Clinical and molecular genetic analysis for 7 patients from 5 pedigrees with 17a-hydroxylase/17, 20 lyase deficiency / 中华医学遗传学杂志

<p><b>OBJECTIVE</b>To investigate the clinical and genetic characteristics of 7 patients from 5 families with 17a-hydroxylase/17,20 lyase deficiency (17OHD) and the CYP17A1 mutation in Chinese.</p><p><b>METHODS</b>Clinical features and laboratory data were collected from 5 families with 17OHD. PCR direct sequencing was performed to screen the mutation of CYP17A1 gene of the patients. Polymerase chain reaction-restriction fragment length polymorphism(PCR-RFLP) and sequencing were performed to screen the mutations of CYP17A1 gene in 288 healthy individuals from Shandong province.</p><p><b>RESULTS</b>Seven patients (5 of them were 46,XX; 2 were 46,XY) had typical clinical presentation of sexual infantilism, hypertension and hypokalemia. Hormone profile indicated decreased plasma cortisol and sex hormones, and elevated blood adrenocorticotrophic hormone (ACTH). TAC329AA and H373L in exon 6 and D487_F489del in exon 8 were identified from the patients. One heterozygote for D487_F489del was identified in 288 healthy controls.</p><p><b>CONCLUSION</b>The TAC329AA and D487_F489del of the CYP17A1 gene were the most frequent mutations in Chinese with 17OHD.There might be certain frequency of heterozygotes for D487_F489del in Chinese population.</p>

Inhibitory effect of 5-aza-2'-deoxycytidine on human gastric cancer xenografts in nude mice / 上海第二医科大学学报

Objective To observe the effect of 5-aza-2'-deoxycytidine(5-aza-CdR)on the normal epithelial specific-1 gene(NES1)and the growth of human gastric cancer xenografts in nude mice,and to explore the possible anti-tumor mechanisms and search for new treatment for gastric cancer.Methods Human gastric caner xenograft model in nude mice was established and treated with 5-aza-CdR.The growth of xenografts in nude mice was observed,and the status of methylation and protein expression of NES1 gene were detected by MSP and immunohistochemistry respectirely.Results After treatment with 5-aza-CdR,the growth of the xenografts in nude mice was greatly inhibited(P

Metabolic Characteristics of Insulin Secretion and Insulin Sensitivity in Isolated Postchallenge Hyperglycemia / 上海第二医科大学学报

Objective To evaluate the metabolic characteristics of insulin secretion and insulin sensitivity in isolated postchallenge hyperglycemia(IPH) and to clarify the factors responsible for the development of IPH. Methods(Eight hundred) and fifty subjects were classified into the following three groups based on the results of a 75-g oral glucose tolerance test(OGTT): normal glucose tolerance(NGT),n=557;isolated impaired glucose tolerance(iIGT),n=146;and IPH,n=147.Insulin secretion(insulinogenic index) and insulin sensitivity(insulin sensitivity index) were identified in the three groups. Results From NGT to iIGT and IPH in these subjects,the insulinogenic index and insulin sensitivity index were gradually decreased(P

Role and mechanism of rosiglitazone on the impairment of insulin secretion induced by free fatty acids on isolated rat islets / 中华医学杂志(英文版)

<p><b>BACKGROUND</b>Prolonged exposure of pancreatic beta-cells to fatty acids increases basal insulin secretion but inhibits glucose-stimulated insulin secretion. Rosiglitazone is a new antidiabetic agent of the thiazolidinediones. However, the relationship between thiazolidinediones and insulin secretion is highly controversial. The aim of this study is to explore the effect and mechanism of rosiglitazone on insulin secretion of islets under chronic exposure to free fatty acids (FFA).</p><p><b>METHODS</b>Pancreatic islets were isolated from the pancreata of male Sprague-Dawley rats by the collagenase digestion and by the dextran gradient centrifugation method. The purified islets were cultured in the presence or absence of rosiglitazone and palmitate for 48 hours. The insulin secretion was measured by radioimmunoassay. The mRNA level of peroxisome proliferator-activated receptor gamma, uncoupling protein 2 (UCP-2) and insulin were determined by real-time polymerase chain reaction (PCR). The cell cytotoxicity assay was measured by cell counting kit-8.</p><p><b>RESULTS</b>Islets exposed to elevated palmitate for 48 hours showed an increased basal and a decreased glucose-stimulated insulin secretion (P < 0.01). The mRNA level of UCP-2 was increased by 3.7 fold in the 0.5 mmol/L concentration of palmitate. When islets were cultured with palmitate (0.5 mmol/L) in the presence of rosiglitazone (1.0 micromol/L), both basal and glucose-stimulated insulin secretion reversed to a pattern of control islets (P < 0.05, P < 0.01). The addition of rosiglitazone in the culture medium decreased the mRNA level of UCP-2 by 2.2 fold, having a statistically significant difference (P < 0.05) as compared with islets cultured with palmitate alone. The cell viability was not affected.</p><p><b>CONCLUSION</b>The protective effects of rosiglitazone on insulin secretion of isolated pancreatic islets under chronic exposure to palmitate might be mediated through the downregulation of UCP-2 expression.</p>