Reduction of growth hormone secretion following clomiphene administration

Serial plasma growth hormone (GH) concentrations were measured every 20 min for 24 hr before and after the administration of clomiphene citrate (100 mg/day for 7 days) to four healthy young adult male subjects. The number of GH secretory episodes and the magnitude of the peak plasma concentrations during both wakefulness and sleep were decreased after the clomiphene treatment periods.     

小檗胺对人慢性粒细胞白血病细胞发生凋亡的诱导机制研究

目的 研究新型p210 bcr/abl抑制剂小檗胺诱导人慢性粒细胞白血病细胞凋亡分子的机制.方法 培养表达内源性p210 bcr/abl蛋白的Ph＋人慢性粒细胞白血病细胞系K562,用小檗胺按指定时间和剂量干预细胞.应用膜联蛋白荧光素（Annexin-V-Fluos）/碘化丙啶（propidium iodide,PI）试剂盒和流式细胞术定量分析凋亡细胞百分比;用cytoperm/cytofix和天冬氨酸特异的半胱氨酸蛋白水解酶-3-McAb-PE定量检测含活化天冬氨酸特异的半胱氨酸蛋白水解酶-3（Caspase-3）细胞百分比;以免疫共沉淀技术（c-abl抗体）和Western印迹[p-Tyr（pY99）抗体]定量分析p210 bcr/abl蛋白磷酸化;p210 bcr/abl蛋白总量直接用Western印迹（c-abl抗体）检测;Hsp90和Hsp70等分子伴侣蛋白水平的变化用Western印迹（Hsp90和Hsp70抗体）.结果 48 h IC50浓度小檗胺（8μg/ml）作用48 h后,45.69% K562白血病细胞表达活化的Caspase-3凋亡分子和48.43%白血病细胞发生凋亡.免疫印迹和免疫共沉淀结果显示,低剂量小檗胺可明显抑制白血病细胞内p210 bcr/abl磷酸化：8μg/ml浓度小檗胺处理6 h后,白血病细胞磷酸化p210 bcr/abl蛋白含量仅为对照组的8.41%,而p210 bcr/abl蛋白总量并无变化.小檗胺还能直接下调p210 bcr/abl分子伴侣Hsp90蛋白水平：白血病细胞经8μg/ml浓度小檗胺处理24h时的Hsp90水平只有对照组的18.37%,而且对能诱导白血病细胞产生凋亡抵抗的Hsp70蛋白水平影响不明显.结论 （1）小檗胺是一种新型p210 bcr/abl蛋白磷酸化抑制剂,能通过抑制p210 bcr/abl蛋白磷酸化和诱导Caspase-3通路介导的Ph＋白血病细胞发生凋亡;（2）与已知Hsp90抑制剂格尔德霉素（GA）不同,小檗胺能直接下调Hsp90蛋白水平,而对与肿瘤细胞凋亡抵抗有关的Hsp70蛋白表达影响不大,这提示小檗胺可能还是一种新型蛋白分子伴侣Hsp90抑制剂,值得进一步研究.     

The effect of modeling and selective attention on pain tolerance

The present study assessed the separate and combined effects of selective attention and modeling on college student's tolerance for pain as measured by a cold pressor test (duration of keeping the hand in ice water). There were four treatment groups: selective attention (A), modeling (M), selective attention and modeling combined (AM), and selective attention plus modeling with cognitions (AMC). In addition, there were three control groups: no treatment (C), experimenter demand (D), and expectancy (E). Using pre-test to post-test difference scores, the four treatment conditions generally produced more pain tolerance than the control conditions, with the possible exception of the E group. The AMC group resulted in the greatest increase in pain tolerance but it was not significantly greater than the M group. There were no differences between the seven groups in their ratings of discomfort following the cold pressor test.     

