The protein C pathway: new insights.
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Biomedical subjects
Publications and source records attributed to W Ding.
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In a study on metabolism of aluminium in rats, two doses of aluminium, 100 mg/kg and 40 mg/kg, were administered through gastric tube in SD rats to observe its storage, distribution in various tissues and 48-hour excretion in urine and feces. Results showed that storage and distribution of aluminium in various tissues were different in two doses during different time periods. Apparent absorption rates of aluminum were 19.07-19.45 and 3.50-7.72 percent and apparent retention rates were 16.89-20.67 and 3.76-13.48 percent 24 and 48 hours after its intake, respectively, in high dose group, and those in low dose group were 29.40-36.58 and 3.76-13.48 percent and 29.27-36.43 and 3.69-13.35 percent, respectively. In high dose group, contents of aluminium in liver 0.5 hours, in kidney one hour, in brain 48 hours after intake were higher than those in other time periods. The highest content of aluminum was in the liver, and the next in the brain and kidney, in low aluminium group, and that in brain of the rats 24 and 48 hours after intake in the high dose group were significantly higher than those in the low dose group (P < 0.01). It suggests that different doses of aluminium had certain affinity to the brain of rats. Cumulative excretion of aluminium in urine and feces accounted for 1.08-1.22 and 0.11-0.31, and 97.01-99.13 and 86.55-96.07 percent of the total intake, respectively, in the high and low dose groups.
The relative ratios of vessel lumen area/total area (EA/TA), vessel wall area/total area (MA/TA) and vessel wall thickness/vessel external diameter (WD/TD) of intra-acinar arteries were studied with image analysor in 35 rats of experimental pulmonary artery hypertension and outcomes of treatment. All the rats were divided into control group (R0), hypertension group (R1) and treated groups (R2), (R3) and (R4). The results showed relative ratios of EA/TA decreased significantly in the palmonary artery hypertension group in comparison with the control and treated groups, while the values of WA/TA and WD/TD increased significantly. The results may be valuable for morphological quantitative study, diagnosis of pulmonary artery hypertension and prediction of the disease prognosis.
The aim of this study is to test the patency rate and safety of the accelerated streptokinase dose regimen for coronary thrombolysis compared with the conventional one. One hundred and four patients entering three hospitals up to 12 hours after the onset of definite acute myocardial infarction were randomizely treated with intravenous accelerated streptokinase dose regimen (1.5 million units/30 min) (group A, 47 cases) and conventional dose regimen (1.5 million units/60 min) (group B, 57 casese). The reperfusion rate of infarct-related arteries determined by clinical evidence of reperfusion was 76.6% (36/47) in group A VS 61.4% (35/57) in group B. There was significant difference in reperfusion rates among patients within 6 hours after the onset of chest pain: 87.9% (29/33) in group A VS 67.4 (29/43) in group B (P < 0.05). The incidence of mild bleeding, allergic reaction, hypotension was 12.8% (6/47), 4.3% (2/47), 12.8 (6/47) respectively in group A vs 21.1 (12/57), 3.5 (2/57), 17.5% (10/57) respectively in group B. Compared to conventional dose regimen, intravenous accelerated streptokinase dose regimen for coronary thrombolysis seems to improve reperfusion rate markedly without increasing adverse events such as bleeding, allergic reaction and hypotension. It suggests that accelerated streptokinase therapy deserves more extensive investigation.
In order to investigate the influences of taurine on thrombolysis serum endothelin (ET) concentration was determined in patients with acute myocardial infarcation (AMI) without urokinase (UK) treatment (group 1) and after treatment with UK (group 2) or UK combined with taurine (group 3). In a rat model with abdominal aorta thrombosed by FeCl3, the changes of serum ET, malodialdehyde (MDA) and intravascular thrombosis were observed in three groups same as in patients. The results were as follows: (1) Serum ET levels of group 1 patients at early phase of onset (6 hours) were significantly higher than those of the controls (47.3 +/- 6.3 ng/L vs 20.4 +/- 9.7 ng/L, P < 0.001). After two days serum ET decreased to normal level. Serum ET levels were significantly higher from 6 to 10 hours after the onset of AMI in group 2 than in group 1 (70.8 +/- 6.6 ng/L vs 56.9 +/- 8.6 ng/L, P < 0.01, at 8 hours). Serum ET levels were significantly lower from 8 hours to a week after onset of AMI in group 3 than in group 2 (33.3 +/- 8.2 ng/L vs 70.8 +/- 6.6 ng/L, P < 0.01, at 8 hours). (2) In the rat model with thrombosis of abdominal aorta, the changes of serum ET were similar to those of AMI patients. In addition serum MDA levels were significantly decreased (20.85 +/- 3.05 mumol/L vs 25.18 +/- 3.53 mumol/L after combined treatment with UK and taurine, P < 0.05). The ratio of cross area of vascular lumen and thrombus was lower after treatment with combination of UK and taurine than treatment with UK alone (0.4650 +/- 0.0928 vs 0.6176 +/- 0.1179, P < 0.05), the results suggested that taurine can decrease significantly serum ET levels, potentiate UK-induced vascular recanlization and reduce ischemia reperfusion injury. Taurine might be useful clinically as an adjunct of thrombolytic therapy.
