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Biomedical subjects

Q Huang

Publications and source records attributed to Q Huang.

At least 181 records · Page 10Linked to original sources

Effects of leptin adipose tissue lipoprotein lipase in the obese ob/ob mouse.

OBJECTIVE: To characterize the adaptations of lipid metabolism, with special emphasis on tissue lipoprotein lipase, to negative energy balance brought by chronic treatment of obese ob/ob mice with leptin. DESIGN: According to a 2 x 2 factorial analysis, lean and obese C57BL/6J mice were subcutaneously infused with leptin (100 micrograms.kg-1.day-1) or vehicle (phosphate-buffered saline) during seven days. RESULTS: Cumulative food intake and final body weight of vehicle-infused obese mice were twofold higher than in lean controls. Leptin decreased cumulative food intake and body weight of obese, but not lean mice. Lipoprotein lipase (LPL) activity in white inguinal and epididymal and brown interscapular adipose tissues of control obese mice was at least twofold higher than in lean mice, but comparable in the vastus lateralis muscle. Leptin treatment of obese mice significantly lowered LPL activity to that of lean mice in all tissues examined. Vehicle-infused obese mice had higher liver triglyceride content and were hypertriglyceridemic compared to lean mice, and triglyceride concentrations in plasma and liver were decreased proportionally after leptin treatment. Leptin lowered glycemia and insulinemia of obese mice to lean levels and decreased plasma corticosterone. Leptin infusion had no notable effect on tissue lipoprotein lipase nor plasma variables of lean mice. CONCLUSIONS: Leptin infusion abolished hyperinsulinemia in the ob/ob mouse, an effect that was probably responsible for the concomitant normalization of adipose LPL activity. This study shows that decreased LPL activity, plasma triglyceride concentrations and hepatic triglyceride production constitute some of the adaptive peripheral adaptations of lipid metabolism, which accompany the reduction in fat mass accretion brought by leptin treatment of the obese ob/ob mouse.

Adipose Tissue↗

Lack of associations between serum leptin, a polymorphism in the gene for the beta 3-adrenergic receptor and glucose tolerance in the Dutch population.

BACKGROUND: The associations between leptin levels and the prevalence of a polymorphism in the beta 3-adrenergic receptor were studied in a cross-sectional analysis of 600 participants in a population-based study, which were stratified for glucose tolerance by an oral glucose tolerance test. METHODS: In a random sample of 600 participants in the Rotterdam study, aged 55-75 years at baseline (309 men, 291 women) the relationships were studied between the presence of Trp64 Arg mutation in the beta 3-adrenergic receptor gene and fasting leptin, glucose and insulin (fasting and after an oral glucose load), and other components of the insulin resistance syndrome. RESULTS: Mean age of the study population was 66.9 years (SD 5.7). Fasting serum leptin levels overall in men and women were 6.1 micrograms/l (SE 0.2) and 21.7 micrograms/l (0.9), respectively, (P < 0.001). These differences were independent of age, body mass index and waist to hip ratio. We identified 73/600 persons who were heterozygotes for the Trp64 Arg polymorphism (allelic frequency 6.1%), but failed to find an association between the presence of this polymorphism and leptin or any measured parameter indicative for obesity, impaired glucose tolerance or type 2 diabetes mellitus. CONCLUSION: Heterozygosity for the Trp64Arg polymorphism of the beta 3-adrenergic receptor gene is not accompanied by obesity, impaired glucose tolerance and type 2 diabetes mellitus in the general elderly Dutch population, and is also not associated with changes in circulating leptin levels.

Aged↗

Tyrosine phosphorylation of paxillin/pp125FAK and microvascular endothelial barrier function.

The transendothelial movement of solutes is a dynamic process controlled by a complex interaction between the cytoskeleton and adhesion proteins. The aim of this study was to examine whether protein tyrosine phosphorylation is involved in the regulation of endothelial barrier function. The apparent permeability coefficient of albumin (Pa) was measured in isolated and perfused coronary venules. Tyrosine phosphatase inhibitors, including phenylarsine oxide and sodium orthovanadate, dose and time dependently increased basal Pa. Western blot analysis of cultured coronary venular endothelial cells revealed that inhibition of tyrosine phosphatase induced an increase in phosphotyrosine content in a number of proteins, including bands at 65-70 and 120-130 kDa, which were identified as paxillin and focal adhesion kinase (pp125FAK), respectively. The time course and dose responsiveness of protein tyrosine phosphorylation were tightly correlated with those of increases in Pa. Furthermore, stimulation of endothelial cells with histamine or phorbol myristate acetate (PMA) enhanced tyrosine phosphorylation of paxillin and pp125FAK, which was blocked by the tyrosine kinase inhibitor damnacanthal. Correspondingly, the increases in venular permeability elicited by histamine and PMA were abolished in damnacanthal-treated venules. Taken together, the data suggest a possible involvement of protein tyrosine phosphorylation in the control of endothelial barrier function. Paxillin and its associated focal adhesion proteins may play a specific role in agonist-induced hyperpermeability responses in the endothelium of exchange vessels.

