In vivo 23Na NMR studies of myotonic dystrophy

Myotonic dystrophy is an inherited multi-system disease. Its pathophysiology leading to muscle malfunction and damage is not well understood. ²³Na NMR spectroscopy was applied here for an in vivo comparative study of the calf muscles of 7 myotonic dystrophy patients at various stages of the disease and 11 healthy volunteers. Both the total sodium content, expressed as the ratio of the ²³Na and ¹H water signals, and the fast transverse relaxation time, T₂₁, determined from the triple quantum-filtered spectra, increased in correlation with the severity of the disease. The results demonstrate that ²³Na NMR enables the quantitation of myotonic dystrophy progression.     

The multifunctionality of FGF-2 in the adrenal medulla

 Chromaffin cells of the adrenal medulla and their tumor counterparts, the pheochromocytoma (PC12) cells, are well-established model systems in neurobiology. The development of sympathoadrenal progenitor cells to chromaffin cells can be studied with regard to developmental signals which trigger the differentiation. With regard to potential treatments of neurological disorders like Parkinson’s disease chromaffin cell grafting can be used as one therapeutical approach. The beneficial effect of chromaffin cell grafts is possibly not only related to the release of dopamine but may also be linked to the release of growth factors. One of the growth factors that is synthesized by chromaffin and PC12 cells is basic fibroblast growth factor (FGF-2). The experimental data available so far, are in agreement with different functional roles of FGF-2. This article summarizes the putative physiological functions of FGF-2 in the adrenal medulla. Three differential functional roles of FGF-2 are discussed: (1) as a differentiation factor for sympathoadrenal progenitor cells; (2) as a target-derived neurotrophic factor for preganglionic sympathetic neurons which innervate adrenal medullary cells; (3) as an auto-/paracrine factor in the adrenal medulla. Accepted: 21 August 1996     

The role of Na+/K+ ATPase activity during low flow ischemia in preventing myocardial injury: A 31P, 23Na and 87Rb NMR spectroscopic study

An increase in intracellular Na⁺ during ischaemia has been associated with myocardial injury. In this study, we determined whether inhibition of Na⁺/K⁺ ATPase activity contributes to this increase and whether Na⁺/K⁺ ATPase activity can be maintained by provision of glucose to perfused rat hearts during low flow, 0.5 ml/min, ischemia. We used ³¹P NMR spectroscopy to determine changes in myocardial energetics and intracellular and extracellular volumes. ²³Na NMR spectroscopy, with DyTTHA^3- present as a shift reagent, was used to measure changes in intracellular Na⁺ and ⁸⁷Rb NMR spectroscopy was used to estimate Na⁺/K⁺ ATPase activity from Rb⁺ influx rates, Rb⁺ being an NMR-sensitive congener of K⁺. In hearts provided with 11 mM glucose throughout ischemia, glycolysis continued and ATP was twofold higher than in hearts without glucose. In the glucose-hearts, Rb⁺ influx rate was threefold higher, intracellular Na⁺ was fivefold lower at the end of ischemia and functional recovery during reperfusion was twofold higher. We propose that continuation of glycolysis throughout low flow ischemia allowed maintenance of sufficient Na⁺/K⁺ ATPase activity to prevent the increase in intracellular Na⁺ that would otherwise have led to myocardial injury.     

系统性红斑狼疮患者外周血中B淋巴细胞活化状况与疾病活动性的关系

目的探讨系统性红斑狼疮患者外周血中B淋巴细胞及其活化状况与疾病活动性的关系。方法应用流式细胞术检测活动期与稳定期系统性红斑狼疮患者外周血中CD19+、CD23+/CD19+及HLA-DR+/CD19+细胞的表达情况;同时应用免疫学方法检测血清中ds-DNA与ANA水平。结果活动期患者CD19+、CD23+/CD19+及HLA-DR+/CD19+细胞表达率均高于稳定期患者及正常对照组,差异均有显著性意义;稳定期患者CD23+/CD19+表达很低,而HLA-DR+/CD19+双阳性细胞表达率高于正常对照组,但差异无显著性意义;且CD23+/CD19+双阳性细胞表达率与病情积分、ds-DNA及ANA均成正相关(P<0.01),而HLA-DR+/CD19+双阳性细胞与三者无相关关系(P>0.05)。结论活动期与稳定期患者均存在B淋巴细胞的克隆性增生与异常活化,B细胞的异常活化是病情活动的直接原因,晚期B细胞的异常活化是系统性红斑狼疮患者难彻底治愈与病情反复的原因之一。     

