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Biomedical subjects

K Katayama

Publications and source records attributed to K Katayama.

At least 19 recordsLinked to original sources

Protective effects of E3330, a novel quinone derivative, on galactosamine/tumor necrosis factor-alpha-induced hepatitis in mice.

Oral pretreatment with E3330, a novel quinone derivative, attenuated liver injury induced with tumor necrosis factor-alpha in galactosamine-sensitized mice. Tumor necrosis factor-alpha is known to induce inflammatory mediators such as leukotrienes and prostanoids. An in vitro study showed that E3330 inhibited the generation of leukotriene B4 and thromboxane B2, but enhanced prostaglandin E2 generation from rat peritoneal exudate cells stimulated with the Ca(2+)-ionophore, A23187. These findings suggest that the protective effect of E3330 on galactosamine/tumor necrosis factor-alpha hepatitis is due at least in part to its inhibition of the generation of leukotrienes. The inhibition of thromboxane B2 generation or the enhancement of prostaglandin E2 generation by E3330 may also contribute to its hepatoprotective effect.

Animals

Deletion mutagenesis of stem cell factor defines the C-terminal sequences essential for its biological activity.

We constructed a series of murine stem cell factor (mSCF) cDNAs which were sequentially truncated at the 3' termini. The resultant six mutant cDNA encode N-terminal 183, 179, 162, 149, 142 and 133 amino acid residues of the mature mSCF protein fused to the heterogeneous C-terminal peptides derived from the linker sequences. Each mutant cDNA was transiently expressed in COS cells, and the cultured supernatant was assayed for its ability to support the growth of a human factor-dependent cell line, TF-1 and to enhance colony formation by murine hematopoietic progenitor cells. The results showed that as few as N-terminal 142 but not 133 amino acid residues of mSCF remained biologically active in vitro, suggesting that the region of 9 amino acids from Asp134 to Ser142 containing a Cys138-mediated disulfide bond may contribute to the C-terminal end of the active subdomain of mSCF.

Amino Acid Sequence

Effect of anti-CD3 antibody on the generation of interleukin-2-activated lymphocytes from tumor tissues of gastrointestinal cancer.

BACKGROUND: The efficiency of anti-CD3 antibody (OKT3) for adoptive immunotherapy using lymphokine-activated killer (LAK) cells generated from tumor-infiltrating lymphocytes (TIL), regional lymph node lymphocytes (RLNL), and peripheral blood lymphocytes (PBL) was investigated. METHODS: TIL, RLNL, and PBL derived from 39 patients with gastrointestinal cancers (16 gastric cancers, 17 colorectal cancers, and 6 esophageal cancers) were cultured for 4 weeks with 200 U/ml of recombinant interleukin-2. To one group, solid-phase 10 micrograms/ml OKT3 was added during the initial culture period (day 2 or 4). Cytotoxicity against K562 cells (NK-like activity) and Daudi cells (LAK activity) and the phenotypes of effector cells generated after culturing for 2-3 weeks were studied. RESULTS: Proliferative responses were significantly increased by OKT3 in each type of effector cell (P less than 0.01); in particular, TIL expanded more by OKT3 than PBL and RLNL (P less than 0.01). The population of CD8+ CD11b- cytotoxic T-cells in OKT3-stimulated groups was significantly larger than that in unstimulated groups (P less than 0.01), whereas no differences were observed with CD4+ cells (helper/inducer T-cells) and CD8+ CD11b+ cells (suppressor T-cells). OKT3 enhanced the NK-like activity of TIL and PBL but did not affect their LAK activity. OKT3 suppressed the NK and LAK activity of RLNL. CONCLUSIONS: OKT3 stimulation did not significantly enhance the LAK activity, but the authors propose that OKT3 could be an effective addition to adoptive immunotherapy using TIL due to an increased proliferation and generation of a large cytotoxic T-cell population.

Aged

Transcriptional mechanisms of type I collagen gene expression are differentially regulated by interleukin-1 beta, tumor necrosis factor alpha, and transforming growth factor beta in Ito cells.

