title stringlengths 0 1.13k | abstract stringlengths 1 15.7k | PMID int64 22 36.5M |
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Plasmacytoid dendritic cells mediate oral tolerance. | Oral tolerance prevents oral sensitization to dietary antigens (Ags), including proteins and haptens, and development of delayed-type hypersensitivity (DTH) responses. We showed here that plasmacytoid dendritic cells (pDCs) prevented oral T cell priming and were responsible for systemic tolerance to CD4(+) and CD8(+) T cell-mediated DTH responses induced by Ag feeding. Systemic depletion of pDCs prevented induction of tolerance by antigen feeding. Transfer of oral Ag-loaded liver pDCs to naive recipient mice induced Ag-specific suppression of CD4(+) and CD8(+) T cell responses to protein and hapten, respectively. Liver is a site of oral Ag presentation, and pDCs appeared to induce anergy or deletion of Ag-specific T cells in the liver relatively rapidly via a CD4(+) T cell-independent mechanism. These data demonstrate that oral tolerance relies on Ag presentation by pDC to T cells and suggest that pDC could represent a key therapeutic target for intestinal and systemic inflammatory diseases. | 18,789,731 |
Regional variation in the denial of reimbursement for bone mineral density testing among US Medicare beneficiaries. | Although the Bone Mass Measurement Act outlines the indications for central dual-energy X-ray absorptiometry (DXA) testing for US Medicare beneficiaries, the specifics regarding the appropriate ICD-9 codes to use for covered indications have not been specified by Medicare and are sometimes ambiguous. We describe the extent to which DXA reimbursement was denied by gender and age of beneficiary, ICD-9 code submitted, time since previous DXA, whether the scan was performed in the physician's office and local Medicare carrier. Using Medicare administrative claims data from 1999 to 2005, we studied a 5% national sample of beneficiaries age > or =65 yr with part A+B coverage who were not health maintenance organization enrollees. We identified central DXA claims and evaluated the relationship between the factors listed above and reimbursement for central DXA (CPT code 76075). Multivariable logistic regression was used to evaluate the independent relationship between DXA reimbursement, ICD-9 diagnosis code, and Medicare carrier. For persons who had no DXA in 1999 or 2000 and who had 1 in 2001 or 2002, the proportion of DXA claims denied was 5.3% for women and 9.1% for men. For repeat DXAs performed within 23 mo, the proportion denied was approximately 19% and did not differ by sex. Reimbursement varied by more than 6-fold according to the ICD-9 diagnosis code submitted. For repeat DXAs performed at <23 mo, the proportion of claims denied ranged from 2% to 43%, depending on Medicare carrier. Denial of Medicare reimbursement for DXA varies significantly by sex, time since previous DXA, ICD-9 diagnosis code submitted, place of service (office vs facility), and local Medicare carrier. Greater guidance and transparency in coding policies are needed to ensure that DXA as a covered service is reimbursed for Medicare beneficiaries with the appropriate indications. | 18,789,740 |
[Frontotemporal dementia: a review]. | Frontotemporal dementia (FTD) is a neurological disorder characterised by the progressive degeneration of the frontal and anterior temporal cortex. FTD, as well as nonfluent progressive aphasia and semantic dementia, belongs to the more generic entity of frontotemporal lobe degeneration. Considering the involvement of the frontal lobe, the initial clinical presentation of FTD may be psychiatric, such as changes in personality or behavioural disorders. Psychiatrists, therefore, have to establish the differential diagnosis with late-onset schizophrenia or affective disorders. An accurate history of the onset of symptoms, thanks to the patient and especially to his/her family, is essential to recognize this dementia. In addition to behavioural changes, memory impairment, and speech disturbances are often present from the beginning. Consensus criteria have been proposed in 1998 that help to bring this diagnosis to mind in clinical practice. The progressive occurrence of personality changes or inappropriate social conducts in the fifth or sixth decade must prompt cognitive evaluation. NEUROCOGNITIVE AND BRAIN IMAGING DATA: A brief cognitive evaluation, such as the frontal assessment battery (FAB) may help to identify a dysexecutive syndrome and to prompt a thorough neuropsychological evaluation. The pattern of neuropsychological impairment reflects the involvement of the frontal lobe and appears different from that of other degenerative diseases, such as Alzheimer's dementia, which involves hippocampal damage. Additional investigations should however be made to detect a potentially curable dementia. Cerebral imaging is essential to the differential diagnosis and also shows evidence for the positive diagnosis of FTD. Structural MRI may initially not show the bilateral atrophy of the frontal lobe, but functional imaging may be helpful in the early stages of the illness by showing evidence of abnormalities in the anterior cerebral hemisphere. PATHOPHYSIOLOGICAL FINDINGS: In recent years, significant advances in the understanding of the pathological characteristics of FTD were made with genetic contribution, especially the discovery of the tau protein involvement. In fact, neuropathological examination with immunohistochemical analysis defines Pick's disease with Pick bodies that belong to tauopathies. Ubiquitinated intraneuronal inclusions may also be found, and some types of FTD have no distinctive pathological feature. However, although a definite diagnosis would only be established after postmortem pathological examination, the clinical, neuropsychological and imaging data enable the early identification of patients with FTD and, subsequently, the appropriate management. Although the prevalence of FTD reaches 1 Alzheimer's disease (AD) to 1.6 FTD in the general population between 45- and 64-year old, only few studies have focused on the treatment of FTD. Some evidence supports the positive effect of serotonergic agents, especially with regard to behavioural symptoms. Selective serotonin reuptake inhibitors or trazodone should therefore be prescribed in preference to acetylcholinesterase medications as in AD. However, no drug yet has the ability to stop or slow down the degenerative process. The management of daily life also bears specificities related to the younger age of these patients and to their behavioural disorders. Caregivers should receive some education about the characteristics of this dementia and should be helped in social management. As concerns aggressive behaviour, neuroleptics should generally be avoided because of poor tolerance. Finally, the outcome is characterized by a rapid loss of autonomy and sometimes by a premature institutionalisation. | 18,789,785 |
Pregnancy-associated plasma protein-A (PAPP-A) and cardiovascular risk. | The search for markers to improve risk prediction for individuals at risk of developing serious cardiovascular events is ongoing. New markers of coronary artery disease progression have been identified in recent years, among which, circulating levels of pregnancy-associated plasma protein-A (PAPP-A) offer an interesting profile. PAPP-A may play a role in the development of atherosclerotic lesions and represent also a marker of atheromatous plaque instability and extent of cardiovascular disease. PAPP-A has been shown to be a marker of adverse outcome in both acute coronary syndrome and stable coronary disease patients. The present article reviews currently available evidence supporting a role for PAPP-A as a marker of cardiovascular risk and discusses some of the pitfalls that may limit its use in clinical practice. | 18,789,800 |
Translation towards personalized medicine in Multiple Sclerosis. | In recent years the realization that the concept 'one drug fits all' - does not work, created the need to shift gears from 'treating the disease' to 'treating the patient', and implementation of 'Personalized Medicine' where treatment is tailored to the individual. In chronic and progressive diseases, such as Multiple Sclerosis (MS), the need for tailored therapeutics is especially imperative, as the consequences of an ineffective medication might be irreversible dysfunction. In recent years accumulating evidence indicates that MS is not a single disease and that patients with different disease subtypes respond differently to a medication. Environment and genetics are among the factors that determine disease subtype and activity, and the patient's response to medication. Additional factors include demographic characteristics such as gender and age, as well as chrono-biological indicators. During the last few years, advances and availability of new technologies have brought genome-wide gene expression profiling studies to many medical fields, including MS. Genomic technologies have also stimulated pharmacogenetics studies, that aim to identify genetic factors that affect response to treatment. However, pharmacogenetics information is still immature to allow its translation to clinical practice in MS. Notably, one of the major limitations in obtaining reproducible data across MS pharmacogenetics studies has been the lack of a consensus as to the appropriate method for determining clinical response. In light of the rapid advances in technology and progress in applying individualized treatment strategies in other diseases, 'Personalized Medicine' for MS seems feasible within the coming years. | 18,789,804 |
Nitric oxide, polyamines and Cd-induced phytotoxicity in wheat roots. | To further explore the biochemical basis of Cd toxicity in developing wheat seedlings, we studied the possible role of nitric oxide (NO) and polyamines as signaling molecules involved in metal-induced root growth inhibition. When used at 0.1 mM, sodium nitroprusside, a NO-releasing compound, inhibited root growth to a similar extent as Cd and enhanced the polyamine contents as Cd also did. Putrescine and spermidine treatments caused significant decreases in root growth with spermine giving the greatest level of inhibition (77% reduction). The simultaneous addition of Cd and inhibitors of putrescine biosynthesis (DFMA and DFMO) prevented increases in putrescine levels but did not restore normal root growth. NO content, as evidenced by the fluorescent probe DAF-FM diacetate, was found to be significantly increased in the roots of both Cd and polyamine treated plants, especially in those exposed to spermine. The effect was specific for NO since the NO scavenger cPTIO almost suppressed the fluorescent signal. Concerning the oxidative status of the root system, only Cd and spermine enhanced lipid peroxidation in roots. At the same time, all treatments led to a significant increase in levels of the non-enzymatic antioxidant defense glutathione. Our results strongly suggest that Cd and spermine treatments induce NO formation in wheat roots which, in turn, is involved in root growth inhibition. | 18,789,805 |
Development of specific T-cell responses to Candida and tetanus antigens in partial DiGeorge syndrome. | Partial DiGeorge syndrome (pDGS) presents with thymic hypoplasia and a variable decrease in T-cell numbers. Although lymphocyte proliferation to mitogens is generally preserved, it is uncertain whether the development of specific cellular immunity in pDGS is similarly preserved. We sought to study the development of antigen-specific T-cell responses in patients with pDGS with regard to their initial CD3 T-cell counts. A retrospective review of 93 patients with pDGS followed at Texas Children's Hospital Allergy and Immunology Clinic from 1991 to 2006 was performed. Serial lymphocyte proliferation to Candida and tetanus antigens was longitudinally analyzed. Antigen-specific lymphoproliferation was compared with initial patient CD3 T-cell counts of less than the 10th percentile (n = 63), the 10th to 50th percentile (n = 20), and greater than the 50th percentile (n = 10) of age-matched normal control values. Tetanus-specific IgG levels and the number of tetanus immunizations were also studied. The median CD3 T-cell counts at baseline in all 3 groups were as follows: 10th percentile, 1188 cells/mm(3) (range, 168-3272 cells/mm(3)); 10th to 50th percentile, 2816 cells/mm(3) (range, 1484-4155 cells/mm(3)); greater than 50th percentile, 4246 cells/mm(3) (range, 2573-6481 cells/mm(3)). Thirty-one (46%) of 68 patients with pDGS who received at least 3 tetanus vaccines had persistent Candida and tetanus-specific cellular immunity, and 24 (35%) did not have immunity to either antigen. Most (22/24) of these patients had CD3 T-cell counts at presentation of less than the 10th percentile of normal values. Protective tetanus-specific IgG titers (>0.10 IU/mL) were detected in all patients tested from the age of 2 to 85 months (n = 72). Some patients with pDGS with low CD3 T-cell counts might not have specific Candida and tetanus cellular immunity. | 18,789,819 |
MicroRNA-27a functions as an oncogene in gastric adenocarcinoma by targeting prohibitin. | MicroRNAs (miRNAs) may function as oncogenes or tumor suppressors. Here, we show that miR-27a is up-regulated in human gastric adenocarcinoma. Suppression of miR-27a inhibits gastric cancer cell growth. Subsequently, prohibitin is identified as a potential miR-27a target, combining bioinformatics and microarray analysis. EGFP report experiment also confirms that the 3' untranslated region (3'UTR) of prohibitin carries the directly binding site of miR-27a. After knockdown of miR-27a in gastric cancer cells, mRNA level and protein level of prohibitin are both elevated. Down-regulation of prohibitin by miR-27a may explain why suppression of miR-27a can inhibit gastric cancer cell growth, further supporting that miR-27a functions as an oncogene. | 18,789,835 |
Pericarditis caused by anaerobic bacteria. | This review describes the microbiology, diagnosis and management of pericarditis due to anaerobic bacteria. The predominant anaerobes isolated from patients with pericarditis are Gram-negative bacilli (mostly Bacteroides fragilis group) as well as Peptostreptococcus, Clostridium, Fusobacterium, Bifidobacterium and Actinomyces spp. Anaerobic bacteria can be recovered from pericarditis resulting from the following mechanisms: (i) spread from a contiguous site of infection, either de novo or following surgery or trauma (pleuropulmonary, oesophageal fistula or perforation, and odontogenic); (ii) spread from a site of infection within the heart, most commonly from endocarditis; (iii) haematogenous infection; and (iv) direct inoculation resulting from a penetrating injury or cardiothoracic surgery. Anaerobic Gram-negative bacilli have increased their resistance to penicillins and other antimicrobial agents in the last two decades. Identification of pathogens and determination of their antimicrobial susceptibility and beta-lactamase production are essential for adequate selection of antibiotic therapy effective against these organisms. | 18,789,852 |
Novel BK channel openers containing dehydroabietic acid skeleton: structure-activity relationship for peripheral substituents on ring C. | A series of dehydroabietic acid (DHAA, 2) derivatives was synthesized and evaluated as BK channel openers in an assay system of CHO-K1 cells expressing hBKalpha channels. Systematic modifications of the peripheral functionality of ring C of DHAA showed that the introduction of a nitro or (thio)urea group in ring C greatly enhanced the BK channel-opening activity. | 18,789,860 |
Painful or painless lower limb dysesthesias are highly predictive of peripheral neuropathy: comparison of different diagnostic modalities. | Dysesthesias of the lower limbs are a common complaint of patients and may be indicative of peripheral neuropathy. Here we investigated the prevalence and type of neuropathy in patients presenting with this complaint and compared the diagnostic performance of different diagnostic modalities. Forty-two patients were recruited prospectively and underwent a clinical examination, nerve conduction studies, quantitative sensory testing (QST), and skin biopsy at the dorsum of the foot. All patients had a correlate for their dysesthesias in at least one diagnostic modality. Most patients (>90%) had signs of small fiber loss or dysfunction. In about half of all patients large fibers were also affected. Nerve conduction studies were abnormal in 23/42 patients (54.8%). Cold or warm detection thresholds in QST were abnormal in 15/42 (35.7%) patients. Decreased intraepidermal nerve fiber density (IENFD) was found in 37 patients (88.1%), including some patients with normal QST findings. Nearly all patients with pathological QST had a reduced IENFD, indicating a high positive predictive value (93%) of QST in screening for reduced IENFD as correlate for neuropathy. Therefore in all patients with lower limb dysesthesias of unknown origin, the non-invasive methods of NCS and QST should be used and potentially complemented by skin biopsy. | 18,789,872 |
Cytotoxicity of lipid-free apolipoprotein B. | To investigate the effect of apolipoprotein B (apoB) on cell viability, we used lipid-free apoB as a model for denatured apoB. Lipid-free apoB had cytotoxicity to J774 macrophages, CHO cells and HepG2 cells, whereas apoB bound to low density lipoprotein (LDL) and lipid-free apolipoprotein A-I had no effect on cell viability. Lipid-free apoB induced apoptosis in J774 macrophages assessed by caspase-3 activation and annexin V binding. LDL receptor, heparan sulfate proteoglycans, and class A scavenger receptor were involved in the binding/uptake of lipid-free apoB, but lipid-free apoB binding/uptake by the cells did not correlate with cytotoxicity. Lipid-free apoB disrupted the lipid bilayer of large unilamellar vesicles containing calcein. We evaluated the interaction between apoB and cellular membrane by monitoring the change in intracellular Ca(2+) concentration using Fura-2, and found that lipid-free apoB rapidly disrupted the cellular membrane in the absence or presence of the inhibitors for cellular binding/uptake mediated by the receptors. Therefore, it is suggested that lipid-free apoB induces cell death by disturbance of the plasma membrane. In addition to other lipid component in modified LDL, apoB itself has an ability to induce apoptosis and plays a crucial role in the development of atherosclerotic lesions. | 18,789,885 |
