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Biomedical subjects

G Qin

Publications and source records attributed to G Qin.

At least 19 recordsLinked to original sources
PubMed2006

The long-term impact of 2-3 years of hormone replacement therapy on cardiovascular mortality and atherosclerosis in healthy women.

OBJECTIVE: The effect of hormone replacement therapy (HRT) on cardiovascular risk is intensely debated. The aim of this study was to investigate the long-term effects of HRT given for a few years on all-cause and cardiovascular mortality and the severity of atherosclerosis. METHODS: This analysis was based on a cohort of 1,458 postmenopausal women (55.8 +/- 6.1 years old) who previously participated in a number of randomized, placebo-controlled, clinical trials assessing the efficacy of 2-3 years of therapy with various estrogen plus progestin combinations for preventing bone loss. Women were followed on average for 9.8 years and came for a follow-up visit. Outcome variables were all-cause and cardiovascular mortality and the severity of atherosclerosis, as estimated by semi-quantitative scoring of vascular calcification in the lumbar aorta on lateral radiographs. RESULTS: A total of 174 women died during the observation period. All-cause mortality was decreased by 30% in the HRT+ group compared with the HRT- group (hazard ratio (HR) 0.70; 95% confidence interval (CI) 0.50-0.97) after adjusting for age, body mass index and smoking. Under the same conditions, similar results characterized mortality from cardiovascular disease (n = 61 deaths; 35.1% of all deaths) and coronary heart disease (n = 39 deaths; 22.4% of all deaths), which were decreased by 46% (HR 0.54, 95% CI 0.29-0.98, p = 0.045) and 53% (HR 0.47, 95% CI 0.21-1.03, p = 0.062), respectively. Furthermore, the mean severity score of aortic calcification at follow-up was significantly lower in hormone-treated compared to non-treated women (p < 0.0001). CONCLUSION: Women who receive 2-3 years of HRT after menopause do not have increased all-cause mortality, and results of the present study suggest relative cardiovascular benefits compared to those who had not used hormones.

Adult↗
PubMed2006

Radiographic measure of aorta calcification is a site-specific predictor of bone loss and fracture risk at the hip.

OBJECTIVE: To investigate whether aorta calcification (AC) - a surrogate marker of atherosclerosis - is an independent indicator of low bone mass density (BMD), accelerated bone loss, and risk of future fractures in postmenopausal women. DESIGN: A prospective epidemiological study. Follow-up period was 7.5 years. SETTING: Community-based sample followed by a research institute. SUBJECTS: A total of 2662 generally healthy postmenopausal women with a mean age of 65.0 +/- 7.1 years at baseline. MAIN OUTCOME MEASURES: Annual rate of changes in BMD (DEXA) and AC (X-rays), vertebral fractures (X-rays), hip fractures (questionnaire). RESULTS: Advanced AC at baseline was significantly associated with lower BMD and accelerated bone loss from the proximal femur. In a multivariate logistic regression model, age (OR 1.1, 95% CI 1.0-1.2, P = 0.02), body mass index (BMI; OR 0.9, 95% CI 0.8-1.0, P = 0.03) and the severity of AC (OR 2.3, 95% CI 1.1-4.8, P = 0.03) were independent predictors of hip fractures. Adjusted OR for vertebral fracture was 1.2 (95% CI 1.0-1.5, P = 0.12). CONCLUSIONS: Aorta calcification seems to independently contribute to the development of osteoporosis in the proximal femur. Further studies are needed to clarify whether effective atherosclerosis prevention lowers hip fracture risk.

Absorptiometry, Photon↗
PubMed2001

Differential effects of acetaminophen pretreatment on hepatic aflatoxin B(1)-DNA binding, cellular proliferation, and aflatoxin B1-induced hepatic foci in rats and hamsters.

