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Biomedical subjects

Y Hashimoto

Publications and source records attributed to Y Hashimoto.

At least 721 records · Page 40Linked to original sources
PubMed1995

Novel after-loading interstitial photodynamic therapy of canine transmissible sarcoma with photofrin II and excimer dye laser.

Novel after-loading interstitial photodynamic therapy was performed in a canine transmissible sarcoma (CTS) model, utilizing photofrin II and an excimer dye laser. First, photofrin II was injected intravenously at a dose of 5 mg/kg, then 48 h later, laser-proof plastic tubing was inserted into the CTS, followed by photoradiation of the tumor from the inside. The mean diameter of tumor necrosis rapidly increased in parallel with increase in total irradiation energy below 240 J/cm; the mean diameter of tumor necrosis was 20.7 mm at an energy of 120 J/cm, and 24.5 mm at 240 J/cm. Beyond 240 J/cm, the diameter gradually increased to 26 mm at 960 J/cm. As a side effect, cutaneous tissue showed a deep open ulcer at 240 J/cm, a shallow open ulcer at 180 J/cm, and a scar healing at 120 J/cm. The thermal effect of laser light is considered negligible below 480 J/cm.

Animals↗
PubMed1995

Cloning, sequencing, and expression of the uroporphyrinogen III methyltransferase cobA gene of Propionibacterium freudenreichii (shermanii).

We cloned, sequenced, and overexpressed cobA, the gene encoding uroporphyrinogen III methyltransferase in Propionibacterium freudenreichii, and examined the catalytic properties of the enzyme. The methyltransferase is similar in mass (27 kDa) and homologous to the one isolated from Pseudomonas denitrificans. In contrast to the much larger isoenzyme encoded by the cysG gene of Escherichia coli (52 kDa), the P. freudenreichii enzyme does not contain the additional 22-kDa peptide moiety at its N-terminal end bearing the oxidase-ferrochelatase activity responsible for the conversion of dihydrosirohydrochlorin (precorrin-2) to siroheme. Since it does not contain this moiety, it is not a likely candidate for synthesis of a cobalt-containing early intermediate that has been proposed for the vitamin B12 biosynthetic pathway in P. freudenreichii. Uroporphyrinogen III methyltransferase of P. freudenreichii not only catalyzes the addition of two methyl groups to uroporphyrinogen III to afford the early vitamin B12 intermediate, precorrin-2, but also has an overmethylation property that catalyzes the synthesis of several tri- and tetra-methylated compounds that are not part of the vitamin B12 pathway. The enzyme catalyzes the addition of three methyl groups to uroporphyrinogen I to form trimethylpyrrocorphin, the intermediate necessary for biosynthesis of the natural products, factors S1 and S3, previously isolated from this organism. A second gene found upstream from the cobA gene encodes a protein homologous to CbiO of Salmonella typhimurium, a membrane-bound, ATP-dependent transport protein thought to be part of the cobalt transport system involved in vitamin B12 synthesis. These two genes do not appear to constitute part of an extensive cobalamin operon.

Amino Acid Sequence↗
PubMed1995

Expression of the Runt domain-encoding PEBP2 alpha genes in T cells during thymic development.

The PEBP2 alpha A and PEBP2 alpha B genes encode the DNA-binding subunit of a murine transcription factor, PEBP2, which is implicated as a T-cell-specific transcriptional regulator. These two related genes share the evolutionarily conserved region encoding the Runt domain. PEBP2 alpha B is the murine counterpart of human AML1, which is located at the breakpoints of the 8;21 and 3;21 chromosome translocations associated with acute myeloid leukemia. Northern (RNA) blots of various adult mouse tissues revealed that the levels of expression of both genes were most prominent in the thymus. Furthermore, transcripts of PEBP2 alpha A and mouse AML1/PEBP2 alpha B were detected in T lymphocytes in the thymuses from day 16 embryos and newborns, as well as 4-week-old adult mice, by in situ hybridization. The expression of the genes persisted in peripheral lymph nodes of adult mice. The transcripts were detected in all the CD4- CD8-, CD4+ CD8+, CD4+ CD8-, and CD4- CD8+ cell populations. The results indicated that both genes are expressed in T cells throughout their development, supporting the notion that PEBP2 is a T-cell-specific transcription factor. Transcripts of mouse AML1/PEBP2 alpha B were also detected in day 12 fetal hematopoietic liver and in the bone marrow cells of newborn mice. The implication of mouse AML1/PEBP2 alpha B expression in hematopoietic cells other than those of T-cell lineage is discussed in relation to myeloid leukemogenesis.

