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Biomedical subjects

H Moriwaki

Publications and source records attributed to H Moriwaki.

At least 19 recordsLinked to original sources

[Construct validity of a new computer-assisted cognitive assessment battery in normal adults].

A computer-assisted battery for neuropsychological tests (CNT) has been designed to screen adults for cognitive impairment. The aim of this study was to gather evidence for the construct validity of CNT and also investigate the relationship between CNT and conventional neuropsychological tests. Subjects were 45 healthy adults (21 men and 24 women), who ranged in age from 20 to 70 years (mean = 33.5, SD = 1.9) with no history of substance abuse, or of psychotic or neurological disorders. The CNT in our study consists of six subtests designed to assess various components of driving, such as digit span, visual scanning, visual and verbal memory, complex reaction time, and vigilance. Mini-mental state test, Kana-hiroi test, word fluency, the auditory-verbal learning test and Raven's colored progressive matrices were also performed as conventional neuropsychological tests. Results showed there were high correlations between each CNT subtests and conventional neuropsychological tests. A factor analysis (with varimax rotation) identified 4 factors with eigen values greater than 1, which accounted for over 70% of the variance. CNT was able to estimate each factor related to cognitive function such as learning and memory, attention, judgment, and visual scanning selectively. CNT may thus be a useful tool for detection of cognitive impairment, although this test has important limitations. Broader applications of these tests will require extensive population-based validation.

Adult

Expression of lectin-like oxidized low density lipoprotein receptor-1 in human and murine macrophages: upregulated expression by TNF-alpha.

Uptake of oxidized low density lipoprotein (Ox-LDL) and subsequent foam cell transformation have been implicated in early atherogenesis. Although multiple molecules, including class A and B scavenger receptors, have been identified as Ox-LDL receptors, additional receptors may also be involved in this process. Here, we provide evidence that lectin-like Ox-LDL receptor-1 (LOX-1), a novel Ox-LDL receptor initially identified in vascular endothelial cells, is also expressed in macrophages in humans and mice. Expression of LOX-1 can be induced after macrophage-like differentiation in vitro in human peripheral blood monocytes and the related cell line THP-1 cells. Furthermore, LOX-1 expression can also be detected in resident peritoneal macrophages, and can be upregulated by an inflammatory cytokine TNF-alpha. These results suggest that LOX-1 in macrophages may play an important role in Ox-LDL uptake and subsequent foam cell formation in this cell type.

Animals

Lysophosphatidylcholine enhances cytokine-induced interferon gamma expression in human T lymphocytes.

Accumulation of substantial numbers of activated T lymphocytes, as well as monocyte/macrophages, in focal areas of arterial intima appears to be a hallmark of atherogenesis. Our previous report demonstrated that lysophosphatidylcholine (lyso-PC), a polar phospholipid component that is increased in atherogenic lipoproteins and atherosclerotic lesions, can upregulate the expression of heparin-binding epidermal growth factor-like growth factor and the interleukin (IL)-2 receptor in cultured human peripheral T lymphocytes. In this study, we show that lyso-PC can also enhance interferon gamma (IFN-gamma) secretion and gene expression in human T lymphocytes. Lyso-PC-induced upregulation of IFN-gamma depended on the presence of IL-2, IL-12, or phytohemagglutinin in culture media and was similarly observed in both CD4+ and CD8+ subsets. Actinomycin D chase by Northern blotting showed that lyso-PC significantly prolonged IFN-gamma mRNA half-lives in human T cells. Transient transfection of IFN-gamma promoter-reporter gene construct in the human T-cell line Jurkat cells demonstrated that lyso-PC stimulated the transcription of IFN-gamma promoter-driven luciferase gene. Analyses of serial deletion mutations of IFN-gamma promoter revealed that the lyso-PC-responsive element is located between base pairs - 102 and -78 of the transcription initiation site of the IFN-gamma gene. Enhanced expression of IFN-gamma in T lymphocytes by lyso-PC may play a crucial role in atherogenesis.

