Laboratory investigation; a journal of technical methods and pathology
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Cerebral ischemia followed by reperfusion induced apoptosis in stroke-prone spontaneously hypertensive rats (SHRSP) but not in Wistar Kyoto rats (WKY). Our in vitro studies revealed that IGF-1 prevented apoptosis caused by nitric oxide- and N-methyl-D-aspartate-mediated toxic agents in cortical neurons isolated from SHRSP. In addition, it was reported that IGF-1 given 1 hour before ischemia significantly attenuated the incidence of myocyte apoptosis after myocardial ischemia and reperfusion. ⋯ Cerebral ischemia followed by reperfusion significantly (p < 0.01) increased the number of apoptotic neurons (235.2 +/- 25.2/1000 neurons) in SHRSP. In contrast, pretreatment with IGF-1 reduced the number of apoptotic neurons in SHRSP (82.8 +/- 11.2/1000 neurons; p < 0.01) under otherwise identical conditions. We concluded that the genetic vulnerability to apoptosis in SHRSP neurons was involved in the pathogenesis of stroke lesions and that this vulnerability was attenuated by the IGF-1 pretreatment.
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Nucleated cells are protected from complement-mediated injury by the expression of membrane-bound regulators of complement activation (mRCA) CD46, CD55, and CD59. Increased expression of these mRCA may be a mechanism by which tumor cells protect themselves from complement-mediated injury and prevent an inflammatory response. In the present study, we have investigated whether human renal tumor cell lines and cultured proximal tubular epithelial cells express CD46, CD55, and CD59 and whether these mRCA influence complement-mediated lysis of these cells. ⋯ We conclude from this work that renal tumor cells and proximal tubular epithelial cells express CD46, CD55, and CD59. Of these mRCA, CD59 is most efficient in preventing complement-mediated lysis of these cells. Expression of mRCA on tumor cells may influence the effectiveness of immunotherapy with tumor-associated mAb.
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The purpose of this study was to assess the phenotypic and functional characteristics of pulmonary microvascular endothelial cells (MVEC) in the acute respiratory distress syndrome (ARDS). Pulmonary MVEC were isolated from the lungs of five patients who developed ARDS, and from four patients who had undergone a lobectomy for lung carcinoma, as controls. Adhesion molecules and other surface molecules were quantitated on these cells by flow cytometry and the cytokines IL-6 and IL-8 were measured in the supernatants by ELISA. ⋯ These findings suggest that ICAM-1 and TNF receptor p75 may have a particular involvement in the pathogenesis of acute lung injury, and that the endothelium may be an important source of cytokines detected in broncho-alveolar lavage during this syndrome. It is tempting to hypothesize that the differences observed result from either a genetic predisposition to ARDS based on MVEC phenotype or to a long-lived MVEC phenotypic change induced by ARDS. By allowing the monitoring of phenotypic and functional parameters, cultures of pulmonary MVEC isolated from ARDS patients may thus represent a useful system to analyze further the mechanisms of acute lung injury and to evaluate the efficacy of drugs, including inhibitors of cytokines and of adhesion molecules.
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Dermal substitutes seeded with cultured fibroblasts have been developed to improve dermal regeneration in full thickness wounds. Because of cell cultivation, 3 weeks are required before patients can be treated with these autologous adipose tissue. This substitute is easily fabricated within hours, which allows immediate treatment of full thickness defects. ⋯ Adipose tissue cell isolates included vascular fragments containing endothelial cells. Seeded in dermal substitutes, these vascular fragments induced hypergranulation tissue formation and caused wound contraction. SF substitutes contained few endothelial cells. As a result, the contraction arresting effect of the seeded stromal cell fraction was effective. Our concept of a cellular dermal substitute seeded with stromal cells from adipose tissue is feasible and allows immediate treatment of full thickness skin defects.
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We previously reported the induction of 73-kilodalton heat-shock protein (HSP73) in injured tubular epithelial cells in rat kidneys with gentamicin-induced acute renal failure. In the present study, we examined serial expression of 90-kilodalton heat-shock protein (HSP90), another major HSP, in this animal model. ⋯ These results demonstrate that HSP90 is induced in the lysosomes and the nucleoli of damaged cells during the course of gentamicin-induced acute tubular injury. HSP90 may have roles in the disposition of degenerated proteins and in the new protein synthesis for the protection and repair of target cells from gentamicin nephrotoxicity.