Search PubMed⌕ Search

Biomedical subjects

Y Muto

Publications and source records attributed to Y Muto.

At least 145 records · Page 8Linked to original sources

Adenovirus-mediated gene transfer using in-situ perfusion of the liver graft.

To establish an efficient technique for adenovirus-mediated gene transfer in liver transplantation, we evaluated the in situ perfusion of liver grafts. The grafts were perfused in situ with 1 x 10(10) of E1-deleted, replication-defective adenoviral vectors encoding the LacZ gene driven by the human CMV promoter, either through the hepatic artery (group 1) or the portal vein (group 2). Group 3 animals served as negative controls; their liver grafts were perfused with lactated Ringer's solution through the portal vein. PCR confirmed the presence of viral DNA in every graft perfused with viral vectors. In X-gal staining, positive staining was observed almost exclusively at the portal triad in group 1, whereas in group 2 minimal staining was observed, predominantly in the parenchymal area. Protein production from the transfected gene was confirmed by a functional protein assay; the values were 0.16% +/- 0.07% liver protein in group 1, 0.13% +/- 0.02% in group 2, and 0.007% +/- 0.0003% in group 3 on postoperative day 2. In conclusion, in situ perfusion of the viral vectors through the hepatic artery resulted in an effective expression of the transfected gene, predominantly at the portal triad.

Adenoviridae↗

The effect of cyclosporin on endothelin levels after orthotopic liver transplantation in rats.

To assess the effects of cyclosporin (CyA) on endothelin-1 (ET-1) in rat liver allograft rejection, we evaluated ET-1 expression in samples obtained from BN(RT1n)-to-BN (group 1) rats, DA(RT1a)-to-BN (group 2) rats, and DA-to-BN rats treated with 5 mg/kg per day of CyA (group 3). Serum and hepatic ET-1 levels, determined by a radioimmunoassay, remained unchanged in group 1. In group 2, the ET-1 levels peaked on postoperative day (POD) 5 in the liver at 344 +/- 31.6 pg/g wet, and on POD 7 in the serum at 38.7 +/- 13.1 pg/ml. In group 3, hepatic and renal ET-1 levels showed a progressive increase until POD 10, while serum ET-1 levels remained unchanged. In conclusion, acute rejection caused a temporary increase in the ET-1 level in both the serum and the liver in the early postoperative period what might have been caused by endothelial damage due to ongoing, acute rejection. CyA caused a time-dependent increase in the ET-1 level in both the liver and the kidney without an increase in the serum ET-1 level. The serum ET-1 level might have been affected by the clearance of ET from the liver or kidney.

Animals↗

Growth suppression and induction of heat-shock protein-70 by 9-cis beta-carotene in cervical dysplasia-derived cells.

The aim of the present study was to determine to what extent 9-cis beta-carotene, one of the most abundant naturally-occurring cis-isomers of beta-carotene, can inhibit the growth of cervical dysplasia-derived cells in comparison with all-trans beta-carotene. We found that 9-cis beta-carotene was dose-dependently more effective than all-trans beta-carotene. Both carotenes induced the intracellular accumulation of heat-shock protein-70 (HSP70), and the treated cells showed morphological changes indicative of apoptosis. The results of the present study strongly suggest that the induction of HSP70 by beta-carotene might be involved in beta-carotene-mediated suppression of the cell growth through apoptosis.

Cell Division↗

Angiotensin converting enzyme inhibitors suppress production of tumor necrosis factor-alpha in vitro and in vivo.

It has been reported that angiotensin converting enzyme (ACE) inhibitors have beneficial effects on insulin resistance and congestive heart failure, in which elevations of serum tumor necrosis factor-alpha (TNF-alpha) level have been indicated. Therefore, in this study, we examined effect of ACE inhibitors on TNF-alpha production both in vitro and in vivo by using human blood mononuclear cells and mice, respectively. LPS (20 micrograms/ml)-induced in vitro TNF-alpha production, measured by bioassay and enzyme-linked immunosorbent assay, was significantly inhibited with captopril, delapril and cilazapril in a concentration of 10(-3) mol/l. A single, oral administration of captopril, delapril and cilazapril at more than 10-fold doses of common clinical use in man significantly inhibited LPS (2 mg/kg)-induced serum TNF-alpha activity in Balb/c mice. These results indicate that ACE inhibitors such as captopril, delapril and cilazapril have an inhibitory effect on TNF-alpha production not only in vitro as previously reported, but also in vivo, although relatively high concentrations and large doses were required in this study.