OBJECTIVE: To evaluate the effect of membrane artificial lung of polypropylene hollow fibres on treatment of type II respiratory failure. METHOD: Seven dogs with respiratory failure were randomly selected, arterial-venous bypass was set up. Domestic-made membrane artificial lung with polypropylene hollow fibres was installed to treat hypoxymia and hypercapnia in animals. Blood gas analyses were done at 30 min, 60 min and 90 minutes respectively. RESULT: The result showed that SO2 reached over 90%, PaO2 ascended from 7.6 +/- 1.3 to 13.6 +/- 1.8 kPa, PaCO2 descended from 11.6 +/- 0.6 to 7.2 +/- 0.5 kPa. CONCLUSIONS: The authors recommand the new instrument was recommanded for treating type II respiratory failure.
The paper deals with the treatment of the pulmonary artery hypertention in rats caused by monocrotaline with garlicin, liqustrazine and berbamine and studies the relationship between the function and structure of pulmonary artery and pulmonary artery hypertension before and after use of hypotensive agents. The results show that there is a close relationship between the function and structure of pulmonary artery and pulmonary hypertension, and the inhibitory effect of garlicin is the strongest among the three herbal medicines. The pathogenesis is also studied.
Vasculitis is an common clinical feature of systemic lupus erythematosus (SLE) in humans and in animal models of this disease. Humoral autoimmunity against endothelial cells has been previously demonstrated in SLE and other autoimmune disorders, but the precise cell surface antigenic targets involved in the initiation and progression of vascular injury are still essentially unknown. In the current studies, we demonstrate the presence of autoantibodies in the sera of MRL/lpr/lpr mice which bind endothelial cell surface antigens by ELISA and also cause complement-dependent cytotoxicity of these cells. These MRL/lpr/lpr sera induced complement-dependent cleavage and release of 35SO4-labeled material containing primarily cell surface heparan sulfate proteoglycans from these cells, and react with heparin (a glycosaminoglycan related to heparan sulfate) by ELISA and liquid-phase competitive inhibition ELISA. These data indicate that antiendothelial cell autoantibodies present in autoimmune MRL/lpr/lpr mice are directed at least in part against cell surface heparan sulfate proteoglycans. Autoantibodies to cell surface heparan sulfate proteoglycan may play a role in vascular endothelial cell injury in these animals through complement-dependent, autoimmune mechanisms.
Inflammation and the response to injury may play an important role in the process of amyloidosis in Alzheimer's disease. We investigated the effect of interleukin-1 (IL-1) and nerve growth factor (NGF) on the metabolism of neuroblastoma proteoglycans. IL-1 and NGF increased the net charge and the net secretion of neuroblastoma proteoglycans. NGF also specifically increased the relative amount of cell-associated and secreted heparan sulfate proteoglycans in these cells. We previously demonstrated that neuroblastoma heparan sulfate proteoglycan binds specifically to the amyloid beta-amyloid peptide involved in Alzheimer's disease. Heparan sulfate glycosaminoglycans synthesized by IL-1-stimulated cells demonstrated an increased relative binding affinity for the beta-amyloid peptide. Thus, IL-1 and NGF induce the hypersecretion and hypersulfation of neuroblastoma heparan sulfate proteoglycans which bind beta-amyloid. These studies link the process of inflammation and repair with alterations in the metabolism of heparan sulfate proteoglycans and amyloid formation in Alzheimer's disease and other disorders.
A critical step in positional cloning is the identification of candidate genes from a large, genetically defined region. Candidate gene isolation by hybrid selection, genomic sequencing, and direct cDNA library screening identified 45 candidate gene fragments (CGFs) from a 600 kb genomic region that contains the BRCA1 gene. These CGFs define a minimum of 15 genes, six of which are newly localized to the BRCA1 region. We present an analysis of the efficiency and the sequences generated for each of these methods. We also compare our CGF set to those reported for the BRCA1 region by three other groups, revealing a surprising lack of overlap among the sets.
