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N Zhang

Publications and source records attributed to N Zhang.

At least 19 recordsLinked to original sources

Supraventricular tachyarrhythmia as a cause of sudden cardiac arrest.

INTRODUCTION: Supraventricular tachyarrhythmias (SVTA) are an accepted cause of cardiac arrest in patients with Wolff-Parkinson-White syndrome (WPW) and hypertrophic cardiomyopathy but their participation in other conditions is less well understood. The purpose of the study was to examine the role of SVTA in sudden cardiac arrest (SCA) by comprehensive evaluation of patients successfully resuscitated from SCA. METHODS: A total of 169 survivors of SCA in the absence of acute myocardial infarction underwent systematic evaluation that included echocardiography, Holter monitoring, coronary angiography and electrophysiological study (EPS) with additional testing in selected cases using provocative drug testing with isoproterenol, ajmaline or ergonovine. RESULTS: SVTA was found as the only possible cause or as the cause facilitating SCA in 29 patients: (1) 3 had a WPW syndrome related to accessory pathway with short refractory period; (2) for 12 patients, SVTA was the cause of cardiovascular collapse; heart disease (HD) was present in 11 cases, but disappeared in two of four with dilated cardiomyopathy after the restoration of sinus rhythm; (3) in 14 patients, SVTA degenerated either in a VF or ventricular tachycardia (VT); HD was present in 12 cases, but disappeared in one; two had no HD and recurrent similar arrhythmia was documented by cardiac defibrillator in one of them. SVTA induced coronary ischemia was the main cause of SCA. CONCLUSION: Rapid SVTA was a cause of SCA, either by cardiovascular collapse or by the degeneration in VT or VF. The complication generally occurred in patients with advanced HD or with rapid SVTA-induced cardiomyopathy and rarely in patients without HD. The incidence of SVTA as the only cause or the facilitating cause of SCAs is probably underestimated, because it is difficult to prove.

Adolescent↗

Clinicopathological features, post-surgical survival and prognostic indicators of elderly patients with hepatocellular carcinoma.

AIM: Comprehensive data regarding elderly patients with hepatocellular carcinoma (HCC) were limited. The present study aims to widen the knowledge based on patients in China. METHODS: Fifty-four elderly (> or =65 years) and 125 non-elderly HCC patients undergoing hepatectomy were enrolled in this retrospective study. Clinicopathological features and post-surgical survival were compared between two groups. Prognostic indicators of elderly patients were defined by uni- and multivariate analyses. RESULTS: Contrast to non-elderly patients, the elderly presented significantly lower rates of HBsAg positivity, Child-Pugh grade A, alpha-fetoprotein (AFP) marked elevation, portal vein tumour thrombosis (PVTT), satellite nodule, and intrahepatic recurrence, smaller tumour sizes, earlier TNM staging and better histological differentiation. No significant differences were found in perioperative mortality rate and post-surgical survival between two groups. PVTT and Edmondson-Steiner grading were identified as independent prognostic indicators of both overall and disease-free survival by multivariate analysis, whereas Child-Pugh grading independently affected the overall survival. CONCLUSIONS: HCC in the elderly seemed to be less HBV-associated, less progressive and less aggressive than that in the non-elderly. Hepatectomy for the elderly could make a satisfactory prognosis and be well tolerated. Some tumour-related factors independently predict the prognosis of elderly HCC patients, and their liver function status should be further valued.

Aged↗

Gamma-aminobutyric acid up- and downregulates insulin secretion from beta cells in concert with changes in glucose concentration.

