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Biomedical subjects

W Zheng

Publications and source records attributed to W Zheng.

At least 181 records · Page 10Linked to original sources
PubMed1998

Determination of lamotrigine in biologic materials by a simple and rapid liquid chromatographic method.

Lamotrigine (LTG), a newly introduced antiepileptic drug, appears to have potential therapeutic advantages for the treatment of patients with partial-onset seizures. Increasing clinical application and research of LTG demand a simpler and more rapid analytical procedure to determine LTG concentration in body fluids and tissues. The authors have developed an effective one-step procedure for sample preparation followed by high-performance liquid chromatography (HPLC) to quantitate LTG in plasma, urine, and brain tissues. Body fluids and brain homogenates were treated with cold acetonitrile to precipitate protein. The samples were fractionated on a 250 x 4.6 mm C18 reversed-phase column with an isocratic mobile system consisting of potassium phosphate buffer, acetonitrile, and methanol (70:16:14). The method had a LTG detection limit of 0.02 microg/ml in plasma and 0.03 microg/ml in urine. The coefficients of variation were <2.7% for intraday and 4.2% for interday analyses. The recovery of LTG added to plasma, urine, and brain homogenate ranged from 98% to 100%. The method was applied to a clinical study to determine plasma and urine concentrations of LTG in subjects receiving a single oral dose of LTG. The calculated pharmacokinetic parameters were comparable to those previously reported. The method proved to be simple, fast, reproducible, and useful in clinical investigation and monitoring of LTG concentrations.

Acetonitriles↗
PubMed1998

The nucleic acid binding activity of bleomycin hydrolase is involved in bleomycin detoxification.

Yeast bleomycin hydrolase, Gal6p, is a cysteine peptidase that detoxifies the anticancer drug bleomycin. Gal6p is a dual-function protein capable of both nucleic acid binding and peptide cleavage. We now demonstrate that Gal6p exhibits sequence-independent, high-affinity binding to single-stranded DNA, nicked double-stranded DNA, and RNA. A region of the protein that is involved in binding both RNA and DNA substrates is delineated. Immunolocalization reveals that the Gal6 protein is chiefly cytoplasmic and thus may be involved in binding cellular RNAs. Variant Gal6 proteins that fail to bind nucleic acid also exhibit reduced ability to protect cells from bleomycin toxicity, suggesting that the nucleic acid binding activity of Gal6p is important in bleomycin detoxification and may be involved in its normal biological functions.

Antibiotics, Antineoplastic↗
PubMed1998

[A case-control study on risk factors of periodontitis].

A 1:1 matched case-control study was conducted to determine the risk factors of periodontitis for the government cadres in Wuhan city. Results showed that dental calculus, cigarette smoking and alcohol consumption were identified as risk factors of periodontitis with odds ratios 5.31, 2.13 and 1.86 respectively. Drinking tea was not found related with periodontitis. In the process of periodontitis, synergetic effect between cigarette smoking, alcohol drinking and dental calculus were noticed. In the general population, the proportions of periodontitis cases attributed to alcohol drinking, cigarette smoking and dental calculus were 25.12%, 24.04% and 46.29% respectively.

Adult↗
PubMed1998

[The diagnosis and treatment of nipple discharge in 253 cases].

Among 253 cases of nipple discharge, 96 cases of them were diagnosed as intracanalicular papilloma(37.9%), 73 cases as cystic disease of breast(28.9%), 41 cases as mammary duct ectasia (16.2%), 35 cases as breast cancer(13.8%) and 8 cases as acute suppurative mastitis(3.2%). The masses beneath areolar region were smaller those outside areola. Finding of cancer cells or suspicious cancer cells through cytologic examination of nipple discharge smear and breast mass puncture usually had important significance. In addition, near infrared ray scanning shows high rate of correct diagnosis; estimation of carcinoembryonic autigen(CEA) in nipple discharge is beneficial to the early diagnosis of malignant diseases.

Adolescent↗
PubMed1998

[Major blood vessel excision and reconstruction in the treatment of retroperitoneal neoplasms].

