Biomedical subjects

W Zheng

Publications and source records attributed to W Zheng.

At least 235 records · Page 13Linked to original sources

PubMed1996

Interaction of biphenylimidazole and imidazoleacrylic acid nonpeptide antagonists with valine 108 in TM III of the AT1 angiotensin receptor.

Interspecies amino acid exchange, based on pharmacological differences between mammalian AT1 and amphibian xAT angiotensin II receptors, previously demonstrated that Val108 in transmembrane III (ValIII:08) is a critical structural requirement for binding the biphenylimidazole, losartan. Here, we investigated a series of biphenylimidazole and imidazoleacrylic acid nonpeptides to determine the general role of Val108 in nonpeptide recognition. Substitution of Val108 in the rAT1b receptor with Ile, the corresponding residue in xATa, significantly reduced ligand affinities from both nonpeptide classes (Fmut values (mutant IC50/rAT1bIC50): losartan > L-162,389 > L-16,313 > L-162,017 = L-163,491 > SB-203,220 > SK&F-108,566). While distinct molecular requirements exist for biphenylimidazole and imidazoleacrylic acid binding, these results suggest that Val108 is a common structural determinant of nonpeptide recognition on the AT1 receptor.

Angiotensin I↗

PubMed1996

Follicle-stimulating hormone receptor is expressed in human ovarian surface epithelium and fallopian tube.

The cellular expression of pituitary gonadotropin receptors in gonadal tissues is poorly defined because of the lack of suitable reagents. In this study, we developed in situ hybridization and reverse transcription polymerase chain reaction techniques for the evaluation of follicle-stimulating hormone receptor (FSHR) expression in the ovary and fallopian tube. Using a single-strand RNA probe, we demonstrated that FSHR mRNA expression is strongest in Graafian follicles. Within these developing follicles, granulosa cells showed the greatest expression, although both theca interna and theca externa were also positive, interna greater than externa. Granulosa cells in both primary and primordial follicles were positive, with primordial follicles showing only weak focal positivity. Ovarian surface epithelium and fallopian tube epithelium, not previously recognized to express FSHR, were both strongly positive. The FSHR expression in the ovary and fallopian tube was confirmed by reverse transcription polymerase chain reaction. Our results indicated that the FSHR is expressed in a cell-specific fashion at different stages of follicular development and is also expressed in ovarian surface and fallopian tube epithelia. The presence of FSHR in ovarian surface epithelium and of gonadotropin-binding sites in ovarian neoplasms provide additional evidence supporting the derivation of epithelial ovarian tumors from the surface epithelium and should promote heightened interest in the gonadotropin theory of ovarian tumorigenesis. More importantly, this study shows the feasibility of evaluating FSHR expression by both in situ hybridization and reverse transcription polymerase chain reaction. Application of these techniques to tumor specimens will help to elucidate the role of gonadotropins and their receptors in the carcinogenesis of gynecological tumors.

Base Sequence↗

PubMed1996

Value of systematic transition zone biopsies in the early detection of prostate cancer.

PURPOSE: A prospective study was done to determine the value of performing 2 systematic transition zone biopsies in addition to systematic sextant peripheral zone biopsies for early detection of prostate cancer. MATERIALS AND METHODS: From January 1 to August 31, 1994 we evaluated 847 consecutive patients referred to us for a suspicious lesion on digital rectal examination or an elevated serum prostate specific antigen level. All patients underwent 2 systematic transition zone biopsies in addition to systematic sextant biopsies of the peripheral zone. RESULTS: Of the transition zone biopsies 68 (24.4%) contained malignancy, including only 8 (2.9%) with cancer found exclusively in the transition zone. The remaining 271 cases (97.1%) had 1 or more positive peripheral zone biopsies and would have been detected with or without additional systematic transition zone biopsies. The same analysis of 552 patients with a negative digital rectal examination yielded 6 (4.1%) exclusively transition zone tumors among 145 cancers detected in this group. CONCLUSIONS: The low additional yield of transition zone biopsies (2.9 to 4.1%) does not warrant their systematic use for the early detection of prostate cancer.

Adult↗

PubMed1996

[Assignment of differentiation-relevant cDNA RA538 on human chromosomes by fluorescence in situ hybridization].

