Biomedical subjects

Ying Zhang

Publications and source records attributed to Ying Zhang.

At least 487 records · Page 27Linked to original sources

PubMed2002

Dopamine D1 receptor changes due to caesarean section birth: effects of anesthesia, developmental time course, and functional consequences.

There is an epidemiological association between increased obstetric complications and disorders involving CNS dopamine dysregulation, such as schizophrenia. In light of this, a rat model of global hypoxia during Caesarean section (C-section) birth has been used to directly test if birth complications can produce long-term dopaminergic dysregulation. Previous studies have shown that, compared to vaginal birth, C-section birth alone (without additional global hypoxia) is sufficient to increase D1-like receptor binding in rat brain at adulthood. The current study examined (1) the developmental time course of changes in D1-like or D2-like receptors following C-section birth; (2) whether C-section birth from isoflurane-anesthetized dams also results in altered D1-like receptor levels, as does C-section from decapitated dams; and (3) behavioral responses to D1 and D2 agonists in rats born vaginally compared to C-section. Increases in nucleus accumbens D1-like receptor binding due to C-section birth were observed only at adulthood (3 months) but not prepubertally (1 month or 2 weeks). D2-like receptor binding levels were unaffected by C-section birth across the three developmental time points. Compared to vaginal birth, D1-like receptors were increased following C-section birth from isoflurane-anesthetized dams, as well as from decapitated dams. Adult rats that had been born by C-section showed enhanced D1 potentiation of D2-induced locomotor behavior. These studies indicate that C-section birth, from either anesthetized or unanesthetized dams, results in postpubertal increases in D1-like receptor binding and enhanced functional responses to D1 receptor activation.

2,3,4,5-Tetrahydro-7,8-dihydroxy-1-phenyl-1H-3-ben↗

PubMed2002

Construction of double-copy glucose isomerase gene engineering strain of Streptomyces diastaticus by homologous recombination.

The plasmid pUT for homologous recombination was constructed by the insertion of the 1.1-kb thiostrepton resistance ( tsr(R)) gene into the E. coli plasmid pUB1-GI1. Plasmid pUTK was produced through ligating the cleaved plasmid pUT by KpnI. After pUT and pUTK were introduced into Streptomyces diastaticus No.7 strain M1033 (SM33) by protoplast transformation, a series of tsr(R) transformants were obtained, further based on enzyme assays. These results for polymerase chain reaction (PCR), DNA sequencing, restriction enzyme digestion, and recovery of cloned fragments from the transformant chromosome demonstrated the plasmid pUT and pUTK had integrated into the SM33 chromosome in three different patterns of single cross-over by homologous recombination. This directly results in double-copy GI gene in the transformant chromosome, of which one is wild-type GI gene, the other mutant GI ( GIG138P, GI1) gene. Among the strains of the three kinds of recombinant patterns, one transformant was chosen and named K1, T2, and T3, respectively. The further identification of the three recombinant strains by PCR, DNA sequencing, restriction enzyme digestion, and Southern hybridization also proved there is a double-copy GI gene within their chromosome. Enzyme activity assay and thermostability analysis indicated that all three engineering strains expressed not only wild-type enzyme but also mutant GI.

Aldose-Ketose Isomerases↗

PubMed2002

Involvement of sigma receptors in the behavioral effects of cocaine: evidence from novel ligands and antisense oligodeoxynucleotides.

