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)

Aggressive chemotherapy of leukemia increases the risk of severe infections during treatment-induced myelosuppression. However, the assessment of an infectious origin of neutropenic fever is often difficult. Leukocyte adhesion molecules such as E-selectin, intercellular adhesion molecule 1 (ICAM-1) and vascular cell adhesion molecule 1 (VCAM-1) are involved in early inflammatory response. We studied plasma concentrations of their soluble isoforms during 48 treatment courses with myeloablative chemotherapy in 32 leukemic patients. There were 35 febrile episodes during neutropenia. Pneumonia was clinically and microbiologically documented in 15 cases, six had proven infections but normal chest radiograph, and 14 were classified as fever of unknown origin. Longitudinal studies revealed a sustained increase of sICAM-1 plasma levels associated with pneumonia. Increase of sICAM-1 plasma levels distinguished patients with pneumonia from those with fever not related to pneumonia (positive predictive value 0.87, negative predictive value 0.94). Plasma levels of sICAM-1 were elevated in both, fungal and non-fungal pneumonia. Increases of sICAM-1 paralleled first radiographic evidence of pulmonary infiltrations in most cases. In contrast, no elevation of sVCAM-1 or sE-selectin was documented during febrile events prior to recovery of leukocyte counts.
 ...
PMID:Increases of sICAM-1 during neutropenic pneumonia in leukemic patients. 930 21

The etiology of drug-induced agranulocytosis is poorly understood. Many drugs that induce neutropenia or agranulocytosis can be metabolized to reactive intermediates that covalently bind to macromolecules. Until now, the myeloid precursor cell or an earlier committed progenitor cell has been favoured as the target for toxicity, due to evidence in some cases of cytotoxic action or antibodies against neutrophils. In the bone marrow, where neutrophils mature, certain components of the stromal microenvironment, e.g. intracellular adhesion molecule 1, vascular cell adhesion molecule 1, CD11b/CD18, heparan sulfate proteoglycans, fibronectin and hemonectin are essential for normal myeloid maturation. This article proposes that drugs implicated in agranulocytosis, or more likely their reactive metabolites, interact with specific components of the extracellular matrix and interfere with the normal regulation of granulopoiesis.
 ...
PMID:Drugs that induce neutropenia/agranulocytosis may target specific components of the stromal cell extracellular matrix. 1053 10

Invasive aspergillosis is characterized by hyphal invasion of the blood vessels, which contributes to the pathogenesis of this disease. During this angioinvasion, Aspergillus fumigatus interacts with the endothelial cell lining of the blood vessels. We investigated the response of vascular endothelial cells to A. fumigatus infection in vitro and in mouse models of invasive pulmonary aspergillosis. Infection with hyphae, but not with conidia, stimulated endothelial cells to synthesize E-selectin, vascular cell adhesion molecule 1 (VCAM-1), interleukin 8, and tumor necrosis factor alpha (TNF-alpha) in vitro. Killed hyphae induced approximately 40% less stimulation than did live hyphae. Endothelial cell stimulation required contact between the hyphae and endothelial cells but not endocytosis of the organisms. Studies with DeltagliP and DeltastuA null mutants of A. fumigatus indicated that the extent of endothelial cell stimulation was not influenced by gliotoxin or other StuA-dependent factors synthesized by A. fumigatus. In neutropenic mice infected with wild-type A. fumigatus, increased pulmonary expression of E-selectin, cytokine-induced neutrophil chemoattractant (KC), and TNF-alpha occurred only when neutropenia had resolved. In nonneutropenic mice immunosuppressed with corticosteroids, A. fumigatus stimulated earlier pulmonary expression of E-selectin, VCAM-1, and KC, while expression of intercellular adhesion molecule 1 and TNF-alpha was suppressed. In both mouse models, expression of E-selectin and KC was associated with high pulmonary fungal burden, angioinvasion, and neutrophil adherence to endothelial cells. Therefore, the expression of leukocyte adhesion molecules and secretion of proinflammatory cytokines by endothelial cells in response to A. fumigatus could enhance the host defense against this organism by contributing to the recruitment of activated leukocytes to sites of angioinvasion.
 ...
PMID:Aspergillus fumigatus stimulates leukocyte adhesion molecules and cytokine production by endothelial cells in vitro and during invasive pulmonary disease. 1849 Apr 55