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Biomedical subjects

Q Han

Publications and source records attributed to Q Han.

At least 55 records · Page 3Linked to original sources
PubMed1998

Unloaded heart in vivo replicates fetal gene expression of cardiac hypertrophy.

The cardiac response to increased work includes a reactivation of fetal genes. The response to a decrease in cardiac work is not known. Such information is of clinical interest, because mechanical unloading can improve the functional capacity of the failing heart. We compared here the patterns of gene expression in unloaded rat heart with those in hypertrophied rat heart. Both conditions induced a re-expression of growth factors and proto-oncogenes, and a downregulation of the 'adult' isoforms, but not of the 'fetal' isoforms, of proteins regulating myocardial energetics. Therefore, opposite changes in cardiac workload in vivo induce similar patterns of gene response. Reactivation of fetal genes may underlie the functional improvement of an unloaded failing heart.

Anastomosis, Surgical↗
PubMed1998

Insulin does not change the intracellular distribution of hexokinase in rat heart.

Preliminary evidence has suggested that hexokinase in rat heart changes its kinetic properties in response to insulin through translocation to the outer mitochondrial membrane. We reexamined this hypothesis in light of tracer kinetic evidence to the contrary. Our methods were as follows. Working rat hearts were perfused with Krebs-Henseleit buffer containing glucose (5 mmol/l) and sodium oleate (0.4 mmol/l). Dynamic glucose uptake was measured with [2-3H]glucose and with 2-deoxy-2-[18F]fluoroglucose (2-[18F]DG). Hexokinase activity was determined in the cytosolic and mitochondrial fractions. Our results are as follows. Uptake of glucose and uptake of 2-[18F]DG were parallel. Insulin (1 mU/ml) increased glucose uptake threefold but had no effect on 2-[18F]DG uptake. The tracer-to-tracee ratio decreased significantly. The Michaelis-Menten constant of hexokinase for 2-deoxyglucose was up to 10 times higher than for glucose. There was no difference in maximal reaction velocity. Two-thirds of hexokinase was bound to mitochondria. Insulin neither caused translocation nor changed Michaelis-Menten constant or maximal reaction velocity. In conclusion, the insulin-induced changes in the tracer-to-tracee ratio are due to a shift of the rate-limiting step for glucose uptake from transport to phosphorylation by hexokinase. Insulin does not affect the intracellular distribution or the kinetics of hexokinase.

Animals↗
PubMed1998

[Relationship between catalase activity, KatG gene and isoniazid-resistance in M. tuberculosis].

OBJECTIVE: To investigate the relationship between catalase activity, KatG gene, gene mutation and INH-resistance in M. tuberculosis. METHOD: Catalase activities in 58 M. tuberculosis isolates were tested, and KatG gene mutations were detected further by PCR-SSCP. RESULT: None of INH-sensitive isolates lacked KatG sequences and all expressed catalase. 8(25%) INH-resistant isolates did not express catalase and 3(10%) lacked KatG gene, most of which were strains of high levels of resistance (MIC > 50 micrograms/ml). 8 INH-resistant isolates were analyzed further by PCR-SSCP and all were found to have KatG gene mutation. CONCLUSION: These findings indicated that lacking of catalase activity and KatG gene deletion occurred mainly in those highly INH-resistant strains, gene mutation other than complete deletion of KatG gene may be the major mechanism of INH-resistance.

Antitubercular Agents↗
PubMed1998

[Alpha1-adrenoceptor subtypes in rabbit penile corpus cavernosum].

OBJECTIVE: To study alpha(1)- adrenoceptor (alpha(1)- AR) subtypes with the functional role and the distribution of its subtypes in rabbit penile corpus cavernosum. METHOD: The rabbit penile corpus cavernosum was studied by using functional experiment and radioligand binding assay. RESULT: In the radioligand binding assay, the maximal binding capacity (Bmax of (125)IBE and alpha(1)-AR) decreased obviously after pretreatment with chloroethylclonidine (CEC), which were 746 +/- 236 fmol/mg protein and 214 +/- 71 fmol/mg protein, respectively. Alpha(1A)-, alpha(1D)-and alpha(1B)-AR took about 20%, 25% and 55%, respectively. In the functional experiments, the maximal contraction induced by norepinephrine (NE) was not decreased significantly after pretreatment with CEC. The pA(2) values of two alpha(1)-AR selective antagonists, 5-MU, BMY7378, for antagonizing NE-induced penile corpus cavernosum contraction had a high correlative association with the pK(I) values for cloned alpha(1A)-AR. CONCLUSION: The functional alpha(1)-AR subtype is alpha(1A)-AR although there are three subtypes in the penile corpus cavernosum.

Adrenergic alpha-Agonists↗
PubMed1997

[Prognosis and adjuvant chemotherapy of axillary node-negative breast cancer patients].

