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Biomedical subjects

W Zhou

Publications and source records attributed to W Zhou.

At least 325 records · Page 18Linked to original sources
PubMed1995

A chimeric IgG4 monoclonal antibody directed against CD18 reduces infarct size in a primate model of myocardial ischemia and reperfusion.

OBJECTIVES: This study attempted to determine whether neutrophil sequestration in reperfused myocardium can be inhibited and infarct size reduced by treatment with a chimeric, monoclonal IgG4 antibody (CLB54) directed against CD18 in a primate model of acute myocardial ischemia and reperfusion. BACKGROUND: Reperfusion injury, in part mediated by neutrophils, may limit the potential benefit of reestablishing infarct-related artery patency in patients with acute myocardial infarction. METHODS: Nineteen closed-chest baboons (10 control, 9 treated with CLB54) had the left anterior descending coronary artery occluded for 90 min, followed by 4 h of reflow. CLB54 (mean [+/- SD] 11 +/- 2 mg/kg body weight) or saline solution was administered intravenously 20 min before reflow. Coronary flow was determined using radiolabeled microspheres, infarct size by triphenyltetrazolium chloride staining, global and regional ventricular function by contrast ventriculography and neutrophil accumulation by a myeloperoxidase assay. RESULTS: Risk region size was the same in both groups. CLB54 treatment reduced infarct size expressed as a percent of the risk region from 41 +/- 20% in the saline-treated group to 19 +/- 17% in the CLB54-treated group (p < 0.02). This was associated with diminished myeloperoxidase activity and greater postreperfusion coronary flow in the risk region in CLB54-treated than in control baboons. Ejection fraction declined to the same extent in both groups, whereas anterior wall regional cord shortening was better preserved in CLB54-treated baboons. CONCLUSIONS: Inhibition of neutrophil sequestration with CLB54 administered before reperfusion reduces infarct size, preserves ischemic zone microvascular perfusion and minimizes the decline of regional wall motion.

Animals↗
PubMed1995

Involvement of intact inositol-1,4,5-trisphosphate-sensitive Ca2+ stores in cell cycle progression at the G1/S boundary in serum-stimulated human fibroblasts.

Thapsigargin, a selective inhibitor of the endoplasmic reticulum Ca2+ pump, has been shown to deplete inositol-1,4,5-trisphosphate-sensitive Ca2+ stores. Here we report that when thapsigargin was introduced to serum-stimulated human fibroblasts at a time point just before the G1/S boundary, it completely inhibited expression of cyclin A, activation of p33CDK2 cyclin-dependent kinase and initiation of DNA synthesis. In contrast, the Ca2+ mobilizing ionophore ionomycin was without effect. These findings indicate that Ca2+ inside the inositol-1,4,5-trisphosphate-sensitive Ca2+ stores plays a pivotal role for traverse across the G1/S transition point.

CDC2-CDC28 Kinases↗
PubMed1995

Expression and tissue localization of donor-specific complement C3 synthesized in human renal allografts.

Recent evidence suggests that the third component of complement, C3, is synthesized in renal tissue, and that increased C3 synthesis occurs in allograft rejection and immune complex-mediated nephritis. However, it is unclear whether intrinsic renal cells or migratory cells in the inflammatory infiltrate, possibly of recipient bone marrow origin, are the source of the C3 detected. This was investigated by determining the C3 allotypes of mRNA and protein produced by transplanted human kidney. Twenty donor-recipient pairs were examined, of which nine pairs had C3 allotypes that were informatively mismatched at the C3 F/S locus. Reverse transcriptase polymerase chain reaction (RT-PCR) followed by amplification refractory mutation system analysis showed intracellular donor-specific mRNA expression in six of these nine cases, at up to 61 days post-transplantation. Nested PCR reactions and the size of PCR products excluded contamination by genomic DNA. Allotype-specific staining of frozen sections of renal cortex demonstrated donor-derived C3 protein in both glomeruli and tubules of all biopsies examined, in a predominantly tubular distribution. These results imply that at least some of the pro-inflammatory effects of complement arise from intrinsic tissue synthesis of donor C3, and that this may represent a previously unrecognized source of tissue injury. The occurrence of local synthesis of C3 of donor allotype may have functional implications related to C3 allotype, and may also be relevant to strategies to inhibit intrarenal complement-mediated injury.

Alleles↗
PubMed1995

Characterization of cholecystokinin receptors and messenger RNA expression in rat pancreas: evidence for expression of cholecystokinin-A receptors but not cholecystokinin-B (gastrin) receptors.

