Gene/Protein Disease Symptom Drug Enzyme Compound
Pivot Concepts:   Target Concepts:
Query: UNIPROT:P02749 (beta2-glycoprotein I)
 836 document(s) hit in 31,850,051 MEDLINE articles (0.00 seconds)

During the isolation and purification of erythroid cell-stimulating factors from fetal tissues and blood, we found that they were almost invariably contaminated with substances that inhibited thymidine incorporation into erythroid cells of fetal bovine liver. We have isolated and partially sequenced three of these inhibitory factors. The first one was a 46-kDa heparin-binding protein from fetal bovine serum with 80% sequence identity with human apolipoprotein H (apo H). Although human apo H had no inhibitory activity on thymidine incorporation, the bovine apo H-like protein inhibited thymidine incorporation with an ID50 of 36 nM. It probably belongs to a group of heparin-binding apolipoproteins such as apo B and E, which have been reported to inhibit hematopoietic cells. The second inhibitor isolated from fetal bovine serum was clearly cytotoxic at a concentration of 1 nM. This 11-kDa peptide seems to be structurally related to the anaphylatoxins. The third inhibitor was isolated from human fetal intestine. The amino-terminal sequence of this protein was nearly identical to the amino-terminal sequence of human phospholipase A2 isolated from pancreas or lung. Bovine liver erythroid cell membranes are particularly sensitive to phospholipases. Since the synthesis and secretion of phospholipase A2 has been reported to be under the control of interleukin-1 or tumor necrosis factor in different cells, it is possible that this enzyme may be secreted locally and play an important role in tissue remodeling during injury or fetal development.
 ...
PMID:Isolation and characterization of three inhibitors of thymidine incorporation into bovine fetal liver cells. 206 6

To investigate the pathogenic versus the protective role of cytokines and toxin-binding factors in Plasmodium falciparum infections, we measured the concentrations of tumor necrosis factor alpha, interleukin-1 alpha (IL-1 alpha), IL-1 beta, IL-1 receptor antagonist, and IL-6, as well as soluble receptors of tumor necrosis factor and IL-6 (sIL-6R) in serum of Gambian children with cerebral malaria, mild or asymptomatic malaria, or other illnesses unrelated to malaria. Because cytokine secretion may be triggered by toxic structures containing phosphatidylinositol (PI), we also measured concentrations of anti-PI antibodies and the PI-binding serum protein beta-2-glycoprotein I. We found increased concentrations of IL-6, sIL-6R, IL-1ra, and some immunoglobulin M antibodies against PI in children with cerebral malaria, but those who died had decreased concentrations of beta-2-glycoprotein I. We conclude that increased concentrations of cytokines and soluble cytokine receptors represent a normal host response to P. falciparum infections but that excessive secretion of cytokines like IL-6 may predispose to cerebral malaria and a fatal outcome while beta-2-glycoprotein I may protect against a fatal outcome of cerebral malaria.
 ...
PMID:Increased concentrations of interleukin-6 and interleukin-1 receptor antagonist and decreased concentrations of beta-2-glycoprotein I in Gambian children with cerebral malaria. 792 98

Mammalian tumor necrosis factor (TNF)-alpha degenerate polymerase chain reaction (PCR) primers were used to amplify a probe from Botryllus schlosseri (colonial ascidian) allogeneic rejection-cDNA library. A PCR product (269 bp) was cloned and sequenced encoding an open reading frame (ORF) of 89 amino acids (aa). This clone, which revealed no similarity to TNF-alpha, but a substantial similarity to mammalian proteins featuring short consensus repeats (SCRs) of the complement control superfamily, was used to probe the rejection-cDNA library. Two partial cDNA clones were isolated and sequenced (Bs.1, 846 bp; Bs.2, 712 bp). The longest ORF in clone Bs.1 (which lacks the 5' end of the cDNA) predicts a protein of 251 aa, which differs from Bs.2 at six nucleotides and four aa. We compare the aa similarity (up to 50.5%) of Bs.1 with the SCR-region of mammalian complement factor H, apolipoprotein H, selectins, and complement receptors type 1 and type 2. A somatomedin B-like domain at the C-terminus of Bs.1 deduced protein was also recorded. We propose that this mosaic and polymorphic botryllid sequence, featuring mammalian-like SCRs, might be an ancestral molecule in the evolution of the chordate's complement-control protein superfamily.
 ...
PMID:Cloning of a urochordate cDNA featuring mammalian short consensus repeats (SCR) of complement-control protein superfamily. 857 24

The antiphospholipid syndrome (APS) is characterized by the presence of antiphospholipid antibodies (aPL) in patients with thromboembolic complications. In APS, most aPL are autoantibodies to beta2-glycoprotein I and prothrombin, which play a major role in the APS pathogenesis. Nevertheless, antibodies with the same antigen specificity are also found in aPL patients with leprosy, in whom thromboembolic complications are uncommon. The in vivo upregulation of the tissue factor (TF) pathway and the imbalance of cytokines have been proposed as potential mechanisms of thrombosis in the APS. We measured the circulating levels of TF, interleukin 6 (IL-6), IL-6 receptor (sIL-6R), tumor necrosis factor (TNF-alpha) and interferon gamma (IFN-gamma) in 83 patients with autoimmune aPL (42 with and 41 without clinical features of definite primary APS), 48 leprosy patients (33 with aPL) and 48 normal controls. There was a trend (P = 0.06) to higher median sTF in patients with autoimmune aPL (139 pg/mL) compared with leprosy patients (103.5 pg/mL) and controls (123 pg/mL). In addition, the frequency of raised sTF levels (> 187 pg/mL) was significantly higher in the group with autoimmune aPL [22.9% (APS 21.4%, non-APS 24.4%)] but not in leprosy (10.4%) compared with controls (4.2%). Elevated levels of IL-6 and TNF-alpha and a trend to lower IFN-gamma were found in patients with definite APS. Leprosy patients with aPL, however, had increased TNF-alpha and IFN-gamma but normal IL-6 levels. Levels of sIL-6R did not differ between controls and either patients with autoimmune aPL or leprosy. The different cytokine profiles as well as differences in circulating levels of TF might contribute to the high thrombotic risk found in patients with autoimmune aPL but not in leprosy related aPL patients.
 ...
PMID:Circulating levels of tissue factor and proinflammatory cytokines in patients with primary antiphospholipid syndrome or leprosy related antiphospholipid antibodies. 1575 17

Rheumatoid arthritis (RA) is a systemic inflammatory disease that presents not only involvement of joints but also endothelial dysfunction, dyslipidemia, and premature atherosclerosis. The death rate in RA is known to be higher than in the general population and clinical cardiovascular events secondary to atherosclerosis are responsible for the excessive death rate. A better understanding of the mechanisms that take part in the pathogenesis of atherosclerosis in RA patients is needed. Thus, the authors review the role of several factors involved in RA atherosclerosis, including disease activity, new cardiovascular risk factors, dyslipidemia and the association of atherosclerosis with the use of anti-rheumatic drugs, glucocorticoids and anti-tumor necrosis factor (TNF) agents. The role of humoral autoimmunity, namely autoantibodies against heat shock proteins, cardiolipin and beta2-glycoprotein I, and its link with atherosclerosis is also discussed. It is likely that the elucidation of the key mechanisms of atherogenesis in RA may determine a positive impact by reducing cardiovascular morbidity and mortality of these patients.
 ...
PMID:Multiple factors determine the increased prevalence of atherosclerosis in rheumatoid arthritis. 1834 21