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Biomedical subjects

S Otani

Publications and source records attributed to S Otani.

At least 145 records · Page 8Linked to original sources
PubMed1996

Detection of lysyl oxidase gene expression in rat skin during wound healing.

Lysyl oxidase (LOX) initiates the crosslinking of the lysine-derived aldehyde and plays an essential role in maturation of collagen, for example in wound healing. Although the activity of this enzyme has been examined in various disorders, and a further intriguing aspect of the relationship between LOX and tumorigenesis has recently emerged, its gene expression pattern in tissues is still unknown. We examined LOX gene expression during wound healing in rat skin. In addition, type III collagen gene expression was studied to determine the formation of fibrils. The LOX mRNA level reached a peak by day 3 after injury, which was earlier than that of type III collagen, and continued at a high level until day 22. The type III collagen mRNA level began to rise from day 3 and had increased intensely by day 22. In situ hybridization revealed grains corresponding to LOX mRNA in the fibroblasts of the granulomatous tissue. These results suggest that LOX is produced before collagen synthesis in preparation for crosslinking in the early phase of wound healing.

Animals↗
PubMed1996

Highly hydrogenated dietary soybean oil modifies the responses to polychlorinated biphenyls in rats.

The effects of dietary highly hydrogenated soybean oil (HSO) upon the changes caused by dietary polychlorinated biphenyls (PCBs) were examined in rats. Six groups of rats were fed the following diets for 30 d: a 20% soybean oil-containing diet (control diet), a diet in which a half of soybean oil was substituted with HSO (HSO-A diet), a diet in which cellulose powder was replaced with HSO (HSO-B diet) and these diets supplemented with 100 ppm PCBs (control + PCBs, HSO-A + PCBs and HSO-B + PCBs diets). Hepatic concentration of PCBs and relative liver weight were markedly decreased in rats fed with the HSO-A + PCBs diet compared with those fed with the other diets containing PCBs. Liver lipids and liver cholesterol were considerably decreased with a reciprocal increase in fecal sterol excretion by rats fed the HSO-A + PCBs and the HSO-B + PCBs diets compared with those fed with the control + PCBs diet. The fatty acid composition in hepatic phospholipids showed an independent increase of the saturated fatty acid content induced by dietary HSO and PCBs. Dietary PCBs also caused decreases in the amounts of monounsaturated and n-3 polyunsaturated fatty acids. These results suggest that dietary HSO prevents accumulation of PCBs in the liver and promotes the excretion of lipids stimulated by PCBs, accompanied by a change in fatty acid metabolism.

Animals↗
PubMed1996

Suppressive effects of chlorophyllin on mutagen-induced umu C gene expression in Salmonella typhimurium (TA 1535/pSK 1002) and tumor promoter-dependent ornithine decarboxylase induction in BALB/c 3T3 fibroblast cells.

The potentially protective role of chlorophyllin, the sodium and copper salt of chlorophyll a against the initiation and promotion stages in carcinogenesis was studied by in vitro short-term assays. Chlorophyllin showed a dose-dependent suppressive effect on 3-amino-1,4-dimethyl-5H-pyrido[4,3-b]indol (Trp-P-1)-induced umu C gene expression of Salmonella typhimurium (TA 1535/pSK 1002) in the presence of metabolizing enzyme mixture. The similar inhibitory effect of chlorophyllin was detected in mitomycin C (MMC)-dependent umu C gene expression in the absence of metabolizing enzyme mixture. Furthermore chlorophyllin also exhibited a dose-dependent inhibition on 12-O-tetradecanoyl-phorbol-13-acetate (TPA)-induced ornithine decarboxylase (ODC) activity of 3T3 fibroblast cells at the same concentrations. However, when chlorophyll a isolated from Japanese tea leaves was applied on the same assay systems as a comparative experiment, chlorophyll a showed much weaker activity compared with that of chlorophyllin. The significance of this finding is discussed from the viewpoint of the protective role of chlorophyllin against carcinogenesis.

3T3 Cells↗
PubMed1996

Phosphorus intake regulates intestinal function and polyamine metabolism in uremia.

