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Biomedical subjects

H Tian

Publications and source records attributed to H Tian.

At least 73 records · Page 4Linked to original sources

Changes in cardiovascular risk factors in different socioeconomic groups: seven year trends in a Chinese urban population.

STUDY OBJECTIVE: To analyse trends in socioeconomic differences in cardiovascular disease risk factors among an urban Chinese population using educational attainment as the socioeconomic indicator. DESIGN: Population surveys with randomly selected independent samples were carried out in 1989 and in 1996. Educational attainment, blood pressure, body mass index, cigarette smoking and lack of leisure time physical activity were determined. SETTING: Urban areas of the city of Tianjin, China. PARTICIPANTS: A total of 14 275 respondents aged 25-64 years. MAIN RESULTS: Diastolic blood pressure increased and the proportion of people without leisure time physical activity decreased in both sexes during the study period. The prevalence of smoking and the number of cigarettes smoked daily increased significantly among men. Smoking decreased in the least educated men and increased in those who had studied at least to college level. Body mass index decreased across all educational strata in women, but blood pressure increased in women with at least college level education. CONCLUSIONS: These data reveal a different picture in trends in the association of education and cardiovascular risk factors from those depicted in developed countries. This highlights the need for an effective intervention programme in the study population.

Adult↗

Correlative factors of insulin resistance in essential hypertension.

Essential Hypertension (EH) is correlated with a metabolic disturbance characterized by insulin resistance (IR). In this study, there were observed in 47 subjects with EH and 30 subjects with normal blood pressure. Serum levels of insulin-like growth factor-1 (IGF-1), serum levels of growth hormone (GH), the activity of erythrocyte insulin receptors (EIR), and ATP levels in erythrocytes, the insulin sensitivity index (ISI) was used to study the correlative factors of essential hypertension. 1. Among patients with EH, ISI, GH, and low-affinity insulin binding sites of EIRs (RT2) were found to be in significantly lower amounts, IGF-1 levels and the KD2 of the erythrocyte insulin receptors were noted to be significantly higher. Compared with the control group, there was a marked difference between EH group and the control group. However, no statistical difference was observed between the hypertensive group and the group with normal blood pressure as regards erythrocyte ATP levels, high-affinity insulin binding sites of EIRs (RT1), and the KD1 of EIRs. 2. In the hypertensive group, the ISI was negatively correlated with mean arterial blood pressure (MBP), a family history of hypertension, the body mass index (BMI), the waist-hip ratio (WHR) and IGF-1 levels (r=-0.614delta, -0.354**, -0.386**, -0.472**, -0.298*, delta p < 0.001, **p < 0.01, *p < 0.05), were positively correlated with RT2 and GH levels (r=0.301**, 0.275*, **p < 0.01, *p < 0.05). There were no statistically significant differences between ISI and age, sex, smoking history, drinking, RT1, KD1, and ATP levels in erythrocytes. 3. The ISI was used as the dependent variable in multiple linear stepwise regression analysis. MBP (X1), a family history of EH (X2), WHR (X3), GH (X4), IGF-1 (X5), RT2 (X6), and the body mass index (X7) was used as independent variables. X1, X2, X3, X5, X6, and X7 were used in the equations. The results indicate that patients with EH also tend to have IR. We suggest that MBP, a family history of hypertension, BMI, WHR, IGF-1, and RT2 might be independent factors affecting IR in cases of essential hypertension.

Adenosine Triphosphate↗

[Study on hepatitis C virus infection of peripheral blood mononuclear cells in chronic hepatitis C patients].

OBJECTIVE: To demonstrate HCV infection and replication in the peripheral blood mononuclear cells (PBMCs) of hepatitis patients by the methods of molecular biology, immunology and electron microscopy. METHODS: HCV RNA and antigens were detected in the PBMCs of 28 patients with chronic hepatitis C by RT-PCR, Immunohistochemistry and electron microscopy, respectively. RESULTS: The positive rate of HCV RNA and HCV antigens were 77.27% (17/22) and 75.00% (21/28), respectively. Two types of spherical HCV-like particles with diameter of approximately 65 nm and 110 nm were observed in cytoplasmic vesicles by electron microscopy in the PBMCs with high titer of HCV RNA and antigens in 10 patients. The budding and shedding of these particles could also be found in the cytoplasmic vesicles. Immunoelectron microscopy using antibodies against HCV core and NS(3) demonstrated that the particles contained HCV antigens. CONCLUSION: HCV can infect and replicate in the PBMCs of patients with chronic hepatitis C.

