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Biomedical subjects

L C Huang

Publications and source records attributed to L C Huang.

At least 37 records · Page 2Linked to original sources

Chiroinositol deficiency and insulin resistance. II. Acute effects of D-chiroinositol administration in streptozotocin-diabetic rats, normal rats given a glucose load, and spontaneously insulin-resistant rhesus monkeys.

The acute effects of administration of D-chiroinositol (D-CI), a component of a putative mediator of insulin action, on plasma glucose were examined in low dose streptozotocin-treated rats and normal rats given a glucose load and the effects on plasma glucose and insulin were determined in five obese rhesus monkeys with varying degrees of spontaneous insulin resistance. Single dose intragastric D-CI (10 mg/kg) administered to streptozotocin-treated rats produced a 30-40% decrease in plasma glucose (P < 0.05) at 30-120 min. Single dose intragastric D-CI (2-15 mg/kg) administered to normal rats 2 h before ip glucose produced a 30-50% decrease (P < 0.05) in plasma glucose. D-CI (10 mg/kg) caused a 50% increase (P < 0.05) in glucose disappearance rates in these rats. Myoinositol (10 mg/kg) was without effect. Intravenously administered single dose D-CI (100 mg/kg) increased both the glucose and insulin disappearance rates by 129 +/- 41% (mean +/- SE; P < 0.06) and 89 +/- 39% (P = 0.01), respectively, in all monkeys between 0-30 min compared to control values. D-CI administration, therefore, lowered elevated plasma glucose in streptozotocin-treated hyperglycemic rats, normal rats given a glucose load, and spontaneously insulin-resistant monkeys with or without noninsulin-dependent diabetes mellitus. Intravenous D-CI also lowered plasma insulin in these monkeys.

Animals↗

Chiroinositol deficiency and insulin resistance. III. Acute glycogenic and hypoglycemic effects of two inositol phosphoglycan insulin mediators in normal and streptozotocin-diabetic rats in vivo.

Two insulin mediators, inositol phosphoglycans, were isolated from bovine liver by methods previously developed for rat liver, i.e. chromatography on an AG 1 x 8 ion exchange column and selective elution with HCl at pH 2.0 and 1.3. The pH 2.0 mediator containing D-chiroinositol stimulated pyruvate dehydrogenase phosphatase, whereas the pH 1.3 mediator containing myo-inositol inhibited cAMP-dependent protein kinase. Each mediator was further purified by thin layer and Bio-Gel P4 column chromatography and injected ip into normal fed rats together with [U-14C]glucose. After 2.5 h, diaphragms were removed, and glycogen isolated. Insulin mediators, like insulin, stimulated [U-14C]glucose incorporation into glycogen by 150-160% in a dose-dependent manner in the nanomolar range. Mediators injected iv in the nanomolar range into low dose streptozotocin-diabetic rats decreased plasma glucose 30-45% in 30-60 min, with a return to basal concentrations after 150-180 min. These in vivo insulin-like effects of mediator were observed without changes in serum insulin concentrations. The pH 2.0 mediator was 50-100 times more active (per nmol organic phosphate) than the pH 1.3 mediator in the ip diaphragm glycogenesis assay. Mediator effects on diaphragm were completely blocked by preincubation with an immunopurified inositol phosphoglycan antibody. Both mediators were equally active iv in lowering plasma glucose (per nmol inositol) at concentrations comparable to those of insulin.

Animals↗

Vulvar neoplasia associated with other primary malignancies.

It is recognized that a significant number of patients with vulvar neoplasia have had previous, concurrent, or subsequent genital tract neoplasia. This has resulted in speculation that there may be a common etiology and, in particular, of the possibility of an infection element. Among 59 cases of vulvar cancer diagnosed at the National Taiwan University Hospital from 1976 to 1991, there were seven cases (12%) associated with other primary malignancies. Carcinoma of the cervix was the most frequent other primary cancer (6/7, 86%). The possible role of human papilloma virus infection in genital neoplasia is discussed.

