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Biomedical subjects

S Wang

Publications and source records attributed to S Wang.

At least 505 records · Page 28Linked to original sources
PubMed2000

Progressive optic axon dystrophy and vacuslar changes in rd mice.

PURPOSE: To examine how the vascular plexuses in the rd mouse retina are affected by the loss of photoreceptors and how this compares with the Royal College of Surgeons (RCS) rat. To examine whether the profound effects of vascular pathology on retinal ganglion cells (RGCs) and their axons seen in RCS rats are also found in rd mice. METHODS: Vascular patterns were studied in flatmounted and sectioned retinas using either nicotinamide adenine dinucleotide phosphate(NADPH)-diaphorase histochemistry or vessel filling with horseradish peroxidase. Optic axons were visualized using RT97 (an antibody against the 200-kDa neurofilament subunit), and RGCs were labeled by retrograde transport of fluorescence label, the Fluorogold, applied to the superior colliculus. RESULTS: The present study showed that in the rd mouse, similar to the RCS rat, vascular complexes developed in association with retinal pigment epithelial cells at the outer border of the retina. The number and distribution of complexes were very different from the rat, but as in the rat, progressive axonal dystrophy was seen in the optic fiber layer. RGC loss, rather than being local was more broadly distributed, but some, at least, appeared to be secondary to axonal dystrophy caused by vessels supplying vascular formation. CONCLUSIONS: Photoreceptor loss in the rd mouse leads to RGC axonal dystrophy and loss. The lesser degree and different distribution of RGC loss caused by abnormal vasculature associated with vascular formations in the outer retina in the rd mouse may be due to the early atrophy of the deep vascular plexus in this animal.

Animals↗
PubMed2000

Pancreatic beta-cell K(ATP) channel activity and membrane-binding studies with nateglinide: A comparison with sulfonylureas and repaglinide.

Nateglinide (A-4166) is an amino acid derivative with insulinotrophic action in clinical development for treatment of type 2 diabetes. The aim of this study was to determine whether nateglinide's interaction at the K(ATP) channel/sulfonylurea receptor underlies its more rapid onset and shorter duration of action in animal models. Binding studies were carried out with membranes prepared from RIN-m5F cells and HEK-293 cells expressing recombinant human sulfonylurea receptor 1 (SUR1). The relative order for displacement of [(3)H]glibenclamide in competitive binding experiments with RIN-m5F cell membranes was glibenclamide > glimepiride > repaglinide > glipizide > nateglinide > L-nateglinide > tolbutamide. The results with HEK-293/recombinant human SUR1 cells were similar with the exception that glipizide was more potent than repaglinide. Neither nateglinide nor repaglinide had any effect on the dissociation kinetics for [(3)H]glibenclamide, consistent with both compounds competitively binding to the glibenclamide-binding site on SUR1. Finally, the inability to measure [(3)H]nateglinide binding suggests that nateglinide dissociates rapidly from SUR1. Direct interaction of nateglinide with K(ATP) channels in rat pancreatic beta-cells was investigated with the patch-clamp method. The relative potency for inhibition of the K(ATP) channel was repaglinide > glibenclamide > nateglinide. Kinetics of the inhibitory effect on K(ATP) current showed that the onset of inhibition by nateglinide was comparable to glibenclamide but more rapid than that of repaglinide. The time for reversal of channel inhibition by nateglinide was also faster than with glibenclamide and repaglinide. These results suggest that the unique characteristics of nateglinide are largely the result of its interaction at the K(ATP) channel.

ATP-Binding Cassette Transporters↗
PubMed2000

Antioxidant properties of pyrrolidine dithiocarbamate and its protection against Cr(VI)-induced DNA strand breakage.

