To elucidate the mechanisms of hypertensive renal injury, we investigated the time course and extent of changes in matrix composition, as well as cell proliferation and infiltration in two-kidney, one clip rats. The nonclipped kidneys from hypertensive and sham-operated control rats (n=5 to 10 in each group) were studied at 7,14,21, and 28 days after clipping. Systolic blood pressure was elevated by day 7 (154±3 versus 111±4 mm Hg in sham group, P<.00l, n=10 each). Hypertension resulted in an early expansion of the interstitial volume by 37%, whereas hypertensive vascular changes and glomerular injury did not become evident until day 21. Immunofluorescence studies revealed an early interstitial accumulation of collagens I, m , IV, V, VI, and flbronectin by day 7. In contrast, the glomeruli showed a mild to moderate increase in collagens I, III, IV, V, laminin, and fibronectln but not collagen VI later 1 HNS may by itself accelerate and maintain high blood pressure 24 and thereby lead to a vicious circle of hypertension and renal injury. 5 The cellular and molecular mechanisms leading to HNS are still poorly understood. Vascular changes have been implicated as primary features of HNS; however, glomerular and interstitial alterations have been described as well. 68Recent studies have provided considerable insight into the molecular and cellular mechanisms causing inflammatory renal injury, in particular with respect to glomerular damage. Studies on HNS during the past decade have focused on hypertensive damage to glomeruli.18 -22 However, interstitial fibrosis may be an even more important determinant of renal injury. This hypothesis was originally raised by Bohle et al 823 and has recently found increased recognition. 24To gain insight into mechanisms, we examined cell proliferation, participation of mononuclear cells, and accumulation of extracellular matrix molecules during the development of HNS. We focused on the tubulointerstitium and examined changes early after the induction of hypertension. We used the contralateral, nonclipped kidney of two-kidney, one clip (2K1C) Goldblatt renovascular hypertensive rats as a model of HNS. -21Our results draw attention to cell proliferation, matrix deposition, and the participation of lymphocytes and macrophages at extraglomerular sites. Methods Animal Model and Experimental DesignRenovascular hypertension was produced by the 2K1C method in male Sprague-Dawley rats (SAVO,

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The present group of diabetic patients showed progressive tubular mCRP staining with declining renal function and increasing severity of histological lesions. Further studies in less proteinuric patients should clarify whether tubular mCRP expression constitutes a progression factor. It also needs to be demonstrated whether mCRP accumulates in tubuli to further stimulate interstitial fibrosis or is mandatory for the resolution of the process. Since mCRP staining was independent of proteinuria we suggest that mCRP is locally produced.

CONCLUSIONS. These data indicate that gastric carcinoma cells of the intestinal and diffuse type differ in their expression of the apoptotic receptors SC-1 and Fas and the tumor suppressor gene product p53. These new data on phenotypic differences support the hypothesis that these two types of stomach carcinoma do not only differ in morphology, growth pattern, and risk factors but also in genetic pathways.

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