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Biomedical subjects

H Takada

Publications and source records attributed to H Takada.

At least 235 records · Page 13Linked to original sources
PubMed1994

[Clinical evaluation of M-VAC (methotrexate, vinblastine, adriamycin and cisplatin) chemotherapy for advanced urothelial cancer].

M-VAC (methotrexate, vinblastine, adriamycin and cisplatin) chemotherapy was performed on 27 patients with advanced urothelial cancer. The patients included 20 with bladder cancer, 4 with upper urinary tract cancer and 3 with both lesions. Complete response (CR) was observed in 2 (7.4 +/- 9.9%) patients and partial response (PR) in 10 (37.0 +/- 18.2%) patients after the treatment, i.e., the overall objective response rate was 44.4 +/- 18.7%. The rate of relapse or recurrence in the patients with CR and PR was 100% and 90.0%, respectively. The mean duration of the response was 18.5 +/- 13.4 months and 10.7 +/- 10.9 months for CR and PR, respectively. The overall survival rate after one year was 30.2%. Bone marrow suppression was the most serious side effect. The white blood cell count became below 1,000/microliters in 10 patients (36.7%). Among them, 4 patients suffered from sepsis. In conclusion, M-VAC chemotherapy was effective for induction therapy against advanced urothelial cancer, although the effective duration was short. Further maintenance therapy should be established.

Adult↗
PubMed1993

Increased release of KC/gro protein, intercrine cytokine family, from hepatocytes of the chronically ethanol fed rats.

In an attempt to clarify the mechanisms of neutrophil-accumulation in the liver of alcoholics, release of KC/gro protein (intercrine cytokine family) from hepatocytes in the chronically ethanol fed rats was examined. Chemotactic activity for rat neutrophils was demonstrated in the culture supernatant of hepatocytes isolated from the ethanol fed rats, which was then inhibited in the presence of antibody against rat KC/gro protein. Immunoblot analysis revealed that the peptide reacted with antiserum against KC/gro protein was demonstrated at a molecular weight of 20-23kDa, and an amount of KC/gro protein released from the hepatocytes of the chronically ethanol fed rats was increased, as compared with that of the control rats.

Alcoholism↗
PubMed1993

Peritoneal gamma delta T cells induced by Escherichia coli infection in mice. Correlation between Thy-1 phenotype and host minor lymphocyte-stimulating phenotype.

We found that gamma delta T cells increased in number in the peritoneal cavity after i.p. inoculation with Escherichia coli (ATCC 26) in mice. The increase of the gamma delta T cells was most prominent on day 5 after inoculation when the pathogens had been already eliminated from the hosts. Two-color flow cytometric (FCM) analysis revealed that these gamma delta T cells in infected C57BL/6 mice expressed Thy-1 Ag on their cell surface. On the other hand, gamma delta T cells induced by E. coli inoculation in C3H/He mice contained Thy-1-negative gamma delta T cells in addition to the Thy-1-positive gamma delta T cells. In both strains, irrespective of Thy-1 Ag expression, these gamma delta T cells were CD5 negative, CD44 positive, L-selectin negative, Ly-6C negative, and IL-2R low positive. Analyses of peritoneal exudate cells (PEC) from several other strains of mice after E. coli inoculation suggested that Thy-1-negative gamma delta T cells appear in mice carrying endogenous superantigen specific for V beta 3, especially mammary tumor virus-6. These findings suggest that Thy-1 Ag expression on the gamma delta T cells appearing in the peritoneal cavity after i.p. E. coli inoculation is correlated to the Mls phenotype of the host mice.

Animals↗
PubMed1993

Enhancement of human hepatocyte growth factor production by interleukin-1 alpha and -1 beta and tumor necrosis factor-alpha by fibroblasts in culture.