Hepacivirus↗

Associations between socioeconomic status and cardiovascular risk factors in an urban population in China.

INTRODUCTION: In developed countries socioeconomic status has been proven to be an important factor in the progression of cardiovascular disease. The present article reports the results of a cross-sectional assessment to investigate the association between socioeconomic status and cardiovascular risk factors in a Chinese urban population. METHODS: In 1996, a behavioural risk factor survey was carried out in Tianjin, the third largest city in China. A sample of 4000 people aged 15-69 years, stratified by sex and 10-year age groups, was drawn randomly from urban areas of the city. The present study covers respondents aged 25-69 years (1615 men and 1592 women). Four socioeconomic indicators (education, occupation, income, and marital status), blood pressure, body mass index, and cigarette smoking were determined in the survey. RESULTS: Educational level seemed to be the most important measure of the four socioeconomic indicators in relation to the cardiovascular risk factors in the study population. People with lower socioeconomic status had higher levels of cardiovascular risk factors. The association between socioeconomic status and cardiovascular risk factors was more consistent among women than men. DISCUSSION: Our findings do not seem to differ from those observed in developed countries.

Adolescent↗

[Identification and visualization of virus-like particles in peripheral blood mononuclear cells].

OBJECTIVE: PBMCs from patients with chronic hepatitis C were examined by electron microscopy (EM), immune EM (IEM) combined with immunohistochemistry to trace the infection and morphology of HCV in the PBMCs. METHODS: The PBMCs from 28 patients with chronic hepatitis C were analyzed firstly for HCV RNA and HCV antigens by RT-PCR and immunohistochemistry respectively. The PBMCs with positive HCV RNA and HCV antigens were then observed by electron microscopy. RESULTS: The positive rate of HCV RNA and HCV antigens were 77.27% (17/22) and 75.00% (21/28), respectively. Two types of polymorphic HCV-like particles with diameter of approximately 65 nm and 110 nm were observed in cytoplasmic vesicles of the PBMCs from HCV Ag positive patients. 10 patients with HCV Ag over expression were studied by electron microscopy and immune election microscopy. The budding phenomenon of the particles could be also visualized in the cytoplasmic vesicles of the PBMCs. Some ultrastructural changes showed an increased ratio of cytoplasm to nucleus and pyknosis of nucleus was also suggestive of the virus infection. CONCLUSIONS: The EM study demonstrated the infection and replication of HCV in the PBMCs of chronic hepatitis C patients by morphology and morphogenesis.

Hepacivirus↗

Diverse behavioural defects caused by mutations in Caenorhabditis elegans unc-43 CaM kinase II.

Calcium/calmodulin-dependent serine/threonine kinase type II (CaMKII) is one of the most abundant proteins in the mammalian brain, where it is thought to regulate synaptic plasticity and other processes. Activation of the multisubunit kinase by calcium is effectively cooperative and can persist long after transient calcium rises. Despite extensive biochemical characterization of CaMKII and identification of numerous in vitro kinase targets, little is known about its function in vivo. Here we report that unc-43 encodes the only Caenorhabditis elegans CaMKII. A gain-of-function unc-43 mutation reduces locomotory activity, alters excitation of three muscle types and lengthens the period of the motor output of a behavioural clock. Null unc-43 mutations cause phenotypes generally opposite to those of the gain-of-function mutation. Mutations in the unc-103 potassium channel gene suppress a gain-of-function phenotype of unc-43 in one tissue without affecting other tissues; thus, UNC-103 may be a tissue-specific target of CaMKII in vivo.

Amino Acid Sequence↗

Apoptosis induction by a novel anti-prostate cancer compound, BMD188 (a fatty acid-containing hydroxamic acid), requires the mitochondrial respiratory chain.