OBJECTIVE: To summarize the experience in the treatment of retroperitoneal tumors involving major blood vessels. METHODS: Twenty five cases with retroperitoneal tumors involving major blood vessels were treated by excision of the tumor and the major blood vessel involved followed by vascular reconstruction. RESULTS: After a careful preoperative evaluation and necessary preparation, the tumor together with the involved blood vessels in all patients are successfully resected and the severed major blood vessels reconstructed. There was no operative death. CONCLUSION: Retroperitoneal neoplasm involving major blood vessels is not a contraindication for surgical resection. The tumor and the involved vessel can be removed en bloc followed by vascular reconstruction. The risk of local tumor recurrence can thus be minimized and better survival achieved.

Adolescent↗
PubMed1998

[Study on the relationship between DNA topoisomerase II activity and multidrug resistance in leukemic cells].

OBJECTIVE: To explore the relationship between DNA topoisomerase II (Topo II) activity and multidrug resistance in acute leukemia(AL). METHODS: Topo II activities were measured in peripheral blood or bone marrow leukemia cells from 17 pretreated patients and 20 after combination chemotherapy by fluorometric assay. In the same time, multidrug resistant p-glycoprotein expression was detected by immunohistochemistry using JSB-1 monoclonal antibody and mdr-1 gene expression was assayed by RT-PCR in 18 post-chemotherapy patients. RESULTS: Topo II activities were significantly higher in pretreated AL patients (0.6415 +/- 0.0561) than in healthy blood donors (0.2304 +/- 0.0591)(P < 0.005) and significantly lower in post-chemotherapy patients (0.3563 +/- 0.1011) than in pretreated ones (P < 0.005). Among 15 poorly responsed patients, 12 were p170 positive and mdr-1 overexpression, 3 case were p170 negative. Topo II activity was also decreased in these poor responsers. CONCLUSION: Decreased Topo II activity may be another factor in multidrug resistance.

ATP Binding Cassette Transporter, Subfamily B, Mem↗
PubMed1998

[Local amyloidosis of stomach].

OBJECTIVE: To improve the diagnostic rate of local amyloidosis of stomach. METHOD: One case of local amyloidosis of stomach was reported and the literatures were reviewed on the etiopathology, clinical features, diagnosis, treatment and prognosis. RESULT: The patient was negative for family history and other chronic disease. Total gastrectomy was taken and was eventually found to have localized amyloidosis of stomach and regional lymph nodes. The amyloidosis was found to be of AA amyloidosis. Multiple biopsy specimens taken from esophagus, duodenum, rectum and bone marrow showed no amyloid deposition. CONCLUSION: Amyloidosis should be considered in the differential diagnosis of gastric tumors, and also should be removed by operation if complications are to be prevented.

Amyloidosis↗
PubMed1998

[Effects of methotrexate on early pregnancy in mice].

Single s.c. injection of MTX at dosages of 8, 24 and 72 mg.kg-1 on day 7 of gestation was found to have a feticide effect in mice. The mortality of fetuses on day 13 of pregnancy was 18.0%, 55.5% and 60.3%, respectively. Treatment with MTX caused a decrease of serum progesterone level on day 13 of pregnancy. Treatment with MTX at a dosage of 24 mg.kg-1 on day 7-9 of gestation terminated total early pregnancy. MTX combined with hCG 10 U/mouse or progesterone 0.2 mg/mouse was shown to have antagonistic effect to terminate early pregnancy. Synergism of RU486 combined with MTX on termination of early pregnancy in mice was observed.

Abortifacient Agents, Nonsteroidal↗
PubMed1998

A prospective cohort study of intake of calcium, vitamin D, and other micronutrients in relation to incidence of rectal cancer among postmenopausal women.