CD4-Positive T-Lymphocytes

Inducible expression of lectin-like oxidized LDL receptor-1 in vascular endothelial cells.

Endothelial dysfunction, or activation, elicited by oxidized LDL (Ox-LDL) or its lipid constituent, has been implicated in the initiation and progression of atherosclerosis. We have recently identified a C-type lectin-like molecule, designated lectin-like Ox-LDL receptor-1 (LOX-1), which acts as a cell-surface receptor for Ox-LDL in cultured vascular endothelial cells. In this study, we provide evidence that LOX-1 expression can be upregulated by tumor necrosis factor-alpha (TNF-alpha) and phorbol 12-myristate 13-acetate (PMA) in cultured bovine aortic endothelial cells. TNF-alpha and PMA upregulated LOX-1 protein and mRNA in a time- and dose-dependent manner. Nuclear runoff assay revealed that TNF-alpha stimulates transcription of the LOX-1 gene. Chinese hamster ovary K1 cells stably expressing LOX-1 internalized 1,1'-dioctadecyl-3,3,3',3'-tetramethylindocarbocyanine perchlorate (DiI)-labeled Ox-LDL but did not significantly internalize acetylated LDL (Ac-LDL), which was effectively suppressed by excess amounts of unlabeled Ox-LDL but not by Ac-LDL. Upregulated expression of LOX-1 by TNF-alpha and PMA was associated with increased uptake of DiI-Ox-LDL that cannot be blocked by excess amounts of unlabeled Ac-LDL. Taken together, LOX-1 is a receptor specific for Ox-LDL, and enhanced uptake of Ox-LDL via this novel receptor on vascular endothelial cells may play an important role in endothelial activation in atherogenesis.

Animals

Tyrosine phosphorylation of platelet endothelial cell adhesion molecule-1 induced by lysophosphatidylcholine in cultured endothelial cells.

Lysophosphatidylcholine (lyso-PC), a biologically active phospholipid, appears to modulate various endothelial cell functions through tyrosine kinase-dependent signaling pathways. In cultured bovine aortic endothelial cells (BAEC), we have found that a 130 kDa protein (p130) was rapidly tyrosine phosphorylated within 2 min and sustained for, at least, 1 hr in response to 10 mumol/L of lyso-PC but not to phorbol myristate acetate (PMA). Prolonged preexposure to PMA did not affect lyso-PC-induced p130 tyrosine phosphorylation, suggesting that mechanisms independent of protein kinase C may be involved. Fractionation of the cell lysates revealed that p130 was detectable in the membrane fraction but not in the cytosolic fraction. Immunoprecipitation followed by immunoblotting of lyso-PC-treated BAEC identified p130 as bovine PECAM-1. Tyrosine phosphorylation of PECAM-1 appears to be one of the earliest events elicited by lyso-PC, and may play a role in lyso-PC-induced modulation of endothelial functions.

Animals

Percutaneous transluminal angioplasty for intracranial arteriosclerotic lesions.

We report 17 cases of intracranial arterial stenosis treated by percutaneous transluminal angioplasty (PTA), including 9 on the intracranial internal carotid (ICA), 4 on the middle cerebral (MCA), and 4 on vertebrobasilar artery (VBA) system. All patients had ischaemic brain symptoms and stenoses of more than 60% (calculated angiographically). We treated four patients by PTA for residual stenoses after thrombolysis for acute occlusion. We used PTA balloon catheters 2.0-3.5 mm in diameter for all procedures. As a rule, the balloon was inflated for 1 min at 6 atm. All arteries were successfully dilated (stenosis less than 50%) except for one treated by PTA for residual MCA stenosis after thrombolysis. The patient died of a massive infarct due to MCA reocclusion caused by arterial dissection. Stenosis recurred in 4 of 16 patients. Repeat PTA was successfully carried out in these cases. However, stenosis recurred in one of these patients 3 months after PTA, but the patient is being followed because he is asymptomatic. PTA of intracranial arteries is effective, but its indications should be based strictly on potential risks, such as acute occlusion derived from arterial dissection.

