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Biomedical subjects

Y Muto

Publications and source records attributed to Y Muto.

At least 181 records · Page 10Linked to original sources

Suppression of mouse skin papilloma by canthaxanthin and beta-carotene in vivo: possibility of the regression of tumorigenesis by carotenoids without conversion to retinoic acid.

Using mouse skin papilloma as a model system, we examined whether the antitumorigenic activity of carotenoids was related to their provitamin A activity. Oral administration of canthaxanthin (CX) or beta-carotene at 200 mg/kg/day for 14 days significantly reduced the cumulative size of papillomas induced on the skin by 9,10-dimethyl-1,2-benzanthracene (p < 0.05), after the accumulation of these carotenoids in the tumors. The levels of a protooncogene, c-myc, were simultaneously suppressed in papillomas in carotenoid-treated mice. Because CX cannot be converted metabolically to retinoids, these results suggested that CX directly inhibited the growth of papillomas. Neither the accumulation of retinoids nor the expression of a retinoic acid-inducible gene, retinoic acid receptor-beta, was found in papillomas of CX- and beta-carotene-treated mice, suggesting that, like CX, beta-carotene might exert the tumor-suppressing effect without being converted to retinoids. Thus a certain antitumorigenic activity of carotenoids appears not necessarily to require their provitamin A activity.

9,10-Dimethyl-1,2-benzanthracene↗

Suppressing effect of perilla oil on azoxymethane-induced foci of colonic aberrant crypts in rats.

We have investigated the modulatory effect of dietary perilla oil which is rich in the n-3 polyunsaturated fatty acid, alpha-linolenic acid, on the development of azoxymethane (AOM)-induced colonic aberrant crypt foci (ACF) in male F344 rats. Animals were given three weekly subcutaneous injections of AOM (15 mg/kg body weight) to induce ACE. The rats were fed a basal diet containing either 12% olive oil, 12% safflower oil, 12% perilla oil, 6% perilla oil plus 6% olive oil, or 3% perilla oil plus 9% olive oil for 5 weeks, starting 1 week before the first dosing of AOM. All rats were sacrificed 2 weeks after the last AOM injection. The amount of food consumed and body weight gain were identical among every dietary group. The frequency of ACF was significantly lower in the rats fed 12% perilla oil than in those fed 12% olive oil or 12% safflower oil (P < 0.01 and P < 0.05, respectively). The suppressive effect of perilla oil was dose-dependent, as the number of ACF was 20.7, 40.7 and 47.4% of those of the 12% olive oil-fed controls in rats fed 12% perilla oil, 6% perilla oil plus 6% olive oil and 3% perilla oil plus 9% olive oil, respectively. Perilla oil significantly reduced ras expression as well as the AgNORs count (cell proliferation biomarkers) in the colonic mucosa, as compared with olive oil or safflower oil (P < 0.01, respectively). Marked increases in n-3 polyunsaturated fatty acids in membrane phospholipid fractions and decreased PGE2 levels were observed in colonic mucosa of perilla oil-fed rats. These results suggest that perilla oil, even in small amounts, suppresses the development of aberrant crypt foci, and is therefore a possible preventive agent in the early stage of colon carcinogenesis.

Animals↗

Synergistic suppression of azoxymethane-induced foci of colonic aberrant crypts by the combination of beta-carotene and perilla oil in rats.

The modulating effect of the combined dietary feeding of beta-carotene and perilla oil, which is rich in alpha-linolenic acid, on the development of azoxymethane (AOM)-induced colonic aberrant crypt foci (ACF) was investigated in male F344 rats. Rats received oral administration of beta-carotene (0, 50 or 200 mg/kg body weight/day) and fed a basal diet containing either 12% olive oil, 3% perilla oil plus 9% olive oil, or 12% perilla oil. A dose-dependent suppressive effect of perilla oil was found. The numbers of ACF were 42.0 and 18.4% of those of the 12% olive oil-fed controls in the rats fed 3% perilla oil plus 9% olive oil and 12% perilla oil, respectively. The development of ACF was also reduced significantly by the addition of dietary beta-carotene in each of the oil-fed groups (P < 0.05, respectively). The suppression by the combination of beta-carotene and perilla oil was synergistic, as the numbers of ACF were 12.9 and 8.9% of those of the 12% olive oil-fed controls in beta-carotene-treated rats fed 3% perilla oil plus 9% olive oil and 12% perilla oil, respectively. beta-carotene plus perilla oil also suppressed the numbers of silver-stained nucleolar organizer regions and the expression of ras mRNA in the colonic mucosa (cell proliferation biomarkers). Following administration of beta-carotene, a significant increase in the concentration of intact beta-carotene molecules was found in the colonic mucosa, livers, and sera. However, no accumulation of retinoids was observed in the colonic mucosa, suggesting that the inhibitory effect may not be related to the provitamin A activity. These results suggest that the combination of beta-carotene and perilla oil may be useful in the prevention of colon cancer.

