PubMed Health⌕ Search

Biomedical subjects

M Ishihara

Publications and source records attributed to M Ishihara.

At least 19 recordsLinked to original sources
PubMed1995

An IRF-1-dependent pathway of DNA damage-induced apoptosis in mitogen-activated T lymphocytes.

Lymphocytes are particularly susceptible to DNA damage-induced apoptosis, a response which may serve as a form of 'altruistic suicide' to counter their intrinsic high potential for mutation and clonal expansion. The tumour suppressor p53 has been shown to regulate this type of apoptosis in thymocytes, but an as yet unknown, p53-independent pathway(s) appears to mediate the same event in mitogen-activated mature T lymphocytes. Here we show DNA damage-induced apoptosis in these T lymphocytes is dependent on the antioncogenic transcription factor interferon regulatory factor (IRF)-1. Thus two different anti-onco-genic transcription factors, p53 and IRF-1, are required for distinct apoptotic pathways in T lymphocytes. We also show that mitogen induction of the interleukin-1 beta converting enzyme (ICE) gene, a mammalian homologue of the Caenorhabditis elegans cell death gene ced-3, is IRF-1-dependent. Ectopic overexpression of IRF-1 results in the activation of the endogenous gene for ICE and enhances the sensitivity of cells to radiation-induced apoptosis.

Animals↗
PubMed1995

Microsatellite polymorphism between the tumor necrosis factor and HLA-B genes in Behçet's disease.

Behçet's disease is associated with the HLA-B51 antigen. However, it has not yet been clarified if the HLA-B51 gene itself is the susceptibility gene related to this disease or if it is some other non-HLA gene in linkage disequilibrium with HLA-B51. Therefore, we screened one of the HSP70 genes, HUM70t (HSP70-Hom), around the class III region and the microsatellite sequence located between the HLA-B and TNF genes for genetic polymorphism in BD. A comparison between patients with BD and healthy controls revealed no significant difference in the frequency of the HUM70t polymorphism. In the microsatellite sequence, Tau-a, in the region between the HLA-B and TNF genes, the frequency of 14 repetitions of GT was increased significantly and that of 11 repetitions was decreased significantly in the patient group. Further, the allelic distributions of the B51 antigen-associated microsatellite polymorphism differed significantly between patients and healthy controls, and in the B51 antigen-negative subjects, analysis of the microsatellite polymorphism also revealed a significant difference in the haplotype frequency between the patient and control groups. These results suggest that the HLA-B51 gene may not be the primary locus responsible for BD, and implicate some other gene(s) located between the TNF and HLA-B genes.

Base Sequence↗
PubMed1995

Clinical features of sarcoidosis in relation to HLA distribution and HLA-DRB3 genotyping by PCR-RFLP.

BACKGROUND: Susceptibility to the development of sarcoidosis has been demonstrated to be associated with HLA-DR5, -DR6, and -DR8 encoded by the DRB1 gene. However, involvement of the DRB3 (HLA-DR52) gene in the development of sarcoidosis remains unclear. METHODS: HLA-DRB3 genotyping was performed using the PCR-RFLP method and the clinical features of the patients with and without the DR3, 5, 6, 8 group antigens were compared. RESULTS: HLA-DRB3 genotyping indicated an association between DRB3*0101 and sarcoidosis. The DR8 haplotype lacking the DRB3 gene has been found to be increased significantly in sarcoidosis, suggesting that the HLA-DRB3 gene is not a primary determinant of predisposition to sarcoidosis. The association of DRB3*0101 with sarcoidosis is attributable to linkage disequilibrium with DR5- and DR6-associated alleles. There were significant decreases in the DR3, 5, 6, 8 group (DR5, DR6, or DR8) antigen frequencies in patients with retinal perivasculitis, high intraocular pressure (or secondary glaucoma), and optic nerve and/or macular lesion. Correlations were observed among the DR3, 5, 6, 8 group antigens, early onset sarcoidosis and disease with fewer intraocular lesions. CONCLUSION: This established a molecular basis for some of the clinical heterogeneity observed in sarcoidosis.

Adolescent↗
PubMed1995

[Usefulness of 3-dimensional image analysis of skull base lesions].

We have evaluated three-dimensional (3D) images of the skull base lesions for planning cranial base surgery. Fifty 3D images were reconstructed from computed tomographies (CT), and/or magnetic resonance (MR) images or MR angiographic images of 30 patients with skull base lesions. These images have provided useful information for pre-operative evaluation. The 3D image reconstructed from CT provides clear information concerning the bone. Conversely, the 3D image from MR images demonstrates soft tissue very clearly, and that from MR angiography provides a detailed description of the vasculature. For skull base lesions, it is essential to evaluate 3D images from the different modalities, especially CT scan and MR image.

