Search PubMed⌕ Search

Biomedical subjects

M Huang

Publications and source records attributed to M Huang.

At least 343 records · Page 19Linked to original sources

Effect of euglycemic hyperinsulinemia on neonatal canine hepatic and muscle metabolism.

The effects of euglycemic hyperinsulinemia on hepatic and muscle metabolism were determined in the fasted newborn dog during the first day of life. Hyperinsulinemia was sustained with a primed constant infusion of insulin whereas euglycemia was maintained with an intravenous infusion of 10% glucose using the insulin clamp technique. Euglycemic hyperinsulinemia caused an increase of glucose utilization from 43.9 +/- 3.7 to 66.5 +/- 5.4 mumol/kg/min (p less than 0.001) and reduced endogenous glucose production to 44.4 +/- 5.4% of basal values obtained before the induction of hyperinsulinemia. Hepatic tissue glycogen, triglycerides, or intermediates were not altered by hyperinsulinemia nor was the incorporation of [3H]glucose into glycogen. However, the hepatic cytoplasmic redox state was more oxidized, and the incorporation of [3H]glucose into triglycerides was higher among hyperinsulinemic pups. Pups who demonstrated incomplete suppression of endogenous glucose production had metabolite perturbation suggestive of ongoing gluconeogenesis. Despite very few changes in hepatic tissue metabolite levels, pups subjected to hyperinsulinemia demonstrated a linear uptake of 2-deoxyglucose into hepatic tissue as a function of circulating insulin levels during hyperinsulinemia. Muscle tissue demonstrated no alterations of tissue metabolites, glycogen, or triglycerides levels or precursor incorporation into these storage pools. Nonetheless, 2-deoxyglucose incorporation into neonatal muscle tissue was a significant linear function of plasma insulin concentration. Total tissue 2-deoxyglucose uptake was lower in muscle tissue than in hepatic tissue (245 +/- 19 versus 514 +/- 20 dpm/g/min) (p less than 0.001).(ABSTRACT TRUNCATED AT 250 WORDS)

Animals↗

Enhancement of inositol phospholipid metabolism and activation of protein kinase C in ras-transformed rat fibroblasts.

The inositol phospholipid metabolism is one of the main pathways of signal transduction in cells. We measured the activities of its key enzymes in v-Ha-ras-transformed 208F rat fibroblasts. In the ras-transformed clones, incorporation of [32P]Pi into intermediates of the inositol phospholipid metabolism was stimulated. The activities of phosphatidylinositol and phosphatidylinositol-4-phosphate kinases in the transformed clones were about 35-50% more than in untransformed cells, indicating increased inositol phospholipid metabolism. However, the activity of diacylglycerol kinase in their membrane fraction was 25-35% less than that of untransformed cells, although the total diacylglycerol kinase activity did not change. The imbalance of these kinases could constitute one of the main reasons leading to the increased level of inositol phosphates and the accumulation of diacylglycerol to 2-2.2 times that in control 208F cells. Phosphatidylinositol-4,5-bisphosphate-phospholipase C activity did not change on the transformation when assayed under various conditions. The increased level of diacylglycerol caused intracellular translocation, activation, and down-regulation of protein kinase C changes which may be one of the essential events in transformation by the v-Ha-ras gene.

Animals↗

The role of adenylate cyclase in relaxation of brain arteries: studies with forskolin.

The natural product, forskolin, which stimulates adenylate cyclase by a direct, non-receptor-mediated mechanism, was studied for its effect on the tension of isolated brain arteries and adenylate cyclase activity of cerebral arteries. Helical strips of bovine and porcine basilar arteries and bovine middle cerebral arteries, which had been precontracted with prostaglandin F2 alpha (PGF2 alpha) or KCl, relaxed potently to administration of forskolin with ED50 values, ranging from 22 to 69 nM. Incubation of forskolin with a broken cell preparation of bovine cerebral arteries resulted in an efficacious stimulation of adenylate cyclase, approximating 5 times basal activity at a forskolin concentration of 1 microM. The metal salts nickel chloride and manganese chloride decreased the potency of vasorelaxation by vasoactive intestinal peptide (VIP), which stimulates adenylate cyclase via the VIP receptor. In contrast, nickel chloride had little effect on vasorelaxation by forskolin. The endogenous nucleoside, adenosine, which acts via the adenosine receptor and adenylate cyclase, relaxed bovine basilar and middle cerebral arteries with ED50 values ranging from 0.26 to 0.94 microM. The data presented support a role for adenylate cyclase in mediating vasodilation of brain blood vessels.