Human hepatocyte growth factor (hHGF) was first purified from plasma of patients with fulminant hepatic failure (Gohda, E., Tsubouchi, H., Nakayama, H., Hirono, S., Sakiyama, O., Takahashi, K., Miyazaki, H., Hashimoto, S., and Daikuhara, Y. (1988) J. Clin. Invest. 81, 414-419) and is now identified to be the same protein as the scatter factor (Weidner, K. M., Arakaki, N., Hartmann, G., Vandekerckhove, J., Weingart, S., Rieder, H., Fonatsch, C., Tsubouchi, H., Hishida, T., Daikuhara, Y., and Birchmeier, W. (1991) Proc. Natl. Acad. Sci. U. S. A. 88, 7001-7005) and tumor cytotoxic factor (Shima, N., Nakao, M., Ogaki, F., Tsuda, E., Murakami, A., and Higashio, K. (1991) Biochem. Biophys. Res. Commun. 180, 1151-1158), and it is known to be produced by fibroblasts in culture. Here we report that inflammatory cytokines such as interleukin-1 (IL-1) and tumor necrosis factor (TNF) stimulate production of hHGF from human embryonic lung fibroblasts, MRC-5, and human gingival fibroblasts, GF-5. Recombinant human IL-1 alpha (rhIL-1 alpha) and recombinant human TNF-alpha (rhTNF-alpha) increased hHGF levels in culture supernatants of MRC-5 and GF-5 cells dose-dependently as determined by an enzyme-linked immunosorbent assay for hHGF. The half-maximal stimulatory concentrations of rhIL-1 alpha and rhTNF-alpha were about 1ng/ml and 10 units/ml, respectively. rhIL-1 beta showed almost the same effect as IL-1 alpha on stimulation of production of immunoreactive hHGF from the two cell lines. However, rhIL-6 failed to show the stimulatory effect on hHGF production by the cells in the range of 2-200 units/ml. Human interferon-beta and -gamma also did not show the stimulatory activity. Stimulation of hHGF production was observed 6-12 h after addition of rhIL-1 alpha or rhTNF-alpha and lasted at least 48 h, and the observed stimulation of hHGF production by cytokines was suppressed by addition of corresponding antiserum. hHGF mRNA levels of MRC-5 cells increased by addition of rhIL-1 alpha and rhTNF-alpha in a dose-dependent manner as determined by Northern blot analysis using cDNA for hHGF as a probe. In addition, results from nuclear run-off transcription experiments showed that the two cytokines regulated increasing hHGF gene expression at transcriptional levels rather than a change in mRNA stability. These observations indicate that the inflammatory cytokines modulate the production and secretion of hHGF by fibroblasts and may play an important role for tissue repair and regeneration.

Blotting, Northern↗
PubMed1993

The effects of lobenzarit disodium, a novel immunomodulator, upon murine coxsackievirus B3 myocarditis.

The aim of this study is to test the therapeutic efficacy of immunomodulation with lobenzarit disodium (CCA) upon coxsackievirus B3 (CB3) myocarditis. Two-week-old C3H/He mice were inoculated with 10(3) plaque-forming units of CB3. CCA, 2.5 mg/kg per day, was administered subcutaneously daily on days 0-14 (Experiment I; group 2) and days 14-28 (Experiment II; group 4). Both treated groups were compared to infected controls (groups 1 and 3). For the analysis of splenic lymphocyte subsets, additional mice in untreated and treated groups were killed on day 7, and the percentages of Thy 1.2 (CD3), L3T4 (CD4) and, Ly 2 (CD8) subsets were analyzed by laser flow cytometry (Experiment III). In Experiment I, the survival rate did not differ significantly between groups 1 and 2. Cellular infiltration in the CCA group was less severe. Myocardial virus titers and serum neutralizing antibody titers did not differ significantly between the two groups. In Experiment II, the survival rates between the two groups did not differ significantly. Myocardial necrosis in the CCA group was less severe compared to the control. In Experiment III, the percentages of Thy 1.2 (CD3) and L3T4 subsets (CD4) of the treated group were significantly higher than those of the control group. Thus, CCA increased splenic T cells and improved cardiac pathology in acute murine CB3 myocarditis.

