Gene/Protein Disease Symptom Drug Enzyme Compound
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Query: UMLS:C0027947 (neutropenia)
 17,527 document(s) hit in 31,850,051 MEDLINE articles (0.00 seconds)

Colony-stimulating factors, a complex family of cytokines often referred to as hematopoietic growth factors, are a family of glycoprotein hormones that regulate production and differentiation of hematopoietic cells. The study of colony-stimulating factors was originally confined to stimulation and formation of clonal colonies in in vitro culture systems. The study of hematopoietic growth factors has since evolved into an expanding number of clinical applications in the treatment of patients with hematopoietic and immunologic diseases. Increased occurrence rates of infection have been demonstrated to be associated with both severity and duration of neutropenia. Sepsis has also been associated with phagocytic functional abnormalities. Both neutropenia and neutrophil dysfunction have been shown, in part, to be corrected by granulocyte colony-stimulating factor or granulocyte-monocyte colony-stimulating factor. In clinical trials to date, neither of these growth factors has shown significant toxicity. This article discusses the possible use of these and other growth factors in the treatment of sepsis.
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PMID:Colony-stimulating factors in the modulation of sepsis. 792 98

Macrophage colony-stimulating factor (M-CSF) is a homodimeric glycoprotein which stimulates differentiation of progenitor cells to mature monocytes and enhances production of hemopoietic growth factors from mature monocytes such as granulocyte-macrophage CSF, granulocyte CSF and megakaryocyte potentiator, suggesting that M-CSF administration enhances production of monocytes, neutrophils and platelets. Since the commercial availability of M-CSF in 1991, serial M-CSF infusions at a daily dose of 8 million units have been performed in patients with acute myeloid leukemia in complete remission after combination chemotherapy. Although M-CSF infusion reduced the duration of neutropenia in 3 of 5 patients, it reduced the duration of pyrexia over 37 degrees C in all patients, and that over 38 degrees C in 4 of 5 patients. Average durations of pyrexia and parenteral antibiotic injections were significantly shorter in M-CSF than in control courses. Although M-CSF infusion reduced the duration of thrombopenia in 2 of 5 patients, it reduced total platelet units transfused in 4 of 5 patients. The average number of platelet units transfused after combination chemotherapy was significantly lower in M-CSF than in control courses. In mice, M-CSF injection increased the serum concentration of reactive nitrogen intermediates which inhibited the growth of L1210 cells, and increased the survival rate of mice previously injected with them. These results indicate that M-CSF may be a promising agent not for improving patients' quality of life after cancer chemotherapy, but also in cancer immunotherapy.
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PMID:Macrophage colony-stimulating factor for cancer therapy. 819 2

We have reported that lactoferrin, a 77-kDa iron-binding glycoprotein found in secondary neutrophil granules, provides a useful marker of fecal leukocytes in fecal specimens from patients with inflammatory diarrhea (R. L. Guerrant, V. Araujo, E. Soares, K. Kotloff, A. A. M. Lima, W. H. Cooper, and A. G. Lee, J. Clin. Microbiol. 30:1238-1242, 1992). In order to determine the usefulness of this marker of neutrophilic inflammation in different body fluids, we examined blood, gingival swabs, sputum, and saliva using antilactoferrin antibodies (lactoferrin latex agglutination [LFLA]). LFLA titers in whole blood samples were < or = 1:4 in all eight samples from patients with neutropenia (absolute neutrophil count [ANC] = < 150 polymorphonuclear cells [PMNs] per microliter), < or = 1:8 in samples from 13 individuals with moderate leukocyte counts (ANC = 150 to 8,000), and 1:8 to 1:32 in samples from six patients with neutrophilia (ANC > 8,000). While the overlap precludes a useful role in the identification of neutropenia, these data confirm that lactoferrin titers of > 1:100 indeed indicate inflammation in fluid specimens. On quantitative elution of lactoferrin from gingival swabs, all 7 patients with dental plaque had titers of 1:200 to 1:400; 9 of 12 patients with clinical gingivitis had LFLA titers of 1:200 to 1:1,600, while all 7 individuals with healthy gums and teeth and 4 edentulous patients had LFLA titers of < or = 1:100. Eight purulent sputum samples had titers of > or = 1:400 (7 were 1:1,600) while 11 normal saliva samples showed titers of < or = 1:100. Lactoferrin titers in sputum, gingival swabs, and whole blood correlate with the presence of neutrophils or inflammation in these specimens and may offer a convenient rapid test for inflammatory processes.
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PMID:Correlation of lactoferrin with neutrophilic inflammation in body fluids. 857 44

