High molecular weight kininogen: localization in the unstimulated and activated platelet and activation by a platelet calpain(s)

High mol wt kininogen (HMWK), the major cofactor-substrate of the contact phase of coagulation, is contained within and secreted by platelets. Studies have been performed to localize platelet HMWK in both the unstimulated and activated platelet and to ascertain the effect of platelet enzymes on HMWK itself. On platelet subcellular fractionation, platelet HMWK was localized to alpha-granules, and platelets from a patient with a deficiency of these granules (gray platelet syndrome) had 28% normal platelet HMWK. Platelet HMWK, in addition to being secreted from the platelet, was also localized to the surface of the platelet when activated. Using a competitive enzyme- linked immunosorbent assay for HMWK as an indirect antibody consumption assay, the external membrane of thrombin-activated platelets as well as the releasate from these stimulated platelets had 17 ng HMWK antigen/10(8) platelets available, whereas unstimulated platelets and their supernatant had only 4.9 and 4.2 ng HMWK/10(8) platelets present, respectively. The anti-HMWK antibody consumption by activated normal platelets was specific for membrane-expressed platelet HMWK, since activated platelets from a patient with total kininogen deficiency did not adsorb the anti-HMWK antibody. Enzymes in the cytosolic fraction of platelets cleaved 125I-HMWK (mol wt 120,000) into a mol wt 100,000 polypeptide as well as smaller products at mol wt 74,000, mol wt 62,000, mol wt 47,000, and a few components below mol wt 45,000. No cleavage products were observed when DFP and leupeptin were present. The cleavage of HMWK was specifically prevented by inhibitors of calcium-activated cysteine proteases (leupeptin, N-ethylmaleimide, iodoacetamide, and EDTA) but not by inhibitors of serine proteases (DFP, benzamidine, soybean trypsin inhibitor, or aprotinin). Platelet cytosol increased the coagulant activity of exogenous purified HMWK with maximum HMWK coagulant activity (35-fold) occurring within ten minutes of exposure to platelet cytosol. Treatment of platelet cytosol with leupeptin prevented the increase in the coagulant activity of exogenous HMWK. These studies indicate that activated platelets express platelet HMWK on their external membrane and platelet enzymes can cleave and increase the coagulant activity of exogenous HMWK.     

Clinical implications of increased plasma levels of CD8 in patients with hairy cell leukemia

Plasma levels of soluble T-suppressor/cytotoxic antigen (sCD8) were measured at diagnosis or before systemic treatment in 69 patients with hairy cell leukemia (HCL). The 49 nonsplenectomized patients were characterized by high concentrations of sCD8 antigen as compared with 17 controls (P less than .0001). The median sCD8 level in non- splenectomized patients was 1,050 U/mL (range: 160 to 2,400 U/mL) and was significantly higher (P less than .0001) than the median of 275 U/mL (range: 20 to 1,080 U/mL) in splenectomized patients. The relationship of sCD8 to clinical response to subsequent interferon alpha (IFN alpha) treatment was analyzed. Patients who showed subsequent hematologic response with normalization of all blood counts had significantly lower levels of sCD8 concentrations at diagnosis than those who did not (P = .0056). Furthermore, normalization of sCD8 during IFN alpha treatment paralleled the achievement of normal counts in peripheral blood, whereas soluble interleukin-2 receptor (sIL-2R) levels remained high in most patients after 12 to 15 months of treatment. We speculate that activation of suppressor/cytotoxic T cells might play a role in myelosuppression, and its modulation during treatment with IFN alpha correlates with normalization in peripheral blood counts.     