To investigate whether high intakes of calcium and other micronutrients (carotene, retinol, and vitamins C, D, and E) are related to reduced risks of rectal cancer, we analyzed data from a large cohort study of postmenopausal Iowa women who responded to a mailed survey in 1986. After 9 years of follow-up, 144 incident rectal cancer cases were ascertained among the 34,702 women at risk. Intake levels of micronutrients at baseline were derived from self-reported data on vitamin supplements and dietary intake of 127 foods included in a semiquantitative food frequency questionnaire. After adjustment for total energy intake and other potential confounding factors, a dose-response inverse association was observed between total calcium intake and the risk of rectal cancer: adjusted relative risks (RRs) were 1.00, 0.90, and 0.59 (trend test, P = 0.02) from the lowest to the highest calcium intake tertiles. High intakes of dietary and supplement calcium were both related to a slightly reduced risk of rectal cancer, but neither of the trend tests was statistically significant. Reduced risks of rectal cancer were also observed for high intake of carotene and vitamins A, C, and D, although none of the associations were statistically significant. For vitamin D, the adjusted RRs were 1.00, 0.71, and 0.76 (trend test, P = 0.20) for increasing intake tertiles. Compared with women who consumed low levels of both total calcium and vitamin D, those in the highest intake group of both nutrients were at a 45% reduced risk of rectal cancer (RR, 0.55; 95% confidence interval, 0.32-0.93). This study supports the hypothesis that high intake of calcium and possibly other micronutrients may be beneficial in the prevention of rectal cancer.

Aged↗
PubMed1998

Focus-2D: a new approach to the design of targeted combinatorial chemical libraries.

A strategy for rational design of targeted combinatorial libraries is described. The aim of this approach is to select a subset of available building blocks for the library synthesis that are most likely to be present in the active compounds. Building blocks that are used in the underlying combinatorial chemical reaction are randomly assembled to produce virtual combinatorial library compounds, which are represented by various chemical descriptors. Stochastic algorithms (simulated annealing, genetic algorithms, neural net methods) are used to search the potentially large structural space of virtual chemical libraries in order to identify compounds similar to lead compound(-s). The selection of a virtual molecule as a candidate for the targeted library is based either on its chemical similarity to a biologically active probe or on its biological activity predicted from a pre-constructed QSAR equation. Frequency analysis of building block composition of the selected virtual compounds identifies building blocks that can be used in combinatorial synthesis of chemical libraries with high similarity to the lead compound(-s). This method is applied to rational design of the library with bradykinin potentiating activity. Twenty eight bradykinin potentiating pentapeptides were used as a training set for the development of a QSAR equation, and, alternatively, two active pentapeptides, VEWAK and VKWAP, were used as probe molecules. In each case, the frequency distribution of amino acids in the top 100 peptides suggested by the method resembles the frequency distribution of amino acids found in the active peptides. The results obtained after GA optimization also compared favorably with those obtained by the exhaustive analysis of all possible 3.2 millions pentapeptides.

Algorithms↗
PubMed1997

The role of hormone replacement therapy in the risk for breast cancer and total mortality in women with a family history of breast cancer.

BACKGROUND: The risks and benefits of hormone replacement therapy (HRT) are of considerable interest and importance, especially in terms of whether they differ among subsets of women. OBJECTIVE: To determine whether HRT is associated with increased risks for breast cancer and total mortality in women with a family history of breast cancer. DESIGN: Prospective cohort study. SETTING: Population-based sample of midwestern post-menopausal women enrolled in an observational study of risk factors for cancer. PARTICIPANTS: Random sample of 41,837 female Iowa residents 55 to 69 years of age. MEASUREMENTS: Incidence rates of and relative risks for breast cancer (n = 1085) and total mortality (n = 2035) through 8 years of follow-up were calculated by using data from the State Health Registry of Iowa and the National Death Index. RESULTS: A family history of breast cancer was reported by 12.2% of the cohort at risk. Among women with a family history of breast cancer, those who currently used HRT and had done so for at least 5 years developed breast cancer at an age-adjusted annual rate of 61 cases per 10,000 person-years (95% CI, 28 to 94 cases); this rate was not statistically significantly higher than the rate in women who had never used HRT (46 cases per 10,000 person-years [CI, 36 to 55 cases]). Among women with a family history, those who used HRT had a significantly lower risk for total mortality than did women who had never used HRT (relative risk, 0.67 [CI, 0.51 to 0.89]), including total cancer-related mortality (relative risk, 0.75 [CI, 0.50 to 1.12]). The age-adjusted annual mortality rate for women using HRT for at least 5 years was 46 deaths per 10,000 person-years (CI, 19 to 74 deaths); this is roughly half the rate seen in women who had never used HRT (80 deaths per 10,000 person-years [CI, 69 to 92 deaths]). CONCLUSIONS: These data suggest that HRT use in women with a family history of breast cancer is not associated with a significantly increased incidence of breast cancer but is associated with a significantly reduced total mortality rate.