The aim of platelet inhibitory therapy in cardiology is to prevent undesired thrombus formation and, thus, to prevent complications of cardiovascular diseases. In Germany, 5 substances are approved for antiplatelet therapy. Acetylsalicylic acid, an inhibitor of platelet cyclooxygenase, has been shown to be effective at both high and low doses in the secondary prevention of myocardial infarction, coronary heart disease, and cerebrovascular disease. In addition, acetylsalicylic acid is effective in reducing the complications of unstable angina pectoris and coronary angioplasty, and in reducing the occlusion rate of aortocoronary bypass grafts. The addition of dipyridamole to acetylsalicylic acid has not been shown to result in any additional benefit in many clinical studies. Ticlopidine, an antagonist of ADP-induced platelet aggregation has been similarly effective as acetylsalicylic acid in the treatment of coronary heart disease. The principal side effect of the drug, the occurrence of neutropenia in about 1% of treated patients, makes regular blood cell counts mandatory during treatment. In the secondary prevention of cerebrovascular disease, the drug may be superior to acetylsalicylic acid. Trapidil is an anti-platelet substance which acts on platelets through various mechanisms including inhibition of the release of "platelet derived growth factor". In 3 smaller randomized studies, trapidil has been found to reduce the restenosis rate after coronary angioplasty. Abciximab, the Fab-fragment of an antibody against the platelet fibrinogen receptor glycoprotein 11b/IIIa has been shown to be effective in the prevention of acute and long-term complications of high-risk coronary angioplasty.
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PMID:-New aspects in antithrombotic therapy--platelet inhibitors-. 864 75

Hemopoietic Growth Factors (GF) are glycoprotein hormones that regulate the proliferation and differentiation of hematopoietic progenitor cells and of mature blood cell function. In last years GFs have moved from the laboratory study to the clinical area, and most of them have been produced on a large scale through recombinant DNA technology. Hemopoiesis and GF sensitivity of marrow cells declines with age, impairing the ability of elderly people to increase the production of GFs under stress conditions. In elderly cancer patients chemotherapy-associated neutropenia very frequently causes fever or infection with dose delay and increased morbidity and mortality rate, therefore in this setting beneficial effects of adjunct treatment with GFs have been proposed. Since reduction in neutropenia and in the risk of infection does not necessarily result in improved remission rate and long-term survival, some recommendations on the use (or abuse) of GFs are reviewed in this paper.
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PMID:Hematopoiesis and growth factors in elderly cancer patients. 925 12

