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Biomedical subjects

T Yoshimoto

Publications and source records attributed to T Yoshimoto.

At least 433 records · Page 24Linked to original sources
PubMed1996

[Auditory evoked magnetic fields in cases with temporal lobe glioma].

Auditory evoked magnetic field (AEF) is known to be suitable to separate left and right hemispheric activities while auditory evoked potential is not. To evaluate cortical auditory function in ten patients with temporal lobe gliomas, we measured AEF for monaural tone stimuli using a helmet-shaped 66-channel MEG system. Latency of the N 100 m, the most prominent peak with a latency around 90 ms, was measured in the hemisphere contralateral to the stimulus onset. In five patients, the N 100 m latency was within our normal range (mean +/- 2 s.d.). In these five cases, tumor was located in the anterior or the inferior part of the temporal lobe. We observed significant delay of the N 100 m latency in four patients and disappearance of the N 100 m in another patient. In the later five patients, tumor extended to the superior and posterior part of the temporal lobe. AEF can be used to evaluate cortical auditory function noninvasively in cases with temporal lobe gliomas.

Adult↗
PubMed1996

Clinical application of visual evoked fields using an MRI-linked whole head MEG system.

We have demonstrated anatomo-functional correlation of the brain visual function using an MRI-linked whole-head magnetoencephalography system. Visual evoked magnetic fields (VEFs) due to pattern reversal stimuli were measured in seven healthy subjects and 13 patients with intracranial structural lesions. Full-field stimuli evoked the most prominent peak around 100 ms latency (P100m) as a two-dipole pattern over the occipital area in all of the normal subjects and four patients with mild and partial hemianopsia. In five patients with homonymous hemianopsia due to unilateral occipital lesion, a single-dipole pattern of the P100m appeared over the normal occipital area only. In four patients with bitemporal hemianopsia due to pituitary tumors, a single-dipole pattern of the P100m appeared only over the ipsilateral occipital area to the stimulated eye. Using current dipole models, P100m sources were localized at the lateral bottom of the calcarine fissures. Although human occipital lobes are known to be morphologically variable, our results indicate excellent correlation of the cortical anatomy and human visual function. Full-field stimuli, requiring no strict visual fixation, are especially useful for clinical application. A clear two-dipole pattern in the normal VEFs enables us to compare two hemispheric activities.

Adult↗
PubMed1995

Regulatory role of CD38 (ADP-ribosyl cyclase/cyclic ADP-ribose hydrolase) in insulin secretion by glucose in pancreatic beta cells. Enhanced insulin secretion in CD38-expressing transgenic mice.

Cyclic ADP-ribose (cADPR) serves as a second messenger for Ca2+ mobilization in insulin secretion, and CD38 has both ADP-ribosyl cyclase and cADPR hydrolase activities (Takasawa, S., Tohgo, A., Noguchi, N., Koguma, T., Nata, K., Sugimoto, T., Yonekura, H., and Okamoto, H. (1993) J. Biol. Chem. 268, 26052-26054). Here, we produced transgenic mice overexpressing human CD38 in pancreatic beta cells. The enzymatic activity of CD38 in transgenic islets was greatly increased, and ATP efficiently inhibited the cADPR hydrolase activity. The Ca2+ mobilizing activity of cell extracts from transgenic islets incubated in high glucose was 3-fold higher than that of the control, suggesting that ATP produced by glucose metabolism increased cADPR accumulation in transgenic islets. Glucose- and ketoisocaproate-induced but not tolbutamide- nor KCl-induced insulin secretions from transgenic islets were 1.7-2.3-fold higher than that of control. In glucose-tolerance tests, the transgenic serum insulin level was higher than that of control. The present study provides the first evidence that CD38 has a regulatory role in insulin secretion by glucose in beta cells, suggesting that the Ca2+ release from intracellular cADPR-sensitive Ca2+ stores as well as the Ca2+ influx from extracellular sources play important roles in insulin secretion.

ADP-ribosyl Cyclase↗
PubMed1995

Role of NK1.1+ T cells in a TH2 response and in immunoglobulin E production.

Immune responses dominated by interleukin-4 (IL-4)-producing T helper type 2 (TH2) cells or by interferon gamma (IFN-gamma)-producing T helper type 1 (TH1) cells express distinctive protection against infection with different pathogens. Interleukin-4 promotes the differentiation of naïve CD4+ T cells into IL-4 producers and suppresses their development into IFN-gamma producers. CD1-specific splenic CD4+NK1.1+ T cells, a numerically minor population, produced IL-4 promptly on in vivo stimulation. This T cell population was essential for the induction of IL-4-producing cells and for switching to immunoglobulin E, an IL-4-dependent event, in response to injection of antibodies to immunoglobulin D.