OBJECTIVE: To localize the differentiation-relevant cDNA RA538 (3.8kb) onto the human chromosome 8q2. METHODS: A modified non-isotopic labeling technique was used. RESULTS: The cDNA RA538 was obtained by subtraction hybridization from human esophageal cancer cell line EC8712 induced by retinoic acid. Fluorescence in situ hybridization (FISH) using double-labeled probes showed clear and paired hybridization signals at the corresponding regions of both two chromatids in 18 out of 60 metaphases examined. While by single-labeling, only 7 were positive in 60 metaphases observed and the fluorescent spots were seen only at one chromatid. CONCLUSION: The modified FISH protocol is useful for mapping cDNA sequences of a few kilobases.

Antineoplastic Agents↗

PubMed1996

Weight variability and mortality: the Iowa Women's Health Study.

OBJECTIVE: To evaluate the association between weight variability and risk of mortality in women. DESIGN: Prospective cohort study, 1986-1991. SUBJECTS: Participants were a population-based sample of 33,760 Iowa women aged 55-69 y, free of cancer and heart disease, who completed a mailed questionnaire including self-reported weight at ages 18, 30, 40, 50 y, and currently. Weight variability was defined by (1) a measure of deviation from the linear regression of each woman's five weights on age (the root mean squared error, RMSE) and (2) categories of weight gain or loss. MEASUREMENTS: All-cause (n = 1068) and cause-specific mortality. RESULTS: After adjustment for age and the regression slope of weight on age, women who displayed higher weight variability (RMSE) over their adult years had an increased subsequent 6-y mortality. The relative risks of death for increasing quartiles of RMSE were 1.00 (referent), 1.17, 1.45 and 1.82 (ptrend < 0.001). Positive linear trends were seen across quartiles of RMSE for cardiovascular disease, cancer, and for non-cancer/non-cardiovascular deaths. These associations were attenuated increasingly with (1) statistical adjustment for body mass index, waist-to-hip ratio, smoking, education level, physical activity, alcohol intake, marital status and hormone replacement therapy; (2) further adjustment for diabetes and hypertension; and (3) exclusion of women in poor or fair health in 1986. Even so, with all adjustments, relative risks of coronary heart disease mortality for increasing quartiles of RMSE were 1.00 (referent), 1.22, 1.63 and 1.67 (ptrend = 0.049). Using the categorical approach, age-adjusted risks of death were highest in women who had a large weight loss (> 10%) or a large cycle of weight change (> or = 10% loss-gain or gain-loss), compared with women who had a stable weight (within 5%). Adjustment for covariates attenuated these relative risks. CONCLUSIONS: Women who displayed greater weight variability in adulthood had an increased risk of dying in later life, especially from coronary heart disease. However, to a considerable degree this association seems to be due to other unhealthy characteristics and pre-existing disease among those displaying increased weight variability.

Aged↗

PubMed1996

[The postnatal changes of follicle-stimulating hormone receptor mRNA level in rat testis].

It was found in this study that the follicle-stimulating hormone receptor (FSHR) mRNA levels varied between days 2 and 60. The FSHR mRNA rised slightly in the neonatal rat testis and then declined. In the prepuberty the content of FSHR mRNA remained at a Constant level. During the puberty the FSHR mRNA increased to its highest level on days 25 and finally it rised again after days 40.

Animals↗

PubMed1996

[Alteration of mRNA transcripts of rat Sertoli cell secreted proteins and Leydig cell LH/CG-R protein following glycosides of Tripterigium Wilfordii Hook administration].

Our studies were undertaken to assess the male antifertility mechanism of the total glycosides extracted from Tripterigium Wilfordii Hook. f. (GTW). In experimental group I, GTW was given by gastric gavage at a dose of 30 mg/kg per day for 35 days. In experimental group I, GTW was given in the same way at a dose of 10 mg/kg per day for 49 days. The transcripts level analysis indicated that in all the experimental groups ABP, SGP-2 and LH/CG-R mRNA were increased. Two ABP and two LH/CG-R mRNA transcripts with respective molecular sizes of 1.7 kb, 2.3 kb and 1.2 kb, 4.4 kb were identified. ABP and LH/ CG-R mRNA with 1.7 kb and 1.2 kb increased, while those with 2.3 and 4.4 kb remained unchanged. In addition, the changes of different proteins at the mRNA level were shown to be GTW dose-dependent. The morphological features of germ cell degeneration and appearance of germ cells in tubular lumen suggest that the increases in transcripts level of three proteins in testis may not be directly associated with the effect of GTW. The question whether GTW interfere with the function of sertoli cells and leydig cells would be study.

Androgen-Binding Protein↗

PubMed1996

[Molecular bypass, the application of VEGF to gene therapy of limb ischemia].

