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Biomedical subjects

W R Zhang

Publications and source records attributed to W R Zhang.

49 records · Page 3Linked to original sources

Approaches to the molecular cloning of protein-tyrosine phosphatases in insulin-sensitive tissues.

The intrinsic tyrosyl kinase activity of the insulin receptor is regulated by a balance between insulin-induced receptor autophosphorylation, which stimulates the receptor kinase, and enzymatic dephosphorylation of the receptor, which deactivates its kinase activity. The cellular protein-tyrosine phosphatase (PTPase) enzymes responsible for reversing the activated state of the insulin receptor have not been characterized. Our laboratory is interested in identifying and cloning the specific PTPase(s) that regulate the phosphorylation state of the insulin receptor. This chapter will summarize the design and results of our initial molecular cloning studies to identify specific PTPases in insulin-sensitive tissues that may have a potential physiological role in insulin action and clinical insulin resistance.

Amino Acid Sequence↗

An image analysis on pathological changes in pulmonary arteries in chronic obstructive pulmonary disease.

The changes in small pulmonary arteries of 15 patients with chronic obstructive pulmonary disease (COPD) were investigated by light and electron microscopy, image analysis etc. It was found that the structural changes in the pulmonary arteries of the patients with COPD were characterized by muscularization of non-muscular arterioles, media hypertrophy, longitudinal smooth muscle bundles in the intima and fibrosis in both the media and intima. In the course of time, these lesions resulted in thickening of the arterial wall and narrowing of the lumen. Clinically, the patients developed pulmonary hypertension causing cor pulmonale. Initial data on the structure of arterial wall at different segments were compared statistically. There was very significant difference between the COPD and control groups (P less than 0.001). By Fisher's auto-classification (automatic pattern recognition), the rate recognized was correct in more than 90% in the small arteries of less than 200 microns in diameter. It is suggested that these arteriolar changes are closely related to pulmonary hypertension. The image analysis showed that the ratios of MWA/MVA and MWT/MD were of great value in evaluating the degree of the changes in the arteries of the patients with COPD.

Female↗

Immunosuppression of triptolide and its effect on skin allograft survival.

In this study the immunosuppressive properties of triptolide were evaluated. Triptolide was found to inhibit skin allograft rejection in a dose-dependent manner. This inhibitory effect was time dependent. Triptolide at 0.1 mg/kg/day significantly prolonged the graft survival when triptolide was given for 9 days after transplantation, but not before transplantation. In vitro studies showed that triptolide markedly suppressed cytotoxic T-lymphocyte (CTL) induction and mixed lymphocyte reaction (MLR) at concentrations ranging from 0.08 to 10 ng/ml. The inhibition on MLR was also significant when triptolide was added to the cultures at 36 h after initial incubation. Furthermore, exogenous IL-2 did not reverse this inhibitory effect of triptolide. Our results suggest that triptolide inhibits lymphocyte activation at a relatively late stage, and its effect on immune response is not exerted through altering IL-2 production.

Animals↗

Identification of skeletal muscle protein-tyrosine phosphatases by amplification of conserved cDNA sequences.

Specific protein-tyrosine phosphatase (PTPase) enzymes that regulate signal transduction by the insulin receptor in target tissues have not been identified. We evaluated the expression of PTPase homologs in skeletal muscle since this tissue is the major site of insulin-mediated glucose disposal in vivo. A rat skeletal muscle cDNA pool was prepared with a set of degenerate oligonucleotide primers and PTPase cDNA sequences were amplified using pairs of "guess-mers" that were deduced from highly conserved residues within the known catalytic domains of these enzymes. Sequences encoding three "receptor-like" transmembrane PTPases were identified and two of these (known as LAR and LRP) were confirmed to be expressed in muscle by subsequent cDNA library screening and Northern blot analysis. The expression of the LAR and LRP PTPases in skeletal muscle suggests that these enzymes might have a role in the regulation of insulin action in muscle and other insulin-sensitive tissues.

Amino Acid Sequence↗

Gastric cytoprotection by intracisternal interleukin-1 beta in the rat.

The effects of intracisternal (ic) injection of recombinant interleukin-1 beta (IL-1) on absolute ethanol-induced gastric necrotic lesions were studied in conscious rats. IL-1 given ic inhibited ethanol-induced gastric lesions. The cytoprotective effect was dose dependent (ED175 ng/rat), long lasting with a maximal action when given 1-3 h prior to ethanol, blocked by ic injection of a IL-1 receptor antagonist protein (IRAP), and by intraperitoneal injection of indomethacin. IL-1, injected ic, was detected in the peripheral blood. However, IL-1 serum levels were lower after IL-1 injection ic than after ip at a dose giving equal gastric protection. These data show that ic IL-1 induces long lasting gastric protection mediated by interaction with IL-1 receptors and prostaglandin pathways at central and/or peripheral sites that remain to be localized.