Differentiation of transient hyperammonemia of the newborn and urea cycle enzyme defects by clinical presentation

We reviewed clinical data in 33 patients with transient hyperammonemia of the newborn (THAN): six previously unreported cases and 27 from the literature. Thirteen neonates with urea cycle enzyme deficiencies (UCED) served for comparison. No differences were found in the incidence of perinatal complications, route of delivery, Apgar scores, sex, or incidence or time of onset of seizures. On the other hand, neonates with THAN had significantly lower birth weights (mean +/- SEM 2282 +/- 78 gm vs 3336 +/- 222 gm, P less than 0.001) and gestational ages (35.1 +/- 0.5 weeks vs 39.6 +/- 0.5 weeks, P less than 0.001). Mean time of onset of respiratory distress (3.9 +/- 1.4 hours vs 71.5 +/- 26.1 hours, P less than 0.001), ventilatory support (P less than 0.001), lethargy (P less than 0.005), and coma (P less than 0.005) occurred earlier in THAN. Distinctive laboratory findings in patients with THAN included abnormal chest radiographic findings and plasma ammonium concentrations that were higher (1871 +/- 209 microM vs 973 +/- 169 microM, P less than 0.02) at an earlier age. Respiratory distress occurred in all but one patient with THAN before 24 hours; in contrast, only 62% of infants with UCED had respiratory symptoms, and none before 30 hours. In this retrospective study, the clinical presentation alone differentiated THAN from UCED.     

The effect of continuous normalization of serum hemolytic complement on the course of lupus nephritis: A five year prospective study

We have completed a five year prospective study of the effect of continuous normalization of serum hemolytic complement (CH₅₀) in 25 patients with lupus nephritis. At the end of five years 22 patients were being actively followed; 13 in a CH₅₀ controlled group and nine in a CH₅₀ uncontrolled group. Serial renal biopsy specimens were obtained from 19 patients. The results demonstrate a trend toward stabilization of renal histology, creatinine clearance and serum creatinine at a lower final mean dose of prednisone in the complement controlled group.     

Survival of chronic hypercapnic COPD patients is predicted by smoking habits, comorbidity, and hypoxemia

STUDY OBJECTIVES: Chronic hypercapnia in patients with COPD has been associated with a poor prognosis. We hypothesized that, within this group of chronic hypercapnic COPD patients, factors that could mediate this hypercapnia, such as decreased maximum inspiratory mouth pressure (P(I(max))), decreased maximum expiratory mouth pressure (P(E(max))), and low hypercapnic ventilatory response (HCVR), could be related to survival. Other parameters, such as arterial blood gas values, airway obstruction (FEV1), body mass index (BMI), current smoking status, and the presence of comorbidity were studied as well. METHODS: A cohort of 47 chronic hypercapnic COPD patients recruited for short-term trials (1 to 3 weeks) in our institute was followed up for 3.8 years on average. Survival was analyzed using a Cox proportional hazards model. The risk factors considered were analyzed, optimally adjusted for age and gender. RESULTS: At the time of analysis 18 patients (10 male) were deceased. After adjusting for age and gender, P(I(max)), P(E(max)), and HCVR were not correlated with survival within this hypercapnic group. Current smoking (hazard ratio [HR], 7.0; 95% confidence interval [CI], 1.4 to 35.3) and the presence of comorbidity (HR, 5.5; 95% CI, 1.7 to 18.7) were associated with increased mortality. A higher Pa(O2) affected survival positively (HR, 0.6 per 5 mm Hg; 95% CI, 0.4 to 1.0). Pa(CO2) tended to be lower in survivors, but this did not reach statistical significance (HR, 2.0 per 5 mm Hg; 95% CI, 0.9 to 4.3). FEV1 and BMI were not significantly related with survival in hypercapnic COPD patients. CONCLUSION: In patients with chronic hypercapnia, only smoking status, the presence of comorbidity, and Pa(O2) level are significantly associated with survival. Airway obstruction, age, and BMI are known to be predictors of survival in COPD patients in general. However, these parameters do not seem to significantly affect survival once chronic hypercapnia has developed.