Glutathione peroxidase in dried blood spots.

A new procedure utilizing dried blood spots was developed for detecting glutathione peroxidase deficiency. Samples from a known patient with a partial defect and from rats with an induced deficiency were distinguished from respective control groups by their longer defluorescence endpoints. Samples from 100 patients with anemia and 2 phenyl-ketonuric infants on low-protein diets contained glutathione peroxidase activity similar to that in 82 controls, when screened for the enzyme defect by the new procedure.     

Glutathione peroxidase in dried blood spots

Summary A new procedure utilizing dried blood spots was developed for detecting glutathione peroxidase deficiency. Samples from a known patient with a partial defect and from rats with an induced deficiency were distinguished from respective control groups by their longer defluorescence endpoints., Samples from 100 patients with anemia and 2 phenylketonuric infants on low-protein diets contained glutathione peroxidase activity similar to that in 82 controls, when screened for the enzyme defect by the new procedure.     

Mitochondrial abnormalities in fibroblast line GM3093 defective in oxidative metabolism

Summary Fibroblast line GM3093 deficient in the activity of the pyruvate dehydrogenase complex, was derived from a patient reported to have an inherited defect affecting the tricarboxylic acid cycle. Our results suggest a generalized defect consisting of few and abnormal mitochondria and low activities of all mitochondrial enzymes examined.Preliminary reports of aspects of this work appeared as abstracts in Trans. Am. Soc. Neurochem.15 (1984) 178, and Soc. Neurosci.10 (1984) 996.Developmental and Metabolic Neurology Branch.Surgical Neurology Branch.     

Mechanical simulation of renal pelvic wall peristalsis in the rat

Summary A urinary concentrating defect was induced in Munich-Wistar rats by removing the renal pelvis from 1 kidney. This defect was partially corrected by crudely simulating the actions of pelvic wall peristalsis with a mechanical system that cyclically compressed the exposed renal papilla.A portion of this work was conducted at The Mount Desert Island Biological Laboratory, Salsbury Cove, Maine and was supported by NIH grant 2 RO1-AM15972-10 awarded to Dr B. Schmidt-Nielsen. Additional support came from the Maine and Pennsylvania Affiliates of the American Heart Association.     

Copper-induced heart malformations in hamsters.

The injection of copper citrate into pregnant golden hamsters induces a specific pattern of cardiovascular malformations in their embroys. The syndrome consists of double-outlet right ventricle, pulmonary hypoplasia and a ventricular spetal defect.     

Defective phosphoinositide metabolism in primary hypertension

An increase in free cytosolic calcium content has been reported in essential hypertension. Since within the membrane, the phosphoinositides participate in the control of cell calcium homeostasis, we investigated whether impaired phosphoinositide metabolism could account for the calcium handling abnormality observed in hypertensives. In erythrocyte membranes of hypertensives the activity of kinases involved in polyphosphoinositide formation appears to be impaired and could be related to the alteration in calcium handling binding capacity and ATP-dependent calcium transport. In platelets of hypertensives, the hyperactivity of phospholipase C (observed even in the absence of calcium in the external medium) is likely to be responsible for the hypersensitivity of cells to various agonists. These observations are consistent with the hypothesis that in cells from hypertensives, a membrane defect linked to phosphoinositide metabolism is involved in the overall calcium handling defect.     

Defect of incorporation of S in old Swan autoimmune mice thymus (author's transl)]

A diminution of the incorporation of radioactive S in epithelial cells of the thymus of auto-immune Swan mice is shown. This defect of incorporation seems to be in relation to a thymus deficiency.     

The effect of dehydration on the neurohypophyseal blood flow in rats with hereditary diabetes insipidus

Neurohypophyseal blood flow increases in water-deprived rats. This increase is independent of vasopressin release, since it occurs even in rats with hereditary defect of hypothalamic vasopressin synthesis.     

Malignant hyperthermia: molecular defects in membrane permeability

Malignant hyperthermia (MH), a genetically inherited disorder of skeletal muscle, is due to molecular defect in membrane permeability. The alteration in membrane permeability is suggested to be due to enhanced phospholipase A2 activity which is responsible for the increased level in sarcoplasmic Ca2+. The excess Ca2+ is responsible for muscle hyper-rigidity and enhanced rate of glycolysis, resulting in a rapid rate of lactic acid production and a low pH in MH muscle.     

Differences in utilization of tritiated thymidine and tritiated deoxycytidine by rat lymph node cells.

Large lymphoid cells and plasma cells in antigenically stimulated rat lymph nodes retain less label after injection of 3H-CdR than after injection of 3H-TdR. There is no difference amongst small lymphocytes. The data are consistent with a defect in the utilization of 3H-CdR in the late stages of B cell maturation in the rat.     

Suppressor of cytokine signaling 1 blocks mitosis in human melanoma cells

Hypermethylation of SOCS genes is associated with many human cancers, suggesting a role as tumor suppressors. As adaptor molecules for ubiquitin ligases, SOCS proteins modulate turnover of numerous target proteins. Few SOCS targets identified so far have a direct role in cell cycle progression; the mechanism by which SOCS regulate the cell cycle thus remains largely unknown. Here we show that SOCS1 overexpression inhibits in vitro and in vivo expansion of human melanoma cells, and that SOCS1 associates specifically with Cdh1, triggering its degradation by the proteasome. Cells therefore show a G1/S transition defect, as well as a secondary blockade in mitosis and accumulation of cells in metaphase. SOCS1 expression correlated with a reduction in cyclin D/E levels and an increase in the tumor suppressor p19, as well as the CDK inhibitor p53, explaining the G1/S transition defect. As a result of Cdh1 degradation, SOCS1-expressing cells accumulated cyclin B1 and securin, as well as apparently inactive Cdc20, in mitosis. Levels of the late mitotic Cdh1 substrate Aurora A did not change. These observations comprise a hitherto unreported mechanism of SOCS1 tumor suppression, suggesting this molecule as a candidate for the design of new therapeutic strategies for human melanoma.     