Adult↗

In vivo conversion of [3H]myoinositol to [3H]chiroinositol in rat tissues.

We report here the in vivo conversion of [3H]myoinositol to [3H]chiroinositol. After labeling intraperitoneally with [3H]myoinositol for 3 days to reach radioisotope equilibrium in urine, [3H]chiroinositol was isolated from tissues and purified after 6 N HCl hydrolysis by two sequential paper chromatographies and high performance liquid chromatography (HPLC). Percent conversion of [3H]myoinositol to [3H]chiroinositol was highest in urine (36%), liver (8.8%), muscle (8.8%), and blood (7.6%) with intestine, brain, kidney, spleen, and heart decreasing in percentage from 2.8 to 0.7%. Labeling of other inositol isomers including scyllo-, neo-, and epi-, and mucoinositol was minimal, approximately 0.06% of [3H]myoinositol. Glucose was unlabeled, but glucuronate, the product of myoinositol oxidation, was labeled up to 1.5% of the [3H] myoinositol. Acid hydrolysates of combined inositol-containing phospholipids contain significant labeled chiroinositol. [3H]Phosphatidylinositols and [3H]glycosylphosphatidylinositols were extracted from liver, muscle, and blood, isolated by thin layer chromatography, and inositols purified by HPLC after acid hydrolysis. Percent conversion of [3H]myoinositol to [3H] chiroinositol was highest in blood (60.4%) followed by muscle (7.7%) and liver (2.2%).

Animals↗

Rejuvenation of Sequoia sempervirens by Repeated Grafting of Shoot Tips onto Juvenile Rootstocks in Vitro: Model for Phase Reversal of Trees.

Repeated grafting of 1.5-centimeter long shoot tips from an adult Sequoia sempervirens tree onto fresh, rooted juvenile stem cuttings in vitro resulted in progressive restoration of juvenile traits. After four successive grafts, stem cuttings of previously adult shoots rooted as well, branched as profusely, and grew with as much or more vigor as those of seedling shoots. Reassays disclosed retention for 3 years of rooting competence at similar levels as originally restored. Adventitious shoot formation was remanifested and callus development was depressed in stem segments from the repeatedly grafted adult. The reversion was associated with appearance and disappearance of distinctive leaf proteins. Neither gibberellic acid nor N(6)-beneyladenine as nutrient supplements duplicated the graft effects.

Journal Article↗

Age trends in lung cancer.

To investigate the relationship between the stages of cancer development and the age trends in histologic type found at the time of disease diagnosis, we studied 1,669 patients with histologically proven lung cancer. These patients were examined at the National Taiwan University Hospital using Mantel-Haenszel Chi-square testing to determine a linear trend. These patients were divided into three age groups: group 1 (< 45 years), 141 patients (8%); group 2 (45-64 years), 946 patients (57%); group 3 (65 years or more), 582 patients (35%). The ratio of men to women was 1.4 in group 1, 2.5 in group 2 and 2.3 in group 3. In men, there was a significant trend for the proportion of squamous cell carcinoma to increase from 26% to 42% and that of adenocarcinoma to decrease from 52% to 34% as age increased. In women, an age trend for histologic type was not observed. There was also a significant trend for local-stage squamous cell carcinoma in men to increase from 18% in group 1 to 35% in group 2 and to 42% in group 3. In men, but not in women, local-stage large cell carcinoma increased from 20% in group 1 to 31% in group 2 and to 64% in group 3. However, the age-stage trend for other cell types was not significant in men.(ABSTRACT TRUNCATED AT 250 WORDS)

Adenocarcinoma↗

A bacterial model system for chromosomal targeting.

A system that permits efficient site-specific chromosomal targeting of foreign DNA on the Escherichia coli chromosome has been developed, using the FLP site-specific recombination system derived from the yeast 2 mu plasmid. The system demonstrates the feasibility of using site-specific recombination for this purpose, and provides a means to gather information on parameters that may affect chromosomal targeting to guide efforts to establish similar systems in higher eukaryotes. In this model system, the efficiency of integration of foreign DNA is affected by the location of the target site in the chromosome, and the structure of the recombination sites.

