Genetic variations of HSD11B2 in hypertensive patients and in the general population, six rare missense/frameshift mutations.

Mutations in the gene encoding 11beta-hydroxysteroid dehydrogenase type 2, HSD11B2, cause a rare monogenic juvenile hypertensive syndrome called apparent mineralocorticoid excess (AME). In AME, defective HSD11B2 enzyme activity results in overstimulation of the mineralocorticoid receptor (MR) by cortisol, causing sodium retention, hypokalemia, and salt-dependent hypertension. Here, we have studied whether genetic variations in HDS11B2 are implicated in essential hypertension in Japanese hypertensives and the general population. By sequencing the entire coding region and the promoter region of HDS11B2 in 953 Japanese hypertensives, we identified five missense mutations in 11 patients (L14F, n = 5; R74H, n = 1; R147H, n = 3; T156I, n = 1; R335H, n = 1) and one novel frameshift mutation (4884Gdel, n = 1) in a heterozygous state, in addition to 19 genetic variations. All genetic variations identified were rare, with minor allele frequencies less than 0.005. Four of 12 patients with the missense/frameshift mutations showed renal failure. Four missense mutations, L14F, R74H, R147H, and R335H, were successfully genotyped in the general population, with a sample size of 3,655 individuals (2,175 normotensives and 1,480 hypertensives). Mutations L14F, R74H, R147H, and R335H were identified in hypertensives (n = 6, 8, 3, and 0, respectively) and normotensives (n = 8, 12, 5, and 0, respectively) with a similar frequency, suggesting that these missense mutations may not strongly affect the etiology of essential hypertension. Since the allele frequency of all of the genetic variations identified in this study was rare, an association study was not conducted. Taken together, our results indicate that missense mutations in HSD11B2 do not substantially contribute to essential hypertension in Japanese.     

Reconstruction of the nasal tip including the columella and soft triangle using a mastoid composite graft.

This paper describes the use of a composite graft from the mastoid area consisting of full-thickness skin peripherally and selectively localised fascia-fat tissue underneath the skin centrally for immediate reconstruction of moderate defects of the nasal tip including the columella and soft triangle. Mastoid composite grafting is a simple and safe procedure that avoids partial graft loss and provides adequate augmentation of soft tissue, easy reshaping of the new nostril rim, minimal post-operative shrinkage, and no donor-site morbidity. Then, it results in a satisfactory nasal appearance with adequate tip projection and symmetry. This procedure may represent a preferred method of nasal tip reconstruction.     

Effect of leptin on the regulation of placental hormone secretion in cultured human placental cells.

Placenta is an important source of leptin during pregnancy that contributes to the high plasma leptin levels in pregnant women. Leptin and its functional receptors are synthesized in trophoblast cells that, in turn, secrete gestational hormones supporting a paracrine or autocrine role for leptin in the endocrine activity of the placenta. In the present study we examined the effect of leptin on in vitro release of gestational hormones (human chorionic gonadotropin (hCG), human placental lactogen (hPL), progesterone, estrogens and testosterone) by human term placental cells in culture. Placentas at term were obtained immediately after delivery from mothers with uncomplicated pregnancies. Progesterone, hCG, hPL, estradiol, estrone, estriol and testosterone levels were measured by different assays in culture media of cells maintained in monolayer culture after incubation for 12, 24, 48 or 72 h with leptin or placebo. Incubation with leptin did not modify hCG, hPL, progesterone, estriol and estrone secretion for any of the doses and times assayed. However, leptin led to a dose-dependent decrease in estradiol release. This effect was observed when treatment with recombinant human leptin spanned from 12 to 72 h. At this time an increase in testosterone levels was observed in leptin-treated cells versus placebo. These results indicate that leptin can be considered a gestational hormone implied in the endocrine function of the placenta, with an important role in control of the production of steroid reproductive hormones in placental cells in vitro.     

β-胡萝卜素立体异构体对环磷酰胺处理小鼠免疫功能的比较研究

就β-胡萝卜素立体异构体对环磷酰胺处理小鼠的免疫功能影响进行了比较研究。结果显示β-胡萝卜素立体异构体对外磷酰胺造成的免疫功能低下具有不同程度的改善作用，提高胸腺和脾脏指数，增强脾脏细胞对刀豆素A（ConA）的反应性和NK活性，血清溶菌酶含量也有所增加。综合各项指标，9-顺式和全反式混合物的作用最明显，提示一定浓度的9-顺式对于提高β-胡萝卜素对机体的总体作用是有一定意义的。     

Influence of the Compliance of the Pump Housing and Cannulas of a Paracorporeal Pneumatic Ventricular Assist Device on Transient Pressure Characteristics

Abstract: The dependence of transient pressure characteristics of a ventricular assist device (VAD) on the compliance of its housing and cannulas was investigated in a mock circulation. The peak rate of change of pressure ( dP/dt _max) values was greater in the cannulas than other compartments and was associated with valve closure-induced pressure oscillations. When cannula compliance was increased from 0.0057 to 0.0129 cm³/mm Hg, these values decreased by ˜20%, and outflow cannula pressure oscillation frequency decreased from 17.5 Hz by 35%. This trend was also apparent in the inflow. A VAD housing compliance increase from 0.0162 to 0.0483 cm³/mm Hg caused a dP/dt _max decrease of 30% in both the blood chamber and the outflow cannula. The effect of this change on the inflow was weaker implying that housing absorbs the energy associated with outflow deceleration more effectively than the inflow. These findings suggest that increasing VAD housing and cannulas compliance can improve hydrodynamic performance.     

