Cutaneous blistering secondary to acute carbon-monoxide intoxication.
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Acute Disease↗
Biomedical subjects
Y Gao
Publications and source records attributed to Y Gao.
Prevalence of and factors associated with glucosamine use in Canada.
OBJECTIVE: Glucosamine is commonly used for the treatment of osteoarthritis, and its use is increasing in the general population. The Canadian Multicentre Osteoporosis Study (CaMos) provided an opportunity to examine the prevalence of glucosamine use across age and gender groups, and to assess the factors associated with its use. METHOD: CaMos is a random, population-based sample of 9423 Canadians. Baseline assessments took place in 1996-1997 and the 5-year follow-up assessments in 2001-2002. The primary outcome of this analysis was glucosamine use at year 5. Prevalence estimates were age- and sex-standardized to the Canadian population. A number of factors potentially associated with glucosamine use were identified from the literature. Multivariable logistic regression was used to identify variables associated with glucosamine use. RESULTS: At 5 years, complete data were available for 7652 of the original 9423 participants (81.2%). For men, glucosamine use increased from 0.9% to 4.7% (weighted values), and for women, it increased from 1.3% to 8.2%. Glucosamine use was higher among older participants, those living in western Canada, and those with arthritis, back pain, higher calcium intake from supplements, physical activity and prior glucosamine use. CONCLUSIONS: Glucosamine use increased substantially over 5 years, and its use is associated with a number of factors. Some may use glucosamine to manage pain and symptoms of arthritis and back pain, while others use it as a preventive measure to maintain health.
Adult↗
Effects of restraint stress on the expression of proteins involved in synaptic vesicle exocytosis in the hippocampus.
Chronic restraint stress has been associated with induction of morphological changes in the hippocampus. Postsynaptically, these changes include decreased length and branching of apical dendrites from CA3 pyramidal neurons, while presynaptically, depletion and clustering of synaptic vesicles have been observed. However, the molecular correlates of these changes remain poorly defined; while some studies have identified changes in the levels of some presynaptic proteins, none have assessed the coordinate expression of components of the membrane fusion complex, including synaptobrevin, syntaxin, and synaptosomal-associated protein 25 kDa, and their major regulatory molecules synaptotagmin, synaptophysin, and synapsin. Therefore, we undertook to assess the immunoreactivity of these proteins in hippocampal slices obtained from rats subjected to either acute (one 6 h session) or chronic (21 days at 6 h per day) of restraint stress. Specifically, we observed a significant increase in synaptobrevin immunoreactivity in the inner molecular layer of the dentate gyrus (54.2%; P=0.005), the stratum radiatum in the CA1 subfield (55.5%; P=0.007), and a region including the stratum lucidum and the proximal portion of the stratum radiatum in the CA3 subfield (52.7%; P=0.002); we also observed a trend toward increased synaptophysin levels in the stratum lucidum/radiatum of the CA3 subfield (8.0%; P=0.051) following chronic, but not acute, restraint stress. In that synaptobrevin has been associated with replenishment of the "readily-releasable" pool of synaptic vesicles and the efficiency of neurotransmitter release, the present results suggest that stress-induced changes in synaptobrevin may at least in part underlie the previously observed changes in synaptic and neuronal morphology.
Analysis of Variance↗
Distribution of polycyclic aromatic hydrocarbons in soils at Guiyu area of China, affected by recycling of electronic waste using primitive technologies.
The concentration, distribution, profile and possible source of polycyclic aromatic hydrocarbons (PAHs) in soil were studied in Guiyu, an electronic waste (E-waste) recycling center, using primitive technologies in Southeast China. Sixteen USEPA priority PAHs were analyzed in 49 soil samples (0-10 cm layer) in terms of individual and total concentrations, together with soil organic matter (SOM) concentrations. The concentrations of a sum of 16 PAHs ranged from 44.8 to 3206 microgkg(-1) (dry weight basis), in the descending order of E-waste open burning sites (2065 microgkg(-1))>areas near burning sites (851microgkg(-1))>rice fields (354 microgkg(-1))>reservoir areas (125microgkg(-1)). The dominant PAHs were naphthalene, phenanthrene and fluoranthene, which were mainly derived from incomplete combustion of E-waste (e.g. wire insulations and PVC materials), and partly from coal combustion and motorcycle exhausts. All individual and total PAH concentrations were significantly correlated with SOM except for naphthalene and acenaphthylene. Principal component analysis was performed, which indicated that PAHs were mainly distributed into three groups in accordance with their ring numbers and biological and anthropogenic source. In conclusion, PAH concentrations in the Guiyu soil were affected by the primitive E-waste recycling activities.