Adjuvants, Immunologic↗
PubMed1993

Enhancement of coxsackievirus B3 myocarditis in mice by lobenzarit disodium through inhibition of splenic pan T cells.

OBJECTIVE: The aim was to test the efficacy of the immune system modulator lobenzarit disodium in the treatment of coxsackievirus B3 myocarditis. METHODS: Two week old C3H/He mice were inoculated with 10(3) plaque forming units of coxsackievirus B3. Lobenzarit disodium, 25 mg.kg-1.d-1, was given subcutaneously daily on days 0-14 (experiment I; group 2) and days 14-28 (experiment II; group 4). Both treated groups were compared to infected controls for each experiment (groups 1 and 3). For the analysis of splenic lymphocyte subsets, additional mice in untreated and treated groups were killed on d 7, and the percentages of Thy 1.2 (CD3), L3T4 (CD4), Ly 2 (CD8) subsets were analysed by laser flow cytometry (experiment III). RESULTS: In experiment I, the survival rate in the lobenzarit treated group was significantly lower than in the controls (2/11 v 8/11). Cellular infiltration and myocardial necrosis in the lobenzarit group were more severe. Myocardial virus titres and serum neutralising antibody titres did not differ significantly between the two groups. In experiment II, the survival rate (7/9 v 13/13) and cardiac pathology between the two groups did not differ significantly. In experiment III, the percentage of the Thy 1.2 subset (CD3) in the treated group was significantly lower (p < 0.05) than in the control group, at 36.0(SD 2.9)% v 42.8(5.8)%. CONCLUSIONS: Lobenzarit disodium decreased splenic pan T cells and aggravated both clinical course and cardiac pathology in acute murine coxsackievirus B3 myocarditis.

Animals↗
PubMed1993

Role of oxygen derived free radicals in the pathogenesis of coxsackievirus B3 myocarditis in mice.

OBJECTIVE: The aim was to test the role of oxygen derived free radicals in the development of myocarditis. This involved investigating the effects of polyethylene glycol conjugated superoxide dismutase (PEG-SOD, an enzyme catalysing the conversion of O2.- to H2O2) and polyethylene glycol conjugated catalase (PEG-catalase, accelerating the reaction of H2O2 to H2O and O2) upon coxsackievirus B3 (CB3) myocarditis. METHODS: Two week old male C3H/He mice were inoculated intraperitoneally with 10(3) plaque forming units of CB3. PEG-SOD, 1 x 10(3) U.kg-1 x d-1, and PEG-SOD, 1 x 10(3) U.kg-1 x d-1, plus PEG-catalase, 1 x 10(3) U.kg-1 x d-1, were injected subcutaneously daily on days 0 to 14. Treated groups were compared to the infected control. RESULTS: On day 7, there were no significant differences in pathological scores among the three groups. On day 14, the cellular infiltration, myocardial necrosis, and calcification scores were significantly lower in the PEG-SOD group and the PEG-SOD plus PEG-catalase group than in the control. There were no significant differences in pathological scores between the PEG-SOD group and the PEG-SOD plus PEG-catalase group. There were no differences in the myocardial virus titres on day 7 among the three groups. On day 14, virus was not detected from the myocardium in any of the three groups. CONCLUSIONS: The results suggest that superoxide anion is mostly responsible for myocyte injury in CB3 myocarditis in mice, and that hydrogen peroxide formed as a result of dismutation of superoxide anion may not play a significant role in the development of myocarditis. Superoxide anion is one of the most important factors in free radical mediated injury in CB3 myocarditis in mice and the administration of PEG-SOD alone has therapeutic potential in clinical CB3 myocarditis.

Animals↗
PubMed1993

Site-directed mutagenesis of a hexapeptide segment involved in substrate recognition of phenylalanine dehydrogenase from Thermoactinomyces intermedius.