Base Sequence↗

Insulin mediators are the signal transduction system responsible for insulin's actions on human placental steroidogenesis.

To test the hypothesis that insulin mediators serve as the signal transduction system for insulin's steroidogenic actions in human placental cytotrophoblasts, we examined the effects of two inositolglycan insulin mediators, the insulin pH 2.0 chiro-inositol mediator (IM-pH 2.0) and the insulin pH 1.3 myo-inositol mediator (IM-pH 1.3), on cytotrophoblastic steroidogenesis. When human cytotrophoblasts were incubated in medium supplemented with androstenedione for 24 h, treatment with IM-pH 2.0 or IM-pH 1.3 suppressed aromatase activity by 15% (P less than 0.05) and 49% (P less than 0.05), respectively, compared to insulin, which suppressed aromatase activity by 21% (P less than 0.05). When cytotrophoblasts were incubated in medium supplemented with pregnenolone for 24 h, treatment with IM-pH 2.0 or IM-pH 1.3 stimulated 3 beta-hydroxysteroid dehydrogenase (3 beta HSD) activity by 145% (P less than 0.05) and 168% (P less than 0.05), respectively, compared to insulin, which stimulated 3 beta HSD activity by 63% (P less than 0.05). Suppression of aromatase activity and stimulation of 3 beta HSD activity by inositolglycan mediators were both concentration dependent. Moreover, preincubation of cytotrophoblasts with the antiinositolglycan antibody alpha IGP completely abolished insulin's ability to either inhibit aromatase or stimulate 3 beta HSD activity. These results indicate that insulin mediators mimic insulin's effects on cytotrophoblastic aromatase and 3 beta HSD activities and suggest that inositolglycan mediators are the signal transduction mechanism responsible for insulin's regulation of human placental steroid hormone biosynthesis.

3-Hydroxysteroid Dehydrogenases↗

Anti-inositolglycan antibodies selectively block some of the actions of insulin in intact BC3H1 cells.

We have studied the mechanism of generation of insulin mediators by using specific antibodies raised against the oligosaccharide anchor of membrane proteins. These antibodies (i) block the in vitro effects of purified insulin mediators and (ii) block the insulin-induced stimulation of pyruvate dehydrogenase in intact BC3H1 myocytes but not insulin-stimulated glucose uptake, generation of diacylglycerol, or generation of insulin mediators. When added to intact cells in the presence of insulin, these antibodies induce the accumulation of insulin mediator activity in the extracellular medium. We therefore conclude that these anti-inositolglycan antibodies block some of the effects of insulin by inhibiting the uptake of specific insulin mediators generated outside the cell.

Animals↗

Rat liver insulin mediator which stimulates pyruvate dehydrogenase phosphate contains galactosamine and D-chiroinositol.

It has been established that insulin treatment of cells, isolated plasma membranes, or whole animals leads to the generation of low molecular weight mediators which serve as intermediates in the signalling pathway. At least two distinct classes of mediator have been described, based on differences in apparent molecular weight, isoelectric point and biological activity (Cheng, K., and Larner, J. (1985) Ann. Rev. Physiol. 45, 407-424). Recently, Saltiel's (Saltiel, A.R., and Cuatrecasas, P. (1986) Proc. Natl. Acad. Sci. U.S.A. 83, 5793-5797) and Mato's (Mato, J.M., Kelly, K.L., Abler, A., and Jarett, L. (1987) J. Biol. Chem. 262, 2131-2137) laboratories have described an insulin "modulator" which was apparently derived from glycosylphosphoinositol linker, similar to those known to anchor proteins to the external surface of the cell membrane (Low, M.G. (1987) Bioch. J. 244, 1-13). In this paper, we report that highly purified preparations of the insulin mediator which stimulates pyruvate dehydrogenase phosphatase contain mannose, galactosamine, and D-chiroinositol. These determinations are based upon analyses using paper chromatography and gas chromatography/mass spectroscopy. Nitrous acid deamination of the mediator resulted in release of inositol phosphate, indicating that the galactosamine and D-chiroinositol are linked. Although the presence of chiroinositol in modulator from H35 hepatoma cells has been recently reported (Mato, J.M., Kelly, K.L., Abler, A., Jarett, L., Corkey, B.E., Cashel, J.A., and Zopf, D. (1987) Bioch. Biophys. Res. Comm. 146, 764-770), the optical identity of the inositol remained unknown until the present report. Likewise, the presence of galactosamine rather than glucosamine in insulin mediator is a novel finding. These findings, coupled with those of Saltiel and Mato's groups, provide clear evidence for the existence of multiple forms of insulin mediators. Additionally, the results presented here afford further confirmation for the formation of insulin mediators from glycosyl-phosphoinositol linkers.