Regulation of the procollagen type I (Pro alpha 1) gene in cultured Ito cells by diverse cytokines was studied. Specifically, we have examined the effect of interleukin-1 beta (IL-1 beta), tumor necrosis factor alpha (TNF alpha), and transforming growth factor beta (TGF beta) on collagen biosynthesis, levels of Pro alpha 1 (I) mRNA, and rate of transcription of Pro alpha 1 (I) gene. TGF beta stimulated procollagen synthesis at least 2-fold at every concentration tested (5-20 ng/ml), whereas TNF alpha inhibited it at the same concentrations. In contrast to what occurs in dermal fibroblasts, IL-1 beta (5-20 units/ml) preferentially inhibited procollagen production as measured by [3H]proline incorporation. A similar pattern was obtained when total protein synthesis was analyzed by [25S]methionine radiolabeling. Interestingly, while TGF beta-treated cells exhibited greater than 3-fold increase in steady-state levels of Pro alpha 1 (I) mRNA, the treatment with IL-1 had no effect on procollagen mRNA levels. TNF alpha treatment resulted in a 2-fold decrease in the amount of collagen mRNA. The treatment with combinations of cytokines indicated that collagen gene expression in Ito cells is differentially regulated by these cytokines. Furthermore, nuclear run-off transcription experiments were performed. The results obtained suggest that TGF beta regulates increasing collagen type I gene expression at transcriptional levels, and TNF alpha inhibits the transcriptional rate of Pro alpha 1 (I) gene. It is noteworthy that IL-1 beta acts on collagen type I gene regulation by a separate mechanism at a posttranscriptional level.

Animals

Polymorphism of a long-chain cycloparaffin (CH2)120.

The polymorphism of a long-chain cycloparaffin (CH2)120 and chain packing in its crystals were discussed on the basis of some results obtained mainly by transmission electron microscopy. Monoclinic and orthorhombic single crystals of (CH2)120 were isothermally grown together from a dilute solution in p-xylene. Lozenge-shaped orthorhombic single crystals were more frequently observed than lath-shaped monoclinic ones. The basal surfaces of orthorhombic and monoclinic single crystal platelets were decorated with vapor-deposited polyethylene [PE]. Orthorhombic single crystals of (CH2)120 with the (110) twin boundary and monoclinic ones with the (100) twin boundary were also observed. Rod-like edge-on crystals of (CH2)120 were grown from a dilute p-xylene solution onto the (001) surface of alkali halides. The crystal system of the (CH2)120 edge-on crystals depended on the kind of substrate. The monoclinic crystal was grown on NaCl, the orthorhombic one on KBr and KCl. The monoclinic form of (CH2)120 edge-on crystal was transformed to the orthorhombic one by annealing on NaCl. In both monoclinic and orthorhombic edge-on crystals, the molecular plane determined by two zigzag stems in a molecule of (CH2)120 was parallel to the substrate surface and the molecular axis (crystallographic c-axis) was perpendicular to the longer side of the rod-like edge-on crystals. The sub-cell dimensions of the stem chains in both forms of (CH2)120 crystals were very similar to those of monoclinic and orthorhombic PE crystals, respectively.

Crystallization

Detection of the minus strand of hepatitis C virus RNA by reverse transcription and polymerase chain reaction: implications for hepatitis C virus replication in infected tissue.

The combination of reverse transcription and polymerase chain reaction is a very powerful tool for the detection of hepatitis C virus RNA in sera of patients with hepatitis C virus infection. However, when studying the presence of this virus in tissue using polymerase chain reaction, it may be difficult to distinguish between blood viral particles adhering to the tissue and viral RNA contained within the tissue. Because hepatitis C virus has a single-stranded RNA of positive polarity, a minus-strand RNA is expected to be found in hepatitis C virus-replicating tissues as a template for the synthesis of genomic RNA. To see whether the detection of the minus strand of hepatitis C virus RNA by polymerase chain reaction can be used for the determination of hepatitis C virus-replicating tissues, we examined the presence of the minus strand of hepatitis C virus RNA in the plasma, peripheral blood mononuclear cells and liver specimens of patients with hepatitis C virus infection. The plus-strand RNA was detected in the plasma, peripheral blood mononuclear cells and the liver specimens, but the minus-strand RNA was only detected in the liver. These results suggest that hepatitis C virus replicates in the liver but not in peripheral blood mononuclear cells. This detection method for the minus strand of hepatitis C virus RNA should be useful for determining hepatitis C virus replication in tissues other than liver tissue.

Adult

Postoperative complications and survival after pancreatoduodenectomy in patients aged over 70 years.

An analysis of postoperative complications and survival was conducted in 31 patients undergoing pancreatoduodenectomy (PD) for carcinoma of the pancreas or periampullary carcinoma. Of them, 11 were over 70 years of age and 20 were under 70. Anastomotic leakage was the most common complication after PD. Definite pancreatic leakage was found in one patient in the over 70 group, and one case each of pancreatic, biliary, and gastric leakage were found in the under 70 group. All complications were treated conservatively without any further operative intervention. The overall morbidity rate was 41.9% (13/31), being 45.5% (5/11) in the over 70 group and 40.0% (8/20) in the under 70 group, and no operative deaths occurred within 30 days after surgery. The cumulative survival rate of the patients aged over 70 years with carcinoma of the pancreas or periampullary carcinoma did not differ significantly from the rate of those under 70. It was thus concluded that PD achieves an adequate prognosis and survival in patients over 70 years of age.