Effects of acetaminophen (AAP) pretreatment on hepatic aflatoxin B1 (AFB(1))-DNA binding, cellular proliferation, and AFB(1)-induced glutathione S-transferase placental form (GST-P) positive hepatocytes and foci have been examined in young male rats and hamsters. Intraperitoneal (i.p.) dosing of 600mg AAP 3h before AFB(1) i.p. injection showed three-fold more AFB(1)-DNA binding in hamsters and 40% less binding in rats. Cell proliferation analyzed by bromodeoxyuridine incorporation was not significant (0.4-0.6%) 24-96h after AAP (600mg) treatment of rats; however, proliferation was stimulated and was maximum (11%) in hamsters at 72h after AAP treatment. Dosing of rats with AFB(1) alone at 0.5 or 2.5mg level gave an appreciable number of GST-P positive minifoci (two to nine cells) with a few foci larger than 100 microm; pretreatment with AAP (300 or 600mg) 48h before 0.5 or 2.5mg AFB(1) had no effect on the number and focal area of foci. In hamsters, 1 or 2mg AFB(1) alone yielded GST-P positive hepatocytes without any minifoci. Pretreatment with AAP (600mg) 48 or 72h before 1 or 2mg AFB(1) produced increases in both GST-P positive hepatocytes and minifoci. Thus, marked changes are observed after AAP pretreatment in hamsters compared to rats.

Acetaminophen↗
PubMed2001

Preselective gene therapy for Fabry disease.

Fabry disease is a lipid storage disorder resulting from mutations in the gene encoding the enzyme alpha-galactosidase A (alpha-gal A; EC ). We previously have demonstrated long-term alpha-gal A enzyme correction and lipid reduction mediated by therapeutic ex vivo transduction and transplantation of hematopoietic cells in a mouse model of Fabry disease. We now report marked improvement in the efficiency of this gene-therapy approach. For this study we used a novel bicistronic retroviral vector that engineers expression of both the therapeutic alpha-gal A gene and the human IL-2Ralpha chain (huCD25) gene as a selectable marker. Coexpression of huCD25 allowed selective immunoenrichment (preselection) of a variety of transduced human and murine cells, resulting in enhanced intracellular and secreted alpha-gal A enzyme activities. Of particular significance for clinical applicability, mobilized CD34(+) peripheral blood hematopoietic stem/progenitor cells from Fabry patients have low-background huCD25 expression and could be enriched effectively after ex vivo transduction, resulting in increased alpha-gal A activity. We evaluated effects of preselection in the mouse model of Fabry disease. Preselection of transduced Fabry mouse bone marrow cells elevated the level of multilineage gene-corrected hematopoietic cells in the circulation of transplanted animals and improved in vivo enzymatic activity levels in plasma and organs for more than 6 months after both primary and secondary transplantation. These studies demonstrate the potential of using a huCD25-based preselection strategy to enhance the clinical utility of ex vivo hematopoietic stem/progenitor cell gene therapy of Fabry disease and other disorders.

3T3 Cells↗
PubMed2001

Antigenic load and peripheral chimeric levels in entire and partial liver allograft recipients.

Orthotopic partial liver transplantation (PLT) models were developed in rats to explore the unique role of the liver in transplant tolerance. In PVG rats, syngeneic PLT established that surgical reduction to one-third of the liver and orthotopic transplantation permitted survival. Allogeneic PLT in the PVG to DA liver-tolerant model, both 50% and 33%, did not affect the tolerogeneic property of the liver, with all PLT recipients surviving indefinitely. Blood samples taken at various time points for detection of donor cells using flow cytometry showed a steady increase in donor cell chimerism in both PLT and whole liver transplantation (WLT) recipients that persisted throughout the 3-month observation period. At each time point, the level of donor cell chimerism in PLT was higher than that in WLT. We conclude that transplantation of one-third of the liver is compatible with survival in rats. Reduction of antigenic load by means of hepatectomy does not affect the tolerogenic effect of the liver in the PVG to DA LT model because of the remarkable regeneration capability of the liver. Peripheral chimeric levels increase progressively after WLT, suggesting that this is an ongoing immunological phenomenon. The earlier and increased chimerism after PLT may be associated with liver regeneration.

