Gene/Protein Disease Symptom Drug Enzyme Compound
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Query: UMLS:C0432222 (SEM)
 47,337 document(s) hit in 31,850,051 MEDLINE articles (0.00 seconds)

The glycoprotein complex GPIIb-IIIa of the platelet membrane and CD18 of the monocyte membrane have been established as being the central figure for the adhesion processes of the corresponding cells. The molecular structure of these 2 GPs bears some similarities. It was proposed recently that LFA-1 and Mo-1 (CD18 family) and GPIIb-IIIa might be encoded by the same gene. For this purpose, we studied the expression of Mo-1, Mo-2 (as control) receptors on monocytes and GPIIIa and GPIIb-IIIa on platelets of two GT patients as compared to normal healthy subjects. Monoclonal antibodies anti Mo-1, MO-2, AP-3 and AP-2 were used to measure the expression of the respective antigens by indirect immunofluorescence procedure. The fluorescence of the labelled cells was analysed with an Ortho Cytofluorograph 50-H. The resulting Mean Fluorescence Intensity (MFI) values of AP-2 and AP-3 showed that the patients had a total absence of GPIIb-IIIa antigens. However, Mo-1, as well as those of control Mo-2, in patients (MO-1: 672 and 716; Mo-2: 453 and 637) were similar to that of normal subjects (Mo-1: 735 +/- 74; Mo-2: 585 +/- 35; mean +/- SEM). Therefore, the normal expression of Mo-1 receptors on the monocytes of Glanzmann's thrombasthenia patients suggests different genomic regulations for Mo-1 antigens on the monocyte and GPIIb-IIIa complex on the platelet.
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PMID:Normal expression of the adhesive structure Mo-1 on monocytes from patients with Glanzmann's thrombasthenia. 201 Jul 2

Platelet autoantigen-autoantibody-monocyte interaction was studied by utilization of a specific monoclonal antibody (MoAb) 10E5 to trap and immobilize the GPIIb-GPIIIa complex on microtiter plates. Peripheral blood mononuclear cells (PBMC) or purified monocytes formed distinct morphologic clusters after incubation with immobilized antigen for 18 hours at 37 degrees C. PBMC of 18 and 19 patients with autoimmune thrombocytopenic purpura (ATP) formed 48 +/- 6.8 (SEM) clusters/well compared with 7.4 +/- 1.0 for control subjects, P less than .001. The number of clusters per well correlated inversely and exponentially with platelet count, r = -.8, n = 21, indicating that the GPIIb-GPIIIa autoantigen is pathophysiologically relevant. Binding of ATP PBMC to immobilized GPIIb-GPIIIa could be inhibited by F(ab')2 fragments of immunoglobulin (Ig) G of ATP patients, indicating that monocyte IgG bound to autoantigen by its F(ab')2 domain. Optimal cluster formation could be obtained with normal monocytes if preincubated with ATP IgG but not with F(ab')2 fragments of ATP IgG, indicating that ATP IgG binds to monocytes by its Fc domain. Armed monocytes (ie, normal monocytes preincubated with ATP IgG) bound to immobilized autoantigen 5.8-fold greater than normal monocytes incubated with immobilized autoantigen opsonized with ATP IgG. Armed monocyte adhesion could be inhibited 81% from 18.9 +/- 1.6 to 3.6 +/- 0.5 clusters/well by prior fixation with 0.1% formalin, whereas fixation of IgG before arming of monocytes was not inhibitory. MoAb MM41, directed against the alpha m-chain of the Mac-1 adhesive protein receptor of monocytes, inhibited cluster formation by 79%. Thus, (1) armed monocyte interaction with autoantigen is considerably more effective than monocyte interaction with opsonized autoantigen; (2) armed monocyte interaction requires specific F(ab')2-antigen recognition; and (3) monocyte-autoantigen interaction requires a secondary nonimmunologic adhesive event.
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PMID:Regulation of autoimmune anti-platelet antibody-mediated adhesion of monocytes to platelet GPIIb/GPIIIa: effect of armed monocytes and the Mac-1 receptor. 218 3

