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Biomedical subjects

M Hashimoto

Publications and source records attributed to M Hashimoto.

At least 613 records · Page 34Linked to original sources
PubMed1994

[Percutaneous radiofrequency coagulation therapy for liver tumor: experimental study].

We invented a newly devised local thermal therapy using radiofrequency energy for treating liver tumors. This method was investigated for evaluating its safety and effectiveness. In vitro study, the maximum size of coagulated albumen was 5.5 to 6.2mm in diameter, and 9.8 to 11.3mm in length. In vivo study using rabbit's liver, the range of coagulated tissue by radiofrequency energy was localized around the tip of the needle. Percutaneous radiofrequency coagulation therapy will be the effective therapy for liver tumor regardless of tumor vascularity.

Animals↗
PubMed1994

Platelet release reaction during EDTA-induced platelet agglutinations and inhibition of EDTA-induced platelet agglutination by anti-glycoprotein II b/III a complex monoclonal antibody.

To characterize the nature of EDTA-induced platelet agglutination, the spontaneous release of beta-thromboglobulin (beta-TG) and platelet factor 4 (PF4) was examined during EDTA-induced platelet agglutinations. A slight release of beta-TG and PF4 was observed when EDTA-anticoagulated whole blood from cases with EDTA-induced platelet agglutination was kept for 60 minutes, whereas a high spontaneous release of these proteins was found from normal blood anticoagulated with EDTA. These findings imply that EDTA-dependent platelet agglutinin may stabilize the platelet membrane surfaces. Secondly, we found that pretreatment of fresh blood with anti-glycoprotein (GP) II b/III a complex monoclonal antibody dramatically reduced EDTA-induced platelet agglutinations. This study indicated that the binding sites of EDTA-dependent antibody might be GP II b/III a complex. The use of an anti-GP II b/III a complex monoclonal antibody may be useful in avoiding analytical errors in some cases with EDTA-induced pseudothrombocytopenia.

Adenosine Diphosphate↗
PubMed1994

Site-directed mutagenesis in hemoglobin: functional and structural role of the penultimate tyrosine in the alpha subunit.

The penultimate tyrosine in the hemoglobin subunit is considered to be one of the most important residues for the normal structure and function of hemoglobin. To elucidate the functional and structural role of the penultimate residue in the alpha-subunit, we prepared new artificial mutants; Hb Y140 alpha Q, in which Tyr-140 alpha is replaced by a nonaromatic residue, Gln, and Hb Y140 alpha F, which loses its hydrogen bond to Val-93 alpha by the substitution of Phe for Tyr. HB Y140 alpha Q exhibited a markedly increased oxygen affinity and almost completely diminished cooperativity, whereas Hb Y140 alpha F showed similar but less extensively impaired function, indicating that the aromatic residue at the penultimate position in the alpha-subunit contributes to the stabilization of the T-quaternary structure as does the corresponding residue in the beta-subunit. However, the deoxygenated forms of these mutants bear significant T-state character in their spectroscopic properties observed at high protein concentrations. The tetramer-dimer equilibrium data of the mutants suggested that a significant part of the functional alterations observed for dilute solution appears to result from partial dissociation into alpha beta dimers rather than direct destabilization of the T-quaternary structure in the deoxygenated form. Therefore, we can conclude that the penultimate tyrosine in the alpha-chain plays a key role not only in the stabilization of the T-state but also in the subunit assembly.(ABSTRACT TRUNCATED AT 250 WORDS)

Allosteric Regulation↗
PubMed1994

Intraperitoneal injection of 1-oleoyl-2-docosahexaenoyl phosphatidylcholine enhances discriminatory shock avoidance learning in rats.

Effects of injection of 1-oleoyl-2-docosahexaenoyl-sn-glycero-3-phosphorylcholine (ODHPC) on learning ability were investigated in rats using discriminatory shock avoidance learning task. When ODHPC (2 mumol) was intraperitonealy administered 5 min before the beginning of the first trial of learning task from the second to fifth sessions, avoiding rates of the ODHPC-injected group were significantly higher than those of the control group. However, any injection of ODHPC derivatives, such as 1-oleoyl-2-docosahexaenoyl-diacylglycerol, 1,2-dioleoyl-sn-glycero-3-phosphorylcholine, glycerophosphorylcholine, docosahexaenoate, oleate and choline chloride, did not affect learning. These results suggest that intraperitoneal ODHPC injection enhances learning ability by its specific conformation.