China↗
Identification of STAT3 as a specific substrate of breast tumor kinase.
Breast tumor kinase (Brk) is a non-receptor tyrosine kinase distantly related to the Src family kinase. It is expressed in more than 60% of breast tumors, but the biological role of this kinase remains to be determined. Only a limited number of substates have been identified for Brk, and the link of Brk to tumorigenesis remains largely unknown. In this study, we provide evidence that the signal transducer and activator of transcription 3, STAT3, is a physiological target of Brk. Activation of STAT3 previously has been linked to oncogenesis, and results in this study demonstrate that STAT3 is tyrosine phosphorylated and transcriptionally activated in cells expressing endogenous Brk. Signal transducer and activator of transcription 3 is specifically targeted since other STAT members are not responsive to Brk expression. Signal transducer and activator of transcription 3 activation requires the catalytic activity of Brk, and expression of both STAT3 and Brk stimulate cellular proliferation. In addition, we have identified a negative regulator of Brk, the suppressor of cytokine signaling, SOCS3. The SOCS3 protein is known to block signaling mediated by cytokine receptors, and here we find that SOCS3 is able to repress the activity of the Brk non-receptor tyrosine kinase.
Animals↗
High-resolution profiles of trace metals in the pore waters of riverine sediment assessed by DET and DGT.
The techniques of DET (diffusive equilibrium in thin films) and DGT (diffusive gradients in thin films) were applied to obtain high-resolution vertical profiles of trace metals in freshwater sediments. In the framework of the EU-Interreg project Stardust (http://www.vliz.be/projects/stardust/) between France and Belgium, in which the mobility of sediment bound metals is investigated, sediment samples were collected from the Upper Scheldt River (at Helkijn, Belgium) and the Leie River (at Warneton, located at the Belgian-French border). Intra- and inter-laboratory comparisons of the gel techniques were carried out between the two laboratories involved. In general, a good agreement was observed, taking sediment heterogeneity into account. At both stations, metal pore water profiles show more or less similar tendencies although the sediment at Warneton was more anoxic than at Helkijn. A strong correlation between Fe and Co was found at Helkijn as well as at Warneton. The metal gradients at the water/sediment interface were calculated from the high resolution profiles and the conventional, low resolution profiles. Significant differences were observed.
Arsenic↗
Gain of 1q25-32, 12q23-24.3, and 17q12-22 facilitates tumorigenesis and progression of human squamous cell lung cancer.
To explore the genetic changes involved in the stepwise development of lung cancer, we have determined the genetic events associated with the histological progression from normal bronchial epithelium to squamous cell carcinoma. Comparative genomic hybridization was used to identify chromosomal imbalances in 54 microdissected samples, including squamous metaplasia, dysplasia, carcinoma in situ, and invasive tumour derived from 23 patients with squamous cell carcinoma of the lung. Histopathological progression was accompanied by an increased number of chromosomal abnormalities. Gains of 1q25-32, 12q23-24.3, and 17q12-22, in particular, were detected at high frequencies in both carcinoma in situ and invasive tumours and were found more often in the cases with lymph node metastases than in those without. Our previous expression profiling of squamous cell carcinomas had identified overexpression of laminin5 gamma2, a gene located at 1q25-31. Therefore, this was investigated at the protein level by immunohistochemical analysis in 336 samples of squamous cell carcinoma of the lung. Consistent with the genomic data for this region, the expression level of laminin5 gamma2 was higher in the primary tumours with lymph node metastases than in tumours without metastases (p = 0.012). These data suggest that gains of genes from 1q25-32, 12q23-24.3, and 17q12-22 facilitate tumorigenesis and progression of squamous cell carcinoma of the lung, and may serve as potential predictors for this disease.
Aged↗
Ten-year experience with living related donated splenic transplantation for the treatment of hemophilia A.