AIMS/HYPOTHESIS: The role of gamma-aminobutyric acid (GABA) and A-type GABA receptors (GABA(A)Rs) in modulating islet endocrine function has been actively investigated since the identification of GABA and GABA(A)Rs in the pancreatic islets. However, the reported effects of GABA(A)R activation on insulin secretion from islet beta cells have been controversial. METHODS: This study examined the hypothesis that the effect of GABA on beta cell insulin secretion is dependent on glucose concentration. RESULTS: Perforated patch-clamp recordings in INS-1 cells demonstrated that GABA, at concentrations ranging from 1 to 1,000 micromol/l, induced a transmembrane current (I(GABA)) which was sensitive to the GABA(A)R antagonist bicuculline. The current-voltage relationship revealed that I(GABA) reversed at -42+/-2.2 mV, independently of glucose concentration. Nevertheless, the glucose concentration critically controlled the membrane potential (V (M)), i.e., at low glucose (0 or 2.8 mmol/l) the endogenous V (M) of INS-1 cells was below the I(GABA) reversal potential and at high glucose (16.7 or 28 mmol/l), the endogenous V (M) of INS-1 cells was above the I(GABA) reversal potential. Therefore, GABA dose-dependently induced membrane depolarisation at a low glucose concentration, but hyperpolarisation at a high glucose concentration. Consistent with electrophysiological findings, insulin secretion assays demonstrated that at 2.8 mmol/l glucose, GABA increased insulin secretion in a dose-dependent fashion (p<0.05, n=7). This enhancement was blocked by bicuculline (p<0.05, n=4). In contrast, in the presence of 28 mmol/l glucose, GABA suppressed the secretion of insulin (p<0.05, n=5). CONCLUSIONS/INTERPRETATION: These findings indicate that activation of GABA(A)Rs in beta cells regulates insulin secretion in concert with changes in glucose levels.

Animals↗

Activin receptor-like kinase 7 induces apoptosis of pancreatic beta cells and beta cell lines.

AIMS/HYPOTHESIS: Activin receptor-like kinase 7 (ALK7), a member of the type I receptor serine/threonine kinases of the TGF-beta superfamily, was recently reported to regulate cell proliferation and apoptosis. We hypothesised that ALK7 may play a role in modulating pancreatic beta cell proliferation and/or apoptosis. METHODS: We detected ALK7 expression in beta cells using RT-PCR, immunostaining and western blotting. Constitutively active, dominant negative or wild-type ALK7 was introduced into beta cells using adenoviral delivery. Proliferation was assessed using (3)H-thymidine incorporation and apoptosis was quantified using terminal deoxynucleotidyl transferase biotin-dUTP nick end labelling detection, DNA degradation analysis and caspase-3 assays. RESULTS: Induction of constitutively active ALK7 in beta cells resulted in growth inhibition and enhanced apoptosis; no effect was seen with INS-1 cells expressing wild-type or dominant negative ALK7. Elevated glucose concentrations and fatty acid (palmitate) markedly increased expression levels of ALK7 transcripts and proteins in INS-1 and rat islets and increased beta cell apoptosis. Activation of ALK7 increased Smad2 phosphorylation, reduced protein kinase B (Akt) kinase activity and was associated with increased levels of the bioactive forms of caspase-3, whereas co-expression of constitutively active ALK7 with dominant negative Smad2 or constitutively active Akt significantly diminished ALK7-induced growth inhibition and apoptosis in INS-1 cells. Although overexpression of constitutively active Akt significantly reduced ALK7-induced growth inhibition and ALK7-enhanced beta cell apoptosis, ALK7-stimulated Smad2 phosphorylation was not affected. CONCLUSIONS/INTERPRETATION: These results suggest that the pancreatic beta cell apoptosis induced by ALK7 activation occurs via the activation of two distinct downstream pathways: the suppression of Akt activation and the activation of the Smad2-caspase-3 cascade.

Activin Receptors, Type I↗

Characterization of epitopes for neutralizing monoclonal antibodies to classical swine fever virus E2 and Erns using phage-displayed random peptide library.

