deficient OT-I CD8(+) T cells were analyzed 9 days after co-injection with control or IL-4-expressing OVA(+) tumor cells into RAG-2(-/-)gamma c(-/-) mice, CD8 levels were highest on WT donor cells from mice that received the control tumor and lowest on IFN-gamma-deficient donor cells from mice that received the IL-4-expressing tumor. The latter CD8(low) cells displayed markedly impaired binding of OVA(257-264)/MHC tetramers and peptide/MHC-dependent degranulation. The data reveal an unexpected role for IFN-gamma in tuning the CD8 co-receptor during primary CD8(+) T cell activation both in vitro and in vivo. | 18,988,742 |
Analytical distributions for stochastic gene expression. | Gene expression is significantly stochastic making modeling of genetic networks challenging. We present an approximation that allows the calculation of not only the mean and variance, but also the distribution of protein numbers. We assume that proteins decay substantially more slowly than their mRNA and confirm that many genes satisfy this relation by using high-throughput data from budding yeast. For a two-stage model of gene expression, with transcription and translation as first-order reactions, we calculate the protein distribution for all times greater than several mRNA lifetimes and thus qualitatively predict the distribution of times for protein levels to first cross an arbitrary threshold. If in addition the fluctuates between inactive and active states, we can find the steady-state protein distribution, which can be bimodal if fluctuations of the promoter are slow. We show that our assumptions imply that protein synthesis occurs in geometrically distributed bursts and allows mRNA to be eliminated from a master equation description. In general, we find that protein distributions are asymmetric and may be poorly characterized by their mean and variance. Through maximum likelihood methods, our expressions should therefore allow more quantitative comparisons with experimental data. More generally, we introduce a technique to derive a simpler, effective dynamics for a stochastic system by eliminating a fast variable. | 18,988,743 |
MALDI-TOF MS genotyping of polymorphisms related to 1-carbon metabolism using common and mass-modified terminators. | Large cohort studies may provide sufficient power to disentangle the role of polymorphisms related to 1-carbon metabolism and chronic diseases, but they require fast, accurate, high-throughput genotyping techniques. MALDI-TOF mass spectrometry has been adapted to rapid fine mapping using various approaches for allele discrimination. We developed a genotyping method based on MALDI-TOF MS and compared assay performance for formats based on standard and mass-modified terminators. The assay includes 20 polymorphisms of 14 genes involved in 1-carbon metabolism (BHMT 742G>A, CBS 844ins68 and 699C>T, CTH 1364G>T, DHFR del19, NOS3 -786T>C and 894G>T, FOLR1 1314G>A, MTHFD1 -105T>C and 1958G>A, MTHFR 677C>T and 1298A>C, MTR 2756A>G, MTRR 66A>G and 524C>T, SLC19A1 80G>A, SHMT1 1420C>T, TCN2 67A>G and 776C>G, and TYMS 1494del6). Missing calls were observed for 4.7% of the DNA samples, attributed to failed liquid sample handling. Highly accurate genotyping was obtained by mass-modified as well as standard ddNTPs, with an average error rate of < or =0.1% by analysis of sample duplicates. A semiquantitative approach enabled unambiguous identification of the CBS 844ins68. Cluster plots of the relative allele intensities showed allele-specific bias according to type of minisequencing terminator and revealed a potential structural variation in the BHMT gene. MALDI-TOF MS-based genotyping using either standard or mass-modified terminators allows the accurate determination of single nucleotides as well as structural genetic variants. This was demonstrated with 20 polymorphisms involved in 1-carbon metabolism. | 18,988,749 |
Fluid shear stress induces arterial differentiation of endothelial progenitor cells. | Endothelial progenitor cells (EPCs) are mobilized from bone marrow to peripheral blood and contribute to angiogenesis in tissues. In the process, EPCs are exposed to the shear stress generated by blood flow and tissue fluid flow. Our previous study showed that shear stress promotes differentiation of EPCs into mature endothelial cells. In this study, we investigated whether EPCs differentiate into arterial or venous endothelial cells in response to shear stress. When cultured EPCs derived from human peripheral blood were exposed to controlled levels of shear stress in a flow-loading device, the mRNA levels of the arterial endothelial cell markers ephrinB2, Notch1/3, Hey1/2, and activin receptor-like kinase 1 increased, but the mRNA levels of the venous endothelial cell markers EphB4 and neuropilin-2 decreased. Both the ephrinB2 increase and the EphB4 decrease were shear stress dependent rather than shear rate dependent. EphrinB2 protein was increased in shear-stressed EPCs, and the increase in ephrinB2 expression was due to activated transcription and not mRNA stabilization. Deletion analysis of the ephrinB2 promoter indicated that the cis-element (shear stress response element) is present within 106 bp 5' upstream from the transcription initiation site. This region contains the Sp1 consensus sequence, and a mutation in its sequence decreased the basal level of transcription and abolished shear stress-induced ephrinB2 transcription. Electrophoretic mobility shift assays and chromatin immunoprecipitation assays showed that shear stress markedly increased binding of Sp1 to its consensus sequence. These results indicate that shear stress induces differentiation of EPCs into arterial endothelial cells by increasing ephrinB2 expression in EPCs through Sp1 activation. | 18,988,767 |
