Biomedical subjects

M Yamamura

Publications and source records attributed to M Yamamura.

At least 181 records · Page 10Linked to original sources

PubMed1990

Inhibitory effect of selenium on hamster pancreatic cancer induction by N'-nitrosobis(2-oxopropyl)amine.

The effect of selenium intake on the development of pancreatic cancer was investigated in female Syrian golden hamsters. Four-week-old hamsters were divided into 2 groups according to the selenium level in their drinking water and were fed a purified diet containing less than 0.05 ppm selenium. Starting 4 weeks later, groups received 10 s.c. injections at weekly intervals of N'-nitrosobis(2-oxopropyl)amine (BOP) dissolved in saline, while controls received saline alone. When the animals were killed 18 weeks after the last injection, palpable tumors were less frequent in the high-selenium group than in animals receiving low-selenium supplement, the numbers of histologically diagnosed cancerous lesions also being significantly reduced by high selenium intake. The selenium level and glutathione peroxidase activity in serum and pancreas were significantly greater in the high-selenium group. Moreover, selenium levels and glutathione peroxidase activity were both significantly higher in tumor-bearing tissue. The results suggest that glutathione peroxidase is involved as an intermediate factor in prevention of carcinogenesis by selenium.

Animals↗

PubMed1990

Effect of dietary molybdenum on esophageal carcinogenesis in rats induced by N-methyl-N-benzylnitrosamine.

The influence of dietary molybdenum on esophageal carcinogenesis induced by N-methyl-N-benzylnitrosamine (2.5 mg per kg of body weight once a week for 20 wk s.c.) was studied in male F344 rats. The tumor incidence and tumor development in the esophagus were significantly lower in the rats in the high-molybdenum (2 ppm) diet group than in the rats in the low-molybdenum (0.032 ppm) diet group; i.e., 44.4% (0.6 +/- 0.8) and 73.2% (2.2 +/- 2.0), respectively. The molybdenum levels in the esophagus-forestomach, liver, and serum were significantly higher in the high-molybdenum diet group than in the low-molybdenum diet group. Xanthine oxidase activity in the esophagus and forestomach in the high-molybdenum diet group was significantly higher than that in the low-molybdenum diet group, whereas liver and serum xanthine oxidase activities were not significantly different between these two groups. These results suggest that xanthine oxidase in the esophagus plays a significant role in the inhibitory effect of molybdenum on esophageal carcinogenesis.

Animals↗

PubMed1990

[Application of a new compact and cell dense continuous culture system for LAK cells generated from cryo-preserved lymphocytes].

Recently, the adoptive immunotherapy using lymphokine activated killer (LAK) cells has been applied for various cancer patients. It is quite useful to generate LAK cells from cryo-preserved lymphocytes in order to make a rational treatment schedule. We made basic studies on the induction of LAK cells from frozen lymphocytes using our high yield continuous cell culture system. It was demonstrated that our culture bag can be used to proliferate frozen lymphocytes cultured in interleukin-2 (IL-2) to thirty four-fold the initial cell number in 14 days with comparable cytotoxicity to that of fresh lymphocytes cultured in the same system.

Cryopreservation↗

PubMed1990

Prognostic significance of serosal invasion and free intraperitoneal cancer cells in gastric cancer.

Survival rates after curative gastrectomy for advanced gastric cancer among 238 patients in whom the cancer was invading the serosa were compared with 283 patients without serosal invasion. Generalized Wilcoxon estimates for 5-year survival rate were 47.1 per cent for patients exhibiting serosal invasion and 75.9 per cent for patients without serosal invasion. The frequency of lymph node metastasis increased proportionately with the extent of serosal invasion: 18.4 per cent in cases of S0; 53.8 per cent in cases of S1; 80.0 per cent in cases of S2; and 91.4 per cent in cases of S3. The higher the aggregate total of S (serosal invasion) and n (lymph node metastasis) factors, the lower the 5-year survival rate. In addition, patients with serosal invasion had a propensity for peritoneal dissemination of cancer cells; the percentage of cases with intraperitoneal free cancer cells increased with the extent of serosal invasion. It is worth noting that when cancer infiltration proceeded to the deeper layers and was accompanied by nodal metastasis, cancerous invasion of the perinodal fatty tissue was frequently evident. Therefore, unfavourable prognosis after curative resection in gastric cancer patients with serosal invasion may be largely dependent on whether or not the cancer has invaded the peritoneal cavity and the perinodal fatty tissue.