It has been previously demonstrated that guinea pig pancreas possesses both cholecystokinin-A (CCK-A) receptors and CCK-B (gastrin) receptors. In contrast to guinea pig pancreas, it is not known whether CCK receptors in rat pancreas are CCK-A receptors, CCK-B (gastrin) receptors, or both. Thus, in the present study, we characterized CCK receptors in rat pancreas at the receptor and mRNA level. 125I-Bolton-Hunter-labeled CCK octapeptide (125I-BH-CCK-8), the specific CCK-A and CCK-B (gastrin) receptor antagonists L364,718 and L365,260, and 125I-labeled gastrin-I were utilized to characterize CCK receptors in normal rat pancreas. Additionally, we utilized 32P-labeled cDNA probes of the CCK-A receptor and CCK-B (gastrin) receptor coding regions in order to examine the expression of CCK receptor subtypes in normal rat pancreas at the mRNA level. The dose-inhibition curve of CCK-8 inhibiting binding of 125I-BH-CCK-8 was significantly best fit by a two-site model with a high-affinity site (Kd = 0.68 +/- 0.13 nM) and a low-affinity site (Kd = 656 +/- 289 nM). L364,718 inhibited binding of 125I-BH-CCK-8 with high affinity, whereas no high-affinity inhibition for L365,260 to inhibit binding of 125I-BH-CCK-8 was detected. L364,718 was 627 times as potent as L365,260 in inhibiting binding of 125I-BH-CCK-8. No saturable binding was present for 125I-labeled gastrin-I. Gastrin-17-I did not inhibit binding of 125I-BH-CCK-8.(ABSTRACT TRUNCATED AT 250 WORDS)

Animals↗
PubMed1995

Infectivity and risk factors of hepatitis C virus transmission through sexual contact.

HCV infection among heterosexuals with multiple partners and family members of patients with hepatitis C, and HCV RNA in the body fluid of these patients were investigated. The results showed that the HCV infection in heterosexuals with multiple partners, which was related to sexual activity, was much higher than that of healthy pregnant women. The HCV RNA in the saliva, semen or vaginal discharge of patients with hepatitis C was at detectable level. Among the patient's relatives, none of the children but 2 spouses were found to be infected with HCV. We concluded that sexual contact might play some role in HCV transmission.

Adolescent↗
PubMed1995

Initiation of disjunctive smooth pursuit in monkeys: evidence that Hering's law of equal innervation is not obeyed by the smooth pursuit system.

Monkeys generated disjunctive smooth pursuit eye movements when they tracked visual targets that moved toward or away from them. Eye acceleration was computed during the initial 100 msec of pursuit (the open-loop interval) for various target trajectories. The initial acceleration of either eye was a function of the target's motion with respect to that eye, regardless of whether or not the pursuit was conjugate or disjunctive, or performed with one eye occluded. Eye movements produced by fusional vergence could be separated temporally from eye movements produced by smooth pursuit using step-ramp paradigms. The separation of the two responses demonstrates that the fusional vergence system operates in parallel with the smooth pursuit system, presumably to minimize disparity, but not to generate disjunctive components of smooth pursuit eye movements.

Animals↗
PubMed1995

Identification of N-glycosylation sites in the gonadotropin-releasing hormone receptor: role in receptor expression but not ligand binding.

The asparagine residues of the three N-glycosylation consensus sequences in the mouse gonadotropin-releasing hormone receptor were mutated to determine which residues were glycosylated and the function of glycosylation. Photoaffinity labelled Gln4 and Gln18 receptor mutants exhibited lower apparent molecular weight on SDS polyacrylamide gel electrophoresis, while the Gln102 receptor showed wildtype mobility. This indicates that the receptor is glycosylated at Asn4 and Asn18 but not at Asn102. Binding affinities of all the mutant receptors were normal, indicating that carbohydrate moieties are not involved in ligand binding interactions. However, expression of the Gln4 and Gln18 receptors were substantially decreased, indicating a role for glycosylation in receptor expression or stability. All the glycosylation site mutants were capable of normal signal transduction, as indicated by their ability to stimulate inositol phosphate production.

Animals↗
PubMed1995

Calcium, calmodulin and cell cycle progression.

