Residues Val254, His256, and Phe259 of the angiotensin II AT1 receptor are not involved in ligand binding but participate in signal transduction

The role of the external third of helix VI of the angiotensin II (AII) AT1 receptor for the interaction with its ligand and for the subsequent signal transduction was investigated by individually replacing residues 252-256 by Ala, and residues 259 or 261 by Tyr, and permanently transfecting the resulting mutants to Chinese hamster ovary (CHO) cells. Binding experiments showed no great changes in affinity of any of the mutants for AII, [Sar1]-AII, or [Sar1, Leu8]-AII, but the affinity for the nonpeptide antagonist DuP753 was significantly decreased. The inositol phosphate response to AII was remarkably decreased in mutants V254A, H256A, and F259Y. These results indicate that AT1 residues Val254, His256, and Phe259 are not involved in ligand binding but participate in signal transduction. Based in these results and in others from the literature, it is suggested that, in addition to the His256 imidazole ring, the Phe259 aromatic ring interacts with the AII's Phe8, thus contributing to the signal-triggering mechanism.     

Cell-mediated cytotoxicity: a predictor of chronic rejection in pediatric HLA haploidentical renal transplants

BACKGROUND: Recipient antidonor cytotoxic T-cell activity has been associated with graft loss and acute rejection in renal allograft recipients. The role of immunologic mechanisms in the development of chronic graft rejection is controversial. We analyzed all living related renal transplants performed at Children's Hospital (Boston, MA) from 1983 to 1995 to assess whether cell-mediated cytotoxicity, determined in vitro and measured before transplantation, was predictive of chronic rejection. METHODS: Eighty-three patients were studied retrospectively. Fifty-seven patients with one haplotype-matched renal transplants from living related donors were studied to determine the association between cell-mediated lympholysis (CML) level, acute rejection, chronic rejection, and graft failure. Acute rejection was defined by the decision to treat. Chronic rejection was defined by histology and/or the absolute serum creatinine value using an increasing serum creatinine level >1.0 mg/dl for children less than 3, a creatinine level >1.5 mg/dl for children between 3 and 10 years of age, and a creatinine level >2.0 mg/dl for children above 10 years of age. Return to dialysis or retransplantation was considered graft failure. RESULTS: Of the 57 haploidentical patients, there were 33 males and 24 females. The mean age at transplant was 11.1 years (SD=6.7). Twelve patients developed chronic rejection, 24 patients developed acute rejection, and 7 patients had graft failure. Pretransplant cytotoxic T lymphocyte activity was associated with chronic rejection (P=0.001) and graft failure (P=0.013) but only marginally with acute rejection (P=0.058). Controlling for age and sex, Cox's proportional hazards model revealed that CML level was predictive of time to chronic rejection (P<0.01) but not acute rejection (P=0.11). It was estimated that every 1-unit increase in CML level raises the monthly risk of chronic rejection by 7%. Ten children received HLA-identical kidneys from their siblings. There were no episodes of chronic rejection after 5 years. Two patients with high CML levels had episodes of acute rejection; both patients responded to treatment. CONCLUSION: Our data demonstrate an association between pretransplant cell-mediated cytotoxicity and the occurrence of chronic rejection in living related one-haploidentical renal transplants in pediatric patients.     

Bilateral arachnoid cysts, seizures and severe encephalopathy: case report

A case is presented of a 3 1/2-year-old girl with a clinical picture of very severe psychomotor retardation, autistic behavior, and repetitive convulsive episodes starting in the neonatal period and resistant to any pharmacological treatment. Electroencephalography showed generalized abnormalities. Magnetic resonance imaging of the brain disclosed arachnoid cysts in both temporal fossae with marked hypoplasia of both temporal lobes. It is proposed that the severity of symptoms is related to the magnitude of underlying anatomical lesions as well as the associated intractable epilepsy.     

Prolongation and enhancement of postischemic c-fos expression after fasting

BACKGROUND AND PURPOSE: A rapid but transient expression of c-fos after cerebral ischemia has been extensively documented. However, the mechanism of this induction and whether induction of c-fos is neuroprotective or detrimental to the brain after ischemia is presently not clear. Fasting before transient cerebral ischemia has been shown to reduce delayed neuronal necrosis and infarct volume. The purpose of the present study was to examine the effect of preischemic fasting for 24 hours on the expression of c-fos after transient focal cerebral ischemia. METHODS: Focal cerebral ischemia was induced by temporary occlusion of the right middle cerebral artery and both common carotid arteries for 60 minutes. Male Long-Evans rats weighting 250 to 300 g were randomly divided into two groups: fed (control group) and food deprived for 24 hours (fasted group) before ischemic surgery. Infarct volumes were measured on the basis of triphenyltetrazolium chloride-delineated infarct areas, and plasma glucose levels were determined by the glucose oxidase method. Temporal and spatial expression of c-fos was assessed by Northern blot analysis, in situ hybridization, and immunohistochemistry. RESULTS: Fasting for 24 hours before 60 minutes of ischemia resulted in a 26.6% decrease in preischemic plasma glucose levels and a 74.5% reduction in infarct volumes in the fasted group compared with the control group. A rapid but transient induction of c-fos mRNA was observed in the ischemic cortex in control animals after 60 minutes of ischemia. Fasting not only prolonged but also enhanced the intensity of c-fos expression in the ischemic cortex. Regional c-fos expression was also different between these two groups. CONCLUSIONS: The results support the contention that c-fos expression may be compatible with its purported neuroprotective role in selected experimental paradigms. The signaling mechanisms underlying the effect of fasting and subsequent lowering of plasma glucose levels on postischemic c-fos expression remain to be explored.     