Gain-of-function mutation of FGFR3 results in impaired fracture healing due to inhibition of chondrocyte differentiation. | Fracture healing is a complicated regeneration process which to some extent recapitulates bone development. Fibroblast growth factor receptor 3 (FGFR3) has a negative regulatory effect on endochondral ossification, and FGFR3 is also expressed in prehypertrophic and hypertrophic chondrocytes during fracture healing. However, the actual role of FGFR3 during bone regeneration is not fully understood. Therefore we investigated the role of FGFR3 in fracture repair using a non-stabilized fracture model. Fracture repair in gain-of-function mutation of FGFR3 (Fgfr3(G369C/+)) mice was delayed, with more cartilage callus on day 14 and residue of cartilage in the callus on day 21. Histologic, in-situ hybridization and qRT-PCR analysis showed that differentiation of mesenchymal cells into chondrocytes and hypertrophic differentiation was delayed in Fgfr3(G369C/+) mice during fracture healing. These results indicated that activating mutation of FGFR3 could lead to impaired bone repair due to inhibition of chondrocyte differentiation. | 18,789,890 |
Expression and characterization of the integral membrane domain of bacterial histidine kinase SCO3062 for structural studies. | Bacterial histidine kinases play an important role in the response to external stimuli. Structural studies of the histidine kinase transmembrane domain are challenging due to difficulties in protein expression and sample preparation. After carrying out expression screening of a series of histidine kinases, we investigated sample preparation methods for obtaining high quality samples of the periplasmic and transmembrane domain (PTD) of the bacterial histidine kinase SCO3062. Various sample conditions were tested for their ability to give homogeneous NMR spectra of the SCO3062 PTD with well-resolved resonances. Circular dichroism and 3D (15)N-edited NOESY spectrum results demonstrate that the SCO3062 PTD is predominantly alpha-helical. This method should be applicable to the NMR analysis of other transmembrane proteins. | 18,789,898 |
Dietary omega 3 fatty acids and the developing brain. | The omega-3 fatty acids are essential dietary nutrients and one of their important roles is providing the fatty acid with 22 carbons and 6 double bonds known as docosahexaenoic acid (DHA) for nervous tissue growth and function. Inadequate intakes of omega-3 fatty acids decrease DHA and increase omega-6 fatty acids in the brain. Decreased DHA in the developing brain leads to deficits in neurogenesis, neurotransmitter metabolism, and altered learning and visual function in animals. Western diets are low in omega-3 fatty acids, including the 18 carbon omega-3 fatty acid alpha linolenic acid found mainly in plant oils, and DHA, which is found mainly in fish. The DHA status of the newborn and breast-fed infant depends on the maternal intake of DHA and varies widely. Epidemiological studies have linked low maternal DHA to increased risk of poor child neural development. Intervention studies have shown improving maternal DHA nutrition decreases the risk of poor infant and child visual and neural development. Thus, sufficient evidence is available to conclude that maternal fatty acid nutrition is important to DHA transfer to the infant before and after birth, with short and long-term implications for neural function. However, genetic variation in genes encoding fatty acid desaturases also influence essential fatty acid metabolism, and may increase requirements in some individuals. Consideration of omega-3 fatty acid to include brain development, optimizing omega-3 and omega-6 fatty acids in gestation and lactation, and in fatty acid nutrition support for intravenous and formula-fed neonates is important. | 18,789,910 |
Motoneuronotrophic factor analog GM6 reduces infarct volume and behavioral deficits following transient ischemia in the mouse. | Motoneuronotrophic factor (MNTF) is an endogenous neurotrophin that is highly specific for the human nervous system, and some of the observed effects of MNTF include motoneuron differentiation, maintenance, survival, and reinnervation of target muscles and organs. MNTF is a neuro-signaling molecule that binds to specific receptors. Using In Silico Analysis, one of the active sites of MNTF was identified as an analog of six amino acids (GM6). The effect of chemically synthesized GM6 on ischemic stroke was studied in the middle cerebral artery occlusion (MCAo) mouse model. Mice were subjected to 1 hur of ischemia followed by 24 h of reperfusion. Mice were injected intravenously with a bolus of GM6, at various doses (1 and 5 mg/kg) immediately after the start of reperfusion and examined for changes in physiological parameters, neurological deficits and infarct volume. GM6 was able to penetrate the blood brain barrier, and at both 1 and 5 mg/kg showed a significant protection from infarct damage, which translated to improvement of neurological deficits. Administration of GM6 demonstrated no changes in HR, BP, pO(2), pCO(2), or pH. A significant increase over the control group in CBF after reperfusion was observed with GM6 administration, which helped to mitigate the ischemic effect caused by the blockage of blood flow. The time window of treatment was assessed at various times following cerebral ischemia with GM6 demonstrating a significant protective effect up to 6-12 h post ischemia. In addition, GM6 increased neurogenesis, and decreased apoptosis and inflammation in the mouse brain following cerebral ischemic injury. These data suggest that GM6 is neuroprotective to the brain following IV injection in the mouse model of MCAo. | 18,789,909 |
Reactivity of 5-HT1A receptor in adult rats after neonatal noradrenergic neurons' lesion--implications for antidepressant-like action. | The aim of this study was to assess the 5-HT1A receptor reactivity after neonatal noradrenergic neurons' lesion. DSP-4 (N-(2-chloroethyl)-N-ethyl-2-bromobenzylamine), 50 mg/kg, was administered 30 min after a selective serotonin reuptake inhibitor (SSRI)--zimelidine (10 mg/kg) on the 1st and 3rd day of life. Zimelidine was used to prevent serotonin (5-HT) depletion. 5-HT1A autoreceptor is involved in the regulation of 5-HT release as well as the pathogenesis of depression. During a microdialysis study of anaesthetized rats, the 5-HT1A receptor agonist, R-(+)-8-OH-DPAT (0.1 mg/kg), decreased 5-HT release in the medial prefrontal cortex of control rats but this effect was significantly attenuated in DSP-4-treated animals (10-12 weeks old). To further determine which type of receptor, either pre or postsynaptically located, is involved in the attenuated response to the 5-HT1A receptor agonist in lesioned rats, behavioral tests were conducted. In the forced swimming test, DSP-4 treated rats after saline injection, displayed shorter immobility time in comparison to control rats. R-(+)-8-OH-DPAT (0.5 mg/kg) evoked an antidepressant-like effect in control and DSP-4 treated rats in a learned helplessness paradigm as well as the forced swimming test. The results of this study provided further support for the exclusive desensitization of 5-HT1A autoreceptor in adult rats with neonatal lesion of the central noradrenergic system. | 18,789,911 |
Identification of a xylosyltransferase II gene haplotype marker for diabetic nephropathy in type 1 diabetes. | Proteoglycans are major components of the glomerular basement membrane, being responsible for their permeability properties. Type 1 diabetic patients have an altered proteoglycan metabolism, which contributes to microvascular complications like diabetic nephropathy. Xylosyltransferase II (XT-II) is a chain-initiating enzyme in the biosynthesis of basement membrane proteoglycans and catalyzes the transfer of xylose to selected serine residues in the core protein. Thus, genetic variations in the XT-II coding gene XYLT2 might be implicated in the initiation and progression of late diabetic complications. Genotyping of 6 genetic variations in the XYLT2 gene and haplotype analysis was performed in 697 type 1 diabetic patients (358 with and 338 without diabetic nephropathy). The haplotype analysis of 6 XYLT2 polymorphisms revealed one haplotype (GATTCG) to be significantly less frequent among type 1 patients with diabetic nephropathy (p=0.002, OR=0.13, 95% CI=0.03-0.59). The haplotype GATTCG consist of the XYLT2 variations c.166G>A, c.177A>G, c.342T>C, IVS6-9T>C, c.1569C>T and c.2402C>G. No genotype-phenotype interactions were revealed. Our data show that a XYLT2 haplotype is associated with nephropathy in type 1 diabetic patients. | 18,789,912 |
fMRI reveals cognitive and emotional processing in a long-term comatose patient. | We report on a 41-year old woman with prolonged comatose unresponsiveness following traumatic head injury. Structural MRI showed bilateral midbrain damage and ventriculomegalia. Functional MRI revealed robust cortical responses to visual, auditory and tactile stimulation. Speech stimuli moreover consistently elicited activation in Broca's and Wernicke's areas. Familiar speakers and direct addressing evoked significantly stronger amygdala activation than unfamiliar speakers and neutral phrases. This study hence demonstrates the potential of functional neuroimaging in the investigation of residual higher cortical functions in unresponsive comatose patients. | 18,789,930 |
Alcohol and nicotine consumption exacerbates choroidal neovascularization by modulating the regulation of complement system. | The objective of the present study was to investigate the effect of alcohol and nicotine consumption on the pathogenesis of choroidal neovascularization (CNV) in rats after laser-photocoagulation. Confocal microscopic analysis demonstrated an increase in CNV complex size in rats fed with alcohol (2.3-fold), nicotine (1.9-fold), and the combination of alcohol and nicotine (2.7-fold) compared with the control groups. Immunohistochemical analysis revealed that alcohol and nicotine consumption increased MAC deposition and VEGF expression in laser spots. Expression of CD59 by RT-PCR and Western blot was drastically reduced in the animals that were fed with alcohol, nicotine and alcohol and nicotine compared to those fed with water alone and this was associated with exacerbation of CNV. | 18,789,935 |
Effects of molecular weight and hydrolysis conditions on anticancer activity of fucoidans from sporophyll of Undaria pinnatifida. | Hydrolyzed fucoidans, from sporophyll of Undaria pinnatifida, were used to determine the effects of molecular weight (Mw) and hydrolysis conditions on cancer cell growth. Native fucoidans showed anticancer activity of 37.6%. When hydrolyzed in boiling water with HCl for 5 min, fucoidans (Mw = 490 kDa) significantly increased anticancer activity to 75.9%. However, fucoidans hydrolyzed in a microwave oven showed little improvement of anticancer activity and even exhibited the inhibition activity below 30% when treated more than 90s. This suggests that anticancer activity of fucoidans could be significantly enhanced by lowering their Mw only when they are depolymerized by mild condition. | 18,789,961 |
Immunization with plasmid DNA encoding influenza A virus nucleoprotein fused to a tissue plasminogen activator signal sequence elicits strong immune responses and protection against H5N1 challenge in mice. | DNA vaccination is an effective means of eliciting both humoral and cellular immunity. Most of influenza vaccines targeted at hemagglutinin (HA) show efficient immunogenicity for protecting subjects against influenza virus infection. However, major antigenic variations of HA may facilitate the virus in developing resistance against such vaccines. DNA vaccines encoding conserved antigens protect animals against diverse viral subtypes, but their potency requires further improvement. In the present study, a DNA vaccine encoding the conserved nucleoprotein (NP) with a tissue plasminogen activator (tPA) signal sequence (ptPAs/NP) was generated, and immune responses were examined in vaccinated mice. A higher level of NP expression and secretion was observed in lysates and supernatants of the cells transfected with ptPAs/NP when compared to a plasmid encoding the wild-type full-length NP (pflNP). Immunofluorescence studies showed the cytoplasmic localization of the NP protein expressed from ptPAs/NP, but not from pflNP. In mice, the ptPAs/NP vaccine elicited higher levels of the NP-specific IgG and CD8(+) T cell-stimulating responses than that of pflNP. Vaccination with ptPAs/NP efficiently cleared the homologous H5N1 influenza virus in the infected lungs and induced partial cross-protection against heterologous, highly pathogenic H5N1 strains in mice. Our results may contribute to the development of protective immunity against diverse, highly pathogenic H5N1 virus subtypes. | 18,789,973 |
Development of fluorescent in situ hybridization for Cryptosporidium detection reveals zoonotic and anthroponotic transmission of sporadic cryptosporidiosis in Sydney. | Cryptosporidium is the most common non-viral cause of diarrhea worldwide. Of the 5 described species that contribute to the majority of human infections, C. parvum is of major interest due to its zoonotic potential. A species-specific fluorescence in situ hybridisation probe was designed to the variable region in the small subunit of the 18S rRNA of C. parvum and labeled with Cy3. Probe specificity was validated against a panel of 7 other Cryptosporidium spp. before it was applied to 33 human faecal samples positive for cryptosporidiosis which were obtained during the period from 2006-2007. Results were compared to PCR-RFLP targeting the 18S rDNA. FISH results revealed that 19 of the 33 isolates analysed were identified as C. parvum. Correlation of PCR-RFLP and FISH was statistically significant (P<0.05), resulting in a calculated correlation coefficient of 0.994. In this study, species identification by FISH and PCR-RFLP provided preliminary evidence to support both anthroponotic and zoonotic transmission of sporadic cases of cryptosporidiosis in the Sydney basin. In conclusion, FISH using a C. parvum-specific probe provided an alternative tool for accurate identification of zoonotic Cryptosporidium which will be applied in the future to both epidemiological and outbreak investigations. | 18,789,979 |
Temporal feature of BOLD responses varies with temporal patterns of movement. | Which brain sites represent the final form of motor commands that encode temporal patterns of muscle activities? Here, we show the possible brain sites which have activity equivalent to the motor commands with functional magnetic resonance imaging (fMRI). We hypothesized that short-temporal patterns of movements or stimuli are reflected in blood-oxygenation-level-dependent (BOLD) responses and we searched for regions representing the response. Participants performed two temporal patterns of tapping and/or listened to the same patterns of auditory stimuli in a 3T fMRI. The patterns were designed to have the same number (11) of events and the same duration, but different temporal distribution of events. The 11 events were divided into two parts (10 repetitive taps and one stand-alone tap) and the interval of the two parts was 3s. The two patterns had reverse order of the two parts. The results revealed that different temporal patterns of auditory stimuli were represented in different temporal features of BOLD responses in the bilateral auditory cortex, whereas different temporal patterns of tapping were reflected in contralateral primary motor cortex and the ipsilateral anterior cerebellum. In bilateral premotor cortex, supplementary motor area, visual cortex, and posterior cerebellum, task-related BOLD responses were exhibited, but their responses did not reflect the temporal patterns of the movement and/or stimuli. One possible explanation is that the neuronal activities were similar for the two patterns in these regions. The sensitivity of the BOLD response to the temporal patterns reflects local differences in functional contributions to the tasks. The present experimental design and analysis may be useful to reveal particular brain regions that participate in multiple functions. | 18,789,981 |
Sperm membrane lipid liposomes can evoke an effective immune response against encapsulated antigen in BALB/c mice. | In an earlier study, we provided strong evidence that liposomes made of sperm membrane lipids (spermatosomes) can deliver entrapped molecules to the cytosol of target cells. Now we have evaluated the immunological behavior of spermatosome-encapsulated soluble antigen ovalbumin (OVA) in BALB/c mice. Spermatosome-mediated antigen delivery can affect both cytosolic and endosomal antigen-processing pathways, simultaneously, leading to the generation of CD4+ T-helper and CD8+ cytotoxic T-cell responses. Isotype studies revealed that immunization with spermatosome-encapsulated OVA elicits mainly IgG2a and IgG1 subclasses of antibodies. A potential vaccine candidate should impart long-lasting protection against infection; to this end, immunization with spermatosome-encapsulated OVA resulted in expression of CD44 and CD62L cell-surface markers on T cells, suggestive of a desirable memory response. We conclude that spermatosome encapsulation is a useful strategy for vaccine production, because it enhances the immunological activity of the encapsulated antigen. | 18,789,993 |