Adult↗

PubMed1990

Response of fibronectin to liver regeneration after hepatectomy.

The relationship between plasma fibronectin concentration and the regenerative process in liver remnants after hepatectomy was studied in 12 patients and in male Sprague-Dawley rats with and without cirrhosis. Plasma fibronectin levels were reduced immediately after hepatectomy in humans and rats. Patients and rats without cirrhosis displayed preoperative fibronectin levels within 1 mo and 1 wk, respectively, but low fibronectin levels persisted longer in those with cirrhosis. Plasma fibronectin levels correlated well with the degree of hepatic regeneration in the patients with cirrhosis (r = 0.4227; p less than 0.05) and without cirrhosis (r = 0.8148; p less than 0.001), and also with the percentage of change in liver weight during regeneration in the rat with thioacetamide-induced cirrhosis (r = 0.4905; p less than 0.01) or in the rat without cirrhosis (r = 0.6422; p less than 0.001). These results suggest that plasma fibronectin is a useful marker for the detection of regenerating liver.

Adult↗

PubMed1990

Immunohistochemical analysis of the relationship between CEA localization and mononuclear cell infiltration in human colorectal carcinoma.

Thirty cases of colorectal adenocarcinoma were immunohistochemically examined to clarify the relationship between the degree of differentiation of cancer cells reflected by the mode of CEA localization and the infiltration pattern of mononuclear cells in the carcinoma tissues. Leu 1+, Leu 2a+, Leu 3a + 3b+ T lymphocytes, Leu 7+ cells, and IgA-containing plasma cells tended to be distributed more in areas where CEA was localized over the entire surface of the cancer cells or in their surrounding stroma than where CEA was located along the apical surface or within the cytoplasm. Carcinoma cells with the pattern of CEA staining at the former site were previously shown to be less differentiated than those at the latter. There were also CEA-containing phagocytes which were often observed where T cells and IgA plasma cells had aggregated. We speculated that the dedifferentiation of cancer cells might cause the host immune response, especially the cellular immunity, in malignant lesions.

Adenocarcinoma↗

PubMed1990

Effect of medium-chain triglycerides (MCT) as an energy substrate after hepatectomy in rats with streptozotocin-induced diabetes.

The suitability of energy substrates used by the remnant liver after a 70% partial hepatectomy was studied in relation to the hepatic energy status in diabetic rats. Rats with streptozotocin-induced diabetes mellitus underwent 70% hepatectomy, and were divided into three groups receiving total parenteral nutrition (TPN) for 24h. One group received standard TPN without fat, while two other groups received standard TPN with medium-chain triglycerides (MCTs) or long-chain triglycerides (LCTs) as a 10% lipid emulsion. All rats of the TPN group without fat died within 24h. Blood ketone body ratios (aceto-acetate/beta-hydroxybutyrate), energy charge levels of the remnant liver, and cumulative amounts of 14CO2 in the expired breath during the 6h following 14C-labeled fat emulsion administration (MCT or LCT) were all significantly higher in the MCT group than in the LCT group 24h after hepatectomy. These findings suggest that medium-chain fatty acids (MCFAs) as an energy substrate are superior to long-chain fatty acids (LCFAs) during the immediate posthepatectomy phase in diabetics.

Animals↗

PubMed1990

Synthesis and central nervous system actions of thyrotropin-releasing hormone analogues containing a dihydroorotic acid moiety.

A series of thyrotropin-releasing hormone (TRH) analogues in which the pyroglutamic acid residue was replaced by (S)-4,5-dihydroorotic acid (Dio-OH) and the related derivatives were prepared. Their central nervous system actions based on spontaneous locomotor activity, antagonistic effect on reserpine-induced hypothermia, and antagonistic effect on pentobarbital anesthesia were evaluated and the structure-activity relationships are discussed. Of these, (1-methyl-(S)-4,5-dihydroorotyl)-L-histidyl-L-prolinamide (14b) showed the most potent activities, which were 30-90 times greater than those of TRH. Moreover, the thyrotropin-releasing activity of 14b was about 50 times weaker than that of TRH, and compound 14b (TA-0910) was selected as a potent candidate.

