RENAL FUNCTION IN CHRONICALLY CATHETERIZED CONSCIOUS DIABETIC RATS USING CONSTANT AND SERVO-CONTROLLED INFUSION

1. Infusion experiments were performed on chronically catheterized conscious rats to assess kidney function before and after the induction of diabetes mellitus with streptozotocin. 2. Two infusion regimens were used, a conventional constant-infusion protocol and a novel computer-driven, servo-controlled fluid replacement technique. The latter enables body fluid status to be maintained throughout a study occasion by servo-controlled replacement of spontaneous urinary fluid losses. 3. The chronically catheterized conscious rat infused using a servo-controlled system appears to be the optimum model for a study of diabetic renal function. The conscious preparation circumvents problems associated with anaesthesia and acute surgery. The servo-controlled infusion protocol maintains the altered fluid status of the diabetic condition. Both hyperfiltration and polyuria, characteristics of human diabetes often absent in anaesthetized and/or constantly infused diabetic rats, were seen in all conscious servo-controlled diabetic animals. 4. The new regimen enables a more accurate assessment of renal function in experimental diabetes than with previous protocols. It should prove useful in future studies, particularly those assessing the role of anti-diabetic drugs on the kidney.     

Unexplained diarrhoea and failure to thrive in 2 siblings with unusual facies and abnormal scalp hair shafts: a new syndrome

A family is described in which 2 siblings born to healthy parents presented with abnormal facies, persistent diarrhoea, and early death. Exhaustive pathological and biochemical investigations failed to find a cause. The scalp hair of both babies had an abnormal amino-acid composition, and presented an appearance that was unique on scanning electron microscopical examination; this fact and the clinical picture probably represents a new syndrome.     

Modulation of implantation-associated integrin expression but not uteroglobin by steroid hormones in an endometrial cell line

In order to test the hypothesis that integrin and uteroglobin (UG) expression in cultured endometrial cells are affected by hormone treatment, Ishikawa-CH endometrial cancer cells were cultured and exposed to oestradiol or oestradiol and progesterone regimens and assayed using immunohistochemistry. We evaluated the intensity of immunohistochemical staining for the integrin monomers alpha(v) and beta1, the dimers alpha(v)beta3 and alpha(v)beta6, and for the secretory protein uteroglobin under various experimental conditions. Cells grown in control media stained positively for the integrin monomers alpha(v) and beta1, the dimer alpha(v)beta3, and for UG. Oestradiol and sequential oestradiol/progesterone reversibly suppressed staining for the dimer alpha(v)beta3. Hormone treatment had no effect on the staining of the beta1 and alpha(v) monomers or UG. The alpha(v)beta6 dimer antibody did not stain under any experimental treatment conditions. These data indicate that expression of the integrin complex alpha(v)beta3 is reversibly suppressed by oestradiol in Ishikawa cells and that these cells may be a good model for studying hormone-driven molecular changes in endometrium.      

Influence of clinical status on the association between plasma total and unbound bilirubin and death or adverse neurodevelopmental outcomes in extremely low birth weight infants

Objectives: To assess the influence of clinical status on the association between total plasma bilirubin and unbound bilirubin on death or adverse neurodevelopmental outcomes at 18–22 months corrected age in extremely low birth weight infants. Method: Total plasma bilirubin and unbound bilirubin were measured in 1101 extremely low birth weight infants at 5 ± 1 days of age. Clinical criteria were used to classify infants as clinically stable or unstable. Survivors were examined at 18–22 months corrected age by certified examiners. Outcome variables were death or neurodevelopmental impairment, death or cerebral palsy, death or hearing loss, and death prior to follow‐up. For all outcomes, the interaction between bilirubin variables and clinical status was assessed in logistic regression analyses adjusted for multiple risk factors. Results: Regardless of clinical status, an increasing level of unbound bilirubin was associated with higher rates of death or neurodevelopmental impairment, death or cerebral palsy, death or hearing loss and death before follow‐up. Total plasma bilirubin values were directly associated with death or neurodevelopmental impairment, death or cerebral palsy, death or hearing loss, and death before follow‐up in unstable infants, but not in stable infants. An inverse association between total plasma bilirubin and death or cerebral palsy was found in stable infants. Conclusions: In extremely low birth weight infants, clinical status at 5 days of age affects the association between total plasma bilirubin and death or adverse neurodevelopmental outcomes at 18–22 months of corrected age. An increasing level of UB is associated a higher risk of death or adverse neurodevelopmental outcomes regardless of clinical status. Increasing levels of total plasma bilirubin are directly associated with increasing risk of death or adverse neurodevelopmental outcomes in unstable, but not in stable infants.     

