Biomedical subjects

X Wu

Publications and source records attributed to X Wu.

At least 325 records · Page 18Linked to original sources

PubMed2000

Allelic variants of the follistatin gene in polycystic ovary syndrome.

In an earlier study of 37 candidate genes for polycystic ovary syndrome (PCOS), the strongest evidence for genetic linkage was found with the region of the follistatin gene. We have now carried out studies to detect variation in the follistatin gene and assess its relevance to PCOS. By sequencing the gene in 85 members of 19 families of PCOS patients, we found sequence variants at 17 sites. Of these, 16 sites have variants that are too rare to make a major contribution to susceptibility; the only common variant is a single base pair change in the last exon at a site that is not translated. In our sample of 249 families, the evidence for linkage between PCOS and this variant is weak. We also examined the expression of the follistatin gene; messenger RNA levels in cultured fibroblasts from PCOS and control women did not differ appreciably. We conclude that contributions to the etiology of PCOS from the follistatin gene, if any, are likely to be small.

Alleles↗

PubMed2000

The transcription factor dHAND is a downstream effector of BMPs in sympathetic neuron specification.

The dHAND basic helix-loop-helix transcription factor is expressed in neurons of sympathetic ganglia and has previously been shown to induce the differentiation of catecholaminergic neurons in avian neural crest cultures. We now demonstrate that dHAND expression is sufficient to elicit the generation of ectopic sympathetic neurons in vivo. The expression of the dHAND gene is controlled by bone morphogenetic proteins (BMPs), as suggested by BMP4 overexpression in vivo and in vitro, and by noggin-mediated inhibition of BMP function in vivo. The timing of dHAND expression in sympathetic ganglion primordia, together with the induction of dHAND expression in response to Phox2b implicate a role for dHAND as transcriptional regulator downstream of Phox2b in BMP-induced sympathetic neuron differentiation.

Animals↗

PubMed2000

Lentiviral vector transduction of hematopoietic stem cells that mediate long-term reconstitution of lethally irradiated mice.

Lentiviral vectors efficiently transduce human CD34(+) cells that mediate long-term engraftment of nonobese diabetic/severe combined immunodeficient mice. However, hematopoiesis in these animals is abnormal. Typically, 95% of the human cells in peripheral blood are B lymphocytes. To determine whether lentiviral vectors efficiently transduce stem cells that maintain normal hematopoiesis in vivo, we isolated Sca-1(+)c-Kit(+)Lin(-) bone marrow cells from mice without 5-fluorouracil treatment, and transduced these cells in the absence of cytokine stimulation with a novel lentiviral vector containing a GFP (green flourescent protein) reporter gene. These cells were transplanted into lethally irradiated C57Bl/6 mice. In fully reconstituted animals, GFP expression was observed in 8.0% of peripheral blood mononuclear cells for 20 weeks posttransplantation. Lineage analysis demonstrated that a similar percentage (approximately 8.0%) of GFP-positive cells was detected in peripheral blood B cells, T cells, granulocytes and monocytes, bone marrow erythroid precursor cells, splenic B cells, and thymic T cells. In secondary transplant recipients, up to 20% of some lineages expressed GFP. Our results suggest that quiescent, hematopoietic stem cells are efficiently transduced by lentiviral vectors without impairing self-renewal and normal lineage specification in vivo. Efficient gene delivery into murine stem cells with lentiviral vectors will allow direct tests of genetic therapies in mouse models of hematopoietic diseases such as sickle cell anemia and thalassemia, in which corrected cells may have a selective survival advantage.

Animals↗

PubMed2000

Improved controlled release study of lomustine.

Lomustine (CCNU) microcapsules was prepared by improved recoacervation method, then mixed microcapsules with 0.7% collagen swelling solution to prepare the emulsion, spreaded the emulsion on the plate to form membrane and cross-linked it, the membrane would be planted into body and was expected to release at steady speed. The concentration of CCNU and the CCNU content of microcapsules were measured by ultraviolet spectrophotometry to observe the release of CCNU be slow and constant, approach to 0-class release approximately.

Absorbable Implants↗

PubMed2000

pH-responsive swelling behavior of collagen complex materials.