Animals↗

Neutrophil-dependent augmentation of PAF-induced vasoconstriction and albumin flux in coronary arterioles.

Platelet-activating factor (PAF) has been implicated in the pathogenesis of ischemic heart disease, reperfusion injury, and inflammatory reactions. Although neutrophils have been shown to primarily mediate PAF-induced microvascular dysfunction, the vasoactive effect of PAF and its neutrophil-dependent mechanism have not been directly and systematically studied in coronary resistance vessels. Therefore, the aim of this study was to examine the effects of PAF on coronary arteriolar function and neutrophil dynamics using an isolated and perfused microvessel preparation. Topical application of PAF to the vessels induced a dose-dependent decrease in the diameter but an increase in the apparent permeability coefficient of albumin. Disruption of the endothelium abolished the vasomotor response to PAF, and perfusion of neutrophils significantly augmented PAF-induced changes in vasomotor tone and permeability. Furthermore, the interaction between neutrophils and the endothelium was studied in the intact perfused coronary arterioles. Under control conditions, there were no adherent neutrophils observed in the vessels at varied intraluminal flow velocities. However, administration of PAF caused neutrophil adhesion to the endothelium of coronary arterioles at low flow velocities. Western blot analysis indicated that PAF upregulated the expression of intercellular adhesion molecule-1 in cultured coronary microvascular endothelial cells. Taken together, the results suggest that 1) PAF induces vasoconstriction and hyperpermeability in coronary arterioles via an endothelium-dependent and neutrophil-mediated mechanism, and 2) PAF is able to stimulate neutrophil adhesion in coronary arterioles under a condition of low flow rate.

Animals↗

Effects of leptin on corticotropin-releasing factor (CRF) synthesis and CRF neuron activation in the paraventricular hypothalamic nucleus of obese (ob/ob) mice.

The effects of leptin on the levels of CRF messenger RNA (mRNA) in the paraventricular hypothalamic nucleus (PVN), on the activation of the PVN CRF cells, and on the plasma levels of corticosterone were investigated in lean (+/?) and obese (ob/ob) C57BL/6J male mice. Murine leptin was s.c. infused using osmotic minipumps. The treatment period extended to 7 days, and the daily dose of leptin delivered was 100 microg/kg. The mice were killed either in a fed state or following 24 h of total food deprivation. The starvation paradigm was employed to enhance the activity of the hypothalamic-pituitary-adrenal axis in obese mice. In situ hybridization histochemistry was performed to determine the PVN levels of CRF mRNA and the arcuate nucleus levels of neuropeptide Y mRNA. The activity of the PVN CRF cells was estimated from the number of PVN cells colocalizing CRF mRNA and the protein Fos. Leptin led to a reduction in body weight gain and fat deposition. These effects were seen in both +/? and ob/ob mice and were observed to be particularly striking in obese mutants, in which leptin also caused an important reduction in food intake. Leptin also was found to affect plasma levels of corticosterone. It lowered the high corticosterone levels of obese mutants, an effect that appeared more evident in food-deprived than in fed mice. Finally, leptin prevented the induction of CRF synthesis in the PVN and the activation of the PVN CRF neurons observed in food-deprived ob/ob mice and hindered the elevation of arcuate nucleus neuropeptide Y synthesis in ob/ob mice. Together these results suggest a role for leptin in the excessive response of the hypophysiotropic CRF system of the ob/ob mouse.

Adipose Tissue↗

[Relationship of lipoprotein(a) to fibrinolytic activities in healthy subjects].

Plasma tissue-type plasminogen activator(tPA) and plasminogen activator inhibitor(PAI-1) and lipoprotein(a) [Lp(a)] in 133 healthy subjects were determined. The results demonstrated that PAI-1 activity was higher in Lp(a) > or = 0.3 g.L-1 group than Lp(a) < 0.3 g.L-1 group (P < 0.05). Univariate statistical analyses showed Lp(a) concentration was positively associated with PAI-1 activity (P < 0.01), but not with age, sex, body mass index, blood lipids or tPA activity.