Pyrrolidine dithiocarbamate (PDTC) is considered an antioxidant and is frequently used to study the role of free radical reactions in various biological processes and against free radical-induced cellular injuries. However, its antioxidant properties are not characterized. In this study, electron spin resonance (ESR) was used to investigate the antioxidant potential of PDTC with hydroxyl radical (*OH) and superoxide anion radicals (O2*-). The Fenton reaction [Fe(II) + H2O2 --> Fe(II) + *OH + OH-)] and xanthine and xanthine oxidase were used as sources of *OH and O2*- radicals, respectively. The results show that PDTC effectively scavenges *OH radicals with a reaction rate constant of approximately 2.73 x 10(10) M(-1) s(-1), which is comparable to other efficient *OH radical scavengers, such as ascorbate and glutathione. PDTC is also able to scavenge O2*- radicals. Through its antioxidant properties, PDTC protects against Cr(VI)-induced DNA strand breakage.

Antioxidants↗
PubMed2000

Fluidity and fatty acid components of erythrocyte membranes in diabetic retinopathy.

BACKGROUND: Recently, numerous anomalies of erythrocyte rheology and function have been reported in diabetic patients. These changes are thought to be related to the alteration of erythrocyte membrane fluidity and may play an important role in diabetic retinopathy (DR). Nonetheless, the principal factors contributing to fluidity change remain undetermined. The influence of erythrocyte membrane fatty acid components on membrane fluidity and retinopathy was evaluated in patients with type 2 diabetes. METHODS: The fatty acid components and fluidity of erythrocyte membranes in 63 patients with type 2 diabetes with and without retinopathy were examined using high-performance liquid chromatography and fluorescence polarization. RESULTS: The content and composition of erythrocyte membrane arachidonate (C20:4n-6) was significantly lower in diabetics than in controls, and diabetics had significantly increased erythrocyte membrane microviscosity compared with controls. Furthermore, membrane microviscosity was higher in diabetics with DR than those without DR. In the diabetic patients, arachidonic acid contents of erythrocyte membranes were significantly, inversely correlated with erythrocyte membrane microviscosity, fasting blood glucose, glycosylated hemoglobin, triglycerides and cholesterol, and positively correlated with the insulin sensitivity index. CONCLUSIONS: The results suggest that erythrocyte membrane fatty acid components may contribute to alterations in membrane fluidity in patients with type 2 diabetes. Alterations in membrane fluidity may play an important role in the development of diabetic microangiopathy.

Aged↗
PubMed2000

Role of molecular oxygen in the generation of hydroxyl and superoxide anion radicals during enzymatic Cr(VI) reduction and its implication to Cr(VI)-induced carcinogenesis.

Electron spin resonance (ESR) spin trapping measurements provide evidence for the generation of hydroxyl radicals (*OH) in the reduction of Cr(VI) by glutathione reductase (GSSG-R) in the presence of NADPH as a cofactor. Catalase inhibited the *OH generation, while the addition of H2O2 enhanced it, indicating that the *OH radical generation involves a Fenton-like reaction. The metal chelator, deferoxamine, inhibited the *OH generation with a concomitant generation of a deferoxamine nitroxide radical. EDTA and 1,10-phenanthroline also inhibited the *OH generation. Experiments performed under argon atmosphere decreased the yield of the *OH formation, showing that molecular oxygen plays a critical role. ESR spin trapping and measurements of fluorescence change of scopoletin in the presence of horseradish peroxidase show that reduction of Cr(VI) by GSSG-R/NADPH generates superoxide anion radicals (O2*-) as well as H2O2. It can be concluded that *OH radical is generated by the reaction of H2O2 with Cr(V), which is produced by enzymatic one-electron reduction of Cr(VI). H2O2 is produced by the reduction of molecular oxygen via O2*- as an intermediate. The *OH radicals generated by these reactions are capable of causing DNA strand breaks, which can be inhibited by catalase, formate, and experiments performed under argon.

Carcinogenicity Tests↗
PubMed2000

The immunomarker of aging and the modulatory effect of Chinese medicinal herbs on the dysfunction of lymphocytes in the elderly.