Animals↗
PubMed1994

Genetic changes in atypical hyperplasia and lymphoma with angioimmunoblastic lymphadenopathy and dysproteinaemia in the same patients.

The transition between atypical hyperplasia and lymphoma with angioimmunoblastic lymphadenopathy and dysproteinaemia (AILD) was studied in serial lymph node biopsy specimens from five patients using DNA analysis with Southern blot analysis, polymerase chain reaction, chromosomal analysis, and immunophenotyping. The chromosomal analysis showed additional abnormalities as the disease progressed to those present initially, and immunological staining showed a corresponding increase in the numbers of CD4- and Ki67-positive cells. In the first biopsy from each patient a diagnosis of atypical hyperplasia with AILD was made and lymphoma excluding by the finding of only a few atypical lymphoid cells and the preservation of follicles with germinal centres. DNA analysis of lymph nodes at this stage showed either germ lines or oligoclonal rearrangements of the T-cell receptor (TCR) and immunoglobulin heavy chain genes. In the final biopsy, when a diagnosis of lymphoma with AILD was made, either a monoclonal rearrangement of the TCR was observed or one of the rearranged bands had increased in density. These results suggest selective proliferation of a clone of abnormal cells may account for the progression of atypical hyperplasia to lymphoma with AILD.

Base Sequence↗
PubMed1994

Does interleukin-1 mediate tumour necrosis factor alpha-induced fever in rabbits?

We investigated the humoral mechanisms involved in tumour necrosis factor alpha (TNF alpha)-induced fever in rabbits. No change in lymphocyte-activating factor activity was detected in serum drawn during TNF alpha-induced fever. The pyrogenic activity of recombinant rabbit interleukin-1 beta (IL-1 beta) was entirely abolished by pre-incubation with anti-IL-1 beta antiserum from the goat. Fever induced by intravenous (i.v.) injection of IL-1 beta was significantly diminished by i.v. infusion of the antiserum. However, i.v. infusion of the antiserum for 1 h did not affect fever induced by i.v. injection of TNF alpha, when the antiserum infusion began either simultaneously with, or 2 h after, the injection of TNF alpha. Furthermore, intracerebroventricular injection of the anti-serum did not affect TNF alpha-induced fever. The intracerebroventricular administration of naloxone (an opioid receptor antagonist) significantly diminished TNF alpha-induced fever. The results suggest that IL-1, both in the blood circulation and in the brain, may not be involved in TNF alpha-induced fever. Similar to the contribution of eicosanoids, the opioid system in the brain seems somehow to contribute to the mechanism of the development of fever induced by TNF alpha in rabbits.

Animals↗
PubMed1994

Production of soluble ICAM-1 from human endothelial cells induced by IL-1 beta and TNF-alpha.

The present study was designed to establish the effects of cytokines on soluble ICAM-1 (sICAM-1) production by human endothelial cells (EC) and ICAM-1 expression on these cells and the effects of purified sICAM-1 on lymphocyte-EC adhesion. Expression of ICAM-1 and production of sICAM-1 were measured by a specific ELISA method. ICAM-1 expression was enhanced by IL-1 beta, TNF-alpha, and most effectively by IFN-gamma. IL-4, IL-6, M-CSF, or GM-CSF showed no effects on ICAM-1 expression. IL-4 (100 units/ml) or IL-6(100 units/ml) abolished the enhancing effect of IL-1 beta, while TNF-alpha (1, 10, 100 units/ml) synergized with IL-1 beta to promote ICAM-1 expression in EC. In contrast with the transient increase of cell-associated ICAM-1 expression after activation by IL-1 beta, which peaked 40 h poststimulation and declined thereafter, sICAM-1 continued to accumulate in culture supernatants even after 48 h poststimulation in IL-1 beta-stimulated EC. IL-1 beta treatment resulted in an increase in adhesion. sICAM-1, purified from cell-free supernatants obtained after a 48-h culture of EC in IL-1 beta by affinity chromatography using monoclonal ICAM-1 antibody coupled to Sepharose beads, significantly inhibited lymphocyte EC adhesion. Preincubation of lymphocytes with conditioned medium of EC cultured with 100 units/ml IL-1 beta for 48 h, which contained a considerable amount of sICAM-1, resulted in a significant inhibition of lymphocyte adhesion to IL-1 beta-stimulated EC. These results suggest that there is a cumulative increase in sICAM-1 concentration in the vicinity of cytokine-stimulated EC and that this sICAM-1 modulates ICAM-1-mediated cell to cell interaction.