Acute Disease↗
PubMed1995

Lyme disease in Japan. Analysis of Borrelia species using rRNA gene restriction fragment length polymorphism.

BACKGROUND: Lyme disease is sporadically observed in Japan since the first report in 1987. We have experienced 19 cases of Lyme disease. In 12 out of 13 trials we succeeded in isolating Borrelia strains (JEM1-12) from erythema migrans (EM) lesions. Recently, Borrelia burgdorferi sensu lato was classified into at least three distinct subgroups, B. burgdorferi sensu stricto, B. garinii and B. afzelii. OBJECTIVE: In order to characterize Lyme disease in Japan, we summarized the clinical features of our cases and investigated the nature of the isolated Borrelia strains. METHODS: The 12 Borrelia strains were analyzed by restriction fragment length polymorphism (RFLP) of ribosomal RNA gene. RESULTS: Most of our 19 patients were in stage I with EM as the main clinical manifestation. RFLP analysis using 12 strains isolated from the patients indicated that 8 strains (group IV, V) were different from the three aforementioned genospecies. CONCLUSION: Clinical data from the present study substantiate the view that Japanese Lyme disease has a relatively milder course. We speculate that this may be related to the specific Borrelia strains in Japan.

Adult↗
PubMed1995

Ionic lead, but not other ionic metals (Ni2+, Co2+ and Cd2+), suppresses 2-methoxy-4-aminoazobenzene-mediated cytochrome P450IA2 (CYP1A2) induction in rat liver.

Male F344 rats were pretreated with lead nitrate, nickel chloride, cobalt chloride or cadmium chloride, and their effects on the induction of cytochrome P450 (CYP) enzymes, mainly CYP1A2 enzyme, with 2-methoxy-4-aminoazobenzene (2-MeO-AAB) in the livers were comparatively examined by enzymatical, immunochemical, and molecular biological methods. When rats were pretreated with each ionic metal, the total CYP amount in the liver microsomes decreased, as compared with that of rats treated with 2-MeO-AAB alone. However, among the ionic metals used only lead reduced the levels of the mRNA and protein of CYP1A2 induced with 2-MeO-AAB in the rat liver, and decreased the microsomal activity (per CYP) for CYP1A2-mediated mutagenesis. Furthermore, ionic lead, but not other ionic metals, showed an ability to induce a placental form of glutathione S-transferase (GST-P). The level of CYP1A2 induced with 2-MeO-AAB was decreased along with increase in that of the induced GST-P.

Animals↗
PubMed1995

Benzylphthalimides and phenethylphthalimides with thalidomide-like activity on the production of tumor necrosis factor alpha.

Benzylphthalimide analogs (P1P's) and phenethylphthalimide analogs (P2P's) have been found to exhibit thalidomide-like activity on the production of tumor necrosis factor (TNF)-alpha by the human leukemia cell line, HL-60, stimulated by 12-O-tetradecanoylphorbol-13-acetate (TPA). Structure-activity relationships are discussed on the basis of the TNF-alpha production-enhancing activity. Benzylphthalimide (P1P-00) exhibited which is weaker than that of thalidomide, but introduction of a methyl group at the ortho-position of the benzyl moiety (P1P-10) resulted an increase to a level comparable with that of thalidomide. Phenethylphthalimide (P2P-00) is more potent than thalidomide, and its fluorinated derivative, 2-phenethyl-4,5,6,7-tetrafluoro-1H-isoindole-1,3-dione (FP2P-00), exhibited potent activity at very low concentrations.

HL-60 Cells↗
PubMed1995

Immunoselective cell growth inhibition by antibody-adriamycin conjugates targeting c-erbB-2 product on human cancer cells.

