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)

Recent advances in basic science and clinical trials have demonstrated that IFNs and myeloid hematopoietins play crucial roles in host defense against pathogens and immune surveillance. Here we have reviewed the biologic functions of GM-CSF, G-CSF, IFN-alpha and IFN-gamma. For patients with neutropenia resulting from cytotoxic chemotherapy, bone marrow transplantation, congenital agranulocytosis and cyclic neutropenia, therapeutic uses of GM-CSF and G-CSF were reviewed. Application of these growth factors to patient management represents a major contribution of biotechnology to a difficult area of therapeutics in febrile, neutropenic patients. Because IFN-alpha plays crucial roles in antiviral responses, its clinical applications in hepatitis B and C, human papilloma virus, HIV infection and malignancy were discussed. The use of IFN-gamma in bacterial prophylaxis in patients with chronic granulomatous disease was also presented. Advances in clinical applications of IFNs and hematopoietic growth factors serve as a paradigm for further development to investigate the use of other important cytokines in modern therapeutics.
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PMID:Biology and therapeutic uses of myeloid hematopoietic growth factors and interferons. 904 17

The term WHIM syndrome (WHIMS) is an acronym describing a rare primary immunodeficiency disorder characterized by warts, hypogammaglobulinemia, immunodeficiency, and myelokathexis, the unusual association of neutropenia with bone marrow myeloid hypercellularity. WHIMS was recently associated with mutations in the gene encoding the chemokine receptor CXCR4 and as such is the first disease ascribed to abnormalities of chemokine signaling. We report a sporadic case of WHIMS in a woman presenting with recurrent infections and human papilloma virus-related genital dysplasia.
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PMID:Sporadic case of warts, hypogammaglobulinemia, immunodeficiency, and myelokathexis syndrome. 1627 83

WHIM syndrome is a condition in which affected persons have chronic peripheral neutropenia, lymphopenia, abnormal susceptibility to human papilloma virus infection, and myelokathexis. Myelokathexis refers to the retention of mature neutrophils in the bone marrow (BM), which accounts for degenerative changes and hypersegmentation. Most patients present heterozygous autosomal dominant mutations of the gene encoding CXCR4. Consequently, aberrant CXCL12/CXCR4 signaling impairs the receptor downregulation causing hyperactivation (gain-of-function) that affects BM homing for myelopoiesis and lymphopoiesis and the release of neutrophils in the bloodstream. We report the case of a 26-year-old female with severe foot and hand cutaneous warts since childhood, recalcitrant genital condylomatas, bacterial infections, and intraepithelial cervical neoplasia. Laboratory tests revealed severe B lymphopenia and HPV high and low risk types. HIV testing was negative. Not only CXCR4 but also GATA2, NEMO, and CD40L gene mutations were excluded. BM smears revealed, in the presence of a normal cellularity, hyperplasia of myeloid cells (MPO positive) and karyorrhexis, especially in neutrophils and eosinophils. Of note, neutrophils with altered lobation of nuclei connected by long thin chromatin filaments were observed. Our patient presented a clinical and histological picture reminiscent of WHIM in the presence of normal peripheral neutrophil counts and wild-type CXCR4 gene. Although the BM did not reveal a classical pattern of myelokathexis, the observation of consistent signs of neutrophil dysplasia has fuelled the hypothesis of a novel WHIM variant or a novel immunodeficiency. We speculate that abnormalities that affect CXCR4/CXCL12 pair, including GRK levels or activity, might be responsible for this WHIM-like disorder.
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PMID:Dysplasia of Granulocytes in a Patient with HPV Disease, Recurrent Infections, and B Lymphopenia: A Novel Variant of WHIM Syndrome? 2851 28