Adult

Effect of intra-hepatoarterial infusion of MMC and CDDP for gastric cancer patients with liver metastases.

The influence of operative treatment and chemotherapy on the prognosis in 93 gastric cancer patients with liver metastasis was studied. Chemotherapy included the systemic administration of mitomycin C (MMC) (39 patients), an intra-hepatoarterial infusion of MMC (MMC IAC group) (19 patients) and an intra-hepatoarterial infusion of MMC and cisplatin (CDDP) (MMC + CDDP IAC group) (24 patients). Either MMC or MMC and CDDP were given in 1-4 courses every 3-4 weeks from the first one to two post operative weeks. The response rate was 4 per cent (1/23), 29 per cent (5/17) and 73 per cent (17/23) for MMC systemic administration, MMC IAC and MMC + CDDP IAC, respectively, with a significantly high rate of effectiveness for the MMC + CDDP IAC. In addition, regarding the median survival period, the MMC + CDDP IAC group showed 11.8 months, as compared with 2.9 months for other chemotherapeutic treatments, indicating a good prognosis regardless of any possible resection of the primary lesion. A Cox proportional hazard model revealed the treatment by MMC + CDDP IAC alone to be a significant independent factor. These results indicated that MMC + CDDP intra-arterial chemotherapy is an effective approach to gastric cancer with liver metastasis.

Adult

Effects of alpha-interferon on gamma-interferon production of peripheral blood mononuclear cells in hepatitis B virus carriers.

We studied gamma-interferon production of phytohemagglutinin-stimulated peripheral blood mononuclear cells in response to alpha-interferon in hepatitis B virus carriers and healthy individuals. The magnitude of gamma-interferon production was significantly higher in patients with anti-HBe antibody than in patients with HBe antigen and healthy individuals. Furthermore, alpha-interferon augmented the production of gamma-interferon of peripheral blood mononuclear cells from patients with active liver injury [serum alanine aminotransferase (ALT), greater than 40 U/L], but not that from patients with inactive liver injury (serum ALT, less than 40 U/L) or healthy individuals. These results suggested that alpha-interferon could enhance the cellular immune response against hepatitis B virus by augmenting the endogenous production of gamma-interferon in patients with active liver injury, implying that the responsiveness to alpha-interferon might be responsible for liver cell injury.

Adult

Hepatitis B virus markers and antibodies to hepatitis C virus in Japanese patients with hepatocellular carcinoma.

Sera from Japanese patients with chronic liver disease were tested for hepatitis B virus (HBV) markers and antibodies to hepatitis C virus (anti-HCV), and the results were correlated to the presence of hepatocellular carcinoma. In chronic non-A, non-B liver disease, anti-HCV prevalence was high both in patients with hepatocellular carcinoma (78/89, 88%) and without it (66/84, 79%), while previous HBV infection was more common in patients with hepatocellular carcinoma (65/89, 73%) than in those without it (46/84, 55%) (P less than 0.05). Coexistence of anti-HCV and antibodies to HBV was observed frequently in patients with hepatocellular carcinoma (56/89, 63%) compared with patients without it (39/84, 46%) (P less than 0.05). In chronic HBV carriers, anti-HCV was more common in patients with hepatocellular carcinoma (12/38, 32%) than in those without it (3/62, 5%) (P less than 0.01). These results suggest that infection with the two viruses may be a risk factor for more serious liver disease.

Aged

Suppressive effects of E3330, a novel quinone derivative, on tumor necrosis factor-alpha generation from monocytes and macrophages.

E3330 [(2E)-3-[5-(2,3-dimethoxy-6-methyl-1,4-benzoquinoyl)]-2-nonyl-2- propenoic acid], a novel synthesized hepatoprotective compound, has suppressive effects on tumor necrosis factor-alpha (TNF-alpha) generation from monocytes/macrophages in vitro. E3330 (1-100 microM) reduced lipopolysaccharide (LPS, 10 mg/ml or 1 microgram/ml)-induced TNF-alpha generation from rat resident and Propionibacterium acnes (P. acnes)-elicited peritoneal macrophages, rat and human monocytes, rat Kupffer cells, and splenic mononuclear cells in a concentration-dependent manner. E3330 also (1-100 microM) suppressed TNF-alpha generation stimulated with egg-albumin immune complex in rat P. acnes-elicited peritoneal macrophages. Northern blot analysis showed that LPS-induced expression of TNF-alpha messenger RNA (mRNA) in human blood monocytes was suppressed by E3330. These findings indicate that E3330 has a suppressive effect on TNF-alpha generation from monocytes/macrophages, regardless of origin or species, and this effect is based in part on the suppression of TNF-alpha mRNA expression.