Adolescent↗
PubMed1995

[Transcranial magnetic stimulation of the accesory nerve--investigation of the site and mechanism of excitation in the cat].

The site where transcranial magnetic stimulation excites the accessory nerve was studied in 5 cats. Transcranial magnetic stimulation of the accessory nerve was recorded from the right trapezius. The accessory nerve was stimulated electrically at the C1 level, jugular tubercle and jugular foramen. The latencies of the compound muscle action potentials (CMAPs) for each portion were measured and compared with the magnetic response, which was coincidental with that of the jugular tubercle. The accessory nerve was then transected in steps distally from the C1 level, and CMAPs following magnetic stimulation were recorded at each step. The CMAPs disappeared following the nerve transection at the jugular tubercle. The results of both approaches in this study conclude that transcranial magnetic stimulation excites the accessory nerve at jugular tubercle. This stimulation site was anatomically coincidental with that of the facial nerve and trigeminal nerve in being right before the point where the nerve bends. Following the accessory nerve transection at the C1 level, the amputation stump was moved cranially, and CMAPs disappeared. CMAPs recorded after the accessory nerve was returned to its original position. These examinations suggested that sudden alteration of the traveling lie of the nerve participates in the mechanism of transcranial magnetic stimulation.

Accessory Nerve↗
PubMed1994

KP-10, a novel protein kinase C substrate in intact mouse epidermal cells, is phosphorylated by novel protein kinase C eta and/or zeta.

Recently this group found an endogenous substrate protein for Ca(2+)-independent novel protein kinase C (nPKC), i.e. KP-10 (pI 4.7/25,500 M(r)), in primary cultured mouse epidermal cells [Nishikawa, K. et al. (1992) Cell. Signal. 4, 757-776]. In the present study, the nPKC isozymes which phosphorylate KP-10 in these cells were determined. Western blot analysis revealed that PKC alpha, eta and zeta were present in epidermal cell 105,000 g supernatants and that the content of PKC zeta was much higher than those of PKC alpha and eta. Neither PKC beta, delta nor epsilon was detected in the 105,000 g supernatants. Phosphatidylserine and phorbol 12-myristate 13-acetate (PMA)-dependent KP-10 phosphorylating activity was immunoprecipitated by anti-PKC eta and zeta antibodies, but not by antiPKC alpha antibody. These results suggest that PKC eta and/or zeta phosphorylate KP-10 and play pivotal roles in intracellular signal pathways in intact epidermal cells.

Amino Acid Sequence↗
PubMed1994

Discrimination by means of pulsed-field gel electrophoresis between strains of Campylobacter jejuni Lior type 4 derived from sporadic cases and from outbreaks of infection.

The cleavage patterns of the genomic DNA in 42 strains of Campylobacter jejuni Lior type 4, obtained from sporadic cases and from outbreaks of infection were analysed by means of pulsed-field gel electrophoresis (PFGE). The cleavage of DNA with SmaI and SalI restriction enzymes showed 16 distinct fragment patterns in 20 sporadic isolates, indicating that they were heterogeneous. On the other hand, the patterns of 22 isolates derived from two outbreaks showed the same unique restriction patterns, respectively. PFGE may therefore prove useful for subclassifying strains of C. jejuni Lior type 4 and for discriminating between strains derived from sporadic cases and those derived from outbreaks of infection.

Bacterial Typing Techniques↗
PubMed1994

Seasonal variations of nasal resistance in allergic rhinitis and environmental pollen counts. III: Efficacy of antiallergic agents.

We previously reported that, in a patient with Japanese cedar pollinosis, preseasonal increase in total nasal airway resistance (NAR) possibly caused from circannual endogenous rhythm was suppressed by preseasonal systemic administration of antiallergic agent. In this study, in order to determine the influence of preseasonal use of a topical antiallergic agent and seasonal administration of a peroral antiallergic agent, we made measurement of nasal airway resistance and pollen counts under the previous respective conditions in separated years. Preseasonal high mean values of total NAR for a couple of weeks was not suppressed by the preseasonal topical administration of ketotifen nasal spray in 1992 which was a low pollen season (974/cm2). However, the patient did not complained of severe episodes of hay fever at all throughout the season. Preseasonal increases in mean values of total NAR were observed in 1993 which was a high Japanese cedar pollen season (4,875/cm2) with NAR the same as untreated seasons. This may have been because the patient was not treated with preseasonal use of peroral azelastine. On extremely high Japanese cedar pollen count days further increased NAR occurred in the patient. The patient experienced relatively severe hay fever episodes, but used no other anti-histamine nor topical steroid during the season.

Administration, Topical↗
PubMed1994

Structural features in heparin which modulate specific biological activities mediated by basic fibroblast growth factor.