Aged↗
PubMed1997

The cysteine-peptidase bleomycin hydrolase is a member of the galactose regulon in yeast.

Bleomycin hydrolase is a cysteine peptidase discovered through its ability to detoxify the anti-cancer glycopeptide, bleomycin. Although found in all tissues in mammals and in both eukaryotes and prokaryotes, the normal cellular function of this peptidase is not known. We had previously reported the purification of bleomycin hydrolase from yeast based on its unexpected ability to bind DNA. Recently we collaborated in solving the crystal structure of this protein, revealing a hexameric ring organization. We now report that the molecular characterization of the gene encoding yeast bleomycin hydrolase is also surprising. The transcription of the gene is regulated by galactose. Furthermore, this regulation is conveyed by a binding site for the Gal4 regulatory protein in its promoter, prompting the designation of this gene as GAL6. Gal6p also appears to have a negative effect on the GAL system as a deletion of the gene leads to a 2-5-fold higher expression of the GAL1, GAL2, GAL7, and MEL1 genes. The GAL6 deletion does not affect the expression of another inducible gene, HSP26. Neither the peptidase nor the nucleic acid binding activity of Gal6p as assayed is apparently required to convey this regulation, implying yet another function for this new member of the GAL regulon.

Base Sequence↗
PubMed1997

Identification of critical amino acid residues of Saccharomyces cerevisiae carbamoyl-phosphate synthetase: definition of the ATP site involved in carboxy-phosphate formation.

Carbamoyl-phosphate synthetases (CPSases) utilize two molecules of ATP at two homologous domains, B and C, with ATP(B) used to form the enzyme-bound intermediate carboxy-phosphate and ATP(C) used to phosphorylate the carbamate intermediate. To further define the role of one CPSase peptide suggested by affinity labeling studies to be near the ATP(B) site, we have carried out site-directed mutagenic analysis of peptide 234-242 of the Saccharomyces cerevisiae arginine-specific CPSase. Mutants E234A, E234D, E236A, E236D and E238A were unable to complement the CPSase-deficient yeast strain LPL26 whereas mutants Y237A, E238D, R241K, R241E and R241P supported LPL26 growth as well as wild-type CPSase. Kinetic analysis of E234A and Y237A indicated impaired utilization of ATP(B) but not of ATP(C). D242A, a temperature-sensitive mutant, retained no detectable activity when assayed in vitro. These findings, together with the affinity labeling data and primary sequence analysis, strongly suggest that the yeast CPSase peptide 234-242 is located at the ATP(B) site and that some of its residues are important for functioning of the enzyme. D242 appears to occupy a critical structural position and E234, E236 and E238 appear to be critical for function, with the spatial arrangement of the carboxyl side chain also critical for E234 and E236.

Adenosine Triphosphate↗
PubMed1997

The transcription factor GATA-3 is necessary and sufficient for Th2 cytokine gene expression in CD4 T cells.

CD4 T cells potentiate the inflammatory or humoral immune response through the action of Th1 and Th2 cells, respectively. The molecular basis of the differentiation of these cells from naive T cell precursors is, however, unclear. We found that GATA-3 was selectively expressed in Th2 cells. GATA-3 is expressed at a high level in naive, freshly activated T cells and Th2 lineage cells, but subsides to a minimal level in Th1 lineage cells as naive cells commit to their Th subset. Antisense GATA-3 inhibited the expression of all Th2 cytokine genes in the Th2 clone D10. GATA-3 directly activated an IL-4 promoter-luciferase reporter gene in M12 cells. In transgenic mice, elevated GATA-3 in CD4 T cells caused Th2 cytokine gene expression in developing Th1 cells. Thus, GATA-3 is necessary and sufficient for Th2 cytokine gene expression.