基于踪迹挖掘的自动缺陷警报分类方法

缺陷检测一般包括静态分析与人工确认两个阶段.静态缺陷检测工具报告大量警报,但是主要的警报确认工作仍然由人工完成,这是一件费时费力的工作.巨大的确认投入,会导致测试人员和管理人员拒绝使用该静态检测工具.为了辅助警报确认工作,提出一种基于警报踪迹挖掘的警报分类方法,使用该方法挖掘警报踪迹进而将代码结构相似警报分为一类,使得分类后的最终警报报告更加易于人工确认.实验表明,该方法能够在较大规模的软件测试过程中分类测试结果,提高警报确认效率.     

The effect of dehydration on the neurohypophyseal blood flow in rats with hereditary diabetes insipidus

Summary Neurohypophyseal blood flow increases in water-deprived rats. This increase is independent of vasopressin release, since it occurs even in rats with hereditary defect of hypothalamic vasopressin synthesis.Acknowledgment. The technical assistance of D. Vilimovská is acknowledged.     

Malignant hyperthermia: Molecular defects in membrane permeability

Summary Malignant hyperthermia (MH), a genetically inherited disorder of skeletal muscle, is due to molecular defect in membrane permeability. The alteration in membrane permeability is suggested to be due to enhanced phospholipase A₂ activity which is responsible for the increased level in sarcoplasmic Ca²⁺. The excess Ca²⁺ is responsible for muscle hyper-rigidity and enhanced rate of glycolysis, resulting in a rapid rate of lactic acid production and a low pH in MH muscle.     

Differences in utilization of tritiated thymidine and tritiated deoxycytidine by rat lymph node cells

Summary Large lymphoid cells and plasma cells in antigenically stimulated rat lymph nodes retain less label after injection of³H-CdR than after injection of³H-TdR. There is no difference amongst small lymphocytes. The data are consistent with a defect in the utilization of³H-CdR in the late stages of B cell maturation in the rat.     

Défaut d'incorporation du soufre dans le thymus des souris autoimmunes Swan âgées

Summary A diminution of the incorporation of radioactive S in épithelial cells of the thymus of auto-immune Swan mice is shown. This defect of incorporation seems to be in relation to a thymus deficiency.     

基于AVR单片机的车载DVD/VCD面板组件自动检测系统

本文提供了一种基于AVR单片机的车载DVD／VCD面板组件自动检测系统设计方案，介绍了目前国内相关检测技术方法，分析了其不足之处和未来的发展方向，给出新设计系统的构成和工作原理。该检测系统已经用于深圳某大型港资电子公司的生产线，与传统检测方法相比较极大地提高了工作效率和可靠性。     

Molecular mechanisms in male determination and germ cell differentiation

Sex determination and gametogenesis are key processes in human reproduction, and any defect can lead to infertility. We describe here the molecular mechanisms of male sex determination and testis formation; defects in sex determination lead to a female phenotype despite the presence of a Y chromosome, more rarely to a male phenotype with XX chromosomes, or to intersex phenotypes. Interestingly, these phenotypes are often associated with other developmental malformations. In testis, spermatozoa are produced from renewable stem cells in a complex differentiation process called spermatogenesis. Gene expression during spermatogenesis differs to a surprising degree from gene expression in somatic cells, and we discuss here mechanistic differences and their effect on the differentiation process and male fertility.Received 23 January 2004; received after revision 30 March 2004; accepted 6 April 2004     

Endothelium-derived nitric oxide and vascular physiology and pathology

In 1980, Furchgott and Zawadzki demonstrated that the relaxation of vascular smooth muscle cells in response to acetylcholine is dependent on the anatomical integrity of the endothelium. Endothelium-derived relaxing factor was identified 7 years later as the free radical gas nitric oxide (NO). In endothelium, the amino acid L-arginine is converted to L-citrulline and NO by one of the three NO synthases, the endothelial isoform (eNOS). Shear stress and cell proliferation appear to be, quantitatively, the two major regulatory factors of eNOS gene expression. However, eNOS seems to be mainly regulated by modulation of its activity. Stimulation of specific receptors to various agonists (e.g., bradykinin, serotonin, adenosine, ADP/ATP, histamine, thrombin) increases eNOS enzymatic activity at least in part through an increase in intracellular free Ca²⁺. However, the mechanical stimulus shear stress appears again to be the major stimulus of eNOS activity, although the precise mechanisms activating the enzyme remain to be elucidated. Phosphorylation and subcellular translocation (from plasmalemmal caveolae to the cytoskeleton or cytosol) are probably involved in these regulations. Although eNOS plays a major vasodilatory role in the control of vasomotion, it has not so far been demonstrated that a defect in endothelial NO production could be responsible for high blood pressure in humans. In contrast, a defect in endothelium-dependent vasodilation is known to be promoted by several risk factors (e.g., smoking, diabetes, hypercholesterolemia) and is also the consequence of atheroma (fatty streak infiltration of the neointima). Several mechanisms probably contribute to this decrease in NO bioavailability. Finally, a defect in NO generation contributes to the pathophysiology of pulmonary hypertension. Elucidation of the mechanisms of eNOS enzyme activity and NO bioavailability will contribute to our understanding the physiology of vasomotion and the pathophysiology of endothelial dysfunction, and could provide insights for new therapies, particularly in hypertension and atherosclerosis.