Amyloid-beta peptide decreases glutamate uptake in cultured astrocytes: involvement of oxidative stress and mitogen-activated protein kinase cascades. | Alzheimer's disease (AD) is a progressive neurodegenerative disorder primarily characterized by excessive deposition of amyloid-beta (Abeta) peptides in the brain. One of the earliest neuropathological changes in AD is the presence of a high number of reactive astrocytes at sites of Abeta deposition. Disturbance of glutamatergic neurotransmission and consequent excitotoxicity is also believed as implicated in the progression of this dementia. Therefore, the study of astrocyte responses to Abeta, the main cellular type involved in the maintenance of synaptic glutamate concentrations, is crucial for understanding the pathogenesis of AD. This study aims to investigate the effect of Abeta on the astrocytic glutamate transporters, glutamate transporter-1 (GLT-1) and glutamate-aspartate transporter (GLAST), and their relative participation to glutamate clearance. In addition we have also investigated the involvement of mitogen-activated protein (MAP) kinases in the modulation of GLT-1 and GLAST levels and activity and the putative contribution of oxidative stress induced by Abeta to the astrocytic glutamate transport function. Therefore, we used primary cultures of rat brain astrocytes exposed to Abeta synthetic peptides. The data obtained show that Abeta(1-40) peptide decreased astroglial glutamate uptake capacity in a non-competitive mode of inhibition, assessed in terms of tritium radiolabeled d-aspartate (d-[(3)H]aspartate) transport. The activity of GLT-1 seemed to be more affected than that of GLAST, and the levels of both transporters were decreased in Abeta(1-40)-treated astrocytes. We demonstrated that MAP kinases, extracellular signal-regulated kinase (ERK), p38 and c-Jun N-terminal kinase, were activated in an early phase of Abeta(1-40) treatment and the whole pathways differentially modulated the glutamate transporters activity/levels. Moreover it was shown that oxidative stress induced by Abeta(1-40) may lead to the glutamate uptake impairment observed. Taken together, our results suggest that Abeta peptide downregulates the astrocytic glutamate uptake capacity and this effect may be in part mediated by oxidative stress and the differential activity and complex balance between the MAP kinase signaling pathways. | 18,790,019 |
Salting-out taste-masking system generates lag time with subsequent immediate release. | Salting-out effects were utilized for developing a multiparticulate system balancing numbness masking and high bioavailability. A "salting-out taste-masking system" consisting of a drug core containing acetaminophen as a model drug, a salting-out layer containing sodium carbonate (Na(2)CO(3)) and hydroxypropylmethylcellulose (HPMC), and a water-penetration-control layer consisting of cetanol was designed and prepared. The system successfully generated a long lag time while achieving immediate drug release. In the system, the Na(2)CO(3) release rate was slower and the lag time was longer than when the water-penetration-control layer was not present. During the release of Na(2)CO(3) from the system, the release of HPMC and drug was suppressed. These results indicated that the water-penetration-control layer maintained a high concentration of Na(2)CO(3), prevented HPMC's dissolution, and generated a long lag time of drug release. The system generated longer lag time and released drug more immediately than formulation containing the water-penetration-control layer of same thickness without the salting-out layers. These results indicated the salting-out layers were necessary for obtain a long lag time and subsequent immediate drug release. This novel taste-masking system has the potential to be a useful multiparticulate dosage form for effective, safe, and user-friendly drug therapy. | 18,790,028 |
Microemulsion based vaginal gel of fluconazole: formulation, in vitro and in vivo evaluation. | The objective of the present investigation was to develop and evaluate microemulsion based gel for the vaginal delivery of fluconazole (FLZ). The solubility of FLZ in oils and surfactants was evaluated to identify components of the microemulsion. The ternary diagram was plotted to identify the area of microemulsion existence. Various gelling agents were evaluated for their potential to gel the FLZ microemulsion without affecting its structure. The bioadhesive potential and anti-fungal activity of the FLZ microemulsion based gel (FLZ-MBG) was determined in comparison to the marketed clotrimazole gel (Candid V gel) by in vitro methods. The vaginal irritation potential of the FLZ-MBG was evaluated in rabbits. The clinical efficacy of the FLZ-MBG and Candid V gel was evaluated in females suffering from vaginal candidiasis. The FLZ microemulsion exhibited globule size of 24 nm and polydispersity index of 0.98. Carbopol ETD 2020 could successfully gel the FLZ microemulsion without disturbing the structure. The FLZ-MBG showed significantly higher (P<0.05) in vitro bioadhesion and anti-fungal activity as compared to that of Candid V gel. The FLZ-MBG did not show any signs of vaginal irritation in the rabbits. The small-scale clinical studies indicated that the FLZ-MBG shows faster onset of action than Candid V gel although no difference was observed in the clinical efficacy. | 18,790,032 |
Serum bilirubin levels, UGT1A1 polymorphisms and risk for coronary artery disease. | Low levels of the antioxidative serum bilirubin are associated with vascular aging and an increased risk for coronary artery disease (CAD). UGT1A1 is the major gene influencing bilirubin concentrations. Therefore, we investigated an association of bilirubin levels and two polymorphisms in the promoter of UGT1A1 (-53(TA-repeat) polymorphism and T-3279G) in 477 patients with premature, familial CAD and 619 age- and sex-matched controls. Bilirubin concentrations were significantly lower in cases than in controls (0.62+/-0.36 vs. 0.76+/-0.41 mg/dl for men, p=1.2 x 10(-10); and 0.42+/-0.29 vs. 0.55+/-0.23 mg/dl, p=1.9 x 10(-9) for women). Both polymorphisms showed a strong association with bilirubin levels with higher levels for homozygote carriers of the minor allele. These associations were most pronounced in male controls and patients (p=5.9 x 10(-26) and p=3.4 x 10(-16), respectively, for the -53(TA-repeat) polymorphism). Logistic regression analysis revealed low bilirubin levels but not the UGT1A1 polymorphisms to be significantly associated with CAD: OR (95% CI) 0.90 (0.86-0.94), p=2.6 x 10(-6) for men and 0.77 (0.68-0.87), p=3.2 x 10(-5) for women, respectively for each 0.1mg/dl increase of bilirubin. These results indicate that it is rather decreased bilirubin levels in general than the changes in the genetic variation of this gene that increase the risk for CAD. | 18,790,042 |
Involvement of the PI3K/Akt pathway in estrogen-mediated regulation of human CYP7B1: identification of CYP7B1 as a novel target for PI3K/Akt and MAPK signalling. | The steroid hydroxylase CYP7B1 metabolizes neurosteroids, cholesterol derivatives, and estrogen receptor (ER) ligands. Previous studies identified CYP7B1 as a target for regulation by estrogen. The present study examines the mechanism for estrogen-mediated regulation of the human CYP7B1 gene promoter. Treatment with LY294002, a specific inhibitor of phosphatidylinositol 3-kinase (PI3K), abolished ER-mediated up-regulation of a CYP7B1 promoter-luciferase reporter in HepG2 cells, whereas overexpression of PI3K or Akt significantly increased estrogenic up-regulation of CYP7B1. Overexpression of dominant-negative mutant Akt abolished ER-mediated stimulation of CYP7B1 in HepG2 cells. Data indicated no binding of ER to CYP7B1 promoter sequences, suggesting that ER interacts with the PI3K/Akt pathway without binding to the gene. At low ER levels, overexpression of Akt suppressed CYP7B1 promoter activity, suggesting that its effect on CYP7B1 is different when estrogens are absent. In HEK293 cells, CYP7B1 transcription was much less affected by Akt, indicating that the mechanism for up-regulation of CYP7B1 is different in different cell types. Other experiments indicated that MAPK signalling may affect basal CYP7B1 levels. The current results, indicating that regulation of CYP7B1 by ER can be mediated via the PI3K/Akt signal pathway, a regulatory pathway important for cellular survival and growth, suggest an important role for CYP7B1 in cellular growth, particularly in connection with estrogenic signalling. | 18,790,053 |
Is emotional contagion special? An fMRI study on neural systems for affective and cognitive empathy. | Empathy allows us to simulate others' affective and cognitive mental states internally, and it has been proposed that the mirroring or motor representation systems play a key role in such simulation. As emotions are related to important adaptive events linked with benefit or danger, simulating others' emotional states might constitute of a special case of empathy. In this functional magnetic resonance imaging (fMRI) study we tested if emotional versus cognitive empathy would facilitate the recruitment of brain networks involved in motor representation and imitation in healthy volunteers. Participants were presented with photographs depicting people in neutral everyday situations (cognitive empathy blocks), or suffering serious threat or harm (emotional empathy blocks). Participants were instructed to empathize with specified persons depicted in the scenes. Emotional versus cognitive empathy resulted in increased activity in limbic areas involved in emotion processing (thalamus), and also in cortical areas involved in face (fusiform gyrus) and body perception, as well as in networks associated with mirroring of others' actions (inferior parietal lobule). When brain activation resulting from viewing the scenes was controlled, emotional empathy still engaged the mirror neuron system (premotor cortex) more than cognitive empathy. Further, thalamus and primary somatosensory and motor cortices showed increased functional coupling during emotional versus cognitive empathy. The results suggest that emotional empathy is special. Emotional empathy facilitates somatic, sensory, and motor representation of other peoples' mental states, and results in more vigorous mirroring of the observed mental and bodily states than cognitive empathy. | 18,790,065 |
Cloning and functional analysis of the proximal promoter region of the three GnRH genes from the silver sea bream (Sparus sarba). | Gonadotropin-releasing hormone (GnRH) is a neuropeptide that plays a major role in releasing pituitary gonadotropin and controlling vertebrate reproduction. In this study, three GnRH cDNAs, GnRH-I (sbGnRH; 348 bp), GnRH-II (cGnRH-II; 557 bp), and GnRH-III (sGnRH; 483 bp), were cloned from the brain of the silver sea bream (Sparus sarba). In order to understand how the expression of the GnRH isoforms was regulated in the brain, the promoter of each gene was cloned and analyzed. We found regulatory motifs in the promoters that were conserved in the GnRH promoters of tilapia and zebrafish, suggesting that these motifs play a critical role in GnRH regulation. We performed functional analyses and examined tissue-specific expression for each GnRH promoter using EGFP reporter fusions in zebrafish. The GnRH-I promoter was active in the forebrain area, including the olfactory bulb-terminal nerve area and peripheral preoptic areas; the GnRH-II promoter was active in the midbrain; and the GnRH-III promoter was active in the olfactory bulb. These results show that the GnRH promoters of the silver sea bream GnRH genes exhibit tissue-specific activity. | 18,790,071 |
Time out: an analysis. | Ensuring patient safety in the OR includes performing a time out to help prevent wrong site surgery. The circulating nurse, in the role of patient advocate, usually is the OR team member who initiates the time out. A correctly performed time out includes verifying the correct patient; procedure; site (eg, organ, limb, vertebral level, laterality); surgeon; and position, as well as that proper equipment, instrumentation, and implants are available. Unacceptable time outs can be categorized as borderline, contrary, related, illegitimate, or invented cases. Health care systems should follow the Joint Commission's Universal Protocol and should have tools in place to ensure that patients will undergo correct site surgery. | 18,790,103 |
Recent developments in tandem mass spectrometry for lipidomic analysis. | This review will focus on the role of mass spectrometry in the emerging field of lipidomics. Particular emphasis will be placed on recent developments in the use of tandem mass spectrometry methods in lipid analysis using low-energy collision induced dissociation (CID). After a brief discussion on ionization techniques, novel ion-activation methods that allow for increased sensitivity and selectivity will be critically discussed. Examples will be drawn from the analysis of higher order lipids, specifically triacylglycerols (TAGs) and glycerophospholipids, as the numerous positional isomers and head groups present in these classes of lipids continue to pose a significant analytical challenge to the field of lipidomics. The role of bioinformatics in the development of lipidomics will also be discussed. | 18,790,128 |
Liquid chromatography electrospray ionization and matrix-assisted laser desorption ionization tandem mass spectrometry for the analysis of lipid raft proteome of monocytes. | Lipid rafts are dynamic assemblies of cholesterol and glycolipid that form detergent-insoluble microdomains within membrane lipid bilayers. Because rafts can be separated by flotation on sucrose gradients, interrogation by mass spectrometry (MS) provides a valuable new insight into lipid raft function. Here we combine liquid chromatography (LC) electrospray ionization (ESI) and matrix-assisted laser desorption ionization (MALDI) MS/MS to corroborate and extend our previous description of lipid raft proteomes derived from the monocytic cell line THP-1. Interestingly, LC-ESI and MALDI MS/MS identify largely non-overlapping, and therefore, potentially complementary protein populations. Using the combined approach, we detected 277 proteins compared to 52 proteins obtained with the original gel-based MALDI MS. We confirmed the presence of 47 of the original 52 proteins demonstrating the consistency of the lipid raft preparations. We demonstrated by immunoblotting that Rac 1 and Rac 2, two of the 52 proteins we failed to confirm, were indeed absent from the lipid raft fractions. The majority of new proteins were cytoskeletal proteins and their regulators, proteins implicated in membrane fusion and vesicular trafficking or signaling molecules. Our results therefore, confirm and extend previous evidence indicating lipid rafts of monocytic cells are specialized for cytoskeletal assembly and vesicle trafficking. Of particular interest, we detected SNAP-23, basigin, Glut-4 and pantophysin in lipid rafts. Since these proteins are implicated in both vesicular trafficking and gamete fusion, lipid rafts may play a common role in these processes. It is evident that the combination of LC-ESI and LC-MALDI MS/MS increases the proteome coverage which allows better understanding of the lipid raft function. | 18,790,130 |
ESI-MS characterization of a novel pyrrole-inosine nucleoside that interacts with guanine bases. | Based on binding studies undertaken by electrospray ionization-mass spectrometry, a synthetic pyrrole-inosine nucleoside, 1, capable of forming an extended three-point Hoogsteen-type hydrogen-bonding interaction with guanine, is shown to form specific complexes with two different quadruplex DNA structures [dTG(4)T](4) and d(T(2)G(4))(4) as well as guanine-rich duplex DNA. The binding interactions of two other analogs were evaluated in order to unravel the structural features that contribute to specific DNA recognition. The importance of the Hoogsteen interactions was confirmed through the absence of specific binding when the pyrrole NH hydrogen-bonding site was blocked or removed. While 2, with a large blocking group, was not found to interact with virtually any form of DNA, 3, with the pyrrole functionality missing, was found to interact non-specifically with several types of DNA. The specific binding of 1 to guanine-rich DNA emphasizes the necessity of careful ligand design for specific sequence recognition. | 18,790,136 |
Choledocholithiasis, endoscopic retrograde cholangiopancreatography, and laparoscopic common bile duct exploration. | With the litany of advances in laparoscopy and endoscopy, much has improved regarding management of choledocholithiasis. This article examines the different approaches currently available to remove common bile duct stones, with an examination of the literature supporting different approaches and the techniques involved. | 18,790,152 |
Laparoscopic versus open ventral hernia repair. | Ventral hernia repair remains one of the most common operations performed by general surgeons. Despite the frequency with which this procedure is performed, there is little agreement and extensive controversy as to the cause of most of the hernias, or the ideal approach to repair these complicated problems. This article attempts to identify and provide some clarification of these controversial issues in abdominal wall reconstruction after ventral herniation based on the available literature. | 18,790,156 |
Recent advances and controversies in pediatric laparoscopic surgery. | Children represent a unique group of patients who are likely to greatly benefit from minimally invasive surgery (MIS). The promise of less postoperative pain, smaller scars, shorter hospital stays, and a faster return to school continues to drive growth in this area. The development of pediatric-specific techniques and documentation of improved outcomes form a critical gateway to widespread application of pediatric MIS. A brief perspective on current approaches to MIS for pediatric congenital and acquired disease is provided in this report. Technical departures from standardized adult MIS and the rationale for their modification are highlighted. | 18,790,157 |