Infection of cells with classical swine fever virus (CSFV) is mediated by the interaction of envelope glycoproteins E2 and Erns with receptor molecules on the cell surface. These proteins are also the major antigens for eliciting neutralizing antibodies and conferring protective immunity. Here we report the identification of multiple neutralizing epitopes on these proteins by screening a phage-displayed random peptide library with CSFV-specific neutralizing monoclonal antibodies. Two different E2-specific neutralizing mAbs (a18 and 24/10) were found to bind to a common motif SPTxL, which is similar to the sequence SPTTL of the E2 protein (aa 289-293), indicating that this is likely to be an immunodominant epitope. Similarly, an immunodominant epitope corresponding to the sequence DKN of Erns (aa 117-119) was identified for two independent Erns-specific neutralizing antibodies, b4-22 and 24/16, respectively. Another binding motif, CxNNxTC, was identified for mAb 24/16, but not for b4-22. Sequencing analysis of the genes coding for the light chain of these mAbs was conducted to ensure that all mAbs were derived from different hybridomas, rather than from different subclones of a common parent line. Inhibition studies using immunofluorescent antibody assay and virus neutralization test demonstrated that the mimotope peptides truly mimicked the antibody binding determinants on the viral proteins. The detailed mapping data for these neutralizing epitopes will be useful for development of improved diagnostic tests and perhaps a peptide-based vaccine for this important swine disease.

Amino Acid Motifs↗

Chemical ablation of the gallbladder: clinical application and long-term observations.

BACKGROUND: We investigated whether minicholecystostomy followed by chemical ablation of the gallbladder could be used as a alternative to cholecystectomy in patients at high risk for complications of surgery. METHODS: From January 1990 through January 2003, 34 patients at high risk underwent minicholecystostomy. Six weeks after the operation, microwave irradiation was provided to burn the mucosa of the cystic duct at locations at 3, 6, 9, and 12 o'clock around the orifice. Each location was treated eight times at 50 mA for 10 sec. Then chemical ablation of the gallbladder was performed by infusing 95% ethanol into the gallbladder cavity for 30 min. For each sclerosis course, the procedure was repeated every 4 h for a total of eight times. Approximately 2 weeks later, the drainage tube was removed from the gallbladder after cholecystography showed that no cavity other than the lumen of the tube remained in the gallbladder. RESULTS: Patients tolerated the procedure well and were followed with ultrasonography for 2-14 years (mean, 9). Twenty-nine patients had no complications or side effects, and five patients developed a 1.5- to 3- cm mucocele in the gallbladder. The long-term success rate of sclerotherapy was 85.3% (29/34). No recurrent cholecystitis, new stone or formation, canceration were encountered at the site of the gallbladder. CONCLUSIONS: Minicholecystostomy followed by chemical ablation of the gallbladder was a safe, effective, and simple procedure for treating high-risk patients with acute cholecystitis and/or cholelithiasis.

Aged↗

Identification of candidate markers associated with agronomic traits in rice using discriminant analysis.

Plant genetic mapping strategies routinely utilize marker genotype frequencies obtained from progeny of controlled crosses to declare presence of a quantitative trait locus (QTL) on previously constructed linkage maps. We have evaluated the potential of discriminant analysis (DA), a multivariate statistical procedure, to detect candidate markers associated with agronomic traits among inbred lines of rice (Oryza sativa L.). A total of 218 lines originating from the US and Asia were planted in field plots near Alvin, Texas, in 1996 and 1997. Agronomic data were collected for 12 economically important traits, and DNA profiles of each inbred line were produced using 60 SSR and 114 RFLP markers. Model-based methods revealed population structure among the lines. Marker alleles associated with all traits were identified by DA at high levels of correct percent classification within subpopulations and across all lines. Associated marker alleles pointed to the same and different regions on the rice genetic map when compared to previous QTL mapping experiments. Results from this study suggest that candidate markers associated with agronomic traits can be readily detected among inbred lines of rice using DA combined with other methods described in this report.

Asia↗

Inhibition of angiogenesis is associated with reduced islet engraftment in diabetic recipient mice.