Anesthesia↗

PubMed1990

Specific inhibitory effect of dietary eicosapentaenoic acid on N-nitroso-N-methylurea-induced mammary carcinogenesis in female Sprague-Dawley rats.

We have investigated the effects of two qualitatively different types of unsaturated fatty acids on N-nitroso-N-methylurea (NMU)-induced mammary carcinogenesis in female Sprague-Dawley rats. Semipurified diets containing 4.7% eicosapentaenoic acid (EPA) plus 0.3% linoleic acid or 5% linoleic acid were prepared. Animals maintained on these diets were given an i.v. injection of NMU (50 mg/kg body wt) at 50 days of age and killed 20 weeks later. Both tumor incidence and tumor number per rat were significantly lower in the EPA diet group (60.0% and 2.3 +/- 2.5 versus 93.3% and 5.1 +/- 4.5 respectively) for the 5% linoleic acid diet. Furthermore, the average weight of tumor material (total) per rat was significantly lower in the EPA as compared to linoleic acid diet group (2.9 +/- 4.2 g and 11.4 +/- 12.2 g respectively). Analysis of phospholipid fatty acids in the mammary tumors in the EPA diet group showed a higher proportion of C16:0, C18:2, omega-3 fatty acids C20:5 and C22:6 and a lower proportion of C20:4. Furthermore, mammary tumors in rats fed the EPA diet demonstrated significant reduction in prostaglandins. The results thus suggest that inhibition by EPA of NMU-induced mammary carcinogenesis may be mediated via the modulation of lipid metabolism and associated reduction in prostaglandin synthesis.

Animals↗

PubMed1990

Impaired superoxide production in peripheral blood neutrophils of germ-free rats.

A method of separating neutrophils from the peripheral blood of rats with 95% purity is described. To determine the role of antigenic stimulation in neutrophil function, neutrophils from germ-free (GF) rats were compared with those of conventional (CV) rats. Neutrophil counts were lower in GF rats but the total number of monocytic cells was the same. To measure phagocytic killing, superoxide anion production was determined and found to be lower in GF neutrophils (2.1 +/- 0.5 nmol/min/10(6) cells) than in CV neutrophils (9.5 +/- 2.9 nmol/min/10(6) cells). Myeloperoxidase activity was found to be twofold higher in GF neutrophils. When a recombinant human granulocyte colony-stimulating factor (rhG-CSF) was intravenously injected, superoxide production did not change in either GF or CV neutrophils, but the myeloperoxidase activity of neutrophils in both types of rats decreased. rhG-CSF increased the number of neutrophils in both GF (10-fold) and CV rats (three- to fourfold).

Animals↗

PubMed1990

Pharmacological study of TA-0910, a new thyrotropin-releasing hormone (TRH) analog, (I): Effects on the central nervous system by oral administration.

Effects of orally administered TA-0910, a new thyrotropin-releasing hormone (TRH) analog, on the central nervous system (CNS) were investigated and compared with those of TRH. TA-0910 shortened the duration of pentobarbital-induced sleep and antagonized reserpine-induced hypothermia at 0.3 mg/kg or more in mice. TA-0910 enhanced the spontaneous motor activity at the higher dose of 30 mg/kg in mice. The drug also activated acute spontaneous EEGs in rabbits at 1 mg/kg. TRH produced these effects at about 100 times higher doses than TA-0910. In antagonizing pentobarbital-induced sleep, the dose ratios of i.v. versus p.o. of TA-0910 and TRH were about 1/10 and 1/100, respectively. The duration of the antagonistic action of TA-0910 on pentobarbital-induced sleep in mice was about 8 times longer than that of TRH when administered orally as well as intravenously. These potent and long-acting TA-0910 effects on the CNS are discussed in connection with its biotransformation.

Administration, Oral↗

PubMed1990

Increased ability of peripheral blood B cells from patients with rheumatoid arthritis to produce interleukin 1 in vitro.