PURPOSE: This study examined an immunomarker of aging and evaluated the modulatory effect of Chinese medicinal herbs (CMH) on the immune function of lymphocytes in the elderly. METHODS: Forty-seven elderly and fifteen young persons were selected as study subjects. Peripheral blood lymphocytes (PBL) were isolated by Ficoll-Hypaque gradient centrifugation. The responsive proliferation was investigated by means of the 3H-TdR incorporation procedure. The phenotype and receptor of lymphocytes were measured using indirect immunofluorescence. RESULTS: Both Rg1 and Gy-P significantly increased the responsive proliferation of lymphocytes in the elderly, p < 0.001 and p < 0.05, respectively. Rg1 also had a stimulatory effect on the receptor, CD25, and phenotype, CD45RA, CD45RO, in lymphocytes in aged persons. The immunomarker of aging was established by multiparametric indications on the basis of study at the cellular and molecular levels. CONCLUSION: The possibility exists that a lowered immune function can be reversed with modulation. In the near future, a highly purified, nontoxic, and more effective immunomodulator could be produced from CMH as an antiaging drug.

Adjuvants, Immunologic↗
PubMed2000

Short-term exposure to homocysteine depresses rat aortic contractility by an endothelium-dependent mechanism.

The effect of short-term exposure to homocysteine (Hcy) on the contractile characteristics of rat aortic tissue was assessed both in vitro and in vivo. The contractile response of Hcy-treated aortic rings in culture for 1 or 4 days was unchanged from control responses. By comparison, aortic rings from animals injected with Hcy showed marked attenuation of response compared with controls injected with saline, cysteine or methionine. The contractile response to K+ was decreased within 24 hours of Hcy injection, whereas the response to both K+ (-27%) and noradrenaline (-56%) was significantly decreased by 4 days. In contrast, the contractile response to phorbol-12,13-dibutyrate was not different between Hcy and control groups. Intimal rubbing completely restored the responsiveness of Hcy-treated tissue to K+ and noradrenaline. By comparison, L-NAME only partially restored contractile responsiveness, while the cyclooxygenase inhibitor indomethacin had no effect on contractile attenuation induced by Hcy. Western blot analysis showed a 2-fold increase of endothelial nitric oxide synthase (eNOS) and a 3-fold increase in inducible nitric oxide synthase (iNOS) protein expression in the aortic endothelial cells from Hcy-injected rats. The results indicate an early detectable effect of Hcy on the in vivo contractile properties of vascular smooth muscle. The effect is endothelium-mediated and may vary depending on the agonist studied. The mechanism is uncertain but appears to involve increased nitric oxide (NO) production. Finally, the data suggest that attenuation of contraction may not be due to a direct effect of Hcy but that the compound is modified or acts indirectly in vivo.

Animals↗
PubMed2000

[Expression of CPP32, Fas and Fas ligand and the relationship between their expression and viral antigens in chronic hepatitis].

OBJECTIVE: To study the significance of Fas-Fas ligand (FasL)-CPP32 mediated hepatocytic apoptosis and the relationship between their expression and hepatitis C virus (HCV) antigens in pathogenesis of chronic hepatitis C (CHC). METHODS: The expression of Fas and FasL proteins and CPP32 protease and their mRNAs was detected by immunohistochemistry and in situ hybridization respectively. Meanwhile, HCV core protein and nonstructural protein NS(3) and NS(5) were examined on the sequential liver tissue sections from 65 cases of patients with CHC and 5 cases of normal subjects. The positive staining was quantified by image analysis. RESULTS: In CHC liver tissues, CPP32 protease, Fas and their mRNAs were mainly expressed in the hepatocytes, especially in the HCV core protein-positive hepatocytes and their surroundings, but FasL protein and its mRNA were expressed dominantly in the infiltrating mononuclear cells in the portal area and hepatic sinusoid. According to the increase of histological activity index (HAI) in the CHC liver tissues, the expression of the three proteins (protease) and their mRNAs were upregrulated obviously. CONCLUSION: The results suggest i) that Fas-FasL-CPP32 system is associated with HAI of CHC, ii) that HCV core antigen may affect the expression of CPP32 and Fas hepatocytes apoptosis.

Caspase 3↗
PubMed2000

Activation of androgen response element by cadmium: a potential mechanism for a carcinogenic effect of cadmium in the prostate.