Administration, Oral↗

Incidence of anaerobic infections among patients with pulmonary diseases: Japanese experience with transtracheal aspiration and immediate bedside anaerobic inoculation.

We conducted a study to assess the precise incidence of anaerobic infections among patients with pulmonary diseases in Japan. To avoid false-negative results of anaerobic cultures, we used percutaneous transtracheal aspiration and subsequent immediate bedside anaerobic inoculation onto a set of plates with appropriately selected culture media. Fifty-six episodes of pulmonary disease occurred in 50 patients; anaerobes were isolated in 20 (36%) of these episodes. Bacteria were recovered in 30 (94%) of 32 episodes not associated with prior antimicrobial therapy, and anaerobes were isolated in 15 (47%) of these 32 episodes. Rates of anaerobic isolation in episodes of pneumonia (7 of 14), lung abscess (3 of 3), and acute exacerbation of chronic lower respiratory tract infection (5 of 15) that were not associated with prior antimicrobial therapy were 50%, 100%, and 33%, respectively.

Bacteria, Anaerobic↗

Oral supplementation with branched-chain amino acids improves transthyretin turnover in rats with carbon tetrachloride-induced liver cirrhosis.

The hypothesis that dietary branched-chain amino acid (BCAA) supplementation improves the impaired protein turnover in male Donryu rats with carbon tetrachloride-induced liver cirrhosis was tested. We supplemented cirrhotic rats orally for 2 wk with BCAA solution [26.67 mg BCAA/(100 g body weight . d)], a conventional amino acid mixture [4.25 mg BCAA/(100 g body weight . d)] or saline and fed these three groups the AIN76 basal diet to have similar intakes of total energy and total nitrogen. Normal rats without liver cirrhosis were fed the basal diet similar to the above (noncirrhotic controls). After supplementation, rats were fed intravenous transthyretin (thyroxine-binding prealbumin) doubly labeled with 125I-tyramine-cellobiose and 131I. Kinetic indices including production rate of transthyretin were analyzed from plasma transthyretin disappearance curves. Tissue sites of transthyretin degradation were assayed using a trapped ligand technique by measuring 125I-tyramine-cellobiose levels. The production rate of transthyretin was significantly lower in cirrhotic rats supplemented with saline (mean 25.46 X 10(-3) . h(-1)) compared with noncirrhotic controls (45.08 X 10(-3) . h(-1)) (P < 0.05). This was corrected by supplementing cirrhotic rats with BCAA (37.05 X 10(-3) . h(-1), P < 0.05) but not with conventional amino acid mixture (22.49 X 10(-3) . h(-1)). The accelerated degradation of transthyretin in muscles of cirrhotic rats was improved by BCAA (P < 0.05). In conclusion, dietary supplementation with BCAA improves the impaired transthyretin turnover in rats with liver cirrhosis.

Administration, Oral↗

Adult T-cell leukemia/lymphoma with a giant gastric tumor: a case report.

A rare case of adult T-cell leukemia/lymphoma with a giant exophytic gastric tumor invading the anterior abdominal wall is presented. The patient was a 52-year-old woman, who had a history of strongyloidiasis. Although the patient was serologically positive for HTLV-I antibody, there were no lymphoma cells in the peripheral blood or systemic lymphadenopathy. After two cycles of combination chemotherapy, the tumor was surgically resected. The pathological diagnosis of the resected specimen was T-cell lymphoma of the diffuse mixed cell type. Flow-cytometric analysis of the lymphoma showed a CD4+ and CD8+ phenotype. One month after surgery, the patient developed hypercalcemia, resulting in acute renal and respiratory failure, and died. The prognosis of lymphoma-type ATL is known to be extremely poor, and thus we should bear in mind that ATL can take the form of a primary gastric mass without leukemic manifestations.