Rapid reestablishment of a functional microvasculature in transplanted islets is crucial for islet survival and function. To illustrate the importance of angiogenesis in islet engraftment, we took a loss-of-function approach to block angiogenesis in newly transplanted islets and determined the extent of islet engraftment in correlation with islet mass and glycemic control in diabetic recipient mice. Diabetic mice were transplanted with a marginal mass of 200 islets under the renal capsule, followed by once-daily oral administration of saline or 150 mg/kg of C-statin, a potent angiogenic inhibitor, for 14 days. Blood glucose profiles and the amplitude of glucose-stimulated insulin secretion in engrafted islets were determined. At 30 days posttransplant, islet grafts were retrieved for the determination of insulin content and vascular density by immunohistochemistry. When compared to sham-treated controls, diabetic recipient mice receiving a daily oral dose of C-statin exhibited significantly impaired blood glucose profiles and diminished glucose-stimulated insulin secretion in response to glucose challenge, correlating with significantly reduced intragraft insulin content and vascular density. Selective inhibition of angiogenesis was associated with reduced islet mass in diabetic mice. These data extend our view that rapid onset of angiogenesis is crucial for islet survival and engraftment and support the development of therapeutic strategies to stimulate angiogenesis in newly implanted islets for enhancing islet engraftment and improving the outcome of marginal islet transplantation.

Angiogenesis Inhibitors↗

Comparison of intravenous ibutilide vs. propafenone for rapid termination of recent onset atrial fibrillation.

This study was to evaluate the efficacy and safety of ibutilide and propafenone given intravenously in converting recent onset atrial fibrillation (AF). Eighty-two consecutive patients with AF (onset in 2 h to 90 days) were randomly assigned to receive two 10-min infusions, 10 min apart, of either ibutilide (1 mg) or propafenone (70 mg). The treatment was considered successful if sinus rhythm occurred within 90 min after the beginning of infusion. Ibutilide had a significantly higher rate of cardioversion than propafenone (70.73 vs. 48.78%, p = 0.043). The patients with shorter AF duration or smaller left atrium diameter had a higher success rate. Nonsustained monomorphic ventricular tachycardia was the most serious adverse effect of ibutilide in 9.76% of patients, and hypotension and heart pause were the major serious adverse events in 17.07% of patients treated with propafenone. Ibutilide is more effective than intravenous propafenone for the cardioversion of recent onset AF, and the adverse effects are rare and transient.

Adult↗

An update on the impact of Staphylococcus aureus enterotoxins in chronic sinusitis with nasal polyposis.

Nasal polyps in adults, characterized by abundant eosinophils, local overproduction of immunoglobulin E, and often associated with asthma, have been appreciated as an eosinophilic inflammation, potentially of allergic origin, but unrelated to a bacterial impact. Evidence accumulates, however, that Staphylococcus aureus colonizes chronic rhinosinusitis with, but not without polyps, with significantly increased prevalence. The germs release enterotoxins, which act as superantigens and induce a topical multiclonal IgE-formation as well as a severe, possibly steroid-insensitive eosinophilic inflammation. Recently, S. aureus could be demonstrated to reside intraepithelially, and potentially to release superantigens into the tissue from within the epithelial cells. An immune defect, either in the innate or adaptive immunity, might be responsible for this phenomenon. Follicle-like structures and lymphocyte accumulations, specifically binding enterotoxins, can be found within the polyp tissues, giving rise to local IgE formation. The superantigen-induced immune response also leads to a modulation of the severity of the eosinophilic inflammation, and may be linked to lower airway co-morbidity in polyp patients. Interestingly, IgE antibodies to enterotoxins can be found in the majority of aspirin-sensitive polyp tissues, associated with a substantial increase in ECP and IL-5. The possible role of S. aureus enterotoxins in polyp disease in Europe, the US and Asia has meanwhile been supported by several studies, demonstrating the presence of IgE antibodies to enterotoxins and inflammatory consequences in nasal polyp tissue. First studies also point to an involvement of S. aureus derived enterotoxins in lower airway disease, such as severe asthma and exacerbated COPD, clearly suggesting a clinical need for diagnosis and treatment of the germ and its related effects. Therapeutic approaches are so far empirical, and need further study, also serving to proof the clinical relevance of the concept.

