Biomedical subjects
Publications and source records attributed to Y Wu.
Study on trace elements content change in hair during the period of gestation for 52 lying-in women was performed. The quantitative results for 7 elements have been obtained and the change tendencies for other 7 elements without standard value have been observed on the basis of a self comparison method for each individual.
The interaction of cytochrome C with cystine as promoter was studied by synchronous fluorescence spectroscopy. After cystine was added into cytochrome C solution, the synchronous flurorescence spectra of tyrosine and tryptophan residues in cytochrome C were monitered with time. The results indicated that the lysine residues in cytochrome C molecules combine with cystine slowly. It induced the small conformational change of cytochrome C molecules.
Replication errors (RER) are frequently seen in both sporadic and hereditary forms of colorectal cancer. In hereditary nonpolyposis colorectal cancer (HNPCC), RER is associated with defects in DNA mismatch repair genes. Two of these genes, MSH2 and MLH1, account for a major share of this cancer syndrome. In order to assess the role of these genes in sporadic RER+ colorectal carcinoma, we have carried out a mutation analysis of MSH2 and MLH1 by two-dimensional (2-D) DNA electrophoresis, including heteroduplexing and separation in a denaturing gradient. All exons were amplified using multiplex PCR and were separated on the basis of both size and base pair composition under a single set of experimental conditions. Exons showing a spot position different from normal were sequenced. In screening 33 unselected, sporadic RER+ colorectal tumors, a germline mutation accompanied by loss of heterozygosity in tumor tissue was found in two patients. They were among the 4 patients out of the 33 screened that were diagnosed before the age of 50 years. In 8 of the remaining 31 tumors (26%), presence of somatic mutations (9 in total) could be demonstrated. While suggesting involvement of other genes in a substantial part of sporadic RER+ colorectal carcinomas, our results also demonstrate a clear role of MSH2 and MLH1 in these sporadic tumors and show that young sporadic RER+ colorectal carcinoma patients have a high probability of germline mutations. This has important implications for genetic testing and management of young colorectal cancer patients and their families.
In 1995, 234 adults from Qidong, Jiangsu Province, People's Republic of China, where hepatocellular carcinoma is the leading cause of cancer deaths and exposure to dietary aflatoxins is widespread, were enrolled and followed in a Phase II chemoprevention trial. The goals of the study were to define a dose and schedule of oltipraz for reducing levels of validated aflatoxin biomarkers and to characterize dose-limiting toxicities. Healthy eligible individuals, including those infected with hepatitis B virus, were randomized to receive either 125 mg of oltipraz daily, 500 mg of oltipraz weekly, or placebo. Blood and urine specimens were collected to monitor toxicities and evaluate biomarkers over the 8-week intervention period and subsequent 8-week follow-up period. Unique trial aspects included a synchronous follow-up schedule, daily observed administration of all medications, timely international data transference, and use of biomarkers as outcomes. One hundred thirty-two participants took their medications without interruptions, approximately 77% contributed all nine urine samples, and 78% contributed all seven blood samples. Fifty-one participants (21.8%) reported clinical adverse events. An extremity syndrome, developing soon after the start of treatment, was the only event that occurred more frequently (P = 0.002) among the active groups (18.4 and 14.1% of the daily 125 and weekly 500 mg arms, respectively) compared with placebo (2.5%). The oltipraz arms did not differ in symptom type or severity, and there were no indications of exacerbated drug intolerance among the few participants infected with hepatitis B virus. The good compliance with an intense follow-up schedule shows that chemoprevention trials with biomarker end points may be conducted in such populations.
GM2 gangliosidosis are caused by a beta-hexosaminidase A enzyme deficiency. Mutations in the gene leaving residual enzyme activity give rise to juvenile and adult forms of the disease which have a great clinical heterogeneity. We report three cases which have been considered for some time as Kugelberg-Welander disease. beta-hexosaminidase A was determined with the sulfated synthetic substrate, 4-méthylumbelliferyl-N-acetylglucosamine 6-sulfate (4-MUGS), which allowed the diagnosis. Two of these cases from one family had normal values of hexosaminidase A in serum as found in the B1 variant. Compound mutations were detected. The B1 variants had a classical B1 mutation (G533-->A) and a new mutation located on exon 11. The patient of the second family had the classical mutation of adult GM2 gangliosidosis (Gly269-->Ser) and a new mutation on exon 1, at the initiation codon.