Animals↗
PubMed2001

Chemical constituents from Dendrobium densiflorum.

5-[2'-(3"-Hydroxy-5"-methoxyphenyl)-ethyl]-1,3-benzodioxole and 7-hydroxy-2-methoxy-1,4-phenanthrenedione, along with 16 known compounds were identified from the stems of Dendrobium densifiorum Lindl. ex Wall. (Orchidaceae). The structure of a previously reported compound dendroflorin obtained from the plant was revised on the basis of spectroscopic analysis. Among the identified compounds, five were found to exhibit anti-platelet aggregation activity in vitro.

Animals↗
PubMed2001

[Lignans from Schisandra propinqua (Wall.) Hook. f. et Thoms].

Three dibenzocyclooctadiene lignans were isolated from the stems of Schisandra propinqua (Wall.) Hook.f.et Thoms. Their structures were identified as interiotherin A (I), benzoylisogomisin O (II) and gomisin G (III) by spectroscopic analysis. Compound I was first discovered in Schisandra genus. Compounds II and III were originally isolated from S. propinqua.

Lignans↗
PubMed2001

[Study on the epidemiology and factors influencing the behavior of school children in Taiyuan].

OBJECTIVE: To study the epidemiological features and factors influencing behavior problems of school children in Taiyuan. METHODS: One thousand five hundred and ninety-seven school children aged 6 - 11 years selected from three schools differently located in three city proper were measured by Achenbach Child Behavior Checklist. RESULTS: Pervaleuce rate of children having behavior problems averaged 12.34%, with 12.40% in boys and 12.27% in girls. If was found higher in Hexi than in other two schools. The total scores of CBCL hyperkinesia and discipline violation among boys were higher than that of girls. The score including depression, somatic problem, and social withdraw of girls was found higher than that of boys. The result of multiple regression indicated that factors as interest in study, easy rearing, and good living condition when mother was in pregnancy were possibly benefit to behavior development in children, while beating and scolding children, indifference toward children, and particular preference of diet seemed to be the main risk factors affecting children's behavior. CONCLUSION: There appeared different rates of childrens behavior problems among pupils. The scores of CBCL were different between boys and girls. It is essential to adopt comprehensive measures for the prevention of behavior problems in children.

Child↗
PubMed2001

Effects of combined ozone and air pollution particle exposure in mice.

Epidemiologic studies indicate that ozone (O3*) and air pollution particles can exacerbate asthma symptoms. We investigated whether coexposure to inhaled particles and O3 causes a synergistic effect on airway responsiveness and allergic inflammation in a murine (BALB/c) model of ovalbumin (OVA)-induced asthma. Half of the mice were sensitized by intraperitoneal injection of OVA and then exposed to OVA aerosol on 3 successive days to create the asthmatic phenotype; the other half were sensitized to OVA and exposed to phosphate-buffered saline (PBS) to create the nonasthmatic control group. On the same 3 days that the OVA or PBS challenge was administered, mice were further divided into groups that were exposed for 5 hours to concentrated ambient particles (CAPs; mass values ranging from 63 to 1,569 microg/m3 for 1 day's exposure), 0.3 ppm O3, both, or neither (n > or = 61 total mice per exposure group for all 12 experiments). Whole-body plethysmography was used to measure airway responsiveness after challenge with aerosolized methacholine (MCh). Enhanced pause (Penh), an index that closely correlates with pulmonary resistance (Hamelmann et al 1997), was measured daily in each mouse immediately after pollutant exposure and, for 7 of the 12 experiments (n > or = 36/exposure group), beginning 24 hours after the final OVA or PBS challenge. Using several complementary statistical models, we found that exposure to CAPs alone caused a small but significant increase in Penh in both normal and asthmatic mice immediately after exposure (an increase of approximately 1% per 100-microg/m3 increase in CAPs). No increase in Penh was found in animals exposed to O3 alone or to filtered air. Compared with control animals, no combination of exposure atmosphere plus asthma produced a synergistic effect on Penh. By 24 hours after the last OVA or PBS challenge, any enhanced response induced by pollutant exposure had declined to control levels. The pollutant exposures did not significantly increase airway inflammation (assessed by bronchoalveolar lavage [BAL] fluid analysis beginning 24 or 48 hours after the final OVA or PBS challenge). Because CAPs are a heterogeneous mixture of particles, elemental analysis was conducted and associations between specific elemental groupings (present in daily samples) and airway responsiveness were analyzed. This analysis showed that increased Penh in asthmatic mice exposed to CAPs plus O3 was associated with the AlSi fraction of CAPs. No such association was found in control mice or in asthmatic mice not exposed to O3. We conclude that CAPs exposure causes an immediate, short-lived (< 24-hour), small increase in airway responsiveness in mice and that changes in airway physiology are correlated with specific elements found within the particle mixture.