This article deals with an natural collagen blended with chitosan, poly(vinyl alcohol)(PVA). We investigated the swelling properties of collagen and collagen complex in the solution with different pH, and the swelling/deswelling behavior of collagen and collagen-chitosan complex when changing the pH of the medium from 5.4 to 1.8 and in the reverse. The results show that the swelling degree of collagen and collagen complex are dependent to pH of the solution, and the swelling behavior of collagen and collagen-chitosan complex are pH-responsive.

Absorption↗

PubMed2000

Gamma-radiation-induced single cell DNA damage as a measure of susceptibility to lung cancer: a preliminary report.

The comet assay is a sensitive and rapid method for detecting DNA single-strand and double-strand breaks and the individual cell's DNA repair profile. This pilot study was designed to determine whether the comet assay could measure inherited susceptibility to lung cancer. We applied the comet assay in the alkaline condition to test the DNA damage in gamma-irradiated and untreated cultured peripheral blood lymphocytes of 31 cases with previously untreated lung cancer and 39 controls. For each culture, 200 consecutive cells were examined and the number of cells with DNA uncoiling under electrophoresis ( ) was recorded. The comet tail length (the radius of the nucleus plus the length of the migrated DNA) at 400-fold magnification was measured for the first 50 identified comet cells. The mean number of induced comet cells was significantly higher in cases (96.0+/-45.7) than matched controls (68.9+/-35.8) (P<0.05). However, no significant difference was observed in induced comet tail length between cases and controls. When we categorized the number of comet cells by the 75th percentile value in the controls, a higher number of comet cells was associated with significantly increased risk for lung cancer [odds ratio = 4.8 (confidence intervals of 1.5, 15.2)] after adjustment for age, sex, ethnicity and smoking status. The number of gamma-irradiation-induced comet cells (r=0.499, P<0.05) and comet tail length (r=0.520, P<0.05) correlated with the results on a previously reported lung cancer susceptibility marker, bleomycin sensitivity. Also, the number of gamma-irradiation-induced comet cells correlated with the results of the benzo[alpha]pyrene diol epoxide mutagen sensitivity assay, which quantifies induced chromatid breaks (r=0.275, P<0.05). The comet assay might be a simple and inexpensive tool for detecting genetic susceptibility to lung cancer.

Adult↗

PubMed2000

Association between delayed cardioprotection of aged rat myocytes and activation of mitogen-activated protein kinase.

OBJECTIVE: To study the cardioprotective effects of hypoxic preconditioning (HPC) on aged rat ventricular myocytes and the cellular mechanism of protection. METHODS: In the model of hypoxia/reoxygenation (H/R) of isolated ventricular myocytes of aged rat, the effects of HPC on aged rat ventricular myocytes against lethal H/R stimulated ischemia/reperfusion (I/R) injury 24 hours later and the changes of mitogen-activated protein kinase (MAPK) system were observed in the present study. RESULTS: HPC attenuated the lactate dehydrogenase (LDH) release and ATP depletion in myocytes and increased the viability of myocytes. It was also found that MAPK and its down-stream kinase--S6 kinase were also activated after HPC. CONCLUSION: There is delayed cardioprotection in cardiac myocytes of aged rat and the cellular mechanism underlying might involve the activation of MAPK system.

Adenosine Triphosphate↗

PubMed2000

[Experimental study on value of carcino-embryonic gama-glutamyl transferase isoenzymes for monitoring carcinogenesis of hepatocytes].

OBJECTIVE: To explore the value of gama-glutamyl transferase (GGT) abnormal expression in monitoring carcinogenesis of hepatocytes. METHODS: The kinetic alterations of rat (SD) liver pathology, enzymatic histochemistry, total RNA levels, different molecular form GGT and its isoenzymes were investigated on experimental hepatomas inducing with 0.05% 2-fluoenylacetamide (2-FAA). RESULTS: The GGTs of livers were overexpressed during canceration, liver GGT specific activities (U/g) including soluble and membrane-combined GGT activities of each group in experiment rats were significantly higher (q=4.90, P<0.01) than those of control group. The total RNA concentration was highly positively correlated with liver GGT specific activities or serum GGT activities (r=0.90, r=0.79, P<0.01). The mixed isoenzyme patterns of control rats' and embryo rats' GGT were found in sera and livers of experimental rats, the carcino-embryonic GGT bands can be detected at early stages of rat hepatocyte canceration. CONCLUSIONS: The present data suggest that GGT is a sensitive enzyme for carcinogenesis of hepatocytes, the analysis of carcino-embryonic GGT is a useful marker for early diagnosis of rat hepatoma.