OBJECTIVE: To investigate the feasibility of using VEGF gene directly for treating limb ischemia. METHODS: The human VEGF165 cDNA was cloned into the eukaryotic expression vector pcDNA3 under the control of cytomegalovirus immediate-early promoter/enhancer. When gene suture was used, the recombinant plasmid was transferred into the hindlimb's adductor of rat, of which the distal extreme of external iliac artery was ligated and the femoral artery was completely excised. With RT-PCR, Western blot, immunohistochemistry analysis, and angiography, the expression and biological effects of VEGF gene in experimental animals were investigated. RESULTS: Seven days after initiation of therapy, the transcription and expression of VEGF gene in experimental group were significantly higher than those of control groups. The results from angiography, feet temperature measuring and observation of clinical symptom showed that the transfer of VEGF gene can stimulate the formation of focal neovessles, establish colleteral circulation, augment blood perfusion, and ameliorate distal limb necrosis. CONCLUSION: These findings reveal that the "molecular bypass" using VEGF gene may represent a potential therapeutic modality for treating tissue ischemia.

Animals↗

PubMed1996

Statistical geometry analysis of proteins: implications for inverted structure prediction.

The topology of folded proteins from the representative dataset of well-defined three-dimensional protein structures is studied using a statistical geometry approach. Amino acid residues in protein chains are represented by C alpha atoms, thus reducing the protein three-dimensional structure to a set of points in three dimensional space. The Delaunay tessellation of a protein structure generates an aggregate of space-filling irregular tetrahedra, or Delaunay simplices. Each simplex objectively defines four nearest neighbor C alpha atoms, i.e. four nearest neighbor residues. The statistical analysis of residue composition of Delaunay simplices reveals nonrandom preferences for certain quadruplets of amino acids. These nonrandom preferences are used to develop a fitness function that evaluates sequence-structure compatibility. Using this fitness function, several tested native proteins score the highest among 100,000 random sequences with average protein amino acid composition. The statistical geometry approach, based solely on first principles, provides a unique means for protein structure analysis and has direct implications for inverted protein structure prediction.

Amino Acid Sequence↗

PubMed1995

Prior immunity-related medical conditions and pancreatic-cancer risk in Shanghai.

To investigate the role of immunity-related medical conditions in the etiology of pancreatic cancer, we analyzed data from a population-based case-control study of pancreatic cancer conducted in Shanghai during 1992 and 1993. Information on prior histories of selected auto-immune diseases and allergic conditions was obtained from 108 incident pancreatic-cancer cases and 275 age- and gender-frequency matched controls by face-to-face interviews using a structured questionnaire. A prior history of auto-immune diseases was associated with a 2-fold elevated risk of pancreatic cancer (95% CI = 1.0-4.2), with an indication of a dose-response relation for the number of reported diseases. In contrast, a prior history of allergic condition was related to reduced risk (OR = 0.6, 95% CI = 0.4-1.1). With the possible exception of drug allergy, such an inverse association was seen for virtually all allergic conditions., although none of the OR was statistically significant. This study suggests that host immune function may be involved in the etiology of pancreatic cancer. Further investigations into the mechanism of these observed associations are warranted.

Adult↗

PubMed1995

Retinol, antioxidant vitamins, and cancers of the upper digestive tract in a prospective cohort study of postmenopausal women.

Very few prospective studies have reported previously on the association of micronutrient intake and the risk of cancers of the upper digestive tract (mouth, pharynx, esophagus, and stomach) in western populations. During 7 years of follow-up in the Iowa Women's Health Study, from 1986-1992, 59 of the 34,691 at-risk cohort members developed cancers of the upper digestive tract. The association of retinol and antioxidant vitamins (carotene and vitamins C and E) were evaluated separately for cancers of the mouth/pharynx/esophagus (n = 33) and stomach (n = 26). After adjustment for age, smoking, and total energy intake, higher intakes of carotene and vitamins C and E were related to lower risks of both oral/pharyngeal/esophageal and gastric cancers, while retinol was associated with lower risk of gastric cancer only. The dose-response relation between gastric cancer risk and intake of carotene was clear and statistically significant, with relative risks of 0.6 and 0.3, respectively, observed among women in the upper two versus the lowest tertiles of intake. This study provides further evidence that higher intake of antioxidant vitamins may be important in the prevention of cancers of the upper digestive organs.

Aged↗

PubMed1995

Genetic transfer of a nonpeptide antagonist binding site to a previously unresponsive angiotensin receptor.

