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Biomedical subjects

A Wang

Publications and source records attributed to A Wang.

At least 199 records · Page 11Linked to original sources

Localization of Bax and Bcl-2 proteins, regulators of programmed cell death, in the human central nervous system.

Bax and Bcl-2 proteins are identified as regulating molecules for programmed cell death. In the central nervous system, programmed cell death or apoptosis is considered to be an important phenomenon that is related to neuron vulnerability to a variety of toxic effects, including ischaemic insult. In this study, localization of Bax and Bcl-2 proteins was investigated in the human central nervous system using autopsy cases without any neurological disorder. Results were compared with findings in the rat. Most neurons in human cerebral cortex, basal ganglia and brain stem were positive for both Bax and Bcl-2 proteins, whereas Purkinje cells in cerebellum and neurons in hippocampal CA1, CA2 and CA3 regions were positive for Bax but negative or weakly positive for Bcl-2. Glial cells examined in all sections were negative for both proteins. Choroid plexus, ependymal cells and arachnoid villi showed positive reactivity for both proteins. A possible relationship between the localization of Bax or Bcl-2 proteins and the cell vulnerability in central nervous system is discussed.

Animals↗

Different expression patterns of cyclins A, D1 and E in human colorectal cancer.

The expressions of cyclins A, D1 and E at the protein level were investigated by Western blotting in human colorectal carcinomas and in adjacent non-neoplastic colorectal mucosas. Cyclin E was higher in the cancer tissue than in the non-neoplastic mucosa in 92% patients (35 out of 38 cases). However, the cyclin A expression of the mucosa was higher than that of the cancer tissue in 63% (25 out of 40 cases) cases, and only 4 (10%) cancers had higher cyclin A expression. Eleven cancers (27%) demonstrated expression equivalent to that in the mucosa. Equal expression of cyclin D1 in cancer and mucosal tissues was found in 51% cases (20/39), lower expression of cyclin D1 by cancer tissues was demonstrated in 41% cases (16/39) and only three cancers showed higher expression than the mucosa. Proliferating-cell nuclear antigen immunohistochemistry revealed that the labeling index of the cancer tissue was 43.5 +/- 8.3% while that of the mucosa was only 14.8 +/- 5.1%. These results proved that colorectal cancers express high levels of cyclin E, consistent with a high rate of cell proliferation, whereas most of such cancer lose control of cyclin A and cyclin D1 expression.

Adult↗

Comparison of the size and morphology of UHMWPE wear debris produced by a hip joint simulator under serum and water lubricated conditions.

This paper investigates the effect of lubricant on the size and morphology of ultra-high molecular weight polyethylene (UHMWPE) wear debris produced by a hip joint simulator. Bovine serum and water were chosen as the lubricants for comparison. When bovine serum was used as lubricant, the majority of the wear debris produced was submicron sized and equiaxed or elongated in shape; no transfer film was found on the femoral heads. When water was used as lubricant, large pieces of thin UHMWPE flakes about 2-3 mm across were produced and patches of transfer films were observed on the femoral heads. These large flakes were comprised of numerous smaller thin flakes compacted together. While the size and shape of the wear debris produced with serum lubrication are similar to those reported from clinical studies in total hip replacement, the debris produced with water lubrication bears no resemblance to what has been seen clinically.

Animals↗

Behavioral measures of anxiety during opiate withdrawal.

Heightened anxiety is a major component of the withdrawal syndromes associated with ethanol and sedative hypnotic medications. Because of similarities between the opiate and sedative-hypnotic withdrawal syndromes as well as data implicating heightened noradrenergic tone with opiate withdrawal, we investigated changes in anxiety measures identified by plus-maze and social interaction testing during opiate withdrawal. Because Sprague Dawley rats had very low levels of entry into plus-maze open arms, further studies were conducted using the Long-Evans strain. Long-Evans rats received continuous infusions of morphine sulfate at 44 mg/kg per day delivered by osmotic pump over 7 days while control animals received inert implants. During the first 3 days of withdrawal, the number and time of entries into open and closed arms of a plus-maze was recorded. Both social and aggressive behaviors were scored durings pairings of groups of two socially naive animals. Body weight was significantly reduced in morphine-treated animals prior to and during withdrawal. Both the number of entries into open plus-maze arms and the time spent in open areas increased over the 3 days of testing. However, no difference in plus-maze activity was detected between morphine-treated and control subjects. On the third day of withdrawal, social interaction time was greater in pairs of withdrawn and control subjects compared to pairs of two control subjects. In conclusion, behavioral measures of anxiety are not increased during opiate withdrawal.