Chronic Disease↗

Changes in regional cerebral blood flow under hypothermic selective cerebral perfusion.

OBJECTIVE: Currently the most frequently used perfusion technique during aortic arch surgery to prevent cerebral damage is hypothermic selective cerebral perfusion (SCP). Changes in cerebral blood flow (CBF) are known to occur during these procedures. We investigated regional changes of CBF under conditions of SCP in a porcine model. METHODS: In this blinded study, twenty-three juvenile pigs (20 - 22 kg) were randomized after cooling to 20 degrees C on CPB. Group I (n = 12) underwent SCP for 90 minutes, while group II (n = 11) underwent total body perfusion. Fluorescent microspheres were injected at seven time-points to calculate total and regional CBF. Hemodynamics, intracranial pressure (ICP), cerebrovascular resistance (CVR) and oxygen consumption were assessed. Tissue samples from the neocortex, cerebellum, hippocampus and brain stem were taken for a microsphere count. RESULTS: CBF decreased significantly (p = 0.0001) during cooling, but remained at significantly higher levels with SCP than with CPB throughout perfusion (p < 0.0001) and recovery (p < 0.0001). These findings were similar among all regions of the brain, certainly at different levels. Neocortex CBF decreased 50%, whereas brain stem and hippocampus CBF decreased by only 25 % during total body perfusion. All four regions showed 10 - 20% less CBF in the post-CPB period. CBF during SCP did not fall by more than 20% in any analysed region. The hippocampus turned out to have the lowest CBF, while the neocortex showed the highest CBF. CONCLUSION: SCP improves CBF in all regions of the brain. Our study characterizes the brain specific hierarchy of blood flow during SCP and total body perfusion. These dynamics are highly relevant for clinical strategies of perfusion.

Animals↗

Studies on the epidemiology of bluetongue virus in China.

Sentinel herds of large ruminants were established at five centres in Yunnan Province, Peoples Republic of China, between 1995 and 1997. The application of a sensitive antigen capture ELISA to facilitate virus isolation procedures led to the isolation of 108 strains of bluetongue (BLU) virus. Serotypes isolated included types 1, 2, 3, 4, 9, 11, 12, 15, 16, 21 and 23. Virus transmission occurred over a period of 1-3 months at each of the four positive sites, giving an overall BLU virus transmission period for the province of 5 months, from early June to early November. The greatest level of transmission took place in July and August. The duration of viraemia in individual animals varied from 1 to 7 weeks, with a mean calculated for each serotype between 6 and 20 days. The study represents the first detailed investigation of the epidemiology of BLU in China utilizing sentinel herds.

Animals↗

Clinical applications of plasma shock wave lithotripsy in treating postoperative remnant stones impacted in the extra- and intrahepatic bile ducts.

BACKGROUND: Choledochofiberscopy with basket extraction has been used widely to treat postoperative remnant stones in the bile duct system. However, it remains difficult to extract stones impacted in the bile duct system or stones too large to pass through the T-tube fistula. This report describes the efficacy and safety of plasma shock wave lithotripsy (PSWL) in fragmenting and eliminating such remnant stones from the bile duct. METHODS: In 52 patients, 117 remnant stones were fragmented with PSWL and subsequently extracted with choledochofiberscopy. The efficacy and safety of PSWL were observed during and after the procedure. RESULTS: After 116 of 117 remnant stones (99.1%) impacted in the extra- and intrahepatic bile ducts were fragmented successfulIy with PSWL, they were extracted with choledochofiberscopy. There were no significant complications during and after the procedure. CONCLUSION: It appears that PSWL is an effective and safe method for fragmenting remnant stones impacted in the bile duct system and stones too large to pass through the T-tube fistula.