Animals↗

PubMed2000

Apoptosis, cellular proliferation and expression of p53 in human uterine leiomyomas and myometrium during the menstrual cycle and after menopause.

BACKGROUND: Cell proliferation, apoptosis and expression of p53 proteins were studied in human uterine leiomyomas and myometrium during the menstrual cycle and after menopause. METHODS: Expression of ki-67 and p53 was analyzed by immunohistochemistry and by immunoblotting. Apoptosis was detected by in situ 3' end labelling of cells with DNA fragmentation. RESULTS: In both the proliferative and the secretory phases, ki-67 expression was higher in leiomyomas than in myometrium and both tissues showed higher expression in the secretory than in the proliferative phase. No difference in apoptotic index was observed between leiomyomas and myometrium or between the proliferative and secretory phases. After menopause, the expression of ki-67 as well as the apoptotic index was lower than in the proliferative and secretory phases and no significant difference between tissues was seen. Both leiomyomas and myometrium showed negative staining for p53. Immunohistochemical results regarding p53 were confirmed by Western blot. CONCLUSIONS: Our findings indicate that sex steroids influence the growth of leiomyomas by stimulating cell proliferation rather than by affecting apoptosis. The rate of cell proliferation is higher in fertile age than after menopause and appears to be enhanced under the influence of progesterone.

Adult↗

PubMed2000

Genetic variants of myeloperoxidase and lung cancer risk.

The cytochrome P450 family of enzymes is responsible for many of the initial metabolic conversions of procarcinogenic compounds in tobacco smoke to reactive metabolites. However, other enzyme-based systems such as myeloperoxidase (MPO) may also be involved in this metabolic process. MPO is a phase I metabolic enzyme that has a polymorphic region upstream of the gene that appears to reduce transcriptional activity. The polymorphic G-->A nucleotide base shift negates the binding region for the general transcription factor SP1. Thus, individuals with the variant allele may be provided with a protective effect due to decreased metabolic conversion of carcinogenic compounds in tobacco smoke. This study has investigated the hypothesis that individuals with the variant allele may be at a reduced risk for lung cancer. Our results demonstrate that the protective effects of the MPO variant allele reduced overall lung cancer risk in Caucasians by 48% (OR = 0.52, 95% CI 0.30-0.90, P = 0.02). There was a 72% protective effect (OR = 0.28, 95% CI 0.12-0.61, P < 0.05) evident in men but not in women. Additionally, in younger individuals (<61 years) there was a statistically significant 72% reduction in risk (OR = 0.28, 95% CI 0. 11-0.69, P < 0.05) but not in older individuals. A protective effect was observed for current smokers (OR = 0.24, 95% CI 0.10-0.58, P < 0. 05) but not in former smokers and those who had never smoked. These data demonstrate that there is a reduction in lung cancer risk associated with a variant allele of MPO that is evident in men, younger individuals and current smokers.

Base Sequence↗

PubMed2000

Correlation between bone mineral density and sexual hormones in healthy Chinese women.

Osteoporosis is a common disease in women, but not in men. It is usually induced by the deficiency of estrogen after menopause. The lumbar spine is most often affected. We examined 74 healthy Chinese women in whom we measured serum estradiol (E2), estriol (E3), and total testosterone (TTT) by radioimmunoassay (RIA). The bone mineral density (BMD) of the total lumbar spine in the anterior (TLS-A) and lateral (TLS-L) position, the region of interest (ROI) of lateral spine (M-IALS), the forearm, and the total hip (TH) were scanned by a dual-energy X-ray absorptiometer. We found that (1) E2 and all BMD determinations declined significantly after menopause (p < 0.05 for all), except the BMD of TH; (2) the BMD of TLS-L, TH, and forearm correlated significantly with E2 (r = 0.2986, p < 0.05), E3 (r = 0.3380, p < 0.05), and TTT (r = 0.2867, p < 0.05), respectively, by partial correlation analysis. In conclusion, BMD at different sites of the skeleton correlated with the level of different sex hormones. It seems that BMD at different sites of the body is controlled by different sex hormones. Whether this phenomenon should be considered in the choice of hormone replacement therapy, or in improving the BMD diagnostic standard, needs further study.

