Gene/Protein Disease Symptom Drug Enzyme Compound
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Query: UNIPROT:P30536 (PBS)
 9,886 document(s) hit in 31,850,051 MEDLINE articles (0.00 seconds)

The present study was designed to investigate the role of 5-lipoxygenase (5LO) metabolites in an endotoxin (LPS)-induced model of the adult respiratory distress syndrome (ARDS) in the rat. The therapeutic value of two 5LO inhibitors and a specific LTB4 and a LTD4 receptor antagonist were examined. Rats were treated 1 hr prior to administration of aerosolized LPS. Rats were either unexposed (n = 11), or pretreated with vehicle sham (n = 63), 50 mg/kg phenidone t.i.d. (n = 7, n = 10 for assessment of mortality), 30 mg/kg SK&F 103842 b.i.d. (n = 6), 50 mg/kg SK&F 106203 t.i.d. (n = 11), or 5 mg/kg SK&F 107324 b.i.d. (n = 6) 1 hr prior to the administration of aerosolized endotoxin (LPS, 7 mg/kg) or phosphate-buffered saline (PBS, n = 22). Twenty-four hours later, blood samples were collected for hematologic evaluation and after wet lung weight was determined, broncho-alveolar lavage (BAL) was performed to measure cells counts and total protein (TP). 5LO inhibition and LTD4 receptor antagonism reduced LPS-induced mortality to zero compared to 35% in rats pretreated with vehicle sham. Pretreatment with the LTD4 receptor antagonist attenuated the LPS-induced increased in wet/dry lung weight (W/D) whereas 5LO inhibition reduced TP increases. Both 5LO inhibition and LTD4 receptor antagonism attenuated the LPS-induced BAL erythrocyte increase. The LPS-induced thrombocytopenia was attenuated by phenidone, the 5LO receptor antagonist. We conclude that the increased microvascular permeability was associated with the formation of 5LO products since 5LO inhibition lessened the severity of the LPS-induced increase in W/D and TP.(ABSTRACT TRUNCATED AT 250 WORDS)
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PMID:Therapeutic intervention in a rat model of adult respiratory distress syndrome: II. Lipoxygenase pathway inhibition. 193 27

The identification of antibodies to platelet-specific antigens is important for correctly diagnosing neonatal alloimmune thrombocytopenia, posttransfusion purpura and refractoriness due to platelet-specific antibodies. However, the serologic identification of these platelet-specific antibodies is complicated by the presence of anti-HLA antibodies. We examined and compared the diagnostic usefulness of acid-treated and chloroquine-treated platelets for the discrimination of platelet-specific antibodies from anti-HLA antibodies. The viability of acid-treated platelets is 83.4%, which is better than that of chloroquine-treated platelets (52.6%). The antigenicity of HLA class I antigens of acid-treated platelets was significantly reduced compared with that of PBS- or chloroquine-treated platelets. On the other hand, platelet surface glycoprotein Ib and glycoprotein IIb/IIIa, and platelet-specific antigens were stable following acid or chloroquine treatment. Chloroquine-treated platelets were not suitable targets for analysis by immunofluorescence flow cytometry because of nonspecific fluorescence derived from platelet damage. We conclude that acid-treated platelets are more suitable targets than chloroquine-treated platelets for screening for platelet-specific antibodies and also for analyses of the specificity of platelet-specific antibodies.
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PMID:Acid treatment of platelets as a simple procedure for distinguishing platelet-specific antibodies from anti-HLA antibodies: comparison with chloroquine treatment. 223 61

A method for detection of anticardiolipin (ACL) antibodies with enzyme-linked immunosorbent assay was developed. Microtitre plates were coated with cardiolipin at a concentration of 20 micrograms/ml by evaporation under 4 degree centigrade overnight. Non-specific binding of diluted sera was eliminated by blocking of plates with 10% fetal calf serum in phosphate buffered saline (FCS/PBS) for 2 hours at room temperature. Sera (50 microliters/well) at a dilution of 1:100 were incubated for 2 hours at room temperature. Horseradish peroxidase conjugated rabbit anti-human IgG, IgM, IgA at a dilution of 1:2000, 1:1000, 1:500 respectively was added to the wells, and incubated for one and half hours at room temperature. The results were read at 490nm after incubation with substrates at 37 degree centigrade. 85 patients with systemic lupus erythematosus (SLE), 45 with rheumatoid arthritis (RA), 25 with progressive systemic scleroderma (PSS), and 18 primary Sjogren's syndrome were tested. The frequency of ACL antibody in SLE (48%) was much higher than that in RA (11%), PSS (12), SS (5.5). Three isotypes of ACL (IgG, IgM, IgA) were detected in the study with predominance of IgG isotype. ACL antibody was significantly associated with thrombosis, cutaneous vasculopathy, thrombocytopenia, and spontaneous abortion in patients with SLE. Strong relationship between ACL antibody and lupus anticoagulant was found. There was no correlation between ACL and anti-DNA antibodies, nor was ACL and VDRL test. The level of ACL antibody could be reduced by use of corticosteroids.
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PMID:[Measurement of anticardiolipin antibodies and its significance in systemic lupus erythematosus]. 250 Mar 15