Animals

Enhanced expression of HLA class I by inhibited replication of hepatitis B virus.

HLA class I display on hepatitis B virus (HBV)-infected hepatocytes is important for limiting HBV infection. However, the effect of HBV replication on HLA class I expression on host cells has not been determined. Since acyclovir is known to inhibit HBV replication of the novel cell line HB611, which was transfected with HBV genome using human hepatoblastoma cells as the recipient and continuously replicates HBV DNA, we analyzed HLA class I expression on acyclovir-treated HB611 by quantitative flow cytometry. The results demonstrated that acyclovir treatment clearly increases the level of HLA class I on HB611, and suggested that HBV replication inhibits expression of HLA class I on infected hepatocytes. This effect of HBV replication on the host cell may be a means by which HBV evades immune surveillance to maintain chronic infection.

Acyclovir

Sesame seed lignans and gamma-tocopherol act synergistically to produce vitamin E activity in rats.

Vitamin E activity of sesame seed, which contains only gamma-tocopherol, a compound that has vitamin E activity equal to only 6-16% that of alpha-tocopherol, was examined in two experiments. In the first experiment, groups of rats were fed four diets: vitamin E-free control diet, alpha-tocopherol-containing diet, gamma-tocopherol-containing diet and sesame seed-containing diet. Changes in red blood cell hemolysis, plasma pyruvate kinase activity, and peroxides in plasma and liver, as indices of vitamin E activity, were examined. The sesame seed diet has high vitamin E activity, whereas this activity was low in the gamma-tocopherol diet. In plasma and liver, alpha-tocopherol was found in high concentration only in the alpha-tocopherol-fed group, and gamma-tocopherol was found in high concentration only in the sesame seed-fed group, with negligible amounts of gamma-tocopherol in liver of the gamma-tocopherol-fed group. In the second experiment, two diets containing sesame lignan (sesaminol or sesamin) and gamma-tocopherol were tested. Results in both of the sesame lignan-fed groups were comparable to those observed in the sesame seed-fed group in Experiment 1. These experiments indicate that gamma-tocopherol in sesame seed exerts vitamin E activity equal to that of alpha-tocopherol through a synergistic interaction with sesame seed lignans.

Animals

Effect of changing afterload and inotropic states on inner and outer ventricular wall thickening.

Effect of changing afterload and inotropic states on inner and outer ventricular wall thickening. Am. J. Physiol. 263 (Heart Circ. Physiol. 32): H109-H116, 1992.--To study the differing behaviors of the inner (IH) and outer halves (OH) of the left ventricular (LV) free wall during an increasing afterload and changing inotropic states, we determined the LV pressure (LVP) and transmural (TM) and OH wall thickness (WTTM and WTOH) by sonomicrometry in 11 anesthetized dogs. The percent systolic wall thickening (% delta WT) and the fractional contribution (FC) were calculated. At rest, % delta WT of TM, IH, and OH were 22 +/- 1 (mean +/- SE), 33 +/- 3, and 13 +/- 2 (P less than 0.01 vs. IH), respectively. The FC of IH and OH were 74 +/- 5 and 29 +/- 4% (P less than 0.01 vs. IH), respectively. During increasing afterload by aortic constriction (AC) without drugs, % delta WT in IH was reduced to 22 +/- 2%, associated with unchanged % delta WT in OH (12 +/- 3%), whereas the FC of IH and OH were not altered from resting values. During AC with dobutamine infusion (3 micrograms.kg-1.min-1), the % delta WT and FC in each layer were not reduced from resting values. On the other hand, during AC with propranolol (2 mg bolus iv), the reduction of % delta WT in IH was greater (from 29 +/- 4 to 15 +/- 6%, P less than 0.01) than that in OH (from 11 +/- 2 to 10 +/- 3%; P less than 0.01 vs. IH). The FC in the IH was decreased (56 +/- 16%) by AC with propranolol, so that the difference in FC between IH and OH became insignificant (FCOH 40 +/- 13%, P greater than 0.1 vs. FCIH).(ABSTRACT TRUNCATED AT 250 WORDS)

Animals