Adult↗

PubMed2000

Contribution of nitrosobenzene to splenic toxicity of aniline.

To elucidate the mechanism(s) of splenic toxicity of aniline, studies were conducted with nitrosobenzene (NB), an N-oxidized metabolite of aniline. Male Sprague-Dawley rats were given 0.025, 0.05, 0.1, or 0.2 mmol/kg/d of NB in 0.5 ml of 0.25% agar by gavage for 4 d; control rats received the vehicle only. Animals were euthanized at 24 h following the last dose. NB treatment resulted in decreased erythrocyte counts, whereas methemoglobin content increased at 0.1- and 0.2-mmol/kg doses. Spleen weight to body weight ratios were greater by 55 and 81% at O.1- and 0.2-mmol/kg NB doses, respectively. Total iron content in the spleens of NB-treated rats showed dose-dependent significant increases, and the nonheme iron followed a similar pattern. Splenic lipid peroxidation showed a dose-dependent response and was greater by 19, 56, 74, and 85% at the 4 doses, respectively. Malondialdehyde (MDA)-protein adducts, as quantitated by a competitive enzyme-linked immunosorbent assay (ELISA), were markedly greater in all the NB-treated groups, with the highest increase of 248% at 0.2 mmol/kg. Furthermore, NB exposure also resulted in greater protein oxidation (carbonyl content) in the spleens at 0.1- and 0.2-mmol/kg doses. These results suggest that NB is a splenotoxin and therefore can contribute to the splenic toxicity of aniline. Results of this study further support our earlier findings that oxidative stress is a potential mechanism in the splenotoxicity of aniline.

Aniline Compounds↗

PubMed2000

Statistical models for analysis of cytogenetic biomarkers.

BACKGROUND: Bleomycin-induced chromosomal breaks (CB) and sister chromatid exchange (SCE) in peripheral blood lymphocytes have been shown to be sensitive cytological markers for susceptibility to DNA damage in patients with various types of cancer and in healthy controls. Factors such as age, sex, smoking, and alcohol consumption could affect the values of some of these biomarkers and should be considered as covariates when analyzing cytogenetic biomarkers because these factors can affect the frequency of CB and SCE. METHODS: We propose a statistical method using negative binomial (NB) distribution to evaluate the numbers of CB and SCE. In order to determine the best model to represent the frequency of CB and SCE, we compared the NB model with the widely used Poisson model and log-transformed normal model by using generalized linear models. To demonstrate the better fit of the NB model, we analyzed three different data sets from studies conducted at The University of Texas M.D. Anderson Cancer Center. The first set was a case-control study of lung cancer in a population of African Americans and Mexican Americans (286 cases and 156 controls), the second set consisted of 311 head and neck cancer patients, and the third set consisted of 105 Hodgkin's disease patients. RESULTS: For CB; the estimates of the variability for Hodgkin's disease, head and neck, and lung cancers were 487.24, 502.82, and 520.15, respectively. For SCE, the estimates of the variability for Hodgkin's disease was 9777.01. For CB, the dispersion estimates under the three models (Poisson, NB, and Normal) for Hodgkin's disease, head and neck, and lung cancers were: 12.30, 1.20, 0.85; 8.94, 1.05, 0.22; and 10.10, 1.05, 0.25, respectively. For SCE (Hodgkin's disease only), the dispersion estimates under the three models (Poisson, NB, and Normal) were 30.91, 1.11, 0.10, respectively. CONCLUSIONS: Our results demonstrate that the NB model provides a better interpretation and fit for the frequency of CB and SCE in different cancer types. Therefore, we recommend it as a model for the analysis of cytogenetic biomarkers.

Biomarkers↗

PubMed2000

Clinical observation and experimental study on compound hypoglycemic decoction for hyperglycemia.

