Gene/Protein Disease Symptom Drug Enzyme Compound
Pivot Concepts:   Target Concepts:
Query: UMLS:C0038002 (splenomegaly)
 9,873 document(s) hit in 31,850,051 MEDLINE articles (0.00 seconds)

Overall, the results of the analysis of 12 studies of VC production and polymerization workers demonstrate an enormously elevated risk of liver malignancies, the possibility of a twofold increased risk of brain and central nervous system tumors and perhaps, also, of malignancies of the lymphatic and hematopoietic system. However, the role of other agents cannot be excluded in the etiology of nonhepatic malignancies. Bronchogenic carcinoma does not appear to be increased from exposures to VC monomer, although a relationship to PVC dust was suggested in one study. These conclusions must be considered in light of limited data on workers followed more than 25 years from onset of exposure. Considering the numbers of observed and expected deaths in all studies, it would appear that the excess of malignancies at nonhepatic sites is less than the excess of liver tumors. Data presented elsewhere in this volume (Nicholson and Henneberger, 1983) suggest that exposure reductions in 1974 may have virtually eliminated the VC-associated risk of liver cancer if the current U.S. standard is met. To the extent that VC exposure is associated with other cancers, a similar risk reduction would be expected. Raynaud's phenomenon, acroosteolysis, scleroderma-like skin lesions, hepato- and splenomegaly with noncirrhotic hepatic fibrosis, and severe portal hypertension have been associated with past heavy exposures to VC. Evidence exists that the liver disease and portal hypertension may progress following cessation of exposure. However, all of the above syndromes were found largely in heavily exposed individuals. Their occurrence would be much less likely in workers exposed only to concentrations currently allowed. Pulmonary deficits, X-ray abnormalities, and, perhaps, lung cancer have been associated with VC/PVC exposure. Because of the possible contribution of PVC dust to these findings, engineering controls during polymer drying, bagging and usage are warranted.
 ...
PMID:Occupational hazards in the VC-PVC industry. 671 69

Hajdu-Cheney syndrome is an autosomal dominant disorder of acroosteolysis, skull deformities, characteristic facial abnormalities, osteoporosis, joint laxity, early loss of teeth, hearing loss, and a hoarse voice. We report on an 8 1/2-year-old boy with Hajdu-Cheney syndrome and cystic kidney disease, congenital heart disease, hydrocephalus, cleft lip and palate, hydrosyringomyelia, club feet, splenomegaly, hypospadias, vertebral anomalies, and upper airway obstruction. A review of 44 patients did not uncover any other patients with all of these manifestations, nor any patient with upper airway obstruction. Hajdu-Cheney syndrome appears to encompass a broader phenotype than previously recognized. The documentation of these additional anomalies is valuable because the findings of acroosteolysis and osteoporosis can present later in the course.
 ...
PMID:Severe Hajdu-Cheney syndrome with upper airway obstruction. 918 63

Notch receptors play a central role in skeletal development and homeostasis. Hajdu Cheney Syndrome (HCS) is a rare disease associated with mutations of NOTCH2 that lead to the translation of a truncated, presumably stable, NOTCH2 protein. As a consequence, a gain-of-NOTCH2 function is manifested. We report a subject presenting with HCS and her child, both harboring a new heterozygous mutation in Exon 34 of NOTCH2 upstream of the PEST domain. The subject presented with osteoporosis, fractures, acroosteolysis and splenomegaly but did not have neurological complications, cardiovascular defects or polycystic kidneys. Sequencing of genomic DNA revealed a previously unreported mutation at nucleotide 6667C>T leading to a Gln2223Ter protein product in the subject and her son. Preclinical studies have demonstrated that the bone loss in HCS is secondary to enhanced osteoclastogenesis and bone resorption, and the same mechanism may operate in humans. Accordingly, the case we report was treated and responded to therapy with denosumab with an increase in bone mineral density (BMD). However, acroosteolysis progressed and was not modified by denosumab. In conclusion, we report a case of HCS associated with a novel mutation in NOTCH2 and its response to denosumab on BMD.
 ...
PMID:Hajdu Cheney Syndrome; report of a novel NOTCH2 mutation and treatment with denosumab. 2841 Nov 9