We recently developed a class of novel anti-prostate cancer compounds, cyclic hydroxamates that elicit a potent apoptotic response in many tumor cells cultured in vitro (D.G. Tang et al., Biochem. Biophys. Res. Commun., 242: 380-384, 1998). The lead compound, termed BMD188, induces programmed cell death in a variety of prostate cancer cells in vitro as well as in vivo (L. Li et al., Anticancer Res., 19: 51-70, 1999). BMD188 kills androgen-independent prostate cancer cells as well as prostate cancer cells with a multidrug-resistance phenotype. The apoptotic effect of BMD188 in prostate cancer cells does not depend on cell cycle, p53 status, or its purported target, arachidonate 12-lipoxygenase, but does require caspase activation and seems to involve mitochondria. To synthesize more specific and effective anti-prostate cancer hydroxamic acid compounds, it is important to understand their mechanism(s) of action. In the present study, we studied the role of mitochondrial respiratory chain (MRC) in BMD188-induced apoptosis in androgen-independent prostate cancer PC3 cells and compared its effect with that of staurosporine (STS), a widely used apoptosis inducer. Several lines of evidence indicate that BMD188-induced cell death depends on MRC: (a) the death could be significantly inhibited by several complex-specific respiration inhibitors; (b) respiration-deficient rho0 cells were more resistant than wild-type parent cells to apoptosis induction by BMD188; and (c) BMD188 induced a rapid increase in reactive oxygen species in mitochondria, an up-regulation of cytochrome c oxidase subunits, a biphasic alteration (i.e., an early hyperpolarization, followed by later hypopolarization) in the mitochondrial membrane potential (delta psi(m)), dramatic changes in mitochondrial morphology and distribution prior to caspase activation, and an abnormal proliferation of mitochondria at the ultrastructural level. By contrast, STS-induced PC3 apoptosis seemed not to depend on MRC. Taken together, the data suggest that the MRC represents a functional target for anti-prostate cancer hydroxamates.

Antineoplastic Agents↗

Catecholamine synthesis is mediated by tyrosinase in the absence of tyrosine hydroxylase.

Catecholamine neurotransmitters are synthesized by hydroxylation of tyrosine to L-dihydroxyphenylalanine (L-Dopa) by tyrosine hydroxylase (TH). The elimination of TH in both pigmented and albino mice described here, like pigmented TH-null mice reported previously (Kobayashi et al., 1995; Zhou et al., 1995), demonstrates the unequivocal requirement for catecholamines during embryonic development. Although the lack of TH is fatal, TH-null embryos can be rescued by administration of catecholamine precursors to pregnant dams. Once born, TH-null pups can survive without further treatment until weaning. Given the relatively rapid half-life of catecholamines, we expected to find none in postnatal TH-null pups. Despite the fact that the TH-null pups lack TH and have not been supplemented with catecholamine precursers, catecholamines are readily detected in our pigmented line of TH-null mice by glyoxylic acid-induced histofluorescence at postnatal day 7 (P7) and P15 and quantitatively at P15 in sympathetically innervated peripheral organs, in sympathetic ganglia, in adrenal glands, and in brains. Between 2 and 22% of wild-type catecholamine concentrations are found in these tissues in mutant pigmented mice. To ascertain the source of the catecholamine, we examined postnatal TH-null albino mice that lack tyrosinase, another enzyme that converts tyrosine to L-Dopa but does so during melanin synthesis. In contrast to the pigmented TH-null mice, catecholamine histofluorescence is undetectable in postnatal albino mutants, and the catecholamine content of TH-null pups lacking tyrosinase is 18% or less than that of TH-null mice with tyrosinase. Thus, these extraordinary circumstances reveal that tyrosinase serves as an alternative pathway to supply catecholamines.

Adrenal Glands↗

Evidence for the head domain movement of the rieske iron-sulfur protein in electron transfer reaction of the cytochrome bc1 complex.

The three-dimensional structure of the mitochondrial cytochrome bc1 complex suggests that movement of the extramembrane domain (head) of the Rieske iron-sulfur protein (ISP) may play an important role in electron transfer. Such movement requires flexibility in the neck region of ISP, since the head and transmembrane domains of the protein are rather rigid. To test this hypothesis, Rhodobacter sphaeroides mutants expressing His-tagged cytochrome bc1 complexes with cysteine substitution at various positions in the ISP neck (residues 39-48) were generated and characterized. The mutants with a single cysteine substitution at Ala42 or Val44 and a double cysteine substitution at Val44 and Ala46 (VQA-CQC) or at Ala42 and Ala46 (ADVQA-CDVQC) have photosynthetic growth rates comparable with that of complement cells. Chromatophore membrane and intracytoplasmic membrane (ICM) prepared from these mutants have cytochrome bc1 complex activity similar to that in the complement membranes, indicating that flexibility of the neck region of ISP was not affected by these cysteine substitutions. Mutants with a double cysteine substitution at Ala42 and Val44 (ADV-CDC) or at Pro40 and Ala42 (PSA-CSC) have a retarded (50%) or no photosynthetic growth rate, respectively. The ADV-CDC or PSA-CSC mutant ICM contains 20 or 0% of the cytochrome bc1 complex activity found in the complement ICM. However, activity can be restored by the treatment with beta-mercaptoethanol (beta-ME). The restored activity is diminished upon removal of beta-ME but is retained if the beta-ME-treated membrane is treated with the sulfhydryl reagent N-ethylmaleimide or p-chloromercuribenzoic acid. These results indicate that the loss of bc1 complex activity in the ADV-CDC or PSA-CSC mutant membranes is due to disulfide bond formation, which increases the rigidity of ISP neck and, in turn, decreases the mobility of the head domain. Using the conditions developed for the isolation of His-tagged complement cytochrome bc1 complex, a two-subunit complex (cytochromes b and c1) is obtained from all of the double cysteine-substituted mutants. This suggests that introduction of two cysteines in the neck region of ISP weakens the interactions between cytochromes b, ISP, and subunit IV.

