[Risk factors and trend of changes in hypertension and coronary heart disease in Daqing].
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Biomedical subjects
Publications and source records attributed to R Hu.
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Serum thyroid hormones were measured in 62 cases of acute cerebrovascular apoplexy. Compared with the control group, T3, FT3 were markedly lowered and rT3, T4 and TSH were significantly increased with lowered T3/rT3 ratio. The patients were divided into two groups, according to whether there was hemorrhage in their CSF. Changes of serum thyroid hormones in cerebral haemorrhage were more remarkable than those observed in cerebral thrombosis. 16 cases with increased T4, FT4 were diagnosed as euthyroid hyperthyroxinemia. It was found that the amount of thyroid hormone changes appeared to be in proportion to the severity of acute cerebrovascular apoplexy. The determination of serum thyroid hormones would be useful in evaluating the severity of the strokes and in studying the thyroid function in acute cerebrovascular apoplexy.
Thromboembolism is a common and serious complication of total hip replacement. Methods of prophylaxis include combinations of physical compression of the legs and anticoagulation. Results of treatment are difficult to document and quantitate. The authors reviewed 122 patients who underwent hip arthroplasty with intermittent pneumatic calf compression, intravenous administration of dextran and platelet inhibitors. In 20% of them, clinically suspected pulmonary embolism was confirmed by ventilation perfusion lung scanning. The true incidence of pulmonary embolism is probably greater than this and it appears that the prophylactic regimen used in this study does not confer any benefit.
Transplantation of human tissues has become increasingly popular, and associated with this increase are reports of the transmission of diseases including acquired immune deficiency syndrome. To reduce the risk of transmitting disease through transplantation, careful scrutiny of current tissue transplantation procedures is necessary. Bone banking in Canada was evaluated by questionnaire, sent to the head operating room nurse of every Canadian hospital listed in the 1986 Canadian Medical Directory as having 100 or more beds. From this questionnaire, the authors identified 60 bone banks in Canada, many of which failed to meet recommended guidelines. The authors review the literature relating to bone banking procedures and present in detail the results of their survey.
Two monoclonal antibodies, UCD/AB 6.11 and UCD/PR 10.11, were evaluated for their patterns of immunohistochemical reactivity in a survey of paraffin-embedded human tissues by the avidin-biotin-immunoperoxidase technique. By two-dimensional immunoblotting, UCD/AB 6.11 reacts with keratin number 18 and UCD/PR 10.11 identifies both keratin numbers 8 and 18, the major keratins found in human simple epithelial cells. Both antibodies have excellent signal-to-noise ratios, and specifically react with simple epithelia, transitional epithelia, mesothelia and tumors derived from such tissues, making them superior immunological reagents. They do not react with neural, muscle, hematopoietic, connective or most epidermal tissues. However, within a given tissue or cell type, differences in the distributions of the antigens recognized by these two antibodies can be observed, raising the possibility of differential expression, modification, or masking of the keratin epitopes revealed by UCD/AB 6.11 and UCD/PR 10.11.
Treatment of thoracolumbar spine burst fracture with a neurologically intact patient is controversial, with advocates of operative and nonoperative approaches. Of 404 patients in a prospective spinal trauma study, 21 had burst fractures, were neurologically intact, and had greater than 1-year followup. This group was analyzed to evaluate treatment with early mobilization using a thoracolumbar total contact orthosis. The average time in a brace was 6 months. Two patients had pulmonary embolus treated successfully with anticoagulants. No patient required subsequent surgery for increasing kyphosis or neurologic deficit. Change in K angle at followup was 4.6 degrees (+/- 5.7) and change in anterior vertebral height was 6.1 degrees (+/- 10). All patients had a satisfactory pain score and most individuals returned to full employment. It is concluded that it is not necessary to routinely treat patients operatively with burst fractures if they fulfill the following criteria: 1) neurologically intact; 2) kyphosis angle less than 35 degrees; 3) other injuries do not preclude the use of a total contact orthosis; and 4) the patient is capable of understanding and cooperating with the treatment regime. These criteria are irrespective of the CT findings of posterior vertebral retropulsion and spinal canal narrowing.
