Search PubMed⌕ Search

Biomedical subjects

T Nishimura

Publications and source records attributed to T Nishimura.

At least 145 records · Page 8Linked to original sources

Neural plasticity detected in short- and long-term cochlear implant users using PET.

The interaction of listening to words and watching sign language in short-term and long-term cochlear implant (CI) users who have learned sign language after becoming deaf was measured using PET. In short-term CI users the auditory cortex was inactive while in long-term CI users it was fully activated with the simultaneous presentation of auditory and visual input. The result suggests the possibility that the interference of rival modalities may be diminished with experience and the preference switchover from the visual input to the auditory input could be accomplished by means of the neural plasticity persisting in the mature human auditory cortex.

Adolescent↗

Functional brain areas used for the lifting of objects using a precision grip: a PET study.

Positron emission tomography (PET) was performed in 10 normal volunteers to investigate regional cortical and subcortical activation induced by the lifting of an object repetitively using a precision grip between the index finger and thumb. Data were obtained for three object weights (4, 200 and 600 g) and a resting condition. Grip and lift forces on a similar object and the activity of selected muscles in the hand, arm and shoulder were also recorded in separate lifting trials. A comparison between all movement conditions and the resting condition revealed significant activation of the primary motor (M1), primary sensory (S1), dorso-caudal premotor (PM), caudal supplementary motor (SMA) and cingulate motor (CMA) cortices contralateral to the hand used. On the ipsilateral side, activation of the M1, caudal SMA and inferior parietal cortex (BA 40) was also found. In the subcortical areas, the bilateral hemispheres and right vermis of the cerebellum, left basal ganglia and thalamus were activated. Behavioral adaptation to a heavier object weight was revealed in a nearly proportional increase of both grip and lift forces, prolonged force application period and a higher level of hand and arm muscle activities. An increase in the rCBF associated with these changes was noted in several cortical and subcortical areas. However, consistent object weight-dependent activation was observed only in the M1/S1 contralateral to the hand used.

Adult↗

Enhanced expression of cellular prion protein gene by insulin or nerve growth factor in immortalized mouse neuronal precursor cell lines.

In order to understand the fundamental and putative roles of PrP(c) in the central nervous system, neuronal cell lines were established. Cells were immortalized by recombinant retrovirus vector-mediated transduction of SV40 T-antigen gene. Among these, two cell lines were selected based on their RT-PCR expressions of neuron-specific neurofilament (NF-H, NF-M) and cell morphology. These cell lines showed the properties of neuronal progenitor cells in antigenicity, morphology and responses to differentiating agents. Expression of PrP(c) was detected by immunocytochemical analysis. These cell lines responded to differentiating agents such as dibutyl cyclic AMP (dcAMP) and phorbol 12-myristate 13-acetate (PMA) before developing into neuronal-like cells. Neurite extensions were observed 20 min after incubation with the differentiating agents. Treatment with nerve growth factor (NGF) and insulin induced cell differentiation and enhanced expression of PrP gene (Prnp) mRNA and protein. The latter phenomenon was not inhibited by wortmannin, which is a specific inhibitor of phosphatidylinositol 3-kinase. These results suggest that PrP(c) plays an important role in the differentiation-mediated classic signaling pathway of neuronal cell.

Androstadienes↗

alpha-galactosylceramide induces early B-cell activation through IL-4 production by NKT cells.

alpha-Galactosylceramide (alpha-GalCer), a glycolipid antigen, specifically activates natural killer T (NKT) cells by a CD1d-restricted mechanism. In this work, we found that in vivo administration of alpha-GalCer resulted in the activation of B cells in addition to NKT cells, namely, alpha-GalCer administration caused upregulation of the early activation marker, CD69, on both NKT and B cells. In addition, expression of B7.2 and I-A(b) on B cells was greatly upregulated by alpha-GalCer. However, serum levels of IgE, IgG1, and IgG2a were not significantly changed within 48 h. In the present experiments, it was also demonstrated that the upregulation of CD69 expression by alpha-GalCer was strongly blocked by anti-IL-4 monoclonal antibody. Moreover, B-cell activation by alpha-GalCer was not observed in NKT-deficient mice. These results suggested that antigen-stimulated NKT cells might play a critical role not only in early defense mechanisms but also in early B-cell activation through IL-4 production.