Base Sequence↗

Structure and reaction mechanisms of multifunctional mitochondrial cytochrome bc1 complex.

The cytochrome bc1 complex from bovine heart mitochondria is a multi-functional enzyme complex. In addition to electron and proton transfer activity, the complex also processes an activatable peptidase activity and a superoxide generating activity. The crystal structure of the complex exists as a closely interacting functional dimer. There are 13 transmembrane helices in each monomer, eight of which belong to cytochrome b, and five of which belong to cytochrome c1, Rieske iron-sulfur protein (ISP), subunits 7, 10 and 11, one each. The distances of 21 A between bL heme and bH heme and of 27 A between bL heme and the iron-sulfur cluster (FeS), accommodate well the observed fast electron transfers between the involved redox centers. However, the distance of 31 A between heme c1 and FeS, makes it difficult to explain the high electron transfer rate between them. 3D structural analyses of the bc1 complexes co-crystallized with the Qu site inhibitors suggest that the extramembrane domain of the ISP may undergo substantial movement during the catalytic cycle of the complex. This suggestion is further supported by the decreased in the cytochrome bc1 complex activity and the increased in activation energy for mutants with increased rigidity in the neck region of ISP.

Animals↗

Changes in blood pressure, body mass index, and salt consumption in a Chinese population.

BACKGROUND: The prevalence of hypertension among the population of Tianjin is one of the highest in China. We attempted to assess the changes in blood pressure, body mass index, and salt consumption in Tianjin from 1989 to 1996. METHODS: Two independent cross-sectional population surveys with the representative samples of 14,046 persons in 1989 and 2,000 persons in 1996 were carried out in Tianjin. A salt surveillance system was established with four salt consumption surveys (in 1992, 1993, 1994, and 1996) to estimate the changes in salt consumption at the household level. RESULTS: From 1989 to 1996, the prevalence of hypertension and obesity decreased among people aged 45-64 years in both genders. Mean systolic blood pressure decreased significantly in women and leveled off in men. Diastolic blood pressure increased significantly. Body mass index remained unchanged. The unfavorable trends were mainly attributable to the negative changes in younger people (15-34 years) in both genders. There were no changes in salt consumption between 1992 and 1996 at the house level. CONCLUSIONS: There was a favorable development in prevalence of hypertension and obesity among individuals in the age group of 45-64 years in the study population. Health education needs to pay more attention to young people.

Adolescent↗

Determination of zinc contents in rabbits with cerebral ischemia by NAA and ICP-AES.

Cerebral ischemia is an important cerebral vascular disease, and zinc is a necessary trace element for humans. In this work, a cerebral ischemia model of rabbit was established by operation. The samples of brain and serum in the animal models were collected. The Zn contents in the samples were determined by neutron activation analysis and inductively coupled plasma-atomic emission spectrometry. The results show the Zn contents in brain decreased 2 mo after cerebral ischemia, and Zn contents in serum decreased even more obviously. In addition, a positive correlation of Zn contents between left and right cerebral hemispheres was observed, and the positive correlation between brain and serum was also observed. A test of Chinese medicine was also carried out in the work. Two Chinese medicines were fed to rabbits with cerebral ischemia in the experiments. The results showed they probably can prevent the decrease of Zn contents in serum.

Animals↗

Structural basis of multifunctional bovine mitochondrial cytochrome bc1 complex.