Two monoclonal anti-platelet antibodies, 3B2 and 8G11, have been raised that are specific for normal human platelets. 3B2 is unique in that it has decreased reactivity for platelets from 16 patients with autoimmune thrombocytopenic purpura [mean platelet count, 65,000 +/- 6,000 (SEM)]. With 8G11 in an enzyme-linked immunosorbent assay, the mean of the ratios of patient platelet OD to control platelet OD was 0.95 +/- 0.07, whereas with 3B2, the mean of the ratios of patient platelet OD to control OD was 0.24 +/- 0.04, P less than 0.001. With 3B2 the mean of the OD ratios of five patients with autoimmune thrombocytopenic purpura in remission (greater than 150,000 platelets per mm3) compared to controls was 0.80 +/- 0.14. 3B2 did not react with platelets from a patient with Glanzmann's thrombasthenia, in which membranes lack glycoproteins IIb and IIIa (GPIIb and GPIIIa). Platelet membranes were run on crossed immunoelectrophoresis against a rabbit polyclonal anti-human platelet membrane antibody with 125I-labeled purified 3B2 in an intermediate spacer gel. 3B2 reacted with the GPIIb-GPIIIa-Ca2+ complex in the presence of excess Ca2+ and with GPIIb alone in the presence of excess EGTA. When Triton X-100-solubilized platelet membranes were immunoprecipitated with 3B2 plus rabbit anti-mouse IgG, reduced, and run on NaDodSO4/polyacrylamide gel electrophoresis, a single protein band was obtained with a molecular weight of 120,000 (the molecular weight of GPIIb). Thus, the reactivity of monoclonal antibody 3B2 with GPIIb or the GPIIb-GPIIIa-Ca2+ complex appears to be inhibited by the presence of autoantibody on platelets.
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PMID:A monoclonal anti-platelet antibody with decreased reactivity for autoimmune thrombocytopenic platelets. 641 61

Thrombocytopenia is a common occurrence in sick newborn babies. Despite this, platelet production in the newborn has rarely been assessed, principally because of the difficulties of obtaining bone marrow, especially on a serial basis. We have developed two miniaturized assay systems to study megakaryocyte (MK) progenitor cell differentiation, from BFU-MK and CFU-MK to mature MK, by culturing mononuclear cells purified from 0.5-1 ml of neonatal peripheral blood. BFU-MK and CFU-MK were assayed in agar, whilst total cultured MK precursors and mature MK were assessed in liquid culture. In both systems, MK lineage cells were identified morphologically and by an anti-IIb/IIIa antibody (CD61). Normal ranges for MK precursors in term neonates were established from cord blood studies of 40 healthy term babies and compared with cord blood studies in 16 non-thrombocytopenic pre-term babies (gestational age range 24-36 weeks). Pre-term babies had greater numbers of all MK precursors than term babies: BFU-MK 414 +/- 61 v 151 +/- 18 colonies/ml (mean +/- SEM); CFU-MK 2444 +/- 337 v 869 +/- 64 colonies/ml; total MK precursors 213 +/- 36 v 54 +/- 6 x 10(3) cells/ml and mature MK 20 +/- 4 v 7 +/- 1 x 10(3) cells/ml. In addition, in newborn babies (n = 22), with no evidence of platelet consumption, circulating MK progenitor numbers at birth correlated with platelet numbers. These data indicate that in the newborn the measurement of circulating MK precursors provides a good indicator of megakaryocytopoiesis, and hence platelet production, and therefore is a useful and practical way of investigating neonatal thrombocytopenia.
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PMID:Circulating megakaryocytes and their progenitors (BFU-MK and CFU-MK) in term and pre-term neonates. 783 75