Cadmium is a transition metal that has been widely used in industry. Epidemiological and animal studies have demonstrated a carcinogenic effect of cadmium on the prostate. Although it has been established that androgen is required for this cancer-inducing process, it is not clear how cadmium interacts with androgen. In this study, the carcinogenic mechanism of cadmium was explored with a focus on interaction of androgen and cadmium at the gene transcription level. An androgen response luciferase reporter was used for analysis of the cadmium activity in the transient transfection assay. Human prostate epithelial cells (LNCap) and liver cells (HepG2) were transfected by the reporter. The result showed that cadmium was able to activate the reporter in the absence of androgen, and that this activation was dependent on the presence of androgen receptor. Cadmium could enhance the androgen response when both androgen and cadmium were applied together to the reporter-transfected cells. Activation of the reporter by cadmium was not associated with cell proliferation or interleukin 6 (IL-6) production, which was proposed to be involved in cadmium-induced carcinogenesis in other experimental systems. Cadmium exhibited a weak ability to induce AP-1. The results demonstrate that cadmium has an androgen-like activity in prostate epithelial cells, and this activity implies a new mechanism for the carcinogenic effect of cadmium in the prostate.

Androgens↗
PubMed2000

Chlamydia trachomatis mouse pneumonitis lung infection in IL-18 and IL-12 knockout mice: IL-12 is dominant over IL-18 for protective immunity.

BACKGROUND: Interferon (IFN)-gamma is a key to protective immunity against a variety of intracellular bacterial infections, including Chlamydia trachomatis. Interleukin (IL)-18, a recently identified Th1 cytokine, together with IL-12 is a strong stimulator for IFN-gamma production. We investigated the relative roles of IL-18 and IL- 12 in protective immunity to C. trachomatis mouse pneumonitis (MoPn) infection using gene knockout (KO) and wild-type (WT) mice. MATERIALS AND METHODS: Mice were intranasally infected with C. trachomatis MoPn and protective immunity was assessed among groups of mice by daily body weight changes, lung growth of MoPn, and histopathological appearances at day 10 postinfection. The corresponding immune responses for each group of mice at the same postinfection time point were evaluated by measuring antigen-specific antibody isotype responses and cytokine profiles. RESULTS: Our results showed that IL-18 deficiency had little or no influence on clearance of MoPn from the lung, although KO mice exhibited slightly more severe inflammatory reactions in lung tissues, as well as reduced systemic and local IFN-gamma production, compared with WT mice. Results with IL-18 KO mice were in sharp contrast to those observed with IL-12 KO mice that showed substantially reduced clearance of MoPn from the lungs, substantial reductions of antigen-specific systemic and lung IFN-gamma production, decreased ratio of MoPn-specific immunoglobulin G (IgG)2a/IgG1, and severe pathological changes in the lung with extensive polymorphonuclear, instead of mononuclear, cell infiltration. Exogenous IL-12 or IL-18 was able to increase IFN-gamma production in IL-18 KO mice; whereas, only exogenous IL-12, but not IL-18, enhanced IFN-gamma production in IL-12 KO mice. Caspase-1 is the key protease for activation of IL-18 precursor into the bioactive form, and caspase-1 KO mice also displayed similar bacterial clearance and body weight loss to that in WT mice at early stages of MoPn infection. This further confirmed that IL-18 was not essential for host defense against chlamydia infection. CONCLUSIONS: These results suggest that IL-12, rather than IL-18, plays the dominant role in the development of protective immunity against chlamydia lung infection, although both cytokines are involved in the in vivo regulation of IFN-gamma production.

Animals↗
PubMed2000

HER2 promoter controlled specific expression of the reporter gene in ovarian cancer cell line.