Mutational analysis based on the pharmacological differences between mammalian and amphibian angiotensin II receptors (AT receptors) previously identified 7 aa residues located in transmembrane domains (TMs) III (Val-108), IV (Ala-163), V (Pro-192, Thr-198), VI (Ser-252), and VII (Leu-300, Phe-301) of the rat AT receptor type 1b (rAT1b receptor) that significantly influenced binding of the nonpeptide antagonist Losartan. Further studies have shown that an additional 6 residues in the rAT1b receptor TMs II (Ala-73), III (Ser-109, Ala-114, Ser-115), VI (Phe-248), and VII (Asn-295) are important in Losartan binding. The 13 residues required for Losartan binding in the mammalian receptor were exchanged for the corresponding amino acids in the Xenopus AT receptor type a (xATa receptor) to generate a mutant amphibian receptor that bound Losartan with the same affinity as the rAT1b receptor (Losartan IC50 values: rAT1b, 2.2 +/- 0.2 nM: xATa, > 50 microM; mutant, 2.0 +/- 0.1 nM). To our knowledge, this is the first report of a gain-of-function mutant in which the residues crucial to formation of a ligand binding site in a mammalian peptide hormone receptor were transferred to a previously unresponsive receptor by site-directed mutagenesis. Ala substitutions and comparison of mammalian and amphibian combinatorial mutants indicated that TM III in the rAT1b receptor plays a key role in Losartan binding. Identification of residues involved in nonpeptide ligand binding will facilitate studies aimed at elucidating the chemical basis for ligand recognition in the AT receptor and peptide hormone receptors in general.

Amino Acid Sequence↗

PubMed1995

Association of body mass index and body fat distribution with risk of lung cancer in older women.

Obesity has been associated with an increased risk of cancer at a number of sites. A notable exception appears to be lung cancer, for which several studies suggest a modest inverse association. However, cigarette smoking is directly associated with lung cancer and inversely associated with body mass index. To investigate the hypothesis that body mass index is associated with lung cancer independent of cigarette smoking, the authors analyzed data from a prospective cohort study of 41,837 Iowa women aged 55-69 years at baseline in 1986. In addition, they examined whether central adiposity (high waist/hip ratio) was associated with lung cancer incidence. Through 1992 (6 years of follow-up), 233 cases of lung cancer were identified through the State Health Registry of Iowa. The body mass index at several ages was calculated from self-reports of height at baseline and weights at ages 18, 30, 40, and 50 years and at baseline. Current and former smokers generally had lower mean body mass indices than did nonsmokers at all ages except 18 years. Cases generally had lower body mass indices than did noncases at all ages except 18 and 30 years but, among current smokers, cases had higher mean body mass indices than did noncases at all ages except baseline, although the differences were not statistically significant. An apparent positive association of a high waist/hip ratio with lung cancer in the total cohort was found to be primarily accounted for by a higher waist/hip ratio in current and former smokers. When stratified by smoking status and adjusted for other risk factors, including age and pack-years of smoking, the body mass index at baseline, body mass index at age 50 years, and waist/hip ratio were not associated with lung cancer. The results of multivariate analyses suggest that the inverse association of body mass index with lung cancer can be explained by smoking status and that the positive association of waist/hip ratio with lung cancer can be explained by pack-years of smoking.

Age Distribution↗

PubMed1995

Dietary intake of energy and animal foods and endometrial cancer incidence. The Iowa women's health study.

To assess the relations of dietary intake of energy and animal foods to endometrial cancer risk, dietary analyses were performed using data from a prospective cohort study of over 23,000 postmenopausal Iowa women who responded to a mailed questionnaire in 1986 and were followed through the end of 1992 for cancer incidence and total mortality. Usual intakes of 127 food items were measured by a semiquantitative food frequency questionnaire. After 7 years of follow-up, 216 incident endometrial cancer cases had been ascertained. There was no statistically significant association of dietary intake of energy and most animal foods with endometrial cancer incidence over the 7-year follow-up period. Stratified analyses, however, suggested that intake of energy from plant foods may be inversely associated with endometrial cancer risk in the latter years of follow-up (trend test, p = 0.03), while high intake of energy and foods from animal sources related to slightly, but not statistically significantly, elevated risks of this cancer in the earlier years of follow-up. The only significant dose-response relation observed in food group analyses was for processed meat and fish, for which a significant 50% excess risk of endometrial cancer was found among women in the highest versus the lowest tertile of intake. This study suggests that dietary intake of energy and most animal foods is not related to or is only weakly related to the risk of endometrial cancer among postmenopausal US women.

Cohort Studies↗

PubMed1995

Acquired neuromyotonia: evidence for autoantibodies directed against K+ channels of peripheral nerves.