Pharmacological and molecular biological tools were used to validate the involvement of sigma receptors in the actions of cocaine. Radioligand binding studies demonstrated significant levels of sigma receptors in the brain and heart, where cocaine interacts preferentially with the sigma(1) subtype. In behavioral pharmacological studies using mice, nine novel sigma receptor antagonists significantly attenuated cocaine-induced convulsions, while structural analogs with weak interactions with sigma receptors were ineffective. In contrast to the protection provided by the antagonists, a classical sigma receptor agonist exacerbated the convulsive effects of cocaine. The antagonists also attenuated cocaine-induced lethality, with the best compound protecting against death even when administered as a post-treatment. At doses where the antagonists had no effect on baseline locomotor activity, they significantly attenuated the locomotor stimulatory effects of cocaine, suggesting their ability to block the psychomotor as well as the toxic effects of cocaine. To further validate that the anti-cocaine effects were achieved by interfering with cocaine's access to sigma receptors, antisense oligodeoxynucleotides against sigma(1) receptors were shown to attenuate the convulsive and locomotor stimulatory effects of cocaine. Together, the studies support the involvement of sigma receptors, particularly the sigma(1) subtype, in the behavioral effects of cocaine.

Animals↗

PubMed2002

A mortality cost of virginity at older ages in female Mediterranean fruit flies.

Mortality rates were measured over the lifetime of 65,000 female Mediterranean fruit flies, Ceratitis capitata, maintained in either all-female (virgin) cages or cages with equal initial numbers of males, to determine the effect of sexual activity and mating on the mortality trajectory of females at older ages. Although a greater fraction of females maintained in all-female (virgin) cages survived to older ages, the life expectancy of the surviving virgins was less than the life expectancy of surviving non-virgins at older ages. This was due to a mortality crossover where virgin flies experience lower mortality than mated flies from eclosion to Day 20 but higher mortality thereafter. These results suggest that there are two consequences of mating--a short-term mortality increase (cost) and a longer term mortality decrease (benefit).

Aging↗

PubMed2002

Life history response of Mediterranean fruit flies to dietary restriction.

The purpose of this study was to investigate medfly longevity and reproduction across a broad spectrum of diet restriction using a protocol similar to those applied in most rodent studies. Age-specific reproduction and age of death were monitored for 1200 adult males and 1200 females, each individually maintained on one of 12 diets from ad libitum to 30% of ad libitum. Diet was provided in a fixed volume of solution that was fully consumed each day, ensuring control of total nutrient consumption for every fly. Contrary to expectation and precedence, increased longevity was not observed at any level of diet restriction. Among females, reproduction continued across all diet levels despite the cost in terms of increased mortality. Among males, life expectancy exceeded that of females at most diet levels. However, in both sexes, mortality increased more sharply and the pattern of survival changed abruptly once the diet level fell to 50% of ad libitum or below, even though the energetic demands of egg production has no obvious counterpart in males. We believe that a more complete picture of the life table response to dietary restriction will emerge when studies are conducted on a wider range of species and include both sexes, more levels of diet, and the opportunity for mating and reproduction.

Age Factors↗

PubMed2002

Long dwell-time exposure of human chorionic villi to transvaginal ultrasound in the first trimester of pregnancy induces activation of caspase-3 and cytochrome C release.

Bioeffects after exposure to ultrasound are correlated to its duration. Although diagnostic ultrasound has been suggested to induce apoptosis, the underlying signal transduction pathway remains elusive. In this study, women in the first trimester of pregnancy were exposed to transvaginal diagnostic ultrasound with 5.0-MHz frequency for 0, 10, 20, or 30 min. The chorionic villi were obtained 4 h after exposure and activation of caspase-3 and cytochrome c release were analyzed by Western blotting. In contrast with the 0- and 10-min groups, cleavage products of active caspase-3 and cytochrome c release significantly increased in 20- and 30-min groups in a time-dependent manner. We show that long-duration exposure to transvaginal ultrasound activates effector caspase-3-mediated apoptotic cascade of chorionic villi in the first trimester of pregnancy. This occurs through the intrinsic death pathway involved in cytochrome c release. Our findings provide a molecular rationale for discriminant use of transvaginal ultrasound at the early stage of pregnancy.

Adult↗

PubMed2002

Conditions that may affect the results of susceptibility testing of Mycobacterium tuberculosis to pyrazinamide.