Discordance in spirometric interpretations using three commonly used reference equations vs national health and nutrition examination study III. | Spirometry plays an essential role in the diagnosis and management of pulmonary diseases. The accurate interpretation of spirometric data depends on comparison to a reference population to identify abnormalities in ventilatory function. National guidelines recommended the use of the National Health and Nutrition Examination Study (NHANES) III data set as the preferred reference population for those persons 8 to 80 years of age in the United States. To determine the effect of using NHANES III reference equations, compared to those of Crapo et al (Crapo), Knudson et al (Knudson), or Morris et al (Morris), on spirometric interpretations in non-Hispanic white patients. We conducted a cross-sectional study of all white patients undergoing spirometry testing at our hospital from January 2000 through May 2007. Patients were classified as normal, restricted, obstructed, or mixed, based on the American Thoracic Society (ATS)/European Respiratory Society (ERS) guidelines, using the Crapo, Knudson, Morris, and NHANES III prediction equations. Differences in the classifications based on the reference data set were evaluated. At total of 8,733 subjects (62.4% male subjects) were identified, with a mean age of 53 years. Discordance was most common when the results from prediction equations by Knudson and Morris were compared to those of NHANES III (45.5% and 35.3%, respectively). Diagnostic recategorizations occurred less frequently when the prediction equations by Crapo were compared with those of NHANES III (15.9%). Relative to NHANES III, the prediction equations by Knudson, Crapo, and Morris tend to overclassify obstruction and underclassify restriction. There is significant discordance between the prediction equations put forth by Crapo, Knudson, Morris, and the NHANES III. Our data suggest that the diagnostic reclassification of many patients undergoing pulmonary function testing will occur when ATS/ERS guidelines are implemented. Pulmonologists and other physicians interpreting spirometry need to be aware of the presence and nature of these changes. | 18,988,777 |
Tumors stimulate platelet delivery of angiogenic factors in vivo: an unexpected benefit. | The interaction between platelets and the tumor microenvironment results in the modulation of angiogenesis, although the mechanisms governing this regulation remain unclear. This study explores the differences in the communication between wounded tissues and healthy, tumor-conditioned, and frozen platelets. Platelet-rich plasma obtained from healthy (PRP) or tumor-bearing (TPRP) mice was applied to dorsal, full-thickness wounds on diabetic mice. Wound healing was evaluated using macroscopic criteria and a staging system based on angiogenesis and stromal cell proliferation. Proteomic analysis was used to compare the levels of angiogenic proteins contained in the platelet preparations. TPRP-treated wounds reached 90% wound closure 5.6 to 9.5 days earlier than PRP-treated and nontreated wounds, respectively. TPRP induced a fourfold increase in stromal cell proliferation compared with nontreated wounds, and a 2.5-fold increase compared with PRP-treated wounds. TPRP induced the highest stimulation of angiogenesis with a fourfold increase compared with nontreated controls. On day 21, wounds treated with TPRP showed a typical architecture with thick collagen bundles. Although the levels of angiogenesis regulators detected via SELDI-ToF were similar between the PRP and TPRP treatment regimens, the enhanced healing capacity of TPRP suggests improved platelet delivery as indicated by frozen TPRP preparations that had lost most of their pro-angiogenic drive. In conclusion, these results show that intact tumor-conditioned platelets display an improved ability to deliver angiogenesis regulators to wounded tissues. | 18,988,799 |
Matrix metalloproteinase-1 and thrombin differentially activate gene expression in endothelial cells via PAR-1 and promote angiogenesis. | Many tumor types express matrix metalloproteinase-1 (MMP-1); its collagenase activity facilitates both tumor cell invasion and metastasis. MMP-1 expression is also associated with increased angiogenesis; however, the exact mechanism by which this occurs is not clear. MMP-1 proteolytically activates protease activated receptor-1 (PAR-1), a thrombin receptor that is highly expressed in endothelial cells. Thrombin is also present in the tumor microenvironment, and its activation of PAR-1 is pro-angiogenic. It is currently unknown whether MMP-1 activation of PAR-1 induces angiogenesis in a similar or different manner compared with thrombin. We sought to determine the mechanism by which MMP-1 