Phenylalanine dehydrogenase from Thermoactinomyces intermedius and leucine dehydrogenase from Bacillus stearothermophilus show a 59% sequence similarity in their substrate-binding domains, although their substrate specificities are different. We prepared a phenylalanine dehydrogenase mutant enzyme whose inherent hexapeptide segment (124F-V-H-A-A-129R) in the substrate-binding domain was replaced by the corresponding part of leucine dehydrogenase (M-D-I-I-Y-Q) in order to investigate the mechanism of substrate recognition by phenylalanine dehydrogenase. The catalytic efficiencies (kcat/Km) of the mutant enzyme with aliphatic amino acids and aliphatic keto acids as substrates were 0.5 to 2% of those of the wild-type enzyme. In contrast, the efficiencies for L-phenylalanine and phenylpyruvate decreased to 0.008 and 0.035% of those of the wild-type enzyme, respectively. These results suggest that the hexapeptide segment plays an important role in the substrate recognition by phenylalanine dehydrogenase.

Amino Acid Oxidoreductases↗
PubMed1993

Induction of inflammatory cytokines by a soluble moiety prepared from an enzyme lysate of Actinomyces viscosus cell walls.

A carbohydrate-rich and immunobiologically active component, M1Av, was prepared from an M-1 endo-N-acetylmuramidase digest of cell walls of Actinomyces viscosus ATCC 19246 by CM Sephadex C-25 and Sephadex G-100 chromatography. M1Av stimulated thioglycolate-induced peritoneal macrophages from C3H/HeN and C3H/HeJ mice to release cell-free tumour necrosis factor (TNF) and interleukin (IL)-6, and a cell-associated thymocyte activating factor, probably IL-1. An intravenous (i.v.) injection of M1Av induced increased levels of TNF and IL-6 in the serum of C3H/HeN mice that had been primed with 100 micrograms of muramyldipeptide (MDP) i.v. However, M1Av did not induce TNF release in C3H/HeJ mice similarly primed with MDP. Simultaneous administration of M1Av (100 micrograms, i.v.) and galactosamine (18 mg, intraperitoneally) killed C3H/HeN, but not C3H/HeJ mice. M1Av was shown to be practically free of endotoxin by the Limulus test. These findings indicate that the solubilised A. viscosus cell-wall carbohydrate moiety induced inflammatory cytokines both in vitro and in vivo.

Actinomyces viscosus↗
PubMed1993

Treatment of an infant with congenital sodium diarrhea by oral rehydration.

We have been following a male case of congenital sodium diarrhea (CNaD), who had a distended abdomen, passed watery stools with high sodium concentration, and showed metabolic acidosis in the first week of life. He also showed hyponatremia, low urine sodium, high serum aldosterone and high renin activity. Other possible causes of secretory diarrhea were ruled out. The initial effective treatment was oral supplements of water and electrolytes lost in the fecal fluid: with this he gained weight, and hyponatremia and metabolic acidosis were corrected. Loperamide hydrochloride was administered to increase intestinal absorption of sodium, as the serum prostaglandin was high. Watery diarrhea then improved, but as he passed acholic stools, we stopped and postponed the treatment for a while; the stools then became watery again. Although diarrhea has persisted, he has not shown any abnormalities in growth or psychomotor development for the first two years of life.

Alkalosis↗
PubMed1993

Cytokine induction by extracellular products of oral viridans group streptococci.