This study found that 5/6-nephrectomized uremic rats showed secondary hyperparathyroidism as reflected by an increase in their serum parathyroid hormone (PTH) level in association with a decrease in serum 1,25-dihydroxyvitamin D [1,25-(OH)2D]. These changes recovered partially upon phosphorus restriction. Calcium absorption and gene expression of calbindin-D9k were decreased in uremia and were also improved by phosphorus restriction. In uremia, intestinal spermidine/spermine N1-acetyltransferase activity was decreased, while ornithine decarboxylase (ODC) activity and its gene expression were potentiated. Enhancement of c-fos and c-jun gene expressions was also observed in uremia. These phenomena suggest that the intestinal villus may proliferate in uremia. Phosphorus restriction prevented increases in the expression of ODC, c-fos and c-jun observed in uremia. Since phosphorus restriction caused a rise in the serum 1,25-(OH)2D level, the role of 1,25-(OH)2D in uremia-induced intestinal dysfunction was examined. A single injection of 1,25-(OH)2D3 to uremic rats caused an increase in the steady-state calbindin-D9k mRNA level, and decreases in steady state c-fos and ODC mRNA levels, suggesting that the deficiency of 1,25-(OH)2D3 is responsible for intestinal dysfunction in uremia. In conclusion, altered polyamine metabolism caused by 1,25-(OH)2D deficiency is intimately involved in intestinal dysfunction and the development of the proliferative state of the intestinal villus in uremia.

Absorption↗
PubMed1996

Effect of vitamin E deficiency on inhibition of liver regeneration by long-term administration of alcohol.

The effects of vitamin E (VE) deficiency on liver regeneration suppressed by long-term administration of alcohol were studied. Male rats were divided into two groups: the alcohol group and the control group. In addition, each group was subdivided into two groups according to the presence or not of VE. Altogether, four groups were provided: a group maintained on the VE-deficient alcohol diet (group EA), a group maintained on the VE-deficient control diet (group EC), a group maintained on the ordinary alcohol diet (group A), and a group maintained on the ordinary control diet (group C). After pair-feeding for 6 weeks, partial hepatectomy was performed to determine the omithine decarboxylase (ODC) activity, polyamine levels, lipid peroxide levels, and DNA synthesis, DNA synthesis at 24 hr after partial hepatectomy was suppressed significantly in the alcohol administration group, regardless of the presence or not of VE DNA synthesis at 48 hr after partial hepatectomy tended to show low values in group EA, compared with group A. As for the hepatic ODC activity, group EA showed the lowest value at 4 hr after partial hepatectomy. Of polyamines, the putrescine level in group EA at 4 hr after partial hepatectomy was significantly low, compared with the other three groups. The levels of spermidine and spermine decreased by long-term administration of alcohol, but the effect of VE deficiency was not found. The lipid peroxide level increased significantly in the VE-deficient diet administration group, but the effect of alcohol administration was not found. These results suggested that the decrease in putrescine after ODC suppression by VE deficiency in addition to the decrease in spermidine and spermine caused by long-term alcohol administration were concerned with suppression of DNA synthesis later.

Animals↗
PubMed1996

Overexpression of c-myc messenger RNA in primary and metastatic lesions of carcinoma of the stomach.

BACKGROUND: Although c-myc expression in carcinoma of the stomach has been reported to be involved in progression of the disease, little is known about the mechanism or significance of its expression. STUDY DESIGN: We measured c-myc messenger RNA (mRNA) levels by Northern blot hybridization in 51 primary gastric carcinoma lesions and 15 metastatic lesions accompanied by normal mucosal tissues from the same patients. The extent of c-myc mRNA expression in malignant lesions was determined and compared with that in normal mucosal tissues. The clinical and pathologic significance of c-myc mRNA expression was investigated. RESULTS: In 35 (68.6 percent) of 51 primary gastric carcinomas c-myc mRNA was overexpressed. Expression was found to be more frequent and stronger in early lesions than in advanced lesions (90 percent, 6.15-fold compared with 54.8 percent, 2.42-fold, p < 0.05). However, c-myc mRNA expression in the primary lesions showed little influence on either the histologic features or the disease progression. C-myc mRNA levels were higher in every metastatic lesion than in the primary lesions (9.89-fold compared with 3.04-fold, p < 0.05). CONCLUSIONS: These observations suggest that c-myc mRNA overexpression may play a role in the early development of primary lesions as well as in the formation of metastatic lesions of carcinomas of the stomach.

Blotting, Northern↗
PubMed1996

[Preanesthetic evaluation of cardiovascular reserve in a patient with dilated cardiomyopathy].