promotes angiogenesis and to compare the effects of MMP-1 with those of thrombin. Our results demonstrate that via PAR-1, MMP-1 activates mitogen-activated protein kinase signaling cascades in microvessel endothelial cells. Although thrombin activation of PAR-1 also induces signaling through these pathways, the time-course of activation appears to vary. Gene expression analysis revealed a possible consequence of these signaling differences as MMP-1 and thrombin induce expression of different subsets of pro-angiogenic genes. Furthermore, the combination of thrombin and MMP-1 is more angiogenic than either protease alone. These data demonstrate that MMP-1 acts directly on endothelial cells as a pro-angiogenic signaling molecule and also suggest that the effects of MMP-1 may complement the activity of thrombin to better facilitate angiogenesis and promote tumor progression. | 18,988,801 |
Photoexcited CRY2 interacts with CIB1 to regulate transcription and floral initiation in Arabidopsis. | Cryptochromes (CRY) are photolyase-like blue-light receptors that mediate light responses in plants and animals. How plant cryptochromes act in response to blue light is not well understood. We report here the identification and characterization of the Arabidopsis CIB1 (cryptochrome-interacting basic-helix-loop-helix) protein. CIB1 interacts with CRY2 (cryptochrome 2) in a blue light-specific manner in yeast and Arabidopsis cells, and it acts together with additional CIB1-related proteins to promote CRY2-dependent floral initiation. CIB1 binds to G box (CACGTG) in vitro with a higher affinity than its interaction with other E-box elements (CANNTG). However, CIB1 stimulates FT messenger RNA expression, and it interacts with chromatin DNA of the FT gene that possesses various E-box elements except G box. We propose that the blue light-dependent interaction of cryptochrome(s) with CIB1 and CIB1-related proteins represents an early photoreceptor signaling mechanism in plants. | 18,988,809 |
Consciousness and anesthesia. | When we are anesthetized, we expect consciousness to vanish. But does it always? Although anesthesia undoubtedly induces unresponsiveness and amnesia, the extent to which it causes unconsciousness is harder to establish. For instance, certain anesthetics act on areas of the brain's cortex near the midline and abolish behavioral responsiveness, but not necessarily consciousness. Unconsciousness is likely to ensue when a complex of brain regions in the posterior parietal area is inactivated. Consciousness vanishes when anesthetics produce functional disconnection in this posterior complex, interrupting cortical communication and causing a loss of integration; or when they lead to bistable, stereotypic responses, causing a loss of information capacity. Thus, anesthetics seem to cause unconsciousness when they block the brain's ability to integrate information. | 18,988,836 |
Biology, politics, and the emerging science of human nature. | In the past 50 years, biologists have learned a tremendous amount about human brain function and its genetic basis. At the same time, political scientists have been intensively studying the effect of the social and institutional environment on mass political attitudes and behaviors. However, these separate fields of inquiry are subject to inherent limitations that may only be resolved through collaboration across disciplines. We describe recent advances and argue that biologists and political scientists must work together to advance a new science of human nature. | 18,988,845 |
Global protein stability profiling in mammalian cells. | The abundance of cellular proteins is determined largely by the rate of transcription and translation coupled with the stability of individual proteins. Although we know a great deal about global transcript abundance, little is known about global protein stability. We present a highly parallel multiplexing strategy to monitor protein turnover on a global scale by coupling flow cytometry with microarray technology to track the stability of individual proteins within a complex mixture. We demonstrated the feasibility of this approach by measuring the stability of approximately 8000 human proteins and identifying proteasome substrates. The technology provides a general platform for proteome-scale analysis of protein turnover under various physiological and disease conditions. | 18,988,847 |
Fat metabolism links germline stem cells and longevity in C. elegans. | Fat metabolism, reproduction, and aging are intertwined regulatory axes; however, the mechanism by which they are coupled remains poorly understood. We found that germline stem cells (GSCs) actively modulate lipid hydrolysis in Caenorhabditis elegans, which in turn regulates longevity. GSC arrest promotes systemic lipolysis via induction of a specific fat lipase. Subsequently, fat mobilization is promoted and life span is prolonged. Constitutive expression of this lipase in fat storage tissue generates lean and long-lived animals. This lipase is a key factor in the lipid hydrolysis and increased longevity that are induced by decreased insulin signaling. These results suggest a link between C. elegans fat metabolism and longevity. | 18,988,854 |
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