Adult↗

[The structure, function and mutation of Rb gene promoter in normal individuals and retinoblastoma patients].

OBJECTIVE: To investigate the DNA sequence of the 5' untranslated region of the Rb gene in normal individuals and retinoblastoma patients and identify the elements involved in transcription regulation of Rb gene. METHODS: SSCP analysis and direct genomic DNA sequencing were used to identify variations or alterations in DNA of normal adult WBC and tumor DNA of retinoblastoma patients. The different DNA fragments located in the 5' untranslated region of Rb gene were amplified and inserted into an expression plasmid with a CAT reporter gene. The capacity of transcription regulation of isolated DNA fragments was determined by CAT assay. RESULTS: A 240 bp DNA fragment located between -327(-)-87 bp upstream of the first starting codon was shown to be the sequence with essential promoter function. The Sp1/RBF-1, ATF and E2F binding sites were present in this region and positive and negative elements were found further upstream and downstream. Four of 5 naturally occurring mutations were identified in either Sp1/RBF-1 or ATF binding sites from 302 patients with retinoblastoma. All these mutants had reduced CAT activity. However, 100 cases of normal adults did not show any variant DNA sequence in the same region. CONCLUSION: The promoter DNA sequence of Rb gene is quite stable. Its variation usually leads to reduction in promoter activity which may be associated with genetic susceptibility to retinoblastoma.

Adult↗

[Effect of Zhongfeng Naodeping Granule on hippocampal excitatory amino acid and neuron of stroke-prone spontaneously hypertensive rats with hemorrhagic apoplexy].

OBJECTIVE: To observe the effects of Zhongfeng Naodeping Granule (ZFNDPG) on hemorrhagic apoplexy. METHODS: The stroke-prone spontaneously hypertensive rats (SHRsp) were used to study effects of ZFNDPG on hemorrhage apoplexy. Excitatory amino acid (EAA) concentration in hippocampus sector, neuronal density and ultrastructural changes in hippocampal CA1 sector were measured. RESULTS: In pathological model group glutamate (Glu) and aspartate (Asp) concentration elevated obviously. With the ZFNDPG treating SHRsp of hemorrhagic apoplexy, Glu and Asp concentration in hippocampal sector could be markedly inhibited, compared with model group, P < 0.05-0.01. Neuronal morphology was observed: neurone injury was mild and neuronal density increased in hippocampal CA1 sector of treatment group, compared with model group, P < 0.01. Electron microscopy showed: edema, degeneration and necrosis caused by hemorrhagic apoplexy were improved after the ZFNDPG treatment. CONCLUSIONS: Effects of protecting neurone for SHRsp on hemorrhagic apoplexy might be associated with that ZFNDPG inhibited concentration of EAA.

Animals↗

[Surgical treatment of infective endocarditis].

OBJECTIVE: To summarize the experience of surgical treatment of infective endocarditis in 28 patients. METHOD: Open heart surgery under cardiopulmonary bypass was performed in all patients: valve replacement (24), VSD repair and tricuspid annuloplasty (3), and Bentall (1) 17 mechanical and 7 homograft valves were placed. RESULT: Two died in hospital, 4 died from infection, 1 had periprosthetic leakage and incompetence respectively. 22 survivors showed improved heart function. CONCLUSION: Combined medication and surgical treatment is superior to antibiotic treatment in long-term survival and convalescence. Infective reccurrence, reinfection and advanced heart failure are major risk factors after operation.

Adolescent↗

[Effect of RNA against hepatic fibrosis in rabbits infected with Schistosoma japonicum].

AIM: To study the effect of ribonucleic acid (RNA) against schistosomal hepatic fibrosis in rabbits. METHODS: 54 rabbits were randomly and equally divided into normal group, infected group, and RNA group. On the 40, 70, 100th day after RNA i.m. injection, 6 rabbits from each of the above 3 groups were killed and their plasma and liver were examined by way of biochemistry and pathology. RESULTS: Compared with the infected group the collagen fiber of liver in RNA group was less produced, the hepatic cellular nucleolus was enlarged, the number of rough endoplasmic reticulum (RER) and the granules on the RER were increased, the collagen fiber around fat-storing cell was decreased, the content of hyaluronic acid in plasma, the hydroxyproline level in liver tissue, the percentage of collagen fiber distribution and the collagen fiber level in liver tissue of RNA group were significantly reduced. CONCLUSION: RNA might play a role in the prevention of schistosomal hepatic fibrosis.