Proliferation of mammalian cells both in vivo and in vitro is dependent upon physiological concentrations of extracellular Ca2+. Growth factor stimulation of quiescent cells at the G0/G1 border usually results in a rapid mobilization of Ca2+ from both intra- and extracellular pools. However, Ca2+ influx is also required for later phases of cell cycle transition, especially in the late G1 phase for initiation of DNA synthesis. Available evidence indicates that calmodulin plays the major and essential roles in the Ca(2+)-dependent regulation of cell proliferation. Ca2+ and calmodulin act at multiple points in the cell cycle, including the initiation of the S phase and both initiation and completion of the M phase. Ca2+ and calmodulin stimulate the expression of genes involved in the cell cycle progression, leading to activation of cyclin-dependent kinases p33cdk2 and p34cdc2. Ca2+ and calmodulin are also involved in activation of enzymes participating in nucleotide metabolism and DNA replication, as well as nuclear envelope breakdown and cytokinesis. Ca2+/calmodulin-dependent protein kinase II and protein phosphatase calcineurin are both involved in the Ca2+ and calmodulin-mediated signalling of growth regulation. As compared to normal cells, growth of transformed cells is independent of extracellular Ca2+ and much less sensitive to calmodulin antagonists, suggesting the existence of derangements in the Ca2+ and calmodulin-mediated growth regulation mechanisms.

Animals↗
PubMed1995

Tissue synthesis of complement as an immune regulator.

Evidence is accumulating that a variety of tissues produce complement components, and that production in each tissue is differentially regulated by inflammatory cytokines. This locally produced complement could have protective or injurious actions, depending upon local circumstances. Techniques for analysing separately the contributions of local complement synthesis and complement derived from the circulation are now becoming available. We argue that an appreciation of the role of local complement synthesis may help to explain many features of organ- and tissue-specific immunological disease.

Animals↗
PubMed1995

Surface charge and calcium channel saturation in bullfrog sympathetic neurons.

Currents carried by Ba2+ through calcium channels were recorded in the whole-cell configuration in isolated frog sympathetic neurons. The effect of surface charge on the apparent saturation of the channel with Ba2+ was examined by varying [Ba2+]o and ionic strength. The current increased with [Ba2+]o, and the I-V relation and the activation curve shifted to more positive voltages. The shift of activation could be described by Gouy-Chapman theory, with a surface charge density of 1 e-/140 A2, calculated from the Grahame equation. Changes in ionic strength (replacing N-methyl-D-glucamine with sucrose) shifted the activation curve as expected for a surface charge density of 1 e-/85 A2, in reasonable agreement with the value from changing [Ba2+]o. The instantaneous I-V for fully activated channels also changed with ionic strength, which could be described either by a low surface charge density (less than 1 e-/1,500 A2), or by block by NMG with Kd approximately 300 mM (assuming no surface charge). We conclude that the channel permeation mechanism sees much less surface charge than the gating mechanism. The peak inward current saturated with an apparent Kd = 11.6 mM for Ba2+, while the instantaneous I-V saturated with an apparent Kd = 23.5 mM at 0 mV. This discrepancy can be explained by a lower surface charge near the pore, compared to the voltage sensor. After correction for a surface charge near the pore of 1 e-/1,500 A2, the instantaneous I-V saturated as a function of local [Ba2+]o, with Kd = 65 mM. These results suggest that the channel pore does bind Ba2+ in a saturable manner, but the current-[Ba2+]o relationship may be significantly affected by surface charge.

Animals↗
PubMed1995

RNA polymerase bypass at sites of dihydrouracil: implications for transcriptional mutagenesis.

Dihydrouracil (DHU) is a major base damage product formed from cytosine following exposure of DNA to ionizing radiation under anoxic conditions. To gain insight into the DNA lesion structural requirements for RNA polymerase arrest or bypass at various DNA damages located on the transcribed strand during elongation, DHU was placed onto promoter-containing DNA templates 20 nucleotides downstream from the transcription start site. In vitro, single-round transcription experiments carried out with SP6 and T7 RNA polymerases revealed that following a brief pause at the DHU site, both enzymes efficiently bypass this lesion with subsequent rapid generation of full-length runoff transcripts. Direct sequence analysis of these transcripts indicated that both RNA polymerases insert primarily adenine opposite to the DHU site, resulting in a G-to-A transition mutation in the lesion bypass product. Such bypass and insertion events at DHU sites (or other types of DNA damages), if they occur in vivo, have a number of important implications for both the repair of such lesions and the DNA damage-induced production of mutant proteins at the level of transcription (transcriptional mutagenesis).

