Expression of the polycystin-1 C-terminal cytoplasmic tail increases Cl channel activity in Xenopus oocytes

Expression of the polycystin-1 C-terminal cytoplasmic tail increases Cl(-) channel activity in Xenopus oocytes. Background. Cyst expansion in autosomal-dominant polycystic kidney disease (ADPKD) is characterized by active Cl(-) secretion in excess of solute reabsorption. However, the connections between elevated epithelial Cl(-) secretion and loss-of-function or dysregulation of either ADPKD gene polycystin-1 (PC1) or polycystin-2 (PC2) remain little understood. Methods. Cl(-) transport in Xenopus oocytes expressing the CD16.7-PKD1 (115-226) fusion protein containing the final 112 amino acid (aa) of the PC1 C-terminal cytoplasmic tail, or in oocytes expressing related PC1 fusion protein mutants, was studied by isotopic flux, two-electrode voltage clamp, and outside-out patch clamp recording. Results. Expression in oocytes of CD16.7-PKD1 (115-226) increased rates of both influx and efflux of (36)Cl(-), whereas CD16.7-PKD1 (1-92) containing the initial 92 aa of the PC1 C-terminal cytoplasmic tail was inactive. The increased Cl(-) transport resembled CD16.7-PKD1 (115-226)-stimulated cation current in its sensitivity to ADPKD-associated missense mutations, to mutations in phosphorylation sites, and to mutations within or encroaching upon the PC1 coiled-coil domain, as well as in its partial suppression by coexpressed PC2. The NS3623- and 4, 4'-diisothiocyanatostilbene-2, 2'-disulfonic acid (DIDS)-sensitive (36)Cl(-) flux was not blocked by injected ethyleneglycol tetraacetate (EGTA) or by the cation channel inhibitor SKF96365, and was stimulated by the cation channel inhibitor La(3+), suggesting that CD16.7-PKD1 (115-226)-associated cation conductance was not required for (36)CI(-) flux activation. Outside-out patches from oocytes expressing CD16.7-PKD1 (115-226) also exhibited increased NS3623-sensitive Cl(-) current. Conclusion. These data show that CD16.7-PKD1 (115-226) activates Cl(-) channels in the Xenopus oocyte plasma membrane in parallel with, but not secondary to, activation of Ca(2+)-permeable cation channels.     

Immunomorphological characteristics of animals with different levels of orientation and exploratory behavior

We revealed some relationships between the level of orientation and exploratory behavior, functional activity of the immune system, and structural and functional organization of the CNS in animals. Significant differences in brain morphology and expression of cytokine IL-1, type I IL-1 receptor, and erythropoietin receptor genes in brain cells were detected in (CBA×C57Bl/6)F1 mice with different initial levels of orientation and exploratory behavior. Immunocompetent cells of mice with high and low levels of exploratory behavior differ by spontaneous and mitogen-induced proliferative activity. The formation of humoral and cellular immune response in these animals causes opposite changes in exploratory behavior and the type of these changes depends on the initial level of this behavioral reaction.Translated from Byulleten Eksperimentalnoi Biologii i Meditsiny, Vol. 138, No. 10, pp. 466–469, October, 2004     

Search for HHV-8 associated diseases reservoir and spread paths of HHV-8 in Russia

Summarized in the paper are study results of human herpesvirus type 8 (HHV-8) and of its association with Kaposi's sarcoma (KS). The data obtained denotes that the share of individuals producing the antibodies to HHV-8 in a majority of studied patients was low and ranged form 0 to 5.5%, which is indicative of a low degree of the virus spread in population. At the same time, a high share of persons with antibodies to HHV-8 was detected among HIV-infected homosexuals (71.4%), kidney recipients (26.0%) and among AIDS-KS patients (78.6%). It was also unexpectedly high among patients with T- and B-cell lymphomas (50%), encephalopathy (27.3%) and with stomach cancer (41.8%): the appropriate parameters were 7-12-fold higher versus healthy subjects. The HHV-8 markers, i.e. virus specific antibodies and/or nucleotide sequences of the virus, were detected in blood serum and ejaculate of a significant number of patients with different pathologies of the prostate. Such detection of viral markers in the above categories of patients is suggestive of that sexual contacts with such patients are decisive for the HHV-8 spread in population.     