HBsAg(+) donor as a kidney transplantation deceased donor. | The organ shortage and high prevalence of hepatitis B (HB) infection in the general population are important issues in Taiwan. It is difficult for us to abandon HBsAg(+) donors. Hereby we present our experience transplanting kidneys from deceased donors with HB virus infection. From November 1977 to March 2007, 21 patients with end-stage renal disease received kidney grafts from 12 HBsAg(+) deceased donors (3.92% of 306 donors). One of the 12 donors was hepatitis Be antigen (HBeAg) (+), and 5 displayed antibody to hepatitis core antigen (anti-HBc) (+). Four of the 21 recipients were HBsAg(+) before transplantation. Four HBsAg(+) recipients remained surface antigen positive after transplantation. One of them died of an intracranial hemorrhage. Two (11.76%) of the other 17 HBsAg(-) recipients became HBsAg(+), 1 of whom died of hepatic failure and the other of sepsis. The other 15 HBsAg(-) recipients (88.23%) remained HBsAg(-) after transplantation. They displayed normal serum levels of aspartate aminotransferase/alanine aminotransferase during the follow-up period. The 5-year patient and graft survivals were 85.15% and 61.14%, respectively. Although the number of patients is relatively small, it does suggest that a kidney allograft from an HBsAg(+) deceased donor transplanted to an HBsAg(+) or (-) recipient is safe. This strategy shortens the waiting time. Additional prophylactic HB immunoglobulin and antiviral medications are also suggested. Frequent surveillance after transplantation is essential. | 18,790,163 |
Outcome of laparoscopic living donor nephrectomy: current status and trends in Japan. | Laparoscopic nephrectomy (LN) has been accepted for donors in living donor kidney transplantation. But the current status of LN in living donors is not clarified yet in Japan. In this study, we surveyed 124 Japanese kidney transplantation centers to investigate the outcomes of living donor LN in 2006. Of 124 centers, 100 responded, and 52 performed LN. These centers performed 831 living donor nephrectomies, including 589 LN, and 242 open procedures. In 52 centers, 20 were performed as hand-assisted (HA) LNs, 23 non-HA (pure laparoscopic), five both HA and non-HA, and four laparoscope-assisted. Eighteen centers used a peritoneal approach, 31 used a retroperitoneal approach and three, both. Among 589 LN donors, three experienced life-threatening complications of bleedings and intestinal injury, but all of them survived. Blood transfusions were performed in nine donors (1.5%), and open conversions of LN in 33 (5.6%). Minor complications not requiring a long hospital stay were reported in 45. The mortality of LN was 0. Among the 589 recipients, there was one case of primary nonfunction after venous injury at the operation. Twenty eight recipients (4.8%) needed hemodialysis after transplantation because of delayed graft function. Urinary tract complications were noted in 11 recipients (2.5%). This survey presented the current status of LN in Japan. | 18,790,168 |
Expression of transforming growth factor-beta1 and hypoxia-inducible factor-1alpha in renal transplantation. | Chronic allograft nephropathy (CAN) includes pathologic changes of interstitial fibrosis, tubular atrophy, and fibrous intimal thickening. Transforming growth factor (TGF)-beta1 is a fibrogenic cytokine involved in renal allograft fibrosis. Hypoxia-inducible factor (HIF)-1alpha is induced as an adaptive response to hypoxia triggering the production of fibrogenic cytokines such as TGF-beta1. Between January 1995 and February 2005, we performed 71 renal allograft biopsies in 61 recipients. Immunohistochemical studies were performed with an immunoperoxidase technique using as the primary antibody either a rabbit anti-human TGF-beta1 polyclonal or a mouse anti-human HIF-1alpha monoclonal reagent. The glomerular TGF-beta1 expression in recipients diagnosed with glomerulonephritis was significantly greater than other pathologic groups (P < .05), and the glomerular TGF-beta1 expression in the heavy proteinuria group (> or =2.5 g/d) was significantly greater than the low proteinuria group (<1.0 g/d; P < .05). The tubular and interstitial TGF-beta1 and HIF-1alpha expressions in CAN were greater than in other groups (P < .05). The tubular TGF-beta1 expression among the graft loss group was significantly greater than the graft function group (P < .05). | 18,790,176 |
Use of alemtuzumab (Campath-1H) as induction therapy in pediatric kidney transplantation. | Alemtuzumab (Campath-1H) is a monoclonal antibody directed against CD52-positive B and T lymphocytes. Initial results of its use as an induction agent in adult renal transplantation have been encouraging. We report a case series of four low-risk pediatric renal transplantation patients who received 20 to 40 mg of alemtuzumab as induction followed by a steroid-free regimen consisting of a calcineurin inhibitor and mycophenolate mofetil. No infusion-related reactions occurred. Patients were aged 9 to 14 years with a mean creatinine of 1.2 mg/dL (range = 0.5-2.3 mg/dL) at a mean follow-up of 10 months (range = 4-16 months). One patient experienced biopsy-proven acute cellular rejections at 4 and 12 months posttransplantation, which were steroid sensitive. Lymphopenia post-alemtuzumab induction started to improve at 3 months posttransplantation. Two patients who received 40 mg of alemtuzumab experienced repeated infections that responded to 7-day courses of antibiotics. There was no cytomegalovirus disease detected. From these preliminary results, alemtuzumab seems to show a promising role to achieve adequate graft function with a steroid-free regimen among low-risk pediatric patients. | 18,790,199 |
Postrenal transplantation urologic complications. | We sought to explore the incidence, risk factors, clinical presentation, management options, and outcomes of post renal transplant urologic complications. Between November 1993 and December 2005, we performed 646 renal transplantation procedures in 373 males and 273 females, of whom 81 were children. Kidney grafts were obtained from 461 living and 185 cadaveric donors. The medical records were retrospectively reviewed for urologic complications. Affected patients presented clinically with impaired kidney function: the diagnosis was confirmed by ultrasound scanning, isotope renal scanning, magnetic resonance urography, and/or antegrade urography. Ureteric stricture was managed by percutaneous antegrade ureteric dilatation and stenting, or by surgical reconstruction. Urine leak was treated by prolonged bladder drainage or surgical reconstruction. Renal stones were treated with extracorporeal shockwave lithotripsy. Urologic complications were detected in 31 recipients (4.8%), including 21 males and 10 females, among whom 4 were children. They had received kidney grafts from 19 living and 12 cadaveric donors. Urologic complications were ureteric strictures in 15 (2.58%), urine leaks in 15 (2.58%), and ureteric stone in 1 (0.17%) recipients. There was no graft loss to urologic complications. The incidence of post-kidney transplant urologic complications was 4.8%. They were more common among male recipients and after cadaveric kidney transplantation. Although ureteric stricture presented late posttransplantation and was more common among children (4.23%), urine leak presented early and was more common in the elderly (4.69%). All urologic complications were successfully managed, with no graft loss. | 18,790,231 |
Association of C-509T and T869C polymorphisms of transforming growth factor-beta1 gene with chronic allograft nephropathy and graft survival in Korean renal transplant recipients. | Transforming growth factor-beta1 (TGF-beta1) has been associated with the promotion of renal allograft interstitial fibrosis and thereby chronic allograft nephropathy (CAN). The literature on TGF-beta1 polymorphisms and their importance in graft survival and CAN is not conclusive. TGF-beta1 gene polymorphisms (C-509T and T869C) were examined in a group of 207 Korean renal transplant recipients using real-time polymerase chain reaction assays. The CAN group (n = 18) was defined by a typical biopsy confirming CAN or chronic calcineurin inhibitor nephrotoxicity. The rest of the patients were classified into the No CAN group (n = 189). No significant differences were observed in the genotype distributions of both C-509T and T869 polymorphisms between the two groups. Allele frequencies and age-, sex-, HLA mismatch-adjusted odds ratio of each genotype as assessed by logistic regression analysis were also not significantly different between the two groups. Linkage disequilibrium coefficients between polymorphisms indicated that investigated polymorphisms of TGF-beta1 (D' = 0.98) were in tight linkage. However, there were no significant differences in the frequencies of the reconstructed haplotypes between the two groups. Kaplan-Meier method and log-rank tests did not indicate any statistically significant effects of TGF-beta1 gene polymorphisms on graft survival. TGF-beta1 gene polymorphisms (C-509T, T869C) are not significantly associated with an increased risk of development of CAN and graft survival in Korean renal transplant recipients. | 18,790,234 |
Possible mechanism by which rapamycin increases cyclosporine nephrotoxicity. | It is well known that the combination of cyclosporine A (CsA) with rapamycin produces serious nephrotoxicity. Herein we suggest a mechanism by which rapamycin increases CsA nephrotoxicity. Previously, we demonstrated that activation of Akt/protein kinase B protects against cyclosporine nephrotoxicity and prevents apoptosis. Recently, it has been shown that Akt phosphorylation activates mammalian target of rapamycin (m-TOR) and inhibits programmed cell death including apoptosis and autophagy. Akt is believed to be an importance factor for cell survival. In theory, blockade of the Akt pathway through inhibition of m-TOR may increase cyclosporine-induced apoptosis. We added cyclosporine and rapamycin to cultures of ER52K proximal renal tubule cells, leading to a significantly decreased survival rate. The nephrotoxicity was associated with increased apoptosis by cleavage of caspase-3 and decreased phosphorylation of m-TOR and AktSer473, findings that support this hypothesis. This nephrotoxic effect may explain the clinical finding that patients treated with rapamycin alone exhibited better renal function than those treated with concomitant cyclosporine therapy. | 18,790,238 |
Cognitive behaviour therapy-based intervention by community health workers for mothers with depression and their infants in rural Pakistan: a cluster-randomised controlled trial. | The treatment of perinatal depression is a public-health priority because of its high prevalence and association with disability and poor infant development. We integrated a cognitive behaviour therapy-based intervention into the routine work of community-based primary health workers in rural Pakistan and assessed the effect of this intervention on maternal depression and infant outcomes. We randomly assigned 40 Union Council clusters in rural Rawalpindi, Pakistan, in equal numbers to intervention or control. Married women (aged 16-45 years) in their third trimester of pregnancy with perinatal depression were eligible to participate. In the intervention group, primary health workers were trained to deliver the psychological intervention, whereas in the control group untrained health workers made an equal number of visits to the depressed mothers. The primary outcomes were infant weight and height at 6 months and 12 months, and secondary outcome was maternal depression. The interviewers were unaware of what group the participants were assigned to. Analysis was by intention to treat. The study is registered as ISRCTN65316374. The number of clusters per group was 20, with 463 mothers in the intervention group and 440 in the control group. At 6 months, 97 (23%) of 418 and 211 (53%) of 400 mothers in the intervention and control groups, respectively, met the criteria for major depression (adjusted odds ratio (OR) 0.22, 95% CI 0.14 to 0.36, p<0.0001). These effects were sustained at 12 months (111/412 [27%] vs 226/386 [59%], adjusted OR 0.23, 95% CI 0.15 to 0.36, p<0.0001). The differences in weight-for-age and height-for-age Z scores for infants in the two groups were not significant at 6 months (-0.83 vs -0.86, p=0.7 and -2.03 vs -2.16, p=0.3, respectively) or 12 months (-0.64 vs -0.8, p=0.3 and -1.10 vs -1.36, p=0.07, respectively). This psychological intervention delivered by community-based primary health workers has the potential to be integrated into health systems in resource-poor settings. | 18,790,313 |
Epidemiology and diagnosis of acute kidney injury. | The development of recent standardized definitions of acute kidney injury (AKI) has allowed us to begin understanding pediatric AKI epidemiology and risk factors and to stratify outcome by AKI severity. AKI incidence will vary with illness severity of the population studied and definition type, ranging from less than 1% when need for dialysis is used to 82% when less conservative definitions (such as > or =1.5 times baseline serum creatinine) are used to define AKI. The most common AKI causes are secondary, such as sepsis, nephrotoxic medication, and ischemia, each leading to acute tubular necrosis (ATN). Children undergoing cardiopulmonary bypass surgery, stem cell transplantation, or with multiple organ dysfunction syndrome are at high risk for these events. A key feature in diagnosis and management includes identifying the presence of ATN versus a reversible hypovolemic state because patients with ATN may quickly develop fluid overload with overaggressive fluid therapy, requiring dialytic removal. Despite advances in acute pediatric dialysis therapy and in overall care of critically ill children, severe AKI still is associated with a high mortality rate, necessitating more research in early AKI identification and therapeutic trials. | 18,790,363 |
The timing of carotid endarterectomy post stroke. | The timing of carotid endarterectomy (CEA) post stroke remains a controversial area. Most authorities have advocated waiting at least 2 to 6 weeks after stroke before performing a CEA. More recently, these recommendations have been challenged. This article reviews the background leading to advocacy of delayed CEA after stroke, current literature recommendations regarding CEA after subacute stroke, current literature regarding neuroradiologic imaging findings and their implications in decision making regarding CEA after stroke, and the role of CEA for stroke in evolution. | 18,790,378 |
Bowel management for paediatric patients with faecal incontinence. | This review assesses the incidence and aetiology of faecal incontinence in childhood. We then systematically address the presentation, clinical assessment, investigation and management of these children. Under management, both medical and surgical approaches and their complications are discussed. | 18,790,425 |
Subtle renal duplication as an unrecognized cause of childhood incontinence: diagnosis by magnetic resonance urography. | Urinary incontinence in young girls who have been toilet trained may be due to an ectopic ureter inserting below the urinary sphincter. This diagnosis is frequently delayed, is psychologically distressing, and may be missed at physical examination. Findings at ultrasound evaluation may be subtle and imaging with computed tomography or intravenous urography exposes young patients to ionizing radiation. We report two cases of girls with urinary incontinence where magnetic resonance (MR) urography revealed subtle renal duplication which implied the presence of an ectopic duplicated ureter with infrasphincteric insertion. These cases stress the importance of examining the kidneys, rather than the perineum, at MR, ultrasound and intravenous urogram evaluation, and show the value of MR urography as a safe alternative to computed tomography and intravenous urography for making this diagnosis. | 18,790,427 |
Characterizing and optimizing immune responses to leukaemia antigens after allogeneic stem cell transplantation. | Allogeneic stem cell transplantation remains a curative treatment for haematological malignancies resistant to other treatment approaches through the unique graft-versus-leukaemia effect (GvL). However, the lack of specificity of this response results in the targeting of normal tissue, and the morbidity and mortality associated with graft-versus-host disease (GvHD). Further improvements in exploiting the GvL effect to prevent relapse in high-risk leukaemias while minimizing toxicity have focused on the use of targeted anti-leukaemic immunotherapy. These strategies include the use of vaccines against minor histocompatibility antigens (HA-1, HA-2 and H-Y) and leukaemia-specific antigens (proteinase 3, Wilms' tumour 1 and BCR-ABL), and the adoptive transfer of leukaemia-specific T cells. The unique post-transplant milieu, which is characterized by lymphopenia, regulatory T-cell depletion and the release of growth factors, offers the opportunity to promote the expansion of engrafted T cells and enhance the specific GvL response. Techniques to reduce regulatory T-cell control over T-cell responses to leukaemia antigens could further enhance GvL reactivity. Finally, these approaches to increase GvL effects would be facilitated by transplant approaches to deplete GvHD alloresponses selectively while preserving GvL reactivity. | 18,790,448 |
Neuroprotection by hypothalamic peptide proline-rich peptide-1 in Abeta25-35 model of Alzheimer's disease. | This work sought to determine the effects of hypothalamic proline-rich peptide (PRP)-1 in a rat model of Alzheimer's disease. Complex histochemical, electrophysiologic, and behavioral analyses were performed on intact or diseased Wistar rats (n = 28). Pathologic conditions were induced by bilateral intracerebroventricular injection of amyloid peptide Abeta25-35. The diseased rats received systemic administration of PRP-1 or placebo control. Abeta25-35 caused cellular neurodegeneration with marked glial reaction in the hippocampal complex and almost full destruction of the dentate fascia, which was not observed in conditions of PRP-1 administration after Abeta25-35 injection. Hippocampal neurons of intact animals responded to high-frequency (tetanic) stimulation of entorhinal cortex of ipsilateral cerebral hemisphere by tetanic and posttetanic potentiation of a different intensity and duration, which was accompanied by posttetanic depression. Abeta25-35 led to significant changes in the level and pattern of hippocampal neuronal activity, indicating the absence of both tetanic and posttetanic activity. Poststimulus activity manifestations rarely occurred and rapidly decreased after repeated trials. This indicated the focal character of lesion. Regular administration of PRP-1 for 4 weeks resulted in optimal restoration of electrophysiologic parameters. PRP-1 maintained the initial learning level achieved in a behavioral study in a Morris water maze. Systemic administration of PRP-1 possesses neuroprotective effects and can prevent the neurodegeneration in hippocampus induced by Abeta25-35. This suggests that PRP-1 could be a potential therapeutic agent for specific neurodegenerative diseases. | 18,790,460 |