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The immunomodulating effects of the A fragment of recombinant human interferon-alpha 2 (rIFN-alpha 2) generated by thermolysin treatment was compared to that of the intact rIFN-alpha 2 and lymphoblastoid IFN. The A fragment was similar to intact IFN in augmenting natural killer (NK) activity and suppressing the proliferation of certain cell lines, but it failed to inhibit human polyclonal immunoglobulin production; rIFN-alpha 2 and lymphoblastoid IFN were equally effective in suppressing this in vitro system. These data suggest that the A fragment mediates certain, but not all, of the immunomodulating properties of IFN-alpha 2.
Scatchard analyses of the equilibrium binding of radiolabeled human interferon-alpha2 (huIFN-alpha2) to Madin-Darby bovine kidney cells previously exposed to subsaturating concentrations of IFN-alpha showed approximately a 50% decrease in the number of cell surface receptors and no change in the apparent dissociation constant, Kd, compared with cells not exposed to interferon. The steady state equations describing the interaction of polypeptide ligands with cell surface receptors under physiological conditions (Wiley, H.S., and Cunningham, D.D. (1981) Cell 25, 433-440) have allowed us to determine, under steady state conditions, the rate of insertion of receptors into the cell membrane, the endocytic rate constant of occupied receptors, the rate constant of turnover of unoccupied receptors, and the rate of hydrolysis of internalized ligand. Our results indicate that occupied and unoccupied interferon receptors are cleared from the cell surface at approximately the same rate. This suggests that the down-regulation of the huIFN-alpha2 receptor on Madin-Darby bovine kidney cells by huIFN-alpha2 differs from that of several other surface receptors for polypeptide hormones and growth factors analyzed on cultured cells in that the binding of huIFN-alpha2 to its receptor does not increase the rate of receptor endocytosis.
This paper reports the isolation and some properties of L-amino acid oxidase from Ophiophagus hannah venom. The differences between L-amino acid oxidase from Ophiophagus hannah and that from other sources in specific activity, properties and the spectrum of isozymes are noticeable. The result of electrophoresis on polyacrylamide gel shows that this purified enzyme is homogenous. The molecular weight determined by gradient polyacrylamide gel slab (4--30%) is around 15 X 10(4) dalton. The molecular weight of the subunit determined by SDS gradient gel electrophoresis (4--30%) is around 7.3 X 10(4) dalton. Therefore, this enzyme is composed of two subunits. The absorption spectrum reveals that there are two FADs in each molecule. The optimum pH of enzymic reaction is around 8.7--9.0 when L-leucine is used as substrate. The inhibition of the products is noticeable when substrate concentration goes beyond 3mM. This enzyme is heat stable and its activity would not decrease obviously after heating at 55 degrees C for 40 min. A linear relationship between enzyme concentration and reaction rate was noticed when enzyme concentration was below 5.7 micrograms/ml.
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The cardiovascular effects of therapeutic doses of tricyclic antidepressants are reviewed and their clinical significance discussed. At standard therapeutic doses these antidepressant drugs produced small changes in heart rate and several intervals of the EKG in some patients, but clinically significant effects on the EKG are usually seen only in patients with high blood levels of the drugs; these high plasma levels are often above those needed for therapeutic antidepressant effects. In contrast, the orthostatic hypotension induced by antidepressants usually occurs at dosages and blood levels within the therapeutic range, and, therefore, this side-effect may be of greater clinical significance in standard clinical treatment with antidepressants. A review of recent studies suggest that adequate doses of antidepressants may be used safely in geriatric depressed patients and in many patients with stable preexisting cardiac disease. However, more frequent monitoring of plasma levels of antidepressants and EKGs may be particularly important in these groups of patients.
An indirect immunoperoxidase method is described, which can readily detect viral antigens in paraffin sections of primary, transplanted, and metastatic mammary tumors of mice. In addition to having the obvious advantage of not being limited to fresh specimens, immunoperoxidase staining of paraffin sections proved to be superior in many respects when compared with immunofluorescence and frozen sections. Immunoperoxidase staining of paraffin sections is permanent and provides the kind of histological detail required for precise cytological identification and localization with light microscopy. All of 25 tumors and 4 metastatic lesions showed evidence of glycoprotein gp52 as well as other mouse mammary tumor viral antigens. The pattern and intensity of the stain were related to the degree of histologic differentiation of the tumor. Wide variations in expression of viral antigens by individual malignant cells were observed within the same tumor.