OBJECTIVE: Construct a retrovirus vector that expresses the downstream gene specifically in ovarian cancer cells so as to increase the specificity of gene therapy. METHODS: HER2 promoter obtained by PCR was cloned into P(LXSN); mutant GFP cDNA was inserted just downstream of this promoter. Transfect SK-OV3 and MCF-7 cell lines with the new vector, P(LHGSN). RESULTS: Three days after transfection with P(LHGSN), green fluorescence was observed in SK-OV3 cells while not in MCF-7 cells. CONCLUSION: HER2 promoter can control tumor specific expression of the reporter gene in ovarian cancer cell lines. With proper modification, the vector is expected to be useful in tumor specific gene therapy of ovarian cancers.

Female↗
PubMed2000

Preliminary evaluation of 15-[18F]fluoro-3-oxa-pentadecanoate as a PET tracer of hepatic fatty acid oxidation.

UNLABELLED: The liver is an important site of fat oxidation. Abnormalities of hepatic mitochondrial fatty acid oxidation (HMFAO) are associated with obesity, type II diabetes, alcoholic hepatitis, and nonalcoholic steatohepatitis. Noninvasive assessment of HMFAO by PET has been impeded by the lack of a specific radiotracer. METHODS: No-carrier-added 15-[18F]fluoro-3-oxa-pentadecanoate (FOP) was synthesized and evaluated in living rats and isolated rat livers. RESULTS: FOP showed high uptake and slow clearance of radioactivity from livers in living rats. Inhibition of HMFAO by pretreatment of fasting rats with the carnitine palmitoyltransferase-I (CPT-I) inhibitor reduced the liver-to-blood ratio by 64%. In isolated rat livers, perfused in normoxic (95% O2) and hypoxic (15% O2) conditions with glucose (5 mmol/L) and palmitate (0.15 mmol/L), the externally measured kinetics of FOP showed reversible binding in tissue. The kinetics were adequately fit by a catenary 2-compartment model for estimation of tracer distribution volumes (DVs). The DVs of both compartments were found to correlate with fractional palmitate oxidation rate (FPOR) in experiments in normoxic and hypoxic conditions. The correlation was particularly strong for the slower second compartment (DV2 [mL/g dry weight] = 34.1 FPOR [mL/min/g dry weight] - 0.7, r = 0.89). Relatively small levels of diffusible metabolites of FOP were formed in vivo and in isolated rat liver. CONCLUSION: The selective uptake of FOP by liver and the high sensitivity of hepatic FOP DV to changes of HMFAO with CPT-I inhibition and hypoxia suggests potential usefulness for the 3-oxa fatty acid analog in assessments of hepatic mitochondrial oxidation of exogenous fatty acids with PET. These data emphasize that further studies are required to clarify the intracellular disposition of FOP in the liver and test its validity as a tracer of HMFAO over a broad range of conditions.

Animals↗
PubMed2000

An enzymologic study on bone marrow cells in patients with aplastic anemia treated by supplementing the kidney and removing blood stasis.

The content of cytochrome oxidase (CCO), succinate dehydrogenase (SDH) and neutrophil alkaline phosphatase (NAP) in bone marrow cells in 68 cases of aplastic anemia before and after treatment was determined by computerized graphical analysis and compared with that of normal volunteers (control group). The significantly lowered CCO and SDH levels and the markedly increased NAP content before treatment (P < 0.01) became approximately normal after that of supplementing the kidney and removing blood stasis (P > 0.05).

Adolescent↗
PubMed2000

Specific regulatory inhibition of transfected HepG(2) with HCV 5'NCR by antisense phosphorothioate oligodeoxynucleotides.

OBJECTIVE: To screen efficient and specific new drugs against hepatitis C virus (HCV) and find the best target sequence of antisense oligodeoxynucleotides (ASODNs) targeting at HCV gene. METHODS: Fifteen S-ASODNs targeting at the 5'NCR and start AUG of HCV RNA were designed and synthesized according to the predicted RNA secondary structure of the HCV 5'NCR and the adjacent AUG region. HepG(2) cells were co-transfected with pHCV-neo4 and S-ASODN. The inhibitory effects of S-ASODNs on gene expression controlled by HCV 5'NCR were determined by the assay of luciferase activity. RESULTS: Five S-ASODNs, i.e. HCV65, HCV279, HCV363, HCV349 and HCV352, showed sequence-specific and dose-dependent inhibitory activities with an inhibition rate of more than 80% at a concentration of 100 nmol/L. According to 50% inhibitory concentrations, the inhibitory activity of HCV363 was the best. On the other hand, ASODNs had only little non-specific effect by negative control trials. In addition, the results also indicated that there were some coordinate effects between ASODNs at different targets. CONCLUSION: Stem-loop 2a and 3d of HCV 5'NCR and the start AUG of polyprotein precursor are candidate targets of S-ASODNs.