A 58-year-old man experienced episodes of fever, vomiting, and diarrhea over a 2-year period. The laboratory evaluation during these attacks consistently disclosed thrombocytopenia, leukopenia, and elevated liver enzymes. A liver biopsy performed at one of these attacks showed a typical picture of granulomatous hepatitis. In retrospect, all episodes seemed to be associated with the ingestion of quinine. Indeed, such a correlation was established by a challenge with quinine. By using flow cytometry, quinine-dependent IgG antibodies to platelets were detected in the patient serum. By a two-color flow cytometric assay, the patient serum was also found to hold quinine-dependent antibodies specific for neutrophils, T lymphocytes, and B lymphocytes. Moreover, serum absorbed with neutrophils in the presence of quinine continued to react with platelets, T lymphocytes, and B lymphocytes; serum that was absorbed with mononuclear cells continued to react with neutrophils and platelets. These experiments indicated that the antigen targets were different on platelets, neutrophils, and lymphocytes. Further, the patient serum in the presence of quinine immunoprecipitated surface-labeled platelet proteins with electrophoretic mobilities closely resembling those of glycoprotein (GP) Ib/IX and GPIIb/IIIa. By a modified monoclonal antibody-specific immobilization of platelet antigens assay, the patient serum in the presence of quinine reacted with platelet GPIb/IX and GPIIb/IIIa. Also, the patient serum in the presence of quinine immunoprecipitated an uncharacterized 15-kD double-band from surface-labeled granulocyte proteins. We conclude that our patient's thrombocytopenia, neutropenia, and lymphocytopenia were caused by quinine-dependent antibodies and that these antibodies recognized cell lineage-specific epitopes.
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PMID:Multiple quinine-dependent antibodies in a patient with episodic thrombocytopenia, neutropenia, lymphocytopenia, and granulomatous hepatitis. 938 97

Immune responses to platelet and neutrophil alloantigens are involved in the pathogenesis of several clinical syndromes including: neonatal alloimmune thrombocytopenia (NATP), post-transfusion purpura (PTP), refractory responses to platelet transfusion, neonatal alloimmune neutropenia (NAN), transfusion-related acute lung injury (TRALI), and chronic benign autoimmune neutropenia of infancy. Initially, platelet alloantigens were only characterized serologically. Subsequently, they were localized to specific platelet surface glycoprotein structures and ultimately defined to the level of nucleic acid polymorphisms on platelet glycoprotein genes. These advances allowed the tools of molecular biology to be applied to typing for platelet alloantigens. The advantages of such typing methods include: 1) patient platelets are no longer required for the typing assays, and therefore, platelet types can be established on extremely thrombocytopenic samples (by using peripheral blood white blood cells [WBC]); 2) The genotyping methods eliminate the requirement for rare serologic reagents. A number of different genotyping methods have been developed. These include: restriction fragment length polymorphism (RFLP), sequence specific primers (SSP), and Dot-Blot hybridization. Clinical applications of this methodology include: determining the platelet genotype of fetuses at risk for NATP, in the diagnosis of PTP, and identifying causes of refractory responses to platelet transfusions. Analogous to platelet alloantigens, a limited number of neutrophil alloantigens can now be determined by molecular biologic methods. The new methods obviate the need to isolate fresh neutrophils for serologic typing and do not require rare serologic reagents. To date, molecular polymorphisms associated with alloantigens on the neutrophil Fc gamma RIIIb surface glycoprotein have been elucidated. These include the allo-antigens NA1, NA2, and SH.
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PMID:Platelet and neutrophil alloantigen genotyping in clinical practice. 957 76

Macrophage colony-stimulating factor (M-CSF) was found to be a glycoprotein with a molecular weight of 85 kDa which stimulated macrophage colony formation of mouse bone marrow cells in a semisolid agar culture system in 1978. M-CSF stimulates differentiation of progenitor cells to mature monocytes, and prolongs the survival of monocytes. It enhances expression of differentiation antigens and stimulates chemotactic, phagocytic and the killing activities of monocytes. Macrophage CSF also stimulates production of several cytokines such as granulocyte-macrophage CSF, granulocyte CSF and interleukin (IL)-6 by priming monocytes, and directly stimulates production and secretion of IL-8 and reactive nitrogen intermediates. In addition to the stimulation of hematopoiesis, M-CSF also stimulates differentiation and proliferation of osteoclast progenitor cells and cytotrophoblasts. Proteoglycan type M-CSF, which contains chondroitin sulfate chains, was found in 1992. In a large-scale double-blind controlled study on acute myeloid leukemia (AML), it has been shown that the administration of M-CSF to patients after consolidation chemotherapies shortens the periods of neutropenia and thrombopenia after chemotherapy and reduces the incidence and shortens the duration of febrile neutropenia, as well as shortening the period required to finish three courses of intensive consolidation therapy.
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PMID:Biological activities and clinical application of M-CSF. 963 77