During an etiological study of Kawasaki disease (mucocutaneous lymph node syndrome [MCLS]), we found that dominant viridans streptococcal strains on tooth surfaces and in the throat of both MCLS patients and non-MCLS control children formed erythrogenic and biologically active, extracellular products. In this study, we demonstrated that erythrogenic culture supernatant concentrates of representative strains (two Streptococcus mitis and two Streptococcus oralis), when injected intravenously, induced serum tumor necrosis factor alpha, interleukin-6 (IL-6), and gamma interferon in muramyldipeptide- or Propionibacterium acnes-primed C3H/HeN mice. The concentrates also induced tumor necrosis factor alpha, IL-6, and thymocyte-activating factor (essentially IL-1) in murine peritoneal macrophage, human monocyte, and human whole-blood cultures. An erythrogenic, heat-labile extracellular protein fraction (F-1) that was concentrated from the culture supernatants of a representative S. mitis strain exhibited the above-mentioned cytokine-inducing activity. This partially purified F-1 fraction also induced thymocyte-activating factor and IL-6 in human umbilical vascular endothelial cell and gingival fibroblast cultures.

Animals↗
PubMed1993

Urinary epidermal growth factor in patients with gliomas: significance of the factor as a glial tumor marker.

Epidermal growth factor (EGF) content in urine from patients with glial tumors was examined by radioimmunoassay techniques with labeled human EGF and its rabbit EGF polyclonal antibody. There was no cross-reaction with transforming growth factor-alpha, which has a common receptor with EGF. Forty glial tumors were divided into three groups according to the clinical stage: Samples from Group A patients were obtained before therapy and/or after biopsy; in these patients a large volume of tumor was apparent on computerized tomography (CT). Group B samples were obtained after gross total removal of the tumor and/or chemo- and radiation therapy; these patients showed a small volume of residual tumor on CT. Samples from Group C patients were obtained after gross tumor total removal and/or chemo- and radiation therapy; no tumor was detected on CT scans in these patients. Urinary EGF levels in Group A samples were statistically significantly higher than in samples from healthy individuals (p < 0.001), Group B patients (p < 0.10), and Group C patients (p < 0.02). In addition, high-grade glial tumors in Group A cases showed a significantly higher level of urinary EGF than low-grade tumors in Group A patients (p < 0.05), or patients with meningioma (p < 0.02), metastatic brain tumor (p < 0.05), and cerebral infarction (p < 0.001). Longitudinal changes of urinary EGF levels in glioma patients mostly synchronized with the clinical course and therapeutic interventions. Therefore, urinary EGF, as a glial tumor marker, may be of practical value for diagnosing a malignant glioma and evaluating for the efficacy of chemo- and radiation therapy.

Adolescent↗
PubMed1993

[A clinical study of 17 cases of penile cancer].

A clinical evaluation of 17 patients with penile cancer treated in our hospital from 1965 to 1991 were surveyed. They were between 34 and 74 years old with a mean age of 63.8 years. The average interval between the onset and the first visit was 22.8 months. Fourteen patients (83%) complained of the manifestation of a tumor and 14 patients (83%) were phimotic. The stage classified according to Jackson was Stage I for 6, Stage II for 6, Stage III for 4 and Stage IV for 1 patient. At the first visit, the inguinal lymph nodes were palpated in 8 patients and metastasis was confirmed in 5 (63%) of them. Surgical treatment was given to 15 patients (88%) (radical or partial penectomy was performed in most cases). Chemotherapy was given to 9 patients (60%) (main chemotherapeutic agent was bleomycin) and irradiation to 5 patients (30%). The overall 3-year survival rate was 71%, and 5-year survival rate was 56%. The 5-year survival rate in the low stage group (Stage I, II) was 75%, while that in the high stage group (Stage III, IV) was 0%, showing a significant difference.

Adult↗
PubMed1993

Production of chemotactic factor, interleukin-8, from hepatocytes exposed to ethanol.