Animals↗

Effect of proline on lactate dehydrogenase activity: testing the generality and scope of the compatibility paradigm.

The k(cat) and K(m) kinetic parameters of the labile enzyme rabbit muscle lactic dehydrogenase were determined as a function of the concentration of proline, a solute (osmolyte) accumulated in the cells of many organisms to protect them against environmental stresses. Proline is believed to protect against the stress(es) without altering the functional activity of cellular macromolecules, a property defining it as a "compatible osmolyte." In the range of 0-2 M proline, K(cat) and K(m) values for both substrates are essentially unchanged, but between 2 M and 4 M proline, k(cat) decreases by a factor of 3 to 4, whereas K(m) values are only modestly changed, if at all. These results are consistent with the proposal that compatible osmolytes do not affect functional activity, that the property of compatibility expressed by such osmolytes is generic without regard to the evolutionary history of the protein, and that the organic osmolyte concentration range over which compatibility is exhibited is extensive. In short, the results are in full accord with the principal hypothesis of "compatible osmolytes" in detail and scope.

Animals↗

Inhibition of mitogenesis and c-fos induction in mesangial cells by heparin and heparan sulfates.

When rat renal mesangial cells (RMC) or vascular smooth muscle cells are released from quiescence by serum stimulation they express c-fos mRNA transiently at 30 to 60 minutes and progress in synchrony to S phase. Heparin causes significant suppression of [3H]-thymidine incorporation into DNA in S phase and a decrease and delay of entry of cells into S/G2. Added at the time of serum stimulation, heparin (1 microgram/ml or less) causes a decrease in the subsequent expression of c-fos mRNA in RMC, and a similar effect is observed with heparan sulfate chains isolated from RMC-cultures themselves. Although these cells internalize and degrade heparin, the timing of the maximal effect indicates an extracellular action of heparin. In keeping with this idea, 125I-heparin binds specifically to a single class of high affinity sites on the cell surface. The effect of heparin on c-fos induction may be independent of interaction with cytokines or cytokine receptors; its magnitude is not diminished when heparin-binding substances are removed from serum by heparin-Sepharose. Furthermore, direct activation of protein kinase C (PKC) with a phorbol ester in the absence of serum likewise induces c-fos and 1 microgram/ml heparin inhibits this response by 65%. Phorbol ester caused an increase in the proportion of histone H1-active PKC associated with the cell membrane fraction, from approximately 25% to 70% of total activity. Heparin affected neither the total activity of the kinase nor the proportion associated with the membrane. When PKC was inhibited with staurosporine, only very low levels of c-fos were induced by serum. We conclude that low concentrations of heparin and heparan sulfate suppress the mitogenic response of mesangial cells to serum and inhibit c-fos mRNA induction through an effect of cell surface-bound glycosaminoglycan on a signalling pathway downstream of PKC.

Animals↗

Differential regulation of airway epithelial integrins by growth factors.

The pattern of integrin expression on human airway epithelium changes significantly in injury or inflammation. In particular, two integrins, the fibronectin receptor, alpha 5 beta 1 and the fibronectin/tenascin receptor alpha v beta 6, are expressed at low or undetectable levels in normal airways in vivo but are induced in response to airway epithelial injury. We investigated the effects of various growth factors known to be present in the airways on the expression of constitutively expressed and inducible airway epithelial integrins using flow cytometry. In primary cultures of human airway epithelial cells, transforming growth factor-beta 1 (TGF beta 1) dramatically increased expression of alpha v beta 6 and essentially did not affect the expression of any other integrin, including alpha 5 beta 1. In contrast, epidermal growth factor (EGF) upregulated surface levels of both alpha v beta 6 and alpha 5 beta 1. Together, TGF beta 1 and EGF had an additive effect on alpha v beta 6 and alpha 5 beta 1 expression while increasing levels of alpha 2 beta 1 and decreasing expression of alpha 3 beta 1- and alpha 6-containing integrins. In contrast, the transformed airway epithelial cell line, BEAS-2B, expressed a markedly different repertoire of integrins. Integrin expression on BEAS-2B cells was not affected by any of the growth factors tested in this study. These results demonstrate that, in primary cultures of human airway epithelial cells, the pattern of integrin expression can be dramatically altered by growth factors. The inducible integrins, alpha v beta 6, and alpha 5 beta 1 are most subject to regulation by growth factors and expression of each of these can be differentially regulated. The differential regulation of the two principal fibronectin receptors on airway epithelial cells suggests that they may mediate different cellular responses to fibronectin.

