Gene/Protein Disease Symptom Drug Enzyme Compound
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Query: UNIPROT:P06889 (Mol)
 630,302 document(s) hit in 31,850,051 MEDLINE articles (0.00 seconds)

The CD11b (Mol) molecule is a member of a family of surface glycoproteins that are essential for adhesion-dependent granulocyte functions. Brief exposure of granulocytes to human granulocyte-macrophage colony-stimulating factor (GM-CSF) in vitro increases the surface expression of CD11b and increases granulocyte adhesiveness. To assess the possible in vivo significance of these observations we studied the effect of GM-CSF on CD11b, CD11a (LFA-1), and CD11c (gp 150, 95) expression on granulocytes from nine adult patients with sarcoma who were receiving GM-CSF as part of a phase I trial. GM-CSF was administered as a continuous infusion at a dose of 32 or 64 micrograms/kg/d. Granulocyte CD11b, CD11a, and CD11c expression was determined by indirect immunofluorescence staining of whole blood, thereby minimizing in vitro manipulation. A transient leukopenia developed within 15 minutes of initiation of GM-CSF treatment that was associated with a marked increase in the surface antigen density of CD11b. A mean 1.7-fold increase (P = .001) in the percentage of CD11b-positive granulocytes and a mean 2.1-fold increase (P = .002) in CD11b surface antigen density was noted after 12 hours of treatment. No change in CD11a or CD11c expression was observed over the first 12 hours. The level of CD11b expression was followed in six patients for up to 5 days of treatment with GM-CSF. Compared with the 12-hour value, three of six patients showed a subsequent decrease in CD11b expression, two remained constant, and one showed a continued increase in CD11b surface density. Fluorescence-activated cell sorting of granulocytes into high- and low-density CD11b-positive groups revealed a preponderance of immature myeloid forms in the low-density CD11b fraction, which suggests that the late decrease in CD11b expression in some patients may be related to a greater proportion of circulating immature myeloid forms in the peripheral blood. This study suggests that GM-CSF administered as a continuous infusion rapidly upregulates the expression of granulocyte CD11b in vivo. The influence of this phenomenon on in vivo granulocyte aggregation may be clinically relevant with regard to the toxicity of GM-CSF and deserves further investigation.
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PMID:Granulocyte-macrophage colony-stimulating factor induces the expression of the CD11b surface adhesion molecule on human granulocytes in vivo. 304 45

Fibronectin is found in a soluble form in plasma as well as in an insoluble form in tissues. It is produced by cultured endothelial cells and can be localized in vitro and in vivo between adjacent endothelial cells as well as underneath endothelial cells in association with their collagenous matrix, where it is believed to influence cell adhesion. Fibronectin is susceptible to proteolytic cleavage by enzymes released from activated leukocytes. In the present study, cultured rat endothelial cells developed a fibrillar fibronectin network in their extracellular matrices in addition to releasing soluble, intact fibronectin (440 kDa) into their culture medium. Exposure of monolayers of cultured endothelial cells to activated polymorphonuclear leukocytes (PMNs) results in disruption of the fibrillar matrix fibronectin, damage to the endothelial cell monolayer, and presence of fibronectin fragments in the culture medium. In addition, acute leukocyte activation and peripheral leukopenia in vivo as induced by the intravenous infusion of foreign test particles also resulted in the appearance of low-molecular-weight fibronectin fragments in plasma. In the in vivo studies, the appearance of fibronectin fragments preceded the release of intact 440-kDa fibronectin in the plasma after its acute depletion by particle injection. Thus, activated leukocytes, adherent to an endothelial surface in vitro and in vivo, may result in degradation of matrix fibronectin and the release of fibronectin fragments into the extracellular environment. In vivo fibronectin fragments in blood may serve as a stimulus for the subsequent synthesis and/or release of intact plasma fibronectin.
Exp Mol Pathol 1988 Jun
PMID:Release of fibronectin fragments from endothelial cell monolayers exposed to activated leukocytes: relationship to plasma fibronectin levels after particle infusion. 337 62

The aim of the study is to investigate the relation between the hematological recovery in patients after high dose chemotherapy and peripheral blood stem cell (PBSC) rescue and the number of reinfused previously collected stem cells assessed by the number of mononuclear cells (MNCs), CFU-GMs and CD34(+) cells in th harvest. Forty nine patients mobilized with different techniques were transplanted. Our data indicate that the number of reinfused MNCs and CFU-GMS has a statistical significant relationship with the duration of leukopenia and thrombocytopenia following high dose chemotherapy and PBSC rescue in patients with various malignancies.
Blood Cells Mol Dis 1995
PMID:Relation between hematological recovery and number of transplanted mononuclear cells in patients after high dose chemotherapy with peripheral blood stem cell rescue. 867 76