The effects of amalgam restorations on plasma mercury levels and total antioxidant activity. | This study evaluated the effects of amalgam restorations on plasma mercury levels and total antioxidant activities (TAA). The study was comprised of 48 subjects ranging in age from 20 to 32 years. Of these, 33 had dental amalgam restorations and 15 had no dental amalgam restorations. In those patients with amalgams, the total number of amalgam restorations and surfaces were counted, and the total and occlusal areas (mm(2)) of restorations were measured using a Counting Measurement Machine. Blood samples were collected from all participants. Plasma mercury levels were measured using an Atomic Absorption Spectrometer and Hydride System, and plasma TAA levels were measured using an Antioxidant Assay Kit. Statistical analysis was performed using the SPSS 10.01 software program. Data was evaluated by t test and correlation analysis. Plasma mercury (P-Hg) levels were found to be significantly higher in subjects with amalgam restorations when compared to subjects without amalgams (p<0.01); the differences in P-TAA levels between subjects with and without amalgams were not found to be statistically significant (p>0.05). No significant correlations were found between P-Hg concentrations and P-TAA levels (p>0.05). Significant positive correlations were found between P-Hg concentrations and the number of amalgam restorations (p<0.01), number of amalgam surfaces (p<0.05), total amalgam surface area (p<0.05) and amalgam occlusal surface area (p<0.01). However, no significant correlations were found between these parameters and P-TAA (p>0.05). The results of our study showed that dental amalgams are a major source of plasma mercury; however, amalgam restorations were not found to have a significant effect on plasma-total antioxidant activities. | 18,790,473 |
Patient dignity in an acute hospital setting: a case study. | Nurses have a professional duty to respect patients' dignity. There is a dearth of research about patients' dignity in acute hospital settings. The study investigated the meaning of patient dignity, threats to patients' dignity, and how patient dignity can be promoted, in acute hospital settings. A qualitative, triangulated single case study design (one acute hospital), with embedded cases (one ward and its staff, and 24 patients). The study was based on a 22-bedded surgical ward in an acute hospital in England. Twenty-four patients, aged 34-92 years were purposively selected. There were 15 men and 9 women of varied socio-economic backgrounds. They could all communicate verbally and speak English. Twelve patients, who had stayed in the ward at least 2 days, were interviewed following discharge. The other 12 patients were observed and interviewed on the ward. The ward-based staff (26 registered nurses and healthcare assistants) were observed in practice. 13 were interviewed following observation. Six senior nurses were purposively selected for interviews. The data were collected during 2005. The Local Research Ethics Committee gave approval. Unstructured interviews using topic guides were conducted with the 24 patients, 13 ward-based staff and 6 senior nurses. Twelve 4-h episodes of participant observation were conducted. The data were analysed thematically using the framework approach. Patient dignity comprised feelings (feeling comfortable, in control and valued), physical presentation and behaviour. The environment, staff behaviour and patient factors impacted on patient dignity. Lack of environmental privacy threatened dignity. A conducive physical environment, dignity-promoting culture and other patients' support promoted dignity. Staff being curt, authoritarian and breaching privacy threatened dignity. Staff promoted dignity by providing privacy and interactions which made patients feel comfortable, in control and valued. Patients' impaired health and older age rendered them vulnerable to a loss of dignity. Patients promoted their own dignity through their attitudes (rationalisation, use of humour, acceptance), developing relationships with staff and retaining ability and control. Patients are vulnerable to loss of dignity in hospital. Staff behaviour and the hospital environment can influence whether patients' dignity is lost or upheld. | 18,790,477 |
Surface modification of polypropylene macroporous membrane to improve its antifouling characteristics in a submerged membrane-bioreactor: H(2)O plasma treatment. | To improve the antifouling characteristics of polypropylene hollow fiber macroporous membranes in a submerged membrane-bioreactor for wastewater treatment, the membranes were surface modified by H(2)O plasma treatment. Structural and morphological changes on the membrane surface were characterized by X-ray photoelectron spectroscopy (XPS) and field emission scanning electron microscopy (FE-SEM). The change of surface wettability was monitored by contact angle measurement. The static water contact angle of the modified membrane reduced obviously with the increase of plasma treatment time. The total surface free energy and its dispersive component decreased, while the polar component increased with the increase of treatment time. The relative pure water flux for the modified membranes increased gradually with the increase of plasma treatment time. The tensile strength and the tensile elongation at break for the membranes decreased after plasma treatment. After continuous operation in a submerged membrane-bioreactor for about 68 h, flux recovery after water and caustic cleaning, flux ratio after fouling were improved by 2.0, 3.6 and 22.0%, while reduction of flux was reduced by 1.1% for the 1 min H(2)O plasma treated membrane, compared to those of the unmodified membrane. | 18,790,513 |
Anthropogenic effects on the subsurface thermal and groundwater environments in Osaka, Japan and Bangkok, Thailand. | Anthropogenic effects in both Osaka and Bangkok were evaluated to compare the relationships between subsurface environment and the development stage of both cities. Subsurface thermal anomalies due to heat island effects were found in both cities. The Surface Warming Index (SWI), the departure depth from the steady geothermal gradient, was used as an indicator of the heat island effect. SWI increases (deeper) with the magnitude of heat island effect and the elapsed time starting from the surface warming. Distributions of subsurface thermal anomalies due to the heat island effect agreed well with the distribution of changes in air temperature due to the same process, which is described by the distribution of population density in both Osaka and Bangkok. Different time lags between groundwater depression and subsidence in the two cities was found. This is attributed to differences in hydrogeologic characters, such as porosity and hydraulic conductivity. We find that differences in subsurface degradations in Osaka and Bangkok, including subsurface thermal anomalies, groundwater depression, and land subsidence, depends on the difference of the development stage of urbanization and hydrogeological characters. | 18,790,519 |
Thrombolysis with alteplase 3-4.5 h after acute ischaemic stroke (SITS-ISTR): an observational study. | Intravenous alteplase is approved for use within 3 h of ischaemic stroke onset, although a meta-analysis of randomised controlled trials suggests treatment benefit up to 4.5 h. We compared outcome in patients treated between 3 h and 4.5 h versus those treated within 3 h, who were recorded in the in the Safe Implementation of Treatments in Stroke (SITS), a prospective internet-based audit of the International Stroke Thrombolysis Registry (ISTR). We compared 664 patients presenting with ischaemic stroke and given intravenous altepase (0.9 mg/kg total dose) between 3 h and 4.5 h with 11 865 patients treated within 3 h. All patients were otherwise compliant with European summary of product characteristics criteria and had been documented in the international stroke treatment registry between Dec 25, 2002, and Nov 15, 2007. Outcome measures were symptomatic intracerebral haemorrhage within 24 h (haemorrhage type 2 associated with National Institutes of Health Stroke Scale [NIHSS] > or = 4 points deterioration), and mortality and independence (modified Rankin scale of 0-2) at 3 months. In the 3-4.5-h cohort, treatment was started at a median of 55 min later after symptom onset (195 min [IQR 187-210] vs 140 min [115-165], p<0.0001), median age was 3 years younger (65 years [55-73] vs 68 years [58-74], p<0.0001), and stroke severity was lower (NIHSS score 11 [7-16] vs 12 [8-17], p<0.0001) than in the 3-h cohort. We recorded no significant differences between the 3-4.5-h cohort and the within 3-h cohort for any outcome measure--rate of symptomatic intracerebral haemorrhage: 2.2% (14 of 649) versus 1.6% (183 of 11 681) (odds ratio [OR] 1.18 [95% CI 0.89-1.55], p=0.24; adjusted OR 1.32 [1.00-1.75], p=0.052); mortality: 12.7% (70 of 551) versus 12.2% (1263 of 10 368) (OR 1.02 [0.90-1.17]; p=0.72; adjusted OR 1.15 [1.00-1.33]; p=0.053); and independence: 58.0% (314 of 541) versus 56.3% (5756 of 10231) (OR 1.04 [0.95-1.13], p=0.42; adjusted OR 0.93 [0.84-1.03], p=0.18). Alteplase remains safe when given at 3-4.5 h after ischaemic stroke, offering an opportunity for patients who cannot be treated within the standard 3-h timeframe. Boehringer-Ingelheim, European Union Public Health Executive Authority. | 18,790,527 |
Drug delivery from gold and titanium surfaces using self-assembled monolayers. | Currently available drug-eluting stents (DES) use polymers for coating and releasing drugs. Increasing evidence suggests that inflammatory and hypersensitive reactions are caused by such polymer coatings. This study focused on developing new techniques for delivering drugs directly from metal implant surfaces. Hydroxyl-terminated self-assembled monolayers (SAMs) were coated on Au and Ti surfaces. Therapeutic self-assembled monolayers (TSAMs) were prepared by chemically attaching the model drug, flufenamic acid, to SAM coated metal surfaces. Three different methods of esterification (acid chloride esterification, dry heat esterification, and direct esterification) were explored to attach flufenamic acid to SAMs. TSAMs were characterized using X-ray photoelectron spectroscopy, fluorescence microscopy, atomic force microscopy, and contact angle goniometry. These techniques collectively confirmed the attachment of drug onto SAM coated metal surfaces. In vitro drug release was investigated by immersing TSAM coated metal specimens in tris-buffered saline (TBS) at 37 degrees C for 28 days. TBS was analyzed at 1, 3, 7, 14, 21, and 28 days for the amount of drug eluted using high performance liquid chromatography. Large data scatter was observed for the release profiles of TSAMs prepared by acid chloride esterification. TSAMs prepared by dry heat and direct esterification methods showed an initial burst release of the drug followed by a sustained slow release for up to 2 weeks. Thus, this study suggests the potential for using self-assembled monolayers as an alternate system for delivering drugs from coronary stents and other metal implants. | 18,790,530 |
Does methodology matter in eyewitness identification research? The effect of live versus video exposure on eyewitness identification accuracy. | The present study examined the effect of mode of target exposure (live versus video) on eyewitness identification accuracy. Adult participants (N=104) were exposed to a staged crime that they witnessed either live or on videotape. Participants were then asked to rate their stress and arousal levels prior to being presented with either a target-present or -absent simultaneous lineup. Across target-present and -absent lineups, mode of target exposure did not have a significant effect on identification accuracy. However, mode of target exposure was found to have a significant effect on stress and arousal levels. Participants who witnessed the crime live had higher levels of stress and arousal than those who were exposed to the videotaped crime. A higher level of arousal was significantly related to poorer identification accuracy for those in the video condition. For participants in the live condition however, stress and arousal had no effect on eyewitness identification accuracy. Implications of these findings in regards to the generalizability of laboratory-based research on eyewitness testimony to real-life crime are discussed. | 18,790,535 |
Calcifying epithelial odontogenic tumor of the maxilla with ulcerative stomatitis: a case report. | Calcifying epithelial odontogenic tumor (CEOT) is a rare benign odontogenic tumor, known as Pindborg tumor. Although ulcer formation was reported in one previously involving the peripheral maxilla, such change of the overlying mucosa has been reported in intraosseous CEOT. We report maxillary CEOT in a patient who complained of spontaneous pain due to extensive ulcer formation of the oral mucosa. | 18,790,551 |
Use of negative air pressure by nasal suction during maxillary sinus floor lift: audit of 13 consecutive sinus grafts. | A common and serious intraoperative complication of sinus floor lift is perforation of the sinus lining. Several strategies to prevent or treat it have had varying results. We report the results of an audit of 13 consecutive sinus grafts in 11 patients in which nasal suction was used to facilitate raising the sinus lining, and to reduce the risk of perforation. | 18,790,552 |
Relationship between uterine morphology and peripheral concentrations of sex steroid hormone in wild Japanese black bears (Ursus thibetanus japonicus). | Developing a better understanding of the reproductive physiology and breeding condition peculiar to wild Japanese black bears (Ursus thibetanus japonicus) is crucial for estimation of their habitat distribution. The aim of this study was to clarify the changes in morphology of the genital organs, cellular proliferation in the endometrium and sex steroid hormone concentrations along with the reproductive cycle in Japanese black bears. Samples were collected from a total of 24 female Japanese black bears (1-15 presumptive years old) that were caught in the wild in Iwate prefecture during the period between August 1999 and September 2005. Twenty-two out of the 24 animals were hunted from May to October. The ovaries from the 24 animals and the uteri from 23 animals were observed macroscopically and histologically to examine the relationship between morphology of the genital organs and the month of the year the animal was caught. The staining pattern of proliferating cell nuclear antigen (PCNA) in the endometrium was characterised. Peripheral concentrations of oestradiol-17beta and progesterone were determined by radioimmunoassay. All the animals that had a corpus luteum (n=12) were captured from August to October. The thickness of the endometrium in the animals captured from August to October (n=16) was significantly greater than those in animals captured from May to July (n=5) (P<0.05). From August to October, the thickness of the endometrium and the ratio of the area of the uterine glands to the area of the endometrium in the animals with a corpus luteum (n=12) were significantly greater than those without a corpus luteum (n=4) (P<0.01). Positive PCNA staining was only observed in the uteri of two animals captured in May. There was a significantly positive correlation between plasma progesterone concentrations and the thickness of the endometrium (rho=0.589, P<0.05). There were also significantly positive correlations between the progesterone to oestradiol-17beta ratio (P4/E2 ratio) and the thickness of the endometrium (rho=0.710, P<0.05), and between the P4/E2 ratio and the ratio of the uterine gland area in the endometrium (rho=0.626, P<0.01). These data suggest that the corpus luteum is formed during or just after the breeding season and that the cells in the endometrium and the uterine glands, which proliferate in the early breeding season, grow and develop under the influence of progesterone and oestradiol-17beta during the period of delayed implantation in Japanese black bears. | 18,790,579 |
Liquid nitrogen ingestion leading to massive pneumoperitoneum without identifiable gastrointestinal perforation. | Liquid nitrogen (LN) ingestion is unusual, but may be encountered by poison centers, emergency physicians, and general surgeons. Unique properties of LN produce a characteristic pattern of injury. A 19-year-old male college student presented to the Emergency Department complaining of abdominal pain and "bloating" after drinking LN. His presentation vital signs were remarkable only for mild tachypnea and tachycardia. On physical examination, he had mild respiratory difficulty due to abdominal distention. His abdomen was tense and distended. Abdominal X-ray studies revealed a massive pneumoperitoneum. At laparotomy, he was found to have a large amount of peritoneal gas. No perforation was identified. After surgery, the patient made an uneventful recovery and was discharged 5 days later. At 2-week clinic follow-up, he was doing well without complications. Nitrogen is a colorless, odorless gas at room temperature. Due to its low boiling point (-195 degrees C), LN rapidly evaporates when in contact with body surface temperatures. Therefore, ingested LN causes damage by two mechanisms: rapid freezing injury upon mucosal contact and rapid volume expansion as nitrogen gas is formed. Patients who ingest LN may develop gastrointestinal perforation and massive pneumoperitoneum. Because rapid gas formation may allow large volumes to escape from tiny perforations, the exact site of perforation may never be identified. In cases of LN ingestion, mucosal injury and rapid gas formation can cause massive pneumoperitoneum. Although laparotomy is recommended for all patients with signs of perforation, the site of injury may never be identified. | 18,790,587 |