Chronic renal failure and its management and nephrolithiasis

Chronic renal failure (CRF) is the most common form of renal disease in dogs and cats. Although CRF occurs in dogs and cats of all ages, it is commonly considered a disease of older animals, and the incidence increases with age. This article presents guide-lines for the diagnosis and conservative management of chronic renal failure in dogs and cats. Nephrolithiasis is uncommon in dogs and cats, accounting for less than 3% of all urinary calculi. The mineral composition of the renolith is important in formulation of therapeutic and preventive management strategies. This article briefly reviews the epidemiology, diagnosis, and management of nephrolithiasis in the dog and cat.     

火电机组运行优化系统的现状与展望

简单回顾了国内外在火电机组运行优化领域的研究历程，列举了目前国内外市场上针对火电机组的各种主流运行优化产品的功能特点和应用情况，分析了国外引进产品和国内自主研发产品在中国当前市场环境下各自的优势和劣势。介绍了当前运行优化系统在国内电站机组的应用现状，阐述了国内外运行优化系统在实际应用中存在的问题，并提出了相应的改进意见。对机组运行优化系统的未来发展进行了展望，指出机组运行优化系统将利用先进技术设备和信息平台，与电站管理紧密结合，在日益规范的市场中不断发展完善，为提高电站经济性发挥更大的作用。     

双螺杆反应挤出模型的研究

详细研究了双螺杆中反应挤出聚合物的动力学模型、流动模型和传热模型。通过实验得到了双螺杆反应器中聚合物的停留时间分布及平均停留时间。     

小波变换应用于输电线路行波故障测距(Ⅱ)

在介绍了单端和双端行波故障测距原理的基础上，着重讨论了诸如母线，行波源，过渡电阻等因素对行波测距的影响，并在理论上对每种算法的测距误差进行了分析，最后根据小波变换模极大值理论实现了行波测距，大量仿真表明，本方法有效且有很高的测距精度。     

电容位移法精确测量磁性薄膜的磁致伸缩系数

介绍了一种精确测量磁性薄膜磁致伸缩系数方法－电容位移法，并自行研制组装了一套测量装置，通过误差分析，仪器的精确标定，对稀土－铁超磁致伸缩薄膜的磁致伸缩系数进行了测量，获得满意的结果。     

Neuropathology of bovine herpesvirus type 5 (BHV-5) meningo-encephalitis in a rabbit seizure model

CI-994 (acetyldinaline) is an orally active anticancer drug currently in Phase 1 clinical trials. To assess its preclinical toxicity, CI-994 was administered orally as suspensions to Wistar rats (10/sex/dose) and in capsules to beagle dogs (3/sex/dose) once daily for two weeks. Doses were 1.5, 5, and 15 mg/kg for rats (9, 30, and 90 mg/m2, respectively), and 0.5, 2, and 5 mg/kg for dogs (10, 40, and 100 mg/m2, respectively). Systemic exposure was dose-proportional based on toxicokinetic analysis in dogs. Severe clinical signs and mortality occurred at the highest dose in both species beginning on Day 10. Neutropenia, lymphocytopenia, thrombocytopenia, lymphoid depletion, bone marrow hypocellularity, and testicular degeneration were observed in both species, primarily at the mid- and high-doses. Despite continued treatment, neutrophil counts in dogs returned to control levels in Week 2. Other microscopic findings in rats included splenic hematopoietic depletion at all doses and epithelial cell necrosis in various tissues at 15 mg/kg. Additional bone marrow changes in dogs involved myeloid and megakaryocyte hyperplasia at 2 mg/kg and abnormal myeloid and megakaryocyte maturation at 2 and 5 mg/kg. Except for the testicular effects in both species, all changes were reversible within a 4-week (rat) or 9-week (dog) recovery period. The results of these studies show that target organ effects of CI-994 principally involve tissues with rapidly dividing cell populations and that bone marrow suppression is the dose-limiting toxicity. CI-994 also seems to interfere with the release and/or maturation of cells in the bone marrow.