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Biomedical subjects

T M Zhang

Publications and source records attributed to T M Zhang.

At least 19 recordsLinked to original sources
PubMed2006

Current knowledge and attitudes about organ donation and transplantation among Chinese university students.

Current attitudes toward organ donation among university students in mainland China and the differences in attitudes between Chinese students in mainland China versus overseas are unknown. To address these issues, we conducted a cross-sectional survey using questionnaires among 922 Chinese undergraduates from mainland China and overseas regions of the world. Data were analyzed by descriptive statistics, Student t tests, chi-square tests, and a logistic regression analysis. We found that blood donors showed significantly better awareness of heart, liver, lung, skin, and tendon donation among commonly transplanted organs/tissues. As to the willingness for cadaveric organ donation, 61.3% of respondents consented, 8.5% objected, and 30.3% answered "not sure." The percentage holding an organ donor card was 15.7% among students from Hong Kong; 3.0%, mainland China; 2.8%, Macau; 2.6%, Taiwan, and 4.0%, other regions of the world. In a logistic regression analysis, female students (odds ratio [OR], 2.24; 95% confidence interval [CI], 1.35 to 3.72) and blood donors (OR, 1.91; 95% CI, 1.10 to 3.32) did, but age and study specialty (medical vs nonmedical) did not show significantly more positive attitudes toward cadaveric organ donation. Compared with students from mainland China, overseas Chinese students from various regions did not show significantly different attitudes toward cadaveric organ donation. In summary, blood donors among university students have a greater knowledge of transplantation and a more positive attitude toward organ donation. Since university students are an important source of blood donors in China, they will be a potential pool of organ donors in the future.

Adult↗
PubMed2006

Characterization and stability investigation of cu,zn-superoxide dismutase covalently modified by low molecular weight heparin.

Cu,Zn-superoxide dismutase (SOD) was chemically modified with low molecular weight heparin (LMWH). To characterize the conjugate, sodium dodecyl sulfate polyacrylamide gel electrophoresis (SDS-PAGE) and native polyacrylamide gel electrophoresis (native PAGE) with protein staining and polysaccharide staining were employed. The stabilities of the modified enzyme to heat, acid, alkali, and trypsin treatment were also investigated. SDS-PAGE of the conjugate presented two major bands, and native PAGE of the conjugate showed similar banding position with protein staining and polysaccharide staining, which was different from that of the unmodified SOD and LMWH/SOD mixture. Moreover, the conjugate migrated faster with increasing extent of the modification. Enhanced heat stability, acid resistance, alkali resistance, and anti-trypsin stability of the modified enzyme were observed compared with those of the unmodified enzyme. Results of the study suggest that covalent linkage in LMWH-SOD can be effectively characterized by electrophoretic techniques and the chemical modification of SOD with LMWH can enhance the stabilities of the enzyme. In addition, native PAGE with protein staining can be used to evaluate the extent of the modification.

Animals↗
PubMed2002

Prevalence of human papillomavirus in cervical cancer: a multicenter study in China.

A large-scale epidemiologic survey on the prevalence of different types of human papillomavirus (HPV) in cervical cancer in China is indicated because of the implications for the development of diagnostic probes and vaccines against cervical cancer. A total of 809 cervical cancer specimens were collected from 5 regions in China including Shanghai, Guangzhou, Sichuan, Beijing and Hong Kong. HPV DNA was detected in 83.7% of the specimens. HPV-16 was present in 79.6%, HPV-18 in 7.5%, HPV-52 in 2.6% and HPV-58 in 3.8% of all HPV-positive specimens. The prevalences of HPV-16 and HPV-18 in Hong Kong were 61.7 and 14.8%, respectively, representing a lower HPV-16 and a higher HPV-18 proportion compared with the other regions. HPV-16 remained the most common HPV infection in both squamous cell carcinoma (SCC) and adenocarcinoma (AC). The proportion of HPV-18 infection was significantly higher in AC than in SCC.

China↗
PubMed2001

Clinicopathological and molecular genetic analysis of 4 typical Chinese HNPCC families.