Aged

High performance liquid chromatographic determination of mercapturic acids in urine of rats administered with m- or p-xylene.

The determination of urinary mercapturic acid, N-acetyl-S-(m-xylyl)-L-cysteine or N-acetyl-S-(p-xylyl)-L-cysteine, was undertaken by HPLC after i.p. administration of m- or p-xylene to rats in order to confirm the structure of thioether which was known to be excreted in small amounts related with the metabolism of m- or p-xylene. The excretion rates of these mercapturic acids were much lower than those previously estimated from thioether determinations. The present study clearly demonstrates the mercapturic acid pathway operates only to limited degree as a metabolic route of m- or p-xylene.

Acetylcysteine

Oral supplementation with branched-chain amino acids improves survival rate of rats with carbon tetrachloride-induced liver cirrhosis.

We investigated whether supplementation with branched-chain amino acids (BCAA) improves survival of rats with carbon tetrachloride (CCl4) -induced cirrhosis. Liver cirrhosis was induced in 40 male Sprague-Dawley rats by administering CCl4 for 15 weeks. Twenty rats each were then assigned to the control and BCAA group and fed a casein diet or a BCAA-supplemented casein diet, respectively, for an additional 17 weeks with repeated injections of CCl4. No significant difference occurred in either mean energy or nitrogen intake or in body or liver weight between the two groups. BCAA-supplementation significantly preserved plasma albumin concentrations (P < 0.05) and inhibited significantly the occurrence of ascites and hyperammonemia (P < 0.05). The survival rate was significantly higher in the BCAA group (P=0.03), while no significant difference was found in liver histology between the groups. These results suggest that BCAA improved survival of rats with CCl4-induced cirrhosis by preventing hypoalbuminemia and hyperammonemia without directly reducing hepatic necrosis and fibrosis.

Administration, Oral

Suppressive effect of low amounts of safflower and perilla oils on diethylnitrosamine-induced hepatocarcinogenesis in male F344 rats.

We have investigated the modulating effects of low amounts of dietary oils rich in polyunsaturated fatty acids (PUFA) on diethylnitrosamine (DEN)-induced hepatocarcinogenesis in male F344 rats. A total of 112 animals were divided into eight groups. Groups 1-4 were given drinking water containing 40 ppm DEN for five weeks. Groups 5-8 served as controls without DEN treatment. Groups 1 and 5 were fed a basal diet containing 5% beef tallow, Groups 2 and 6 were fed a 5% olive oil diet, Groups 3 and 7 were fed a 5% safflower oil diet, and Groups 4 and 8 were fed a 5% perilla oil diet for 21 weeks, starting 1 week before DEN exposure. Beef tallow, olive oil, safflower oil, and perilla oil are rich in saturated fatty acids, a monounsaturated fatty acid, n-6 PUFA, and n-3 PUFA, respectively. All rats were killed 20 weeks after the start of the experiment. Incidences of hepatocellular adenoma and carcinoma were 100% in DEN-treated groups, irrespective of dietary oils. Multiplicities of adenomas in Groups 3 and 4 were significantly (p < 0.05) lower than in Groups 1 and 2. Multiplicity of carcinoma in Group 3 was significantly (p < 0.05) lower than in Group 1. Mean volumes of placental glutathione S-transferase-positive foci per liver and the number of argyrophilic nucleolar organizer region proteins per nucleus in the liver tumors were significantly (p < 0.05) lower in Groups 3 and 4 than in Groups 1 and 2. ras mRNA expression in liver neoplasms was also suppressed significantly (p < 0.05) in Groups 3 and 4 compared with Groups 1 and 2. Significantly (p < 0.05) higher levels of n-6 and n-3 PUFA in the phospholipid fraction of the liver were found in Groups 3 and 4, respectively, than in the other groups. In contrast, a significantly (p < 0.05) decrease in monounsaturated fatty acid was observed in Groups 3 and 4 compared with Groups 1 and 2. These results suggest that safflower oil and perilla oil, rich in n-6 and n-3 PUFA, respectively, alter the membrane fatty acid composition of the liver and suppress the development of liver cell carcinoma in rats.