The bcr-abl oncogene is the molecular counterpart of the Philadelphia chromosome (Ph), which is detected in > 95% of patients with chronic myelogenous leukemia (CML) and 20-30% of adults with acute lymphoblastic leukemia (ALL). Leukemic cells from patients with CML express the p210 form of the bcr-abl oncogene, whereas in adult Ph+ ALL approximately 50% of cases express the p190 form of the bcr-abl oncogene, and the other 50% express the same p210 gene as is found in CML. In this study, we have designed hairpin ribozymes (RZs) specific for the p190 form of the bcr-abl oncogene to inhibit the growth of a p190 Ph+ ALL cell line, Sup-B15. The RZs cleave p190 RNA substrate in a cell-free in vitro assay. In the presence of the liposome, DMRIE-C, the RZs are protected from serum mediated catalysis in vitro. Anti-p190 RZs transfected with DMRIE-C as the vector into K562 cells, which express the p210 bcr-abl oncogene, are stable intracellularly for up to 96 hours. Up to 33% of the DMRIE-C and RZ mixtures are taken up by Sup-B15 cells cultured in suspension. Expression of the p190 bcr-abl protein product is specifically inhibited as demonstrated by Western blot analysis. Cell growth of the Sup-B15 cells is completely inhibited by anti-p190 RZs over four days in culture. Anti-p210 RZs have no significant effect on bcr-abl protein expression or cell growth by Sup-B15 cells. RZs may have a role in purging stem cell populations collected from patients with Ph+ ALL in the context of autologous bone marrow transplantation.
In order to achieve high activity of enzymatic catalysis, the method of permealizing and crosslinking treatment has been suggested for immobilizing cells with endocellular enzymes. Polyethene-polyamine and glutardehyde were used to enhance the activity and stability of E. coli having aspartase entrapped in k-carrageenan gel and intact P. dacunhae cells having aspartate-beta-decarbonoxylase. The strength and enlargement effects, which favor the performance of catalysis in a packed bed reactor and a membrane reactor, respectively, were also obtained from the experiment results.
The present study was designed to explore if there exists a correlation between predominant isotype-defined antibody levels and reinfection in low age groups of the population in an endemic area of schistosomiasis japonica in China. One hundred and thirty-eight individuals aged 3-25 years old were selected for serological investigations including the levels of IgG, IgG4, IgM and IgE, detected by ELISA with soluble egg antigen and soluble adult worm antigen. Results show that age is a determinant for SEA-specific IgG, IgG4, and IgE, and SWA-specific IgG and IgG4 antibody levels, which increased with age, and that SEA- and SWA- specific IgG4 antibody levels are risk factors of reinfection, ie, the risk of reinfection occurrence of the population with high level of SEA or SWA-specific IgG4 is 2.83 or 2.40 times, respectively, that with low level of SEA or SWA-specific IgG4, suggesting that in the endemic area of schistosomiasis japonica, there exists a possibility that in the population aged 3-25 years, SEA and SWA-specific IgG4 antibodies mediate a blocking immunity response.
Oltipraz has been used clinically in many regions of the world as an antischistosomal agent and is an effective inhibitor of aflatoxin hepatocarcinogenesis in rats. This chemopreventive action of oltipraz results primarily from an altered balance in aflatoxin metabolic activation and detoxication. In 1995, a randomized, placebo-controlled, double-blind intervention was conducted in residents of Qidong, People's Republic of China, who are at high risk for exposure to aflatoxin and development of hepatocellular carcinoma. The major study objectives were to define a dose and schedule for oltipraz that would reduce levels of aflatoxin biomarkers in biofluids of the participants, and to further characterize dose-limiting side effects. Two hundred thirty-four healthy eligible individuals, including those infected with HBV, were randomized to receive either 125 mg oltipraz daily, 500 mg oltipraz weekly, or placebo. Blood and urine specimens were collected to monitor potential toxicities and evaluate biomarkers over the 8-week intervention and subsequent 8-week follow-up periods. Overall, compliance in the intervention was excellent; approximately 85% of the participants completed the study. Objective evaluation of adverse events was greatly facilitated by inclusion of a placebo arm in the study design. A syndrome involving numbness, tingling, and pain in the fingertips was the only event that occurred more frequently among the active groups (18 and 14% of the daily 125 mg and weekly 500 mg arms, respectively) compared to placebo (3%). These symptoms were reversible and could be relieved with non-steroidal antiinflammatory agents. A more complete understanding of the chemopreventive utility of oltipraz awaits completion of an assessment of the efficacy of oltipraz in modulating levels of aflatoxin biomarkers.
