Soluble fms-like tyrosine kinase 1 promotes angiotensin II sensitivity in preeclampsia

Preeclampsia is a hypertensive disorder of pregnancy in which patients develop profound sensitivity to vasopressors, such as angiotensin II, and is associated with substantial morbidity for the mother and fetus. Enhanced vasoconstrictor sensitivity and elevations in soluble fms-like tyrosine kinase 1 (sFLT1), a circulating antiangiogenic protein, precede clinical signs and symptoms of preeclampsia. Here, we report that overexpression of sFlt1 in pregnant mice induced angiotensin II sensitivity and hypertension by impairing endothelial nitric oxide synthase (eNOS) phosphorylation and promoting oxidative stress in the vasculature. Administration of the NOS inhibitor l-NAME to pregnant mice recapitulated the angiotensin sensitivity and oxidative stress observed with sFlt1 overexpression. Sildenafil, an FDA-approved phosphodiesterase 5 inhibitor that enhances NO signaling, reversed sFlt1-induced hypertension and angiotensin II sensitivity in the preeclampsia mouse model. Sildenafil treatment also improved uterine blood flow, decreased uterine vascular resistance, and improved fetal weights in comparison with untreated sFlt1-expressing mice. Finally, sFLT1 protein expression inversely correlated with reductions in eNOS phosphorylation in placental tissue of human preeclampsia patients. These data support the concept that endothelial dysfunction due to high circulating sFLT1 may be the primary event leading to enhanced vasoconstrictor sensitivity that is characteristic of preeclampsia and suggest that targeting sFLT1-induced pathways may be an avenue for treating preeclampsia and improving fetal outcomes.     

CENTRAL NEUROGENIC NEUROPROTECTION: PROTECTION OF BRAIN FROM FOCAL ISCHEMIA BY CEREBELLAR STIMULATION

Electrical stimulation of the cerebellar fastigial nucleus (FN) elevates regional cerebral blood flow (rCBF) independently of cerebral metabolism (rCGU) throughout brain. One hour of FN stimulation also reduces, by up to 50%, the volume of the focal ischemic infarction produced by occlusion of the middle cerebral artery in rat. Protected areas correspond to the ischemic penumbra. Neuroprotection, while reversible, persists for weeks after 1h of stimulation. It cannot be attributed to increasing rCBF and/or reducing rCGU to improve matching of flow and metabolism. Conditional stimulation of FN initiates long-lived inhibition of expression of peri-infarction depolarizing waves, possibly by altering potassium-channel function and suppresses induction of inducible nitric oxide synthase (iNOS) and ICAM in cerebral microvessels. The brain contains intrinsic networks which may protect the brain from ischemic injury, possibly by producing widespread and longterm suppression of electrical excitability and/or and expression of proinflammatory molecules.     

Precocious expression of T cell functional response genes in vivo in primitive thymocytes before T lineage commitment

The genes encoding effector molecules of mature T cells, IL-2, perforin and IL-4, were found to be expressed in vivo in the most primitive subsets of thymocytes of adult mice. These subsets have previously been identified by their cell surface markers and by their expression of other T lineage-associated genes. While IL-2, perforin and IL-4 are expressed in distinct patterns, all three are expressed before the induction of RAG-1 and pre-TCR alpha mRNA expression, and are confined to subsets of cells that apparently have not yet undergone commitment to the T lineage. Thus, expression of T cell response genes appears to be one of the earliest markers of lymphocyte differentiation. Activation events marked by CD69 induction occur in these early cell types, but the response gene expression by these cells is separable from CD69 expression. IL-2 and perforin are induced again much later in thymocyte development, during TCR-dependent repertoire selection. At those stages, IL-2 protein and RNA levels per cell are higher, but the fraction of cells expressing IL-2 appears to be much lower than in the most immature stages. In addition, a striking feature of the immature populations is the robust IL-2 expression by presumptive immature NK cells. These findings are discussed in terms of the developmental origins of lineage specificity in T cell response gene regulation.      

预断溃疡性结肠炎自然史的可能性

在提高炎症性肠病(1BD)疗效的同时,因治疗产生的毒性也可能增加,因此筛选出高危患者尤为重要.我们首先需要确定与溃疡性结肠炎(UC)自然史最为相关的临床终点事件,然后明确能预测严重后果的危险因素.     

Endoscopic microscopy of the colon

The authors analyse the results of endoscopic colonomicroscopy at various magnifications in 250 patients. A study of dye absorption in different histological types of colonic tumor made it possible to establish that chromocolonoscopy is an effective method in diagnosing and differentiating some types of tumors and hyperplastic changes in the mucosa of the colon. Adenomas with severe dysplasia of the glandular epithelium, and tumors with a structure of an adenocarcinoma do not readily accept vital staining.     

Hematopoiesis in human embryonic liver organ culture

It was shown by the method of multiple organ cultures on Millipore filters that hematopoiesis of predominantly erythroid type is maintained for a long time (over 1.5 months) in cultures of human embryonic liver. The general morphology of 7–50-day-old cultures was studied and described. The myeloid population of cells (the number of colony-forming units) was virtually exhausted by the 14th–16th day of culture.Laboratory of Bone Marrow Culture and Transplantation, Central Institute of Hematology and Blool Transfusion, Ministry of Health of the USSR. Laboratory of Pediatric Hematology, N. I. Pirogov Second Moscow Medical Institute. First Gynecological Department, No. 49 City Hospital, Moscow. (Presented by Academician of the Academy of Medical Sciences of the USSR, N. A. Fedorov.) Translated from Byulleten' Éksperimental'noi Biologii i Meditsiny, Vol. 83, No. 4, pp. 460–462, April, 1977.     

肾移植的放射性核素评价

核素检查由于无创伤性并可定量测肾功能,已被广泛用于肾移植监测。本文介绍如何应用~(99m)Tc-DTPA等几种放射性药物和显像技术诊断肾移植后各种外科并发症,急、慢性排斥反应,急性肾小管坏死和免疫抑制剂的毒性反应。