AIM: To study the clinicopathological and molecular genetic characteristics of typical Chinese hereditary nonpolyposis cotorectal cancer (HNPCC) families. METHODS: Four typical Chinese HNPCC families were analyzed using microdissection, microsatellite instability analysis, immunostaining of hMSH2 and hMLH1 proteins and direct DNA sequencing of hMSH2 and hMLH1 genes. RESULTS: All five tumor tissues of 4 probands from the 4 typical Chinese HNPCC families showed microsatellite instability at more than two loci (MSI-H or RER+ phenotype). Three out of the 4 cases lost hMSH2 protein expression and the other case showed no hMLH1 protein expression. Three pathological germline mutations (2 in hMSH2 and 1 in hMLH1), which had not been reported previously, were identified. The same mutations were also found in other affected members of two HNPCC families,respectively. CONCLUSION: Typical Chinese HNPCC families showed relatively frequent germline mutation of mismatch repair genes. High-level microsatellite instability and loss of expression of mismatch repair genes correlated closely with germline mutation of mismatch repair genes. Microsatellite instability analysis and immunostaining of mismatch repair gene might serve as effective screening methods before direct DNA sequencing. It is necessary to establish clinical criteria and molecular diagnostic strategies more suitable for Chinese HNPCC families.

Adult↗
PubMed1998

Menadione reduced doxorubicin resistance in Ehrlich ascites carcinoma cells in vitro.

AIM: To study the effect of menadione (Men) reducing doxorubicin (Dox) resistance in Ehrlich ascites carcinoma (EAC) cells resistant to Dox (EAC/Dox cells). METHODS: Glutathione (GSH) content and membrane fluidity were measured by fluorometric assay and fluorescence depolarization assay, respectively. Glutathione S-transferase (GST) activity was measured with 1-chloro-2,4-dinitrobenzene as the substrate. Cell viability was determined by 3-(4, 5-dimethylthiazol)-2, 5-diphenyltetrazolium bromide assay. RESULTS: GSH content, GST activity, and membrane fluidity in EAC/Dox cells were higher than those in EAC cells (P < 0.01). The IC50 (95% confidence limits) for Dox on EAC/Dox cell was 22.3 (15.8-28.8) mg.L-1. Relative resistance of Dox in EAC/Dox cells was 42-fold. Pretreatment of EAC/Dox cells with Men 5 or 10 mg.L-1 decreased intracellular GSH content (P < 0.01). Men 1 mg.L-1 had no obvious effect on GSH content in EAC/Dox cells (P > 0.05), but decreased the elevated membrane fluidity efficiently (P < 0.05). Men had no obvious effect on GST activity in EAC/Dox cells (P > 0.05). IC50 of Dox was reduced to 9.6 (7.8-11.3), 6.0 (2.8-9.2), or 5.3 (3.9-6.7) mg.L-1 in EAC/Dox cells pretreated with Men 1, 5, or 10 mg.L-1. CONCLUSION: Men reduced Dox resistance effectively due in part to its depletion of GSH content in EAC/Dox cells.

Animals↗
PubMed1997

In vivo stimulation of insulin release by the monoethyl, monopropyl, monoisopropyl, monoallyl and diallyl esters of succinic acid.

The methyl esters of succinic acid are potent insulin secretagogues, currently under investigation as possible tools in the treatment of non-insulin-dependent diabetes. The in vivo administration of these esters may result, however, in the undesirable generation of methanol. The present study reveals that other esters of succinic acid, such as the monoethyl, monopropyl, monoisopropyl, monoallyl and diallyl esters, stimulate insulin release when administered intravenously in a dose of 2 mumol/g body weight to anaesthetized fed rats. This indicates that several succinic acid esters, that are not susceptible to lead, through their intracellular hydrolysis, to the production of methanol remain efficient in vivo as insulin secretagogues.

Animals↗
PubMed1997

Protective effects of succinic acid dimethyl ester infusion in experimental endotoxemia.