Air Pollutants↗
PubMed2000

Long-term enzyme correction and lipid reduction in multiple organs of primary and secondary transplanted Fabry mice receiving transduced bone marrow cells.

Fabry disease is a compelling target for gene therapy as a treatment strategy. A deficiency in the lysosomal hydrolase alpha-galactosidase A (alpha-gal A; EC ) leads to impaired catabolism of alpha-galactosyl-terminal lipids such as globotriaosylceramide (Gb3). Patients develop vascular occlusions that cause cardiovascular, cerebrovascular, and renal disease. Unlike for some lysosomal storage disorders, there is limited primary nervous system involvement in Fabry disease. The enzyme defect can be corrected by gene transfer. Overexpression of alpha-gal A by transduced cells results in secretion of this enzyme. Secreted enzyme is available for uptake by nontransduced cells presumably by receptor-mediated endocytosis. Correction of bystander cells may occur locally or systemically after circulation of the enzyme in the blood. In this paper we report studies on long-term genetic correction in an alpha-gal A-deficient mouse model of Fabry disease. alpha-gal A-deficient bone marrow mononuclear cells (BMMCs) were transduced with a retrovirus encoding alpha-gal A and transplanted into sublethally and lethally irradiated alpha-gal A-deficient mice. alpha-gal A activity and Gb3 levels were analyzed in plasma, peripheral blood mononuclear cells, BMMCs, liver, spleen, heart, lung, kidney, and brain. Primary recipient animals were followed for up to 26 weeks. BMMCs were then transplanted into secondary recipients. Increased alpha-gal A activity and decreased Gb3 storage were observed in all recipient groups in all organs and tissues except the brain. These effects occurred even with a low percentage of transduced cells. The findings indicate that genetic correction of bone marrow cells derived from patients with Fabry disease may have utility for phenotypic correction of patients with this disorder.

Animals↗
PubMed2000

Alveolar macrophage cytokine production in response to air particles in vitro: role of endotoxin.

The interaction of air particles and alveolar macrophages (AMs) may result in the release of proinflammatory cytokines. Normal mouse AMs were treated with concentrated air particle (CAPs) suspensions in vitro. After 5 h, cytokine release [macrophage inflammatory protein-2 (MIP-2) and tumor necrosis factor-alpha (TNF-alpha)] and phagocytosis of ambient air particles were measured. CAPs samples collected from urban air (Boston) on different days were used. The CAPs samples and their soluble and solid components caused significant MIP-2 and TNF-alpha production. Variability in the potency of samples collected on different days was observed. Trace endotoxin was measured in CAPs samples (EU/mg: 2.3 +/- 0.7, mean +/- SE, n = 10). A majority of biologic activity (cytokine induction) and endotoxin content was associated with the solid components. Neutralization of endotoxin by polymyxin B abrogated >80% of TNF-alpha induction by CAPs samples, but inhibited MIP-2 production by only approximately 40%. The trace endotoxin present in CAPs caused much more MIP-2 production than predicted by concentration alone (28 +/- 8-fold increase, n = 9), indicating synergistic interaction with other AM-activating components of the particles. Data suggest that low levels of endotoxin may interact with air particles to activate lung macrophages.