Antibodies, Monoclonal↗

Mechanistic and morphological origins of ultra-high molecular weight polyethylene wear debris in total joint replacement prostheses.

The mechanistic and morphological origins of microscopic wear debris generated from UHMWPE articular surfaces in total joint replacement prostheses are investigated in this study. It was found experimentally that the molecular chain structure at the articulating surface of UHMWPE undergoes a re-organization process due to strain accumulation caused by surface traction. This molecular re-organization process creates a fibre-like surface texture that exhibits an anisotropic behaviour similar to a unidirectionally reinforced polymer composite. This composite responds to stresses favourably if loaded along the fibre axis but unfavourably if loaded off axis. Due to the very complex multi-axial motion/loading nature at the articular surfaces in total joint replacements, the stress tensors applied to each localized asperity contact area continuously change their directions and magnitudes. These changes in the localized stress field create an off-axis loading situation at each localized contact zone with respect to the orientation of the molecular chains. Depending on the off-axis angle, failure of the molecular structure occurs in three different ways: tensile rupture at very small off-axis angles, shear rupture at intermediate off-axis angles and transverse splitting at large off-axis angles. These failure mechanisms all produce similar fibre-like wear debris. However, the failure stresses differ significantly among the three modes. According to this molecular wear theory, the preferred polymer microstructure for optimal wear resistance would be a three-dimensionally strong network connected by covalent bonds between molecular chains. For UHMWPE, a three-dimensional molecular network can be created by radiation induced cross-linking. Experiments conducted on both gamma irradiated and unirradiated UHMWPE specimens using a linear wear machine and multi-axial joint simulators confirmed the validity of the molecular wear theory.

Biocompatible Materials↗

Ultrastructural calcification of glomerular immune complexes.

We report a previously undescribed ultrastructural calcification of glomerular immune complex depositions in a patient with lupus nephritis. Such processes give rise to a distinctive ultrastructural calcified microspheriol in electron-dense immune deposits, and were associated with hypercalcemia and nephrocalcinosis. The cause of hypercalcemia in this patient was uncertain, but related to a granulomatous inflammation and abscess of the breast. Whereas ultrastructural microcalcification was associated with hypercalcemia, its distribution in the segmental glomerular lesions suggests that an inflammatory process was contributory. The clinical follow-up indicates that the microcalcifications of immune complexes have not affected the outcome of nephritis and renal function.

Adolescent↗

[Effect of dihydroetorphini hydrochloride on mice parturition].

OBJECTIVE: To determine the effect of dihydroetorphini hydrochloride (DHE) on parturition of mice. METHODS: 180 pregnant mice were divided equally into 6 groups. DHE was administered intramuscularly (i.m.) to mice group A, B and C at the dose levels of 1, 2 and 4 micrograms/kg respectively. Morphine hydrochloride 200 micrograms/kg (hypodermic) was given to group D and procaine hydrochloride 1000 micrograms/kg i.m. for group E, while for group F as control distilled water was given. Each preparation was given to the pregnant mice 3 times, i.e. 18 hours before the date of confinement, during labor and 2 hours postpartum. RESULTS: No effects on mice parturition were found in group A, B, E, and F. The percentage of cyanosis in newborn mice of group C and D was 13.8% and 22.8% respectively, which was significantly higher than that (7.4%) in group F. CONCLUSION: DHE is safer than morphine and procaine for analgesia during labor, and no adverse effects of DHE at dose levels of 1 microgram/kg and 2 micrograms/kg were observed on mice parturition.

Abdominal Pain↗

[The coronary artery structure and early atherosclerotic lesions of 80 young adults cases in the Ningbo fishing region].