AIM: Six cases of hemophilia A treated with living related donated splenic transplantation (LRDST) were performed over 10 years. METHODS: We reviewed the six consecutive cases of LRDST from 1992 to 2002. Three patients received whole spleen allografts and the other three, partial spleen allografts. All allografts were transplanted to the extraperitoneal space in the right iliac fossa by an end-to-end anastomosis between the splenic artery and the internal iliac artery and an end-to-side anastomosis between the splenic vein and the external (or common) iliac vein. After the operation, a combined regimen with cyclosporine, azathioprine, anti-lymphocyte globulin, OKT3, was administered to suppress the immune reaction. RESULTS: The functional period of the allografts varied between 30 days to 4 years. Patient factor-VIII (F-VIII) levels rose from less than 5% before operation to 15% to 56% postoperatively. One patient died from central nervous system complications. Another lost his graft because exogenous F-VIII was not supplemented in timely fashion at the onset of rejection. And the third could no longer afford the expensive immunosuppressive drugs at 2 years after the operation and eventually lost the spleen. The remaining three patients presently have regained self-support, among whom one has survived for 4 years. CONCLUSION: Though the sample pool is relatively small, our clinical observations tend to confirm LRDST as a feasible, effective treatment for hemophilia A.
Drug Therapy, Combination↗
Propylthiouracil-induced anti-neutrophil cytoplasmic antibody-associated vasculitis.
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Adult↗
A genome scan for quantitative trait loci associated with body weight at different developmental stages in chickens.
A genome scan to detect quantitative trait loci (QTL) affecting body weight in chickens was conducted on 238 F(2) chickens from a reciprocal cross of Silky Fowl and White Plymouth Rock using 125 microsatellite markers covering 23 autosomes and the Z chromosome. Two types of QTL were considered: static QTL (SQ) and developmental QTL (DQ). Static QTL affected the body weight from hatch to time t, and DQ affected the body weight from time t-1 to time t. Six SQ and nine DQ were detected. Of these QTL, four reached a genome-wide significance of 5% or better, with SQ1 and DQ1 being the most significant QTL. Static QTL1 was on chromosome 1 between GCT0006 and MCW0106 and explained 4.05-9.80% of the phenotypic variation in body weights from 3 to 12 weeks of age. At 9, 10 and 11 weeks, the genome-wide significance thresholds of SQ1 were <1%. Developmental QTL1 was located on chromosome 1 between MCW0168 and GCT0006, and explained 2.75% of the phenotypic variation for body weight from week 7 to 8 with a genome-wide significance level <1%. The results suggest that body weight from hatch to time t and developmental growth from time t-1 to time t may involve two different sets of genes or gene actions.
Animals↗
Identification of single-nucleotide polymorphisms in 5' end and exons of the PRKAG3 gene in Hubbard White broiler, Leghorn layer, and three Chinese indigenous chicken breeds.
5'-AMP-activated protein kinase plays an important role in regulating the level of ATP in the presence of metabolic stress. Previous studies revealed that polymorphisms in 5'-AMP-activated protein kinase gamma 3 subunit (PRKAG3) gene are associated with meat quality in pigs. In the present study, single-nucleotide polymorphisms (SNPs) in the 5'-end and exons of chicken PRKAG3 gene were identified with the method of single-strand conformation polymorphism in Hubbard ISA White broiler, Leghorn layer, and three Chinese indigenous chicken breeds, Tibet Chicken, Shouguang Chicken and Beijing Yellow Chicken. Two SNPs in the 5'-end of the gene and 10 SNPs in exons 3, 4, 9 and 11, of which three caused amino acid substitutions, were identified in the PRKAG3 gene of the five chicken breeds. The results will facilitate further study on the association between the mutations of PRKAG3 and chicken meat quality.
5' Flanking Region↗
Development of a predictive pharmacokinetic model for a novel cyclooxygenase-2 inhibitor.
A predictive population pharmacokinetic model was developed for a novel cyclooxygenase-2 (COX-2) inhibitor CS-706, using data from 130 subjects in 3 phase 1 trials after single or multiple doses of CS-706 (2- to 800-mg doses daily, up to 14 days) and validated using sparse data from a separate study. A 2-compartment model described the data. Typical apparent clearance (CL/F) was 47.2 L/h and was reduced by 43% at doses greater than 200 mg. Apparent clearance was decreased by 38% in female subjects and by 64% and 15%, respectively, in poor/intermediate CYP 2D6 and poor CYP 2C9 metabolizers. Typical apparent volume of the central compartment was 166 L and increased with body weight. Bioavailability increased by 42% after nighttime doses and decreased saturably with increasing dose (50% reduction at 221 mg). Predicted exposures in Japanese subjects were reduced relative to whites because of a lower frequency of poor metabolizers. The model may aid in optimizing the design of future studies and predicting exposures in other subpopulations.