Pyrazinamide (PZA) is an important front-line anti-tuberculosis drug that is active only at acid pH. However, acid pH causes significant difficulty for PZA susceptibility testing. A common problem in PZA testing is false resistance caused by large bacterial inocula. This study investigated the relationship of false resistance to numbers of bacilli, pH and other factors that potentially affect susceptibility to PZA. Large inocula (10(7-8) bacilli/ml) of M. tuberculosis H37Ra caused significant increase in medium pH from 5.5 towards neutrality, and thus produced false resistance results. The increase in medium pH was determined to be a function of live bacilli; heat-killed bacilli had little or no effect. Susceptibility to PZA and its active derivative pyrazinoic acid (POA) was comparable on 7H11 agar medium, but POA was less active than PZA in liquid medium containing bovine serum albumin (BSA), suggesting that susceptibility to PZA or POA was reduced in the presence of BSA, because of its neutralising effect on medium pH and significant POA binding. A 3-month-old H37Ra culture was shown to be more susceptible to PZA exposure than a 4-day log-phase culture, suggesting that PZA is more active for non-growing bacilli. Finally, reserpine, an inhibitor of POA efflux pump, increased susceptibility to PZA even near neutral pH 6.8, with an MIC of 400 mg/L compared with 1,000 mg/L without reserpine. These findings should have implications for understanding the mode of action of PZA and for PZA susceptibility testing.

Antitubercular Agents↗

PubMed2002

Salicylate reduces susceptibility of Mycobacterium tuberculosis to multiple antituberculosis drugs.

Salicylate induces multiple antibiotic resistance in various bacterial species. Here we investigated the effect of salicylate on the susceptibility of Mycobacterium tuberculosis to a range of antituberculosis (anti-TB) drugs. In the presence of salicylate, the killing effects of isoniazid (INH), rifampin (RMP), ethambutol (EMB), streptomycin (STR), and p-aminosalicylate (PAS) were reduced, as shown with a tetrazolium redox dye viability assay and a bacterial survival assay. Salicylate-induced resistance was more pronounced for PAS, STR, and EMB but was not apparent for INH and RMP when salicylate and the anti-TB agents were incorporated into 7H11 plates. The significance of these findings for TB treatment needs to be further evaluated in vivo.

Antitubercular Agents↗

PubMed2002

Tuberculosis drug targets.

Despite the availability of the BCG vaccine and chemotherapy, tuberculosis (TB) remains a leading infectious killer worldwide. The recent rise of TB and especially the alarming increase of drug-resistant TB call for urgent need to develop new anti-TB drugs. Lengthy chemotherapy and increasing emergence of drug-resistant strains pose a significant problem for effective control. The need for a lengthy TB therapy is a consequence of the presence of persistent Mycobacterium tuberculosis, not effectively killed by current anti-TB agents. A list of new drug candidates along with proposed targets for intervention is described. Recent advances in the knowledge of the biology of the organism and the availability of the genome sequence provide a wide range of novel targets for drug design. Gene products involved in controlling vital aspects of mycobacterial metabolism, persistence, virulence and cell wall synthesis would be attractive targets. It is expected that the application of functional genomics tools, such as microarray and proteomics, in combination with modern approaches, such as structure-based drug design and combinatorial chemistry to biology-based targets, will lead to the development of new drugs that are not only active against drug-resistant TB but also can shorten the course of TB therapy.

Animals↗

PubMed2002

The effect of estrogen use on levels of glucose and insulin and the risk of type 2 diabetes in american Indian postmenopausal women : the strong heart study.