Animals↗

[Study on the structures of poly (urea) urethane by FTIR and 1H NMR methods].

Using the FTIR and 1H NMR methods, the structures, relative ratio and inventory ratio of segmented poly (urea) urethanes which are synthesized with different extenders (1,4-butandiol, ethylene diamine and their mixtures)have been studied successfully and the ratationship between the branch ratio and inventory ratio has been determined.

English Abstract↗

Differential display detects altered gene expression between cataractous and normal human lenses.

PURPOSE: To identify and analyze differentially genes expressed between lens epithelia dissected from age-related cataractous and noncataractous human lenses. METHODS: RNAs from 50 pooled cataractous and 25 pooled noncataractous epithelia were compared by reverse transcription-polymerase chain reaction differential display (RT-PCR-DD). Two differentially displayed bands were chosen for further study. These were reamplified, cloned, and sequenced. Expression of these genes was further evaluated in pooled and individual epithelia by RT-PCR with gene-specific primers. RESULTS: Significant differences in gene expression were detected between the cataractous and the noncataractous epithelia. Three mRNAs displayed higher levels and 12 mRNAs displayed lower levels of expression in the cataractous samples compared with that in the noncataractous samples. Of the mRNAs expressed at higher levels, one was identified as metallothionein IIa (METII). Of the mRNAs with decreased expression, one was identified as protein phosphatase 2A regulatory subunit (P2A-RS). Overexpression of METII and underexpression of P2A-RS were confirmed in pooled and individual epithelia. CONCLUSIONS: These results provide evidence that age-related cataract is associated with alterations in the expression of multiple epithelial genes including METII and P2A-RS. METII is a detoxification protein induced by oxidative stress, and P2A-RS is a mitotic suppressor involved in cell-cycle control. These results implicate these proteins and their associated functions in the maintenance of lens transparency.

Adult↗

The integration of a novice user interface into a professional modeling tool.

This paper describes a software tool, the Oncology Thinking Cap (OncoTCAP) and reports on our efforts to develop a novice user interface to simplify the task of describing biological models of cancer and its treatment. Oncology Thinking Cap includes a modeling tool for making relationships explicit and provide dynamic feedback about the interaction between cancer cell kinetics, treatments, and patient outcomes. OncoTCAP supports student learning by making normally invisible processes visible and providing a representational tool that can be used to conduct thought experiments. We also describe our novice interface and report the results of initial usability testing.

Cell Cycle↗

Disruption of alpha3 connexin gene leads to proteolysis and cataractogenesis in mice.

Gap junction channels formed by alpha3 (Cx46) and alpha8 (Cx50) connexin provide pathways for communication between the fiber cells in the normal transparent lens. To determine the specific role of alpha3 connexin in vivo, the alpha3 connexin gene was disrupted in mice. Although the absence of alpha3 connexin had no obvious influence on the early stages of lens formation and the differentiation of lens fibers, mice homozygous for the disrupted alpha3 gene developed nuclear cataracts that were associated with the proteolysis of crystallins. This study establishes the importance of gap junctions in maintaining normal lens transparency by providing a cell-cell signaling pathway or structural component for the proper organization of lens membrane and cytoplasmic proteins.

Aging↗

Vitamin D receptor genotype is associated with radiographic osteoarthritis at the knee.

Osteoporosis and osteoarthritis are age-related disorders of the skeleton with genetic components. Low bone density is a risk factor for osteoporotic fracture while osteoarthritis is associated with increased bone density. The 1,25-dihydroxyvitamin D3 receptor (VDR) gene locus was previously found to be associated with bone density. We therefore studied the relationship between radiographic osteoarthritis at the knee and VDR genotype in a population-based sample (n = 846), using molecular haplotyping of anonymous intragenic DNA polymorphisms. Radiographic osteoarthritis was defined using the Kellgren score, which is based on the assessment of osteophytes and joint space narrowing (JSN). We show that one VDR haplotype allele is significantly overrepresented in individuals with knee osteoarthritis and associated with a 2.27-fold increased relative risk (95% confidence interval 1.46, 3.52). Adjustment for bone density at the femoral neck did not change these results, indicating that the association is not mediated by bone density. The association appeared to be largely explained by the presence of osteophytes rather than JSN. Our results indicate a role of the VDR gene in the pathogenesis of osteophytes while linkage disequilibrium with another nearby gene, i.e., the collagen type IIa1 gene encoding the most abundant protein in cartilage, might contribute to the association.