In a previous paper, we demonstrated proteinous chemotactic factors released from hepatocytes exposed to ethanol. In this study, we further characterized the chemotactic factors released from ethanol-treated hepatocytes. After fractionating the conditioned medium with gel chromatography, we demonstrated chemotactic activity at molecular weights of around 20 and 40 kD. When the conditioned medium was mixed with antiserum against interleukin-8, chemotactic activity was almost completely abolished. In addition, antiserum against interleukin-8 completely reduced chemotactic activity of the 20-kD chemotactic factor but did not influence the chemotactic activity of the 40-kD chemotactic factor. After gel electrophoresis of the conditioned medium, the protein reacted with antibody against interleukin-8 was demonstrated at a molecular weight of 20 kD but was not found at a molecular weight of 40 kD. These results suggest that a major part of the proteinous chemotactic factors released from hepatocytes exposed to ethanol could be a dimer form of interleukin-8, one of the proinflammatory cytokines, possibly contributing to the pathogenesis of alcoholic hepatitis.

Animals↗
PubMed1993

The antiseptic effect of a quick drying rubbing type povidone-iodine alcoholic disinfectant solution.

A quick drying rubbing type disinfectant of non-water non-towel type is an antiseptic method suitable for practical use in intensive care units where emergency situations are common. We determined the antiseptic efficacy and safety of a quick drying rubbing type povidone-iodine alcoholic disinfectant solution (HAD Hand Wash) in comparison with benzalkonium chloride alcoholic lotion. The bacterial reduction rate obtained by hand washing with a single 3 ml application was 93.8% for HAD Hand Wash and 94.1% for benzalkonium chloride alcoholic lotion. Thus, excellent antiseptic efficacy was obtained with both disinfectants. Roughening of hand skin which appeared in association with HAD Hand Wash solution was transient and mild in nature in all of the cases, indicating the high safety of this disinfectant. It is justified to say from these findings that HAD Hand Wash is useful as a hand and finger disinfectant.

Antisepsis↗
PubMed1993

Comparison of bactericidal activities of various disinfectants against methicillin-sensitive Staphylococcus aureus and methicillin-resistant Staphylococcus aureus.

Various disinfectants were compared in terms of the duration of bactericidal activity against methicillin-sensitive Staphylococcus aureus (MSSA), and methicillin-resistant Staphylococcus aureus (MRSA), among S. aureus isolated in our hospital. Strains of S. aureus which showed minimum inhibitory concentrations of cloxacillin of less than 1.56 micrograms/ml and of 3.13 micrograms/ml or higher were designated MSSA and MRSA respectively. There was no difference in sensitivity to disinfectants between MSSA and MRSA. There was a great variation in the duration of bactericidal activity of chlorhexidine gluconate against these species with the majority requiring contact times of between 2 minutes and over 20 minutes. All strains except for one strain of MRSA were killed within 20 seconds after disinfection with benzalkonium chloride. All strains were killed within 20 seconds after disinfection with alkyldiaminoethylglycine hydrochloride or povidone-iodine.

Benzalkonium Compounds↗
PubMed1993

[Chronic inflammatory demyelinating polyneuropathy in childhood].

Clinical, electrophysiological and histopathological findings in 6 children with steroid-responsive acquired demyelinating neuropathy are presented. The clinical features and nerve conduction findings are basically similar to those of chronic inflammatory demyelinating neuropathy (CIDP) in adults, although early-onset cases had prominent pes cavus deformity and thickened nerves, which are rare findings in acquired neuropathies in adults. The diagnostic criteria of adult CIDP can be adopted for most of the cases, however, repeated electrophysiological tests may be required to identify multifocality of the nerve lesion, especially when conduction block is not apparent before treatment. The biopsied sural nerves showed many thinly-myelinated fibers, subperineurial and endoneurial edema, and cellular infiltrations. Varied fascicular involvements were common. Two cases with almost complete or considerable loss of myelinated fibers in the biopsied sural nerve revealed good clinical response to steroid therapy. The degree of nerve degeneration in the sural nerve thus, may not be helpful to estimate the prognosis and the responsiveness to treatment. Therapeutic trials should be employed when the main conduction findings are those of demyelinating neuropathies, even if genetically-determined neuropathy is suggested from the clinical pictures.

Adolescent↗