Adult↗
Functional alpha(1)-adrenoceptor subtypes in human submandibular glands.
alpha(1)-Adrenoceptor has been discovered to exist in many human tissues and mediates important physiological functions. The purpose of this study was to detect the expression, distribution, and function of alpha(1)-adrenoceptor subtypes in human submandibular glands. alpha(1A)- and alpha(1B)-Adrenoceptor mRNAs were identified by reverse-transcription/polymerase chain-reaction (RT-PCR), and their proteins were detected by Western blotting. No expression of the alpha(1D)-adrenoceptor mRNA and protein was found. By in situ hybridization and immunohistochemistry, alpha(1A)- and alpha(1B)-adrenoceptor mRNAs and proteins were shown to be widespread in both ductal and acinar cells. By confocal microscopy, phenylephrine (stimulating both alpha(1A)- and alpha(1B)-adrenoceptors) or A61603 (alpha(1A)-selective agonist) induced an increase in intracellular calcium by 2.33 +/- 0.18-fold and 1.81 +/- 0.43-fold, respectively, while 5-methylurapidil (alpha(1A)-selective antagonist) partly blocked calcium mobility stimulated by phenylephrine. The results indicated that functional alpha(1A)- and alpha(1B)-adrenoceptors were expressed in human submandibular glands, and might contribute to the regulation of saliva synthesis and secretion.
Adrenergic alpha-1 Receptor Agonists↗
FK506 in the treatment of children with nephrotic syndrome of different pathological types.
OBJECTIVE: To evaluate the efficacy of FK506 in the treatment of children with nephrotic syndrome of different underlying pathology. METHODS: 12 patients were treated with FK506 with a dosage of 0.1 - 0.15 mg/kg/d while corticosteroid dose was tapered stepwise. This therapeutic course lasted 3 - 6 months during which the plasma concentration ofFK506 was monitored. RESULTS: 12 children with different pathological types nephrotic syndrome were treated with FK506, including 4 cases of MCN, 6 cases of MsPGN, and 1 case of MPGN and 1 case of FSGS. After 2-month duration, 8 patients got complete remission including 4 cases of MCN and 4 cases of MsPGN and 3 children including 1 case of MsPGN, 1 case of MPGN, and 1 case of FSGS got partial remission. Only 1 child with MsPGN was considered to be a treatment failure. The overall response rate was 91.67% with the plasma concentration of FK506 maintained at 5 approximately 12 ng/ml, and the response time was 10 - 38 days. After 1-month duration, all patients except one experienced a reduction in proteinuria to normal levels or a partial response (50% reduction in protein excretion), significant increase in serum albumin, decrease in serum cholesterol and triglyceride and disappearance of edema. 2 months later, in 11 patients, blood biochemical values had returned to normal levels. The drug was generally well-tolerated. 3 patients had anorexia, nausea, vomiting. 2 patients experienced transient elevated serum creatinine which was reversible after the adjustment of dosage. 3 patients had minor changes in urine NAG. Only 2 of all patients relapsed. CONCLUSION: FK506 is one of the effective immunosuppressants. In this study, FK506 in combination with a small doses of steroid while decreasing FK506 dosage plays a role in consolidating the curative effect and preventing relapse. In conclusion, FK506 may be effective in the treatment of nephrotic syndrome.
Adolescent↗
Randomised clinical trial investigating the effects of combined administration of octreotide and methylglucamine diatrizoate in the older persons with adhesive small bowel obstruction.
OBJECTIVE: To investigate the effects of combined administration of octreotide and methylglucamine diatrizoate in the older persons with adhesive small bowel obstruction. PATIENTS AND METHODS: One hundred and sixty-two consecutive patients who had suffered from adhesive intestinal obstruction without clinical evidence of strangulation or gangrene were randomised into two groups, a control group (treated conservatively, n=82) and a contrast group (treated with combined administration of octreotide and methylglucamine diatrizoate, n=80). A laparotomy was performed in both the two groups if symptoms of strangulation developed or the obstruction did not resolve spontaneously after 72 h. RESULTS: Statistically significant rapid reduction in pain score, lower amount of nasogastric drainage, shorter hospital stay, lower operative rate and lower postoperative morbidity were observed in the contrast group. Among the non-operative patients, earlier passage of stool and gas, earlier first oral intake and shorter duration of nasogastric tube placement were significantly more frequently observed in the contrast group. No difference in the rate of readmission was found between the two groups. CONCLUSIONS: Combined administration of octreotide and methylglucamine diatrizoate accelerates resolution of small bowel obstruction by a specific therapeutic effect and is safe for the older persons.