OBJECTIVE: To determine whether the hepatovenous intrahepatic anastomoses exist in normal humans. METHODS: A total of 13 livers were isolated during the early autopsies of normal men who died in accidents. Perfusion venography of the branches of hepatic veins using meglucamine diatrizoate was performed in 6 cases. This method of investigation has not been reported in the literature. In one case, a portal venography was done. In the remaining 6 cases, liver substance stainings were done by injecting ink through the middle hepatic vein, and the tissue sections of these livers were observed under light microscope. RESULTS: There were intrahepatic anastomoses between the hepatic veins within the liver. These anastomoses belonged to the 4th or 5th branch of hepatic vein near the capsule. There were also anastomoses between the middle hepatic vein and the hepatic short veins. Shunts existed between the portal veins and hepatic veins. CONCLUSIONS: The detection of anastomoses of intrahepatic veins in normal individuals provide anatomical rationale for the performance of irregular hepatectomy, as well as rationale for the ligation of one or two hepatic veins should such veins be traumatized or invaded by liver cancer.
Examination of plain Merchant-view X-rays of the patellofemoral joint is often used to diagnose patellofemoral joint malalignment and to qualify the pathology. As digital image processing becomes more widespread, an image processing algorithm is being developed for medical personnel to easily display, manipulate and analyze digitized plain Merchant-view X-ray films on personal computers. The method provides measurement of the kinematic parameters: sulcus angle (SA), patellofemoral congruence angle (PFC), lateral patellar angle (LPA), patellar rotation angle (PR), and lateral patellar displacement (LPD). Smooth edges of the patella and the femur are obtained by using image enhancement, edge detection and morphological thinning techniques based on the thresholds chosen manually for boundary detection. Six landmarks for determining the kinematic parameters are marked automatically on the edges of patella and femur. Parameter measurements for twelve X-ray films of six patients are calculated for analysis and comparison with hand calculated parameters. The goal is develop an algorithm that can evaluate the geometry of the patellofemoral joint, and is cost effective.
OBJECTIVE: To investigate the effect of second-trimester maternal serum markers AFP, beta-hCG, uE3, for prenatal screening of the fetal defects. METHODS: In 677 women the triple markers were measured. Some factors that may affect the testing such as maternal weight, gestational age, were adjusted on analyzing the result of the testing. Each woman, who underwent the triple screening, will be followed up until her fetus was delivered. RESULTS: Among the women who were screened, 11 patients who presented at least one marker positive were identified as having an abnormal fetus, and the positive rate was 1.6%. While 32 women were confirmed to be false positive with a rate of 4.7%. Another 11 women had fetal demise on second-trimester, which had been proved to be not caused by fetal abnormality. CONCLUSION: Maternal triple serum markers may take as a routine protocol for prenatal screening of the fetal defects.
OBJECTIVE: To observe the changes of tissue lithium content and its relationship with glucose metabolism in spontaneous hereditary diabetic Chinese hamsters (SHDCH). METHODS: Twenty diabetic and ten normal Chinese hamsters were paired and separated randomly into four groups: controls (C), diabetics (D), controls treated with lithium carbonate (CT) and diabetics treated with lithium carbonate (DT). The lithium carbonate treatment was administrated with drinking water containing lithium carbonate (0.2 mg/ml). Blood glucose levels were determined at 0, 1, 3, 5, 6th month, and insulin levels at 1, 3, 6th month. The lithium contents in liver, kidney and muscles were determined at the end of 6th month, using wet digestion assay and ICP-AES. Concentrations of fructosamine, lactic acid, GPT, BUN were also evaluated. RESULTS: The data showed that in Group D the lithium levels in hepatic tissue were lower than in Group C (P < 0.05), and lithium contents in kidney and muscle also decreased. In Group DT, the lithium contents in tissues were higher than in Group D (P < 0.05) and similar to Group C. Blood glucose levels and fructosamine concentrations decreased while insulin and lactic acid levels did not alter significantly. GPT and BUN levels did not change in both Group CT and Group DT. CONCLUSIONS: There is lithium deficiency in hepatic, renal and muscular tissues from diabetic Chinese hamsters. Low-dose and six-month-treatments of lithium carbonate can improve tissue lithium deficiency and glucose metabolism, and do not damage liver and kidney functions.