Angiotensin-Converting Enzyme Inhibitors↗

Inhibitory effect of nicotinamide on in vitro and in vivo production of tumor necrosis factor-alpha.

Nicotinamide, a pellagra-preventive factor, has multiple functions such as inhibition of poly-ADP-ribose synthetase, inhibition of inducible nitric oxide synthase, free radical scavenging and suppression of major histocompatibility complex class II expression and ICAM-1 expression on endothelial cells. In addition to these, we have found an inhibitory effect of nicotinamide on production of tumor necrosis factor-alpha (TNF-alpha) in vitro and in vivo. Lipopolysaccharide (LPS)-induced in vitro TNF-alpha production by human peripheral blood mononuclear cells, measured by enzyme-linked immunosorbent assay (ELISA), was significantly inhibited with more than 1 x 10(-3) mol/l of nicotinamide, while interleukin-1-beta was not inhibited and interleukin-6 was slightly inhibited even with 10(-2) mol/l. Oral administration of nicotinamide with more than 62.5 mg/kg also significantly inhibited LPS-induced serum TNF-alpha production measured by ELISA and bioassay in Balb/c mice. Thus, nicotinamide has an inhibitory effect on TNF-alpha production that may be beneficial to TNF-alpha-mediated diseases.

Animals↗

Retinoids exacerbate rat liver fibrosis by inducing the activation of latent TGF-beta in liver stellate cells.

Liver stellate cells (SCs) play central roles in both the storage of retinol and the development of liver fibrosis. The present study is aimed to understand the mechanism by which retinoic acid (RA, an active metabolite of retinol) enhances hepatic fibrosis in rats. We tested the effect of 9-cis-RA on several aspects in vitro rat SC cultures, including the activity of cellular plasminogen activator (PA), messenger RNA (mRNA), and protein levels of transforming growth factor-beta (TGF-beta) mRNA level of type-I procollagen, and the activity of type-I collagenase. Employing the rat liver fibrosis model produced by porcine serum, we also estimated the effect of oral administration of a stable RA analog on the progression of the fibrosis, as well as on hepatic TGF-beta contents. In vitro SC cultures, 9-cis-RA enhanced cellular PA and plasmin levels thereby induced plasmin-mediated activation of latent TGF-beta. Active TGF-beta generated self-stimulated its synthesis as well as that of collagen and suppressed the production of collagenase in an autocrine manner. In in vivo rat models, an RA analog accelerated the porcine serum-induced fibrosis by enhancing TGF-beta contents and, thus, collagen levels in the liver, although the RA analog alone was not fibrogenic. These results suggest that RA exacerbated liver fibrosis, at least in part, by inducing the activation and production of latent TGF-beta in liver SCs.

Adipocytes↗

Clinical efficacy of lactulose in cirrhotic patients with and without subclinical hepatic encephalopathy.

Seventy-five cirrhotic patients with hyperammonemia in the past or at the time of the study were randomly divided into two groups (treated with lactulose or nontreated) in 14 hospitals in Japan. Thirty-six cirrhotic patients were diagnosed as having subclinical hepatic encephalopathy (SHE), and 39 were diagnosed as non-SHE. SHE was diagnosed when the results of all three of the quantitative psychometric tests used (number connection test, and symbol digit and block design tests of the Wechsler adult intelligence scale [revised]) were abnormal as compared with age-matched normal values. The mean number of abnormal psychometric test results and the prevalence of SHE were used for a quantitative evaluation of the efficacy of the lactulose treatment. Twenty-two of the SHE patients were treated with lactulose (45 mL/d) for 8 weeks, and the other 14 SHE patients did not receive lactulose. In the SHE patients administered lactulose, the results of the quantitative psychometric evaluation were significantly improved at 4 and 8 weeks after the beginning of the lactulose administration. The SHE had disappeared in 10 (50%) of the 20 treated patients at week 8, but it persisted in 11 (85%) of the untreated 13 patients. We concluded that lactulose treatment in cirrhotic patients with SHE is effective with respect to psychometric tests.

Administration, Oral↗

Proton NMR study of triantennary complex type N-linked glycan chains: assignment of proton chemical shifts of the beta-Man residue in a basic unit of the triantennary glycan chain having a GlcNAc beta 1-->6 Man alpha 1-->6 Man beta-->sequence.