Rapid diagnosis of acute bacterial meningitis: role of a broad range 16S rRNA polymerase chain reaction. | Acute bacterial meningitis is a significant cause of morbidity and mortality throughout the world. It can be difficult to diagnose, as the symptoms and signs are often non-specific. To evaluate the performance of an in-house semi-nested polymerase chain reaction (PCR) assay targeting the 16S rRNA gene of Eubacteria for the rapid diagnosis of acute bacterial meningitis using cerebrospinal fluid (CSF) specimens. A total of 112 CSF samples from 112 patients were used in the study. Among these, 32 samples were obtained from confirmed cases of Streptococcus pneumoniae, six samples were obtained from confirmed cases of Haemophilus influenzae, one sample from a confirmed case of Neisseria meningitidis, and 10 cases of clinically suspected acute bacterial meningitis. The remaining 63 CSF samples were obtained from patients with non-infectious illnesses (n = 47) of the central nervous system (CNS) and autopsy-confirmed tuberculous meningitis (n = 16). The assay had an overall sensitivity of 93% (95% confidence interval [CI] 0.81-0.98, negative predictive value = 95%) and a specificity of 98% (95% CI 0.92-1.0, positive predictive value = 98%). These preliminary findings suggest that the semi-nested PCR assay targeting the 16S rRNA gene may be used as a rapid test for the diagnosis of acute bacterial meningitis. | 18,790,588 |
A report of post-traumatic Eagle's Syndrome. | This paper reports the case of a 39-year-old woman who presented with symptoms of Eagle's Syndrome and an ossified stylohyoid ligament (SHL). Symptoms had developed immediately after trauma to the neck. No injury to the SHL was radiologically observable, but the causal relationship between the trauma and the occurrence of symptoms was evident. A new symptom of Eagle's Syndrome mimicking osteoathrosis of the temporomandibular joint was observed. The risk of misdiagnosis of temporomandibular disorders and the etiological role of neck trauma in Eagle's Syndrome are discussed. | 18,790,603 |
The efficacy of aripiprazole in the treatment of multiple symptom domains in patients with acute schizophrenia: a pooled analysis of data from the pivotal trials. | To examine the efficacy of aripiprazole across symptoms in patients with acute exacerbation of schizophrenia or schizoaffective disorder. Data were pooled from five, 4-6-week acute studies. PANSS Total, Positive, Negative, and General Psychopathology Subscale improvements were analyzed, as well as all 30 individual PANSS items. Aripiprazole had statistically significant decreases versus placebo on PANSS subscales at Week 4, similar to those seen with haloperidol. Aripiprazole-treated patients also showed significant decreases versus placebo in 26 of the 30 PANSS items (all p<0.05). Aripiprazole demonstrates statistically and clinically significant efficacy across a range of symptoms in schizophrenia. | 18,790,605 |
The evaluation of a trial of syringe vending machines in Canberra, Australia. | Syringe vending machines (SVMs) have been trialled in Canberra, Australian Capital Territory, Australia, as an intervention aiming to increase the availability of sterile injecting equipment for use by IDUs. This study evaluated the 12-month trial. A utilisation-focused evaluation model, with both formative and summative components, was employed. Four SVMs were installed, each dispensing packs containing four 1 mL syringes and associated injecting paraphernalia. The trial participants were the clients of the SVMs and other key informants. The core measurements used were the number of syringes dispensed in Canberra by SVMs and other outlets, SVM clients' demographics and experiences of and attitudes towards SVMs, perceived impacts of SVMs on needle sharing, unsafe disposal of used syringes in the vicinity of SVMs, and community and stakeholder attitudes. The trial was implemented successfully, with no adverse consequences identified. The SVMs appear to be serving both the usual clients of the other outlets for sterile injecting equipment (community pharmacies and the Needle Syringe Program outlets) and others who are reluctant to use such outlets or find them inconvenient. The out-of-business-hours provision of syringes through the SVMs was particularly welcomed by both SVM clients and other stakeholders. The continuing operation of the initial four SVMs is widely supported, and additional machines are requested by clients and others. Owing to the success of the trial in terms of feasibility and outcomes for both IDUs and for the broader community, it is desirable that providing sterile injecting equipment through SVMs continues and be expanded as an integral component of harm reduction strategies. | 18,790,622 |
Patients at risk for long-term sick leave because of low back pain. | Ten percent of patients with low back pain (LBP) are not able to resume work within 3 months of sick leave, accounting for 90% of all medical and indemnity costs. To quantify the relative contribution of sociodemographic, clinical, occupational, and psychological risk factors in determining the non-return to work after 3 months of compensated LBP and to develop a screening tool to identify patients who require further guidance and rehabilitation. A 6-month prospective cohort study of disabled workers applying for compensation benefit because of LBP during a 6-month period in the Belgian compulsory health insurance system. Three hundred and forty-six patients. Patients unable to resume work within 3 months of sick leave were classified as bad outcomes. Consecutively, injured workers applying for income replacement benefits between October 2003 and March 2004 because of LBP were followed 6 months after the start of the sick leave period. All subjects underwent a standardized physical examination and completed a battery of 12 self-report questionnaires. Forty-seven percent of the population had not resumed work 3 months after the start of the sick leave period. The risk factors for sickness absence more than 3 months were Oswestry disability index (odds ratio for each point increase: 1.04; 95% confidence interval: 1.02-1.06), fear of avoidance severity score (odds ratio for each point increase: 1.05; confidence interval: 1.02-1.09), blue collar worker (odds ratio: 2.18; confidence interval: 1.21-3.92), LBP for less than 12 weeks before sick leave (odds ratio: 0.32; confidence interval: 0.17-0.64), and pain behavior (odds ratio for each point increase: 1.72; confidence interval: 1.25-2.39). A multivariate screening test based on five questions identified 80% of the patients unable to resume work after 3 months of sick leave (specificity: 56.6; cut off: 0.4). A questionnaire comprising a limited set of items allows a practical screening of LBP patients unlikely to resume work. | 18,790,677 |
Binding of calcium ions to Ras promotes Ras guanine nucleotide exchange under emulated physiological conditions. | Both Ras protein and calcium play significant roles in various cellular processes via complex signaling transduction networks. However, it is not well understood whether and how Ca(2+) can directly regulate Ras function. Here we demonstrate by isothermal titration calorimetry that Ca(2+) directly binds to the H-Ras.GDP.Mg(2+) complex with moderate affinity at the first binding site followed by two weak binding events. The results from limited proteinase degradation show that Ca(2+) protects the fragments of H-Ras from being further degraded by trypsin and by proteinase K. HPLC studies together with fluorescence spectroscopic measurements indicate that binding of Ca(2+) to the H-Ras.GDP.Mg(2+) complex remarkably promotes guanine nucleotide exchange on H-Ras under emulated physiological Ca(2+) concentration conditions. Addition of high concentrations of either of two macromolecular crowding agents, Ficoll 70 and dextran 70, dramatically enhances H-Ras guanine nucleotide exchange extent in the presence of Ca(2+) at emulated physiological concentrations, and the nucleotide exchange extent increases significantly with the concentrations of crowding agents. Together, these results indicate that binding of calcium ions to H-Ras remarkably promotes H-Ras guanine nucleotide exchange under emulated physiological conditions. We thus propose that Ca(2+) may activate Ras signaling pathway by interaction with Ras, providing clues to understand the role of calcium in regulating Ras function in physiological environments. | 18,790,720 |
Sirolimus affects cardiomyocytes to reduce left ventricular mass in heart transplant recipients. | The cellular mechanisms underlying cardiac hypertrophy may result from changes in cardiac myocyte growth and differentiation. We tested whether sirolimus, an immunosuppressive agent that inhibits mTOR, a protein that regulates cell division and differentiation, might modify cardiac hypertrophy after cardiac transplantation. Fifty-eight cardiac transplant recipients were withdrawn from treatment with calcineurin inhibitors (CNIs) and treated with sirolimus. Eighty-three control subjects were maintained on CNIs. After 12 months, left ventricular (LV) mass decreased from 196.15 +/- 48.28 to 182.21 +/- 43.56 g (P = 0.05) and LV mass index from 99.25 +/- 20.08 to 93.82 +/- 20.22 g/m(2) (P = 0.031) in sirolimus-treated subjects but did not change in controls. The left atrial volume index of sirolimus-treated subjects decreased from 52.44 +/- 17.22 to 48.40 +/- 15.14 cc/m(2) (P = 0.008) and increased from 52.07 +/- 19.45 to 57.03 +/- 19.93 cc/m(2) (P = 0.0012) in controls. The difference between the groups was independent of blood pressure. The number of cells in myocardial biopsies positive for p27Kip1, a protein induced by mTOR inhibition, increased in sirolimus-treated subjects (P = 0.0005) and did not change in controls (P = 0.54) suggesting sirolimus acted directly on myocardium. Sirolimus may inhibit adverse ventricular remodelling resulting in cardiac hypertrophy and have potential in the treatment of conditions in which severe hypertrophy compromises cardiac function. | 18,790,727 |
Ubiquitination and endocytosis of cell adhesion molecule DM-GRASP regulate its cell surface presence and affect its role for axon navigation. | DM-GRASP, cell adhesion molecule of the immunoglobulin superfamily, has been shown to promote growth and navigation of axons. We here demonstrate that clustering of DM-GRASP in the plasma membrane induces its rapid internalization via dynamin- and clathrin-dependent endocytosis, which is controlled by phosphatidylinositol 3-kinase and mitogen-activated protein kinase ERK. The clustering of DM-GRASP activates ERK; the intensity and duration of ERK activation by DM-GRASP do not depend on rapid clathrin-mediated internalization of DM-GRASP. Moreover, the preference of retinal ganglion cell axons for DM-GRASP-coated micro-lanes requires clathrin-mediated endocytosis for the appropriate axonal turning reactions at substrate borders. Because the intracellular domain of DM-GRASP does not contain motifs for direct interactions with the endocytosis machinery, we performed a yeast two-hybrid screen to identify intracellular proteins mediating the uptake of DM-GRASP and isolated ubiquitin. Immunoprecipitation of DM-GRASP coexpressed with ubiquitin revealed that one or two ubiquitin(s) are attached to the intracellular domain of cell surface-resident DM-GRASP. Furthermore, elevated ubiquitination levels result in a decrease of cell surface-resident DM-GRASP as well as in the amount of total DM-GRASP. The endocytosis rate is not affected, but the delivery to multivesicular bodies is increased, indicating that DM-GRASP ubiquitination enhances its sorting into the degradation pathway. Together, our data show that ubiquitination and endocytosis of DM-GRASP in concert regulate its cell surface concentration, which is crucial for its function in axon navigation. | 18,790,729 |
Mitogen-activated protein kinase kinase 1/2 inhibitors and 17-allylamino-17-demethoxygeldanamycin synergize to kill human gastrointestinal tumor cells in vitro via suppression of c-FLIP-s levels and activation of CD95. | Prior studies have noted that inhibitors of mitogen-activated protein kinase (MAPK) kinase 1/2 (MEK1/2) enhanced geldanamycin lethality in malignant hematopoietic cells by promoting mitochondrial dysfunction. The present studies focused on defining the mechanism(s) by which these agents altered survival in carcinoma cells. MEK1/2 inhibitors [PD184352; AZD6244 (ARRY-142886)] interacted in a synergistic manner with geldanamycins [17-allylamino-17-demethoxygeldanamycin (17AAG) and 17-dimethylaminoethylamino-17-demethoxy-geldanamycin] to kill hepatoma and pancreatic carcinoma cells that correlated with inactivation of extracellular signal-regulated kinase 1/2 and AKT and with activation of p38 MAPK; p38 MAPK activation was reactive oxygen species dependent. Treatment of cells with MEK1/2 inhibitors and 17AAG reduced expression of c-FLIP-s that was mechanistically connected to loss of MEK1/2 and AKT function; inhibition of caspase-8 or overexpression of c-FLIP-s abolished cell killing by MEK1/2 inhibitors and 17AAG. Treatment of cells with MEK1/2 inhibitors and 17AAG caused a p38 MAPK-dependent plasma membrane clustering of CD95 without altering the levels or cleavage of FAS ligand. In parallel, treatment of cells with MEK1/2 inhibitors and 17AAG caused a p38 MAPK-dependent association of caspase-8 with CD95. Inhibition of p38 MAPK or knockdown of BID, FAS-associated death domain, or CD95 expression suppressed MEK1/2 inhibitor and 17AAG lethality. Similar correlative data were obtained using a xenograft flank tumor model system. Our data show that treatment of tumor cells with MEK1/2 inhibitors and 17AAG induces activation of the extrinsic pathway and that suppression of c-FLIP-s expression is [Mol Cancer Ther 2008;7(9):2633-48]. | 18,790,746 |
Interleukin-8 signaling attenuates TRAIL- and chemotherapy-induced apoptosis through transcriptional regulation of c-FLIP in prostate cancer cells. | Chemotherapy-induced interleukin-8 (IL-8) signaling reduces the sensitivity of prostate cancer cells to undergo apoptosis. In this study, we investigated how endogenous and drug-induced IL-8 signaling altered the extrinsic apoptosis pathway by determining the sensitivity of LNCaP and PC3 cells to administration of the death receptor agonist tumor necrosis factor-related apoptosis-inducing ligand (TRAIL). TRAIL induced concentration-dependent decreases in LNCaP and PC3 cell viability, coincident with increased levels of apoptosis and the potentiation of IL-8 secretion. Administration of recombinant human IL-8 was shown to increase the mRNA transcript levels and expression of c-FLIP(L) and c-FLIP(S), two isoforms of the endogenous caspase-8 inhibitor. Pretreatment with the CXCR2 antagonist AZ10397767 significantly attenuated IL-8-induced c-FLIP mRNA up-regulation whereas inhibition of androgen receptor- and/or nuclear factor-kappaB-mediated transcription attenuated IL-8-induced c-FLIP expression in LNCaP and PC3 cells, respectively. Inhibition of c-FLIP expression was shown to induce spontaneous apoptosis in both cell lines and to sensitize these prostate cancer cells to treatment with TRAIL, oxaliplatin, and docetaxel. Coadministration of AZ10397767 also increased the sensitivity of PC3 cells to the apoptosis-inducing effects of recombinant TRAIL, most likely due to the ability of this antagonist to block TRAIL- and IL-8-induced up-regulation of c-FLIP in these cells. We conclude that endogenous and TRAIL-induced IL-8 signaling can modulate the extrinsic apoptosis pathway in prostate cancer cells through direct transcriptional regulation of c-FLIP. Therefore, targeted inhibition of IL-8 signaling or c-FLIP expression in prostate cancer may be an attractive therapeutic strategy to sensitize this stage of disease to chemotherapy. | 18,790,747 |
An orally bioavailable small-molecule inhibitor of Hedgehog signaling inhibits tumor initiation and metastasis in pancreatic cancer. | Recent evidence suggests that blockade of aberrant Hedgehog signaling can be exploited as a therapeutic strategy for pancreatic cancer. Our previous studies using the prototype Hedgehog small-molecule antagonist cyclopamine had shown the striking inhibition of systemic metastases on Hedgehog blockade in spontaneously metastatic orthotopic xenograft models. Cyclopamine is a natural compound with suboptimal pharmacokinetics, which impedes clinical translation. In the present study, a novel, orally bioavailable small-molecule Hedgehog inhibitor, IPI-269609, was tested using in vitro and in vivo model systems. In vitro treatment of pancreatic cancer cell lines with IPI-269609 resembled effects observed using cyclopamine (i.e., Gli-responsive reporter knockdown, down-regulation of the Hedgehog target genes Gli1 and Ptch, as well as abrogation of cell migration and colony formation in soft agar). Single-agent IPI-269609 profoundly inhibited systemic metastases in orthotopic xenografts established from human pancreatic cancer cell lines, although Hedgehog blockade had minimal effect on primary tumor volume. The only discernible phenotype observed within the treated primary tumor was a significant reduction in the population of aldehyde dehydrogenase-bright cells, which we have previously identified as a clonogenic tumor-initiating population in pancreatic cancer. Selective ex vivo depletion of aldehyde dehydrogenase-bright cells with IPI-269609 was accompanied by significant reduction in tumor engraftment rates in athymic mice. Pharmacologic blockade of aberrant Hedgehog signaling might prove to be an effective therapeutic strategy for inhibition of systemic metastases in pancreatic cancer, likely through targeting subsets of cancer cells with tumor-initiating ("cancer stem cell") properties. | 18,790,753 |