Adenylyl Cyclases↗

Modified responsiveness of v-Ha-ras-transfected rat fibroblasts to growth factors and a tumor promoter.

The correlation of the phenotypic changes of v-Ha-ras transfected cells with the expression of p21ras and the modified responses to growth factors and a tumor promoter were examined. Transfection of the v-Ha-ras gene together with the neomycin-resistance gene into 208F rat fibroblasts yielded transformed clones characterized by morphological changes, anchorage-independent growth, and tumorigenicity in nude mice. The degrees of these biological alterations were parallel with the expression of mRNA and protein of the ras gene. In ras-transformed cells, anchorage-independent growth was stimulated by epidermal growth factor (EGF), insulin, bombesin, and fibroblast growth factor, whereas in the parental 208F cells, anchorage-independent growth was observed only in the presence of EGF, and there were many fewer EGF-induced colonies than those in the ras-transformed clones. A tumor promoter, 12-O-tetradecanoylphorbol-13-acetate (TPA) also augmented anchorage-independent growth of ras-transformed cells and induced morphological changes in monolayer cultures without altering the expression of the ras gene or phosphorylation of the p21ras protein. Retinoic acid inhibited the TPA-induced anchorage-independent growth. These results showed a good correlation of the expression of p21ras with the phenotypic changes and the increased sensitivity of the p21ras-expressing cells to the stimulation of growth factors and tumor promoter.

Animals↗

Surgical management of soft tissue sarcomas, with an analysis of 313 cases.

From 1964 to 1978, 313 patients, 192 males and 121 females, with soft tissue sarcoma underwent surgery in our hospital. All patients have been followed up for over 5 years. One hundred ninety patients (60.7%) had recurrence of the tumor after previous surgery. The tumor was located in the head in 55 cases, in the trunk in 136, and in the extremities in 122 cases. Regional lymph node metastases occurred in 23 patients (7.4%). Fibrosarcoma, neurofibrosarcoma, and rhabdomyosarcoma were the types most commonly encountered in this series. The 5-year survival rate, according to the extent of surgical resection for 117 patients with local resection, was 47.9%; for 75 patients with wide local resection, 62.7%; for 43 patients with amputation, 18.6%; and for 78 patients with local resection combined with irradiation, 48.7%. For the whole series, the 5- and 10-year survival rates were 47.6% and 35.8%, respectively. The 5-year survival rates of stages I, II, III, and IV (TNM classification) were 60%, 46.9%, 40%, and 22.2%, respectively.

Adult↗

A transcriptionally defective long terminal repeat within an endogenous copy of mouse mammary tumor virus proviral DNA.

Mouse mammary tumor virus proviral DNA is endogenous to most inbred strains of mice but in many strains is not transcriptionally active. This inactivity may be due to defects in the proviruses themselves or to position effects mediated by DNA sequences flanking the proviral units. The transcriptional competence of long terminal repeats (LTRs) derived from endogenous proviral DNA at genetic loci Mtv-8, Mtv-9, and Mtv-17 of the C57BL/6 mouse strain was examined with a transient transfection assay in which gene expression was monitored by expression of chloramphenicol acetyltransferase. LTRs from Mtv-8 and Mtv-9 were able to direct glucocorticoid-induced chloramphenicol acetyltransferase expression in this assay, while the LTR from Mtv-17 was only about 5% as effective. Analysis of chimeric LTRs indicated that the glucocorticoid-inducible transcriptional enhancer element within the Mtv-17 LTR is active when linked to a functional promoter from Mtv-8, whereas the promoter from Mtv-17 is defective in directing hormone-induced gene expression, even when linked to the Mtv-8 glucocorticoid-responsive enhancer. The DNA sequence of transcriptional control regions of the LTRs of all three endogenous proviral units was determined; this analysis revealed that the source of the defect in Mtv-17 is a single G-to-A transition at position-75 with respect to the site of transcription initiation that resides within the previously defined binding site for the transcription factor nuclear factor 1. Competition experiments with a gel electrophoresis mobility shift assay indicated that the affinity of nuclear factor 1 for DNA derived from Mtv-17 is significantly less than for comparable sequences derived from Mtv-8.

