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

The effects of branched-chain amino acid metabolites on granulocyte-macrophage progenitor cell proliferation in marrow culture are reported. Isovalerate and propionate profoundly suppress granulopoiesis at both 3.2 and 6.4 mM concentrations, whereas methylmalonate and other metabolites suppress to a lesser degree. The parent branched-chain amino acids leucine, isoleucine, and valine do not suppress in vitro granulopoiesis at similar concentrations. Because the concentrations of the organic acids tested fall within the pathophysiologic ranges observed in patients with isovaleric, propionic, and methylmalonic acidemias, we suggest that elevated in vivo levels of isovalerate, propionate, and to a lesser degree methylmalonate are responsible for the neutropenia observed in these disorders.
 ...
PMID:Suppression of granulopoietic progenitor cell proliferation by metabolites of the branched-chain amino acids. 396 82

Recombinant human interleukin 3 (rhIL-3, expressed in Escherichia coli) is a hematopoietic growth factor with protean biological effects on bone marrow in animal models, including enhanced granulocyte and platelet production and the capacity to ameliorate chemotherapy-induced bone marrow toxicity. We, therefore, undertook a Phase I trial in patients with advanced solid tumors and normal bone marrow function. Cohorts of four to six patients each received daily s.c. doses of rhIL-3 (SDZ-ILE-964; Sandoz) at dose levels of 1. 0, 2.5, 5.0, and 10.0 microgram/kg according to the following schedule: cycle 1, rhIL-3 days 1-14; cycle 2, carboplatin (350 mg/m2) on day 1 and etoposide (100 mg/m2) on days 1-3; and cycle 3, carboplatin (350 mg/m2) on day 1, etoposide (100 mg/m2) on days 1-3, and rhIL-3 on days 4-17. Each cycle was a total of 28 days. An analysis of 20 patients entered into all four escalating dose levels revealed that, during cycle 1, absolute neutrophil count (ANC) increased from a median baseline of 6,643/mm3 to a median of 12,692/mm3, and platelets increased from a median baseline of 314,000/mm3 to a median of 465,000/mm3. When cycle 2 was compared with cycle 3, the median ANC nadir increased from 192/mm3 to 988/mm3, and the mean ANC nadir increased from 458/mm3 to 1,297/mm3. Median platelet count nadirs increased from 29,000/mm3 to 84,000/mm3, and the mean nadir platelet counts increased from 72,000/mm3 to 129,000/mm3. Total days on which platelets were <50,000/mm3 was 52 for cycle 2 and 19 for cycle 3. The maximum tolerated dose of rhIL-3 was 5.0 microgram/kg/day; dose-limiting toxicities included fatigue, chills, fever, and headache. These data suggest a clear but variable biological activity observed with IL-3, as measured by the reduction in the depth and duration of thrombocytopenia and/or neutropenia when cycle 2 was compared with cycle 3. rhIL-3 is a promising cytokine that may help to ameliorate the bone marrow toxicity observed with the use of chemotherapeutic agents.
 ...
PMID:Phase I trial of recombinant interleukin 3 before and after carboplatin/etoposide chemotherapy in patients with solid tumors: a southwest oncology group study. 981 5

There is dearth of information on the haematologic complications of HIV/AIDS in this country. The aim of this work was to evaluate the importance of peripheral blood and bone marrow changes in a population of adult Nigerians managed for symptomatic HIV infection at the OAUTHC, Ile-Ife, between 1995 and 2001. The study was prospective. Peripheral blood cells counts (haemetocrit value, total and differential leucocyte counts, and platelet counts) and bone marrow cytology of serologically confirmed HIV/AIDS patients seen within the study period were studied. The associated opportunistic disorder (s) was noted for each patient. Individuals with conditions that are ordinarily associated with haematologic disorders (e.g. cancer and inherited haemoglobinopathies) and patients diagnosed in pregnancy were not included. Significant levels of differences in mean values of blood cells within groups were determined by student's t-test. Seventy-two patients were recorded, out of which 49 (68%) were evaluable. There were 32 (65%) males and 17 (35%) females, all aged between 21 and 51 (median = 36) years. None of the patients had conventional antiretroviral therapy. Lymphopenia (lymphocytes < 2 x 10(9)/l) was seen in 64.4% of the patients, 50% and over 40% of the patients had moderate-severe anaemia and neutropenia, respectively. Blood cells values were not significantly different between patients with mild disease and those with moderate-severe diseases. The most characteristic marrow abnormality was the abundance of naked nuclei of megakarycytes in 20 (60.1%) of the patients. Dysplatic changes were evident in 15 (45.5%) of the bone marrow specimens studied. Such changes are characterised by dysgranulopoiesis, Pelger-Huet anomaly in some of the mature granulocytes, vacuolation of some erythroid and myeloid cells, unilobular micromegakaryocytes and megaloblastic erythroid precursors (15.1% of the marrow).
 ...
PMID:Peripheral blood and bone marrow changes in patients with acquired immunodeficiency syndrome. 1805 Jul 79