Air Pollutants↗
PubMed2000

Variegation of retroviral vector gene expression in myeloid cells.

We have comparatively evaluated the efficiency of a series of retroviral vectors transducing the gp91-phox gene, whose defects are responsible for impaired production of superoxide anion (O2-) by phagocytic cells and lead to the X-linked form of chronic granulomatous disease (X-CGD). These vectors included four constructs based on the MoMuLV backbone and expressing gp91-phox from the viral long terminal repeat (LTR) or from internal promoters, and one construct based on the myelotropic FMEV vector. Expression of the therapeutic gene from the MoMuLV LTR was unsatisfactory after transduction of the PLB985 X-CGD knockout cell line and of primary CD34+ hematopoietic progenitors from X-CGD patients. The presence of either constitutive or inducible internal promoters did not result in important improvements in the efficiency of O2- production and lowered the titers of the viral preparations. In contrast, sustained levels of superoxide generation were obtained upon transduction with the FMEV vector. To analyze the efficiency of transgene expression at the single cell level, over 150 cellular clones were generated from bulk cultures of PLB985 X-CGD cells transduced with this vector, each one representative of an individual transduction event. These clones revealed a markedly heterogeneous pattern of gp91-phox expression, ranging from complete silencing to full restoration of superoxide production. Within each clone, expression of the therapeutic gene correlated with the number of expressing cells rather than with the average levels of expression from each cell, indicating that at the single cell level, the proviral promoter is regulated by a binary, on/off mechanism. Moreover, both transduced bulk and clonal cell populations displayed a tendency to a progressive extinction of expression over time, with a mechanism involving LTR methylation. The design of novel retroviral vectors escaping silencing is highly desirable for efficient gene therapy.

Gene Expression↗
PubMed2000

In vivo evaluation of a morpholino antisense oligomer directed against tumor necrosis factor-alpha.

Morpholino antisense oligomers directed against the cytokine tumor necrosis factor (TNF-alpha) can specifically inhibit production of TNF-alpha by macrophages in vitro. To evaluate the efficacy of morpholino antisense in vivo, we characterized a mouse model of increased pulmonary TNF-alpha production and inflammation in response to aerosolized endotoxin. Pretreatment of mice by intranasal (i.n.) insufflation of oligomers (30 microl of 100 microM/ml) 12 hours prior to lipopolysaccharide (LPS) exposure resulted in specific and consistent inhibition of TNF-alpha production by the oligomer MAS-2, whereas no effect was observed with a sequence-scrambled control (% inhibition 31.5 +/- 3.5 vs. 1.3 +/- 8.0, respectively, p < 0.005). Dose-response analysis showed similar efficacy for MAS-2 at 25-100 microM/ml and diminished effects with lower concentrations. Inhibition of TNF-alpha did not alter the increase in neutrophils seen in bronchoalveolar lavage (BAL) fluid, a result consistent with observations using i.n. administration of neutralizing anti-TNF-alpha antibody or TNF receptor knockout mice. The results establish that morpholino oligomers directed against cytokine targets can function in vivo. Additional studies of other targets and administration protocols to improve efficacy are warranted.

Administration, Intranasal↗
PubMed2000

Chemoprevention of aflatoxin B1-initiated and carbon tetrachloride-promoted hepatocarcinogenesis in the rat by green tea.