Antineoplastic Combined Chemotherapy Protocols↗

Treatment with a novel lipid A analogue, FS-112, and partial hepatectomy causes submassive liver necrosis and impaired liver regeneration in mice.

A novel experimental model of submassive liver necrosis with impaired regeneration has been established. A novel lipid A analogue, FS-112, was injected intravenously into male BALB/c mice, followed 2 days later by a 70% partial hepatectomy. Over the next 9 days, mice became severely jaundiced, with a peak total bilirubin (TBil) concentration of (mean +/- s.d.) 12.9 +/- 2.1 mg/dL 7 days postoperatively. In contrast, the TBil concentration in vehicle-treated mice remained less than 2 mg/dL. Significant elevations of L-alanine:2-oxoglutarate aminotransferase (ALT) were also observed 3-7 days after the operation in mice pretreated with FS-112, compared with mice pretreated with the vehicle. Submassive liver necrosis was observed with extensive mononuclear cell infiltration in mice treated with FS-112 and subjected to partial hepatectomy. Furthermore, both the BrdU and the proliferating cell nuclear antigen (PCNA) labelling index (LI) 1 day following partial hepatectomy in mice pretreated with FS-112 (8.6 +/- 4.3 and 7.9 +/- 4.2%, respectively) were significantly lower than levels in vehicle-treated mice (25.8 +/- 3.8 and 26.5 +/- 10.5%, respectively). The time course of changes in the BrdU LI in liver specimens from mice treated with both FS-112 and partial hepatectomy did not increase, even 3, 5, and 7 days postoperatively. Excellent liver regeneration with a PCNA LI 10-fold higher than the resting level was observed in mice treated with D-galactosamine hydrochloride. These results strongly suggest that this animal model of submassive liver necrosis may be suitable for clarifying the mechanisms of impaired liver cell regeneration often seen in fulminant hepatitis.

Animals↗

Reduction of intestinal apo A-IV mRNA levels in the cirrhotic rat.

In the present study, intestinal apo A-IV synthesis was investigated using a carbon tetrachloride (CCl4)-induced cirrhosis rat model. Triglyceride (TG) content in rat cirrhotic liver was increased markedly by 170% (P < 0.001) and apo B was increased by 20% (P < 0.05) compared with control levels. These results reflected the steatotic change in the liver. In contrast, TG levels in the small intestine of cirrhotic rats decreased significantly (P < 0.01). In addition, intestinal apo A-IV (jejunum P < 0.001; ileum P < 0.01) and its mRNA levels (jejunum P < 0.01; ileum P < 0.05) were also reduced. The decreased apo A-IV content in the jejunum was confirmed by immunohistochemical analysis. These results indicate that intestinal apo A-IV synthesis in cirrhosis is suppressed, at least under the condition of an overnight fast. Therefore, decreased intestinal apo A-IV synthesis may relate to the decreased ability to absorb fat in cirrhosis, but a fat-loading study will be necessary to confirm this hypothesis. It is unknown from the present study why serum apo A-IV level is not significantly decreased, despite a reduction in apo A-IV synthesis. The clearance of apo A-IV by the liver may be delayed or apo A-IV synthesis may be rather markedly enhanced during fat absorption in liver cirrhosis.

Animals↗

Effect of recombinant human granulocyte colony-stimulating factor on combination therapy with aztreonam and clindamycin for infections in neutropenic patients with hematologic diseases.

The present multicenter study was performed to evaluate the effect of recombinant human granulocyte-colony stimulating factor (rhG-CSF) on combination therapy using aztreonam (AZT) and clindamycin (CLDM) to treat severe infection in neutropenic patients with hematologic diseases. Forty-three neutropenic patients with infections (rhG-CSF group) were treated with AZT (2 g) and CLDM (600 mg) 2-3 times daily as well as rhG-CSF (Lenograstim or Filgrastim: 2-5 mu/kg/day). The clinical efficacy of this regimen was compared to that obtained in 44 febrile neutropenic patients, with hematologic diseases, who received only AZT and CLDM in a previous study (historical control group). The overall efficacy rate was 69.8% (30/43) in the rhG-CSF group and 65.9% (29/44) in the historical control group. Although the neutrophil count was significantly increased and C-reactive protein tended to be lower in the rhG-CSF group, the daily maximum body temperature profiles of the 2 groups were nearly the same. These results suggest that rhG-CSF is of little benefit in the treatment of single infectious episodes in neutropenic patients, and that appropriate antibiotic therapy is more important.