Twenty-four patients with rheumatoid arthritis (RA) and 20 normal controls were examined for the ability of their peripheral blood B cells to produce interleukin 1 (IL-1) with or without lipopolysaccharide (LPS). B cells were purified from peripheral blood by negative selection methods (i.e., removal of adherent cells and sheep red blood cell rosette-forming cells, followed by treatment with monoclonal antibodies (OKT3 and OKM1) and complement). The amount of IL-1 in B cell culture supernatants (SN) was measured by thymocyte and fibroblast proliferation assays and an enzyme-linked immunosorbent assay for IL-1 alpha and beta. As a group, cultured B cells from patients with RA, both spontaneously and when stimulated with LPS, produced higher levels of IL-1 than those from normal controls. IL-1 production by RA B cells with LPS had a weak but positive correlation with disease activity. Moreover, RA B cell culture SN with elevated levels of IL-1 had a synergistic effect on the growth of anti-human IgM (anti-mu) stimulated B cells. In separate experiments, the growth of RA B cells was significantly promoted by IL-1 beta both with and without anti-mu stimulation. These results suggest that B cell-derived IL-1 may be involved in the B cell clonal expansion of RA through its own activity as a B cell stimulatory factor.

Adolescent↗

PubMed1990

Role of endogenous prostaglandin E2 in interleukin 1 production by peripheral blood monocytes from patients with rheumatoid arthritis.

We studied the effect of endogenous prostaglandin E2 (PGE2) on interleukin 1 (IL-1) production by peripheral blood monocytes from patients with rheumatoid arthritis (RA). IL-1 production by RA monocytes was not different from that of monocytes from normal controls, when the cells were either unstimulated or stimulated with lipopolysaccharide (LPS, 20 micrograms/ml), as measured by two different bioassays (thymocyte or fibroblast proliferation assay) and enzyme-linked immunosorbent assay. However, IL-1 production by LPS-stimulated monocytes from RA patients cultured in medium containing indomethacin, an inhibitor of PGE2 synthesis, was significantly greater than that of monocytes from normal controls. In addition, the levels of PGE2 in culture supernatants of unstimulated or LPS-stimulated monocytes from RA patients were higher than in culture supernatants of monocytes from normal controls. Moreover, the increase of in vitro IL-2 production by RA T cells stimulated by phytohemagglutinin (PHA) was observed when monocytes were removed from peripheral blood mononuclear cells. These results indicated that peripheral blood monocytes from RA patients could produce IL-1 in excess in vitro, but that in vivo IL-1 production by RA monocytes and IL-2 induction by RA T cells might be negatively regulated by endogenous PGE2.

Adult↗

PubMed1990

Effect of administration of fibronectin or aprotinin on liver regeneration after experimental hepatectomy.

Following 70% hepatectomy, male Sprague-Dawley strain rats were given purified human plasma fibronectin and/or aprotinin intraperitoneally after hepatectomy and were divided into 4 groups: Group FA (40 mg/kg of FN and 25,000 KIU/kg of aprotinin), Group F (40 mg/kg of fibronectin), Group A (25,000 KIU/kg of aprotinin), and Group C which served as a control. The liver regeneration rate 72 hours after hepatectomy in Groups FA and F, and the plasma FN levels at 24 and 72 hours following hepatectomy in groups with FN, were significantly higher than that of the control group. The incorporation of 3H-thymidine into DNA and the phagocytic index of the reticuloendothelial system at 24 hours in Groups FA and F, and the mitotic index at 72 hours after hepatectomy in Group FA were significantly increased as compared to the control. But the supplementation of 20 mg/kg of indomethacin to the 4 groups resulted in significant suppression of 3H-thymidine uptake 24 hours after hepatectomy. Moreover, plasma fibronectin levels in rats correlated well with the phagocytic index and DNA synthesis 24 hours following partial hepatectomy. These results suggest that fibronectin may act as an activator of the reticuloendothelial system, related to prostaglandins, in the process of liver regeneration.

Animals↗

PubMed1990

[A clinical evaluation of distant metastases from a hepatocellular carcinoma with reference to location, frequency, symptoms, treatment & prognosis].

A clinical analysis of patients with hepatocellular carcinoma (HCC) associated with a distant metastases has been undertaken by the authors. Studied were eight patients (Group A) whose distant metastases were detected at the time of their initial examination, and 24 patients (Group B) whose distant metastases had been diagnosed during the course of treatment of their primary lesions. Complications arising from liver cirrhosis in Group A was less than in Group B. The location of the metastases were the bone in 16, the lung and the adrenal gland in four, the brain and the skin in two and the kidney in one. The mean survival times were 4.6 months (Group A), and 6.3 months (Group B). The cause of death was chiefly a progression of the primary lesion, except for one brain metastases. This analysis had shown that treatment of a bone metastasis is necessary for the relief of pain, and that care should be taken for the prevention of a fracture or paralysis, and that control of the primary lesion is necessary for improving the chances of survival.