Monoclonal antibodies targeting c-erbB-2 protooncogene product p185 were conjugated with adriamycin via a pH-sensitive spacer. The resultant antibody-adriamycin conjugates showed immunoselective binding, internalization and cytotoxicity to p185-positive human breast cancer cell SKBr-3 and gastric cancer cell MKN-7, but not to normal human lymphocytes.

Antibiotics, Antineoplastic↗
PubMed1995

Analysis of antitumor properties of effector cells stimulated with a cell wall preparation (WPG) of Bifidobacterium infantis.

Intestinal Bifidobacterium species are thought to be beneficial in animal and human intestines. We studied the mechanisms of Bifidobacteria in antitumor activity using a cell wall preparation (WPG) of B. infantis (Cancer Res., 45, 1300, (1985)). WPG enhanced the in vitro antitumor activities of mouse peritoneal exudate cells elicited with proteose-peptone (P-PEC) and thioglycollate broth (TG-PEC), determined by cytostatic ([3H]thymidine uptake inhibition) and cytolytic ([3H]uridine release) assays. Tumor necrosis factor-alpha (TNF-alpha) and reactive nitrogen intermediates (RNI) play a role in such augmented cytotoxicity, because anti-TNF-alpha antibody almost completely blocked the increased cytolytic activity of P-PEC in the presence of WPG. Moreover, WPG induced RNI in the supernatant of TG-PEC in a dose-dependent manner. The mRNA expression of several cytokines (IL-1 beta, IL-6, IL-10, IFN-alpha and TNF-alpha) was induced in BALB/c mouse peritoneal cells 3 h after an intraperitoneal injection of WPG (3 h WPG-PEC). However, this expression disappeared from 24 h WPG-PEC, except for that of IFN-alpha. IFN-gamma was not induced. Kinetic studies of the tumor neutralizing activities of the WPG-PECs by means of the in vivo Winn assay revealed that the activity emerged at 1.5 h, became maximal at 3 h and disappeared at 24h. These results indicated that Bifidobacterial WPG is a Biological Response Modifier (BRM) with characteristics similar to those of other bacterial BRMs.

Animals↗
PubMed1995

Possible involvement of peripheral-type benzodiazepine receptors in erythroid differentiation of human leukemia cell line, K562.

Possible involvement of the peripheral-type benzodiazepine receptor (PBR) in hemin/protoporphyrin-induced erythroid differentiation of human leukemia K562 cells was investigated by the use of the ligands, diazepam and PK11195. Diazepam itself exhibited differentiation-inducing activity on K562 cells. The PBR-specific antagonist, PK11195, dose-dependently inhibited both diazepam-induced and hemin/protoporphyrin-induced K562 cell differentiation. The results imply that PBR is involved in the erythroid differentiation of K562 cells.

Cell Differentiation↗
PubMed1995

N-Alkylphthalimides: structural requirement of thalidomidal action on 12-O-tetradecanoylphorbol-13-acetate-induced tumor necrosis factor alpha production by human leukemia HL-60 cells.

Phthalimide analogs N-substituted with n-butyl, tert-butyl, hexyl and adamantyl groups were designed and prepared as simplified analogs of thalidomide and methylthalidomide. All the compounds prepared except N-n-butylphthalimide showed thalidomidal activity on 12-O-tetradecanoylphorbol-13-acetate-induced tumor necrosis factor (TNF)-alpha production by human leukemia HL-60 cells. Among the investigated compounds, including thalidomide and methylthalidomide, N-adamantylphthalimide showed the most potent TNF-alpha production-enhancing activity.

Humans↗
PubMed1995

Synergists for retinoid in cellular differentiation of human promyelocytic leukemia cells HL-60.

4-[5H-2,3-(2,5-Dimethyl-2,5-hexano)-5-methyldibenzo[b, e]diazepin-11-yl]benzoic acid (4) enhanced the differentiation-inducing activity of retinoic acid (1) and of a synthetic retinoid Am80 (2) toward human promyelocytic leukemia cells HL-60, although 4 alone did not induce differentiation. The synergistic effect of 4 on the activities of retinoids was also seen in suppression of proliferation of HL-60 cells.

Cell Differentiation↗
PubMed1995

[Chemistry of benzoxazinoids produced by plants as phytoalexin].