In order to study the coronary artery structure in relation to early atherosclerotic lesions of young adults residing in a fishing region, coronary arteries from 80 autopsies of people aged 15 to 39 years who died from accidents were collected and studied by pathohistological, immunohistochemical and morphometric methods. The results showed an 18.67% prevalence of Sudanophilic lesions in the right, coronary artery, the thickness of the intima of the left anterior descending branch increased with increasing age in males, but no significant difference was observed in females, the density of the coronary artery cell nuclei decreased with increasing age. The prevalence of fatty streaks and stenosis of left anterior descending branch was 25.0% and 5.0% respectively, and that of the left circumflex branch was 7.5% and 3.9% respectively. The amount of chondroinn sulfate proteoglycan in the left anterior descending branch was 23.3 +/- 8.8% in intima and 12.0 +/- 4.0% in the media. The above findings suggest that the custom of eating large amounts of sea food may have a beneficial effect on lipid deposit, smooth muscle cell proliferation, thickness of intima and percentage of proteoglycan. Thus it is one of the important factors for the low incidence of coronary heart disease in this fishing region.

Adolescent↗

[A prospective study on post-transfusion hepatitis C].

A cooperative prospective study on the clinical epidemiology of post-transfusion hepatitis C virus (HCV) infection was carried out from April 1993 to November 1994 in four medical schools in China, namely, Peking Union Medical College (PUMC), Western China Medical University (WCMU), Shanghai Medical University (SMU) and Beijing Medical University (BMU). A screen test on anti-HCV was done for the healthy donors of four groups. Anti-HCV positive rate was found to be 14.49% in professional blood donors, 5.60% in rural donors and 0.42% in urban volunteer donors. The positive rate of anti-HCV in blood recipients followed more than three months after transfusion was quite different in the four institutes, being 15.34% (14/91) in PUMC, 24.59% (15/61) in WCMU, 13.18% (12/91) in SMU and 1.53% (1/65) in BMU. During the same period post-transfusion hepatitis B virus infection rate decreased as compared with that in the past. It is concluded that the screen test on anti-HCV in blood donors can not completely rule out post-transfusion HCV infection.

Blood Donors↗

[Regulation of purine biosynthetic genes expression in Salmonella typhimurium. V. Nucleotide sequences evidence without purJ gene].

Previous genetic analysis showed that AICAI transformylase, IMP cyclohydrolase and GAR synthetase are encoded by purJ, purH and purD respectively, and which constitute a operon, mapped on 90 min in genetic map of Salmonella typhimurium But recent study in E. coli indicated that the genes encoding for above three enzymes only have purH and purD, without purJ gene. Report here is the DNA sequences evidence for abence of purJ gene in Salmonella typhimurium.

Escherichia coli↗

Effects of a naturally occurring compatible osmolyte on the internal dynamics of ribonuclease A.

Osmolytes are small organic solutes accumulated intracellularly by many organisms as they adapt to environmental stresses. Compatible osmolytes, a functional class of osmolytes, increase protein stability while having little or no effect on protein function. To investigate the interrelationships between protein stability, function, and internal dynamics, a hydrogen exchange (HX) quench method was established and used to study the effects of sucrose (a typical compatible osmolyte) on the structural fluctuations of ribonuclease A. It was found that the HX rates of the amide protons with intermediate rates are not affected by 1 M sucrose, but the slow-exchanging amide protons exchange even slower in 1 M sucrose. The protection factors of the slow-exchanging protons fall into a comparatively narrow range while those of the intermediate-exchanging protons vary widely. In agreement with the two-process model [Woodward, C.K., & Hilton, B. D. (1980) Biophys. J. 32, 561-575], we conclude that for those slow-exchanging amide protons, the exchange occurs mainly from the compact unfolded state ensemble of the protein. The internal dynamics leading to slow exchange involve exposure of large protein surface areas, similar to that which occurs upon the unfolding of protein. Because sucrose opposes such an increase in protein surface area exposure, both the slow HX rates and the protein stability are affected by sucrose. For those amide protons with fast and intermediate HX rates, the exchange occurs mainly from the native state ensemble of the protein. The internal dynamics involved in the exchange are localized without much surface area change, and functionally important structural fluctuations are likely to occur within this dynamic range.(ABSTRACT TRUNCATED AT 250 WORDS)

Animals↗

Effect of fluvastatin on lipoprotein profiles in treating renal transplant recipients with dyslipoproteinemia.

