CONTEXT: Hyperplasia of @entity3243 in @entity1 with @entity177 is classified into diffuse (DH) and nodular ( @entity5155 ) types, and @entity5155 is often refractory to routine medical therapy. OBJECTIVE: Although it is considered that the parenchymal cells initially proliferate diffusely and then some of them are transformed to form nodules consisting of monoclonal cells, the underlying molecular mechanism for such a transformation is not fully understood. In this study we tried to identify the genes that are up-regulated in @entity5155 . DESIGN AND SETTING: The cDNA population prepared from DH was subtracted from that prepared from @entity5155 by a PCR-based cDNA subtraction method. The resultant cDNAs were cloned and sequenced. To confirm the up-regulation of the identified genes, a total of 35 @entity3243 (18 DH, 16 @entity5155 , and one mixed) obtained from 21 @entity1 were analyzed. RESULTS: One of the nuclear genes identified was the @entity15144 gene, which encodes type Ialpha regulatory subunit (RIalpha) of @entity268 -dependent protein kinase (PKA). Immunohistochemical analysis demonstrated that RIalpha was abundantly expressed in the nodular region, whereas the adjacent diffuse region displayed relatively low expression. Northern and Western blot analyses demonstrated up-regulation of RIalpha expression in most @entity5155 tested. Determination of PKA activities revealed that free PKA activities measured in the absence of @entity268 in the assay were inversely correlated with RIalpha expression, indicating the functional significance of RIalpha up-regulation. CONCLUSIONS: These results suggest that the aberrant expression of RIalpha is involved in the diffuse to nodular transformation of @entity1373 of @entity3243 by impairing @entity268 /PKA signal transduction.

Up-regulation of the gene encoding protein kinase A type I alpha regulatory subunit in nodular hyperplasia of @entity3243 in @entity1 with XXXX .

@entity1 :: ('9606', 'Species') :: ['patients'] @entity268 :: ('CHEBI:17489', 'Chemical') :: ['cAMP'] @entity1373 :: ('MESH:D006965', 'Disease') :: ['hyperplasia'] @entity5155 :: ('MESH:C536394', 'Disease') :: ['NH'] @entity177 :: ('MESH:D051437', 'Disease') :: ['chronic renal failure'] @entity15144 :: ('5573', 'Gene') :: ['PRKAR1A'] @entity3243 :: ('MESH:D010282', 'Disease') :: ['parathyroid glands']
@entity177 :: (MESH:D051437,Disease) :: ['chronic renal failure']