Adenine↗
PubMed1995

[Effects of scopolamine on serotonin in the spinal cord and atria of morphine-dependent rats].

The effects of scopolamine on serotonin (5-HT) in the spinal cord and atria of morphine-dependent rats were studied. Levels of 5-HT and its metabolite, 5-hydroxyindolactic acid (5-HIAA) in the spinal cord and atria were analyzed by HPLC-ECD method. The results showed that contents of 5-HT, 5-HIAA in the spinal cord of morphine-dependent rats were statistically higher than those of controls (P < 0.01, n = 6), and that scopolamine inhibited morphine's effect by decreasing 5-HT, 5-HIAA in the spinal cord. After acute abstinence (1d), the contents of 5-HT in the spinal cord in natural withdrawal group were decreased, but increased in scopolamine group. After chronic abstinence (6d), the contents of 5-HT in the spinal cords in the two groups were all increased to above normal level. The results also showed that scopolamine did not affect the increasing of 5-HT in atria induced by morphine. The data support a role of muscarinic receptor on changes of 5-HT metabolism in the spinal cord in morphine-dependent rats.

Animals↗
PubMed1995

[Effect of scopolamine on morphine levels in serum and urine in rats].

Free morphine and conjugated morphine were determined by radioimmunoassay. Excretion of conjugated morphines in urine was increased significantly by treatment with scopolamine in a dose-related manner in morphine-dependent Sprague-Dawley rats (n = 8). Conjugated morphine in serum was increased by administration of scopolamine greater than that of controls at 2h, and both free and conjugated morphine in serum were enhanced at 24h after last injection of morphine in morphine-dependent rats (n = 6). After use of scopolamine (0.5mg/kg, bid, ip) for 3d the rats (n = 6) received single injection of morphine (10mg/kg, sc), the levels of free morphine were increased greater than those of controls at 2 and 10h. The data showed that scopolamine may not only induced the metabolism of morphine in liver, but also facilitated subcutaneous absorption of morphine, which result in enhancing the excretion of morphine.

Animals↗
PubMed1995

Clinical studies of primary angle closure glaucoma.

The ocular anatomic features, pupil-blocking force, status of angle synechia closure and positivity of provocative tests were compared between the primary chronic angle closure glaucoma (PCACG) and primary acute angle closure glaucoma (PAACG) by ultrasonic biometry, computerized image processing technique of the anterior ocular segment, gonioscopy and provocative tests. The studies showed that the anterior chamber depth of PAACG was shallower than that of PCACG, the pupil-blocking force of PAACG was stronger than that of PCACG, the status of angle synechia closure of PCACG was mainly creeping synechia closure and the positivity of mydriasis test after iridectomy was much higher (37.93%) in PCACG than that (11.43%) in PAACG. These facts suggested that the mechanisms of the angle closure of more than half of PCACG cases be multiple, besides the mechanism of pupillary block. Therefore, the authors emphasize that the pupillary block must be eliminated as well as the other mechanisms for the treatment of PCACG. The criteria of diagnosis and principles of management of PCACG were proposed.

Adult↗
PubMed1995

[The effects of combined hepatectomy and immuno-chemotherapy on postoperative recurrence rate of primary liver cancer].

121 cases with primary liver cancer were divided into four groups: OP: resection only (30 cases); OC: combined operative resection and chemotherapy (27 cases); OI: combined operative resection and immunotherapy (31 cases); OI: combined operative resection and immuno-chemotherapy (33 cases). The results showed that one year recurrence rate was 56.7%, 40.7%, 32.3% and 27.3%, respectively. The recurrence rate of group OI and group OIC were significantly lower than that of group OP and group OC. It indicated that combined operation and immuno-chemotherapy is useful in preventing post operative recurrence.

Antineoplastic Combined Chemotherapy Protocols↗
PubMed1995

Effect of massotherapy on the in vivo free radical metabolism in patients with prolapse of lumbar intervertebral disc and cervical spondylopathy.

The endogenous free radical scavenger superoxide dismutase (SOD) and blood catalase (CAT) in 2 groups of patients with prolapse of lumbar intervertebral disc and cervical spondylopathy were lower than that of the healthy control group, while the -SH reflecting the metabolic disturbance of free radical was higher. After massotherapy, blood SOD and CAT were increased, while lipid peroxide (LPO), -SH in urine were decreased, demonstrating that there are distinct parallel relationships existing in the changes of these enzymes in blood and urine.

Adult↗