The chemical shifts of ring protons of the beta-Man residue in a triantennary complex type N-linked glycan chain having a GlcNAc beta 1-->6(GlcNAc beta 1-->2)Man alpha 1-->6 Man beta sequence were unambiguously determined by two-dimensional proton nuclear magnetic resonance (1H-NMR) spectroscopic methods. The chemical shift of H4 (3.84 ppm) of the beta-Man residue was for the first time revealed to be different from those (approximately 3.77 ppm) of biantennary and alternative type of triantennary glycans having a GlcNAc beta 1-->2 Man alpha 1-->6 Man beta sequence, but quite close to that (3.86 ppm) of a pentaantennary glycan containing a GlcNAc beta 1-->6 residue on the Man alpha 1-->6 Man beta sequence. Thus, the addition of GlcNAc beta 1-->6 residue on the Man-4' residue, whose formation is catalyzed by GlcNAc transferase V, is considered to cause a down-field shift of beta-Man H4 in the complex-type N-glycan chains. One possible explanation of this phenomenon is that the conformation of Man alpha 1-->6 arm is folded back toward the proximal core region, as is the case with the complex-type N-glycan chains with the bisecting GlcNAc residue.

Acetylglucosamine↗

Perilla oil prevents the excessive growth of visceral adipose tissue in rats by down-regulating adipocyte differentiation.

We examined the effect of dietary oils with different fatty acid compositions on the growth of visceral adipose tissue in rats. Rats were fed for 4 mo starting at weaning a basal diet containing (12 g/100 g diet) perilla oil rich in (n-3) polyunsaturated fatty acids (PUFA), safflower oil rich in (n-6) PUFA, olive oil rich in monounsaturated fatty acid, or beef tallow rich in saturated fatty acids. The amount of food consumed and body weight gain did not differ among the four dietary groups. The weight of the epididymal fat pad and the serum triglyceride concentration in perilla oil-fed rats were significantly lower (P < 0.05) than those of olive oil- and beef tallow-fed groups. The product of [(volume of individual adipocytes) x (number of adipocytes in epididymal fat pad)], which presumably represents total adipocyte volume in the fat pad, was significantly lower (P < 0.05) in perilla oil-fed rats than in beef tallow- and olive oil-fed groups. Expression of the late genes of adipocyte differentiation, peroxisome proliferator-activated receptor alpha, adipocyte P2 and adipsin, was significantly (P < 0. 05) down-regulated in epididymal fat tissue of rats that had been fed perilla oil rather than beef tallow or olive oil, whereas expression of the early gene, lipoprotein lipase, was not significantly affected. Greater levels (P < 0.05) of (n-3) PUFA in the membrane phospholipid fraction of the fat tissue were observed in perilla oil-fed rats than in the other dietary groups. These results suggest that perilla oil or (n-3) PUFA prevents excessive growth of adipose tissue in rats at least in part by suppressing the late phase of adipocyte differentiation.

Adipocytes↗

Clinicopathologic features of resected primary adenosquamous carcinomas of the liver.

Four cases of resected adenosquamous carcinoma of the liver were clinicopathologically reviewed, together with immunohistochemical findings. Although no lymph node metastases were seen and a curative resection was achieved in all cases, two patients had recurrences in the peritoneum and distant organs such as the pericardium and pleura relatively soon after the operation. Of the remaining two cases, one patient died during the postoperative period and the other died of coexistent hilar cholangiocarcinoma. Together these findings suggest that this disease tends to spread locally and distantly in the early phase of tumor growth and shows aggressive biological behavior. In an immunohistochemical study, involucrin was a specific marker for the squamous component and CA19-9 was a marker for the adenomatous component.

Aged↗

Effect of lactulose on short-chain fatty acids and lactate production and on the growth of faecal flora, with special reference to Clostridium difficile.