The significance of postoperative chemotherapy was studied in 439 cases of unilateral primary breast cancer which were proved histologically with no axillary lymph node metastasis. The survival rate was analyzed by life table method. The prognosis of node negative breast cancer patients was mainly associated with tumor size. 10 year survival rate of patients with tumor less than 3 cm treated operativel and by operation combined with chemotherapy was 92.60% and 94.13% respectively. If tumor size was larger than 3 cm, the ten year survival rate of the patients treated operatived was 79.89%, and that of the patients with combined theropy 96.02%. The prognosis was statistically different between the two groups. As to age, status of menopause, pathologral type, kind of surgery and status of ER, the prognosis of patients treated by combined therapy was better than that of patients treated by operation alone. The postoperative chemotherapy was not significantly beneficial to breast cancer patients with tumor less than 3 cm.

Adenocarcinoma↗
PubMed1997

[Male breast cancer: experience with 42 cases].

Data were collected on 42 men with breast cancer treated at department of surgery, cancer hospital in Shanghai between 1960 to 1996. We studied several clinical features and the importance of established prognostic factors. Observation for 76 months showed the 5 year survival rate was 57.1%, and the total survival was 64.3%. Prognostic indicator analysis showed that only axillary lymph node status proved to have a prognostic impact. Tumor size, age did not show any prognostic influence. Because of less cases, we can not use Cox's regression model to do multivariate analysis.

Adult↗
PubMed1997

[Cox proportion hazard model multivariate analysis of prognosis of 1,484 axillary node-negative breast cancer patients].

OBJECTIVE: To study the prognosis of axillary node-negative breast cancer patients. METHODS: The data were analyzed in 1,484 consecutive axillary node-negative breast cancer patients. Twenty-two individual variables were evaluated statistically using the cumulative survival rate by the computer's Cox multivariate analysis model. RESULTS: Menopausal status, times of pregnancy, duration before diagnosis, pregnancy-associated, tumor size, intramammary lymph node, postoperative radiotherapy and postoperative adjuvant tamoxifen therapy were independent predictors of prognosis. CONCLUSION: Parts of high risk group among axillary node-negative breast cancer patients could be identified by clinical parameters. Postoperative radiotherapy or ovarian ablation was not indicated for axillary node-negative breast cancer patients. Tamoxifen as postoperative adjuvant therapy should not be restricted to postmenopausal or ER-positive patients. The selection of high risk patients with axillary node-negative breast cancer who should receive adjuvant chemotherapy remains to be investigated at present.

Adult↗
PubMed1997

Estrogen receptor-negative breast cancer cells transfected with estrogen receptor exhibit decreased tumour progression and sensitivity to growth inhibition by estrogen.

Breast cancer containing estrogen receptors (ER) are responsive to antiestrogen treatment and have a better prognosis compared with ER-negative tumors. The loss of estrogen receptors appears to be associated with a progression to less-differentiated cells. We transfected the human ER into the ER-negative breast cancer cell line MDA-MB-231 cells. We found that expression of adequate ER is strong associated with the ability of human breast cancer cell growth inhibition and progression. Compared with nontransfected or mock-transfected cells, ER-transfected cells exhibited growth slower, forming smaller colonies in soft agar and growth inhibited by estrogen and tamoxifen. Therefore reactivation or transfection of the estrogen receptor gene can be considered as therapeutic approaches to hormone-independent breast cancer.

Breast Neoplasms↗
PubMed1997

p53 independent G1 arrest and apoptosis induced by adriamycin.

The biological activity of adriamycin was investigated in human breast carcinoma (HBC) cells, Adriamycin inhibited the growth of a number of HBC cell lines and induced G1 arrest followed by apoptosis. In MCF-7 cells that harbor wild-type p53, adriamycin-induced G1 arrest and apoptosis was accompanied by p53-independent regulation of WAF1/CIP1 as well as bax mRNA levels. In MDA-MB-231 cells which possess a mutant p53, adriamycin-induced G1 arrest and apoptosis was also associated with a concomitant up-regulation of WAF1/CIP1 mRNA while these cells did not express bax or bcl-2 messages. Thus, adriamycin induces G1 arrest and apoptosis via a unique pathway which appears to involve activation of downstream effectors of p53-independent manner.

Antineoplastic Agents↗
PubMed1997

[The changing vasculo-cardiology in the midst of revolution of modern science and technology].