Animals

Antiproliferative effect of carotenoids on human colon cancer cells without conversion to retinoic acid.

The present study employed two human colon cancer cell lines, DLD-1 and Colo 320DM, to investigate whether the provitamin A activity of carotenoids is necessary for their antitumor effect on colon cancer. Carotenoids, including alpha- and beta-carotene and canthaxanthin, significantly suppressed cell viability [measured by tetrazolium (MTT) assay], DNA synthesis (measured by [3H]thymidine uptake), and cell proliferation (measured by cell counting) and thus showed growth-inhibitory effects on both cancer cell lines. Because canthaxanthin does not have provitamin A activity, these results suggest that the carotenoid directly inhibited the cell growth. Moreover, the effective dose of retinoic acid, an active metabolite of vitamin A, was much higher than that of alpha- or beta-carotene. A retinoic acid-inducible gene, retinoic acid receptor-beta, was not enhanced in either type of cancer cell by treatment with alpha- or beta-carotene. Therefore, like canthaxanthin, alpha- and beta-carotene might also exert their tumor-suppressing effects without being converted to retinoids. These results suggest that a certain antitumor activity of carotenoids may not necessarily require their provitamin A activity.

Carotenoids

Removal of endotoxin and cytokines by plasma exchange in patients with acute hepatic failure.

OBJECTIVES: To compare the circulating concentrations of endotoxin and cytokines in patients with fulminant hepatitis and patients with the severe form of acute hepatitis, and to assess the effects of plasma exchange on the circulating concentrations of these inflammatory mediators in patients with acute hepatic failure. DESIGN: Prospective, consecutive entry study of patients meeting fulminant hepatitis criteria and the severe form of acute hepatitis criteria. SETTING: University hospital, intensive care unit. PATIENTS: Five patients with fulminant hepatitis, eight patients with the severe form of acute hepatitis, two patients with acute-on-chronic hepatic failure, and one patient with postoperative hepatic failure. INTERVENTIONS: Plasma endotoxin, serum tumor necrosis factor (TNF)-alpha, interleukin (IL)-1beta, and IL-6 were determined on admission in five patients with fulminant hepatitis and eight patients with the severe form of acute hepatitis. Circulating concentrations of the inflammatory mediators were measured before and after a single course of plasma exchange in eight patients with acute liver failure, including five patients with fulminant hepatitis, two patients with acute-on-chronic hepatic failure, and one patient with postoperative hepatic failure. MEASUREMENTS AND MAIN RESULTS: TNF-alpha and IL-6 in patients with fulminant hepatitis were significantly higher than in patients with the severe form of acute hepatitis, whereas endotoxin concentrations did not differ between patients with fulminant hepatitis or the severe form of acute hepatitis. IL-1beta was not detectable in patients with either fulminant hepatitis or the severe form of acute hepatitis. Plasma endotoxin concentrations decreased immediately after plasma exchange. Serum concentrations of TNF-alpha and IL-6 were significantly lower after plasma exchange than before plasma exchange. CONCLUSION: TNF-alpha and IL-6 may be important in the pathogenesis of the clinical symptoms that differentiate fulminant hepatitis from the severe form of acute hepatitis, and plasma exchange removes these inflammatory mediators from the circulation of patients with severe liver disease.

Adolescent

Endoscopic papillary balloon dilatation for common bile duct stones: efficacy of combination with extracorporeal shockwave lithotripsy for large stones.