PURPOSE: To observe the clinical efficacy of Compound Hypoglycemic Decoction (CHD) and its effect on serum total cholesterol in model mice. METHOD: The paired t test was used to analyze the data recorded before and after administration of drugs for hyperglycemia induced by intraperitoneal injection of 75% egg yolk emulsion in experimental mice. CHD and Fenofibrate were administered as prevention measures. RESULTS: The total effective rate of serum total cholesterol (TC) decrease in 60 cases of hyperglycemia was 86.66% and that of serum total triglyceride (TG) decrease was 81.81%. The total effective rate of high-density lipoprotein-cholesterol (HDL-C) increase was 75%. The decrease in TC and TG, and the increase of HDL-C after treatment by in-group comparison were all significant (P < 0.05). 21.9% and 22.2% decrease in the total cholesterol was respectively found in the CHD and Fenofibrate groups (both P < 0.05), with no significant difference. CONCLUSION: The hypoglycemic action of Compound Hypoglycemic Decoction was remarkable in clinical practice, and it is very effective in preventing hyperglycemia in experimental mice.

Adult↗

PubMed2000

Bacteriophage infections in the industrial acetone butanol (AB) fermentation process.

The reported incidence and effects of bacteriophage infections occurring in the industrial acetone butanol (AB) fermentation processes operated in the USA, Japan, and Puerto Rico during the earlier part of the twentieth century is reviewed. The growth characteristics and solvent-producing ability of a lysogenic strain of Clostridium madisonii isolated from a phage infection in Puerto Rico was determined in molasses fermentation medium. The host strain harbours a large lysogenic phage belonging to the Siphoviridae and the growth rate of the lysogenic strain was found to be slower than the non-lysogenic parent strain and exhibited reduced solvent production. The history of phage infections that occurred in the South African AB process is documented along with the various remedial actions that were taken to restore production. A more detailed account of the last phage infection that occurred in 1980 involving a small pseudo-lysogenic phage belonging to the Podoviridae is given. This phage infected Clostridium beijerinckii P260 and a number of closely related industrial strains. Factory-scale fermentations contaminated by this phage were compared with equivalent laboratory-scale control fermentations. The effect of the phage infection in the full-scale and laboratory-scale fermentations were monitored. Results obtained in laboratory-based studies included an assessment of the effect of the multiplicity of infection and the timing of phage infection. The general effects and symptoms of phage infections in the industrial AB fermentation are reviewed including gross changes in the fermentation and changes in cell morphology. Common techniques used for the diagnosis of phage infections and approaches for controlling phage contamination in the AB fermentation are discussed. Prevention strategies included good factory hygiene, sterilisation, decontamination and disinfection, and the use of resistant strains immunised against specific phages.

Acetone↗

PubMed2000

Dietary intake of isothiocyanates: evidence of a joint effect with glutathione S-transferase polymorphisms in lung cancer risk.

Isothiocyanates (ITCs) are nonnutrient compounds in cruciferous vegetables with anticarcinogenic properties. One proposed mechanism for their protective action is through down-regulation of cytochrome P-450 biotransformation enzyme levels and induction of phase II detoxifying enzymes. Because ITCs also serve as a substrate for GSTs, we evaluated dietary intake of ITCs and GSTM1 and GSTT1 genotype information in a lung cancer case-control study. There were 503 newly diagnosed lung cancer cases (264 men and 239 women) identified from The University of Texas M. D. Anderson Cancer Center and 465 controls (252 men and 213 women) recruited from enrollees in a local managed care organization. Subjects had an in-person interview including a semiquantitative food frequency questionnaire, and blood samples were obtained for genotyping. Cases reported significantly lower ITC intake per day compared with controls (P = 0.009). There was no main effect associated with the GSTM1 null genotype [odds ratio (OR) = 1.09]. However, there was a statistically significant OR of 1.41 associated with the GSTT1 null genotype. On stratified analysis, low ITC intake and the GSTM1 null genotype were associated with increased lung cancer risk in current smokers, with an OR of 2.22 [confidence interval (CI) = 1.20-4.10). For current smokers with the GSTT1 null genotype, the OR with low ITC intake was 3.19 (CI = 1.54-6.62). The comparable OR in the presence of both null genotypes was 5.45 (CI = 1.72-17.22). These effects were not demonstrable for former smokers by GSTM1 genotype, although the risk for low ITC intake and GSTT1 null genotype was 1.79 (CI = 0.95-3.37). Thus, current smokers who are homozygous null for the GST null genotype and who consume less carcinogenic blocking compounds are at higher lung cancer risk. Some of the inconsistencies reported in the role of GST genotypes in lung cancer risk could be due to unexpected confounding from dietary factors.