A single, blinded placebo-drug trial was conducted to study the efficacy and safety of fluvastatin, a new 3-hydroxy-3-methylglutaryl-coenzyme A reductase inhibitor, in treating dyslipoproteinemia in 16 renal transplant recipients who had been on an immunosuppressive regimen that included cyclosporine (CsA). They were studied for 32 consecutive weeks, with 4 weeks of baseline treatment, 4 weeks of placebo, 12 weeks of treatment with fluvastatin 20 mg daily, and 12 weeks of fluvastatin 40 mg daily. Blood samples were obtained every 4 weeks for measurement of the lipoprotein profiles, which included total cholesterol (TC), triglyceride, low density lipoprotein (LDL)-, high density lipoprotein (HDL)-, HDL2-, HDL3- and very low density lipoprotein-cholesterol (C), apolipoprotein (Apo) A-1, Apo B, and lipoprotein(a). Fifteen patients completed the trial. After 12 weeks of treatment, fluvastatin 20 mg significantly reduced TC by 13.4% (from 6.7 +/- 0.5 [mean +/- SEM] to 5.8 +/- 0.2 mmol/L), LDL-C by 22% (from 4.1 +/- 0.3 to 3.2 +/- 0.2 mmol/L), and Apo B by 13.2% (from 159.6 +/- 8.8 to 138.6 +/- 9.2 mg/dl) (P < 0.005). The subsequent 12-week treatment of fluvastatin 40 mg significantly reduced TC by 16.4% to 5.6 +/- 0.3 mmol/L, LDL-C by 29.3% to 2.9 +/- 0.2 mmol/L, and Apo B by 18.2% to 130.6 +/- 5.5 mg/dl (P < 0.00005). There was no significant change in levels of other lipoproteins, including lipoprotein (a). There were no significant changes in the whole blood trough CsA concentrations, renal and liver function tests, and serum creatine phosphokinase level during treatment when compared with baseline and placebo. No patient complained of myalgia or failed to complete the study due to side effects of the drug. Fluvastatin appears to be safe and effective in treating dyslipoproteinemia in renal transplant recipients who are maintained on CsA.

Adult↗

Basic fibroblast growth factor mediates its effects on committed myeloid progenitors by direct action and has no effect on hematopoietic stem cells.

Basic fibroblast growth factor or fibroblast growth factor-2 (FGF) has been shown to affect myeloid cell proliferation and hypothesized to stimulate primitive hematopoietic cells. We sought to evaluate the effect of FGF on hematopoietic stem cells and to determine if FGF mediated its effects on progenitor cells directly or through the induction of other cytokines. To address the direct effects of FGF, we investigated whether FGF induced production of interleukin-1 beta (IL-1 beta), tumor necrosis factor alpha, IL-6, granulocyte colony-stimulating factor, or granulocyte-macrophage colony-stimulating factor by two types of accessory cells, bone marrow (BM) fibroblasts and macrophages. We further evaluated whether antibodies to FGF-induced cytokines affected colony formation. To determine if FGF was capable of stimulating multipotent progenitors, we assessed the output of different colony types after stimulation of BM mononuclear cells (BMMC) or CD34+ BMMC and compared the effects of FGF with the stem cell active cytokine, kit ligand (KL). In addition, a subset of CD34+ BMMC with characteristics of hematopoietic stem cells was isolated by functional selection and their response to FGF was evaluated using proliferation, colony-forming, and single-cell polymerase chain reaction (PCR) assays. We determined that FGF had a stimulatory effect on the production of a single cytokine, IL-6, but that the effects of FGF on colony formation were not attributable to that induction. FGF was more restricted in its in vitro effects on BM progenitors than KL was, having no effect on erythroid colony formation. FGF did not stimulate stem cells and FGF receptors were not detected on stem cells as evaluated by single-cell reverse transcription PCR. In contrast, FGF receptor gene expression was detected in myeloid progenitor populations. These data support a directly mediated effect for FGF that appears to be restricted to lineage-committed myeloid progenitor cells. FGF does not appear to modulate the human hematopoietic stem cell.

Adipose Tissue↗