Soluble EP2 neutralizes prostaglandin E2-induced cell signaling and inhibits osteolytic tumor growth. | Prostaglandin E2 (PGE2) plays a key role in osteolytic bone metastasis as well as roles in inflammation, cell growth, and tumor development. PGE2 exerts its effects by binding and activating E-prostanoid receptor (EP). In this study, we propose a new approach for blocking EP-mediated cell signaling using a soluble chimeric EP2 fragment. Mammalian expression vectors encoding several human EP2 cDNAs were introduced into 293 cells and the culture medium was tested for their function as a decoy receptor for PGE2. PGE2 binding assays revealed that culture medium containing the second extracellular region of EP2 (FuEP2/Ex2) had binding activity. FuEP2/Ex2 neutralized PGE2-induced cyclic AMP production, cyclic AMP-responsive element binding protein phosphorylation, and subsequent induction of cyclooxygenase-2, interleukin (IL)-1beta, and IL-6 mRNAs. In human osteoblasts, this culture medium neutralized the induction of receptor activator of nuclear factor-kappaB ligand mRNA. A stable transfectant expressing FuEP2/Ex2 was established from human prostate cancer PC-3 cells (PC3-FuEP2/Ex2). PC3-FuEP2/Ex2 cells grew at similar rates to vector control cells under normal culture conditions, although PGE2-induced growth stimulation was suppressed. Intraosseous injection of PC3-FuEP2/Ex2 cells into the tibia of athymic nude mice revealed that the degrees of tumor growth and osteolysis were decreased compared with control cell-injected mice, with decreased osteoclasts and increased apoptotic cells. Furthermore, the cyclooxygenase-2, IL-1beta, and IL-6 mRNA levels were reduced in the tumor lesions. These data suggest that FuEP2/Ex2 is useful for treating osteolytic bone metastasis and cancers that depend on EP signaling for their growth and development. | 18,790,761 |
Administration of PLK-1 small interfering RNA with atelocollagen prevents the growth of liver metastases of lung cancer. | Liver metastasis is one of the most important prognostic factors in lung cancer patients. However, current therapies are not sufficient. RNA interference provides us a powerful and promising approach for treating human diseases including cancers. Herein, we investigated the in vitro effects of PLK-1 small interfering RNA (siRNA) on human lung cancer cell lines and the in vivo usage of PLK-1 siRNA with atelocollagen as a drug delivery system in a murine liver metastasis model of lung cancer. PLK-1 was overexpressed in cell lines and in cancerous tissues from lung cancer patients. PLK-1 siRNA treatment inhibited growth and induced apoptosis in a concentration-dependent manner. To verify in vivo efficacy, we confirmed that atelocollagen was a useful drug delivery system in our model of implanted luciferase-labeled A549LUC cells by detecting reduced bioluminescence after an i.v. injection of luciferase GL3 siRNA/atelocollagen. PLK-1 siRNA/atelocollagen was also successfully transfected into cells and inhibited the progression of metastases. This study shows the efficacy of i.v. administration of PLK-1 siRNA/atelocollagen for liver metastases of lung cancer. We believe siRNA therapy will be a powerful and promising strategy against advanced lung cancer. | 18,790,771 |
Atypical retinoids ST1926 and CD437 are S-phase-specific agents causing DNA double-strand breaks: significance for the cytotoxic and antiproliferative activity. | Retinoid-related molecules (RRM) are novel agents with tumor-selective cytotoxic/antiproliferative activity, a different mechanism of action from classic retinoids and no cross-resistance with other chemotherapeutics. ST1926 and CD437 are prototypic RRMs, with the former currently undergoing phase I clinical trials. We show here that ST1926, CD437, and active congeners cause DNA damage. Cellular and subcellular COMET assays, H2AX phosphorylation (gamma-H2AX), and scoring of chromosome aberrations indicate that active RRMs produce DNA double-strand breaks (DSB) and chromosomal lesions in NB4, an acute myeloid leukemia (AML) cell line characterized by high sensitivity to RRMs. There is a direct quantitative correlation between the levels of DSBs and the cytotoxic/antiproliferative effects induced by RRMs. NB4.437r blasts, which are selectively resistant to RRMs, do not show any sign of DNA damage after treatment with ST1926, CD437, and analogues. DNA damage is the major mechanism underlying the antileukemic activity of RRMs in NB4 and other AML cell lines. In accordance with the S-phase specificity of the cytotoxic and antiproliferative responses of AML cells to RRMs, increases in DSBs are maximal during the S phase of the cell cycle. Induction of DSBs precedes inhibition of DNA replication and is associated with rapid activation of ataxia telangectasia mutated, ataxia telangectasia RAD3-related, and DNA-dependent protein kinases with subsequent stimulation of the p38 mitogen-activated protein kinase. Inhibition of ataxia telangectasia mutated and DNA-dependent protein kinases reduces phosphorylation of H2AX. Cells defective for homologous recombination are particularly sensitive to ST1926, indicating that this process is important for the protection of cells from the RRM-dependent DNA damage and cytotoxicity. | 18,790,775 |
Alcohol increases homocysteine and reduces B vitamin concentration in healthy male volunteers--a randomized, crossover intervention study. | Few studies have examined the effect of alcohol consumption on total homocysteine (tHcy) concentrations. To assess the effect of an 8-week intervention with vodka or red wine on plasma tHcy and B vitamin concentrations in healthy male volunteers. To assess the effect on tHcy according to methylenetetrahydrofolate reductase (MTHFR) 677C>T genotype. A randomized controlled crossover intervention study measuring tHcy and serum folate and vitamin B(12) concentrations was conducted in 78 male subjects (21-70 years). Following a 2-week washout period during which no alcohol was consumed, all subjects consumed 24 g alcohol (either 240 ml red wine or 80 ml vodka)/day for a 2-week period. Following a further 2-week washout, participants consumed the alternate intervention for 2 weeks. A significant increase in plasma tHcy was observed after the 2-week red wine intervention (5%, P = 0.03), and a non-significant increase in tHcy with vodka intervention (3%, P = 0.09). When the two interventions were compared, the change in tHcy did not differ between the vodka and red wine interventions (P = 0.57). There were significant decreases in serum vitamin B(12) and folate concentrations, and this decrease did not differ between interventions. The increase in tHcy observed in both interventions did not vary by MTHFR 677C>T genotype. A 2-week alcohol intervention resulted in a decrease in folate and vitamin B(12) status and an increase in plasma tHcy. The effect of alcohol intervention on tHcy, folate and vitamin B(12) concentrations did not differ between the red wine and vodka intervention groups. | 18,790,817 |
Structural and functional correlates of unilateral mesial temporal lobe spatial memory impairment. | The aim of this study was to explore the effects of preoperative and postoperative lateralized mesial temporal damage on three measures of spatial learning: navigation, object location and plan drawing, and to determine the relationship between volumetry of the hippocampus and memory performance. Fifteen patients with well-characterized unilateral hippocampal sclerosis, 15 patients who had undergone unilateral anterior temporal lobectomy (ATL), and a comparison group consisting of 15 patients with idiopathic generalized epilepsy and 25 neurologically healthy participants explored a novel virtual environment. Volumetric analyses of both hippocampi were conducted on unilateral hippocampal sclerosis and idiopathic generalized epilepsy patients' T(1)-weighted magnetic resonance imaging scans. Performance of temporal lobe epilepsy (TLE) patients (either unilateral hippocampal sclerosis or anterior temporal lobectomy) on the different spatial memory variables, namely navigation, object location and plan drawing, was significantly worse relative to the comparison groups (either idiopathic generalized epilepsy or controls). Patients with right TLE did not differ from patients with left TLE on any of the spatial memory measures. An index of absolute hippocampal asymmetry did not correlate with any of the spatial memory measures. Together, our lesion and volumetry findings suggest that the domain of spatial memory is systematically related to the integrity of both right and left mesial temporal lobe, and is unlikely to be a strongly lateralized function. From the standpoint of cerebral organization (lateralization), the notion of material-specificity, which postulates that all components of verbal and spatial memory are lateralized in their entirety to the left and right hemispheres, respectively, requires modification. Instead it would appear that the notion of task-specificity is a more accurate description of patterns of lateralization of spatial memory. | 18,790,820 |
Bnip3 functions as a mitochondrial sensor of oxidative stress during myocardial ischemia and reperfusion. | Bcl-2/adenovirus E1B 19-kDa protein-interacting protein 3 (Bnip3) is a member of the Bcl-2 homology domain 3-only subfamily of proapoptotic Bcl-2 proteins and is associated with cell death in the myocardium. In this study, we investigated the potential mechanism(s) by which Bnip3 activity is regulated. We found that Bnip3 forms a DTT-sensitive homodimer that increased after myocardial ischemia-reperfusion (I/R). The presence of the antioxidant N-acetylcysteine reduced I/R-induced homodimerization of Bnip3. Overexpression of Bnip3 in cells revealed that most of exogenous Bnip3 exists as a DTT-sensitive homodimer that correlated with increased cell death. In contrast, endogenous Bnip3 existed mainly as a monomer under normal conditions in the heart. Screening of the Bnip3 protein sequence revealed a single conserved cysteine residue at position 64. Mutation of this cysteine to alanine (Bnip3C64A) or deletion of the NH2-terminus (amino acids 1-64) resulted in reduced cell death activity of Bnip3. Moreover, mutation of a histidine residue in the COOH-terminal transmembrane domain to alanine (Bnip3H173A) almost completely inhibited the cell death activity of Bnip3. Bnip3C64A had a reduced ability to interact with Bnip3, whereas Bnip3H173A was completely unable to interact with Bnip3, suggesting that homodimerization is important for Bnip3 function. A consequence of I/R is the production of reactive oxygen species and oxidation of proteins, which promotes the formation of disulfide bonds between proteins. Thus, these experiments suggest that Bnip3 functions as a redox sensor where increased oxidative stress induces homodimerization and activation of Bnip3 via cooperation of the NH2-terminal cysteine residue and the COOH-terminal transmembrane domain. | 18,790,835 |
Bupivacaine blocks N-type inactivating Kv channels in the open state: no allosteric effect on inactivation kinetics. | Local anesthetics bind to ion channels in a state-dependent manner. For noninactivating voltage-gated K channels the binding mainly occurs in the open state, while for voltage-gated inactivating Na channels it is assumed to occur mainly in inactivated states, leading to an allosterically caused increase in the inactivation probability, reflected in a negative shift of the steady-state inactivation curve, prolonged recovery from inactivation, and a frequency-dependent block. How local anesthetics bind to N-type inactivating K channels is less explored. In this study, we have compared bupivacaine effects on inactivating (Shaker and K(v)3.4) and noninactivating (Shaker-IR and K(v)3.2) channels, expressed in Xenopus oocytes. Bupivacaine was found to block these channels time-dependently without shifting the steady-state inactivation curve markedly, without a prolonged recovery from inactivation, and without a frequency-dependent block. An analysis, including computational testing of kinetic models, suggests binding to the channel mainly in the open state, with affinities close to those estimated for corresponding noninactivating channels (300 and 280 microM for Shaker and Shaker-IR, and 60 and 90 microM for K(v)3.4 and K(v)3.2). The similar magnitudes of K(d), as well as of blocking and unblocking rate constants for inactivating and noninactivating Shaker channels, most likely exclude allosteric interactions between the inactivation mechanism and the binding site. The relevance of these results for understanding the action of local anesthetics on Na channels is discussed. | 18,790,854 |
The complete genome sequence of Thermococcus onnurineus NA1 reveals a mixed heterotrophic and carboxydotrophic metabolism. | Members of the genus Thermococcus, sulfur-reducing hyperthermophilic archaea, are ubiquitously present in various deep-sea hydrothermal vent systems and are considered to play a significant role in the microbial consortia. We present the complete genome sequence and feature analysis of Thermococcus onnurineus NA1 isolated from a deep-sea hydrothermal vent area, which reveal clues to its physiology. Based on results of genomic analysis, T. onnurineus NA1 possesses the metabolic pathways for organotrophic growth on peptides, amino acids, or sugars. More interesting was the discovery that the genome encoded unique proteins that are involved in carboxydotrophy to generate energy by oxidation of CO to CO(2), thereby providing a mechanistic basis for growth with CO as a substrate. This lithotrophic feature in combination with carbon fixation via RuBisCO (ribulose 1,5-bisphosphate carboxylase/oxygenase) introduces a new strategy with a complementing energy supply for T. onnurineus NA1 potentially allowing it to cope with nutrient stress in the surrounding of hydrothermal vents, providing the first genomic evidence for the carboxydotrophy in Thermococcus. | 18,790,866 |
The AtrbohD-mediated oxidative burst elicited by oligogalacturonides in Arabidopsis is dispensable for the activation of defense responses effective against Botrytis cinerea. | Oligogalacturonides (OGs) are endogenous elicitors of defense responses released after partial degradation of pectin in the plant cell wall. We have previously shown that, in Arabidopsis (Arabidopsis thaliana), OGs induce the expression of PHYTOALEXIN DEFICIENT3 (PAD3) and increase resistance to the necrotrophic fungal pathogen Botrytis cinerea independently of signaling pathways mediated by jasmonate, salicylic acid, and ethylene. Here, we illustrate that the rapid induction of the expression of a variety of genes by OGs is also independent of salicylic acid, ethylene, and jasmonate. OGs elicit a robust extracellular oxidative burst that is generated by the NADPH oxidase AtrbohD. This burst is not required for the expression of OG-responsive genes or for OG-induced resistance to B. cinerea, whereas callose accumulation requires a functional AtrbohD. OG-induced resistance to B. cinerea is also unaffected in powdery mildew resistant4, despite the fact that callose accumulation was almost abolished in this mutant. These results indicate that the OG-induced oxidative burst is not required for the activation of defense responses effective against B. cinerea, leaving open the question of the role of reactive oxygen species in elicitor-mediated defense. | 18,790,995 |
Joint immobilization of plant growth-promoting bacteria and green microalgae in alginate beads as an experimental model for studying plant-bacterium interactions. | A simple, quantitative experimental model, offering a convenient and basic approach to studies of plant-bacterium interactions, is proposed. This involves immobilizing a unicellular, freshwater microalga, a Chlorella species, serving as the plant, with a plant growth-promoting bacterium, an Azospirillum species, in small alginate beads to allow close interaction and to avoid external interference from bacterial contaminants. | 18,791,009 |
Soil formate regulates the fungal nitrous oxide emission pathway. | Fungal activity is a major driver in the global nitrogen cycle, and mounting evidence suggests that fungal denitrification activity contributes significantly to soil emissions of the greenhouse gas nitrous oxide (N(2)O). The metabolic pathway and oxygen requirement for fungal denitrification are different from those for bacterial denitrification. We hypothesized that the soil N(2)O emission from fungi is formate and O(2) dependent and that land use and landforms could influence the proportion of N(2)O coming from fungi. Using substrate-induced respiration inhibition under anaerobic and aerobic conditions in combination with (15)N gas analysis, we found that formate and hypoxia (versus anaerobiosis) were essential for the fungal reduction of (15)N-labeled nitrate to (15)N(2)O. As much as 65% of soil-emitted N(2)O was attributable to fungi; however, this was found only in soils from water-accumulating landforms. From these results, we hypothesize that plant root exudates could affect N(2)O production from fungi via the proposed formate-dependent pathway. | 18,791,019 |
Comparative mycotoxin profiles of Gibberella zeae populations from barley, wheat, potatoes, and sugar beets. | Gibberella zeae is one of the most devastating pathogens of barley and wheat in the United States. The fungus also infects noncereal crops, such as potatoes and sugar beets, and the genetic relationships among barley, wheat, potato, and sugar beet isolates indicate high levels of similarity. However, little is known about the toxigenic potential of G. zeae isolates from potatoes and sugar beets. A total of 336 isolates of G. zeae from barley, wheat, potatoes, and sugar beets were collected and analyzed by TRI (trichothecene biosynthesis gene)-based PCR assays. To verify the TRI-based PCR detection of genetic markers by chemical analysis, 45 representative isolates were grown in rice cultures for 28 days and 15 trichothecenes and 2 zearalenone (ZEA) analogs were quantified using gas chromatography-mass spectrometry. TRI-based PCR assays revealed that all isolates had the deoxynivalenol (DON) marker. The frequencies of isolates with the 15-acetyl-deoxynivalenol (15-ADON) marker were higher than those of isolates with the 3-acetyl-deoxynivalenol (3-ADON) marker among isolates from all four crops. Fusarium head blight (FHB)-resistant wheat cultivars had little or no influence on the diversity of isolates associated with the 3-ADON and 15-ADON markers. However, the frequency of isolates with the 3-ADON marker among isolates from the Langdon, ND, sampling site was higher than those among isolates from the Carrington and Minot, ND, sites. In chemical analyses, DON, 3-ADON, 15-ADON, b-ZEA, and ZEA were detected. All isolates produced DON (1 to 782 microg/g) and ZEA (1 to 623 microg/g). These findings may be useful for monitoring mycotoxin contamination and for formulating FHB management strategies for these crops. | 18,791,024 |