Animals↗

Establishment of efficient reaggregation culture system for gene transfection into immature T cells by retroviral vectors.

To overcome low efficiency of retroviral infection into immature T cells, we modified reaggregation fetal thymus organ culture by closely packed co-culture with virus-producing cells (VPC). The viral vector was constructed in chimeric vector, pMX, with IRES and tailless-rat CD2 as a surface marker of infected cells. A rearranged TCR beta gene (Vbeta8.2) was further inserted into the construct for investigating effect of the introduced gene in T cell development. Using this system, we succeeded to transfer the viral vector into immature thymocytes at a remarkably higher efficiency compared to conventional methods using medium containing retrovirus. Moreover, the introduced TCR beta gene was expressed on thymocytes of RAG2-deficient mice to induce in the transition of CD4-CD8- double-negative (DN) into CD4+CD8+ double-positive (DP) cells by transducing beta-selection signaling. Thus, our modified reaggregation culture system is useful for studying the molecular mechanism of T cell development due to a highly efficient gene transfer into immature T cells.

Animals↗

High-energy collision-induced dissociation of small polycyclic aromatic hydrocarbons.

High-energy collision-induced dissociation (CID) experiments on polycyclic aromatic hydrocarbons (PAHs) having 2-6 rings, naphthalene, anthracene, phenanthrene, fluoranthene, pyrene and coronene, were performed, and the relative abundances of their fragment ions were investigated as a function of collision energy. The results revealed that the PAHs except naphthalene showed a bimodal-type distribution of positive fragmentation ions, which is closely similar to the fragment-ion distribution reported for the CID of three-dimensional fullerene, C(60)(+) and C(70)(+). The three-ring isomers of anthracene and phenanthrene and the four-ring isomers of fluoranthene and pyrene can be distinguishable in their spectra under an electron ionization energy of 70 eV, but the high-energy CID spectra of the three- and four-ring isomers were almost identical. The fragmentation corresponding to fragment ions in the low-mass region of the bimodal CID spectra could be interpreted by the simple statistical model that fragment ions are formed by random evaporation from the molecular ions after a considerable structural rearrangement, 'phase transition', occurring at some high-energy state.

Gas Chromatography-Mass Spectrometry↗

Alteration of protein composition in mouse thymocytes by signals through T-cell receptor.

To avoid destructive autoimmunity, T-cell precursors (thymocytes) expressing autoreactive T-cell receptor are deleted in the thymus via an apoptotic process by the signals from the T-cell receptor-CD3 complexes. In order to analyze the apoptotic mechanism, we established a cell-free system using the lysates from mouse thymocytes treated in vivo with anti-CD3 monoclonal antibody (mAb). The soluble cytosolic high molecular mass protein fraction from the anti-CD3-treated thymocytes revealed an activity that directly induces nuclear apoptotic morphological changes and DNA fragmentation. This fragmentation activity was not observed in the fraction from the thymocytes without anti-CD3 treatment. Proteins in both fractions were separated by two-dimensional electrophoresis. The silver-stained gels revealed differences in protein spots. These protein spots were identified by database searching of mass spectrometric (MS) and tandem mass spectrometric (MS/MS) data obtained from in-gel tryptic digests of the spots, using an integrated system of liquid chromatography/electrospray ionization/ion-trap mass spectrometry. In this study, the high mobility group protein HMG2 was identified as one of the cytosolic proteins that is increased by the signals from the T-cell receptor, and heterogeneous nuclear ribonucleoprotein A2/B1 and glyceraldehyde 3-phosphate dehydrogenase were found to be decreased by the signals.

Amino Acid Sequence↗

Adhesion mediated by LFA-1 is required for efficient IL-12-induced NK and NKT cell cytotoxicity.