Thrombocytopenia is common in sick preterm babies. Despite this, platelet production in thrombocytopenic preterm babies has rarely been assessed. To address this problem we have developed miniaturized assays to study circulating megakaryocyte (MK) progenitors [burst-forming unit (BFU)-MK and colony-forming unit (CFU)-MK], total cultured MK precursors and mature MK, by culturing mononuclear cells purified from 0.5-1 mL of preterm peripheral blood. MK lineage colonies and cells are identified by an anti-IIb/IIIa antibody (CD61). We prospectively studied circulating BFU-MK/CFU-MK, total cultured MK precursors and mature MK in 63 preterm babies (gestational age 24-34 wk). Twenty-six developed early thrombocytopenia (platelets < 150 x 10(9)/L by 48 h), whereas the remaining 37 babies maintained normal platelet counts. Twenty-one of the 26 thrombocytopenic babies were born to mothers with pregnancy-induced hypertension or were growth retarded. At birth, thrombocytopenic babies had severely reduced numbers of all MK precursors compared with nonthrombocytopenic babies: BFU-MK 82 +/- 50 versus 663 +/- 174 colonies/mL, mean +/- SEM; CFU-MK 596 +/- 196 versus 3267 +/- 530 colonies/mL; total MK precursors 97 +/- 30 versus 301 +/- 49 x 10(3) cells/mL and mature MK 8 +/- 2 versus 37 +/- 8 x 10(3) cells/mL, respectively. Thrombocytopenia resolved by d 10 in all babies accompanied or preceded by a recovery to normal numbers of circulating MK progenitors. Eighteen (69%) of the thrombocytopenic babies were also neutropenic (neutrophils < 2 x 10(9)/L); in these babies neutrophil progenitor cells (CFU-granulocyte/monocyte) were also severely reduced compared with the nonthrombocytopenic babies (539 +/- 280 versus 1937 +/- 348 colonies/mL, mean +/- SEM). This indicates that the principal cause of the thrombocytopenia and neutropenia is reduced platelet and neutrophil production occurring as a consequence of reduced numbers of MK and CFU-granulocyte/monocyte progenitors, respectively. Taken together these data suggest the hematologic abnormalities characteristic of newborns born to mothers with pregnancy-induced hypertension or with intrauterine growth retardation are a consequence of dysregulation of fetal hemopoiesis occurring proximal to committed MK and neutrophil progenitors, most likely at the level of the primitive multipotent hemopoietic stem cell.
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PMID:Circulating megakaryocytes and their progenitors in early thrombocytopenia in preterm neonates. 879 56

ADAM15, a member of the ADAM (a disintegrin and metalloprotease) family, is a membrane protein containing both protease and adhesion domains and may, thus, be involved in tumor invasion and metastasis. The aim of this study was to analyze the expression of ADAM15 and its potential ligand, integrin alpha(v)beta3 (CD51/CD61), in lung carcinoma cell lines and tissues. Most small cell lung carcinomas (SCLCs) and non-SCLC cell lines were ADAM15, alpha(v) and beta3 integrin mRNA positive. Half of the cell lines expressed ADAM15, and three expressed the alpha(v)beta3 heterodimer at the cell surface as shown using flow cytometry. Paraffin sections of pulmonary epithelial tumors, including SCLCs (n=26), squamous cell cancer (SCCs, n=27) and adenocarcinomas (ACs, n=17) were stained with antibodies to the ectosolic and cytosolic domain of ADAM15 and alpha(v)beta3 integrin complex. The results were scored (0-12, according to Remmele's score). Normal epithelial cells of the lung were negative or slightly positive for ADAM15 (score<2). The score was always significantly higher for tumor cells. ACs showed the strongest staining (tumor center; ADAM15ecto; mean+/-SEM; 5.47+/-1.04), whereas SCLCs only showed weak ADAM15 expression (2.67+/-0.42; SCCs: 3.62+/-0.62). Frequently, significantly stronger ADAM15 expression has been shown in tumor cells located at the front of invasion compared with those within solid formations. Overall analysis of all tumor specimens and each tumor type revealed no significant correlation between tumor stage or degree of differentiation and ADAM15 ectosolic or cytosolic domain expression in tumor cells. Both molecules are often co-localized in the same tumor cells in ADAM15- and alpha(v)beta3 integrin-positive carcinomas. In summary, lung carcinoma cell lines and tissues were frequently ADAM15 positive.
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PMID:Expression of ADAM15 in lung carcinomas. 1575 94