Unwashed human thrombocytes are best suitable for the immunological activation in PBS-glucose solution. The immunological aggregability of the blood platelets increases in this solution up to more than 1 hour. Rabbit-anti-human-Ig-L-chain (chi) or -anti-human-C1q serum aggregate once washed thrombocytes. The combined application of both antisera has a potencive effect. Soluble human-IgG-rabbit-anti-human-IgG-antibody-F(ab')2-complexes produce a strong thrombocyte aggregation in an intermediate human IgG excess. 4 minutes past heating of human IgG at 63 degrees C a mixture of IgG aggregates (AHGG) arises which activates blood platelets maximally. The AHGG can be stored at -20 degrees C up to at least 4 weeks. Therapeutical aspirin concentrations inhibit the AHGG induced thrombocyte aggregation. Plasma from patients with idiopathic thrombocytopenia inhibits the AHGG mediated platelet aggregation less than plasma from healthy persons.
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PMID:[Immunologic aggregation of human blood platelets and its inhibition in vitro]. 294 39

Antiphospholipid antibodies are strongly associated with arterial and venous thrombosis and with fetal loss. Recently an experimental model for antiphospholipid syndrome (APLS) was established in our laboratory. In this model, mice are immunized passively or actively with anticardiolipin antibodies and acquire the syndrome, which is characterized by prolonged activated partial thromboplastin time (APTT), thrombocytopenia, low fecundity rate, and fetal loss. In a normal process of pregnancy, lymphokines affect fetal implantation and development. Cytokines from the colony stimulating factor family, like GM-CSF and IL-3, were shown to be positive signals for implantation and to promote placental development and fetal growth. Given our preliminary findings of low IL-3 in mice with APLS and the efficacy of IL-3 in preventing fetal loss in a strain of mice prone to fetal resorption, our aim in the present study was to examine the effect of murine recombinant IL-3 (mrIL-3) on pregnant mice induced with experimental APLS. Mice were passively transfused to the tail vein, 24 h following mating, with anticardiolipin antibodies. The mice were divided into two groups: one group was injected intraperitoneally with mrIL-3 on days 6.5, 8.5, and 10.5 after mating, while the control group was injected with PBS. When the mice were killed on day 15 of pregnancy a 32% +/- 4.2 resorption rate was observed in the anti-cardiolipin-immunized group, which was reduced to 4% +/- 0.3 following treatment with mrIL-3. The thrombocytopenia associated with the experimental APLS was also corrected following lymphokine administration. IL-3 may be effective in prevention of recurrent fetal loss in APLS.
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PMID:Prevention of fetal loss in experimental antiphospholipid syndrome by in vivo administration of recombinant interleukin-3. 847 80

Ox-LDL is thought to play a major role in atherogenesis. The mechanisms mediating the deleterious influences of Ox-LDL include foam cell formation and cell cytotoxicity. The production of anti-Ox-LDL antibodies results in the formation of immune complexes which are taken up at enhanced rate by macrophages, leading to foam cell formation. APS is characterized by repeated venous and arterial thromboembolic phenomena, recurrent fetal loss and thrombocytopenia, associated with the presence of antibodies to negatively charged phospholipids (aPL) (i.e. cardiolipin, phosphatidylserine). Phospholipids bear structural resemblance to LDL, and several studies have indeed proved that aPL display cross-reactivity with anti-Ox-LDL antibodies. In this study we assessed the capacity of oxidized and native forms of LDL to aggravate the clinical picture of experimentally induced APS in naive mice. Mice were actively immunized intradermally with anticardiolipin antibodies and developed a clinical picture resembling APS in humans. Subsequently, the mice were infused with either Ox-LDL, native LDL or PBS, and similar regimens were applied to controls. APS mice infused with Ox-LDL were found to exhibit a significantly more severe form of the disease in comparison with native LDL- and PBS-infused mice, expressed by lower platelet counts (261,000/mm3, 535,000/mm3 and 455,000/mm3, respectively), longer activated partial thromboplastin time (aPTT) (99 +/- 12 s, 63 +/- 8 s and 74 +/- 8 s, respectively) and higher fetal resorption rates (72.7%, 34.4% and 32.6%, respectively). The results of this study show that Ox-LDL, compared with native LDL, aggravates the clinical manifestations of experimental APS and suggest that cross-reactivity of Ox-LDL with phospholipids may provide a pathogenic explanation for this effect.
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PMID:Oxidized low-density lipoprotein (Ox-LDL) but not LDL aggravates the manifestations of experimental antiphospholipid syndrome (APS). 915 90