In rats injected with bacterial lipopolysaccharide (LPS; 5 gamma mg/g body weight [BWT]), the toxin provokes death within 24 h in 23% of the animals and, in surviving rats, causes a decrease in BWT, hyperlactacidemia, hyperlipacidemia, and hyperketonemia, as well as depletion of both liver and muscle glycogen content. In the liver, LPS severely lowers the ATP and total adenine nucleotide content, ATP/ADP ratio, and adenylate charge. In hepatocytes from LPS-injected rats, the oxidation of D-glucose is first increased 2 h after administration of the toxin, despite close-to-normal phosphorylation of the hexose. In hepatocytes prepared from rats killed 24 h after injection of LPS, the phosphorylation of D-glucose, its incorporation into glycogen, and its oxidation are all severely impaired. This sequence of changes, which coincides with a decreased ratio between pyruvate and lactate production from exogenous D-glucose, is comparable to that found with agents that uncouple oxidative phosphorylation. The injection of LPS also alters the metabolic response of hepatocytes to the dimethyl ester of succinic acid (SAD), in terms, for instance, of the sparing action of the ester upon both the production of 14CO2 by hepatocytes prelabeled with L-[U-14C] glutamine and the output of NH4+, and its inhibitory action on glycogenolysis and futile cycling in the reactions catalyzed by glucokinase and glucose-6-phosphatase. Nevertheless, the infusion of SAD protects the rats against the deleterious effect of LPS upon such variables as the plasma concentration of free fatty acids and beta-hydroxybutyrate, the liver ATP content, and the oxidation of D-glucose, as well as the pyruvate/lactate ratio, in hepatocytes prepared from the LPS-injected rats. The infusion of SAD also virtually suppresses lethality in the LPS-injected animals. It is proposed, therefore, that the infusion of succinic acid esters may represent a novel therapeutic approach in endotoxemia and multiple-organ failure.

Adenine Nucleotides↗
PubMed1996

D-glucose generation from [2-13C]pyruvate in rat hepatocytes: implications in terms of enzyme-to-enzyme channelling.

In rat hepatocytes exposed to [2-13C]pyruvate, newly formed glucose was more efficiently labeled in the carbon C5 than C2, as well as in the carbon C6 than C1, suggesting enzyme-to-enzyme channeling of D-glyceraldehyde 3-phosphate between glyceraldehyde-3-phosphate dehydrogenase and phosphofructoaldolase. Likewise the C1/C2 and C6/C5 ratios for 13C abundance in newly formed glucose, which largely exceeded the C3/C2 ratio of lactate or alanine and could reflect reversibility in the fumarase reaction, were compatible with the enzyme-to-enzyme tunneling of symmetrical Krebs cycle intermediates in the sequence of reactions catalyzed by succinyl-CoA synthetase, succinate dehydrogenase, and fumarase. This study further indicates that the major fraction of pyruvate is metabolized via pyruvate carboxylase rather than pyruvate dehydrogenase.

Animals↗
PubMed1996

Enzyme-to-enzyme channelling of Krebs cycle metabolic intermediates in Caco-2 cells exposed to [2-13c]propionate.

The generation of 13C-labelled lactate by colon carcinoma cells of the Caco-2 line incubated for 120 min in the presence of [2-13C]propionate (10 mM) was assessed by 13C NMR. About 10% of the total amount of 13C-labelled lactate was recovered in the cell pellet and displayed a [2-13C]lactate/[3-13C]lactate isotopomer ratio of 1.18 +/- 0.01. An even higher isotopomer ratio of 1.53 +/- 0.14 was observed in the case of 13C-labelled lactate released by the cells into the incubation medium. These findings indicate that, in the Caco-2 cells, metabolic intermediates of the Krebs cycle undergo enzyme-to-enzyme channelling in the sequence of reactions catalysed by succinyl-CoA synthetase, succinate dehydrogenase and fumarase.

Caco-2 Cells↗
PubMed1996

Effects of the methyl esters of pyruvate, succinate and glutamate on the secretory response to meglitinide analogues in rat pancreatic islets.

The insulinotropic action of the meglitinide analogues KAD-1229, A-4166 and repaglinide was examined in rat pancreatic islets deprived of exogenous nutrient or incubated in the presence of nutrient secretagogues such as D-glucose and the methyl esters of pyruvic acid, succinic acid and glutamic acid. The meglitinide analogues exerted little effect on insulin release in the absence of exogenous nutrient or in the presence of methyl pyruvate. They caused obvious stimulation of insulin output in the presence of D-glucose, dimethyl succinate or dimethyl glutamate. It is proposed, therefore, that suitable esters of dicarboxylic nutrients could be used to potentiate the secretory response to meglitinide analogues in non-insulin-dependent diabetes mellitus.

