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Biomedical subjects

Y Muto

Publications and source records attributed to Y Muto.

At least 325 records · Page 18Linked to original sources

Inhibitory effect of acyclic retinoid (polyprenoic acid) on hepatic fibrosis in CCl4-treated rats.

A study was conducted to examine the inhibitory effect of acyclic retinoid (polyprenoic acid) on the development of hepatic fibrosis induced by CCl4 in rats. Oral administration of the compound brought about a significant reduction in both serum and tissue levels of immunoreactive prolyl hydroxylase, a key enzyme of collagen formation. The result indicated that the rate of collagen synthesis in the liver was decreased which was consistent with histological findings. Acyclic retinoid also decreased both AST and ALT activities in serum, demonstrating the reduction in hepatic parenchymal damage. This cytoprotective effect on parenchymal cells may be related, at least in part, to inhibition of hepatic fibrosis. No significant side effects were observed, despite a long-term administration of the acyclic retinoid. The present findings suggest the potential scope of therapy of hepatic fibrosis by retinoid.

Alanine Transaminase↗

Enhanced tumor necrosis factor and interleukin-1 in an experimental model of massive liver cell necrosis/fatal hepatitis in mice.

Studies were conducted to investigate possible roles of tumor necrosis factor (TNF) and interleukin-1 (IL-1) in liver cell necrosis/fatal hepatitis in mice which were injected with Propionibacterium acnes (P.acnes) and subsequently 7 days later with a small dose of lipopolysaccharide-endotoxin (LPS). Higher serum levels of TNF were observed in the model, and enhanced production of both TNF and IL-1 was also found in hepatic as well as splenic adherent cells that were isolated from mice pretreated with P.acnes and were stimulated by LPS in vitro. When TNF substituted for LPS in the model, fatal hepatitis was also induced within 24 hrs, although the replacement of LPS by IL-1 resulted in no lethality. Moreover, when a combination of a near non-lethal doses of TNF and IL-1 substituted for LPS, 100% lethality was observed within 4 hrs. These results strongly suggest that both TNF and IL-1 are crucial soluble factors which are released by infiltrating macrophages in both liver and spleen, and are responsible for the development of liver cell necrosis/fatal hepatitis. In particular, TNF is one of the principal mediators of liver injury and IL-1 may potentiate the lethal effect of TNF in an LPS-related experimental model of massive liver cell necrosis.

Animals↗

Anti-hepatitis C virus antibody prevails in fulminant hepatic failure.

Serial serum samples obtained from 27 patients with fulminant hepatic failure (FHF) in a variety of etiology were tested for anti-hepatitis C virus antibody (anti-HCV). Seven out of 10 patients (70%) with FHF due to hepatitis B virus (HBV) infection were positive for anti-HCV, showing a significantly higher rate than that in acute HBV hepatitis (0/17, 0%): In particular, all 3 post-transfusion HBV-FHF cases were found to be positive for the antibody. The incidence of anti-HCV in sporadic non-A non-B (NANB)-FHF patients (7/11, 64%) tended to be greater than that in acute sporadic NANB hepatitis as recently surveyed in this country. In addition, anti-HCV was also detected in a patient with hepatitis A virus (HAV)-FHF and in 2 out of 4 drug-induced FHF patients. Moreover, anti-HCV appeared earlier in FHF (median; 27.5 days, n = 9) regardless of etiology, when compared to acute NANB hepatitis (3 to 6 months). Hence, co-infection and/or superinfection of HCV with enhanced antibody response may play an important role in the development of this fatal disease.

Acute Disease↗

Effects of intraperitoneal transplantation of microcarrier-attached hepatocytes on D-galactosamine-induced acute liver failure in rats.

A study was conducted to investigate morphologic as well as metabolic characteristics of microcarrier-attached hepatocytes in culture, and also to evaluate the effect of intraperitoneal transplantation of the microcarrier-attached hepatocytes on acute hepatic failure in rats induced by D-galactosamine (GalN). Rat hepatocytes were isolated by collagenase perfusion, and cultured on collagen-coated microcarriers. Protein synthesis estimated by [14C] leucine incorporation was four-fold higher in microcarrier culture than in cell suspension. The rates of albumin, transthyretin and bile acid syntheses in hepatocytes cultured on microcarriers were similar to those in monolayer culture. When microcarrier-attached hepatocytes were intraperitoneally transplanted into rats with Galn-induced acute liver failure, a marked improvement in survival rate was observed as compared with control rats which received injections of microcarriers alone (80% vs 0% beyond 6 days of transplantation). Mean serum glutamate oxaloacetate transaminase (SGOT), serum glutamate pyruvate transaminase (SGPT), methionine and glucose levels were similar in both groups, while serum bilirubin and ammonia levels were lower (P less than 0.1, P less than 0.05) in rats transplanted with the microcarrier-attached hepatocytes. Immunohistochemical examinations revealed that the transplanted hepatocytes around microcarriers had albumin synthesis activity, whereas almost no albumin synthesis was demonstrated in recipient liver. In conclusion, intraperitoneal transplantation of the microcarrier-attached hepatocytes will provide sufficient metabolic support, representing detoxication of ammonia (and presumably bilirubin) and synthesis of albumin, to allow GalN-damaged liver function to restore. Microcarrier culture of isolated hepatocytes seems to be one of the most appropriate tools for an artificial liver support.