Human interleukin 4 regulates the phenotype of lymphocytes generated during mixed lymphocyte culture and inhibits the IL-2-induced development of LAK function in normal and leukaemic cells

This study examined the immunoregulatory role of recombinant interleukin 4 (IL-4), also known as B-cell stimulating factor 1, on the generation of cytotoxic effector cells from normal and leukaemic human blood mononuclear cells. When tested on cells from normal individuals, the addition of IL-4 to mixed lymphocyte cultures led to a dose-dependent proliferation of T-helper cells (CD3, 4 positive) with a concomitant decrease in phenotypic and functional cytotoxic T cells and natural killer (NK) cells. IL-4 also inhibited the interleukin-2 (IL-2)-induced generation of lymphokine-activated killer (LAK) activity when added at the beginning of mixed lymphocyte culture. When tested on mature leukaemic NK cells, IL-4 also inhibited the ability of IL-2 to induce LAK function using a short-term culture system. These results show that IL-4 acts on both normal and leukaemic cells and suggests that it acts at more than one level during the development of LAK function.     

No impact of repeated endoscopic screens on gastric cancer mortality in a prospectively followed Chinese population at high risk.

BACKGROUND: Gastric cancer (GC) is the leading cause of cancer deaths in China. Our study prospectively evaluated the impact of repeated endoscopic screens on GC mortality in a high-risk population in China. METHODS: Between 1989 and 1999, a population-based gastroscopic screening was conducted in 4,394 residents of Linqu County, China, a region with the highest rates of GC worldwide. Residents ages 35 to 64 years received initial gastroscopies with biopsies in 1989. Repeated endoscopies were performed in 1994 and 1999. Cancer occurrences and deaths were actively monitored throughout the entire period until July 2000. Mortality from GC was compared with expected values based on mortality rates obtained for Linqu in the 1990-1992 Chinese Cancer Mortality Survey. RESULTS: Between March 1989 and July 2000, 39,303 person-years were accumulated; 85 new GCs occurred, 29 (34.5%) were in early stage. Fifty-eight cases (68%) were identified at one of the screens. The number of observed deaths from GC (37) was close to the expected (36.8). The standardized mortality ratio was 1.01 (95% CI 0.72-1.37) for the entire cohort, 1.13 (95% CI 0.77-1.57) for males, and 0.65 (95% CI 0.26-1.32) for females. CONCLUSIONS: Despite high population coverage with repeated screens, no reduction in GC mortality was observed in this high-risk population in China.     

神经外科麻醉对体感诱发电位的影响

目的探讨神经外科手术麻醉对体感诱发电位（SEP）的影响,以期为麻醉和手术处理提供依据。方法随机抽取我科17例全麻手术病人,分成颅内疾病手术组（A组）与脊柱、脊髓疾病手术组（B组）,于术前、麻醉（诱导完成）、术始、术中、术毕和术后6个时程连续监测SEP的潜伏期、波幅及波形并记录。结果麻醉后SEP潜伏期延长5.96%,波幅下降24.00%,未出现波形消失的情况。结论麻醉抑制SEP,表现为潜伏期延长和波幅下降,但未出现波形消失的情况。     

甲睾酮对小鼠生殖系统发育及生精功能的影响

目的 探讨甲睾酮对雄性小鼠精子的产生及生殖器官的影响.方法 将48只昆明小白鼠随机分为4组,每组12只,每天分别向各组灌胃甲睾酮16 mg/kg,32 mg/kg,64 mg/kg 和等量蒸馏水(对照组),连续10 d.结果 与对照组比较,甲睾酮16 mg/kg组精子活率最高为66.22%(P<0.05);甲睾酮64mg/kg组睾丸指数、精子畸形率、精子密度都极显著和显著地升高(P<0.01和P<0.05),且睾丸组织有较明显的病理学损伤.结论 适量甲睾酮能提高精子活率,大剂量使精子活率降低且畸形率升高.     

乡镇疾病预防控制体制与工作模式探讨

为了解湖州市乡镇疾病预防控制工作现状，探讨新型乡镇疾病预防体制与工作模式，我们对全市乡镇卫生院疾病预防控制工作进行了调查研究。