Animals↗
PubMed1995

Defective IgE production by SJL mice is linked to the absence of CD4+, NK1.1+ T cells that promptly produce interleukin 4.

SJL mice produce little or no IgE in response to polyclonal stimulation with anti-IgD antibody and fail to express interleukin 4 (IL-4) mRNA in the spleen 5 days after injection of anti-IgD, in contrast to other mouse strains that produce substantial amounts of IgE and IL-4. Because IL-4 is critical in IgE production, the possibility that SJL mice are poor IgE producers because their naive T cells fail to differentiate into IL-4 producers must be seriously considered. IL-4 itself is the principal factor determining that naive T cells develop into IL-4 producers. A major source of IL-4 for such differentiation is a population of CD1-specific CD4+ T cells that express NK1.1. These cells produce IL-4 within 90 min of anti-CD3 injection. T cells from SJL mice fail to produce IL-4 in response to injection of anti-CD3. Similarly, SJL T cells and CD4+ thymocytes do not produce IL-4 in response to acute in vitro stimulation. SJL T cells show a marked deficiency in CD4+ cells that express the surface receptors associated with the NK1.1+ T-cell phenotype. This result indicates that the SJL defect in IgE and IL-4 production is associated with, and may be due to, the absence of the CD4+, NK1.1+ T-cell population.

Animals↗
PubMed1995

Structure, organization, and transcription units of the human alpha-platelet-derived growth factor receptor gene, PDGFRA.

Isolation and characterization of genomic clones encoding human alpha-platelet derived growth factor receptor (HGMW-approved symbol PDGFRA) revealed that the gene spans approximately 65 kb and contains 23 exons. The 5'-untranslated region of the mRNA is encoded by exon 1, and a large intron of 23 kb separates exon 2 encoding the translation initiator codon AUG and the signal sequence. The locations of exon/intron boundaries in the extracellular immunoglobulin-like domains, the transmembrane domain, the two cytoplasmic tyrosine kinase domains, and the kinase insertion domain are very similar to those in c-kit and macrophage colony stimulating factor-1 receptor genes. The transcription start site was mapped to a position 393 bp upstream of the AUG translocation initiator codon by S1 mapping and primer extension analysis. The 5'-flanking region of the gene lacks a typical TATA box but contains a typical CCAAT box and GATA motifs. This region also contains potential sites for AP-1, AP-2, Oct-1, Oct-2, and Sp1. The 5'-flanking region of the gene was fused to the luciferase reporter gene, and transcription units of the gene were determined.

Base Sequence↗
PubMed1995

Homozygous deletion of the MTS1/p16 and MTS2/p15 genes and amplification of the CDK4 gene in glioma.

Loci on chromosome 9p are frequently deleted in several malignant tumors, suggesting the presence of putative tumor suppressor genes. The MTS1/p16 and MTS2/p15 genes on 9p are considered to be candidates. Binding of p15 and p16 cell cycle-regulatory proteins to the cyclin dependent protein kinase CDK4 inhibits CDK4/cyclin D dependent phosphorylation of retinoblastoma protein. We analysed the DNAs from 37 gliomas of several grades of malignancy for allelic loss of chromosome 9p and aberrations of the MTS1/p16 and MTS2/p15 genes. We detected losses of one allele and homozygous deletions at loci, including those of the MTS1/p16 and MTS2/p15 genes, in 10 and 3 tumors, respectively. However, we did not detect any tumor-specific mutation in the two genes. The CDK4 gene was amplified in two malignant gliomas without homozygous deletion of the MTS1/p16 and MTS2/p15 genes and one malignant glioma with an allelic loss of the genes. These data suggest that aberrations of the genes coding for components of the cell cycle-regulatory system occurred in at least 15 of 37 gliomas.

Alleles↗
PubMed1995

Differential gene expression of vascular natriuretic peptide receptor subtype in artery and vein.

Although the vasorelaxation by natriuretic peptide (NP) is much less potent in the vein than in the artery, mechanism underlying the phenomenon remains unknown. Since NP receptor consists of three subtypes with different functions, we determined the mRNA level of each NP receptor subtype in the artery and vein by ribonuclease protection assay. In the aorta, NP-A receptor related to the biological action of NP was the predominant form. By contrast, NP-C receptor related mainly to the clearance of NP was the predominant form in the inferior vena cava: NP-C mRNA level was about two fold higher than in the aorta, while both NP-A and NP-B receptor mRNA levels were about half of that in the aorta. These results provide the molecular basis for the different biological response to NP in the artery and vein. Differential gene expression of NP receptor subtype could be an important determinant of the biological actions of NP.

Animals↗
PubMed1995

Nicotinamide inhibits IRF-1 mRNA induction and prevents IL-1 beta-induced nitric oxide synthase expression in pancreatic beta cells.