An increasing number of cancer treatment centres are using in vivo dosimetry as a quality assurance tool for verifying dosimetry as either the entrance or exit surface of the patient undergoing external beam radiotherapy. Equipment is usually limited to either thermoluminescent dosimeters (TLD) or semiconductor detectors such as p-type diodes. The semiconductor detector is more popular than the TLD due to the major advantage of real time analysis of the actual dose delivered. If a discrepancy is observed between the calculated and the measured entrance dose, it is possible to eliminate several likely sources of errors by immediately verifying all treatment parameters. Five Scanditronix EDP-10 p-type diodes were investigated to determine their calibration and relevant correction factors for entrance dose measurements using a Victoreen White Water-RW3 tissue equivalent phantom and a 6 MV photon beam from a Varian Clinac 2100C linear accelerator. Correction factors were determined for individual diodes for the following parameters: source to surface distance (SSD), collimator size, wedge, plate (tray) and temperature. The directional dependence of diode response was also investigated. The SSD correction factor (CSSD) was found to increase by approximately 3% over the range of SSD from 80 to 130 cm. The correction factor for collimator size (Cfield) also varied by approximately 3% between 5 x 5 and 40 x 40 cm2. The wedge correction factor (Cwedge) and plate correction factor (Cplate) were found to be a function of collimator size. Over the range of measurement, these factors varied by a maximum of 1 and 1.5%, respectively. The Cplate variation between the solid and the drilled plates under the same irradiation conditions was a maximum of 2.4%. The diode sensitivity demonstrated an increase with temperature. A maximum of 2.5% variation for the directional dependence of diode response was observed for angle of +/- 60 degrees. In conclusion, in vivo dosimetry is an important and reliable method for checking the dose delivered to the patient. Preclinical calibration and determination of the relevant correction factors for each diode are essential in order to achieve a high accuracy of dose delivered to the patient.
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The present study has shown that Guizhi Decoction can increase the normal myocardial blood flow in rabbits. The best result can be achieved in twenty minutes after the decoction is given (ig).
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A strong candidate for the 17q-linked BRCA1 gene, which influences susceptibility to breast and ovarian cancer, has been identified by positional cloning methods. Probable predisposing mutations have been detected in five of eight kindreds presumed to segregate BRCA1 susceptibility alleles. The mutations include an 11-base pair deletion, a 1-base pair insertion, a stop codon, a missense substitution, and an inferred regulatory mutation. The BRCA1 gene is expressed in numerous tissues, including breast and ovary, and encodes a predicted protein of 1863 amino acids. This protein contains a zinc finger domain in its amino-terminal region, but is otherwise unrelated to previously described proteins. Identification of BRCA1 should facilitate early diagnosis of breast and ovarian cancer susceptibility in some individuals as well as a better understanding of breast cancer biology.
Protein-tyrosine-phosphatases (PTPases) have been implicated in the regulation of certain tyrosine kinase growth factor receptors in that they dephosphorylate the activated (autophosphorylated) form of the receptors. In order to identify PTPases that potentially act on receptor targets in liver, we used the human leucocyte common antigen-related PTPase (LAR) cDNA [Streuli, Krueger, Hall, Schlossman and Saito (1988) J. Exp. Med. 168, 1523-1530] and isolated two closely related transmembrane PTPase homologues from a rat hepatic cDNA library. Both PTPases had large extracellular domains that contained three immunoglobulin-like repeats and eight type-III fibronectin repeats. Both enzymes had tandem homologous PTPase domains following a single hydrophobic transmembrane domain. One sequence encoded the rat homologue of LAR. The second PTPase, designated LAR-PTP2, had 79 and 90% identity with rat LAR in the respective cytoplasmic PTPase domains, with only 57% sequence similarity in the extracellular domain. The catalytic domains of LAR and LAR-PTP2 prepared by bacterial expression were active in dephosphorylating a variety of phosphotyrosyl substrates but did not hydrolyse phosphoserine or phosphothreonine residues of labelled casein. Both enzymes exhibited rapid turnover numbers of 4-7 s-1 for myelin basic protein and 78-150 s-1 for derivatized lysozyme. LAR and LAR-PTP2 displayed similar PTPase activity towards the simultaneous dephosphorylation of receptors of intact insulin and epidermal growth factor from liver membranes. These data indicate that there is a family of LAR-related PTPases that may regulate the phosphorylation state of receptor tyrosine kinases in liver and other tissues.
Protein-tyrosine phosphatases (PTPases) are among the fastest growing family of enzymes that are closely linked to signal transduction pathways involving reversible tyrosine phosphorylation. In order to identify PTPase homologs expressed in adipocytes that might regulate the action of insulin or growth factors in this tissue, we screened a rat adipocyte cDNA library at reduced stringency with a panel of candidate PTPase probes. After subcloning and sequence analysis of the positive plaques, this approach enabled us to identify the expression of LRP/RPTP-alpha, PTPase 1B, SH-PTP2/Syp, and LAR in adipocytes at an abundance of 16, 7, 6 and 3 per million, respectively. Furthermore, a sequence variant of SH-PTP2/Syp was identified that may have significance in the tissue-specific activity of this enzyme. These data provide insight into PTPase homologs that may have a physiological role in the regulation of phosphotyrosyl turnover in hormone signalling pathways in adipocytes.