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Biomedical subjects

H Chang

Publications and source records attributed to H Chang.

At least 289 records · Page 16Linked to original sources

Effect of exercise training and sucrose feeding on insulin-stimulated glucose uptake in rats with streptozotocin-induced insulin-deficient diabetes.

The effect of exercise training and a sucrose-rich diet on insulin-stimulated glucose disposal was studied in rats with streptozotocin-induced insulin deficiency. Rats were injected with streptozotocin (40 mg/kg), and 3 days later divided into three groups with equal degrees of hyperglycemia. One group of rats was allowed to run spontaneously on exercise wheels, another group remained sedentary but ate a sucrose-rich diet (66% sucrose), and the third also remained sedentary but consumed conventional rat chow. Three weeks later, we determined the effect of these various programs on postabsorptive plasma glucose and insulin levels, as well as on the ability of exogenous insulin to stimulate disposal of a glucose load during a period in which endogenous insulin was suppressed by epinephrine and propanolol. Basal plasma insulin levels were the same in all three groups, but plasma glucose levels were significantly lower (P less than 0.001) in exercise-trained rats, and significantly higher (P less than 0.05) in sucrose-fed rats, than in chow-fed diabetic rats. The inference that exercise training markedly enhanced insulin action in rats with insulin deficiency was borne out by direct estimation of insulin-stimulated glucose disposal. In contrast, sucrose-fed diabetic rats seemed to be more insulin-resistant than chow-fed diabetic rats. These results provide direct evidence that spontaneous exercise can dramatically attenuate the severity of diabetes in insulin-deficient rats by enhancing insulin action. DIABETES 32:165-168, February 1983.

Animals↗

Comparative evaluation of fifteen anti-sickling agents.

Fifteen compounds reported to be inhibitors of gelation or sickling were studied by standard methods. These tests included (1) the determination of the solubility of deoxyhemoglobin S or Csat, (2) evaluation of sickling in whole SS blood at various pO2s, (3) measurement of the oxygen affinity of hemoglobin and blood, and (4) examination of red cell indices and morphology. Among the 4 noncovalent agents tested, butylurea was the most potent inhibitor of gelation and sickling in vitro; however, relatively high concentrations were required compared to the covalent agents. In the latter group, bis-(3,5 dibromosalicyl)-fumarate, nitrogen mustard, and dimethyladipimidate were especially effective inhibitors of gelation and/or sickling. All of these compounds require further development before they can be considered for clinical use.

Anemia, Sickle Cell↗

Identification of 2-imidazolines as anti-sickling agents.

The drugs tolazoline, clonidine, lofexidine, and fenmetozole were found to inhibit the gelation of hemoglobin S in the order of increasing effectiveness. Only the latter, however, reduced the sickling of red cells significantly and normalized the oxygen affinity of SS blood at 5-10 mM concentrations. Since this level of drug is lower than those reported for many other anti-sickling agents to achieve comparable effects, the 2-imidazoline class of compounds may provide important clues for the development of therapy for sickle cell anemia.

Anemia, Sickle Cell↗

Benzodiazepine withdrawal effects.

1. Twenty-nine patients with anxiety neurosis who had completed a one week placebo, three week active drug study on either halazepam or oxazepam were observed for eight weeks for withdrawal effects. Half of the patients received a placebo for the first two weeks of the withdrawal study and half had all medication abruptly stopped. 2. There was no significant difference in the pattern of withdrawal between halazepam, an intermediate range benzodiazepine, and oxazepam, a short acting benzodiazepine. 3. Withdrawal symptoms were apparent, maximally between week 1 and 2 together with possible rebound effects. 4. Patients who received placebo had significantly less severe withdrawal symptoms than those who had their medication abruptly discontinued.

Anti-Anxiety Agents↗

Cholinephosphotransferase activities in microsomes and neuronal nuclei isolated from immature rabbit cerebral cortex: the use of endogenously generated diacylglycerols as substrate.

A neuronal nuclear fraction (N1) and a microsomal fraction (P3) were isolated from homogenates of cerebral cortices of 15-day-old rabbits. A nuclear envelope fraction (E) was prepared from N1. To assay cholinephosphotransferase, diacylglycerols were first generated in the membranes of these subfractions using a phospholipase C (Bacillus cereus) preincubation. With levels of endogenous diacylglycerols producing maximal specific cholinephosphotransferase activities, an activity ratio of 1:1:5 was found for N1, P3, and E, respectively. An independent neuronal nuclear cholinephosphotransferase, concentrated in nuclear membranes, is indicated. With regard to changes in pH and concentrations of MgCl2 and CDP-choline, N1 and P3 activities responded in a similar manner. However, in contrast to P3, N1 activities we much more profoundly inhibited at low levels of Triton X-100 (0.01-0.02 w/v%) and N1 showed quite significant levels of cholinephosphotransferase activity in the absence of a phospholipase C preincubation. Choline phosphotransferase in N1 and P3 showed Km values for CDP-choline (0.028 and 0.031 mM, respectively) which were much lower than corresponding literature values determined using exogenous diacylglycerols as substrates for this enzyme. The presence of cholinephosphotransferase in neuronal nuclear membranes reflects a rather exceptional nuclear autonomy. This may be related to a need to maintain nuclear phospholipid in the absence of a well-developed endoplasmic reticulum at early stages of neuronal development or to synthesize phospholipid in response to functions unique to the nucleus.