OBJECTIVE: To investigate, at transcriptional and translational level in situ, whether the gene expression of the Ki-67 protein in pancreatic carcinoma specimens is altered to get insight of the gene structure and function. METHODS: Forty pancreatic cancer, 5 normal pancreatic and 4 chronic pancreatitis tissues were used in this experiment. A 435 bp cDNA fragment located in codon 2, exon 13 of Ki-67 antigen gene was amplified by the polymerase chain reaction (PCR). The DIG-labeled cRNA probes were transcribed using a commercial DIG RNA labeling kit. Localization of the Ki-67 protein and the specific mRNA was performed by combining immunohistochemistry (ICH) with DIG-labeled in situ hybridization (ISH). RESULTS: Successful localization of the Ki-67 protein mRNA in pancreatic tissue sections, routinely formalin-fixed and paraffin-embedded, was first accomplished in this experiment. Analysis of the Ki-67 mRNA transcription in 17 pancreatic cancer specimens with Ki-67 ICH labeling index > 20% revealed stronger mRNA signals in poorly differentiated specimens with Ki-67 index > 50% than in well differentiated cases with the ICH labeling index of 20%-50%. A high expression of both the mRNA and the protein was observed in pancreatic adenocarcinomas with poor differentiation. CONCLUSIONS: This is the first study in which the abnormal overexpression of the gene encoding Ki-67 protein was detected not only at the protein level, but also at the mRNA level in pancreatic tumours. The abnormal overexpression of the Ki-67 protein might be correlated with the central part, exon 13, of the gene.
OBJECTIVE: To investigate the differences of tumorigenicity and metastasis of marine tumors with different immunogenicity by B7.1 gene transfer. METHOD: Using retroviral-mediated gene transfer, we transduced B7.1 cDNA into a panel of murine tumor lines with different immunogenicity to study the effect of B7.1 costimulation on antitumor immunity. RESULTS: After transduced with B7.1 cDNA, the immunogenic T lymphoma EL4 regressed completely, and tumorgenicity of three nonimmunogenic tumors melanoma B16, mastocytoma P815 and mammary adenocarcinoma MA891 were significantly reduced in syngeneic mice. The experimental metastasis of B16 and spontaneous pulmonary metastasis of MA891 were profoundly suppressed. Moreover, immunization with B7.1 cDNA transduced B16 induced systemic immunity against subsequently inoculated parental B16 tumor, while this immunization method did not provide protective immunity against established parental B16 tumor. CONCLUSION: Our results show that varied extent of antitumor immunity can be induced to abrogate or decrease tumorigenecity and metastasis through B7.1 gene transduction, depending on the immunogenic potential of tumors.
OBJECTIVE: To investigate the effect of the exercise on glucose transporter 4 (GLUT4) gene expression in skeletal muscles of rats with streptozotocin-induced diabetes. METHODS: Three experiment groups of rats were investigated: diabetic non-exercise group; diabetic exercise group; and normal controls. Diabetic exercise rats were swim-trained for 6 weeks. The GULT4 mRNA of skeletal muscle cells was determined with dot blot. RESULTS: There was weak gene expression of GULT4 in diabetic rats, and dot blot revealed that the GLUT4 mRNA decrease 54.9% in skeletal muscle cells compared with the normal control. After 6 weeks exercise training, the hyperglycemia of diabetic exercise rats decreased significantly (from 18.5 +/- 1.9 mmol/L to 14.0 +/- 3.3 mmol/L, t = 4.64 P < 0.01). In muscle cells of diabetic exercise rats, the GLUT4 mRNA increased 56% as compared with the diabetic rats (t = 15.56, P < 0.01). CONCLUSION: Chronic hyperglycemia may inhibit the gene expression of GLUT4 in diabetic rats, which caused the post-receptor insulin resistance in peripheral tissue. Exercise training can improve the impaired GLUT4 expression in diabetic rats, which may contribute to the mechanisms of enhanced insulin sensitivity and decreased hyperglycemia in diabetics mellitus.
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We detected the effect of non-toxic doses of sodium selenite (Se) on the expressing effect of nuclear antigen (EBNA) of Epstein-Barr virus (EBV) in Raji cell line by microfluorescence spectrophoto-quantitation (MFS) and studied the inhibing transformation in B lymphocytes from human umbilical cord blood (BL) with EBV in vitro by Se. We found that Se (0.01-0.50 microgram/ml) can lower EBNA-MFS value 8.4%-21.8% in Raji cell line. The transformation effect of BL with EBV was markedly inhibited by Se (0.1-1.0 microgram/ml) in pretreatment and cotreatment. The inhibition rates of BL transformation were 73.4%-92.1% and 60.3%-77.2% respectively. EBV is associated with nasopharyngeal carcinoma (NPC). The Se levels of serum and hair in NPC patients were markedly lower than those in healthy persons. The results suggest that supplement Se to persons for active expression of EBV gene and NPC patients may help protect againt and treat NPC and diseases associated with EBV.