Sepsis after surgery, trauma, or burn contributes to altered lung endothelial permeability and respiratory failure. Fibronectin (Fn), an opsonic and adhesive glycoprotein, exists in both a soluble form in plasma and an insoluble form in the extracellular matrix (ECM). Recent studies [E. M. Wheatley, P. J. McKeown-Longo, P. A. Vincent, and T. M. Saba, Am. J. Physiol. 265 (Lung Cell. Mol. Physiol. 9): L148-L157, 1993] suggest that the ECM content of Fn may influence lung vascular permeability. We evaluated the incorporation of plasma-derived Fn (pFn) into the ECM of the lung during postoperative sepsis. Postoperative nonseptic and postoperative septic rats were compared, using a model of laparotomy followed by cecal ligation and puncture. To label the pFn pool, rats received intravenously 3 micrograms of purified rat 125I-labeled Fn/100 g body weight 6 h after surgery (laparotomy). 125I-Fn in the deoxycholate detergent-insoluble fraction of tissues was used to quantify matrix-incorporated Fn at 4 h after infusion with 125I-Fn. Septic rats exhibited a peripheral leukopenia as well as reduction in plasma volume, Fn halflife, and total pFn pool. Incorporation of pFn in the liver and spleen of postsurgical septic rats was not different (P > 0.05) from sham-operated (postsurgical nonseptic) rats, but incorporation was significantly decreased (P < 0.05) in vivo in the lung. However, under controlled in vitro conditions, lung tissue harvested from septic or sham-operated rats demonstrated a similar tissue incorporation of soluble 125I-pFn as well as similar rates of retention/turnover of ECM 125I-Fn, based on pulse-chase experiments. These data suggest that the in vivo inflammatory environment in the lung during postoperative sepsis, which cannot be reproduced in vitro, may alter the Fn content of the ECM of the lung. Such reduced levels of pFn in the lung ECM may be a factor influencing lung vascular integrity during postoperative sepsis.
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PMID:Reduced in vivo plasma fibronectin content of lung matrix during postoperative sepsis. 884 89

Heterochromatin protein 1 (HP1) is one of the nonhistone chromosomal components tightly associated with the pericentromeric heterochromatic region in Drosophila. The human homologue of HP1 is recognized by a subpopulation of anti-centromere antibodies (ACA). Such autoantibodies recognize a group of several nuclear proteins with Mr of 23-25 kDa and have been termed 'anti-chromo antibodies (AChA)' because an evolutionarily conserved N-terminal half called the 'chromo domain' of HP1 is the epitope. In this study, 84 ACA sera were examined by immunoblotting with recombinant 25-kDa chromo protein (p25). The p25 antigen was expressed as a glutathione S-transferase-fusion protein in E. coli and purified with glutathione-sepharose. Except for one serum specimen, AChA-positive sera reacted with the N-terminus (a.a 16-106) and/or the C-terminus (a.a. 83-191) of p25. Autoimmune response against the N-terminus of p25 in 33 patients was significantly associated with systemic lupus erythematosus and significantly related to leukopenia, thrombocytopenia and elevated erythrocyte sedimentation rate; C-terminal reactivity in 30 patients was significantly associated with primary Sjogren's syndrome and related to leukopenia. The internal 64-amino acid stretch (a.a 43-106) with DNA-binding activity was not autoantigenic. p25 has two separate homologous regions to Drosophila HP1 at the N- and C-termini; the chromo domain and the chromo shadow domain. Patients with autoimmune response against these conserved domains might form a clinical subset of patients positive for ACA.
Mol Biol Rep 1996
PMID:Epitope analysis of chromo antigen and clinical features in a subset of patients with anti-centromere antibodies. 911 22

The effect of administration of human recombinant erythropoietin on leukocytic cells has been evaluated. In humans the administration of 20,000 U i.v. of rHuEPO caused a rapid and transitory leukopenia that seemed to be caused by a preferential reduction of lymphocytes (2715 +/- 513 mm3 t 0; 1898 +/- 506 t 60', p < 0.002). Pretreatment with imidazole-2-hydroxybenzoate, a drug capable of inhibiting the synthesis of prostaglandins, caused a less marked and later reduction of lymphocytes (2242 +/- 477 t 0; 1560 +/- 318 t 180 minutes, p < 0.001). A less marked and later lymphocytopenia was also shown in subjects affected by chronic renal insufficiency (2907 +/- 726 t 0; 1944 +/- 512 t 180 minutes, p < 0.005).
Hematopathol Mol Hematol
PMID:Rapid and transient lymphocytopenia after i.v. administration of high doses of human recombinant erythropoietin. 943 76