The human recombinant granulocyte colony-stimulating factor (rhG-CSF) is largely used in the treatment of neutropenia occurring during chemotherapy. After injection, this glycoprotein distributes through the whole body. Thus, to obtain high and durable bone marrow concentrations, targeting with polyalkylcyanoacrylate nanoparticles was considered. Two methods of preparation were investigated: anionic polymerization and precipitation of the preformed polymer. By anionic polymerization, it was possible to associate more than 66% of rhG-CSF with nanoparticles (polyisobutyl- or polyisohexylcyanoacrylate nanoparticles) when the glycoprotein was added at the end of the polymerization process. It has been shown that the rhG-CSF was mainly adsorbed on the surface of the nanoparticles and most of the colony stimulating activity was conserved. Using precipitation of performed polyisohexylcyanoacrylate, 90% of rhG-CSF was associated with nanoparticles, the protein being mainly adsorbed onto the nanoparticle surface. In this case, a decrease of the colony stimulating activity was however observed. Whatever the method used, the in vitro release of rhG-CSF from the polyisohexylcyanoacrylate nanoparticles, was progressive during 8 h in seric conditions. Nevertheless, using mice as an animal model, it has been shown that the short-term effects of intravenously injected rhG-CSF were not increased by its association with polyisohexylcyanoacrylate nanoparticles.
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PMID:Polyalkylcyanoacrylate nanoparticles as carriers for granulocyte-colony stimulating factor (G-CSF). 968 43

Preclinical studies have demonstrated that recombinant IFN-alpha (rIFN-alpha) can enhance the tumor associated glycoprotein 72 (TAG-72) on tumors. To determine whether rIFN-alpha could enhance TAG-72 expression in vivo in patients, 15 women with breast cancer were randomized to receive daily injections of rIFN-alpha (3 x 10(6) units/m2 for 14 days) beginning on day 1 (group 1 = 7 patients) or on day 6 (group 2 = 8 patients). On day 3, all patients received a 10-20-mCi tracer dose of 131I-CC49, a high-affinity murine monoclonal antibody reactive against TAG-72, followed by a therapy dose of 60-75 mCi/m2 of 131I-CC49 on day 6. Whole body and single-photon emission computed tomography scans along with whole blood pharmacokinetics were performed following tracer and treatment phases. Hematological toxicity was considerable; reversible grade 3-4 neutropenia and thrombocytopenia was observed in 12 of 15 patients. Twelve of 14 patients tested developed human antimouse antibodies 3-6 weeks after treatment. For group 1 patients, whole blood residence time increased significantly between that predicted from the tracer doses and therapy doses (42.6 +/- 4.7 versus 51.5 +/- 4.8 h, respectively; P < 0.01). The calculated radiation absorbed dose to red marrow from therapy compared to tracer activity was also significantly higher for this group (1.25 +/- 0.35 versus 1. 07 +/- 0.26 cGy/mCi; P < 0.05). Treatment with rIFN-alpha was found to enhance TAG-72 expression in tumors from patients receiving rIFN-alpha (group 1) by 46 +/- 19% (P < 0.05) compared to only 1.3 +/- 0.95% in patients not initially receiving IFN (group 2). The uptake of CC49 in tumors was also significantly increased in rIFN-alpha-treated patients. One partial and two minor tumor responses were seen. In summary, rIFN-alpha treatment altered the pharmacokinetics and tumor uptake of 131I-CC49 in patients at the expense of increased toxicity.
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PMID:Effect of recombinant alpha-interferon on pharmacokinetics, biodistribution, toxicity, and efficacy of 131I-labeled monoclonal antibody CC49 in breast cancer: a phase II trial. 981 42


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