Animals↗

Interleukin-1 is cytoprotective, antisecretory, stimulates PGE2 synthesis by the stomach, and retards gastric emptying.

Human recombinant interleukin 1 beta (IL-1) administered intraperitoneally to rats produced the following gastric effects: 1. It was cytoprotective, preventing gastric mucosal necrosis produced by oral administration of one ml of absolute ethanol to fasted animals. The ED50 was 1200 units/kg (110 ng per animal). IL-1 was 125 times more potent than prostaglandin E2 (on a weight basis), and 6,000 times more potent (on a molar basis). 2. The cytoprotective effect of IL-1 was blocked by indomethacin (inhibitor of prostaglandin synthesis) and by IRAP (a specific interleukin-1 receptor antagonist protein). IRAP did not inhibit cytoprotection induced by PGE2. 3. IL-1 prevented the formation of gastric erosions induced by aspirin. 4. IL-1 inhibited gastric secretion (volume, acid concentration and output), in the pylorus-ligated rat, with an ED50 of 300 units/kg (3.2 ng per animal). 5. Indomethacin and IRAP blocked the antisecretory effect of IL-1. 6. IL-1 retarded gastric emptying, an effect blocked by IRAP, but not by indomethacin. 7. IL-1 increased synthesis of prostaglandin E2 by the gastric mucosa by 111%. IL-1 is the most potent of known agents that are gastric cytoprotective, antiulcer, antisecretory, and delay gastric emptying. It appears to act mostly by stimulating the synthesis of prostaglandins by the stomach. These studies suggest that the stomach possesses IL-1 receptors. These are probably located on parietal cells (that produce acid), on prostaglandin-producing cells, on smooth muscle cells (responsible for gastric emptying), and on as yet unidentified cells involved in gastric cytoprotection. Both IL-1 and IRAP, being natural substances, may play a physiological role in the maintenance of gastric mucosal integrity, and in the regulation of acid secretion and gastric motility.

Animals↗

[Experimental research on the cold-constitution and the heat-constitution (I)].

This paper reports the experimental research on the cold-constitution (CC) and the heat-constitution (HC). The authors have selected the CC and HC in Wistar rats, and have determined adenylate kinase (ADK) activities: energy charge and Na(+)-K(+)-ATPase activities in liver, the amounts of T3, T4, progesterone, testosterone and estradiol in serum, 17-KS in urine. The ADK activities were markedly different between the HC group and the CC group (P less than 0.01). The Na(+)-K(+)-ATPase activities were obvious different between the HC group and the CC group (P less than 0.05). The energy charge of the HC group has increased by 16.1% as compared with the CC group in cells. The contents of T3, T4 of the HC group were higher than the CC group (P less than 0.01). The content of progesterone of the HC group was higher than the CC group as well (P less than 0.01). The contents of E2 and 17-KS had no differences. These results indicated that differences between the CC and the HC were based on the basic metabolism and its regulators.

Adenylate Kinase↗

[The "shen" reaction to trauma--an experimental study].

An experimental study using adult Kunming male mice was designed to observe the Shen reaction to trauma (bone fracture and burn). It was shown that the mice testes of the experimental groups were degenerated and the spermatogenesis disturbed. Under the electron microscope, the granules reduction, pyknosis, vesicular degeneration in the plasma of gonadotrophs and hemorrhage were found. It was revealed that the pathological changes of shen by trauma were mainly attacked on the adenohypophysis-gonadal axis. According to the results of this experimental study, the shen in the hypothesis of "trauma hurts shen" should be related to testes and ovaries (gonadal organs).

Animals↗

Stability of glutathione peroxidase in swine plasma samples under various storage conditions.

The stability of plasma glutathione peroxidase under different temperatures (4 degrees C vs. -15 degrees C), various durations of storage (0, 1, 2, 3, 7, 14, 28 and 56 d), and storage under inert gas (nitrogen (N2)) vs air is described. The glutathione peroxidase activity of swine plasma decreased consistently with storage at either 4 degrees C or -15 degrees C 1-56 d after collection, and differed (P less than or equal to 0.01) from the initial values. Storage under N2 at -15 degrees C slowed the rate of enzyme activity decrease but did not maintain the initial activity. For absolute measurements, it is suggested that swine plasma glutathione peroxidase activity be measured immediately after separation from the blood cells or be assayed within 24 h in plasma samples stored at -15 degrees C with air space displaced by N2. If relative treatment differences in enzyme activity are satisfactory, then assays can be conducted after controlled periods of storage.

Animals↗