A comparison of fibrosis progression in chronic liver diseases

BACKGROUND/AIMS: No study has compared the liver fibrosis progression rates among chronic liver diseases and the risk factors in order to better organize screening strategies. METHODS: A total of 4852 patients were retrospectively studied (chronic hepatitis C (HCV) [n=2313], human immunodeficiency virus (HIV)-HCV co-infection (HIV-HCV [n=180]), hepatitis B (HBV [n=777]), alcoholic liver disease (ALD [n=701]), primary biliary cirrhosis (PBC [n=406]), genetic hemochromatosis (GH [n=383]) auto-immune hepatitis (AIH [n=57]) and delta hepatitis (n=35). The fibrosis progression rates were estimated from birth and from the date of exposure, when known, to the first biopsy. RESULTS: There were highly significant differences in the rates of fibrosis progression, the most rapid being HIV-HCV co-infection (50% cirrhosis percentile at 52 years of age) and the slowest being PBC (50% cirrhosis percentile at 81 years). There was an acceleration of fibrosis progression with aging. Fibrosis progression was slower in females compared with males for HCV, HBV, GH, and PBC. In contrast, in ALD, the fibrosis progression was more rapid in females. CONCLUSIONS: Rates of fibrosis progression differ markedly between the predominant causes of chronic liver disease, and according to age and gender. Patients with HIV-HCV co-infection are at particularly high risk of fibrosis progression.     

“维生素AD、铁营养强化奶的研制”研究报告

目的:研制维生素AD、铁营养强化奶,用于群体有效防治维生素AD、铁缺乏.方法:应用微胶囊技术科学配方成维生素AD、铁营养粉,添加到鲜牛奶中.结果:工业化生产维生素AD、铁营养强化奶.结论:该产品取得了很好的社会效益和经济效益.     

Neuropharmacological activities of MDP

MDP is a synthetic copy of part of the bacterial cell wall which has been shown to be the minimal structure capable of replacing Mycobacteria in Complete Freund Adjuvant. Several hundred analogs of this molecule have been produced and have been studied in various immunopharmacological systems. Special emphasis will be given here to their pyrogenic and somnogenic effects and to certain similarities which exist between MDP and Interleukin-1.     

Elevated plasma glycocalicin levels and decreased ristocetin-induced platelet agglutination in hemodialysis patients

A bleeding diathesis caused by platelet dysfunction is a major cause of morbidity and mortality in patients with uremia. Platelet adhesion to vascular subendothelium is defective in uremia and depends on the interactions of the platelet glycoprotein (GP) Ib/IX complex with the vascular wall. We measured levels of platelet surface GPIb, platelet surface GPIX, plasma glycocalicin (a product of enzymatic cleavage of GPIb), and ristocetin-induced platelet agglutination (RIPA) in patients undergoing chronic hemodialysis compared with patients undergoing peritoneal dialysis and healthy controls. Patients undergoing chronic maintenance hemodialysis have higher levels of platelet surface expression of GPIb (187+/-10 fluorescent units; P < 0.001) than either healthy controls (120+/-4 fluorescent units; P < 0.001) or patients undergoing peritoneal dialysis (127+/-5 fluorescent units; P < 0.001). Similar changes were observed in platelet surface GPIX. Plasma glycocalicin levels were elevated in chronic hemodialysis patients (71+/-5 nmol/L) compared with healthy controls (36+/-3 nmol/L; P < 0.001). Plasma glycocalicin levels also increased progressively throughout the hemodialysis procedure. The slope of RIPA was significantly lower in chronic hemodialysis patients (46+/-3) than in either healthy controls (67+/-4; P < 0.05) or peritoneal dialysis patients (62+/-2; P < 0.05). In conclusion, patients undergoing chronic maintenance hemodialysis have increased plasma glycocalicin levels and decreased RIPA, which may contribute to diminished platelet adhesion to vascular subendothelium and increased bleeding associated with uremia.     

MRI anatomy of the acoustic-facial bundle in vivo.

In this study performed on 5 healthy volunteers the authors used oblique axial, coronal and sagittal MRI sections suitable to be anatomical configuration of the acoustic-facial bundle and were able to individualize the nerves forming this bundle throughout their course, with the sole exception of the intermediate nerve (VII2). They also analysed the relations of these nerves between themselves and with the other elements of the cerebellopontine angle. In addition, a proton-density sequence (SE, 6,000/30 ms) made it possible to differentiate in vivo between the grey matter and the white matter sufficiently to individualize the principal nuclei and tracts of the brain stem, and in particular the main vestibulo-cochlear central pathways.