Acute Disease↗

[Transformation of aplastic anemia to acute myeloid leukemia with myelofibrosis following treatment with granulocyte colony-stimulating factor and erythropoietin].

A 67-year-old female was admitted with fatigue. Peripheral blood examination showed severe pancytopenia. Bone marrow biopsy revealed hypoplastic marrow. She was diagnosed as having aplastic anemia. Steroid pulse therapy was not effective. After treatment with erythropoietin (EPO) and granulocyte colony-stimulating factor (G-CSF), blasts which were positive for CD13, CD33, CD34 and HLA-DR and negative for myeloperoxidase appeared in the peripheral blood. At this time, bone marrow biopsy revealed myelofibrosis with increased blasts. Chromosome analysis showed 46XX, add (1) (p36), add (1) (q44), -2, -5, del (7) (q11), -12, +3mar. She died of pneumonia despite chemotherapy with etoposide. Administration of EPO and G-CSF may have led to the rapid development of leukemia and myelofibrosis.

Aged↗

[Classification and diagnosis of hemolytic anemias].

Hemolysis is characterized by shortening of the red cell life span. When the red cell destruction exceeds the ability of the marrow to increase red cell production to compensate for, hemolytic anemias develop. These conditions are subdivided into hereditary abnormalities and acquired abnormalities. Except for PNH, all types of hemolytic anemia due to intrinsic abnormalities are inherited and those of extrinsic ones are acquired. Extrinsic factors include antibodies, physical trauma, biological agents, chemical agents and physical agents. For determining the specific cause of the conditions, anti-globulin test, morphological observation, analysis of hemoglobin, red cell enzyme assay, screening tests for PNH are needed.

Anemia, Hemolytic↗

[The effect of the season and sexual stress on the concentration of testosterone and estradiol-17beta in the seminal plasma of stallions].

Semen from three stallions was collected weekly for six months (December through May) to determine semen parameters and hormones (testosterone and estradiol-17 beta) in seminal plasma. Once a month three ejaculates were collected at intervals of one hour and examined accordingly. Testosterone and estradiol-17 beta were also determined in peripheral blood plasma (V. jugularis) collected twice a week. Semen parameters (volume, gel-free volume and sperm concentration) were clearly influenced by season. The testosterone concentration in peripheral blood plasma was lowest during December whereas in seminal plasma testosterone concentration gradually increased throughout the experimental period. Testosterone concentrations in seminal plasma were only one tenth of those in peripheral blood. Estradiol-17 beta in blood plasma was highest in April and May whereas no significant differences occurred in seminal plasma. Average monthly concentrations of estradiol-17 beta in blood and seminal plasma were in the range of 27.4 pg/ml to 45.3 pg/ml. Collection of three successive ejaculations led to a significant decrease of ejaculate volume as well as sperm concentration. Ejaculation frequency did not influence testosterone in seminal plasma whereas the concentration of estradiol-17 beta decreased significantly in the second and third ejaculate. The results indicate that estradiol-17 beta in the stallion's semen may be bound to spermatozoa or is accumulated in seminal plasma.

Animals↗

Changes in the ratio of branched-chain to aromatic amino acids affect the secretion of albumin in cultured rat hepatocytes.

The effect of branched-chain amino acids (BCAAs) on the synthesis and secretion of albumin was studied in the primary cultures of rat hepatocytes. The changes in the normal BCAAs/aromatic amino acids (AAAs) ratio reduced the secretion of albumin without altering its mRNA levels. Protein-labeling and pulse-chase experiments showed that a low BCAAs/AAAs ratio reduced the biosynthesis, whereas a high ratio accelerated intracellular decay of albumin. These results suggest that normalization of the BCAAs/AAAs ratio improves albumin synthesis while the excess ratio may induce the degradation of albumin in the cells.

Amino Acids, Branched-Chain↗