The mitochondrial cytochrome bc1 complex is a multifunctional membrane protein complex. It catalyzes electron transfer, proton translocation, peptide processing, and superoxide generation. Crystal structure data at 2.9 A resolution not only establishes the location of the redox centers and inhibitor binding sites, but also suggests a movement of the head domain of the iron-sulfur protein (ISP) during bc1 catalysis and inhibition of peptide-processing activity during complex maturation. The functional importance of the movement of extramembrane (head) domain of ISP in the bc1 complex is confirmed by analysis of the Rhodobacter sphaeroides bc1 complex mutants with increased rigidity in the ISP neck and by the determination of rate constants for acid/base-induced intramolecular electron transfer between [2Fe-2S] and heme c1 in native and inhibitor-loaded beef complexes. The peptide-processing activity is activated in bovine heart mitochondrial bc1 complex by nonionic detergent at concentrations that inactivate electron transfer activity. This peptide-processing activity is shown to be associated with subunits I and II by cloning, overexpression and in vitro reconstitution. The superoxide-generation site of the cytochrome bc1 complex is located at reduced bL and Q*-. The reaction is membrane potential-, and cytochrome c-dependent.

Animals↗

The administration schedule of cyclin-dependent kinase inhibitor gene therapy and etoposide chemotherapy is a major determinant of cytotoxicity.

Cyclin-dependent kinase inhibitors are potent suppressors of cell growth and have been proposed as targets for gene replacement therapy in cancer. Expression of either p16INK4a or p21WAF1 protected cells from the cytotoxic effects of the topoisomerase II inhibitor, etoposide. A lower level of p53 was induced in CDK inhibitor-expressing etoposide-exposed cells suggesting that protection may be due to lower levels of DNA damage in the growth arrested cells. Exposure of human osteosarcoma cells to either p16INK4a or p21WAF1 prior to and during etoposide therapy protected cells against etoposide-induced cell death. Infection of the cells by Ad-p16INK4a or Ad-p21WAF1 following exposure to etoposide resulted in loss of the protective effect with evidence of enhanced growth inhibition. The results suggest that the schedule of administration of DNA damaging etoposide chemotherapy and cell cycle inhibitory therapy is a major determinant of the resulting cytotoxicity.

Antineoplastic Agents, Phytogenic↗

[The significance of detection of hepatitis C virus RNA in peripheral blood mononuclear cells of patients with chronic hepatitis C].

OBJECTIVE: To determine the role of peripheral blood mononuclear cells (PBMCs) in hepatitis C virus (HCV) infection. METHODS: HCV RNA, HCV antigen and Fas antigen were detected in PBMCs of 22 patients with chronic hepatitis C, 21 renal dialysis patients with anti-HCV positive and 12 health blood donors as normal controls. All specimens were studied by electronic microscope (EM). RESULTS: (1) The positive rate of HCV RNA in PBMCs of 22 patients with hepatitis C was 77.3% (17/22). (2) EM showed that HCV particles replicated in PBMCs of the patients with HCV infection, but not in the serum of patients with negative HCV RNA and healthy controls. (3) HCV RNA were positive both in the serum and PBMCs of 8 patients with HCV particles positive and had a close relationship with HCV antigen and Fas antigen. The expression of HCV and apoptosis were found in the cytoplasm of PBMCs in these 8 patients. CONCLUSION: (1) Hepatitis C virus could replicate in PBMCs and produce infectious HCV particles. (2) HCV in PBMCs may act as the source of reinfection for HCV and lead to persistent infection and recurrence.

Adult↗

The hypoxia-responsive transcription factor EPAS1 is essential for catecholamine homeostasis and protection against heart failure during embryonic development.

Mice lacking the hypoxia-inducible transcription factor EPAS1 die at mid-gestation. Despite normal morphological development of the circulatory system, EPAS1-deficient mice display pronounced bradycardia. In addition to the vascular endothelium, EPAS1 is expressed intensively in the organ of Zuckerkandl (OZ), the principle source of catecholamine production in mammalian embryos. EPAS1-deficient embryos contained substantially reduced catecholamine levels. Mid-gestational lethality was rescued by administration of the catecholamine precursor DOPS to pregnant females. We hypothesize that EPAS1 expressed in the OZ senses hypoxia during mid-gestational development and translates this signal into an altered pattern of gene expression, leading to increases in circulating catecholamine levels and proper cardiac function.

Animals↗