Cell Adhesion Molecules↗
PubMed1994

Production of soluble ICAM-1 by mononuclear cells from patients with rheumatoid arthritis patients.

The present study was designed to quantify the level of the soluble form of ICAM-1 (sICAM-1) produced by mononuclear cells (MNC) of rheumatoid arthritis (RA) patients, and to correlate these levels with the disease activity and with the amounts of cytokines or rheumatoid factors (RF) produced by MNC. Unstimulated synovial fluid (SF) MNC produced higher amounts of sICAM-1 than peripheral blood (PB) MNC in RA patients (P < 0.01). sICAM-1 production by PHA-stimulated MNC was higher in RA SF MNC than RA or normal PB MNC (P < 0.01). The amounts of SICAM-1 produced correlated with the amounts of soluble IL-2 receptor produced (P < 0.02) but not with IL-1B or the Lansbury activity index in RA PB MNC. sICAM-1 correlated with the amounts of soluble CD23 and IL-4 produced by normal PB MNC (P < 0.01). The amounts of sICAM-1 correlated with IgG-RF (P < 0.02) and IgM-RF (P < 0.01) produced by unstimulated MNC obtained from the bone marrow (BM) of RA patients. ICAM-1 expression of T-lymphocyte subsets, B lymphocytes, and monocytes obtained from RA PB and RA BM assayed by two-color flow cytometry ranged from 0.1 to 6%, which was not appreciably different from that of normal controls. The monocyte fraction of RA PB MNC produced significantly higher amounts of sICAM-1 than lymphocyte fraction. These results suggest that sICAM-1 produced by MNC may be a marker of cell activation in T and B lymphocytes, in contrast to the transient increase of ICAM-1 expression.

Adult↗
PubMed1994

Methotrexate for steroid-resistant systemic lupus erythematosus.

We here report two patients with steroid-resistant systemic lupus erythematosus (SLE) who were successfully treated with methotrexate (MTX). In both cases, a steroid resistant high fever, associated with mild myositis and pancytopenia were the main common findings, and all these symptoms were alleviated within a few days either by 7.5 mg or 5 mg MTX per week. The number of CD4+ cells increased along with the clinical improvement, whereas the number of CD20+ cells and HLA-DR expressing cells also decreased. Taking into account the side effects of high dose corticosteroids and cyclophosphamides, treatment with a weekly low dose of MTX is known to contribute to an improvement in the long-term prognosis for patients with refractory SLE.

Adult↗
PubMed1994

Prevalence of HCV genotype among patients with chronic liver diseases in the Tokyo metropolitan area.

We examined 613 Toranomon Hospital patients with HCV RNA-positive chronic liver disease to elucidate the viral genotype in the Tokyo metropolitan area. An epidemiological and clinical study was conducted in the 565 patients whose HCV genotype could be determined. The HCV genotypes found were type II, in 414 patients (67.5%); type III, in 103 (16.8%); type IV, in 37 (6.0%); type V, in 4 (0.7%); mixed genotype II and III, in 5 (0.8%); and mixed genotype II and IV, in 2 (0.3%). The HCV genotype could not be determined in 48 patients. Type II was most prevalent. The HCV genotype I was not found at all. There were no significant differences between genotypes in relation to sex, age, history of blood transfusion, or the progression of the disease. It was uncommon to find a history of blood transfusion in the patients with mixed genotypes; however, a high incidence of hepatic disorders was noted among the family members of these patients. Ninety-two percent of the patients with HCV genotype II tested positive for C100-3, while 70.9% of those with type III, and 43.2% of those with type IV tested positive for this antibody. HCV genotype II was most prevalent, and the positivity rate for anti C100-3 in patients with this HCV genotype was significantly higher (P < 0.00001) than that in patients with the other genotypes.