Multipotent-lineage nondominant growth factors, acting alone or in combination with lineage-dominant cytokines, are known to influence both myelopoiesis and thrombocytopoiesis. Interleukin (IL)-3 and IL-11 stimulate and expand multilineage progenitor cells and induce thrombocytopoiesis. These cytokines also act synergistically with various other lineage dominant and lineage-nondominant cytokines in vitro to expand primitive and committed hematopoietic stem cells. In this study we investigated the in vivo effects of IL-3 and IL-11 in combination with the c-mpl ligand, thrombopoietin (rhTPO), on neonatal rat hematopoiesis. Newborn Sprague-Dawley rats (24 36 hours old, weighing 6-8 g) were intraperitoneally injected with rhTPO (10 microg/kg) for 14 days, rmIL-3 (10 microg/kg) for 5 days followed by rhTPO (10 microg/kg) for 9 days, rmIL-3 (10 microg/kg) + rhTPO (10 microg/kg) for 14 days, rhIL-11 (250 microg/kg) + rhTPO (10 microg/kg) for 14 days, or PBS/human serum albumin (HSA) for 14 days. When compared with PBS/HSA, rhTPO at a dosage of 10 microg/kg significantly increased platelet count (10(-9) L) (day 6, 569 +/- 37.1 vs. 1446 +/- 43.8, p < 0.001; day 10, 796 +/- 68.3 vs. 1774 +/- 238.4, p < 0.01; day 14, 850 +/- 64.4 vs. 3441 +/- 98.1 /10(-9) l, p < 0.001) and absolute neutrophil count (ANC) (day 6, 335.2 +/- 59.6 vs. 752 +/- 335.2, p < 0.01; day 12, 664 +/- 54.1 vs. 1520 +/- 158.2, p < 0.01). However, rhTPO has no effect on the circulating hematocrit or red blood cell count. RhTPO-treated animals also displayed higher platelet counts (/10(-9) L) vs. rhIL-11 or rhIL-6 beginning on day 6 (day 6, 1597.6 +/- 134.7 vs. 930.7 +/- 67.3 vs. 863 +/- 19.6, p < 0.01; day 8, 1686 +/- 208.4 vs. 990 +/- 29.4, vs. 977 +/- 34.33, p < 0.05; day 10, 1774 +/- 238.4 vs. 1096 +/- 49.6, vs. 937 +/- 65, p < 0.01; day 14, 2187 +/- 127.5 vs. 1280 +/- 35.8 vs. 951 +/- 50.7 /10(-9) L, p < 0.01). Sequential administration of rmIL-3 followed by rhTPO resulted in no significant increase in platelet counts compared with PBS-HSA/rhTPO. RhTPO + rmIL-3 given simultaneously also had no additive effect on the circulating platelet count compared with rhTPO alone. Similarly, no additive effect on circulating platelet counts was observed with rhIL-11 + rhTPO vs. rhTPO alone. Bone marrow studies showed a significant increase in the number of megakaryocytes per high-power field in all the groups treated with rhTPO vs. control (p < 0.05), but no additive effect was seen in neonatal rats additionally receiving either rmIL-3 or rhIL-11. Colony forming unit (CFU)-Meg colony formation was also significantly increased in all the groups treated with rhTPO vs. control (p < 0.05), with no additive effect observed after the addition of either rmIL-3 or rhIL-11. These data suggest that rhTPO is more effective than rmIL-3 or rhIL-11 in inducing neonatal in vivo thrombocytopoiesis in rats, and that no additive effect is to be expected when rhTPO is combined sequentially with rhIL-3 or simultaneously with either rmIL-3 or rhIL-11. We hope that these preclinical data will provide insight into the design and future application of these thrombopoietic cytokines, alone or in combination, to prevent or treat thrombocytopenia.
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PMID:Sequential treatment with rmIL-3 or simultaneous treatment with rmIL-3 or rhIL-11 with thrombopoietin (TPO) fails to enhance in vivo neonatal rat thrombocytopoiesis. 925 14