Aged↗
Characterization and expression analysis of TNF-related apoptosis inducing ligand (TRAIL) in grass carp Ctenopharyngodon idella.
TRAIL (Apo2 ligand) described as a type II transmembrane protein belonging to the TNF superfamily can induce apoptotic cell death in a variety of cell types. In the present study, a putative cDNA sequence encoding the 299 amino acids of TRAIL (GC-TRAIL) and its genomic organization were identified in grass carp Ctenopharyngodon idella. The predicted GC-TRAIL sequence showed 44 and 41% identities to chicken and human TRAILs, respectively. In a domain search, a tumor necrosis factor homology domain (THD) was identified in the C-terminal portion of TRAILs. The GC-TRAIL gene consists of five exons, with four intervening introns, spaced over approximately 4 kb of genomic sequence. Analysis of GC-TRAIL promoter region revealed the presence of a number of putative transcription factor binding sites, such as Sp1, NF-kappaB, AP-1, GATA, NFAT, HNF, STAT, P53 and IRF1 sequences which are important for the expression of other TNF family members. Phylogenetic analysis placed GC-TRAIL and the putative zebrafish (Danio rerio) TRAIL obtained from searching the zebrafish database into one separate cluster near mammalian TRAIL genes, but apart from the reported zebrafish TRAIL-like protein, indicating that the GC-TRAIL is an authentic fish TRAIL. Expression analysis revealed that GC-TRAIL is expressed in many tissues, such as in gills, liver, trunk kidney, head kidney, intestine and spleen.
Amino Acid Sequence↗
Intrinsic efficacy of antipsychotics at human D2, D3, and D4 dopamine receptors: identification of the clozapine metabolite N-desmethylclozapine as a D2/D3 partial agonist.
Drugs that antagonize D2-like receptors are effective antipsychotics, but the debilitating movement disorder side effects associated with these drugs cannot be dissociated from dopamine receptor blockade. The "atypical" antipsychotics have a lower propensity to cause extrapyramidal symptoms (EPS), but the molecular basis for this is not fully understood nor is the impact of inverse agonism upon their clinical properties. Using a cell-based functional assay, we demonstrate that overexpression of Galphao induces constitutive activity in the human D2-like receptors (D2, D3, and D4). A large collection of typical and atypical antipsychotics was profiled for activity at these receptors. Virtually all were D2 and D3 inverse agonists, whereas none was D4 inverse agonist, although many were potent D4 antagonists. The inverse agonist activity of haloperidol at D2 and D3 receptors could be reversed by mesoridazine demonstrating that there were significant differences in the degrees of inverse agonism among the compounds tested. Aripiprazole and the principle active metabolite of clozapine NDMC [8-chloro-11-(1-piperazinyl)-5H-dibenzo [b,e] [1,4] diazepine] were identified as partial agonists at D2 and D3 receptors, although clozapine itself was an inverse agonist at these receptors. NDMC-induced functional responses could be reversed by clozapine. It is proposed that the low incidence of EPS associated with clozapine and aripiprazole used may be due, in part, to these partial agonist properties of NDMC and aripiprazole and that bypassing clozapine blockade through direct administration of NDMC to patients may provide superior antipsychotic efficacy.
Animals↗
Killed but metabolically active microbes: a new vaccine paradigm for eliciting effector T-cell responses and protective immunity.
We developed a new class of vaccines, based on killed but metabolically active (KBMA) bacteria, that simultaneously takes advantage of the potency of live vaccines and the safety of killed vaccines. We removed genes required for nucleotide excision repair (uvrAB), rendering microbial-based vaccines exquisitely sensitive to photochemical inactivation with psoralen and long-wavelength ultraviolet light. Colony formation of the nucleotide excision repair mutants was blocked by infrequent, randomly distributed psoralen crosslinks, but the bacterial population was able to express its genes, synthesize and secrete proteins. Using the intracellular pathogen Listeria monocytogenes as a model platform, recombinant psoralen-inactivated Lm DeltauvrAB vaccines induced potent CD4(+) and CD8(+) T-cell responses and protected mice against virus challenge in an infectious disease model and provided therapeutic benefit in a mouse cancer model. Microbial KBMA vaccines used either as a recombinant vaccine platform or as a modified form of the pathogen itself may have broad use for the treatment of infectious disease and cancer.
Animals↗