Aged↗

Adjuvant radiation for vulvar carcinoma: improved local control.

PURPOSE: Local recurrence is a significant problem following primary surgery for advanced vulva carcinoma. The objectives of this study were to evaluate the impact of adjuvant vulvar radiation on local control in high risk patients and the impact of local recurrence on overall survival. METHODS AND MATERIALS: From 1980-1994, 62 patients with invasive vulva carcinoma and either positive or close (less 8 mm) margins of excision were retrospectively studied. Thirty-one patients were treated with adjuvant radiation therapy to the vulva and 31 patients were observed after surgery. Kaplan-Meier estimates and the Cox proportional hazard regression model were used to evaluate the effect of adjuvant radiation therapy on local recurrence and overall survival. Independent prognostic factors for local recurrence and survival were also assessed. RESULTS: Local recurrence occurred in 58% of observed patients and 16% in patients treated with adjuvant radiation therapy. Adjuvant radiation therapy significantly reduced local recurrence rates in both the close margin and positive margin groups (p = 0.036, p = 0.0048). On both univariate and multivariate analysis adjuvant radiation and margins of excision were significant prognostic predictors for local control. Significant determinants of actuarial survival included International Federation of Gynecologists and Obstetricians (FIGO) stage, percentage of pathologically positive inguinal nodes and margins of excision. The positive margin observed group had a significantly poorer actuarial 5 year survival than the other groups (p = 0.0016) and adjuvant radiation significantly improved survival for this group. The 2 year actuarial survival after developing local recurrence was 25%. Local recurrence was a significant predictor for death from vulva carcinoma (risk ratio 3.54). CONCLUSION: Local recurrence is a common occurrence in high risk patients. In this study adjuvant radiation therapy significantly reduced local recurrence rates and may improve overall survival in certain subgroups. As salvage rates after developing local recurrence are poor adjuvant vulvar radiation should be considered for patients at risk after primary surgery.

Adult↗

The response of renal tubular epithelial cells to physiologically and chemically induced growth arrest.

Cells respond to a variety of stresses by activating the transcription of a battery of "acute phase" or "stress response" genes. The nature of this response is tailored to the nature of the stress. The extent to which physiologically and pathophysiologically induced growth arrest share common genomic responses is unclear. We therefore compared the effects of a physiologically induced (serum and nutrient depletion) and a chemically induced (2-Br-bis-(GSyl)HQ and 2-Br-6-(GSyl)HQ) stress in renal tubular epithelial cells (LLC-PK1). The response to physiological stress, induced by serum depletion, involves growth arrest characterized by an inhibition of DNA synthesis that occurs in the absence of a decrease in histone mRNA or an increase in gadd153 mRNA, one of the growth arrest and DNA damage inducible genes. In contrast, the chemical-induced stress involves growth arrest accompanied by a decrease in histone mRNA, particularly core histone H2B and H2A mRNA, and the induction of gadd153. Chemical-induced changes in histone mRNA inversely correlate to changes in the expression of a stress gene, hsp70, whose expression is dependent upon the maintenance of appropriate nucleosomal structure.

Animals↗

Lesions of regions for in vitro ventilatory genesis eliminate gasping but not eupnea.

Medullary regions, termed 'pre-inspiratory' and 'pre-Bötzinger', are considered critical for the neurogenesis of rhythmic ventilatory activity of in vitro preparations of the neonatal rat. We examined the influence of destruction of neurons in these regions, by microinjections of kainic acid, upon eupnea and gasping in vivo. Decerebrate, vagotomized, paralyzed and ventilated rats of age 8-15 days were used; the phrenic nerve activity was recorded. Eupnea was not consistently altered following destruction of neurons in any region. However, in the majority of animals, anoxia-induced gasping was not observed following injections of kainic acid into the 'pre-inspiratory' region, 'pre-Bötzinger' complex or lateral tegmental field; the latter region is important for the neurogenesis of gasping in adults. Injections into other regions did not prevent the elicitation of gasping. These results do not support the possibility that neuronal activities which are responsible for respiratory rhythm generation in vitro underlie the neurogenesis of eupnea in vivo.

Animals↗