Adult↗

Dimeric DNA quadruplex containing major groove-aligned A-T-A-T and G-C-G-C tetrads stabilized by inter-subunit Watson-Crick A-T and G-C pairs.

We report on an NMR study of unlabeled and uniformly 13C,15N-labeled d(GAGCAGGT) sequence in 1 M NaCl solution, conditions under which it forms a head-to-head dimeric quadruplex containing sequentially stacked G-C-G-C, G-G-G-G and A-T-A-T tetrads. We have identified, for the first time, a slipped A-T-A-T tetrad alignment, involving recognition of Watson-Crick A-T pairs along the major groove edges of opposing adenine residues. Strikingly, both Watson-Crick G-C and A-T pairings within the direct G-C-G-C and slipped A-T-A-T tetrads, respectively, occur between rather than within hairpin subunits of the dimeric d(GAGCAGGT) quadruplex. The hairpin turns in the head-to-head dimeric quadruplex involve single adenine residues and adds to our knowledge of chain reversal involving edgewise loops in DNA quadruplexes. Our structural studies, together with those from other laboratories, definitively establish that DNA quadruplex formation is not restricted to G(n) repeat sequences, with their characteristic stacked uniform G-G-G-G tetrad architectures. Rather, the quadruplex fold is a more versatile and robust architecture, accessible to a range of mixed sequences, with the potential to facilitate G-C-G-C and A-T-A-T tetrad through major and minor groove alignment, in addition to G-G-G-G tetrad formation. The definitive experimental identification of such major groove-aligned mixed A-T-A-T and G-C-G-C tetrads within a quadruplex scaffold, has important implications for the potential alignment of duplex segments during homologous recombination.

Base Pairing↗

V-shaped scaffold: a new architectural motif identified in an A x (G x G x G x G) pentad-containing dimeric DNA quadruplex involving stacked G(anti) x G(anti) x G(anti) x G(syn) tetrads.

We report the results of an NMR study of unlabeled and uniformly (13)C,(15)N-labeled d(G(3)AG(2)T(3)G(3)AT) in 100 mM NaCl, conditions under which it forms a dimeric quadruplex containing several new topological features. The DNA oligomer chain in each symmetry-related monomer subunit undergoes three sharp turns to form a compact domain, with all the purine bases involved in pairing alignments. The first turn is of the double chain reversal type, the second is of the edgewise type, and the third represents a new alignment, the V-shaped type. Each monomer of the dimeric quadruplex contains two stacked G(anti) x G(anti) x G(anti) x G(syn) tetrads, one of which forms a newly identified A x (G x G x G x G) pentad, through sheared G.A mismatch formation. There is a break in one of the four G-G columns that link adjacent G x G x G x G tetrads within each monomer. This architectural interruption is compensated by a new topological feature of quadruplex architecture, the V-shaped scaffold. The missing G-G column results in an opening that could facilitate insertion of planar ligands into the quadruplex. The dimeric interface contains stacked A.(G.G.G.G) pentads, with each pentad containing four bases from one monomer and a syn G1 from the partner monomer. Several potential ligand-binding pockets, positioned towards either end of the folded architecture, were identifiable in a surface view of the solution structure of the dimeric d(G(3)AG(2)T(3)G(3)AT) quadruplex.

Base Sequence↗

A DNA polymorphism specific to Candida albicans strains exceptionally successful as human pathogens.