inlA premature stop codons are common among Listeria monocytogenes isolates from foods and yield virulence-attenuated strains that confer protection against fully virulent strains. | Previous studies showed that a considerable proportion of Listeria monocytogenes isolates obtained from foods carry a premature stop codon (PMSC) mutation in inlA that leads to production of a truncated and secreted InlA. To further elucidate the role these mutations play in virulence of L. monocytogenes, we created isogenic mutants, including (i) natural isolates where an inlA PMSC was reverted to a wild-type inlA allele (without a PMSC) and (ii) natural isolates where a PMSC mutation was introduced into a wild-type inlA allele; isogenic mutant sets were constructed to represent two distinct inlA PMSC mutations. Phenotypical and transcriptional analysis data showed that inlA PMSC mutations do not have a polar effect on the downstream inlB. Isogenic and natural strains carrying an inlA PMSC showed significantly reduced invasion efficiencies in Caco-2 and HepG2 cell lines as well as reduced virulence in oral guinea pig infections. Guinea pigs were also orally infected with a natural strain carrying the most common inlA PMSC mutation (vaccinated group), followed by challenge with a fully virulent L. monocytogenes strain 15 days postvaccination to probe potentially immunizing effects of exposure to L. monocytogenes with inlA PMSC mutations. Vaccinated guinea pigs showed reduced bacterial loads in internal organs and improved weight gain postchallenge, indicating reduced severity of infections in guinea pigs exposed to natural strains with inlA PMSC mutations. Our data support that (i) inlA PMSC mutations are causally associated with attenuated virulence in mammalian hosts and (ii) naturally occurring virulence-attenuated L. monocytogenes strains commonly found in food confer protective immunity. | 18,791,029 |
African trypanosomes contain 5-methylcytosine in nuclear DNA. | It is currently unclear if there are modified DNA bases in Trypanosoma brucei other than J-base. We identify herein a cytosine-5 DNA methyltransferase gene and report the presence and location of 5-methylcytosine in genomic DNA. Our data demonstrate that African trypanosomes contain a functional cytosine DNA methylation pathway. | 18,791,035 |
Hydrogen peroxide induces hyphal differentiation in Candida albicans. | In this study, we demonstrate that hyphal differentiation is induced by the subtoxic concentration of exogenous H(2)O(2) in Candida albicans. This finding is confirmed by the changing intracellular concentration of H(2)O(2). In order to induce the same level of differentiation, low concentrations of exogenous H(2)O(2) are required for the null mutants of the thiol-specific antioxidant and catalase, while higher concentrations are needed for cells treated with ascorbic acid, an antioxidant chemical. | 18,791,036 |
Glossary for econometrics and epidemiology. | Epidemiologists and econometricians are often interested in similar topics-socioeconomic position and health outcomes-but the different languages that epidemiologists and economists use to interpret and discuss their results can create a barrier to mutual communication. This glossary defines key terms used in econometrics and epidemiology to assist in bridging this gap. | 18,791,041 |
The association of socioeconomic disadvantage with postoperative complications after major elective cardiovascular surgery. | Understanding the mechanism by which both patient- and hospital level factors act in generating disparities has important implications for clinicians and policy-makers. To measure the association between socioeconomic position (SEP) and postoperative complications after major elective cardiovascular procedures. Multicity hospital-based study. Using Hospital Discharge Registries (ICD-9-CM codes), 19 310 patients were identified undergoing five cardiovascular operations (coronary artery bypass grafting (CABG), valve replacement, carotid endarterectomy, major vascular bypass, repair of unruptured abdominal aorta aneurysm (AAA repair)) in four Italian cities, 1997-2000. For each patient, a five-level median income index by census block of residence was calculated. In-hospital 30-day mortality, cardiovascular complications (CCs) and non-cardiovascular complications (NCCs) were the outcomes. Odds ratios (ORs) were estimated with multilevel logistic regression adjusting for city of residence, gender, age and comorbidities taking into account hospital and individual dependencies. In-hospital 30-day mortality varied by type of surgery (CABG 3.7%, valve replacement 5.7%, carotid endarterectomy 0.9%, major vascular bypass 8.8%, AAA repair 4.0%). Disadvantaged people were more likely to die after CABG (lowest vs highest income OR 1.93, p trend 0.023). For other surgeries, the relationship between SEP and mortality was less clear. For cardiac surgery, SEP differences in mortality were higher for publicly funded patients in low-volume hospitals (lowest vs highest income OR 3.90, p trend 0.039) than for privately funded patients (OR 1.46, p trend 0.444); however, the difference in the SEP gradients was not statistically significant. Disadvantaged people seem particularly vulnerable to mortality after cardiovascular surgery. Efforts are needed to identify structural factors that may enlarge SEP disparities within hospitals. | 18,791,046 |
Reporting disease activity in clinical trials of patients with rheumatoid arthritis: EULAR/ACR collaborative recommendations. | To make recommendations on how to report disease activity in clinical trials of rheumatoid arthritis (RA) endorsed by the European League Against Rheumatism (EULAR) and the American College of Rheumatology (ACR). The project followed the EULAR standardised operating procedures, which use a three-step approach: (1) expert-based definition of relevant research questions (November 2006); (2) systematic literature search (November 2006 to May 2007); and (3) expert consensus on recommendations based on the literature search results (May 2007). In addition, since this is the first joint EULAR/ACR publication on recommendations, an extra step included a meeting with an ACR panel to approve the recommendations elaborated by the expert group (August 2007). Eleven relevant questions were identified for the literature search. Based on the evidence from the literature the expert panel recommended that each trial should report the following items: (1) disease activity response and disease activity states; (2) appropriate descriptive statistics of the baseline, the endpoints and change of the single variables included in the core set; (3) baseline disease activity levels (in general); (4) the percentage of patients achieving a low disease activity state and remission; (5) time to onset of the primary outcome; (6) sustainability of the primary outcome; (7) fatigue. These recommendations endorsed by EULAR and ACR will help harmonise the presentations of results from clinical trials. Adherence to these recommendations will provide the readership of clinical trials with more details of important outcomes, while the higher level of homogeneity may facilitate the comparison of outcomes across different trials and pooling of trial results, such as in meta-analyses. | 18,791,055 |
Impact of high and low folate diets on tissue folate receptor levels and antitumor responses toward folate-drug conjugates. | Herein, we present a detailed analysis on the effects of feeding laboratory mice both high and low folic acid (folate)-containing diets as related to associated changes in serum and red blood cell (RBC) folate levels, tissue-derived folate receptor levels, and the ability of folate-drug conjugates to bind and effectuate activity against folate receptor (FR)-positive tumor xenografts. Our data show that serum and RBC folate concentrations sharply drop immediately after mice are switched to low folate diets; however, both parameters reach steady-state, "human-like" levels after 6 weeks. Interestingly, tissue-related folate binding capacities were also lowered during the dietary modulation period, whereas the net uptake of a radiolabeled folate conjugate was simultaneously increased 2.6- and 5-fold in FR-positive kidney and tumor tissue, respectively. Finally, the performances of several clinically and preclinically relevant folate-drug conjugates were evaluated against tumors in mice that were fed high or low folate diets. Except when administered at a dose level 6-fold less than that required to saturate endogenous FRs, no significant loss of antitumor activity was observed. From these findings, we conclude that lowering the dietary intake of folates in mice has little impact on the biological activity of repetitively dosed folate-targeted agents but that low folate diet regimens will reduce serum and RBC folate levels down to levels that more closely approximate the normal human ranges. | 18,791,065 |
Which environments for G x E? A user perspective on the roles of trauma and structural discrimination in the onset and course of schizophrenia. | Now that schizophrenia researchers may be moving from unilateral molecular genetic approaches to models including so-called gene-environment interactions, the question rises which environments may be considered for such research and how a user perspective may inform the field. It is argued that trauma and stigma, or perhaps better structural discrimination, represent 2 important environmental factors that deserve more attention. Experiential evidence, collected by users, suggests that trauma in childhood and/or adulthood, before, during, and after the onset of schizophrenia, as well as stigma/structural discrimination, may play important roles in the onset and course of the disorder. A certain reluctance on the part of the professional schizophrenia research community to take these variables as serious as, eg, interesting but inconclusive etiological signals from prenatal hypoxia, prenatal folate deficiency, and prenatal toxoplasmosis is suggested. This article outlines the concepts of trauma and stigma and their negative consequences for the onset and course of schizophrenia. The importance of research into these factors and their possible relevance for gene-environment interactions is discussed. While gene-environment interaction research using these variables is indicated and may possibly prove productive, it is argued that such efforts may not be useful if no subsequent attempt is made to translate the results to the level of interventions, codeveloped by users, eg, in the area of coping with the vicious circle of environmental adversity that users can become exposed to. | 18,791,078 |
Approach to milk protein allergy in infants. | To provide a practical, evidence-based approach to the diagnosis and management of milk protein allergy in infants. MEDLINE was searched from 1950 to March 2008 using the MeSH heading milk-hypersensitivity. Additional sources were derived from reviews found with the initial search strategy. Evidence was levels I, II, and III. Milk protein allergy is a recognized problem in the first year of life; cow's milk protein allergy is the most common such allergy. Diagnosis is suspected on history alone, with laboratory evaluations playing a supporting role. Confirmation requires elimination and reintroduction of the suspected allergen. Management includes diet modification for nursing mothers and hydrolyzed formulas for formula-fed infants. Assessing the underlying immunopathology can aid in determining prognosis. The therapeutic model presented allows rapid assessment of the presence of allergy, timely management, and surveillance for recurrence of symptoms. Breastfeeding can be continued with attentive diet modification by motivated mothers. | 18,791,102 |
MicroRNA: mechanism of gene regulation and application to livestock. | Posttranscriptional regulation of gene expression plays a role in multiple cellular pathways. MicroRNA (miRNA) are an emerging class of small RNA that regulate gene translation. However, the mechanisms by which miRNA regulate this process remain controversial. By altering posttranscriptional regulation, miRNA have a role in guiding developmental decisions, including cell fate, cell cycle progression, apoptosis, adipocyte differentiation, and processes that alter muscle development and growth. The role of miRNA in developmental decisions that affect animal biology is of significant interest, yet the current literature is limited in livestock models. Therefore, a review of the mechanisms by which miRNA alter gene translation and the current research evaluating miRNA in production livestock is needed. | 18,791,136 |
ASAS Centennial Paper: Impact of animal science research on United States goat production and predictions for the future. | Goat research in the United States has increased but at a rate less than that in production. Research on goat meat includes nutritional quality, packaging, color, sensory characteristics, and preslaughter management. Goat skins have value for leather, but quality of goat leather has not been extensively studied. Research in the production, quality, antibiotic residues, and sensory characteristics of goat milk and its products has aided development of the US dairy goat industry. Limited progress has been made in genetic improvement of milk or meat production. There is need to explore applications of genomics and proteomics and improve consistency in texture and functionality of goat cheeses. New goat meat and milk products are needed to increase demand and meet the diverse tastes of the American public. Despite research progress in control of mohair and cashmere growth, erratic prices and sale of raw materials have contributed to further declines in US production. Innovative and cooperative ventures are needed for profit sharing up to the consumer level. Internal parasites pose the greatest challenge to goat production in humid areas largely because of anthelmintic resistance. Study of alternative controls is required, including immunity enhancement via nutrition, vaccination, pasture management such as co-grazing with cattle, and genetic resistance. Similarly, the importance of health management is increasing related in part to a lack of effective vaccines for many diseases. Nutrition research should address requirements for vitamins and minerals, efficiencies of protein utilization, adjusting energy requirements for nutritional plane, acclimatization, and grazing conditions, feed intake prediction, and management practices for rapid-growth production systems. Moreover, efficient technology transfer methods are needed to disseminate current knowledge and that gained in future research. | 18,791,137 |
Heritability and repeatability of insect bite hypersensitivity in Dutch Shetland breeding mares. | Insect bite hypersensitivity (IBH) is a seasonal recurrent allergic reaction of horses to the bites of certain Culicoides spp. and is found throughout the world. The aim of our study was to estimate the heritability and repeatability of IBH in the Dutch Shetland pony population. A total of 7,924 IBH scores on 6,073 mares were collected during foal inspections in 2003, 2005, and 2006. Mares were scored for clinical symptoms of IBH from June until February by 16 inspectors. Of all mares, 74.4% (n = 4,520) had a single observation, 20.7% (n = 1,255) had 2 observations, and 4.9% (n = 298) had 3 observations in different years. The overall mean IBH prevalence was 8.8%. Heritability was 0.08 (SE = 0.02) on the observed binary scale and 0.24 (SE = 0.06) on the underlying continuous scale. Repeatability was 0.30 (SE = 0.02) and indicates that including repeated observations of the clinical symptoms of IBH will improve the accuracy of breeding values for IBH. We conclude that IBH, based on clinical symptoms, is a heritable trait in the Dutch Shetland pony population. Therefore, the IBH prevalence in this population can be decreased by selection. | 18,791,140 |
Confirmation of quantitative trait loci using a low-density single nucleotide polymorphism map for twinning and ovulation rate on bovine chromosome 5. | Traditional genetic selection in cattle for traits with low heritability, such as reproduction, has had very little success. With the addition of DNA technologies to the genetic selection toolbox for livestock, the opportunity may exist to improve reproductive efficiency more rapidly in cattle. The US Meat Animal Research Center Production Efficiency Population has 9,186 twinning and 29,571 ovulation rate records for multiple generations of animals, but a significant number of these animals do not have tissue samples available for DNA genotyping. The objectives of this study were to confirm QTL for twinning and ovulation rate previously found on BTA5 and to evaluate the ability of GenoProb to predict genotypic information in a pedigree containing 16,035 animals when using genotypes for 24 SNP from 3 data sets containing 48, 724, or 2,900 animals. Marker data for 21 microsatellites on BTA5 with 297 to 3,395 animals per marker were used in conjunction with each data set of genotyped animals. Genotypic probabilities for females were used to calculate independent variables for regressions of additive, dominance, and imprinting effects. Genotypic regressions were fitted as fixed effects in a 2-trait mixed model analysis by using multiple-trait derivative-free REML. Each SNP was analyzed individually, followed by backward selection fitting all individually significant SNP simultaneously and then removing the least significant SNP until only significant SNP were left. Five significant SNP associations were detected for twinning rate and 3 were detected for ovulation rate. Two of these SNP, 1 for each trait, were significant for imprinting. Additional modeling of paternal and maternal allelic effects confirmed the initial results of imprinting done by contrasting heterozygotes. These results are supported by comparative mapping of mouse and human imprinted genes to this region of bovine chromosome 5. | 18,791,147 |
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