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31.
Platelet activation altered the binding of three monoclonal antibodies (monovalent Fab' fragment) directed against the glycoprotein (GP) IIb/IIIa complex. An increased binding of two- to threefold occurred after stimulation with thrombin or phorbol myristate acetate (PMA), with slight but significant increase in the dissociation constants (Kd) of two antibodies (LJ-CP8 and LJ-P9). In contrast, no statistically significant changes were observed with ADP-stimulated platelets. The increased binding of LJ-CP3, but not of the other two antibodies, to activated platelets decreased by 30% to 40% in the presence of EDTA at 22 to 25 degrees C. Platelets stimulated by thrombin or PMA bound more fibrinogen than did those stimulated by ADP, and significant differences in the extent but not in the affinity of fibrinogen binding were observed with various platelet agonists. When the pool of GP IIb/IIIa molecules exposed on the surface of unstimulated platelets was reacted with the monoclonal antibody LJ-CP3 to block ADP-induced fibrinogen binding and platelet aggregation, stimulation with thrombin or PMA still induced substantial binding of antibody and fibrinogen, and aggregation ensued. Therefore, platelets exposed to "strong" agonists exhibit an increased number of surface-oriented epitopes associated with GP IIb/IIIa. The GP IIb/IIIa molecules bearing these newly exposed epitopes are functional in that they can bind fibrinogen and mediate platelet aggregation. 相似文献
32.
Estep M Abawi M Jarrar M Wang L Stepanova M Elariny H Moazez A Goodman Z Chandhoke V Baranova A Younossi ZM 《Obesity surgery》2011,21(11):1750-1757
Background
Three protein products of ghrelin gene (acylated ghrelin, des-acylated ghrelin, and obestatin) are involved in appetite stimulation and suppression. Additionally, there is some evidence suggesting their involvement in metabolic and inflammatory pathways which may be implicated in the pathogenesis of non-alcoholic fatty liver disease (NAFLD). The aim of this study was to examine the relationships of ghrelin gene products in patients with NAFLD.Methods
We included 75 morbidly obese patients with biopsy-proven NAFLD (41 with histologic non-alcoholic steatohepatitis (NASH)) with clinical and laboratory data as well as frozen serum samples from the time of liver biopsy. Fasting serum was assayed for obestatin as well as acylated and des-acyl-ghrelin concentrations using ELISA. Bio-Plex inflammatory cytokine assays were used to profile expression of 17 inflammatory mediators, including IL-6, IL-7, IL-8, G-CSF, CCL2, and MIP-1??.Results
Patients with NASH had twofold higher concentration of des-acyl-ghrelin than patients with non-NASH (2.58 vs. 1.24 pg/ml, P?0.02). Ghrelin concentrations in NASH patients with fibrosis stage ??2 were almost double the concentration of NASH patients with fibrosis stage <2 (8.73 vs. 4.22 pg/ml, P?0.04). Obestatin levels also increased with the fibrosis stage (2.54 vs. 3.46 pg/ml, P?0.03). NAFLD patients with higher fibrosis stage had lower IL-7 concentrations (16.89 vs. 10.68 pg/ml, P?=?0.014). Obestatin levels at baseline significantly correlated with rate of weight loss after bariatric surgery at various time points.Conclusions
This study suggests that products of the GHRL gene may be important for the pathogenesis of NASH and fibrosis. Additional confirmatory studies are needed. 相似文献33.
Nonalcoholic fatty liver disease (NAFLD) is one of the most prevalent liver diseases worldwide, affecting men, women, and children. This is due, in part, to the obesity epidemic, which is associated with increased prevalence of NAFLD. The NAFLD spectrum ranges from simple steatosis to nonalcoholic steatohepatitis (NASH), which is the potentially progressive form. NAFLD is associated with metabolic syndrome and insulin resistance. Treatment recommendations include weight reduction through both diet and physical activity, and weight-loss surgery for extreme obesity. Most medical regimens target components of the metabolic syndrome or oxidative stress associated with the pathogenesis of NASH. These include antiobesity regimens, insulin sensitizers, antihyperlipidemics, and antioxidants. Bariatric surgery is effective for achieving and maintaining weight loss and reversing the complications of metabolic syndrome. On the other hand, the literature lacks well-designed, randomized control trials that assess the efficacy of anti-obesity regimens on histologic and long-term outcomes of NAFLD. 相似文献
34.
The utility of radiological imaging in nonalcoholic fatty liver disease 总被引:49,自引:0,他引:49
Saadeh S Younossi ZM Remer EM Gramlich T Ong JP Hurley M Mullen KD Cooper JN Sheridan MJ 《Gastroenterology》2002,123(3):745-750
BACKGROUND & AIMS: This prospective study evaluates the role of radiological modalities in establishing the diagnosis of nonalcoholic steatohepatitis (NASH). METHODS: Consecutive patients with biopsy-proven nonalcoholic fatty liver disease (NAFLD) were enrolled (2000-2001). Patients with other liver diseases and significant alcohol consumption (>20 g/day) were excluded. Clinicodemographic data were gathered at the time of liver biopsy. Each biopsy specimen was assessed by a hepatopathologist. Each patient underwent a limited abdominal ultrasonography (US), computerized tomography (CT), and magnetic resonance imaging (MRI). Films were interpreted by a radiologist who used a predetermined radiological protocol. Each radiological study was reread by the same radiologist and a second radiologist. RESULTS: Patients with NASH had greater aspartate aminotransferase levels (P = 0.03), greater ferritin levels (P = 0.05), more hepatocyte ballooning (P < 0.0001), and more fibrosis (P = 0.002). None of the radiological features distinguished between NASH and other types of NAFLD. No radiological modality detected the presence of hepatocyte ballooning, Mallory's hyaline, or fibrosis, which are important features in the diagnosis of NASH. The presence of >33% fat on liver biopsy was optimal for detecting steatosis on radiological imaging. CONCLUSIONS: Differences between NASH and nonprogressive NAFLD were not apparent with any radiological modality. Of the pathologic features important for establishing the diagnosis of NASH, only the severity of steatosis was reflected in these radiological modalities. Good intraobserver agreement was evident for each modality (US, CT, and MRI) that was superior to interobserver agreement. 相似文献
35.