Adolescent↗
PubMed1994

What roles does the organum vasculosum laminae terminalis play in fever in rabbits?

Experiments were designed to clarify the role of the brain's organum vasculosum laminae terminalis (OVLT) in the development of fever in rabbits. Rectal and ear skin temperatures were recorded in conscious animals in which the OVLT had been electrolytically destroyed or in which the preoptic anterior hypothalamus (PO/AH) had been transected bilaterally. When the OVLT had been ablated the febrile responses to intravenous injection of interleukin-1 beta (IL-1 beta) or tumour necrosis factor alpha were significantly attenuated, while those to intracerebroventricular injection of IL-1 beta were not affected. Fever induced by intracerebroventricular injection of prostaglandin E2 (PGE2) was prolonged significantly. The febrile responses to intravenous injection of IL-1 beta and to intracerebroventricular injection of PGE2 were attenuated when the transection was located caudally to the anterior wall of the third ventricle and extended laterally more than about 3 mm in the ventricular wall. The results show that the OVLT region is a site through which signals to increase body temperature are transferred from the blood to the brain in rabbits.

Animals↗
PubMed1994

Notes on the acetylcholine-induced relaxation of porcine coronary arteries.

Intact and rubbed coronary arteries responded to acetylcholine (ACh) with contractions in a cumulative dose-dependent manner. The rubbed artery contracted at a lower concentration of ACh (3 x 10(-8) M) than the threshold level of the agonist in the intact artery (10(-7) M). Only in the intact artery was the second cumulative dose-response to ACh (10(-6) M) decreased by 60% (p < 0.05). Pretreatment of the intact artery with methylene blue or NG-monomethyl-L-arginine (L-NMMA) increased the contractile response to ACh. The ACh-induced increase of the cGMP level in the intact artery was eliminated by removal of the endothelial cells and by pretreatment of the artery with either methylene blue or L-NMMA. These findings indicate that the endothelial cells in the coronary artery are responsible for the ACh-induced relaxation, presumably mediated by an endothelium-derived relaxing factor.

Acetylcholine↗
PubMed1994

Serologic and nucleotide sequencing analyses of a novel DR52-associated DRB1 allele with the DR 'NJ25' specificity, designated DRB1*1307.

A novel DR52-associated DRB1* allele, designated DRB1*1307, was encountered in the course of our HLA-DRB1 genotyping study in a Japanese population by PCR-RFLP. Comparison of the nucleotide sequence of its second exon with those of the other known DRB1 alleles revealed that DRB1*1307 was most similar to DRB1*1101, differing by two amino acid substitutions. From a family study, DRB1*1307 was found to segregate with a haplotype of DRB3*0202-DQA1*0501-DQB1*0301, which was also observed with DRB1*1101 in a Japanese population. DRB1*1307 was recognized in three of 652 healthy Japanese controls (gene frequency: 0.24%) with the same DR-DQ haplotype, indicating that DRB1*1307 arose from DRB1*1101 by a gene conversionlike event(s) and/or point mutations. Further, it was also observed that this allele had a strong linkage disequilibrium with HLA-B70 (p < 0.001). This new DRB1*1307 allele was serologically defined as DR 'NJ25,' and it gave an almost identical serologic pattern to DRB1*1406. On sequence comparison, however, no unique amino acid residues conserved in DRB1*1406 and DRB1*1307 but absent in all the other DRB1 alleles could be found, indicating that two amino acid changes at positions 47 and 58 abolished the reactivity against the DR11 antisera.

Alleles↗
PubMed1994

A novel biotinylated heterobifunctional cross-linking reagent bearing an aromatic diazirine.

The synthesis of a p-[(3-trifluoromethyl)diazirine-3-yl]benzoic acid derivative is described as a new carbene generating heterobifunctional cross-linking reagent. The cross-linker carries a biotin moiety in order to make use of avidin-biotin technology for specific manipulation of cross-linked components. To evaluate the ability of this reagent, the inter-subunit cross-linking of egg-white avidin tetramer was investigated. As a typical application of avidin-biotin technology for cross-linking experiments, a chemiluminescent detection method was examined to identify photobiotinylated components. A cross-linked dimeric product with an apparent molecular mass of 38 kDa was clearly visualized by the combined use of a horseradish peroxidase-streptavidin conjugate and a luminol-based chemiluminescent system.