Nitric oxide produced by inducible nitric oxide synthase in islets exerts inhibitory and cytotoxic effects on pancreatic beta cells and is therefore thought to be a potent mediator in the pathogenesis of Type I diabetes mellitus. Here, using isolated rat pancreatic islets, we show that high-concentration nicotinamide (20 mM), but not low-concentration nicotinamide (5 mM), attenuates the interleukin-1 beta-evoked inhibition of glucose-induced insulin secretion by preventing the induction of interferon regulatory factor-1, a transcriptional factor which plays an essential role in inducible nitric oxide synthase gene expression, and the interleukin-1 beta-induced nitric oxide formation. High-concentration nicotinamide also restored an interleukin-1 beta-induced decrease in ATP content in pancreatic beta cells, suggesting that interleukin-1 beta-induced nitric oxide inhibits the mitochondrial function. The present results show the molecular basis of the preventive effect of high-dose nicotinamide on Type I diabetes mellitus.

Adenosine Triphosphate↗
PubMed1995

Cloning, characterization, and tissue distribution of porcine SPAI, a protein with a transglutaminase substrate domain and the WAP motif.

The primary and gene structures and tissue distribution of porcine SPAI-2, a protein that belongs to the WAP protein superfamily and has a sodium-potassium ATPase inhibitory activity, were determined by molecular cloning and Northern analysis. A full-length cDNA clone was isolated from a porcine duodenum cDNA library. The cDNA insert encoded a polypeptide of 187 amino acids, which is composed of three domains: a hydrophobic presequence of 21 amino acids, a prosegment of 105 amino acids ending with Asp126, and the mature SPAI-2 sequence of 61 amino acids beginning with Pro127. The prosegment contained 16 repeats of a hexapeptide that is highly homologous to the repetitive sequence found in the transglutaminase domain of the human elafin, an elastase-specific inhibitor that also belongs to the WAP superfamily. The repetitive sequence was demonstrated to be a good substrate of transglutaminase using a recombinant preparation produced in Escherichia coli. A porcine genomic library was then screened for the SPAI gene. Characterization and sequencing of positive clones indicated that the gene is similar to the elafin gene, having 3 exons encoding the 5'-untranslated region and signal sequence, proSPAI, and 3'-untranslated region, respectively. Northern blot analysis revealed intestine-specific expression of SPAI mRNA; the message was especially abundant in the small intestine. ProSPAI was also found in the circulation. The similarity of proSPAI to elafin in the domain structure, the acid-labile nature of the cleavage site (Asp126-Pro127), and the fact that the major form of SPAI in the plasma is proSPAI strongly suggest that proSPAI is not the precursor but rather it is the native form of SPAI. Like elafin, therefore, SPAI appears to be a new type of biologically active substance with a transglutaminase substrate domain that acts as an anchoring sequence.

Amino Acid Sequence↗
PubMed1995

Cloning, sequencing, and expression of the dipeptidyl peptidase IV gene from Flavobacterium meningosepticum in Escherichia coli.

The dipeptidyl peptidase IV (DP IV, EC 3.4.14.5) gene from Flavobacterium meningosepticum was cloned by Southern and colony hybridizations using probes amplified by PCR, and expressed in Escherichia coli DH1. E. coli DH1 harboring pFDP-H1, which was a subclone derived from the positive clone pFDP-1, showed 3.5-fold higher activity than F. meningosepticum. Nucleotide sequencing analysis revealed an open reading frame of 2133 bp, coding for a protein of 711 amino acids with a predicted molecular weight of 80,626. The expressed enzyme in E. coli DH1/pFDP-H1 was purified about 345-fold with an activity recovery of 12.3%. The molecular weight of the purified enzyme was estimated to be 75,000 by sodium dodecyl sulfate-polyacrylamide gel electrophoresis and 160,000 by gel filtration, respectively, suggesting a dimeric form of the native enzyme. The deduced amino acid sequence of DP IV was homologous to those of the serine proteases of the "prolyl endopeptidase family." A sequence near the C-terminal region and the putative catalytic triad residues were well conserved among these enzymes.

Amino Acid Sequence↗
PubMed1995

Loss of heterozygosity at 11p15 in malignant glioma.

Deletions of loci on chromosome 11p have been found frequently in several malignant tumors including gliomas, suggesting the presence of tumor suppressor genes. We analyzed 38 gliomas [26 malignant gliomas (grades III and IV) and 12 less malignant gliomas (grade I and II)] for loss of heterozygosity using microsatellite sequences on 11p as polymorphic markers. Loss of heterozygosity was found in 8 of 26 malignant gliomas (31%) but not in the less malignant gliomas. In the region with loss of heterozygosity, loci on 11p15.5-pter were commonly deleted. Our results suggest that a putative tumor suppressor gene involved in malignant progression of gliomas is located in an approximately 21-cM region on 11p15.5-pter.

Base Sequence↗