Lactulose exerts a beneficial effect on hepatic encephalopathy by decreasing toxic short-chain (iC4-nC6) fatty acid (isobutyrate, butyrate, isovalerate, valerate, isocaproate and caproate) production. However, the precise mechanism by which lactulose exerts this effect remains uncertain. This study investigated the effect of lactulose on faecal flora, particularly Clostridium difficile, which produces mostly iC4-nC6 fatty acids. An in-vitro faecal incubation system was used to estimate how lactulose influences production of short-chain (C2-nC6) fatty acids and lactate. Faecal specimens were collected from patients with liver cirrhosis, who carried C. difficile in the colon. Supplementation of lactulose along with blood in faecal specimens decreased iC4-nC6 fatty acids production and increased acetate and lactate production, resulting in increased faecal acidity. These changes were statistically significant when compared with supplementation by blood alone. Quantitative faecal culture demonstrated that lactulose supplementation suppressed the growth of C. difficile and Bacteroides spp. (B. fragilis group), iC4-nC6 fatty acids-producing organisms. These results suggest that decreased faecal levels of iC4-nC6 fatty acids after lactulose supplementation may be related to suppression of iC4-nC6 fatty acids-producing faecal organisms, especially C. difficile.

Aged↗

ME-3407, a new antiulcer agent, inhibits acid secretion by interfering with redistribution of H(+)-K(+)-ATPase.

ME-3407 is a newly developed antiulcer drug that markedly promoted the healing of acetic acid-induced chronic ulcers in rats presumably due to potent inhibition of acid secretion. ME-3407 and its metabolites, the sulfoxide of which was preserved, produced dosedependent inhibition of aminopyrine accumulation by rabbit gastric glands stimulated by any agonist, suggesting that the site of their action was downstream from the production of second messengers. Although one of the metabolites, EF-4025, showed some inhibitory effects on functional activities of H(+)-K(+)-ATPase, ME-3407 itself was not a proton pump inhibitor. ME-3407, but not omeprazole, inhibited the stimulation-associated redistribution of H(+)-K(+)-ATPase from microsomes into the apical membranes in addition to delocalizing ezrin, a putative F-actin-membrane linker, from apical plasma membrane. ME-3407 and EF-4025 inhibited myosin light chain kinase (MLCK) and protein kinase A activities. Because another MLCK inhibitor, wortmannin, showed the same properties as ME-3407, i.e., inhibition of aminopyrine accumulation, inhibition of stimulation-associated redistribution of H(+)-K(+)-ATPase, and abnormal distribution of ezrin, we hypothesize that MLCK is one of the potential targets for the drug. We conclude that ME-3407 is a promising drug for treating peptic ulcers, as well as a useful tool for studying mechanisms of parietal cell activation, especially related to the recruitment and recycling of the proton pump.

Acetic Acid↗

Antioxidative mechanism and apoptosis induction by 3-hydroxyanthranilic acid, an antioxidant in Indonesian food Tempeh, in the human hepatoma-derived cell line, HuH-7.

Recently, a new potent antioxidant was isolated from Tempeh (a traditional fermented soybean food in Indonesia) and was identified as 3-hydroxyanthranilic acid (HAA). This study deals with the antioxidant mechanism of HAA under biological systems and the cytokilling function of HAA to human malignant cells. HAA eliminated free radicals and inhibited the formation of fatty acid hydroperoxide in vitro, suggesting that HAA would serve as an antioxidant in the initial reaction in lipid oxidation systems. Actually, HAA inhibited the formation of the dominant product of membrane lipids, 12-hydroxyeicosatetraenoic acid (12-HETE) at a high concentration, while HAA accelerated 12-HETE formation at a low concentration in mammalian tissue. HAA oxidized glutathione and inhibited superoxide dismutase in vitro. Furthermore, HAA inhibited cell growth and induced apoptosis to HuH-7, a human hepatoma-derived cell line. As long as HAA is taken as a component of Tempeh, and not in large doses as a chemical, it may possibly act as a prooxidant rather than an antioxidant in vivo.

12-Hydroxy-5,8,10,14-eicosatetraenoic Acid↗

[Smoldering leukemia with CD7.CD34(+), immunoglobulin heavy chain rearrangement (+) and hypoplastic marrow with myelofibrosis].