Acute Disease↗

Reduction of serum lipoprotein(a) levels in hyperlipidaemic patients with alpha-tocopheryl nicotinate.

The effect of low dose (600 mg/day) alpha-tocopheryl nicotinate on serum lipoprotein(a) (Lp(a] concentration was studied in 28 hyperlipidaemic patients. Serum lipids, lipoproteins and apolipoproteins, except for Lp(a), tended to increase after treatment. In particular, the changes in HDL-cholesterol and apo C-II levels were statistically significant. On the other hand, serum Lp(a) levels in all patients decreased significantly after 2 months of treatment. Furthermore, no difference between before and after treatment was observed in the group with initial Lp(a) levels less than 18 mg/dl, whereas Lp(a) concentrations decreased significantly after treatment in the group with levels greater than or equal to 18 mg/dl. The effects of probucol and alpha-tocopheryl nicotinate on serum Lp(a), total cholesterol and HDL-cholesterol were entirely different. Possible mechanisms of alpha-tocopheryl nicotinate on serum Lp(a) and lipoprotein metabolism are discussed.

Adult↗

A one-step enzyme immunoassay for human manganese superoxide dismutase with monoclonal antibodies.

A one-step enzyme immunoassay for the determination of manganese superoxide dismutase in serum has been developed with two kinds of monoclonal antibodies. Proposed method had high sensitivity (assay range, 0.4-200 ng/ml), good recovery (recovery percentage, 102.9-106.2%) and reproducibility (intraassay, C.V. = 1.87-3.66%; interassay, C.V. = 3.03-10.4%). From these results, it is possible to apply this method to routine clinical analysis and biochemical research with various purposes.

Animals↗

Inhibitory effects of acyclic retinoid (polyprenoic acid) and its hydroxy derivative on cell growth and on secretion of alpha-fetoprotein in human hepatoma-derived cell line (PLC/PRF/5).

Acyclic retinoid (polyprenoic acid) has a slightly different structure from retinoic acid. However, acyclic retinoid acts similarly to retinoic acid, because both bind to cellular retinoic acid-binding protein and cellular retinoid-binding protein. F-type, with the same strong binding affinity. We studied the effects of acyclic retinoid, the 7-hydroxy derivative of acyclic retinoid (7OH-acyclic retinoid) and retinoic acid on a human hepatoma-derived cell line PLC/PRF/5 (Alexander cells). Acyclic retinoid inhibited cell growth with an ID50 value of 14 microM, and reduced cell viability with an LD50 value of 86 microM. The ratios of LD50 value to ID50 value were 6.1 for acyclic retinoid, 2.4 for 7OH-acyclic retinoid and 1.4 for all-trans-retinoic acid. Taking this ratio as a parameter of relative cytotoxicity, we concluded that acyclic retinoid is the least toxic compound. Growth inhibition of cells by acyclic retinoid was associated with the incorporation of 3H-thymidine in the logarithmic phase. Acyclic retinoid reduced secretion of alpha-fetoprotein (AFP) and reciprocally increased secretion of albumin in the culture media, suggesting that acyclic retinoid influences gene expression of these proteins. Thus, acyclic retinoid, one of the less toxic retinoids, inhibits cell growth of human cancer cell line PLC/PRF/5 and appears to alter gene expression of AFP and albumin toward a "normal" direction.

Acrylates↗

Inhibitory effect of acyclic retinoid (polyprenoic acid) on the secretion of alpha-fetoprotein in CCl4-treated rats.

A study was conducted to examine the inhibitory effect of acyclic retinoid (polyprenoic acid) on the secretion of alpha-fetoprotein (AFP) in rats with chronic liver damage induced by CCl4. Oral administration of the compound brought about a significant reduction of serum AFP levels at the time when liver cirrhosis was formed. Acyclic retinoid also decreased the activities of serum aminotransferases and ornithine carbamyl transferase, while it increased serum albumin levels, demonstrating the reduction of hepatic parenchymal damage. Significant negative correlation was observed between serum AFP and albumin levels. This cytoprotective effect of the retinoid on the parenchymal cell may well be related to the inhibition of the synthesis and/or secretion of AFP. No significant side effect was observed, despite a long-term administration of the compound. The present finding will provide a potential scope for the future use of acyclic retinoid for the treatment of chronic liver damage.

Animals↗

R-plasmid mediated transfer of beta-lactam resistance in Bacteroides fragilis.

