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91.
92.
Inhibition of heparanase-mediated degradation of extracellular matrix heparan sulfate by non-anticoagulant heparin species 总被引:12,自引:0,他引:12
Incubation of human platelets, human neutrophils, or highly metastatic mouse lymphoma cells with sulfate-labeled extracellular matrix (ECM) results in heparanase-mediated release of labeled heparan sulfate cleavage fragments (0.5 less than Kav less than 0.85 on Sepharose 6B). This degradation was inhibited by native heparin both when brought about by intact cells or their released heparanase activity. Degradation of heparan sulfate in ECM may facilitate invasion of normal and malignant cells through basement membranes. The present study tested the heparanase inhibitory effect of nonanticoagulant species of heparin that might be of potential use in preventing heparanase mediated extravasation of bloodborne cells. For this purpose, we prepared various species of low-sulfated or low-mol-wt heparins, all of which exhibited less than 7% of the anticoagulant activity of native heparin. N-sulfate groups of heparin are necessary for its heparanase inhibitory activity but can be substituted by an acetyl group provided that the O-sulfate groups are retained. O-sulfate groups could be removed provided that the N positions were resulfated. Total desulfation of heparin abolished its heparanase inhibitory activity. Heparan sulfate was a 25-fold less potent heparanase inhibitor than native heparin. Efficiency of low-mol-wt heparins to inhibit degradation of heparan sulfate in ECM decreased with their main molecular size, and a synthetic pentasaccharide, representing the binding site to antithrombin III, was devoid of inhibitory activity. Similar results were obtained with heparanase activities released from platelets, neutrophils, and lymphoma cells. We propose that heparanase inhibiting nonanticoagulant heparins may interfere with dissemination of bloodborne tumor cells and development of experimental autoimmune diseases. 相似文献
93.
Studies of human polyclonal and monoclonal antibodies binding to lupus autoantigens and cross-reactive antigens 总被引:2,自引:0,他引:2
BACKGROUND: Systemic lupus erythematosus (SLE) is an autoimmune rheumatic disease serologically characterized by production of a variety of autoantibodies. Antibodies to double-stranded (ds) DNA are considered to be a diagnostic marker in SLE and their presence often correlates with active disease. The murine R4A anti-dsDNA antibody was found to cross-react with a peptide, D/EWD/EYS/G (R4A peptide), identified by analysing decapeptides selected from a peptide library. The R4A peptide inhibited binding of antibody to dsDNA and antibody deposition in kidneys in vivo. In other previous work, mice immunized with the peptide in a decapeptide form bound to a polylysine backbone, multiple antigenic peptide, were found to develop both anti-DNA and anticardiolipin antibodies. METHODS: To determine if human anti-DNA antibodies bind R4A peptide, we investigated the binding of monoclonal and polyclonal anti-dsDNA and anticardiolipin antibodies to the R4A peptide from patients with SLE. RESULTS: DNA binding by four immunoglobulin (Ig) G and two IgM human monoclonal anti-DNA antibodies was inhibited by the R4A peptide. While monomeric peptide was unable to inhibit affinity-purified polyclonal anti-DNA antibodies, serum anti-DNA reactivity was inhibited by an octameric form of the peptide in 10 SLE patients. CONCLUSIONS: Human anti-DNA reactivity includes the same fine specificity as that present in murine anti-DNA reactivity. Peptide binding might be a useful surrogate marker for SLE. 相似文献
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96.
Alternative referent standards for cardiac normality. Implications for diagnostic testing 总被引:1,自引:0,他引:1
A Rozanski G A Diamond J S Forrester D S Berman D Morris H J Swan 《Annals of internal medicine》1984,101(2):164-171
The radionuclide ventriculographic exercise response was evaluated in three patient populations representing alternative referent standards for cardiac normality: patients with normal coronary arteriograms, healthy volunteers, and uncatheterized patients with a low probability of coronary artery disease. Disease probability was determined by Bayesian analysis of age, sex, symptoms, and the results of cardiac fluoroscopy, exercise electrocardiography, or thallium scintigraphy. A wide range of ventriculographic responses was noted in the 62 catheterized normal patients; 21 (34%) had an abnormal ejection fraction response and 22 (35%) had an abnormal wall motion response. In contrast, the ejection fraction and wall motion responses were normal in the 9 volunteers. In 90 patients (18 catheterized and 72 uncatheterized) who had low disease probability (less than 1%), abnormal responses were rare; the ejection fraction response was abnormal in only 7% and the wall motion response was abnormal in 8%. Thus, these three populations are not equivalent referent standards of normality. Volunteers and patients with low disease probability provide too strict a standard, and their use can overestimate test specificity; catheterized normal patients, on the other hand, provide too lenient a standard, and their use can underestimate test specificity. 相似文献
97.
Ethanol reduces bone formation and may cause osteoporosis 总被引:10,自引:0,他引:10
INTRODUCTION: The etiology of ethanol-associated osteopenia is not fully understood. In order to define the role of ethanol in the pathogenesis of hepatic osteodystrophy, we compared two groups of alcoholic patients with histologically established alcoholic liver disease. PATIENTS AND METHODS: Twenty-eight patients currently drinking ethanol ("drinkers") and 12 claiming not to have consumed any ethanol for at least six months ("abstainers") were enrolled in the study. In addition, 35 non-alcoholic control subjects without clinical or biochemical evidence of liver disease were also studied. Bone mineral density and various biochemical and hormonal values were measured in each subject; iliac crest biopsies were taken under local anesthesia in the patients and under general anesthesia in the control subjects. RESULTS: Forearm bone mineral densities, spinal bone mineral densities, and iliac crest cancellous bone areas were significantly lower in the alcoholic patients compared with control subjects (p less than 0.01 for all measurements), but these values did not differ between the drinkers and the abstainers. The drinkers, however, had significantly less osteoblastic activity than the abstainers, as assessed by dynamic bone histomorphometry (p less than 0.001). Serum bone Gla-protein concentrations were higher in the abstainers than in the drinkers (p less than 0.001). No differences were seen relating to histologic parameters of bone resorption, although the alcoholic patients who had lower serum free testosterone concentrations than the control subjects also had higher urinary hydroxyproline excretion rates. CONCLUSION: These data suggest that ethanol may be responsible for osteoblastic dysfunction resulting in diminished bone formation and reduced bone mineralization. 相似文献
98.
Jacobi AM Reiter K Mackay M Aranow C Hiepe F Radbruch A Hansen A Burmester GR Diamond B Lipsky PE Dörner T 《Arthritis and rheumatism》2008,58(6):1762-1773
99.
Pap smears occasionally reveal protozoa of the genus Entamoeba in the uterus of intrauterine device (IUD) users, but definitive identification of the species involved has not been possible. Using riboprinting, a technique that compares ribosomal RNA gene sequences, we present evidence that the organism is Entamoeba gingivalis, an inhabitant of the mouth. Colonization most likely occurs via orogenital contact and requires the presence of an IUD and a concomitant bacterial infection. 相似文献
100.