We described an anesthetic management of a patient with abdominal aortic aneurysm associated with dilated cardiomyopathy (DCM) focusing on preanesthetic evaluation of cardiovascular reserve and on intraoperative continuous circulatory monitoring with transesophageal echocardiography (TEE) and continuous cardiac output measurement (CCO). Based on echocardiographic and hemodynamic measurements after a 50 m-walk load, we predicted the allowable range of alteration of preload (LV diastolic dimension; Dd), myocardial performance (arterial blood pressure and ejection fraction) and of heart rate. During anesthesia and operation, we continuously monitored Dd, arterial blood pressure, heart rate and cardiac output, and maintained these variables within the allowable range. The changes in preload after clamping or unclamping of the aorta was promptly reflected by Dd as compared to pulmonary capillary wadge pressure. The CCO was also usuful in detecting abrupt changes in myocardial performance. In conclusion, we suggest preanesthetic stress test to be performed to evaluate cardiovascular reserve and to predict the allowable range of alteration of hemodynamic variables. Continuous monitoring of preload (Dd) by TEE and of myocardial performance by CCO is useful to detect early changes in these variables.

Anesthesia, General↗
PubMed1996

The involvement of polyamines in the proliferation of cultured retinal pigment epithelial cells.

PURPOSE: To investigate the involvement of polyamines (putrescine, spermidine, and spermine) in the proliferation of retinal pigment epithelium (RPE) using cultured bovine RPE cells. METHODS: The polyamine content and the activities of rate-limiting enzymes in polyamine biosynthesis (ornithine decarboxylase [ODC] and S-adenosylmethionine decarboxylase [SAMDC]) and in polyamine biodegradation (spermidine spermine N1-acetyltransferase [SAT]) were measured after proliferative stimulation by 10% fetal calf serum (FCS). DNA synthesis was determined by [3H]thymidine incorporation into the acid-insoluble fraction after the addition of an inhibitor of ODC (alpha-difluoromethylornithine [DFMO]) or SAMDC (methylglyoxal bis[guanylhydrazone] [MGBG]). The effects of exogenous polyamines on DNA synthesis after the additions of inhibitors also were determined. RESULTS: ODC and SAMDC activities were elevated after stimulation by FCS and reached their peaks 16 hours and 4 hours, respectively, after the addition of FCS. SAT activity was not increased. Polyamine content was increased significantly after stimulation by FCS. DFMO did not inhibit DNA synthesis induced by FCS, and only putrescine content was decreased significantly among polyamines. However, MGBG inhibited DNA synthesis in a dose-dependent manner, and the amounts of spermidine and spermine were decreased significantly. Exogenous polyamines, especially spermine, restored MGBG-induced inhibition of DNA synthesis. CONCLUSIONS: Polyamines are essential for the proliferation of cultured bovine RPE cells. These data suggest that, of the polyamines, spermine has the greatest effect on DNA synthesis although other polyamines can substitute for spermine at higher concentrations with similar results. As for polyamine metabolism in RPE proliferation, it is possible that SAMDC is the key enzyme rather than ODC.

Acetyltransferases↗
PubMed1996

[Successful scartectomy and cryoablation for ventricular tachycardia occurring late after correction of tetralogy of Fallot].

A 26-year-old man had a total repair of tetralogy of Fallot at 1 year of age, and had redo surgery for restenosis of the right ventricular outflow tract and small residual VSD at 11 years of age. After the second operation, AV block developed and an endocardial pacemaker system was implanted. For the last 3 years, he had mild febrile episodes, cough, occasional hemoptysis and paroxysmal ventricular tachycardia. Because of his refractory tachycardia and suspected infective endocarditis, he was admitted for further study. Blood culture revealed Peptostreptococcus, echocardiogram showed vegetation around intravenous pacing lead, and electrophysiological study demonstrated delayed potential on the left side of the right ventricular outflow tract. He underwent scartectomy and cryoablation of the focus of the tachycardia which was reconfirmed by epicardial and endocardial mapping during the operation, which involved removal of the endocardial lead and new outflow tract patch repair. His postoperative course was uneventful without any antiarrhythmic drugs. Pathological examination of the scar showed myocardial fibrosis and replacement by fatty tissue which was different from the pathological characters of the arrythmogenic right ventricular dysplasia.

