Gene/Protein Disease Symptom Drug Enzyme Compound
Pivot Concepts:   Target Concepts:
Query: UMLS:C0019045 (hemoglobinopathies)
 2,704 document(s) hit in 31,850,051 MEDLINE articles (0.00 seconds)

Renal medullary carcinoma is an epithelial malignant tumor arising from collecting duct epithelium. The tumor is almost exclusive to young black patients with the sickle cell hemoglobinopathies, mainly sickle cell trait (SCT). Most patients present with metastatic disease and have a worse prognosis. An African-American male with sickle cell disease (HbSCD) who was diagnosed to have renal medullary carcinoma is presented here. The clinical, histologic and radiologic features of this tumor are described. In the setting of advanced disease, treatment modalities have proved largely unsuccessful. Given the shared demographic, clinical and radiographic features of these patients, awareness and early diagnosis may prove essential in improving survival.
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PMID:Renal medullary carcinoma. 1689 89

Sickle cell disease (SCD), the first 'molecular disease' to be identified, has been well characterized as a single amino acid molecular disorder of hemoglobin leading to its pathological polymerization, with resulting red cell rigidity that causes poor microvascular blood flow, with consequent tissue ischemia and infarction. Thus, the manifestations of SCD chronic renal disease have long been considered clinical manifestations of an obstructive vasculopathy of the arterial and capillary microcirculation. Recently, accumulating evidence have indicated that blood vessel functions are affected by SCD, involving abnormal vascular tone and activated endothelium. These abnormalities are particularly prominent in the kidney where specific biochemical conditions in the medulla and papilla favor change in endothelial phenotype and in tubular phenotype that, in turn, may promote dysfunction and destruction of this organ through active endothelin (ET)-1 production and signals. High ET-1 urinary output in SCD subjects at steady state may reflect increased tubular activation of ET-1 production acting on the collecting duct thereby favoring the constant hyposthenuria. Chronically, augmented ET-1 concentrations in the SCD kidney would further aggravate ischemia and sickling through actions on vasa recta and red blood cells. The kidneys suffer multiple ischemic hits during SCD as consequences of vasos-occlusive crisis (VOC). Blockade of ET receptors unraveled the major vasoconstrictive role of ET-1 in the pathophysiology of VOC, stressing the pivotal role of abnormal endothelial phenotype in this hemoglobinopathy and opening potential new therapeutic options. At last, indirect evidence suggest that ET-1 may be involved in the progression of chronic glomerulosclerosis affecting a number of patients. In fact, sickle cell nephropathy is an emerging severe disease that requires pathophysiological studies and development of specific therapies.
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PMID:Endothelin in renal injury due to sickle cell disease. 2189 99

Renal medullary carcinomas (RMCs) and collecting duct carcinomas (CDCs) are rare subsets of lethal high-stage, high-grade distal nephron-related adenocarcinomas with a predilection for the renal medullary region. Recent findings have established an emerging group of fumarate hydratase (FH)-deficient tumors related to hereditary leiomyomatosis and renal cell carcinoma (HLRCC-RCCs) syndrome within this morphologic spectrum. Recently developed, reliable ancillary testing has enabled consistent separation between these tumor types. Here, we present the clinicopathologic features and differences in the morphologic patterns between RMC, CDC, and FH-deficient RCC in consequence of these recent developments. This study included a total of 100 cases classified using contemporary criteria and ancillary tests. Thirty-three RMCs (SMARCB1/INI1-deficient, hemoglobinopathy), 38 CDCs (SMARCB1/INI1-retained), and 29 RCCs defined by the FH-deficient phenotype (FH/2SC or FH/2SC with FH mutation, regardless of HLRCC syndromic stigmata/history) were selected. The spectrum of morphologic patterns was critically evaluated, and the differences between the morphologic patterns present in the 3 groups were analyzed statistically. Twenty-five percent of cases initially diagnosed as CDC were reclassified as FH-deficient RCC on the basis of our contemporary diagnostic approach. Among the different overlapping morphologic patterns, sieve-like/cribriform and reticular/yolk sac tumor-like patterns favored RMCs, whereas intracystic papillary and tubulocystic patterns favored FH-deficient RCC. The tubulopapillary pattern favored both CDCs and FH-deficient RCCs, and the multinodular infiltrating papillary pattern favored CDCs. Infiltrating glandular and solid sheets/cords/nested patterns were not statistically different among the 3 groups. Viral inclusion-like macronucleoli, considered as a hallmark of HLRCC-RCCs, were observed significantly more frequently in FH-deficient RCCs. Despite the overlapping morphology found among these clinically aggressive infiltrating high-grade adenocarcinomas of the kidney, reproducible differences in morphology emerged between these categories after rigorous characterization. Finally, we recommend that definitive diagnosis of CDC should only be made if RMC and FH-deficient RCC are excluded.
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PMID:Reappraisal of Morphologic Differences Between Renal Medullary Carcinoma, Collecting Duct Carcinoma, and Fumarate Hydratase-deficient Renal Cell Carcinoma. 2930