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)

Hermansky-Pudlak syndrome (HPS) has evolved into a group of genetically distinct disorders characterized by oculocutaneous albinism, a storage pool deficiency, and impaired formation or trafficking of intracellular vesicles. HPS-1 results from mutations in the HPS1 gene and affects approximately 400 individuals in northwest Puerto Rico due to a 16-bp duplication in exon 15. Another 13 mutations have been reported in non-Puerto Ricans. HPS1 codes for a 79.3 kDa cytoplasmic protein of unknown function. HPS-1 patients typically develop fatal pulmonary fibrosis in their fourth decade. HPS-2 is caused by mutations in ADTB3A, which codes for the beta3A subunit of the adaptor protein-3 complex, AP3. This coat protein complex has been localized to the TGN as well as to a peripheral endosomal compartment. Evidence indicates that AP3 plays a role in the stepwise process of vesicular trafficking which leads to formation of the melanosomal, platelet dense body and lysosomal compartments. All three known HPS-2 patients had childhood neutropenia and infections. HPS-3 results from mutations in HPS3 and affects central Puerto Ricans homozygous for a 3904-bp deletion removing exon 1. At least 8 non-Puerto Rican patients have other HPS3 mutations, including an IVS5+1G->A splicing mutation in five Ashkenazi Jewish patients. HPS3 codes for a 113.7 kDa protein of unknown function. HPS-3 manifests with mild hypopigmentation and bleeding. All types of HPS are diagnosed by whole mount electron microscopic demonstration of absent platelet dense bodies, and molecular diagnoses are available for the Puerto Rican HPS1 and HPS3 founder mutations. Mouse and Drosophila models provide candidates for new genes causing HPS in humans. These genes will reveal the pathways by which specialized vesicles of lysosomal lineage arise within cells.
 ...
PMID:Disorders of vesicles of lysosomal lineage: the Hermansky-Pudlak syndromes. 1212 11

Wiskott-Aldrich Syndrome (WAS) is a severe X-linked Primary Immunodeficiency that affects 1-10 out of 1 million male individuals. WAS is caused by mutations in the WAS Protein (WASP) expressing gene that leads to the absent or reduced expression of the protein. WASP is a cytoplasmic protein that regulates the formation of actin filaments in hematopoietic cells. WASP deficiency causes many immune cell defects both in humans and in the WAS murine model, the Was(-/-) mouse. Both cellular and humoral immune defects in WAS patients contribute to the onset of severe clinical manifestations, in particular microthrombocytopenia, eczema, recurrent infections, and a high susceptibility to develop autoimmunity and malignancies. Autoimmune diseases affect from 22 to 72% of WAS patients and the most common manifestation is autoimmune hemolytic anemia, followed by vasculitis, arthritis, neutropenia, inflammatory bowel disease, and IgA nephropathy. Many groups have widely explored immune cell functionality in WAS partially explaining how cellular defects may lead to pathology. However, the mechanisms underlying the occurrence of autoimmune manifestations have not been clearly described yet. In the present review, we report the most recent progresses in the study of immune cell function in WAS that have started to unveil the mechanisms contributing to autoimmune complications in WAS patients.
 ...
PMID:Autoimmunity in wiskott-Aldrich syndrome: an unsolved enigma. 2282 11

This study presents a case of metastatic sarcomatoid renal cell carcinoma (RCC) treated with systemic chemotherapy followed by mammalian target of rapamycin inhibitor maintenance therapy. A 63-year-old male presented with lumbago, and lumbar vertebral tumors were detected by magnetic resonance imaging. Subsequent computed tomography (CT) revealed a right renal tumor and CT-guided biopsy of the right renal and left sacroiliac tumors determined pure sarcomatoid carcinoma without a clear cell component. Two cycles of combination chemotherapy comprising of gemcitabine (1,500 mg/m2 on day one) and doxorubicin (50 mg/m2 on day one) resulted in a 20% reduction in the longest diameter of the right renal tumor. However, due to grade 3 neutropenia, the chemotherapy was discontinued and temsirolimus (25 mg once weekly), which binds to the cytoplasmic protein, FKBP-12, and inhibits mTOR, was administered. Stable disease was maintained for 19 months with temsirolimus and no major adverse events, with the exception of grade 2 nausea, were observed. The patient succumbed to their disease at 30 months following the initiation of treatment. These results suggested that systemic chemotherapy followed by temsirolimus maintenance is a feasible treatment option for patients with metastatic sarcomatoid RCC.
 ...
PMID:Successful mammalian target of rapamycin inhibitor maintenance therapy following induction chemotherapy with gemcitabine and doxorubicin for metastatic sarcomatoid renal cell carcinoma. 2495 97