Modern revolution of science and technology exerts profound and overall influences on the basic research, diagnosis and treatment of cardiovascular diseases. The application of molecular biology has been revealing the nature of cause, pathogenic mechanism, physiology and pathology of cardiovascular diseases, while gene therapy is expected to yield a radical cure of these diseases. The products of modern technology including computerized tomography, computer enhanced digital angiography, magnetic resonance imaging, ultrasonic-cardiography, positron emission tomography, single photon emission computerized tomography, percutaneous transluminal coronary angioplasty and other techniques, laser, artificial pacemaker, artificial heart etc. have greatly improved the capacity of diagnosis and therapy of cardiovascular diseases. Now the studies probe not only the levels of organ and cell, but also the levels of protein, nucleic acid and gene. The diagnosis of cardiovascular diseases is focussed on, besides the traditional "four diagnostic methods", i.e. inspection, palpation, percussion and auscultation, precise diagnosis with the help of various advanced medical equipments. As to the treatment, in addition to traditional drugs and surgical operations, new therapeutic methods such as gene therapy and interventional measures are also applied.

Biotechnology↗
PubMed1997

[Preparation and characterization of recombinant retroviral vector containing t-PA cDNA].

A recombinant retroviral vector containing tissue-type plasminogen activator (t-PA) cDNA was constructed and transfected into PA317 viral packaging cells, forming intact virus particles. Under electron microscope the recombinant retroviral particles were composed of envelope, capsid and core. These viral particles were spherical with a diameter of 90-180nm, and spread dispersely in the cells. NIH3T3 cell infected by retrovirus particles were screened with G418. The virus titer of 6 x 10(8) CFU/L was verified by counting the positive clones two weeks after screening. The expression of t-PA was demonstrated in the NIH3T3 cells infected with the recombinant virus.

DNA, Complementary↗
PubMed1996

Cyclic HIV protease inhibitors: synthesis, conformational analysis, P2/P2' structure-activity relationship, and molecular recognition of cyclic ureas.

High-resolution X-ray structures of the complexes of HIV-1 protease (HIV-1PR) with peptidomimetic inhibitors reveal the presence of a structural water molecule which is hydrogen bonded to both the mobile flaps of the enzyme and the two carbonyls flanking the transition-state mimic of the inhibitors. Using the structure-activity relationships of C2-symmetric diol inhibitors, computed-aided drug design tools, and first principles, we designed and synthesized a novel class of cyclic ureas that incorporates this structural water and preorganizes the side chain residues into optimum binding conformations. Conformational analysis suggested a preference for pseudodiaxial benzylic and pseudodiequatorial hydroxyl substituents and an enantiomeric preference for the RSSR stereochemistry. The X-ray and solution NMR structure of the complex of HIV-1PR and one such cyclic urea, DMP323, confirmed the displacement of the structural water. Additionally, the bound and "unbound" (small-molecule X-ray) ligands have similar conformations. The high degree of preorganization, the complementarity, and the entropic gain of water displacement are proposed to explain the high affinity of these small molecules for the enzyme. The small size probably contributes to the observed good oral bioavailability in animals. Extensive structure-based optimization of the side chains that fill the S2 and S2' pockets of the enzyme resulted in DMP323, which was studied in phase I clinical trials but found to suffer from variable pharmacokinetics in man. This report details the synthesis, conformational analysis, structure-activity relationships, and molecular recognition of this series of C2-symmetry HIV-1PR inhibitors. An initial series of cyclic ureas containing nonsymmetric P2/P2' is also discussed.

Animals↗
PubMed1996

Evidence for altered cellular calcium in the pathogenetic mechanism of acute pancreatitis in rats.

Although several pathophysiological sequences, such as protease activation, free radical generation, and inflammatory mediator release, have been described in acute pancreatitis, the precise mechanism by which acute pancreatitis is initiated is unknown. Cellular calcium, a key physiological signaling element in cell function and also a crucial pathological intracellular messenger in cell injury, appears to be involved in the initiation and development of acute pancreatitis. The present study provides several lines of evidence supporting this suggestion. First, verapamil (a calcium channel blocker) administration was associated with a significant protection of rats from acute pancreatitis induced by high doses of cerulein (50 micrograms/kg/hr, subcutaneously), as evidenced both histologically and biochemically. Second, verapamil was found to minimize the increased tissue levels of calcium, platelet-activating factor, and thromboxane B2 detected during acute pancreatitis. Third, acute pancreatitis could be observed in rats with elevated serum calcium levels at low doses of cerulein (5 micrograms/kg/hr, subcutaneously), but could not be observed in rats with normal serum calcium levels treated with low doses of cerulein. It is proposed that cellular calcium, which is a critical signaling component in the synthesis and release of inflammatory mediators and several other events, may be an important factor in the pathogenesis of cerulein-induced acute pancreatitis.

Acute Disease↗
PubMed1996

Hormonal stimulation of calcium mobilization in the isolated perfused rat pancreas.