We described plasmid mediated transfer of resistance to beta-lactam antibiotics between Bacteroides fragilis strains. Ampicillin-resistance was transferred from B. fragilis strain GAI-10150 to a B. fragilis strain JC-101 with a frequency of 10(-6)/input donor by a filter mating technique. A common plasmid band, named pBFKW1, was found in both the donor and the transconjugants. The plasmid was purified by an ethidium bromide-CsCl ultracentrifugation. The molecular size of the plasmid pBFKW1 which seemed to encode the beta-lactam resistance and beta-lactamase production was estimated ca. 40 kb by the analysis of endonuclease digest. Substrate profile of the enzymes derived from the donor and a transconjugant were of cephalosporinase character.

Ampicillin Resistance↗

Recognition of tRNA identity determinants by aminoacyl-tRNA synthetases.

By analyzing aminoacylation activities of variants of isoleucine tRNAs and glutamic acid tRNA from Escherichia coli, it was found that the anticodons are the major determinants for "identities" of these tRNAs. It was also shown that the post-transcriptional modifications are essential to aminoacylation of these tRNAs. Interactions between the tRNAs and the aminoacyl-tRNA synthetases were analyzed by NMR spectroscopy.

Amino Acyl-tRNA Synthetases↗

[A case of local recurrent breast cancer with complete response to combination of systemic chemotherapy and topical use of adriamycin ointment].

A Case of local recurrent breast cancer in a 45-year-old female with complete response to Combination of chemotherapy and topical administration of Adriamycin is reported. The patient had left mastectomy for breast cancer in 1978, and then right mastectomy for breast cancer in 1987. Two years later, she was readmitted to our hospital with right neck lymph node metastasis and local recurrence at right chest wall. Neck lymph node metastasis was treated with irradiation with good response. On the other hand, Adriamycin ointment was applied to recurrent cancer on the right chest. The cancer was gradually diminished in size. Seventy-eight days after treatment, the local chest wall with cancer was resected. Histologically, the entire resected tissue showed no viable cancer cells and Adriamycin concentration in the tissue was extraordinary high (ten to forty fold over on systemic chemotherapy). Adriamycin ointment may be an alternative treatment of choice for local recurrent breast cancer.

Administration, Topical↗

Present status of research on cancer chemoprevention in Japan.

The activities of the research group on cancer chemoprevention supported by the Ministry of Health and Welfare of Japan are summarized. Since the research on cancer chemoprevention is quite new in Japan, this paper describes the present status of the development of possible cancer preventive agents. Acyclic retinoid (E-5166) and sarcophytol A encourage further studies. New inhibitory compounds of experimental carcinogenesis, such as cryptoporic acid, oleanolic acid, mokko lactone and ursolic acid were isolated from plants. The importance of the keen collaboration between natural product chemists and clinicians for further meaningful progress in this research field has been emphasized.

Animals↗

Conformation change of effector-region residues in antiparallel beta-sheet of human c-Ha-ras protein on GDP----GTP gamma S exchange: a two-dimensional NMR study.

The conformations of a truncated human c-Ha-ras gene product [ras(1-171) protein] in the GDP-bound form and in the GTP gamma S-bound form were compared by two-dimensional nuclear Overhauser effect spectroscopy (NOESY). As for the GDP-bound ras(1-171) protein, three NOESY cross peaks were observed in the region of 4.5-6.0 ppm, indicating a regular antiparallel beta-sheet structure. On the ligand exchange from GDP to GTP gamma S, one of the three NOESY cross peaks disappeared and the other two cross peaks were appreciably shifted. By analysis of the effects of specific deuteration of leucine residues and the homonuclear Hartmann-Hahn spectroscopy, the antiparallel beta-sheet was found to consist of residues 38-44 and residues 51-57. The conformations around Ser-39 and Leu-56 are of the regular antiparallel beta-strand type in the GDP-bound state, and largely distorted in the GTP gamma S-bound state, which is probably related to the conformational activation of the effector region of ras proteins by ligand exchange from GDP to GTP gamma S.

Amino Acid Sequence↗

Venous reconstruction for iliofemoral venous occlusion facilitated by temporary arteriovenous shunt. Long-term results in nine patients.

In nine patients with iliofemoral venous occlusion, venous reconstructions using a temporary arteriovenous shunt were performed by open thromboendvenectomy with autogenous vein patch angioplasty in four, expanded polytetrafluoroethylene (ePTFE) bypass grafts (including two with external ring-supported ePTFE) in four, and Palma's procedure in one patient. There was an adequate function in the reconstructed venous segments in two of four who underwent thromboendvenectomy and in all four with ePTFE bypass grafting for nine months to 13 years after surgery. In those with a temporary arteriovenous shunt, prepared to maintain patency of the reconstructed venous segments, blood flow through the shunt exceeded 100 mL/min, determined by an electromagnetic flowmeter. Postoperative shunt closure was readily facilitated, using a looping technique and a 2-0 nylon. The increased blood flow through the graft made feasible by the temporary arteriovenous shunt enhanced the patency of the reconstructed venous graft and hence there was an improvement in the affected limb.

Adolescent↗