Animals↗

Holliday intermediates and reaction by-products in FLP protein-promoted site-specific recombination.

Holliday structures are formed and resolved by FLP protein during site-specific recombination. These structures have been isolated and are visualized in both native and partially denatured states by electron microscopy. No single-strand breaks are found within the junction, indicating that the structure results from a reciprocal exchange of strands. These structures have properties consistent with being reaction intermediates. Double-strand cleavage products and "Y structures" are also detected and appear to be by-products of the reaction. The Y structures are three-armed branched molecules with a covalently closed junction located at the FLP recombination target site. Models are discussed, suggesting that both of these novel structures are made by aberrant cleavages during formation and resolution of the Holliday intermediate.

Bacterial Outer Membrane Proteins↗

The function of Mg-ATP in interactions between the regulatory and catalytic subunits of type I cAMP-dependent protein kinase from rabbit skeletal muscle.

The regulatory subunit of Type I cAMP-dependent protein kinase from rabbit skeletal muscle can bind [3H]cAMP to form the R-[3H]cAMP complex, and the slow phase of the enhanced exchange of free cAMP with [3H]cAMP from the R-[3H]cAMP complexes was studied under various conditions using the equilibrium isotope exchange technique. Results indicate that Mg-ATP and the catalytic subunit are absolutely required for the enhanced exchange reaction to occur, but phosphorylation of the regulatory subunit by Mg-ATP does not play a determining role in the slow rate of the dissociation/association of the Type I protein-kinase in the presence of cAMP and the catalytic subunit. We interpret the role of Mg-ATP as being one in which it may provide the structural attributes required for formation of a stabilized transient state of the cAMP-regulatory subunit-catalytic subunit ternary complex, an obligatory intermediate involved in the dissociation/association of Type I cAMP-dependent protein kinase.

Adenosine Triphosphate↗

Biochemical and ultrastructural study of Leu M1 antigen in Reed-Sternberg cells: comparison with granulocytes and interdigitating reticulum cells.

A group of monoclonal antibodies was shown to react with glycoconjugates containing a sugar sequence--lacto-N-fucopentaose III (LNF-III)--in granulocytes and in some normal nonlymphoid cells. The antibodies including anti-Leu M1, anti-My-1, WGHS 29-1, 534F-8, and 538F-12 of the immunoglobulin M-type were used to study the biochemical properties of LNF-III antigens in granulocytes, interdigitating reticulum cells, and neoplastic cells of Hodgkin's disease. In contrast to the presence of an abundant LNF-III glycolipid in granulocytes, the Hodgkin's neoplastic cells had no LNF-III glycolipid or contained only minimal amounts; however, both LNF-III glycoconjugates isolated from Hodgkin's neoplastic cells and interdigitating reticulum cells appeared to be a similar, if not an identical, 150,000-molecular-weight glycoprotein. The neoplastic cells in Hodgkin's disease appeared to show a biochemical property more closely related to interdigitating reticulum cells than any other cells in the monocyte-granulocyte-histiocyte system.

Antibodies, Monoclonal↗