BACKGROUND: Endoscopic papillary balloon dilatation (EPBD) is generally considered a safe and effective technique for removal of common bile duct (CBD) stones. However, some reports have prompted concern about the risk of pancreatitis following the procedure, and it seems to be more difficult and to require adjunctive procedures more frequently in patients with large stones. AIMS: To analyse the factors influencing pancreatitis after the procedure, and to examine which is the more suitable adjunct for treating large stones, mechanical lithotripsy (ML) or extracorporeal shockwave lithotripsy (ESWL). PATIENTS AND METHODS: EPBD was performed in 92 patients, including 40 with large stones (> or = 12 mm). These 40 patients were randomly assigned to two groups receiving ML or ESWL to fragment stones (20 patients each). RESULTS: Complete ductal clearance was obtained in all 92 patients. Significant elevation of the serum amylase level compared with the prior value (> 300 IU/l) was observed in 26 (28%), and eight (8.7%) developed clinical pancreatitis. To assess the influence of various factors on the amylase level, multivariate analysis was used. The number of stones and the time required for treatment had a significant influence on the incidence of increased amylase level (P < 0.05), and ML also significantly increased it (P < 0.05). On the other hand, the amylase level remained low in the ESWL group. ML caused elevation of amylase level in 11 patients (55%), while three (15%) had elevation after ESWL. CONCLUSIONS: In patients with multiple stones, elevation of the amylase level is more frequent. This seems to be because repeated cannulation and much time is required for treatment. In patients with large stones, the rate was also high if ML was used, but was low when ESWL was used. ESWL may reduce the incidence of pancreatitis.

Aged

Ligand specificity of LOX-1, a novel endothelial receptor for oxidized low density lipoprotein.

Endothelial dysfunction, or activation, elicited by oxidized low density lipoprotein (Ox-LDL) and its lipid constituents has been shown to play a key role in the pathogenesis of atherosclerosis. We recently have identified a novel receptor for Ox-LDL-designated lectin-like Ox-LDL receptor (LOX-1) in vascular endothelial cells. To examine ligand specificity of LOX-1, we established CHO cell lines stably expressing both human and bovine LOX-1 (LOX-1-CHO). LOX-1-CHO bound and degraded 125I-labeled Ox-LDL but did not significantly degrade 125I-labeled acetylated LDL (Ac-LDL). Fucoidin and maleylated BSA (M-BSA), which inhibit 125I-Ox-LDL binding to class A scavenger receptors, did not inhibit 125I-Ox-LDL binding or degradation in LOX-1-CHO. Polyinosinic acid and carrageenan, in contrast, significantly reduced 125I-Ox-LDL binding to LOX-1-CHO by 62% and 60%, respectively. Delipidated and untreated 125I-Ox-LDL were bound and degraded equally in LOX-1-CHO; furthermore, excess amounts of unlabeled, delipidated Ox-LDL inhibited binding and degradation of untreated 125I-Ox-LDL. Taken together, LOX-1 is a receptor for Ox-LDL but not for Ac-LDL. LOX-1 recognizes protein moiety of Ox-LDL, and its ligand specificity is distinct from other receptors for Ox-LDL, including class A and B scavenger receptors.

Animals

Preferential use of branched-chain amino acids as an energy substrate in patients with liver cirrhosis.

We analyzed basal energy metabolism in 20 healthy volunteers and 41 cirrhotic patients by indirect calorimetry. Subjects were then given either glucose, branched-chain amino acids (BCAA) or fatty acids as an energy substrate. Resting energy expenditure (REE), nonprotein respiratory quotient (npRQ), and oxidation rates of glucose (% CHO), protein (% PRO) and fat (% FAT) were analyzed. REE and %FAT were significantly higher and % CHO and %PRO were significantly lower in cirrhosis than in controls. These changes correlated with disease severity. Glucose and BCAA were utilized efficiently as energy substrates and reduced %FAT in cirrhosis. Energy efficacy (increased energy expenditure/energy equivalent of the supplemented nutrient) was significantly higher in BCAA (96 +/- 16%) than in glucose (41 +/- 8%) (p<0.01) and fatty acids (27 +/- 13%) (p<0.05). Patients with cirrhosis have an increased energy requirement. BCAA seems to be the preferred substrate to meet this demand, because its energy efficacy is higher than glucose or fatty acids in cirrhosis.

Amino Acids, Branched-Chain