OBJECTIVE: To examine the associations between estrogen use and levels of insulin and glucose as well as the effect of estrogen use on the risk of type 2 diabetes. RESEARCH DESIGN AND METHODS: This report is based on 857 women who were both nondiabetic and postmenopausal at the baseline examination (1989-1992) and who completed a second examination (1993-1995) an average of 4 years later. The participants were divided into three groups: never, past, and current users based on their baseline estrogen use status. ANCOVA was used to compare the insulin and glucose levels among estrogen use groups. Logistic regression was used to evaluate the association between estrogen use and the incidence of type 2 diabetes. RESULTS: Postmenopausal estrogen use was associated with lower fasting glucose (0.2 mmol/l lower) but higher 2-h glucose levels (0.4 mmol/l higher) compared with never users. It was not significantly associated with the risk of type 2 diabetes compared with past and never users, based on American Diabetes Association or World Health Organization definitions of diabetes or on only a 2-h glucose level > or = 11.1 mmol/l. However, the risk of type 2 diabetes increased with increasing duration of estrogen use among current users, with an odds ratio of 1.10 per year of use (95% CI: 1.01-1.19). CONCLUSIONS: The data suggest that estrogen use in American Indian postmenopausal women may relate to deterioration of glucose tolerance. Longer duration of estrogen use among current users may relate to an increased risk of type 2 diabetes.

Blood Glucose↗

PubMed2002

On-column enzyme-catalyzed microreactions using capillary electrophoresis: quantitative studies.

Capillary electrophoresis and on-column enzyme-catalyzed microreactor techniques were used to quantitate the reaction projects resulting from three model systems: i) the conversion of nicotinamide adenine dinucleotide (NAD) to nicotinamide adenine dinucleotide, reduced form (NADH) in the oxidation of glucose-6-phosphate (glc-6-p) to 6-phosphogluconate by glucose-6-phosphate dehydrogenase (G6PDH, EC 1.1.1.49); ii) the conversion of adenosine triphosphate (ATP) to adenosine diphosphate (ADP) and adenosine monophosphate (AMP) by hexokinase (HK, EC 2.7.1.1) and apyrase (APY, EC 3.6.1.5), respectively, in the conversion of glucose to glucose-6-phosphate and inorganic phosphate, respectively, and; iii) the conversion of fructose-1,6-bisphosphate to dihydroxyacetone phosphate and glyceraldehyde-3-phosphate by fructose-biphosphate aldolase (ALD, EC 4.1.2.13). Single and double microreactor techniques employing direct or indirect detection were used to follow the conversion of substrate to product(s). In addition, electrophoresis conditions including voltage, enzyme concentration, and mixing time of the reaction, were correlated to product distribution profiles.

Adenosine Diphosphate↗

PubMed2002

[In vivo expression of human tissue-plasminogen activator transfected AGZY83-a cells implanted in mice].

OBJECTIVE: To detect the expressing levels of human tissue-plasminogen activator(t-PA) in AGZY83-a cells transfected with pcDNA3.1(+) t-PA in vivo and the feasibility of using transplantation of cells for gene therapy of thrombotic diseases. METHODS: Expression vectors containing the t-PA cDNA gene were transfected into AGZY83-a cells. The transfected AGZY83-a cells were implanted into mice in different regions, and the plasma levels of human t-PA were assayed at intervals. RESULTS: The plasma levels of human t-PA were significantly increased in mice after implantation of transfected AGZY83-a cells and were significantly higher than those of control groups implanted with untransfected AGZY83-a cells. This significant increase lasted at least 105 days. The intraperitoneal implantation group expressed the highest level of human t-PA, a little higher than that of the subcutis implantation group, while both are much higher than that of the quadriceps femoris implantation group which expressed the lowest. CONCLUSION: The implanted transfected AGZY83-a cells are able to stably express high levels of human t-PA, and transplantation of cells transfected with pcDNA3.1(+) t-PA is a new promising method for gene therapy of thrombotic diseases.

Animals↗

PubMed2002

[Overexpression and detection of the mutated glucose isomerase GIG138P and GIG138P-G247D in Streptomyces lividans].

