Cytoprotective effects of adrenomedullin in glomerular cell injury: central role of cAMP signaling pathway

Activation of cAMP signaling pathway was shown to inhibit some pathobiologic processes in mesangial cells (MC). We investigated whether adrenomedullin (ADM), a potent agonist of adenylate cyclase, is synthesized in MC and whether it can, via cAMP, suppress the generation of reactive oxygen metabolites (ROM) and proliferation of cells in glomeruli. With the use of an immunohistologic technique ADM was detected in mesangial and microvascular areas of rat glomeruli. MC grown in primary culture synthesized ADM, and the synthesis was stimulated by TNF alpha and IL-1 beta but not by PDGF and EGF. ADM inhibited ROM generation in MC dose-dependently and caused in situ activation of protein kinase A (PKA). In macrophages (cell line J774) ROM generation was about four times higher than in MC and was inhibited by ADM in a similar way as in MC. The rate of MC proliferation, measured by [3H]-incorporation, and the activity of mitogen-activated protein kinase (MAPK) stimulated by PDGF and EGF were dose-dependently inhibited by ADM; the maximum inhibition (at 10 nM ADM) was about -80%. Mitogenesis of MC and MAPK activity when stimulated to a similar extent by endothelin (ET-1) was inhibited by ADM to a significantly (P < 0.01) lesser degree (-30%). Further, ADM inhibited PDF-stimulated mitogenesis and activation of MAPK in cultured vascular smooth muscle cells (VSMC). The inhibition of PDGF-activated MAPK by ADM in VSMC was reversed by the protein kinase A (PKA) inhibitor, H89. Taken together, results indicate the adrenomedullin (ADM) generated in mesangial cells (MC) can suppress, via activation of the cAMP-protein kinase A (PKA) signaling pathway, reactive oxygen metabolites (ROM) generation in MC and infiltrating macrophages as well as mitogen-activated protein kinase (MAPK)-mediated mitogenesis in MC and vascular smooth muscle cells (VSMC). We suggest that introglomerular ADM may serve as a cytoprotective autoacoid that suppresses pathobiologic processes evoked by immuno-inflammatory injury of glomeruli.     

稳峰技术研究及其应用

研究内嵌~(241)Amα源的NaI探测器在不同工作环境下,所测排放气体中的γ放射性核素能谱的漂移趋势,通过改变探测器的工作温度及工作电压等实验,探索所测能谱的漂移规律,并运用合适的软硬件电路来实现能谱的稳峰功能。这种稳峰技术确保了所测γ放射性核素的准确性及能谱的稳定性,使得在实际应用中能正确辨别γ放射性核素的类别,是详细分析各种放射性核素的排放浓度及排放置的前提。     

基于自相关降噪的混叠转子振动信号分离

航空发动机在运行过程中,传感器测得的振动信号是各振源的混叠信号,且含有很强的噪声。常规的信号处理方法难以分离混叠信号,对机器的健康监测和故障诊断造成了很大的困难。介绍了盲源分离基本原理和方法,指出盲源分离算法在强噪声环境下失效。针对强噪声环境下的混叠振动信号,提出首先通过时延自相关降噪方法对振动信号进行降噪,然后通过盲源分离算法对降噪后的信号分离。仿真结果验证了提出方法的有效性。最后,利用该方法对实测混叠转子振动信号成功实现了降噪和盲分离,为噪声环境下的混叠信号分离提供了一种新的方法。     

高密度PBGA组件的模态试验与仿真研究

为探索高密度板级组件的动态特性,设计了带菊花链的PBGA(塑封焊球阵列)组件,采用模态试验和有限元仿真方法分别获得PBGA组件的模态参数,分析了不同固支方式对PBGA组件一阶固有频率的影响.研究了边6点固支条件下各阶阵型特性并提出了元器件抗振布局设计的原则,结果表明:6螺钉支撑将显著提高组件的一阶固有频率,从两螺钉的1...     