Interleukin 12 (IL-12)-activated NK1.1+TCRalpha beta+ (NKT2) and NK1.1+TCRalpha beta- (NK) cells exhibit cytotoxic activity against a wide variety of tumor cells in the absence of prior sensitization. Here we demonstrate that the integrin adhesion receptor LFA-1 (CD11a/CD18) regulates the cytotoxic activity of IL-12-activated NKT and NK cells against YAC-1 and EL-4 tumor cells. Differentiation in vivo and the expression of the cytolytic effector molecules perforin and Fas-L were comparable in both IL-12-activated NKT and NK cells from LFA-1-/ - and LFA-1+/+ mice. However, LFA-1-/-IL-12-activated NKT and NK cells showed impaired conjugate formation with target cells. These results provide the first genetic evidence for a role for an adhesion receptor in killing by IL-12-activated NK cells.

Animals↗

Assessment of left ventricular function by gated myocardial perfusion and gated blood-pool SPECT: can we use the same reference database?

The purpose of this study was to compare left ventricular (LV) volume and ejection fraction (LVEF) measurements obtained with electrocardiographic gated single-photon emission computed tomographic (SPECT) myocardial perfusion imaging (GS-MPI) with those obtained with gated SPECT cardiac blood-pool imaging (GS-pool). Fifteen patients underwent GS-MPI with technetium-99m-tetrofosmin and GS-pool with technetium-99m-erythrocyte, within a mean interval of 8 +/- 3 days. Eight patients had suspected dilated cardiomyopathy and seven patients had angiographically significant coronary artery disease. End-diastolic volume (EDV), end-systolic volume (ESV) and LVEF measurements were estimated from GS-MPI images by means of Cedars-Sinai automatic quantitative program and from GS-pool images by the threshold technique. Mean differences between GS-MPI and GS-pool in EDV, ESV and LVEF measurements were -2.8 +/- 10.5 ml [95% confidence interval (CI): -8.6 +/- 3.0 ml], 2.6 +/- 7.3 ml (CI: -1.4 +/- 6.6 ml) and -2.3 +/- 5.1% (CI: -5.1 +/- 0.6%), respectively. No significant difference in the mean differences from 0 was found for EDV, ESV or LVEF measurements. Bland-Altman plots revealed no trend over the measured LV volumes and LVEF. For all parameters, regression lines approximated lines of identity. The excellent agreement between GS-MPI and GS-pool measurements suggests that, for estimation of LV volumes and LVEF, these two techniques may be used interchangeably and measurements by one method can serve as a reference for the other.

Adult↗

Estimation of the area at risk in myocardial infarction of rats by means of I-123 beta-methyliodophenyl pentadecanoic acid imaging.

Clinical investigations have suggested that the defects in SPECT images of a free fatty acid analog, I-123 beta-methyliodophenyl pentadecanoic acid (BMIPP) may indicate the ischemic risk area. To elucidate whether I-123 BMIPP can indicate the area at risk of ischemia, ex-vivo autoradiography was performed in rats whose left coronary artery was occluded for 60 min and then reperfused. I-123 BMIPP was injected at the acute stage (n = 10), or the subacute stage (7 days after reperfusion; n = 9). Infarction and the area at risk were identified by triphenyl tetrazolium chloride staining and injection of methylene blue during religation just before sacrifice, respectively. The BMIPP uptake in the risk area was significantly lower than that in the remote area at the acute (risk, 53.7+/-23.3% of the uptake at right ventricle, mean +/- SD; remote, 109.3+/-11.8%; p < 0.01) and subacute (risk, 52.5+/-11.5%; remote, 97.9+/-14.3%; p < 0.01) stages. In addition, the area with reduced uptake of I-123 BMIPP showed a significant correlation with the area at risk both at the acute (r = 0.98, p < 0.01) and subacute (r = 0.92, p < 0.01) stages. In conclusion, the area at risk can be evaluated by I-123 BMIPP both at the acute and subacute stages.

Animals↗

Changes in perfusion and fatty acid metabolism of rat heart with autoimmune myocarditis.

