Progesterone increases mRNA levels of pituitary adenylate cyclase-activating polypeptide (PACAP) and type I PACAP receptor (PAC(1)) in the rat hypothalamus

Pituitary adenylate cyclase-activating polypeptide (PACAP) regulates pituitary hormone biosynthesis and secretion through its cognate receptors. PACAP also plays an important role in the regulation of ovarian steroid biosynthesis. If so, there might be a feedback regulation of hypothalamic PACAP synthesis by the pituitary and by ovarian steroids. In the present study, we used RNase protection assays to determine changes in mRNA levels of PACAP and type I PACAP receptor (PAC(1)) under the conditions of ovariectomy and replacement with ovarian steroids. Progesterone (P) alone or in combination with estradiol (E) induced significant increases in PACAP mRNA level in the medial basal hypothalamus (MBH) and PAC(1) mRNA levels in MBH and the preoptic area (POA). This finding suggests that feedback regulation takes place between the ovary and hypothalamic PACAP neurons. P is known to be a major regulatory feedback factor for hypothalamic luteinizing hormone-releasing hormone (LHRH) neurons, but P receptor is not present in these neurons. Therefore, we examined a possible involvement of PACAP in the feedback regulatory pathway of P to LHRH neurons. After an antisense PAC(1) oligodeoxynucleotide (ODN) was i.c.v.-injected into the third ventricle of E and P-treated rats, LHRH mRNA levels were determined. The ODN markedly decreased the P-induced increase in the LHRH mRNA level. Taken together, the present data suggest that PACAP may play a role as a mediator in the regulation of LHRH synthetic machinery by stimulatory feedback of P.     

Vascular endothelial growth factor gene polymorphisms and risk of primary lung cancer.

Angiogenesis is an essential process in the development, growth, and metastasis of malignant tumors including lung cancer. DNA sequence variations in the vascular endothelial growth factor (VEGF) gene may lead to altered VEGF production and/or activity, thereby causing interindividual differences in the susceptibility to lung cancer via their actions on the pathways of tumor angiogenesis. To test this hypothesis, we investigated the potential association between three VEGF polymorphisms (-460T > C, +405C > G, and 936C > T)/haplotypes and the risk of lung cancer in a Korean population. VEGF genotypes were determined in 432 lung cancer patients and 432 healthy controls that were frequency matched for age and sex. VEGF haplotypes were predicted using Bayesian algorithm in the phase program. Compared with the combined +405 CC and CG genotype, the +405 GG genotype found associated with a significantly decreased risk of small cell carcinoma [SCC; adjusted odds ratio (OR), 0.36; 95% confidence interval (95% CI), 0.17-0.78]. The 936 CT genotype and the combined 936 CT and TT genotype were also associated with a significantly decreased risk of SCC compared with the 936 CC genotype (adjusted OR, 0.47; 95% CI, 0.26-0.85 and adjusted OR, 0.44; 95% CI, 0.24-0.80, respectively). Haplotype CGT was associated with a significantly decreased risk of SCC (adjusted OR, 0.39; 95% CI, 0.18-0.87), whereas haplotype TCC conferred a significantly increased risk of SCC (adjusted OR, 1.63; 95% CI, 1.14-2.33). None of the VEGF polymorphisms studied significantly influenced the susceptibility to lung cancer except SCC. However, haplotypes TCT and TGT were significantly associated with the risk of overall lung cancer, respectively (adjusted OR, 0.38; 95% CI, 0.25-0.60 and adjusted OR, 3.94; 95% CI, 2.00-7.76, respectively). These effects of haplotypes TCT and TGT on lung cancer risk were observed in three major histologic types of lung cancer. These results suggest that the VEGF gene may be contribute to an inherited predisposition to lung cancer.     

A set of SNPs near or within STR regions useful for discriminating native Lake Biwa and introduced “Eurasian” strains of common carp

We present a set of nuclear DNA SNPs useful for discriminating native Lake Biwa and introduced ??Eurasian?? strains of common carp, and further, for detecting their hybridization. Such SNPs were searched around short tandem repeat (STR) regions to be used later as HapSTR markers. A total of 62 microsatellite locus were screened with PCR and direct sequencing. The resultant nucleotide sequences from typical Lake Biwa (n?=?30) and ??Eurasian?? (n?=?24) specimens indicated that a total of 21 SNPs distributed across 7 loci would be useful for the above-mentioned purpose. All of the SNPs can be genotyped by direct sequencing, simultaneously with STR polymorphisms.     

Malignant Hypertension with an Unusual Presentation Mimicking the Immune Mediated Pulmonary Renal Syndrome

A 27-year-old man presented at the emergency room with hemoptysis. His blood pressure was 180/100 mm Hg, and he had no history of hypertension. Chest radiographs showed bilateral infiltration, suggestive of alveolar hemorrhage. His laboratory data were consistent with acute kidney injury. His serum creatinine level increased abruptly; therefore, renal biopsy was performed. Steroid pulse therapy was administered because of a strong suspicion of immune-mediated pulmonary renal syndrome. Renal biopsy showed proliferative endarteritis, fibrinoid necrosis, and intraluminal thrombi in the vessels without crescent formation or necrotizing lesions. Steroid pulse therapy rapidly tapered and stopped. His serum creatinine level gradually decreased with strict blood pressure control. Ten months after discharge, his blood pressure was approximately 120/80 mm Hg with a serum creatinine level of 1.98 mg/dL. Pulmonary renal syndrome is generally caused by an immune-mediated mechanism. However, malignant hypertension accompanying renal insufficiency and heart dysfunction causing end-organ damage can create a pulmonary hemorrhage, similar to pulmonary renal syndrome caused by an immune-mediated mechanism. The present case shows that hypertension, a common disease, can possibly cause pulmonary renal syndrome, a rare condition.     

吸入伊洛前列素对初入高海拔地区青年血流动力学的影响

目的探讨雾化吸入伊洛前列素溶液对初入高海拔地区青年血流动力学的影响。方法将32名受试者随机分为伊洛前列素组(n=16)和对照组(n=16),自海拔1 400 m历时5 d进入5 200 m,从进入海拔5 200 m当天开始,伊洛前列素组4次/d雾化吸入伊洛前列素溶液,连续5 d。对照组用同样的方法吸入生理盐水。于吸入伊洛前列素溶液第5天,用XG-Ⅲ型血液循环功能自动测试仪检测两组受试者的血流动力学。结果伊洛前列素组较对照组P、TPR、ALT、η、BK、PAWP、CCP降低,差异有统计学意义(P<0.05);SV、MAP、BV增高,差异有统计学意义(P<0.05)。结论在高原雾化吸入伊洛前列素溶液对初入高海拔地区青年血流动力学有明显的改善作用。