Avidin↗
PubMed1994

Prognosis of cervical spinal cord injury in correlation with magnetic resonance imaging.

Magnetic resonance (MR) images of 18 patients with a cervical spinal cord injury were analysed for prognostic signs of paralysis. Serial MR images were obtained within 48 hours (acute stage), then 2 weeks (subacute stage) and an average of 12 months (range 6-24 months) after injury. The patterns of signal intensity in the acute stage were divided into two types, slightly-low/low (SL/L) type and slightly-low/high (SL/H) type on T1-weighted images (T1WI) and T2-weighted images (T2WI). The patterns in the subacute stage were divided into two types, high/high (H/H) type and normal/high (N/H) type on T1WI and T2WI. Six patients showed SL/L type in the acute stage and H/H type in the subacute stage. Five of the patients had a paralysis of grade A and one of grade B at admission which remained unchanged after treatment. One patient showed SL/H type in the acute stage and H/H type in the subacute stage. The patient had a paralysis of grade A that improved to no more than grade B. The remaining 11 patients showed SL/H type in the acute stage and N/H type in the subacute stage. Their paralysis was from grade B to D at admission and grade D or E at the follow up. The signal intensity of SL/L type in the acute stage and H/H type in the subacute stage are bad prognostic signs.

Adolescent↗
PubMed1994

A novel zinc finger protein, zic, is involved in neurogenesis, especially in the cell lineage of cerebellar granule cells.

To clarify the mechanism of cerebellar development, we have cloned a gene, named zic, encoding a zinc finger protein that is expressed abundantly in granule cells throughout development of the cerebellum. zic has a significant homology to the zinc finger domain of the Caenorhabditis elegans tra1 gene, the Drosophila cubitus interruptus Dominant gene, and the human GLI oncogene. An in situ hybridization study revealed that zic showed a restricted expression pattern in the granule cells and their putative precursor cells. It is also expressed at an early embryonic stage in the dorsal half of the neural tube. The expression pattern and nuclear localization were confirmed by immunohistochemical study. Furthermore, the bacterially expressed zic protein containing the zinc finger domains bound to the GLI-binding sequence. These findings suggest that zic is one of a number of nuclear factors involved in both differentiation in early development and maintenance of properties of the cerebellar granule cells.

Amino Acid Sequence↗
PubMed1994

Contrasting effects of an angiotensin converting enzyme inhibitor and a calcium antagonist on calcium transients in isolated rat cardiac myocytes.

OBJECTIVE: The aim was to examine the effects of an angiotensin converting enzyme (ACE) inhibitor and a calcium antagonist on intracellular calcium transients in isolated cardiac myocytes from a monocrotaline induced right ventricular hypertrophy model. METHODS: One week after monocrotaline injection, Sprague-Dawley rats were given either an ACE inhibitor (delapril-HCl) or a calcium antagonist (nilvadipine) for two weeks. Using fura-2/AM, calcium transients were measured in single myocytes separated from the right ventricle. RESULTS: The severe right ventricular hypertrophy observed in untreated rats was significantly reduced in drug treated animals. The inhibitory effects of delapril were more prominent than those of nilvadipine, although both drugs reduced right ventricular pressure to the same extent. Calcium transients in delapril treated rats were similar to those in control rats. On the other hand, the calcium transient in nilvadipine treated rats was decreased and its time course was prolonged. The changes were similar to those found in monocrotaline treated rats. The responsiveness of calcium transients to isoprenaline in delapril treated rats was similar to that in control rats. The responsiveness in nilvadipine treated rats was decreased, and was similar to that in monocrotaline treated rats. Delapril improved developed tension and the beta adrenoreceptor responsiveness of developed tension to isoprenaline. CONCLUSIONS: Although delapril and nilvadipine inhibited cardiac hypertrophy in monocrotaline treated rats, significant improvement of contractile function and beta adrenoreceptor responsiveness was observed only in the delapril treated rats. This improvement was partially due to the improvement in calcium transients and the restoration of the beta adrenoreceptor responsiveness of the calcium transient to beta adrenergic stimulation.

Angiotensin-Converting Enzyme Inhibitors↗