To elucidate the molecular basis for endocrine tumorigenesis, ras mutations in human endocrine tumors were analyzed using polymerase chain reaction‐single strand conformation polymorphism (PCR‐SSCP) analysis. Mutations of the H‐, K‐, N‐ras genes were examined in genomic DNAs from 169 successfully amplified primary endocrine tumors out of 189 samples. Four out of 24 thyroid follicular adenomas analyzed contained mutated N‐ras codon 61, and one contained the mutated H‐ras codon 61. One of the 19 pheochromocytomas revealed mutation of the H‐ras codon 13. No mutations of the ras gene were detected in pituitary adenomas, parathyroid tumors, thyroid cancers, endocrine pancreatic tumors, and adrenocortical tumors. Based on these findings we conclude that activation of the ras gene may play a role in the tumorigenesis of a limited number of thyroid follicular adenomas and pheochromocytomas, and that mutation of the ras gene is not frequent in other human endocrine tumors.

Background. The Gs alpha (Gsα) gene can be activated to the putative oncogene gsp by specific point mutations at codons 201 or 227. Such mutations have been reported in growth hormone (GH)‐secreting pituitary adenomas and thyroid tumors. To clarify the role of Gsα gene in human endocrine tumors, 197 tumors were screened for point mutations at codons 201 or 227 of the Gsα gene. Methods. Mutations were detected by primer‐introduced restriction analysis (PIRA) of the polymerase chain reaction (PCR) product of genomic DNA. Results. These Gsα mutations were present in 4 of 53 pituitary adenomas (4 of 43 GH‐secreting adenomas; 1 of these 4 was a GH‐ and prolactin‐secreting adenoma from a patient with familial multiple endocrine neoplasia Type 1), 4 of 66 thyroid tumors (4 of 30 papillary carcinomas), and 1 of 19 adrenocortical adenomas (1 of 6 aldosterone‐secreting adenomas). In contrast, none of these Gsα mutations were detected in parathyroid tumors, endocrine pancreatic tumors, or pheochromocytomas. Conclusions. Gsα mutations at these two loci may play a role in the pathogenesis of a small population of GH‐secreting pituitary adenomas, papillary thyroid carcinomas, and adrenocortical adenomas, but that they are not involved in the pathogenesis of other types of endocrine tumors.

The sulfated flavonoids in Polygonum hydropiper showed potent inhibiton against lens aldose reductase. Among these flavonoids isorhamnetin 3,7-disulfate (5) was most potent. Kinetic analysis showed that 5 exhibited noncompetitive inhibition against both dl-glyceraldehyde and NADPH.

Dihydroflavonol taxifolin and its glycoside, astilbin, from Engelhardtia chrysolepis inhibited rat lens and recombinant human aldose reductase. Taxifolin also inhibited sorbitol accumulation in human red blood cells. Furthermore, this dihydroflavonol aglycone maintained the clarity of rat lens incubated with a high concentration of glucose. These dihydroflavonols may be effective for preventing osmotic stress in hyperglycemia.