Adriamycin has a wide spectrum of antitumor activity with dose related cardiotoxicity as a major side effect. The objective of this study was to investigate the influence of captopril, a sulphydryl containing angiotensin converting enzyme inhibitor, on the cardio- and hematotoxicity of adriamycin in normal rats. A single dose of adriamycin (15 mg/kg) caused myocardial toxicity after 24 h manifested biochemically by elevation of serum enzymes:- Aspartate transaminase (AST, EC: 2.6.1.1), lactate dehydrogenase (LDH, EC: 1.1.1.27), creatine phosphokinase (CPK, EC: 2.7.3.2) and the cardiac iso-enzymes of LDH and CPK. The hematotoxicity was characterized by severe leukopenia and anemia that appeared after 72 h of adriamycin administration. Captopril (60 mg/kg i.p.) 1 h before adriamycin injection ameliorated the biochemical toxicity induced by adriamycin. This was evidenced by a significant reduction in serum enzymes, after 24 and 48 h and a significant reduction of serum cardiac iso-enzymes after 48 h. Also restoration of the white blood cell counts as well as hemoglobin concentration occurred after 72 h of captopril administration. These results suggest that captopril may be benificial as a protective agent against cardio- and hematotoxicity induced by adriamycin.
Biochem Mol Biol Int 1998 Jun
PMID:Captopril ameliorates myocardial and hematological toxicities induced by adriamycin. 967 64

Most chemotherapy agents function by causing damage to the DNA of rapidly dividing cells, such as those in the bone marrow, leading to anemia and leukopenia during chemotherapy and the development of secondary leukemias in the years following recovery from the original disease. We created an animal model of nitrosourea-based chemotherapy using ethylnitrosourea (ENU) to investigate the effect of niacin deficiency on the side effects of chemotherapy. Weanling Long-Evans rats were fed diets containing various levels of niacin for a period of 4 weeks. ENU treatment started after 1 week of feeding and consisted of 12 doses delivered by gavage, every other day. Cancer incidence was also monitored in the following months. ENU treatment caused many of the acute symptoms seen in human chemotherapy patients, including anemia and neutropenia. Niacin deficiency (ND) had several interesting effects, alone and in combination with ENU. Niacin deficiency alone caused a modest anemia, while in combination with ENU it induced a severe anemia. Niacin deficiency alone caused a 4-fold increase in circulating neutrophil numbers, and this population was drastically reduced by ENU-treatment. In the long term, macin deficiency caused an increased incidence of cancer, especially chronic granulocytic leukemias.
Mol Cell Biochem 1999 Mar
PMID:Niacin deficiency increases the sensitivity of rats to the short and long term effects of ethylnitrosourea treatment. 1033 42

T2, a chloroform/methanol extract of the herb Tripterygium wilfordii Hook f, has been used in China for the treatment of autoimmune and inflammatory diseases for many years. Recent experimental evidence has confirmed that T2 has potent anti-inflammatory and immunosuppressive activity, and a United States Food and Drug Administration-approved clinical trial is currently exploring the efficacy of T2 in the treatment of rheumatoid arthritis. Despite the potential therapeutic benefits of T2, there is ample documentation that T2 is toxic, targeting, among other things, the hematopoietic system, and its use has resulted in cases of leukopenia, thrombocytopenia, and aplastic anemia. This investigation was undertaken to characterize the in vitro effects of T2 on primary human CD34-positive (CD34+) bone marrow cells. Our results demonstrate that T2 has a potent inhibitory effect on the clonogenic response of human bone marrow cells to exogenously added hematopoietic growth factors. The inhibition of colony formation by T2 is not the result of direct cytotoxicity or increased apoptosis and indicates a functional suppression of hematopoiesis. Additional experiments demonstrate that T2 also alters transcriptional regulation in bone marrow cells by inhibiting nuclear factor-kappaB. This transcription factor is found in CD34+ bone marrow cells and has been recently shown to be a requirement for colony formation. These results demonstrate that therapeutic concentrations of T2 exert a significant hematotoxic effect by inhibiting growth factor response in CD34+ bone marrow cells and suggest that inhibition of nuclear factor-kappaB may play a role in the blood dyscrasias encountered with the use of this drug.
Mol Pharmacol 2000 Mar
PMID:Hematotoxicity of the chinese herbal medicine Tripterygium wilfordii hook f in CD34-positive human bone marrow cells. 1069 91

The serologic and clinical features of patients from pedigrees multiplex for systemic lupus erythematosus (SLE) were evaluated among three ethnic groups: Hispanics, African-Americans and European-Americans. Data were obtained from a registry of 123 pedigrees, composed of 4 Hispanic, 40 African-American and 79 European-American pedigrees. All patients met at least four criteria for the diagnosis of SLE per the American College of Rheumatology. Clinical information was obtained through review of the medical records and questionnaires completed by the participants. Ethnicity by self-identification was found to be an important factor influencing the prevalence of serologic results and clinical features. Anti-nRNP occurred more frequently in African-Americans (45.7%) than in European-Americans (7.5%) or Hispanics (0%) (p<0.0000001), as did anti-Sm (18.5% vs 1.6% and 0%, respectively) (p<0.000001). Malar rash, photosensitivity and oral ulcers were most frequent in the Hispanic population while proteinuria and leukopenia predominated in the African-American population. Arthritis and lymphopenia were present in a similar proportion in all ethnic groups. These results show that many of the ethnic differences known for isolated cases of SLE are also present in familial cases of SLE.
Cell Mol Biol (Noisy-le-grand) 2001 Nov
PMID:Familial systemic lupus erythematosus: a comparison of clinical manifestations and antibody presentation in three ethnic groups. 1183 71


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