高温SO I CMO S 倒相器瞬态特性的研究

本文主要研究高温SOI CMOS倒相器在（27－300℃）宽温区的瞬态特性。研究结果表明：当采用N^ PN^ 和P^＋PP^ 结构薄膜SOI MOSFET组合，并且其结构参数满足高温应用的要求，则SOI CMOS倒相器实验样品在（27－300℃）具有良好的高温瞬态特性。     

Override of spontaneous respiratory pattern generator reduces cardiovascular parasympathetic influence

We investigated the effects of voluntary control of breathing on autonomic function in cardiovascular regulation. Variability in heart rate was compared between 5 min of spontaneous and controlled breathing. During controlled breathing, for 5 min, subjects voluntarily reproduced their own spontaneous breathing pattern (both rate and volume on a breath-by-breath basis). With the use of this experimental design, we could unmask the effects of voluntary override of the spontaneous respiratory pattern generator on autonomic function in cardiovascular regulation without the confounding effects of altered respiratory pattern. Results from 10 subjects showed that during voluntary control of breathing, mean values of heart rate and blood pressure increased, whereas fractal and spectral powers in heart rate in the respiratory frequency region decreased. End-tidal PCO2 was similar during spontaneous and controlled breathing. These results indicate that the act of voluntary control of breathing decreases the influence of the vagal component, which is the principal parasympathetic influence in cardiovascular regulation.     

Late recurrences of laryngeal papillomatosis

Laryngeal papillomotasis recurred in 2 patients after 44 and 47 years of remission. The recurrence of papillomatosis after such lengthy periods of remission underscores the fact that, while surgical treatment of laryngeal papillomatosis may maintain the airway and voice, and in some cases control clinically overt disease, it does not address the subclinical mucosal human papillomavirus infection that may lead to recurrence many years after surgery.     

Cyclosporine A in the treatment of early rheumatoid arthritis. A prospective, randomized 24-month study

OBJECTIVE: To investigate the efficacy, tolerability and safety of cyclosporine A (CSA) in early rheumatoid arthritis (RA) patients. METHODS: Patients with an early diagnosis of RA, a disease duration of less than 3 years, and without prior disease modifying antirheumatic drug (DMARD) treatment were studied. They randomly received oral CSA (3 mg/kg/day) or oral methotrexate (MTX) (0.15 mg/kg/week). In addition, all patients in both groups received oral prednisone (7.5 mg/day). RESULTS: Fifty-two patients were assigned to the CSA group and 51 to the MTX group. After 24 months of treatment, 48 patients from the CSA group and 48 from the MTX group showed significant clinical improvement. This was evaluated by the duration of morning stiffness, grip strength, the total joint count, joint swelling, and joint tenderness and pain, compared to pre-treatment values. The clinical improvement was also associated with a significant decrease in ESR and CRP values in both groups. No significant radiological deterioration was observed in the CSA patients compared to those treated with MTX after 24 months. Four patients from the CSA group dropped out of the study, two because of a synovitis flare, one because of severe hypertrichosis and one because of severe gingival hyperplasia. Three patients from the MTX group withdrew, one because of disease flare-up and two because of gastrointestinal disturbances. CONCLUSION: Early immunointervention in RA patients appears to be crucial to limit the development of joint damage. Cyclosporine A appears to be effective, well tolerated and safe in the long-term treatment of RA and can therefore be used as a first immunomodulatory drug in the armamentarium for the treatment of RA.     

Characterization of a high capacity calcium transport system in mitochondria of the yeast Endomyces magnusii

The Ca2+ transport system of Endomyces magnusii mitochondria has been shown previously to be activated by spermine. Here we report it to be regulated also by low, physiological ADP concentrations, by the intramitochondrial NADH/NAD+ ratio, and by Ca2+ ions. The combination of all these physiological modulators induced high initial rates of Ca2+ uptake and high Ca2+-buffering capacity of yeast mitochondria, enabling them to lower the medium [Ca2+] to approximately 0.2 microM. The mechanisms of stimulation by these agents are discussed.