Animals↗

The effect of euglycemic hyperinsulinemia on cerebral cortical glucose metabolism in newborn beagles.

There is a paucity of information on the significance of insulin on neonatal cerebral glucose metabolism. The effect of insulin on neonatal cerebral glucose uptake and cerebral cortical metabolic intermediates was investigated with the euglycemic hyperinsulinemic clamp in unanesthetized beagles during the first day of life. Insulin was infused at various rates to sustain an elevated steady state plasma insulin concentration in individual pups. Furthermore, blood glucose and 2-deoxyglucose levels were also maintained ("clamped") in a steady state by infusion of glucose and 2-deoxy-[14C]-glucose. Mean (+/- SD) plasma insulin levels were 20 +/- 12 and 2971 +/- 3386 (33-14330) microU/ml in control and hyperinsulinemic pups. Blood glucose concentration was 4.43 +/- 2.64 mM during basal periods and 4.54 +/- 2.87 mM during the clamp period in study pups. Basal fasting glucose utilization in study pups was 43.9 +/- 24 mumol/kg/min and increased to 60.9 +/- 35.2 mumol/kg/min (p less than 0.001) during hyperinsulinemia. Immediately after the euglycemic hyperinsulinemic clamp or fasting in control pups, the cerebral cortex was frozen to the temperature of liquid nitrogen. No differences were noted for any cerebral cortical intermediate between the two pup groups. In addition, there was no relationship between the cerebral intermediates concentration when analyzed as a function of plasma insulin levels. The uptake of cerebral 2-deoxyglucose was analyzed as a function of plasma insulin concentration (120-6900 microU/ml). Brain tissue demonstrated a positive linear relationship for 2-deoxyglucose uptake as a function of plasma insulin concentration.(ABSTRACT TRUNCATED AT 250 WORDS)

Adenosine Triphosphate↗

Utility of polycation-treated filters for the assay of receptors for VIP.

This study examined the utility of four polycationic agents for treating glass fibre filters used in the receptor binding assay for vasoactive intestinal peptide (VIP). Polyethylenimine (PEI), polybrene, protamine and methylated bovine serum albumin proved satisfactory in terms of low filter binding of free radioligand and retention of membrane-bound radioligand. Their performance was superior or comparable to untreated Millipore EGWP cellulose acetate filters which we had previously utilized but which are no longer manufactured. The results with polycations indicate the importance of ionic interactions between filter, biological membranes and radioligand in determining the performance of a filtration assay for radioligand-receptor binding. At a practical level, PEI has the disadvantage of potential toxicity. The satisfactory performance of the other polycations indicates that they provide safer alternatives to PEI for filtration assay of the VIP receptor and possibly receptors for other basic ligands.

Animals↗

Mechanisms of partial renal infarct hypertension.

Contributions of both the renin-angiotensin and immune systems to the aetiology of renal infarct hypertension were examined in Sprague-Dawley rats. Partial renal infarction was produced by ligating and sectioning two out of three branches of the left renal artery. The right kidney remained intact. Renal infarction resulted in rapid development of stable hypertension. One week following infarction, the plasma renin activity (PRA) increased more than threefold. However, PRA returned to control levels 4 weeks after infarction. Chronic immunosuppressive therapy with cyclophosphamide at most only attenuated the development of renal infarct hypertension associated with this transient renin elevation. However, cyclophosphamide prevented the later maintenance phase of the hypertension, and could also completely reverse established infarct hypertension. Activation of the renin-angiotensin system plays a role in the onset of partial renal infarct hypertension, but an intact immune system is required for maintenance of the hypertension. It is hypothesized that immunological reactions against renal tissue maintain renal infarct hypertension.

Animals↗

The clinical pharmacology of vancomycin in seriously ill preterm infants.