Acquired neuromyotonia is characterized by hyperexcitability of motor nerves leading to muscle twitching, cramps, and weakness. The symptoms may improve following plasma exchange, and injection of immunoglobulin G (IgG) from 1 neuromyotonia patient into mice increased the resistance of neuromuscular transmission to d-tubocurarine. Here we examine nerves and muscle in vitro from mice injected with plasma or purified IgG from 6 neuromyotonia patients or pooled control subjects, and cultured dorsal root ganglion cells after treatment with IgG. Three of the patients had antibodies against human voltage-gated potassium channels labeled with 125I-alpha-dendrotoxin. The quantal release of acetylcholine (quantal content) at end-plates in diaphragms from mice treated with neuromyotonia IgG preparations was increased by 21% relative to control values (p = 0.0053). With one IgG preparation, the duration of the superficial peroneal nerve compound action currents was increased by 93%. The dorsal root ganglion cells treated with this IgG showed a marked increase in repetitive firing of action potentials. All effects were similar to those obtained with aminopyridines. We conclude that at least some patients with acquired neuromyotonia have antibodies directed against aminopyridine- or alpha-dendrotoxin-sensitive K+ channels in motor and sensory neurons, and they are likely to be implicated in the disease process.

4-Aminopyridine↗

PubMed1995

Mucinous adenocarcinoma of the endometrium with intestinal differentiation: a case report.

Mucinous differentiation of endocervical type has been well documented in endometrial carcinoma. However, we describe an unusual case of adenocarcinoma of the endometrium showing diffuse histological, immunohistochemical, and ultrastructural evidence of intestinal differentiation. Although intestinal differentiation has been described in mesodermally derived tissues including endocervix, ovary, and urinary tract, it has not been reported in normal endometrium. One previous case has been reported showing this pattern in endometrial carcinoma. Possible histogenetic mechanisms of this pattern are discussed.

Adenocarcinoma, Mucinous↗

PubMed1995

Endocrine, gonadal and behavioral responses of male crucian carp to the hormonal pheromone 17 alpha,20 beta-dihydroxy-4-pregnen-3-one.

The olfactory-mediated responses to the sex hormone 17 alpha,20 beta-dihydroxy-4-pregnen-3-one (17 alpha,20 beta-P) were studied in spermiated and regressed male crucian carp (Carassius carassius L.). The position and spontaneous locomotor activity of single male crucian carp were continuously recorded in an artificial stream. 17 alpha,20 beta-P (final concentration 10(-11) M) was supplied to one half and its ethanol carrier to the other half of the test area. Milt volume and gonadotropin (GtH-II) concentration in the plasma were also measured. The smell of 17 alpha,20 beta-P significantly increased both the GtH-II concentration in the plasma and the volume of strippable milt in spermiated crucian carp. Behaviorally, the side of the test area scented with 17 alpha,20 beta-P was significantly avoided by spermiated males. None of the described effects of 17 alpha,20 beta-P on spermiated males were observed for the regressed crucian carp. In view of the lack of response from regressed crucian carp we suggest that the observed avoidance behavior of 17 alpha,20 beta-P by spermiated males is a relevant reaction for spawning male crucian carp. The results are well in accordance with responses obtained in the closely related goldfish and gives strong support that the wild male crucian carp use the 17 alpha,20 beta-P signal from the females to prepare for the coming spawning.

Animals↗

PubMed1995

Infant breastfeeding and the risk of childhood lymphoma and leukaemia.

BACKGROUND: A protective effect of breastfeeding on childhood lymphoma has been indicated but supportive evidence is limited. METHOD: Data from a population-based case-control study of childhood cancer in Shanghai, including 82 lymphoma cases and 159 acute leukaemia cases and their age- and sex-matched community controls, were analysed. RESULTS: After adjustment for potentially confounding variables, a slight, although non-significant, reduction in risk of lymphoma was observed among children who were breastfed as infants versus those who were not (odds ratio [OR] = 0.69; 95% CI: 0.3-1.7). The reduction was somewhat greater for children who had been breastfed longer and appeared to pertain primarily to Hodgkin's disease and to cases diagnosed before the age of 6 years. As expected, there was no reduction in risk of acute leukaemia associated with breastfeeding. CONCLUSIONS: Although providing neither strong support for nor refuting the study hypothesis, these data suggest that if breastfeeding does reduce the risk of lymphoma, its protective effect among Chinese children is likely modest in magnitude and concentrated in certain subgroups defined by length of breastfeeding, age at diagnosis and histological subtype of cancer.

Acute Disease↗