5' Untranslated Regions↗
PubMed2000

[The expression of transforming growth factor-beta receptor I and its mRNA in liver tissues of chronic hepatitis B and the clinical significance].

OBJECTIVE: To study the expression of transforming growth factor-beta receptor I (TGF-beta RI) and its mRNA in liver tissues of chronic hepatitis B (CHB) and the relationship between its expression and the pathological injury of hepatic tissues. METHODS: Forty-eight liver specimens from patients with CHB were observed by techniques of immunohistochemistry and in situ nucleic acid hybridization. RESULTS: TGF-beta RI was expressed in the hepatocyte, sinusoid endothelial cell and bile duct epithelial cell, with predominance in the hepatocyte and distribution in small granule or cell membrane. Increased expressing of TGF-beta RI was parallel to the degree of inflammatory activity and fibrosis (r=0.7095, P<0.05; r=0.6915, P<0.05; respectively). The number and the distribution of TGF-beta RI mRNA in the positive cells were coincident to those of its protein. The expression of TGF-beta RI was closely correlated with Tbil (r= 0.3396, P<0.05), PA (r= -0.3430, P<0.05) and ALB (r= -0.4173, P<0.01). CONCLUSION: The TGF-beta RI may involve in the pathological injury of hepatic tissues of CHB.

Activin Receptors, Type I↗
PubMed2000

Suppressive effect of active hexose correlated compound (AHCC) on thymic apoptosis induced by dexamethasone in the rat.

OBJECTIVE: Mushroom extracts are known to have immunomodulating and antitumor effects in humans as well as in animals. In the present study Active Hexose Correlated Compound (AHCC), an extract obtained from several kinds of basidiomycetes was examined for its suppressive effect on thymocyte apoptosis induced by dexamethasone. METHOD: Thymic apoptosis was evaluated by gel electrophoresis and by flow cytometry at 3 h after injection of dexamethasone to rats. RESULTS: When given to rats at 4 % concentration in drinking water for more than 4 days, AHCC suppressed the internucleosomal DNA fragmentation in the thymus induced by dexamethasone. Flow cytometry also revealed that thymic apoptosis induced by dexamethasone was prevented by pretreatment with AHCC. Dexamethasone increased the caspase 3-like activity within 3 h after its treatment and AHCC pretreatment suppressed the increased enzyme activity only slightly. No apparent increase in serum levels of melatonin and interleukin 1beta was observed after AHCC treatment. CONCLUSIONS: These results suggest that AHCC exhibits immuno-modulating effects at least partially by regulating thymic apoptosis.

Adjuvants, Immunologic↗
PubMed2000

[Study on mRNA differential display in Mycobacterium tuberculosis H37Rv and H37Ra].

OBJECTIVE: To study genetic differences between H37Rv and H37Ra by mRNA differential display, paving the way for obtaining virulence-related gene of Mycobacterium tuberculosis (MTB). METHODS: Total RNA was extracted from MTB H37Rv and H37Ra, mRNA differential display was conducted following reverse transcription, polymerase chain reaction, polyacrilamide gel electrophoresis and radiography. The differential bands were recovered, reamplified, sequenced, and then homologous query was done. RESULTS: 10 differential bands between H37Rv and H37Ra were recovered, 2 of which were homologous to H37Rv DNA after query from NCBI database of GenBank. CONCLUSIONS: mRNA differential display is an effective, sensitive method, can display differences between different strains intra- and extra-species and be used in searching Mycobacterium tuberculosis virulence-related gene. Obtained differential bands in this study may cover MTB virulence-related gene.

Animals↗