The shuttle expression vectors pHZGI1 and pHZGI2 were successfully constructed by inserting structural genes of GI containing single mutated site G138P and double mutated site G138P-G247D into E. coli-Streptomyces shuttle vector pHZ-1272, respectively. Then they were transformed into S. lividans TK54 strain by protoplast transformation. SDS-PAGE indicated that two shuttle vectors in TK54 strain expressed obviously specific bands at 42.5 kD after inducted by 2 micrograms/mL thiostrepton. Optical densitometric scan showed that the content of the mutant enzymes GIG138P and GIG138P-G247D were about 19% and 22% of dissoluble proteins, respectively. Western blotting farther proved that GIG138P and GIG138P-G247D were expressed in S. lividans TK54.

Aldose-Ketose Isomerases↗

PubMed2002

Superparamagnetic iron oxide (Feridex)-enhanced MRI in diagnosis of focal hepatic lesions.

OBJECTIVE: To evaluate the diagnostic value of superparamagnetic iron oxide (SPIO)-enhanced magnetic resonance imaging (MRI) for hepatic focal solid lesions. METHODS: SPIO (Feridex)-enhanced MRI examination was performed in 28 cases of hepatic space-occupying lesions defined by CT or MRI or other methods. In post-contrast enhanced examination, the signal intensity and contrast-to-noise ratio (CNR) were measured in lesions and normal hepatic parenchyma in T2-weighted images (T2WI) and were compared with those in pre-contrast enhanced MRI. The number and morphology of the lesions were visualized for qualitative diagnostic analysis. RESULTS: In Feridex-enhanced MRI, the signal intensity of normal hepatic parenchyma was decreased while the CNR between lesions and normal liver tissues significantly improved in comparison with that in pre-contrast enhanced examination. CONCLUSION: Feridex-enhanced T2WI examination significantly improves detection of hepatic lesions and is valuable in diagnosing hepatic focal solid lesions.

Adult↗

PubMed2002

Development of anti-tumor immunity against a non-immunogenic mammary carcinoma through in vivo somatic GM-CSF, IL-2, and HSVtk combination gene therapy.

Gene therapy for cancer using suicide genes such as the herpes simplex virus thymidine kinase gene (HSVtk) has been explored extensively in preclinical and clinical studies. We have improved the use of HSVtk by combining it with two cytokine genes encoding granulocyte/macrophage-colony-stimulating factor (GM-CSF) and interleukin-2 (IL-2), and determined their additive/synergistic effects on tumor regression and inhibition of metastases in the non-immunogenic, spontaneously metastatic mammary tumor model, 4T1. Two adenoviral vectors (AV) were constructed, one carrying HSVtk (AV-TK) and the second (AV-GM/IL2) carrying Gm-CSf and Il2. Only the combination of AV-TK/GCV and AV-GM/IL2 showed a significant decrease in tumor growth and reduction of distant metastases with 25% of the tumors undergoing complete regression. When surgical excision of primary tumors was included in the regimen, local treatment with AV-TK/GCV plus AV-GM/IL2 further enhanced long-term survival. A fraction of the treated mice developed anti-tumor immunity and survived a second challenge with 4T1. Functional analyses demonstrated infiltration of lymphocytes within the tumor and a strong tumor-specific cytotoxic T lymphocyte response in TK- plus cytokine-treated animals. These data indicate that the coexpression of GM-CSF and IL-2 can augment the effect of HSVtk suicide gene therapy.

Adenoviridae↗

PubMed2002

Effect of transforming growth factor-beta(2) on extracellular matrix synthesis in bovine trabecular meshwork cells.