Chemoprevention of hepatocarcinogenesis by green tea (GT) has been examined in young male Fischer rats fed AIN-76A diet with aflatoxin B1 (AFB1) and CCl4 as the initiator and promoter, respectively. Animals were administered AFB1 (0.25 mg/kg body wt ip) twice a week for 2 weeks, and 2 weeks later, CCl4 was injected (0.8 ml/kg body wt ip) once per week for 11 weeks. Rats given 0.5% GT in their drinking water before and during initiation (0-4 wk) or during promotion (6-16 wk) or throughout the experimental period were sacrificed 24 hours after the last dose of CCl4. Bromodeoxyuridine incorporation as a measure of cell proliferation and glutathione S-transferase placentalform- and gamma-glutamyl transpeptidase-positive hepatic foci were analyzed by histochemical methods. Feeding of GT during initiation or promotion inhibited the number of glutathione S-transferase placental form- and gamma-glutamyl transpeptidase-positive hepatic foci by 30-40% and the area and volume by 50%. GT treatment throughout the period inhibited the number of both types of hepatic foci by 60% and the area and volume by 75-80%. Cell proliferation was inhibited 35% by GT given during promotion, whereas inhibition was 65% when GT was given during initiation or throughout the period. These results indicate that GT feeding inhibits initiation and promotion steps of AFB1 hepatocarcinogenesis and that the inhibition of cell proliferation is responsible for the inhibition of promotion.

Aflatoxin B1↗
PubMed2000

[A study on evolution of the term impotence and its classification and diagnosis].

Called "bu qi" (unable to erect) in the pre-Qin period, it was called "yin wei" (yin flabbiness) during Qin-Han to Jin-yuan dynasties, and called "yang wei" (yang flabbiness) since the Ming dynasty, though a few books called it Yin-flabbiness, but both Yang- and Yin- flabbiness didn't appear simultaneously in the same work. It was categorized under seven-injuries, kidney disorders, consumptive diseases, five non-masculine and sexual diseases before the Tang dynasty, and categorized under miscellaneous diseases since Jin dynasty. It was typed into bu ju (non erected), bu jian (non hardened) and bu jiu (non persistent). Some classified on the basis of etiology. It was pointed out that this disorder refers to inability to errect though the patient has a desire to erect, instead of unwilling to erect. The changes of the idea reflect the different levels of recognition in different historical periods.

China↗
PubMed2000

[Studies on Euphorbia fischeriana diterpenoide lactones inhibitory effect on human tumor cells in vitro].

In this paper, two diterpenoide lactones 16-hydroxypseudojolkinolide B and jolkinolide B were isolated from Euphorbia fischeriana Steud. They showed inhibitory effect on human tumor cells both the K562 cell and CNE2 cell and significant dose-effect relationship. The IC50 values of 16-hydroxypseudojolkinolide B on the two human tumor cells were near to that of ADM's.

Antineoplastic Agents, Phytogenic↗
PubMed1999

Circulating alpha-galactosidase A derived from transduced bone marrow cells: relevance for corrective gene transfer for Fabry disease.

Fabry disease is caused by a deficiency of the lysosomal enzyme alpha-galactosidase A (alpha-gal A). We previously engineered a retrovirus encoding human alpha-gal A and demonstrated enzymatic correction of patient cells. Further, we demonstrated metabolic cooperativity, in that corrected cells secrete alpha-gal A that can be taken up and utilized by bystander cells in vitro. In the present study, we created a system to examine and quantitate this phenomenon in vivo. To differentiate from endogenous alpha-gal A, we constructed a retroviral vector (pUMFG/alpha-gal A/FLAG) containing a fusion form of alpha-gal A with a specific tag sequence at the carboxy terminus. The catalytic activity of the fusion protein was identical to wild-type alpha-gal A. The fusion protein was overexpressed in and secreted by transduced patient cells. In uptake studies, the fusion protein was detected in the lysosome-enriched fraction of recipient cells. We then examined the effectiveness of the pUMFG/alpha-g A/FLAG retroviral vector in vivo. Murine bone marrow (BM) cells were transduced and transplanted into irradiated hosts. After 9 weeks, proviral DNA was detected by PCR in peripheral blood and BM mononuclear cells. More importantly, specific fusion protein enzymatic activity could be demonstrated in those cells and in plasma. Thus, we have demonstrated that overexpressed alpha-gal A enters the circulation from transduced BM cells and is stable over a significant period of time.

Animals↗