Aged↗

PubMed2000

D2 dopamine receptor gene polymorphisms among African-Americans and Mexican-Americans: a lung cancer case-control study.

Recent research suggests that variant alleles (A1 and B1) of the DRD2 gene play a role in determining smoking status. However, no studies have evaluated these variant alleles in African-Americans and Mexican-Americans. The primary objective of this study, therefore, was to test the hypothesis that ever smokers in these ethnic groups are more likely than never smokers to have the DRD2 alleles associated with tobacco use (A1 and B1). Furthermore, because of a predicted higher prevalence of smokers in a family because of the patterns of inheritance of the genotypes associated with tobacco use, we also anticipated that individuals with these at-risk DRD2 alleles would be more likely to have a family history of smoking-related cancers. Because other inherited genetic variants may interact with smoking on cancer risk, we also hypothesized that this association might differ between cancer patients and control subjects. PCR was used to perform genotyping on peripheral WBC DNA from 140 lung cancer patients (43 Mexican-Americans and 97 African-Americans) and 222 age-, sex-, and ethnicity-matched controls (111 Mexican-Americans and 111 African-Americans). A personal family history was obtained from each participant. There were no statistically significant differences in the distribution of the DRD2 genotypes between cases and controls, although the frequency of the B1 genotype significantly differed by ethnicity (P = 0.002 for controls and P = 0.001 for cases). The DRD2 genotypes and smoking status showed a correlation among Mexican-American controls, although not among African-American controls. The cigarette pack-years in control subjects for the two ethnic groups combined were 30.8, 21.9, and 18.6 for the A1A1, A1A2, and A2A2 genotypes and 36.5, 20.8, and 18.5 for the B1B1, B1B2, and B2B2 genotypes, respectively. Similar trends were found for the number of cigarettes smoked per day among control subjects. From the standpoint of polymorphisms, however, there was a borderline significantly increased (3.6 times greater) frequency of smoking-related cancers among the first-degree relatives of case subjects with an A1 allele than among those without an A1 allele. There was also an elevated (1.8 times greater) frequency of smoking-related cancer among first-degree relatives of case subjects with a B1 allele compared with patients without a B1 allele, but this finding was not statistically significant. This phenomenon was not observed among control subjects. We noted a trend toward interaction of DRD2 A1 genotypes and case status for increased risk of smoking-related cancer among first-degree relatives. These findings suggest that the variant DRD2 genotypes are associated with a greater likelihood to smoke and a greater smoking intensity, as well as with a familial aggregation of smoking-related cancers. However, a large study is needed to confirm this finding.

Aged↗

PubMed2000

[Prospective study on the relationship between treatment duration of antithyroid drug and remission rate of Graves' disease].

OBJECTIVE: To compare the potential benefits of 36-month treatment with 6- and 18-month treatment of antithyroid drug in patients with hyperthyroidism due to Graves' disease (GD). METHODS: 183 GD patients were studied prospectively. All patients received methimazole (MMI) at decreasing doses for 6, 18 or 36 months. The relapse rates 18 months after MMI withdrawal were compared between the three therapy groups. RESULTS: The relapse rate 18 months after the discontinuation of treatment was higher in patients treated for 6 months than in those treated for 18 or 36 months. There was no significant difference between 18-month and 36-month treatment groups. At the end of therapy, serum thyroid stimulating antibody (TSAB) and TSH receptor antibody (TRAB) titers were greater in patents treated for 6 months (320 +/- 191 for TSAB and 8.72 +/- 5.23 for TRAB) and 18 months (165 +/- 87 and 4.55 +/- 4.17) than in those treated for 36 months (126 +/- 77 and 2.19 +/- 2.64), but no statistical difference was found between the three groups before MMI treatment. TSAB and TRAB titers were higher in patients who relapsed after discontinuation of MMI (287 +/- 94 and 6.14 +/- 2.37, respectively) compared with those who remained euthyroid through the 18-month follow-up period (144 +/- 61 and 1.97 +/- 1.06). CONCLUSIONS: Negative TSAB or TRAB at the end of antithyroid therapy is a good indicator for a long-term remission after treatment withdrawal. However, treatment duration greater than 18 months does not improve remission rate of GD.

Adolescent↗