Hormone-stimulated cellular Ca2+ mobilization in the isolated perfused rat pancreas was investigated by analyzing the efflux profiles of 45Ca2+ from 45Ca(2+)-loaded pancreata following agonist stimulation. The increased 45Ca2+ efflux reflects the enhanced exchange of Ca2+ across the plasma membrane as a result of increased [Ca2+]i. Both high and low concentrations of the cholecystokinin analog, cerulein, applied to the isolated perfused pancreas gave rise to an increased release of 45Ca3+. The patterns of the increase in 45Ca2+ release were consistently different for high and low concentrations of the agonist. Cerulein infused at a concentration of 10(-11) M induced a release of a small but significant amount of 45Ca2+ which could be abolished by 8-(N,N-diethylamine)octyl-3,4,5-trimethoxy-benzoate (TMB-8), but was not affected by ethyleneglycol-bis(beta-aminoethyl ether)-N,N,N',N'-tetraacetic acid (EGTA). Cerulein stimulation at 10(-9) M elicited a marked increase in 45Ca2+ release which was minimized by EGTA, but not by TMB-8. Also, infusion of cerulein stimulated a concentration-dependent amylase secretion response which displayed the same TMB-8- and EGTA-sensitivity pattern as the 45Ca2+ release response. The present study suggests (i) that cellular Ca2+ influx is a prominent feature of the increased 45Ca2+ efflux (i.e., increased [Ca2+]i) induced by pharmacological concentrations of cerulein while physiological concentrations of cerulein cause an increase in [Ca2+]i which is due predominantly to a release of internal Ca2+; and (ii) [Ca2+]i changes are essential for pancreatic enzyme secretion. Although isolated pancreatic acini or cells may lose their sensitivity and physiological responses to various agonists during isolation and preparation, the isolated perfused pancreas is a suitable and very sensitive model in which to study the physiology of Ca2+ mobilization and enzyme secretion.

Amylases↗
PubMed1996

Inhibition of spontaneous apoptosis in human breast cancer.

Breast tumorigenesis proceeds through an accumulation of specific genetic alteration. Breast malignant transformation is dependent on not only the rate of cell production but also on apoptosis, a genetically programed process of autonomous cell death. We investigated whether breast tumorigenesis involved an altered susceptibility to apoptosis and proliferation by examining normal breast epithelium and breast cancer samples. We found there is a great inhibition of spontaneous apoptosis in breast cancer cells compared with normal breast epithelium. The inhibition of apoptosis in breast cancer may contribute to neoplastic transformation.

Apoptosis↗
PubMed1996

Effect of captopril on renal hemodynamics and renal prostaglandins in early type II diabetic patients with normo-or microalbuminuria.

In this study, we investigated the effect of captopril (CPT) on glomerular filtration rate (GFR), effective renal plasma flow (ERPF), filtration fraction (FF), urinary albumin excretion (UAE) and daily urinary excretion of thromboxane B2 (TXB2) and 6-keto- prostaglandin F1a (6-keto-PGF1a) in 29 normotensive non-insulin-dependent diabetes (NIDDM) patients without clinically discernible nephropathy. Before treatment, urinary excretion 6-keto-PGF1a was significantly increased (P < 0.05) in 29 NIDDM patients compared with 25 health subjects matched for age and sex. The values of GFR and FF were significantly higher (P < 0.01 and P < 0.005, respectively) in NIDDM than in normal volunters, whereas ERPF was comparable in both groups. Meanwhile we observed that UAE of early NIDDM was increased before treatment. After CPT treatment, GFR, FF, UAE and urinary excretion of 6-keto-PGF1a were significantly reduce (all P < 0.005) compared with those of NIDDM before treatment. These data indicated that CPT is effective in lowering glomerular filtration pressure and ameliorating microalbuminuria in the normotensive early NIDDM.

6-Ketoprostaglandin F1 alpha↗
PubMed1996

[Effects of tangshenkang capsule on diabetic nephropathy].

To study the effects of Chinese herbal medicine Tangshenkang (TSK) capsule on diabetic nephropathy (DN), 57 patients with DN were randomly divided into two groups, the treated group and the control group, they were treated with TSK capsule and the conventional therapy respectively. There were serious disorders of metabolism in DN patients, that showed the TXB 2/6-keto-PGF1 alpha ratios and lipid peroxidase (LPO) levels were higher than that of healthy people. After 6 weeks treated with TSK capsule the albuminuria levels reduced obviously (decreased 51%), renal plasma flow (RPF) increased, glomerular filtration rate and the LPO levels decreased and a positive correlation was observed between albuminuria levels and TXB 2/6-keto-PGF1 alpha ratios while the clearance rate of creafinin didn't improve significantly. There were no significant difference in the above-mentioned parameters in the control group before and after treatment. These results suggested that TSK capsule possessed a significant effect in improving albuminuria and glomerular function. And the effect of TSK might be due to its adjusting TXB 2/6-keto-PGF1 alpha ratios and its lipid-peroxidation in DN patients.

6-Ketoprostaglandin F1 alpha↗