To examine species-specific aspects of the induction of absorption, distribution, metabolism and excretion (ADME)-related genes, we used 25 000 gene oligonucleotide microarrays to construct a rodent gene-response compendium that compared hepatic gene expression profiles and developed consensus aryl hydrocarbon receptor (AhR), constitutive androstane receptor (CAR) and pregnane X-receptor (PXR) ligand signatures relevant to drug clearance. Twenty-six inducer compounds were chosen from the literature. Rats and mice received one of six dose levels (log2 dose escalation, 32-fold dose range) of each compound daily for 3 days. Animals were necropsied 6-9 h after the last dose, and tissues were collected for RNA analysis. Hepatic gene expression profiles were obtained using Rosetta Resolver expression analysis system, and ADME-related genes were extracted. Cross-talk among nuclear receptors or hepatoxicity at high dose levels resulted in large signatures (usually >1000 genes at p < 0.01) for most compounds. After ADME gene transcript enrichment, agglomerative clustering separated AhR ligands from CAR/PXR ligands, but it was difficult to distinguish CAR from PXR ligands. Consensus signatures were derived from groups of AhR, CAR and PXR ligands; and cross-talk among responding genes was determined. Many compounds had distinct log dose-response profiles, and relative potencies for ligands were established. Robust responses by CYP1A1, CYP2B10 (CAR responsive in mice) and CYP2B15 (CAR responsive in rats) and CYP3A1 (PXR responsive in rats) were used to benchmark the relative potency of different ligands and to determine the relative selectivity for AhR, CAR or PXR. By using a compendium of gene expression profiles, we defined species-specific induction patterns across the ADME transcriptome.
Cellular responses to xenobiotic-induced stress can signal proliferation, differentiation, homeostasis, apoptosis, or necrosis. To better understand the underlying molecular mechanisms after exposure to xenobiotics or drugs, we studied the signal transduction pathways, the mitogen-activated protein kinase (MAPK), and the basic leucine zipper transcription factor Nrf2, activated by different agents in the induction of Phase II drug metabolizing enzymes (DMEs). The MAPKs, characterized as proline-directed serine/threonine kinases, are essential components of signaling pathways that convert various extracellular signals into intracellular responses through serial phosphorylation cascades. Once activated, MAPKs can phosphorylate many transcription factors, such as c-Jun, ATF-2, and ultimately lead to changes in gene expression. Two classes of Phase II gene inducers, which are also cancer chemopreventive agents, were studied: (1) the phenolic antioxidants, namely butylated hydroxyanisole (BHA) and its active de-methylated metabolite t-butylhydroquinone (tBHQ), and phenolic flavonoids such as green tea polyphenols (GTP) and (-)-epigallocatechin-3-gallate (EGCG); and (2) the naturally occurring isothiocyanates, namely phenethyl isothiocyanate (PEITC), and sulforaphane. BHA and tBHQ are both well-known phenolic antioxidants used as food preservatives, and strongly activate c-Jun N-terminal kinase 1 (JNK1), extracellular signal-regulated protein kinase 2 (ERK2), or p38, in a time- and dose-dependent fashion. Free radical scavengers N-acetyl-L-cysteine (NAC), or glutathione (GSH), inhibited ERK2 activation and, to a much lesser extent, JNK1 activation by BHA/tBHQ, implicating the role of oxidative stress. Under conditions where MAPKs were activated, BHA or GTP also activated ARE/EpRE (antioxidant/electrophile response element), with the induction of Phase II genes such as NQO. Transfection studies with various cDNAs encoding wild-type or dominant-negative mutants of MAPKs and/or transcription factor Nrf2, substantially modulated ARE-mediated luciferase reporter activity in the presence or absence of phenolic compounds. Other phytochemicals including PEITC, and sulforaphane, also differentially regulated the activities of MAPKs, Nrf2, and ARE-mediated luciferase reporter gene activity and Phase II enzyme induction. A model is proposed where these xenobiotics (BHA, tBHQ, GTP, EGCG, PEITC, sulforaphane) activate the MAPK pathway via an electrophilic-mediated stress response, leading to the transcription activation of Nrf2/Maf heterodimers on ARE/EpRE enhancers, with the subsequent induction of cellular defense/detoxifying genes including Phase II DMEs, which may protect the cells against toxic environmental insults and thereby enhance cell survival. The studies of these signaling pathways may yield insights into the fate of cells upon exposure to xenobiotics.