Adrenal Gland Neoplasms↗

PubMed1990

Peripheral blood neutrophil function in germfree and conventional rats.

The superoxide anion production and the myeloperoxidase activity between polymorphonuclear cells (PMNs) from conventional and germfree rats were compared. Furthermore, the response to recombinant human granulocyte colony stimulating factor (G-CSF) between both groups of rats was also examined. Our present investigation showed that: (1) the basal superoxide anion production by PMNs in germfree rats (2.1 +/- 0.5 nmol/min/1 x 10(6) PMNs) is less than one fourth of that of conventional rats (9.5 +/- 2.9 nmol/min/1 x 10(6) PMNs). (2) the myeloperoxidase activity of PMNs from germfree rats (38.1 +/- 5.2 nmol/min/1 x 10(6) PMNs) is 1.7 times that of conventional rats (22.4 +/- 4.9 nmol/min/1 x 10(6) PMNs). (3) G-CSF administration increased the number of PMN, 12.4 times in the germfree rats compared with 3.9 times in the conventional rats. (4) the PMNs induced by G-CSF do not differ in the superoxide anion producing activity. However the myeloperoxidase activity decreased in the G-CSF induced PMNs of both groups of rats. From our data, the conventional rats could have a more effective killing activity than the germfree rats. Furthermore, germfree rats may be used as a powerful tool for assay of other biological substances relating to immune system and its regulation.

Animals↗

PubMed1990

Regulation of DNA primase activity by phosphorylation of histone-H1 in regenerating rat liver.

The biological importance of histone H1 was investigated in relation to the cell cycle using liver regeneration in rat. Histone H1 was extracted from the regenerating rat liver at various intervals after partial hepatectomy and the number of phosphate residues was measured. The inhibitory effect of the extracted histone H1 on DNA primase was assayed. The activities of DNA polymerase-alpha, DNA primase and DNA synthesis were also determined in the regenerating rat liver. It was found that: 1) phosphate residue in histone H1 from normal rat liver was between 2-3 mol/mol of histone H1. 2) The number of phosphate residues did not change for the first 16h after partial hepatectomy. 3) A dramatic sudden increase of phosphate residues was detected at 18h after partial hepatectomy. 4) The high levels of phosphate residues remained constant thereafter up to 50h. 5) DNA primase activity was less inhibited by highly phosphorylated than by slightly phosphorylated histone H1. It seems probable that phosphorylation of histone H1 is needed for the releasing of DNA primase activity from its inhibited state, which would start DNA synthesis together with DNA polymerase-alpha.

Animals↗

PubMed1990

[Comparison of ciprofloxacin with polymyxin B for infection prophylaxis in neutropenic patients with acute non-lymphocytic leukemia].

Twenty-four neutropenic patients receiving intensive chemotherapy for acute non-lymphocytic leukemia were studied in a randomized trial comparing ciprofloxacin with polymyxin B for prevention of infections. Both groups (12 patients each group) received amphotericin B for antifungal prophylaxis. 20 febrile episodes occurred in 22 courses of oral prophylactic ciprofloxacin and 22 occurred in 24 courses of oral prophylactic polymyxin B. Patients receiving ciprofloxacin had a mean time to the first infection-related febrile episode of 7.2 days, compared with 4.3 days for the polymyxin B group (p less than 0.01). Patients receiving ciprofloxacin also had fewer days of fever (average 6.5 days versus 9.8 days for the polymyxin B group, p less than 0.02). Duration of administration of parental antibiotics were also shorter in the ciprofloxacin group (p less than 0.001). Although modifications of the empiric antibiotic regimen were required more frequent in patients receiving polymyxin B, this did not reach statistical significance. These results suggest that ciprofloxacin is a more efficacious oral antimicrobial agent than polymyxin B for the prevention of infections in neutropenic patients with acute non-lymphocytic leukemia.

Administration, Inhalation↗