Animals↗
PubMed1997

Characterization of intracellular calcium mobilization by bombesin-related neuropeptides in PC-3 human prostate cancer cells.

BACKGROUND: The objective of this study was to characterize the calcium mobilizing activity of bombesin-related neuropeptides in PC-3 cells. METHODS: Intracellular free Ca2+ concentration ([Ca2+]i) was measured following the administration of bombesin-related neuropeptides using spectrofluorometric monitoring of PC-3 cells loaded with Fura2/AM. RESULTS: Individual neuropeptides induced a rapid rise in [Ca2+]i immediately after stimulation in similar fashion. When two different peptides were administered simultaneously, the [Ca2+]i changes were similar to that produced by each peptide alone. However, simultaneous addition of tyr4-bombesin 100 nM and 2% serum resulted in [Ca2+]i increase greater than either alone. Sequential stimulation by same or different peptides, was not able to induce another response. However, 6 hrs after the first stimulus, a second stimulus was able to induce a similar response. CONCLUSIONS: The data indicate that all members of the bombesin-related family of neuropeptides are capable of triggering calcium mobilization in PC-3 cells via a similar signalling pathway. PC-3 cells become acutely desensitized to additional stimulation of neuropeptide. This desensitization is selective and reversible, requiring approximately 6 hrs for recovery.

Bombesin↗
PubMed1997

Medical history risk factors for non-Hodgkin's lymphoma in older women.

BACKGROUND: It has been suggested that certain medical conditions and drug exposures might suppress the immune system and increase the risk of developing non-Hodgkin's lymphoma (NHL). PURPOSE: We investigated whether specific medical conditions and drug exposures were associated with the risk of NHL in a cohort of older women who were enrolled in the Iowa Women's Health Study. METHODS: A cohort of 41837 women, 55-69 years of age at baseline, was followed prospectively for the development of cancer from 1986 through 1992. These women had completed a baseline questionnaire in January 1986 that inquired about the occurrence and age at onset of specific medical conditions, about family history of cancer, and about the use of selected medications. Follow-up questionnaires were mailed to the women in 1987, 1989, and 1992. Incident cancers and deaths were ascertained through linkages to state and national databases. For most analyses, women with a self-reported history of cancer at baseline (n = 3903) were excluded. Relative risks (RRs) and 95% confidence intervals (CIs), adjusted for age or for age and other variables, were used as a measure of the association between NHL and medical history factors. Reported P values are two-sided. RESULTS: One hundred fourteen incident cases of NHL were identified in the cohort during follow-up. A history of adult-onset diabetes mellitus (i.e., first diagnosed after the age of 30 years) was associated with an increased risk of developing NHL (age-adjusted RR = 2.18; 95% CI = 1.22-3.90). In addition, there was an association between the duration of adult-onset diabetes and increasing risk of NHL (P for trend = .004), with an age-adjusted RR of 2.90 (95% CI = 1.07-7.90) for women with a diagnosis of diabetes for 15 or more years compared with women with no diagnosis of diabetes. Women with a history of blood transfusion were also at increased risk for the development of NHL (age-adjusted RR = 1.95; 95% CI = 1.33-2.85). The risk estimates for diabetes and transfusion history were independent of each other and were not changed substantially after adjustment for other risk factors. History of a previous cancer (excluding hematopoietic and lymphatic cancers) was associated with an increased risk of NHL (age-adjusted RR = 1.92; 95% CI = 1.21-3.06); this risk estimate was attenuated somewhat after adjustment for a history of diabetes, transfusion history, and other major risk factors (RR = 1.66; 95% CI = 1.02-2.69). No statistically significant associations were found between NHL and a history of chronic colitis, nonestrogen steroid use, use of exogenous estrogens, or use of thyroid medications. CONCLUSIONS AND IMPLICATIONS: A history of adult-onset diabetes mellitus, blood transfusion, and a history of cancer (or its treatment) appear to be independent risk factors for NHL in older women.

Age of Onset↗