Animals↗
PubMed1996

Enzyme-to-enzyme channelling of symmetric Krebs cycle intermediates in pancreatic islet cells.

Tumoural islet cells of the RINm5F line were incubated for 120 min in the presence of [2-13C]propionate (10 mmol/l), and the 13C enrichment of lactate released in the incubation medium was monitored by 13C nuclear magnetic resonance. The C3/C2 ratio of resonance areas was much lower than that found with naturally 13C-enriched lactate. This reveals that symmetric Krebs cycle intermediates undergo oriented transfer in the sequence of reactions catalysed by succinate thiokinase, succinate dehydrogenate and fumarase in the mitochondria of islet cells.

Animals↗
PubMed1996

Nutritional efficiency of succinic acid and glutamic acid dimethyl esters in colon carcinoma cells.

The dimethyl esters of succinic acid (SAD) and glutamic acid (GME) were found to be efficiently metabolized in colon carcinoma cells of the Caco-2 line. The rate of [1,4-14C]SAD and [2,3-14C]SAD conversion to radioactive acidic metabolites, CO2, amino acids, pyruvic acid, and lactic acid suggested that the catabolism of the ester-derived succinic acid occurred mainly through the sequence of reactions catalyzed by succinate dehydrogenase, fumarase, and the malic enzyme. This coincided with a marked sparing action of SAD on the utilization of D-[2-(3)H]glucose and D-[5-(3)H]glucose and generation of 14C-labeled acid metabolites, CO2, and lactic acid from D-[U-14C]glucose by the enterocytes. Likewise, the conversion of [U-14C]GME to 14C-labeled amino acids, its oxidation compared with that of [1-(14)C]GME, and the production of NH4+ in the absence or presence of GME indicated efficient catabolism of the latter ester. Like SAD, GME decreased the utilization of D-[5-(3)H]glucose and generation of 14C-labeled acidic metabolites, pyruvate, and CO2 from D-[6-(14)C]glucose, while increasing the generation of 14C-labeled amino acids from the labeled hexose. The oxidation of D-[6-(14)C]glucose was even more severely inhibited by GME. In normal rat intestinal cells, SAM, SAD, and GME also exerted a marked sparing action on D-[U-14C]glucose oxidation. The present findings suggest, therefore, that these esters could possibly be used to sustain ATP generation in intestinal cells.

Adenosine Triphosphate↗
PubMed1995

Morphologic and morphometric evaluation of the effect of ICRF-187 on bleomycin-induced pulmonary toxicity.

Morphologic and morphometric studies were made of the protective effects of ICRF-187 against the pulmonary damage induced by bleomycin in male and female C57/BL6 mice. Sixty minutes prior to the subcutaneous administration of 15 mg/kg of bleomycin, animals received either saline or ICRF-187 (300 or 150 mg/kg) intraperitoneally, twice a week for 4 weeks. The lungs of animals treated with bleomycin alone showed inflammation, hyperplasia of type II epithelial cells, squamous cell metaplasia and fibrosis. The extent of fibrosis was quantified by means of a color videometric system and histologic sections of lung stained according to a modified Masson trichrome method. The severity of these alterations, particularly of fibrosis, was reduced in all groups of animals pretreated with ICRF-187. The fibrosis was reduced to a similar extent in female mice treated with the 300 mg/kg and the 150 mg/kg doses of ICRF-187, from 39.3% to 17.6% and 13.3%, respectively. ICRF-187 induced significantly different degrees of reduction in fibrosis in the 2 groups of male mice treated with the 150 mg/kg and the 300 mg/kg doses, from 30% to 19.7% and 12.2%, respectively. In vitro studies indicated that both ICRF-187 and its open-ring hydrolysis product (ADR-925) remove iron slowly from the bleomycin-iron complex. This observation provides a basis for the concept that ICRF-187 protects by chelating iron involved in the formation of the bleomycin-Fe3+ complex that generates reactive oxygen radicals capable of causing pulmonary damage.