Adult↗
PubMed1995

Expression of immunoreactive human hepatocyte growth factor in human esophageal squamous cell carcinomas.

Hepatocyte growth factor (HGF) is a potent mitogen for epithelial cells that promotes cell motility and invasiveness. In this study, we report that the human esophageal squamous cell carcinoma (SCC) shows a significant elevation of HGF concentration (600 +/- 416 ng/100 mg protein), compared to normal mucosa (80 +/- 183 ng/100 mg protein) (P < 0.01). An association could be established between levels of HGF and decreasing differentiation of 37 SCCs. The 2-year crude survival rates were 51.1% and 68.4% at high and low HGF concentrations, respectively. The results indicate that HGF is significantly increased in human esophageal SCCs, especially of poorly differentiated type. HGF might thus be useful as a biological biomarker for characterization of human esophageal SCCs.

Adult↗
PubMed1995

Randomised trial of effects of interferon-alpha on incidence of hepatocellular carcinoma in chronic active hepatitis C with cirrhosis.

Patients with chronic active hepatitis C and cirrhosis often develop hepatocellular carcinoma. Interferon (IFN) seems to be effective in some patients but whether it prevents carcinogenesis is unknown. In a prospective randomised controlled trial, we evaluated the effects of IFN-alpha in cirrhotic patients with HCV infection because of their high risk of hepatocellular carcinoma. 90 patients with compensated chronic active hepatitis C with cirrhosis were randomly allocated to receive IFN-alpha (6 MU three times weekly for 12-24 weeks) (45 patients) or symptomatic treatment (45 controls), and were followed up for 2-7 years. In nine controls, alanine aminotransferase (ALT) decreased to less than 80 IU/L but did not stay in the normal range. In 19 patients given IFN-alpha, ALT decreased to less than 80 IU/L (in seven patients, it became and stayed normal; p = 0.011, Wilcoxon rank-sum test). However, the mean change in ALT was not significantly different between the two groups. The mean change in peak alpha-fetoprotein values was smaller in patients given IFN-alpha than in controls (p = 0.021). The mean change in the serum albumin level was higher in the IFN-alpha group (p < 0.001). The histological activity index in the 12 IFN-alpha patients undergoing a second biopsy after therapy was improved (p = 0.031). Hepatitis C viral RNA disappeared in seven (16%) of the 45 IFN-alpha patients (95% CI, 7-29%) and in none of the 45 controls (0-8%; p = 0.018). Hepatocellular carcinoma was detected in two (4%, 1-15%) IFN-alpha patients and 17 (38%, 24-54%) controls (p = 0.002, Wilcoxon signed-rank test). The risk ratio of IFN-alpha treatment versus symptomatic treatment was 0.067 (0.009-0.530; p = 0.010 Cox's proportional hazards). IFN-alpha improved liver function in chronic active hepatitis C with cirrhosis, and its use was associated with a decreased incidence of hepatocellular carcinoma.

Antineoplastic Agents↗
PubMed1995

Polyamine metabolism in the rat liver after orthotopic liver transplantation.

We examined the polyamine metabolism in liver transplanted after cold ischemia and effects of putrescine administration on liver injury, liver regeneration, and survival rate after orthotopic liver transplantation in the rat. Male Wistar rats were used as donors and recipients. Grafts were stored in Euro-Collins solution for 6 h at 4 degrees C. Orthotopic liver transplantation was performed by the three cuff technique. The activities of aspartate aminotransferase, alanine aminotransferase and lactate dehydrogenase elevated and peaked 4 h after liver transplantation. Hepatic ornithine decarboxylase and spermidine/spermine N1-acetyltransferase activities were also elevated and peaked 8 h after the operation. In agreement with the increases in ornithine decarboxylase and spermidine/spermine N1-acetyltransferase activities, the putrescine content increased and spermidine content decreased in the transplanted liver. Putrescine administrated intraperitoneally improved the survival rate, decreased serum transaminase level and increased the [3H]thymidine incorporation into the liver DNA. These findings suggest that both biosynthetic and biodegradative pathways are stimulated in liver transplantation, resulting in the increase in the formation of putrescine from ornithine and from spermidine, and that putrescine administration improve the survival rate by protecting the damaged graft after cold ischemia and reperfusion and by stimulating liver regeneration.

Acetyltransferases↗
PubMed1995

Point mutation of ornithine decarboxylase gene in human hepatocellular carcinoma.