Animals↗

SC erythrocytes have an abnormally high intracellular hemoglobin concentration. Pathophysiological consequences.

We have examined 20 SC patients on Percoll-Stractan continuous density gradients and find that they have an elevated mean corpuscular hemoglobin concentration (MCHC). Reduction of the MCHC to normal values results in amelioration of four physiologically important blood abnormalities: decreased oxygen affinity, viscosity of deoxygenated erythrocyte suspensions, rate of sickling, and deoxygenation induced K+ efflux. These observations suggest that the rehydration of SC cells to normal values should be considered a potential approach in the therapeutic manipulation of this disease.

Anemia, Sickle Cell↗

The acylation of 1-acyl-sn-glycero-3-phosphorylcholine by glial and neuronal nuclei and derived neuronal nuclear envelopes: a comparison of nuclear and microsomal membranes.

A neuronal nuclear fraction (N1), a glial nuclear fraction (N2) and a fraction containing microsomal membranes (P3) were isolated from homogenates of cerebral cortices of 15-day-old rabbits. A nuclear envelope fraction (E) was prepared from fraction N1. In comparison with the parent fraction N1, fraction E had a much lower yield of protein (0.077 mg/g cerebral cortex), a low specific DNA content, an eightfold higher specific phospholipid content (0.85 mumol phospholipid phosphate/mg protein) and a very similar phospholipid distribution profile. Using 100, 50, and 25 microM 1-acyl-sn-glycero-3-phosphorylcholine (labelled with [3H]palmitate) and 100 microM oleoyl CoA, the activity of acyl-CoA:1-acyl-sn-glycero-3-phosphorylcholine acyltransferase was studied in vitro. Fractions N1 and N2 had specific activities which were two to three times the specific activities shown for fraction P3. Fraction E was particularly enriched in this acylation activity and had specific activities which were 6 times those of fraction N1 and 11-19 times those of fraction P3. The existence of nuclear acyl-CoA:1-acyl-sn-glycero-3-phosphorylcholine acyltransferase activity was indicated as was a particularly high concentration of this enzyme within the nuclear envelope. In assays of lysolecithin-lysolecithin transacylase activities, fraction N2 (glial nuclei) showed the highest specific activities, being three to four times those of fractions N1 or P3. This transacylase activity (N2) was as high as 40% of the corresponding acyltransferase activity measured in this fraction using oleoyl CoA as acyl donor.

Animals↗

Laser Raman studies on the conformation of Pro-Leu-Gly-NH2.

Laser Raman spectra of Pro-Leu-Gly-NH2, the factor that inhibits release of pituitary melanotropin, have been obtained in the solid state, in dimethylsuloxide and in aqueous solution. The amide I frequencies were observed at 1650 and 1687 cm-1 in the solid state and at 1669 cm-1 in dimethylsulfoxide. The conformation of this tripeptide has been proposed by 1H-NMR studies in [2H]-dimethylsulfoxide and revealed by X-ray analysis to be type II beta-turn. These observed amide I frequencies thus are characteristic of type II beta-turn conformation. The relatively lower amide I frequency, 1645 cm-1, observed in 2H2O indicates that the conformation of the peptide in aqueous solution could be different from those in solid state and in dimethylsulfoxide. pH changes hae no significant effect on aqueous solution spectra, except for the shape of the amide III band. The maximum of the amide III band shifted from 1259 cm-1 at pH 2.0 to 1242 cm-1 at pH 11.7. The amide III peaks in the solid state were at 1234 and 1268 cm-1.

Lasers↗

The fatty acid composition of lipids of neuronal and glial nuclear fractions isolated from 15-day-old rabbit cerebral cortex.

A neuronal nuclear fraction (N1) and a glial nuclear fraction (N2) have been isolated from 15-day-old rabbit cerebral cortex using the Thompson procedure. More than 56% of the homogenate DNA was recovered in the two nuclear fractions, with N1 being the larger by about eightfold. Fractions N1 and N2 had very similar phospholipid distributions, with phosphatidylinositol being a larger component than phosphatidylserine. Fatty acid analyses demonstrated that phosphatidylethanolamine and phosphatidylinositol, individually, had similar fatty acid profiles in fractions N1 and N2, and also in nuclear and microsomal fractions derived from homogenates of nerve cell bodies isolated from cortex of 15-day-old rabbits. In contrast, the nuclear phosphatidylcholines had lower levels of palmitate and higher levels of arachidonate than did microsomal phosphatidylcholines. Molecular species analyses indicated that monoenes (41 mol%), tetraenes (20 mol%), and saturates (13 mol%, composed chiefly of palmitate) were the principal classes of N1 phosphatidylcholines, while the diacyl species of phosphatidylethanolamine of this fraction were characterized by high levels of tetraenes (44 mol%), pentaenes (17 mol%), and hexaenes + polyenes (24 mol%). The neutral glycerides of fraction N1 occurred collectively at a level of 0.05 mol/mol phospholipid. Prominent fatty acids of diacylglycerols included palmitate (31%), oleate (20%), arachidonate (14%), and stearate (13%). Triacylglycerols showed a similar pattern but with relatively high levels of linoleate (11%), while monoacylglycerols consisted almost entirely of palmitate (33%), stearate (35%), and oleate (24%).

Animals↗