The biological activity of basic fibroblast growth factor (bFGF) is influenced greatly by direct binding to heparin and heparan sulphate (HS). Heparin-derived oligosaccharides have been utilized to determine the structural requirements present in the polymer that account for binding to bFGF. We had previously demonstrated that fragments > 6 mer can inhibit the interaction between cell surface heparan sulphate proteoglycan (HSPG) and bFGF, and bFGF-induced proliferation of adrenocortical endothelial (ACE) cells. In contrast, oligosaccharides > 10 mer can enhance the binding of bFGF to its high-affinity receptor or support bFGF-induced mitogenesis in ACE cells (Ishihara et al., J. Biol. Chem., 268, 4675-4683, 1993). We have extended these studies to size- and structure-defined oligosaccharides from heparin, 2-O-desulphated (2-O-DS-) heparin, 6-O-desulphated (6-O-DS-) heparin, carboxy-reduced (CR-) heparin and carboxy-amidomethylsulphonated (AMS-) heparin. Oligosaccharides from these polymers were fractionated on a bFGF-affinity column and were assessed as inhibitors or enhancers of specific bFGF-derived biological activities. The results of these studies indicate that both 2-O-sulphate and the negative charge of the carboxy group [L-iduronic acid (IdoA) residues] are required for specific interactions of heparin-derived oligosaccharides with bFGF and for modulation of bFGF mitogenic activity. In addition, the charge of the carboxy groups in uronic acids can be replaced by other functional groups with a negative charge, such as the amidomethyl sulphonate moiety described here.

Animals↗
PubMed1994

Structural requirements in heparin for binding and activation of FGF-1 and FGF-4 are different from that for FGF-2.

Size- and structure-defined oligosaccharides from heparin, 2-O-desulphated (2-O-DS-) heparin, 6-O-desulphated (6-O-DS-) heparin, carboxy-reduced (CR-) heparin, and carboxyamidomethylsulphonated (AMS-) heparin were utilized in characterizing the structural properties of heparin to specifically bind to basic fibroblast growth factor (FGF-2) and to modulate the mitogenic activity of FGF-2 (Ishihara, M. et al., Glycobiology, 4, 451-458, 1994). The previous results showed that both 2-O-sulphate groups and the negative charge of the carboxy group in iduronate residues are required for specific interaction with FGF-2, but the 6-O-sulphate groups in N-sulphated glucosamine (GlcNS) residues do not influence the interaction with FGF-2. In the present study, the same oligosaccharides were fractionated on a FGF-1- or FGF-4-affinity column, and were assessed as promoters of FGF-1- or FGF-4-induced proliferation of adrenocortical endothelial (ACE) cells and chlorate-treated ACE cells. The present results suggest that the smallest heparin-derived oligosaccharide binding to these growth factors with the highest affinity and promoting their mitogenic activities is a fully N-sulphated decasaccharide enriched in 2-O- and 6-O-sulphated disaccharide units. In contrast to our results with FGF-2, a high content of 6-O-sulphate groups in GlcNS residues is required for specific interaction with FGF-1 and FGF-4.

Binding Sites↗
PubMed1992

Selection of COS cell mutants defective in the biosynthesis of heparan sulfate proteoglycan.

A simple procedure using human basic fibroblast growth factor (FGF) was utilized for the selection of COS cell mutants with defects in the biosynthesis or expression of heparan sulfate proteoglycan (HSPG). Our approach was based on the strong binding affinity exhibited by COS cells to human basic FGF that had been adsorbed to plastic dishes. Cell binding to basic FGF could be inhibited by heparin and heparan sulfate (HS), but not by chondroitin sulfate, dermatan sulfate, keratan sulfate, or hyaluronic acid, suggesting that the cell binding involved an interaction between basic FGF and cell surface heparin-like molecules. COS cells were treated with ethyl methanesulfonate and four stable mutants were subsequently isolated that did not bind strongly to basic FGF adsorbed to plastic. These mutants cell lines (CM-2, CM-8, CM-9, and CM-15) exhibited significantly reduced 35SO4 incorporation into HS (40-70% depending on the cellular pool analyzed). In one of these cell lines, CM-15, the incorporation of [6-3H]glucosamine into HS was unaltered, suggesting that the extent of oligosaccharide polymerization was equivalent to that observed for the wild-type cells. Structural analysis revealed that N-sulfated glucosamine residues were present much less frequently in HS derived from these cells as compared with that derived from wild-type cells. Furthermore, CM-15 was found to be three-fold deficient in HS N-sulfotransferase activity, but contained wild-type levels of HS O-sulfotransferase activities.(ABSTRACT TRUNCATED AT 250 WORDS)

Animals↗