We studied 2,448 patients (<70 years old) undergoing “Brain Dock” at Kurosawa hospital between July 1991 and August 1999. They were grouped in two based on MRI used: 615 patients examined by 0.5 Tesla MRI between July 1991 and December 1995, and 1,833 by 1.5 Tesla MRI between January 1996 and August 1999.
Results: 1) Cerebral ischemic changes were seen in 15.5％. Their risk factors were hypertension, diabetes, smoking, and hyperlipidemia. 2) A detection rate of suspected unruptured cerebral aneurysm rose from 2.1％ to 4.5％ using high-field MRI. 3) Unruptured cerebral aneurysms were found in 37 patients, primarily in the internal carotid cerebral artery (20) and the middle cerebral artery (13), but were rare in the anterior communicating artery (5). The 5−10 mm size aneurysm was recognized 19（48.7％）. ≤ 4mm size aneurysm was 19（48.7％）and ≥ 10mm size aneurysm was 1. 4) Twenty−one of 37 with cerebral aneurysms underwent surgery (neck clipping or coating) and all of them are now leading normal social lives without any neurological deficits. “Brain Dock” using high-field MR imaging thus shows promise in detecting unruptured cerebral aneurysms and preventing subarachnoid hemorrhage.

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 5/6 nephrectomy (Nx) causes a progressive form of chronic renal injury in rats. However, 5/6 Nx seldom induces severe renal injury in mice, and the reason remains unclear. Transforming growth factor-β(TGF-β) is known as a key cytokine involving in organ fibrosis. Connective tissue growth factor (CTGF) is an important downstream mediator of profibrotic activities of TGF-β. Hepatocyte growth factor (HGF) originally identified as a potent mitogen for hepatocyte has been shown to promote tubule repair following acute renal injury. In renal fibrosis, HGF has been assumed to block profibrotic effects of TGF-β, attenuating renal fibrosis. However, such a counteraction between HGF and TGF-β remains to be determined in detail. Then we investigated the mechanism of the anti-fibrotic effects of HGF on renal fibrosis using the 5/6 Nx model in the wild and TGF-β₁ transgenic mice and the co-culture system. In wild type mice, ribonuclease protection assay (RPA) revealed that HGF and TGF-β₁ mRNA levels in the remnant kidneys simultaneously increased at 8 hours after the nephrectomy, then decreased, and increased again at week 4 to 12. CTGF andα1(I)procollagen mRNA levels also increased at 8 hours, then decreased, but didn’t increased again. In the remnant kidneys of 5/6 Nx mice, endogenous HGF seemed to prevent renal fibrogenesis promoted by TGF-β₁. In co-culture system, RPA revealed that TGF-β₁ alone could significantly enhance the expression of α1(I)procollagen mRNA in renal tubulointerstitial fibroblasts (TFB) in the co-culture with renal proximal tubular epithelial cells (PTEC). In contrast, TGF-β₁ with HGF did not enhance the expression ofα1(I)procollagen mRNA in TFB in the co-culture. This enhancement was partially because of additional production of CTGF by PTEC stimulated by TGF-β₁ in the co-culture. In 5/6 Nx TGF-β₁ transgenic mice, excess TGF-β₁ caused significant interstitial fibrosis compared to the 5/6 Nx wild mice at week 12. The supplement of recombinant HGF was demonstrated to suppress CTGF expression thereby preventing renal fibrosis.
In conclusion, profibrotic effects of TGF-β₁ on TFB was enhanced by the co-existence of PTEC, and HGF can modulate such interaction, resulting in the antifibrotic effects. This anti-fibrotic effect of HGF against TGF-β₁ was demonstrated to be mediated by suppressing CTGF mRNA expression in the tubular epithelial cells induced by TGF-β₁.

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 We examined the effects of ligands / activators of the peroxisome proliferated-activated receptor (PPAR) on the expression of the superoxide scavenger enzyme, Cu²⁺, Zn²⁺-superoxide dismutase (CuZn-SOD), Mn²⁺-superoxide dismutase (Mn-SOD), and the superoxide generating enzyme nicotinamide adenine dinucleotide phosphate (NADPH) oxidase in primary cultures of human umbilical vein endothelial cells (HUVEC). Bezafibrate, which is a ligand / activator for PPARα, increased the CuZn-SOD, Mn-SOD, and catalase gene and protein expression levels in endothelial cells. In addition, the levels of mRNA and protein for phorbol myristate acetate (PMA)-stimulated 22-kDaα-subunit (p22phox), 47-kDaα-subunit (p47phox) and 67-kDa α-subunit in NADPH oxidase were decreased by treatment with PPARα ligands / activators. These results suggest that PPARα gene and protein expression in endothelial cells may play a physiological role as not only lipid metabolism but also active oxygen turnover and / or their elimination system, although the details of these mechanisms is now in progress.

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Objective: To investigate the role of the renin-angiotensin system and sodium in the pathogenesis of glomerulosclerosis, I examined the effect of angiotensin converting enzyme inhibitor (ACEI) and angiotensin II receptor blocker (ARB) on blood pressure and renal function in rat with glomerulosclerosis, Milan normotensive rats (MNS).
Method: Experiment 1: Twenty-four 8-week old MNS were divided into three groups as follows (1) Normal-salt diet group (0.5％NaCl), (2) Low-salt diet group (0.1％NaCl), and (3) High-salt diet group (6.0％NaCl). Each diet was given for 32 weeks. Experiment 2: Twenty-four 8-week old MNS were divided into three groups as follows (1) ACEI treated group (Delapril 10mg/kg/day), (2) ARB treated group (CV-116 3mg/kg/day), and (3) placebo treated group (control). Each of these antihypertensive drug was administrated per os for 32 weeks. In both studies, during the experiment, body weight, blood pressure and urinary excretion of protein were measured every four weeks. At the end of study, after measurement of plasma angiotensin I, angiotensin II, aldosterone and renin activity, renal tissues were obtained for light microscopic examination and for measurements of AT1a receptor, AT2 receptor, ecNOS and HO-1 mRNA by using RT-PCR.
Results: Experiment 1: During the experiment, renin-angiotensin system was high level in normal salt-diet group and it was more activated in low salt-diet. There were no significant differences in blood pressure in three groups. Marked glomerulosclerosis and interstitial cell infiltration, which were found in MNS were significantly aggravated by low-salt diet. On the contrary, glomerular changes were significantly ameliorated by high-salt diet. Experiment 2: Systolic blood pressure and urinary excretion of protein in MNS was significantly reduced by administration of ACEI. ACEI treatment induced significant elevation of the expression of AT2 receptor, ecNOS and HO-1 mRNA in the kidney. ARB treatment induced significant reduction of the expression of ecNOS and HO-1 mRNA in the kidney. Marked glomerulosclerosis and interstitial cell infiltration, which were found in the control group were significantly ameliorated by treatment of ACEI. On the contrary, there was no significant improvement in ARB treated group.
Conclusion: From these data, I concluded that histopathological change in the kidney in MNS was determined by the activation of renin-angiotensin system. On the contrary, nitric oxide and heme-oxygenase plays as the protective role in the renal insufficiency. Furthermore, ACEI and ARB were different from renalprotective effect in rat with glomerulosclerosis.

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