Anesthesia during radical surgery for esophageal cancer

The paper summarizes the experience with 245 anesthesias made in 1983 to 2002 during operations for malignant esophageal neoplasms and cardioesophageal cancer. The specific features of the perioperative period, monitoring of the function of vital viscera, the technical features of transhiatal esophagectomy, risk factors of postoperative complications and principles of their prevention are considered. The ways of optimizing anesthesiological protection during radical esophageal operations are discussed.     

Angiotensin II receptor blocker telmisartan: effect on 24-hour blood pressure profile and left ventricular hypertrophy in patients with hypertension

AIM: To study antihypertensive efficacy of monotherapy with telmisartan and its action on left ventricular myocardium remodeling in patients with hypertension. MATERIAL AND METHODS: Telmisartan (40-80 mg/day) was given for 24 weeks to 24 patients aged 37-69 years with I-II degree of blood pressure (BP) elevation and hypertrophy of left ventricular myocardium. Antihypertensive action of telmisartan was assessed by 24-hour BP monitoring. Left ventricular myocardial mass was estimated by echocardiography before and after 24 weeks of therapy. RESULTS: Telmisartan equally decreased both diurnal and nocturnal systolic and diastolic BP (by10.4-11.7%), lowered maximal BP during morning hours, and restored initially disturbed 24-hour BP rhythm. Target BP levels were achieved in 16 patients (70%). Therapy with telmisartan was associated with significant 10.9% reduction of left ventricular myocardial mass index (from 151.6-/+5.4 to 135.1-/+5.9 g/m2, p=0,02) at the account of decreased thickness of left ventricular wall. CONCLUSION: These results give reason for the use of telmisartan for the treatment of patients with hypertensive disease and left ventricular hypertrophy.     

A comprehensive evaluation of the management effectiveness in a multi-specialty hospital

The medical-and-economic efficiency, involving the traditional, newly designed and tested methodic approaches, was evaluated in respect to 19 inhospital department of a multidiscipline hospital in the city of Yekaterinburg. A necessity was proven to use the integral indices in assessing the medical efficiency. The economic and medical efficiencies were found to coincide in 62.5% of cases, which is indicative of that it is not always the case, when the amount of the spent means directly influence the activity output. The study results showed that the technology of integral assessments of the medical-and-economic activity efficiency enables the hospital's manager to define the best and worst functioning units and to make subsequently the appropriate correcting managerial decisions.     

尿微量蛋白与老年2型糖尿病合并缺血性心脏病关系的研究

目的探讨在老年2型糖尿病合并缺血性心脏病患者中尿微量蛋白在加重缺血性心脏病进展方面的作用。方法将66例老年2型糖尿病合并缺血性心脏病患者按24h尿微量蛋白排泄量分为:尿微量蛋白正常组及尿微量蛋白阳性组,分别对血脂、空腹血糖、血清胰岛素、胰岛素敏感指数、纤维蛋白原、颈动脉内-中膜厚度、颈总动脉粥样硬化等级积分、硬化斑块指数、心脏彩超室间隔厚度及射血分数等加重缺血性心脏病进展等指标进行比较分析。结果66例老年2型糖尿病合并缺血性心脏病患者尿微量蛋白阳性组高密度脂蛋白、载脂蛋白A、胰岛素敏感指数、年龄、纤维蛋白原、硬化斑块指数、颈总动脉粥样硬化等级积分、室间隔厚度及射血分数显著高于尿微量蛋白阴性组(P<0.05,P<0.01)。结论尿微量蛋白的出现能够加速糖尿病合并缺血性心脏病的发展进程,它的出现预示着缺血性心脏病的预后不良。     

Detection of carbamyl phosphate synthetase 1 deficiency using duodenal biopsy samples

The activity of urea cycle enzymes was assayed in duodenal biopsy specimens obtained from a female infant who presented with neonatal hyperammonaemia. All enzyme levels were normal except N-acetyl glutamate-dependent carbamyl phosphate synthetase 1 (CPS1) which was half the mean activity in normal control specimens. A similar deficiency of CPS1 was also shown in duodenal specimens from the patient's mother who became slightly symptomatic after relatively high protein meals and during pregnancy, and had spontaneously modified her diet to one with protein restriction. The patient is growing normally on a dietary regimen similar to that spontaneously adopted by her mother. Urea cycle enzyme activity in the duodenal biopsy material from the controls was similar to that found in the normal human liver and appears to have distinct advantages as a means of assaying for urea cycle defects in patients with hyperammonaemia and their relatives.