子宫内膜异位症与nm23-H1基因之间关系的研究

目的　研究nm2 3 H1基因在子宫内膜异位症发生中的作用。方法　采用免疫组化方法研究 2 5例子宫内膜异位症患者的病理组织和 2 2例正常子宫内膜组织中的nm2 3 H1蛋白的表达情况 ;用RT PCR方法研究 2 5例子宫内膜异位症患者的病理组织中nm2 3 H1基因的mRNA的表达情况。结果　子宫内膜异位症组中的nm2 3 H1蛋白表达水平明显低于对照组 (P <0 .0 1) ,子宫内膜异位症组中 ,nm2 3 H1蛋白表达与mRNA表达的结果无显著性差异 (P >0 .0 5 )。结论　nm2 3 H1基因在子宫内膜异位症的发生发展中起一定的作用。     

Targeting angiogenesis in ovarian cancer

Results of standard chemotherapy in ovarian cancer are hampered by the development of drug resistance leading to disease recurrence. This prompted interest in the development of therapies targeting critical pathways responsible for tumor progression. Angiogenesis is a key process that enables ovarian cancer growth and metastasis in the peritoneal space. Its regulation relies on signaling mechanisms initiated by the vascular endothelial growth factor, the platelet-derived growth factor, the fibroblast growth factor, angiopoietins, and others. These pathways are not only important to the modulation of the tumor microenvironment and vasculature, but also control cancer cell proliferation and survival. In this review, we discuss preclinical evidence supporting the rationale for inhibiting these pathways and provide an overview for the clinical development of agents targeting them. Clinical trials evaluating such agents alone and in combination with chemotherapy are ongoing. Early clinical results position antiangiogenic therapy at the forefront of change to the standard treatment of difficult to treat ovarian cancer.     

Assessment of ascending aorta using epiaortic ultrasonography during off-pump coronary artery bypass grafting

BACKGROUND: Use of an aortic partial clamp for proximal anastomosis during off-pump coronary artery bypass is known to increase the risk of fatal complications. The purpose of this study was to assess the management of the ascending aorta evaluated with epiaortic ultrasonography during off-pump coronary artery bypass. METHODS: Intraoperative ultrasonography of the ascending aorta with a 10-MHz probe was performed consecutively in 155 patients undergoing off-pump coronary artery bypass between August 1999 and July 2001. The findings from ultrasonography, surgical modifications, and operative results were analyzed. RESULTS: In 54 patients (34.8%), epiaortic ultrasonography showed atherosclerotic findings in the anterior side of the ascending aorta (group A). The remaining 101 patients had either normal findings or atherosclerotic findings in only the posterior side (group NA). A proximal anastomosis to the aorta was preoperatively planned in 117 patients (group A, 42; group NA, 75). In group A, a graft modification without clamping was implemented in 29 patients (24.8% of 117 patients), whereas the clamp site was modified to a different segment in 13 patients (11.1% of 117 patients). In all 75 patients in group NA, partial clamping was used in the standard fashion. There were no cerebral infarctions or operative deaths related to partial clamping. However, aortic dissection occurred in 1 patient in group NA. CONCLUSIONS: In 35% of patients undergoing off-pump coronary artery bypass, epiaortic ultrasonography identified atherosclerotic findings in the anterior wall of the ascending aorta. This study suggests that revascularization without aortic manipulation during off-pump coronary artery bypass is indicated in as many as 25% of patients.