Animals↗
PubMed1995

Metabolism of succinic acid methyl esters in neural cells.

The metabolism and metabolic effects of succinic acid methyl esters were examined in both NG108-15 mouse neuroblastoma x rat glioma hybrid cells and normal rat brain cells. The conversion of the dimethyl ester of 14C-labeled succinic acid (10 mM) to 14CO2 only represented 5% or less of that found at an equimolar concentration of D-[U- 14C]glucose. Neither the monomethyl nor the dimethyl ester of succinic acid exerted any significant effect upon the metabolism of D-glucose. Likewise, D-glucose (10 mM) failed to significantly affect the oxidation of the dimethyl ester of either [1,4- 14C]succinic acid or [2,3- 14C]succinic acid. It is concluded that, at variance with the situation recently documented in rat pancreatic islets and hepatocytes, the methyl esters of succinic acid are poorly metabolized in neural cells.

Animals↗
PubMed1995

Hydrolysis of succinic acid dimethyl ester in rat pancreatic islets.

The hydrolysis of the dimethyl ester of [1,4-14C]succinic acid and/or [2,3-14C]succinic acid was measured in homogenates of rat pancreatic islets, liver, jejunum, brain, BC3H1 mouse myocytes, NG108-19 mouse neuroblastoma x rat glioma hybrid cells, and Caco-2 human colon adenocarcinoma cells. The specific activity of the enzyme was much higher in liver, jejunum, and Caco-2 cells than in the other cell types. The affinity of the enzyme for succinic acid dimethyl ester (SAD) was also much higher in liver than in islet homogenates. In the latter case, both particulate and cytosolic activity were observed upon subcellular fractionation. The activity found in islet homogenates was commensurate with the rate of SAD hydrolysis in intact cells. While the intracellular pool of acidic metabolites generated from SAD remained fairly stable over a 15- to 120-min incubation and was mainly located in the cytosolic compartment, the amount of acidic metabolites released in the extracellular milieu progressively increased with the length of incubation. Such metabolites included both monocarboxylic and dicarboxylic acids, the latter consisting mainly of succinic acid and, to a much lesser extent, of fumaric acid and malic acid. However, at variance with SAD, succinic acid failed to be taken up by intact islets. There was no close parallelism between the specific activity of the SAD esterase and the extent of SAD utilization in distinct cell types.

Animals↗
PubMed1995

Restricted effect of formycin A and non-glucidic nutrients upon insulin release in islets from rats with hereditary or acquired non-insulin-dependent diabetes.

Pancreatic islets isolated from control rats, Goto-Kakizaki rats and adult rats that were injected with streptozotocin during the neonatal period were incubated for two successive period of 90 min each in the presence of D-glucose (11.1 mM) with or without formycin A (1.0 mM), and in the presence of the dimethyl ester of succinic acid (SAD, 10.0 mM) with or without palmitate (1.0 mM). Although formycin A augmented glucose-stimulated insulin release in both control and diabetic rats, it failed to compensate for the impaired secretory response to D-glucose in the latter animals. Likewise, non-glucidic nutrients such as SAD and/or palmitate failed to display a more efficient insulinotropic action, relative to basal insulin output, in diabetic than control rats. These results indicate that both formycin A and non-glucidic nutrients are unable, through their immediate insulinotropic action, to restore a normal output of insulin in islets of animals with inherited or acquired non-insulin-dependent diabetes.

Animals↗
PubMed1995

Metabolism of succinic acid methyl esters in myocytes.

The metabolism of the dimethyl ester of succinic acid (SAD) was examined in myocytes. When expressed in terms of CO(2) output, the oxidation of SAD (10 mM) only represented 30-40% of that of an equimolar concentration of D-glucose. Except for a modest decrease in D-[5-(3)H]glucose utilization, SAD failed to affect the catabolism of exogenous D-glucose. SAD also failed, like D-glucose, to augment O(2) consumption by the myocytes. These findings indicate that SAD is less efficiently metabolized in myocytes than in hepatocytes or pancreatic islets. It is nevertheless argued that the methyl esters of succinic acid could be efficiently used as nutrients by myocytes in situations of ATP depletion.

Journal Article↗