Ornithine decarboxylase (ODC) plays an important role in cell growth, and its activity is regulated by many mechanisms. The biochemical characteristics of ODC in malignant cells differ from those of ODC in normal cells. To determine whether novel changes occur in ODC in neoplastic tissue, we compared the nucleotide sequence of ODC cDNA obtained from human hepatoma tissue as determined by reverse transcriptase-PCR with that of ODC cDNA obtained from nontumorous tissue in the same patients. There were three point mutations accompanied by replacements of amino acids in hepatoma tissue with other amino acids or a stop codon. In one poorly differentiated hepatoma, codon 415, CAA was converted to TAA, resulting in replacement of Gln-415 by a stop codon. The mutated ODC protein produced by translation in a reticulocyte-lysate protein synthesizing system was truncated and stabilized in an ATP antizyme-dependent degradation system. These findings suggest that formation of a truncated and stabilized ODC protein due to point mutation is one reason why ODC activity is high in human hepatoma tissue.

Base Sequence↗
PubMed1995

Adrenomedullin inhibits the secretion of cytokine-induced neutrophil chemoattractant, a member of the interleukin-8 family, from rat alveolar macrophages.

This study was undertaken to determine the effects of adrenomedullin (AM) on the secretion of cytokine-induced neutrophil chemoattractant (CINC), a member of the interleukin-8 family, from lipopolysaccharide-stimulated rat alveolar macrophages in vitro. AM significantly increased cAMP levels in alveolar macrophages in a dose-dependent fashion. On the other hand, AM significantly inhibited CINC secretion from alveolar macrophages in a dose-dependent fashion, and 8-bromo-cyclic adenosine monophosphate (8-Br-cAMP) also significantly inhibited CINC secretion. These findings suggest that AM may play important roles in the regulation of airway inflammation via a cAMP-dependent mechanism.

8-Bromo Cyclic Adenosine Monophosphate↗
PubMed1995

Cancer induction by an organic arsenic compound, dimethylarsinic acid (cacodylic acid), in F344/DuCrj rats after pretreatment with five carcinogens.

Arsenic (As) is environmentally ubiquitous and an epidemiologically significant chemical related to certain human cancers. Dimethylarsinic acid (cacodylic acid; DMA) is one of the major methylated metabolites of ingested arsenicals in most mammals. To evaluate the effects of DMA on chemical carcinogenesis, we conducted a multiorgan bioassay in rats given various doses of DMA. One-hundred twenty-four male F344/DuCrj rats were divided randomly into 7 groups (20 rats each for groups 1-5; 12 rats each for groups 6 and 7). To initiate multiple organs and tissues, animals in groups 1-5 were treated sequentially with diethylnitrosamine (100 mg/kg body weight, i.p., single dose at the commencement) and N-methyl-N-nitrosourea (20 mg/kg body weight, i.p., 4 times, on days 5, 8, 11, and 14). Thereafter, rats received 1,2-dimethylhydrazine (40 mg/kg body weight, s.c., 4 times, on days 18, 22, 26, and 30). During the same period, the animals were sequentially administered N-butyl-N-(4-hydroxybutyl)nitrosamine (0.05% in the drinking water, during weeks 1 and 2) and N-bis(2-hydroxypropyl)nitrosamine (0.1% in the drinking water, during weeks 3 and 4; DMBDD treatment). After a 2-week interval, groups 2-5 were given 50, 100, 200, or 400 ppm DMA, respectively, in the drinking water. Groups 6 and 7, which were not given DMBDD treatment, received 100 and 400 ppm DMA during weeks 6-30. All rats were killed at the end of week 30. In the initiated groups (groups 1-5), DMA significantly enhanced the tumor induction in the urinary bladder, kidney, liver, and thyroid gland, with respective incidences in group 5 (400 ppm DMA) being 80, 65, 65, and 45%. Induction of preneoplastic lesions (glutathione S-transferase placental form-positive foci in the liver and atypical tubules in the kidney) was also significantly increased in DMA-treated groups. Ornithine decarboxylase activity in the kidneys of rats treated with 100 ppm DMA was significantly increased compared with control values (P < 0.001). In conclusion, DMA is acting as a promoter of urinary bladder, kidney, liver, and thyroid gland carcinogenesis in rats, and we speculate that this may be related to cancer induction by As in humans.

Acetyltransferases↗