Alaska Native Cancer epidemiology in the Arctic

Cancer incidence and its possible relation to environmental contaminants, including radiation, continues to be a perceived health threat for the arctic-dwelling Alaska Native (Inupiat Eskimo) people despite the lack of a direct link to high-dose exposure. To better understand this concern, all known malignancies diagnosed in this population (n = 177) in three consecutive eight-year periods (1971–1994) were evaluated.The most recent average incidence rate (age-adjusted to world standard population) of 315 per 100 000 (95% confidence interval, CI = 248–382) represents a 33% surge (albeit non-significant) in Alaska Native cancer incidence over the initial period studied. The male rate 366 (95% CI = 266–466) for the same period exceeds the female rate 258 (95% CI = 169–347) by 42%. Two patterns of cancer incidence are seen at the village level. One, a 24 y upward trend found in the villages of Barrow, Point Hope and Kaktovik (combined rate of increase significant [P = 0.047]) associated with lung cancer; and the other, a stable trend over the past 16 y, associated with colon and rectal cancer. Lung cancer is the predominant cancer by site and is primarily a male disease. The recent male lung cancer incidence rate of 137 (95% CI = 73–201) exceeds the female rate by greater than five times. Total lung cancer cases are primarily confined to four villages where the incidence significantly (P = 0.0043) exceeds the remaining population. The major female cancers are colon/rectal and breast with cancer of the cervix virtually eliminated. Breast cancer is found primarily in two villages where its excess is significant (P = 0.025).Inupiat Eskimo cancer epidemiology is unique, differing from both the Alaska Native and other Circumpolar populations. At present, this uniqueness cannot be explained by an overt environmental contaminant exposure. Although tobacco very likely plays a central role, it by itself cannot fully explain the extremely high male lung cancer rate and why only specific villages are affected. Genetic predisposition and environmental factors may play a synergistic role as cofactors. A cooperative investigative effort with the Inupiat population is indicated and may go a long way in reducing cancer concern in the region.     

荧光原位杂交技术分析人结肠菌群方法研究

建立荧光原位杂交技术分析人体内结肠菌群的方法。取受试者新鲜粪便 ,选用 5种特异性的 16SrRNA寡核苷酸探针 ,检测粪便样本收集后的保存时间、温度 ,离心条件及样本固定液存放时间对杂交计数结果的影响。结果建立最佳实验条件为 :粪便样本收集后应尽快在 4℃下保存 ,放置时间不要超过 12小时即作处理 ;样本的适宜离心条件为 70 0g 2分钟 ;样本用多聚甲醛固定后在 - 80℃下存放时间不要超过 5个月。该方法具有较好的稳定性 ,可以有效地检出个体之间结肠菌群的差异。     

CYP1B1基因敲除对成年小鼠肝脏脂肪代谢的影响及可能机制

目的探讨CYP1B1对高脂膳食诱导的成年小鼠脂肪代谢的作用。方法 CYP1B1基因敲除(KO)和野生型(WT)雄性成年C57/BL小鼠(6 w龄)各16只,给予低脂(LFD,30%)、高脂肪(HFD,60%)饲料共6 w。小鼠处死后取血清、附睾脂肪和肝脏组织检测相应的生化和分子生物学指标。结果 6 w高脂膳食后,KO小鼠能量摄入总量稍高于WT小鼠,但其体重增量和附睾脂肪组织重量均显著低于WT小鼠;WT小鼠脂肪细胞直径明显大于KO小鼠,且血糖、血清及肝脏组织中甘油三酯(TG)水平亦明显高于KO小鼠;肝脏组织RT-PCR结果显示,CYP1B1基因敲除后,启动脂肪形成的核因子及脂肪合成相关基因如CD36、SREBP1c、SCD1等表达下降,而调控脂肪氧化分解的基因如CPT-1α,UCP-2表达显著上升;蛋白印迹结果显示,CYP1B1基因敲除增强腺苷-磷酸激酶(AMPK)的磷酸化。结论 CYP1B1基因敲除对成年小鼠营养性肥胖的保护作用可能与AMPK磷酸化增强并调控肝脏中脂肪代谢相关基因的表达有关。