A 63-year-old male was admitted because of pneumonia. Peripheral blood findings showed pancytopenia with increase of blasts. A bone marrow specimen showed hypocellular marrow with increase of blasts. The blasts were positive for CD7, CD34, and HLA-DR and negative for other lymphoid antigens and myeloid antigens involving myeloperoxidase. Rearrangement of immunoglobulin heavy chain was demonstrated by Southern blotting analysis. T cell receptor beta, T cell receptor gamma and immunoglobulin light chain rearrangement were negative. A diagnosis of stem cell leukemia was made. In vitro, the blasts did not respond to recombinant human granulocyte colony-stimulating factor (rhG-CSF), cytarabine (Ara-C) and all-trans retinoic acid (ATRA). However, in the blasts of culture without cytokeins, CD33 expression was newly induced. Remission was not obtained by chemotherapies with cyclophosphamide, etoposide, prednisolone and Ara-C. Four months later, marrow specimens showed hypoplasty with myelofibrosis. One year later, the blasts showed CD33 expression with negative myeloperoxidase. The leukemia was transformed to minimally differentiated myeloid leukemia from stem cell leukemia. This condition was thought to be "smoldering leukemia" because of the slow development and refractoriness to chemotherapy. Nineteen months later the patient died due to respiratory failure by pneumonia and pulmonary bleeding despite therapy.

Acute Disease↗

[Werner's syndrome developing acute megakaryoblastic leukemia with der(1;7)].

A 46-year-old man with Werner's syndrome was admitted with epigastralgia and body weight loss. The peripheral blood findings showed anemia, thrombocytosis and eosinophilia. Bone marrow aspiration and biopsy revealed increases in eosinophils and megakaryocytes, myelodysplastic change with 6.6% myeloblast, and myelofibrosis. Chromosomal analysis revealed 46, XY, +der(1;7), -7, del(20). He was diagnosed as having myelodysplastic syndrome with myelofibrosis or essential thrombocythemia. Three months later, pancytopenia appeared with a relative increase of blasts positive for CD41 and negative for myeloperoxidase. He died of respiratory failure due to pneumonia. An autopsy revealed severe myelofibrosis with proliferation of megakaryocytes and blasts. A final diagnosis of acute megakaryoblastic leukemia was made. Werner's syndrome is rare, and it is even more unusual to have the complication of acute leukemia with der (1;7) seen in this case.

Chromosomes, Human, Pair 1↗

Thoracoscopic thoracic splanchnicectomy for chronic pancreatitis with intractable abdominal pain.

The therapeutic advantages of a thoracoscopic thoracic splanchnicectomy (TTS) to relieve the pain of chronic pancreatitis patients was evaluated. The TTS procedure (four bilateral and five unilateral TTS), was performed on nine patients from April 1993 to October 1995. Based on radiographic images, the pancreatic duct of seven cases were diagnosed as being "nondilated" (<3 mm), whereas two cases were "dilated" (> or = 3 mm). A 5-mm thoracoscope was introduced through the fifth intercostal space on the anterior axillary line, and an additional two cannulas were introduced under direct thoracoscopic vision. The sympathetic chain, at a level from Th 5 to 9, was then resected and electrocoagulated. We performed a unilateral TTS corresponding to the symptomatic side; however, if pain relief was insufficient, an additional sympathectomy was done on the other side. The early postoperative course was uneventful, and immediate pain-relief was normally possible after TTS except for three patients who demonstrated minor intercostal neuralgia at the site of the trocars inserted for TTS. Six of nine patients were able to return to their preoperative work of lifestyle at a maximum follow-up of 24 months (the median and mean durations were 15.0 and 13.7 months, respectively). In addition, no postoperative deterioration of either the endocrine or exocrine function of the pancreas was observed. In conclusion, TTS proved to be a safe and reliable procedure for the pain relief of the chronic pancreatitis.

Abdominal Pain↗

An aneurysm of the right gastroepiploic artery.

A palpable mass was unexpectedly found in the upper abdomen of a 67-year-old woman. Computed tomography (CT) and abdominal angiography both indicated an aneurysm of the right gastroepiploic artery. An aneurysmectomy was performed, and the aneurysm was found to be spherical with a diameter of 7.5 x 7.7 cm. The patient was eventually discharged in good condition. The histological findings of the aneurysmal wall revealed medial fibrosis and atherosclerosis. Gastroepiploic artery aneurysms are rare among splanchnic artery aneurysms and most such aneurysms are found to be ruptured. The present report described a quite rare case of an asymptomatic giant gastroepiploic artery aneurysm and also includes a review of the 10 reported cases of gastroepiploic artery aneurysms in the English literature to date. Since gastroepiploic artery aneurysms have a high risk of rupture it is essential that appropriate surgical measures be taken immediately.

Aged↗