2,4-Dihydroxy-7-methoxy-2H-1,4-benzoxazin-3(4H)-one and its desmethoxy derivative (DIMBOA and DIBOA) are major phytoalexins produced by rye, wheat, zea maize and related monocotyledoneae plants. These compounds elicit a wide variety of biological activities including antifungal and mutagenic activities. Structure-activity relationships of these compounds and their derivatives (benzoxazinoids), and the reactivity of benzoxazinoids with nucleophiles are discussed in relation to the molecular mechanism of their biological activity. The electrophilic reaction mechanism of benzoxazinoids and substituent effects of namely 7-methoxy and 2-hydroxy groups are also discussed.

Antifungal Agents↗
PubMed1995

Purification and characterization of intracellular proteinases in Pleurotus ostreatus fruiting bodies.

A serine proteinase (ProA, EC 3.4.22.9) and two metalloendopeptidases (ProB, EC 3.4.99.32 and ProC, 3.4.24.4), have been purified to homogeneity from the fruiting bodies of Pleurotus ostreatus. ProA is a serine proteinase with a mass of 30 kDa, which has amidolytic and esterolytic activities besides proteolysis and catalyzes preferential cleavage of the peptide bonds involving the carboxyl groups of hydrophobic amino acid residues in oxidized bovine insulin B chain. The N-terminal amino acid sequence was VTQTNAPWGLSRL. ProB is a zinc-enzyme with a mass of 18 kDa, which is devoid of lysine, and its N-terminal sequence was ATFVGCSATRQ. The enzyme is inactivated completely by EDTA and 1,10-phenanthroline, and Zn(2+)-depleted ProB can regain the activity with Zn2+, Co2+, or Mn2+. Specific cleavage of Pro29-Lys30 in oxidized bovine insulin B chain, preferential generation of lysylpeptides from proteins, and a high susceptibility of polylysine suggest that ProB splits specifically the peptide bonds involving the alpha-amino group of lysyl residues. ProC is a metalloendopeptidase of a mass of 42.5 kDa, and Zn2+ was the most effective divalent metal ion to activate the EDTA-inactivated enzyme.

Amino Acid Sequence↗
PubMed1995

Involvement of the central nervous system in rheumatoid arthritis: its clinical manifestations and analysis by magnetic resonance imaging.

A rheumatoid arthritis (RA) patient showed high signal intensity in the subcortical region of the frontal and occipital lobes on T2-weighted magnetic resonance imaging (MRI). Histopathological examination in the autopsy specimen revealed severe systemic vasculitis. Additional radiological and laboratory studies revealed that transient cerebral ischemia induced by vasculitis occurred in this patient.

Arthritis, Rheumatoid↗
PubMed1995

Effect of aging on HbA1c in a working male Japanese population.

OBJECTIVE: To evaluate whether there is any change in HbA1c with age and to determine the effects of body mass index (BMI), exercise, and family history of diabetes on this change. RESEARCH DESIGN AND METHODS: A cross-sectional survey of 7,664 male Japanese workers aged 20-59 years was performed. All subjects received a physical examination that included measurement of HbA1c as an indicator of plasma glucose level. The subjects were classified according to their ages and BMIs, and any relationship with HbA1c levels was evaluated. Information on physical activity and family history of diabetes was obtained by a questionnaire. RESULTS: In all BMI groups, HbA1c increased with age. The greatest increase in HbA1c was observed in the 40- to 49-year-old age-group in subjects with a BMI < or = 26 kg/m2 and in the 30- to 39-year-old age-group in subjects with a BMI > 26. HbA1c in the subjects aged 20-29 years did not change with BMI. In contrast, HbA1c in subjects aged 30-59 years was significantly higher in those with a BMI > 26 when compared with those with BMI < or = 20. The age-dependent increase in HbA1c was greater in subjects with a positive rather than negative family history of diabetes. This age-dependent increase was not affected by active participation in sporting activities of mild to moderate intensity for 3 or more days per week. CONCLUSIONS: The age-dependent increase in HbA1c may be a consequence of the aging process itself. Furthermore, both BMI and a hereditary predisposition to diabetes, but not active participation in sports, affect this age-dependent increase in HbA1c.

Adult↗