Kim CH Kallman JB Bai C Pawloski L Gewa C Arsalla A Sabatella ME Younossi ZM 《Obesity surgery》2010,20(2):154-160
Background
Obesity is not only associated with nonalcoholic fatty liver disease (NAFLD) but it also adversely affects the progression of other liver diseases. There are limited data regarding the dietary habits of patients with chronic liver disease. 相似文献36.
37.
38.
Infection with HCV leads to an array of symptoms that compromise health-related quality of life (HRQL). Chronic hepatitis C is treated primarily with pegylated interferon (peg-IFN) and an inosine 5' monophosphate dehydrogenase inhibitor, ribavirin (RBV), with the goal of achieving a sustained virologic response (SVR). SVR reduces the rate of hepatic fibrosis and other disease-related complications and, in turn, increases HRQL. Although combination therapy with peg-IFN and RBV produces SVRs in more than 50% of treated patients, it is associated with side effects that can reduce short-term HRQL, can lead to dose reductions and discontinuations, and may impair treatment response. Fatigue and depression are common symptoms of chronic HCV infection that may also be caused by IFN-based therapy. Hemolytic anemia and IFN-mediated bone marrow suppression are well-known consequences of IFN/RBV therapy, often resulting in dose reductions or discontinuations, and have the potential to affect SVR rates. Management of these symptoms is vital to successful outcomes and generally relies on therapy that is adjunctive to the primary treatment of the viral infection itself. Several new drugs with the potential to increase SVR rates without compromising HRQL are in development. CONCLUSION: The relationship of chronic HCV infection, treatment, and HRQL is complex. Successful treatment of chronic hepatitis C requires an understanding of the intricacies of this relationship and appropriate management of treatment-related symptoms. 相似文献
39.
Elevated platelet count as a cause of abnormal von Willebrand factor multimer distribution in plasma 总被引:3,自引:1,他引:3
Twelve of 19 patients with myeloproliferative disorders showed a decrease of absence of the largest multimers of plasma von Willebrand factor (vWF) that correlated with elevated platelet counts but not with leukocyte counts. This suggested that platelets, rather than leukocytes, may be associated with the pathogenesis of the acquired vWF abnormality seen in these patients. To examine the hypothesis further, we studied 12 patients with reactive thrombocytosis after splenectomy. Increased platelet count (> 5 x 10(11)/L) after splenectomy was associated with vWF abnormalities indistinguishable from those detected in patients with myeloproliferative disorders. Accordingly, there was an inverse correlation between proportion of large vWF multimers and platelet, but not leukocyte, number: normalization of the platelet count was accompanied by restoration of a normal vWF multimeric pattern. These findings suggest that an increase in the number of platelets circulating in blood may favor the adsorption of larger vWF multimers onto the platelet membrane, resulting in their removal from the circulation and subsequent degradation. 相似文献
40.
Changes in carbohydrate expression on endometrial and blastocyst cell
surfaces may play a critical role in the process of implantation. Le(y) is
an oligosaccharide antigen which has been shown to be involved in
blastocyst attachment in the mouse. In the present study,
immunohistochemical distribution of Le(y) in endometrium during
proliferative and secretory phases of normal menstrual cycles in the rhesus
monkey was examined. Endometrial samples were collected on cycle days 7
(n=4), 13 (n= 4), 16 (n=4), 20 (n=4) and 25 (n=3). There was a gradual
increase of Le(y) in luminal surface from proliferative to periovulatory (P
< 0.001), and from periovulatory to postovulatory (P < 0.05), phases.
Le(y) then remained constant in the midsecretory phase and decreased (P
< 0.01) during the premenstrual phase. Le(y) score in glands did not
change between the phases, except in midsecretory phase when it was higher
than that in other phases (P < 0.05). The stromal compartment showed no
statistically significant changes. The profiles of endometrial Le(y) on day
6 after ovulation in mated fecund cycles with or without early luteal phase
mifepristone treatment were also examined. Females were allowed to cohabit
with males during days 8-16 of their ovulatory cycles and were injected
s.c. with vehicle (n=7) only, or with a single dose of mifepristone (2
mg/kg body weight; n=8) on day 2 after ovulation. Significant decreases in
the area and optical absorption of immunoprecipitate were observed in the
epithelial compartment (P < 0.01) following mifepristone treatment.
There was no change in the stromal compartment either in area or in optical
absorption of immunoprecipitate for Le(y) with or without mifepristone
treatment. The expression of Le(y) in the endometrial epithelial
compartment appears to be influenced by progesterone and may be associated
with endometrial receptivity prior to implantation in the rhesus monkey.
相似文献