OBJECTIVE: To investigate the effect of transforming growth factor-beta(2) (TGF-beta(2)) in human aqueous humor on extracellular matrix synthesis in cultured bovine trabecular meshwork cells. METHODS: Cultured 3-5 passage bovine trabecular meshwork cells were divided into control group and experimental group. After treated with 0 ng/L (control), 0.32 x 10(3) ng/L, 1.00 x 10(3) ng/L, 3.20 x 10(3) ng/L TGF-beta(2) for 48 h, collagen, fibronectin and hyaluronic acid synthesis in bovine trabecular meshwork cells were examined respectively by (3)H-proline incorportion and liquid scintillation technique, enzyme linked immunosorbent assay (ELISA) and radioimmunoassay (RIA). RESULTS: In comparison with the control group, TGF-beta(2) significantly promoted the synthesis of collagen at 0.32 x 10(3) ng/L (P < 0.05), 1.00 x 10(3) ng/L (P < 0.01), 3.20 x 10(3) ng/L (P < 0.01), (3)H-proline incorporation increased in a concentration-dependent manner; and 1.00 x 10(3) ng/L (P < 0.05), 3.20 x 10(3) ng/L (P < 0.01) TGF-beta(2) significantly promoted the synthesis of fibronectin in cultured bovine trabecular meshwork cells. 1.00 x 10(3) ng/L (P < 0.01) and 3.20 x 10(3) ng/L (P < 0.01) TGF-beta(2) significantly inhibited the synthesis of hyaluronic acid in the cultured cells. CONCLUSION: The data suggest that TGF-beta(2) play important roles in extracellular matrix age-related changes of normal trabecular meshwork and abnormal deposition of the extracellular matrix in the trabecular meshwork, especially the juxtacanalicular tissue of primary open-angle glaucoma patients.

Animals↗

PubMed2002

Clinical manifestations of low bone mass in amenorrhea patients with elevated follicular stimulating hormone.

OBJECTIVE: To study the characteristics of low bone mass in amenorrhea patients with elevated follicular stimulating hormone (FSH). METHODS: Amenorrhea patients with elevated FSH: Primary amenorrhea 18 cases, secondary amenorrhea 171 cases and age matched controls with normal menstruation, 180 cases. The descriptive parameters were: estrogen, alkaline phosphatase, urinary excretion of calcium to creatine ratio, cortical bone mineral density at the right radius measured by single photon absorptiometry and trabecular bone mineral density at the lumbar vertebra body measured by quantitative computerized tomography. RESULTS: Average E(2) levels in amenorrhea patients is under 150 pmol/L with significantly higher alkaline phosphatase and urine calcium to creatine ratio values than the normal menstruation group. Cortical bone mineral density in the secondary amenorrhea group (655 +/- 69 mg/cm(2)) was significantly lower than that of the normal menstruation group (677 +/- 56 mg/cm(2), P < 0.01). Trabecular bone mineral density in the secondary amenorrhea group (145 +/- 26 mg/cm(3)) was significantly lower than that of the NOR group (192 +/- 28 mg/cm(3), P < 0.001). The disparity with the normal menstruation group is even greater in the primary amenorrhea group. Bone mineral density of the amenorrhea patients was negatively correlated with duration of the menopause. CONCLUSIONS: Serum estrodiol levels in amenorrhea patients was so low that bone turnover was accelerated. This led to insufficient bone accumulation and a dramatically drop in trabecular bone mineral density. The extent was closely related to age of onset of amenorrhea and the duration of ovarian failure.

Adult↗

PubMed2002

[Mosaicplasty osteochondral grafting to repair cartilaginous defects under arthroscopy].

OBJECTIVE: To study mosaicplasty a as method of autogenous osteochondral transplantation in the treatment of cartilaginous defects. METHODS: The technique involves obtaining small cylindrical grafts from the non-weight bearing periphery of the femur at the patellar femoral joint, and transporting them to the prepared recipient site by arthroscopy. RESULTS: Fifteen patients with defects cartilaginous received mosaicptasty osteochondral grafting. Follow up for 12 to 21 months (mean 15 months) showed good results. CONCLUSION: The treatment is indicated for patients with focal cartilaginous defects under the age of 45.

Adult↗