A large proportion of infection-causing isolates of the yeast Candida albicans belong to a general-purpose genotype, identifiable by fingerprinting with the moderately repetitive sequence Ca3. The high prevalence of this group -- up to 70% in some patient categories -- suggests that its members possess genetic determinants, which enhance their success as pathogens compared to other strains. To find such determinants we are comparing the genomes of representatives of the general-purpose genotype cluster with the genomes of other strains. In this paper we describe the identification of a 985 bp HpaII fragment (MU13-4) specific to general-purpose genotype strains. The fragment was present in 90% of these strains, but only in 10% of other strains. The fragment did not hybridize with probe Ca3, used to define the general-purpose cluster. It contains elevated levels of repetitive DNA. Sequences homologous to MU13-4 are dispersed throughout the chromosomes of general-purpose strains but are rarer or absent in other strains, as judged by Southern hybridization. Using the Stanford C. albicans genome database, we have placed the MU13-4 fragment next to a CARE-1 element. We also found 79 significant homologies between parts of MU13-4 and 19 other contigs. Attempts to amplify the region surrounding the polymorphic fragment in non-general-purpose genotype strains suggest, as do the hybridization data, that the polymorphism is created by a deletion in non-cluster strains. These results show that it is possible to identify polymorphisms specific to general-purpose genotype strains. Primers against the fragment will allow PCR-based discrimination between general-purpose genotype strains and other strains, facilitating investigations aimed at determining morbidity and mortality caused by general-purpose genotype strains compared to other strains.

Base Sequence↗

Two-layer sample preparation method for MALDI mass spectrometric analysis of protein and peptide samples containing sodium dodecyl sulfate.

Sodium dodecyl sulfate (SDS) is widely used in protein sample workup. However, many mass spectrometric methods cannot tolerate the presence of this strong surfactant in a protein sample. We present a practical and robust technique based on a two-layer matrix/sample deposition method for the analysis of protein and peptide samples containing SDS by matrix-assisted laser desorption ionization mass spectrometry (MALDI-MS). The two-layer method involves the deposition of a mixture of sample and matrix on top of a thin layer of matrix crystals. It was found that for SDS-containing samples, the intensity of the MALDI signals can be affected by the conditions of sample preparation: on-probe washing, choice of matrix, deposition method, solvent system, and protein-to-SDS ratio. However, we found that, under appropriate conditions, the two-layer method gave reliable MALDI signals for samples with levels of SDS up to approximately 1%. The applications of this method are demonstrated for MALDI analysis of hydrophobic membrane proteins as well as bacterial extracts. We envision that this two-layer method capable of handling impure samples including those containing SDS will play an important role in protein molecular weight analysis as well as in proteome identification by MALDI-MS and MS/MS.

Bacterial Proteins↗

[Effect of aldose reductase expression by transforming growth factor-beta1 on rat mesangial cell].

OBJECTIVE: To screen the responsive genes related to transforming growth factor-beta1 (TGF-beta1) in rat mesangial cell (MsC) transfected by human TGF-beta1 gene, using suppression subtractive hybridization PCR (SSH-PCR); then to detect the expression of aldose reductase gene on cultured rat MsC and renal cortex of rats with anti-Thy1 glomerulonephritis. METHODS: SSH-PCR technique and differential screening for detecting the responsive genes related to TGF-beta1; Semi-quantification RT-PCR and Western blot analysis for identifying the expression of aldose reductase on MsC in vitro and in vivo. RESULTS: Compared with normal MsC, it was proved that 28 responsive genes related to TGF-beta1 in MTG1. There was an expression sequence tag (EST), approximate 337 bp segment, completely identical to the data of aldose reductase gene from GenBank. Elevated levels of aldose reductase mRNA and protein were found on cultured rat MsC treated with TGF-beta1 and renal cortex of rat with anti-Thy1 glomerulonephritis. CONCLUSION: Aldose reductase, rate-limiting enzyme in the polyol pathway, was closely related to TGF-beta1 expression. It is possible that upregulation of aldose reductase expression may be involved in the development of glomerulosclerosis mediated by TGF-beta1.

Aldehyde Reductase↗