The first dose and steady state pharmacokinetics of vancomycin were studied in 16 seriously ill preterm infants (less than or equal to 34 wk gestational age) with documented Staphylococcus epidermidis infections. One infant was dropped from the study due to peripheral flushing occurring during administration of the first dose. Individual vancomycin doses ranged from 9.8 to 17.8 mg/kg and were infused intravenously over 15-37 min. Fifteen infants were studied after the first dose of vancomycin, whereas only 12 of these 15 were able to be studied under steady state conditions. Vancomycin half-life, steady-state volume of distribution, and body clearance averaged 6.0 h, 0.53 liter/kg, and 1.22 ml/min after the first dose and only slight differences were observed in these parameter estimates under steady state conditions. However, substantial accumulation of vancomycin in serum was observed with multiple dosing. Complete 8-h urine collections were possible in 12 of 15 premature infants after the first dose of vancomycin. Overall, 44.6% of the dose was recovered in the urine with a corresponding vancomycin renal ClR averaging 0.88 ml/min. Vancomycin body Cl correlated directly with renal ClR (r = 0.88, p less than 0.001) and body weight (r = 0.8, p less than 0.001). Vancomycin pharmacokinetic parameter estimates Vdss and Cl correlated directly with body weight, surface area, and postconceptional age. No significant relationships were observed between these parameter estimates and gestational age or postnatal age. Fourteen of 15 infants were treated successfully for their underlying infectious process. These data support the use of lower doses of vancomycin than previously recommended for the treatment of preterm infants.

Female↗

Uptake of lung surfactant subfractions into lamellar bodies of adult rabbit lungs.

The goals of this investigation were to determine whether subfractions of alveolar surfactant that have different physical and biochemical properties are preferentially taken up from the alveolar air space into lamellar bodies and to correlate the magnitude of the uptake with the properties of the fractions. Radiolabeled subfractions were obtained by differential centrifugation of lavage fluid from rabbits that had been intravenously injected with radioactive palmitate. The subfractions were P (pellet) 3 (1,000 g, 20 min), P4 (60,000 g, 60 min), P5 (100,000 g, 16 h). Subfractions were instilled into the lungs of anesthetized spontaneously breathing adult rabbits, and lavage and lamellar body fractions were isolated at later times. P3 and P4 were taken up to a larger extent than was P5 or liposomes prepared from a P4 lipid extract. The fractions that were preferentially taken up (P3 and P4) contained surfactant apoprotein (APO) 36, tubular myelin, multilamellar vesicles, and were rapidly adsorbed to an air-water interface. P3 also contained APO 10. These results demonstrate that different forms of surfactant are recycled at different rates and suggest that there is specificity in the recycling process.

Animals↗

The studies of malignant transformation of human epithelial cells induced by diethyl-nitrosamine (NDEA) in vitro.

This is the first report on the diethylnitrosamine-induced malignant transformation of human epithelial cells derived from fetal kidney. The transformed cells have prolonged life span and aneuploid karyotypes. They also form anchorage independent colonies in soft agar. With additional one or two NDEA treatments, these cells could elicit poorly differentiated carcinomas in immunosuppressed new-born rats. This experiment indicates that the human fetal kidney cells seem to be a good material for studying the mechanisms of carcinogenesis of human epithelial cell.

Animals↗

Malignant transformation of human fetal lung fibroblasts induced by nitrosamine compounds in vitro.

This report, for the first time, demonstrates that diethyl-nitrosamine (NDEA) and a new nitrosamine compound-N-1-methylacetonyl-N-3-methylbutyl-nitrosamine (MAMBNA), which are suspicious carcinogens of esophageal cancer (EC) in Linxian, Henan Province, are able to cause the malignant transformation (altered morphology, extended life span, anchorage independent growth, invasiveness, tumorigenicity, etc.) of normal diploid fibroblasts derived from human fetal lung. Besides, the preselection for clonogenic cells, which seem to be more readily to be transformed, in soft agar before carcinogen treatment, could be considered as one of the useful ways in establishment of a model system of malignant transformation of human fibroblasts in vitro.

Cell Transformation, Neoplastic↗