The radioprotective properties of flk2/flt3 ligand (FL) were evaluated in lethally irradiated mice. Optimum survival rates (70-80%) were observed when 5 to 20 microg of FL was administered at both 20 and 2 hours before LD100/30 radiation. Administration of FL well in advance of irradiation was essential for conferring most of the radioprotection, since a single dose given at -20 hours still resulted in a significant survival rate (65%), whereas a single dose given at -2 hours was relatively nonprotective. Histopathologic examination at 7 and 9 days postirradiation revealed significant myelopoietic activity in the bone marrow (BM) of FL-treated mice, suggesting that their survival might be due to sparing of radiosensitive hematopoietic cells. By comparison, the BM of mice treated with phosphate-buffered saline was extremely hypocellular and remained that way until they died of bacterial infection. Hematopoietic assays confirmed a marked stimulation of early white blood cell (WBC) recovery in the BM and blood of FL-protected mice relative to PBS-treated controls. By day 21, FL-protected mice showed circulating WBC numbers that were higher than preirradiation values; however, their BM colony-forming units in culture were still depressed. Moreover, these mice experienced a prolonged anemia and thrombocytopenia. These findings are discussed in light of the restricted subset of hematopoietic progenitors shown to be responsive to FL in vitro.
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PMID:Radioprotective effects of flk2/flt3 ligand. 962 Feb 85

The major goal of this study was to evaluate the effects of tumor necrosis factor-alpha (TNF-alpha), delivered as pGL1-TNF-alpha, on hematological variables, as well as C6 tumor growth in athymic mice treated with and without radiation. pGL1-TNF-alpha was administered intratumorally at low to high doses (15, 150 and 450 microg) in all three phases of this study. In phase A, pGL1-TNF-alpha expression within tumors was dose dependent and transient, with highest levels seen at 18 h after injection, whereas no TNF-alpha protein was detected in plasma. Low erythrocyte counts, hemoglobin, and hematocrit were associated with tumor presence, but the reduction in these variables was most striking in the group receiving 450 microg of pGL1-TNF-alpha, the group that also exhibited thrombocytopenia at 72 h. In phase B, treatment with pGL1-TNF-alpha at 15 or 150 microg resulted in the greatest degree of splenomegaly, increased spontaneous blastogenesis by splenocytes, and high leukocyte and lymphocyte numbers in the spleen. In these same two groups, flow cytometry analyses of spleen cells showed that high levels of natural killer (panNK+) cells, B (CD19+) lymphocytes, and cells expressing the CD71 and CD25 activation markers were present (p < 0.05). An enhancing effect was also noted in some of the measurements with parental plasmid p WS4 and tumor presence. In phase C, the slowest tumor progression was observed in the groups receiving 15 and 150 microg pGL1-TNF-alpha together with radiation; tumor volumes were 51 and 43% smaller, respectively, than for PBS-injected controls by the end of the study. Collectively, these results show that localized treatment with pGL1-TNF-alpha is hematologically nontoxic at low doses and support the premise that activation of lymphocytes may contribute to the antitumor effects of radiation against a highly aggressive brain tumor.
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PMID:Lymphocyte activation with localized pGL1-TNF-alpha gene therapy in a glioma model. 1181 46

Anti-prothrombin antibodies (aPT) are associated with thrombotic manifestations, and their association with reproductive failure is debatable. The aim of this study was to examine whether aPT could induce thrombosis and other clinical manifestations of the anti-phospholipid syndrome (APS). Mice were immunized with either prothrombin, beta2-glycoprotein-I (beta2GPI), or beta2GPI followed by prothrombin. The presence of clinical manifestation of APS, including thrombocytopenia, lupus anticoagulant and fetal resorption rates, was evaluated in all mice groups compared with nonimmunized mice. Thrombosis was studied in a novel ex-vivo model in which the aorta was sutured for 1 min and the presence or absence of visible thrombus was qualitatively evaluated. Immunized mice developed high autoantibody levels directed towards their immunizing autoantigens. The groups immunized with beta2GPI or beta2GPI/prothrombin, but not with prothrombin alone, developed prolonged aPTT, thrombocytopenia and increased fetal resorption rate. All prothrombin-immunized mice as well as most beta2GPI/prothrombin-immunized mice developed visible thrombus within the aorta. Some beta2GPI immunized mice developed very mild thrombus. None of the CFA/PBS-injected or the nonimmunized mice developed such thrombus. Active immunization with prothrombin or beta2GPI/prothrombin is associated with prothrombotic activity of blood in an ex-vivo model. This is the first direct evidence for thrombus induction by aPT.
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PMID:Anti-prothrombin antibodies cause thrombosis in a novel qualitative ex-vivo animal model. 1276 99


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