To elucidate the change in perfusion and aerobic metabolism in myocarditis, tissue counting and dual tracer ex vivo autoradiography with Tl-201 and a free fatty acid analog, I-123- or I-125-labeled (p-iodophenyl)-methyl-pentadecanoic acid (BMIPP), were performed in rats with myocarditis induced by immunization with cardiac myosin. Inflammatory damage was classified histologically. At the acute stage (2-4 weeks after the antigen-injection), total heart uptakes of Tl and BMIPP and the ratio (BMIPP/Tl) were significantly reduced in myocarditis rats (N = 15) compared with the controls (N = 12). Myocardial distribution of Tl and BMIPP was not homogeneous. Relative uptake of Tl and BMIPP (N = 9, 128 regions) was gradually decreased with the extent of inflammation, and the regional BMIPP/Tl was smaller than the control. At the subacute stage (7 weeks after the antigen-injection), total Tl uptake in myocarditis rats (N = 5) recovered to the control level (N = 4), but that of BMIPP was still significantly lower than the control. BMIPP/Tl was still significantly lower in myocarditis. Myocardial distribution of Tl and BMIPP recovered to be more homogeneous. Relative uptake of Tl and BMIPP (N = 6, 78 regions) still gradually but significantly decreased with the extent of inflammation. Regional BMIPP/Tl was still depressed in myocarditis. These results indicate that myocardial perfusion and aerobic metabolism were discrepant and heterogeneously suppressed with severe inflammation during the acute stages, but the difference decreases with time. Examination with Tl-201 and BMIPP may provide information about the severity of myocarditis.

Animals↗

Detection of coronary artery disease by iodine-123-labeled iodophenyl-9-methyl pentadecanoic acid SPECT: comparison with thallium-201 and iodine-123 BMIPP SPECT.

To evaluate the ability to detect coronary artery disease (CAD) with a new iodine-123 labeled branched fatty acid analog, iodophenyl-9-methyl pentadecanoic acid (9MPA), we performed 9MPA, iodine-123 BMIPP and thallium-201 SPECT in patients with CAD. Twenty-four patients (11 with effort angina and 13 with myocardial infarction) were studied. In all patients, 9MPA SPECT was obtained at 15 min after injection. Twenty-three patients underwent stress-redistribution 201Tl SPECT and 9 patients also underwent BMIPP myocardial fatty acid imaging. The regional uptakes of 9MPA, BMIPP and 201Tl were scored semiquantitatively and the segmental agreements were compared among them. In the segment-to-segment comparison, 9MPA showed reduced activity in comparison to stress-redistribution 201Tl imaging. The defect score of 9MPA was significantly greater than that of redistribution 201Tl images (p < 0.001). In addition, segmental 9MPA uptake was lower than BMIPP and its defect score was significantly greater than that of BMIPP (p < 0.05). When coronary angiography was used as the criterion, 9MPA showed higher sensitivity and lower specificity than stress-redistribution 201Tl (p < 0.01). In conclusion, fatty acid metabolic imaging with 9MPA is a sensitive but nonspecific detector of CAD.

Angina Pectoris↗

Early and delayed Tc-99m ECD brain SPECT in SLE patients with CNS involvement.

We compared early and delayed Tc-99m ECD SPECT scans in 32 SLE patients (Group 1, definite neuropsychiatric disorders; Group 2, minor neurologic symptoms or normal) with those of normal controls by visual inspection and semi-quantitative evaluation. With visual interpretation, 13 out of 14 patients in Group 1 (93%) and 7 out of 18 patients in Group 2 (39%) had diffuse uneven decrease in early scans. Seven patients in Group 2 (39%) who had normal early scans demonstrated focal decrease in the medial frontal lobe in delayed scans. With cerebral region to cerebellar ratios, in early scans, the medial frontal lobe in Group 1 and Group 2 was significantly lower than in normal controls, and lateral frontal lobe and occipital lobes in Group 1 were significantly lower than in normal controls. Nevertheless, in delayed scans, every cortical region except for the parietal lobe in Groups 1 and 2 was significantly lower than in normal controls. The retention rates in all regions in SLE patients were significantly lower than in normal controls. No case showed SPECT improvement on follow-up studies in either group in spite of clinical improvement. Delayed Tc-99m ECD brain SPECT of high sensitivity might be useful in detecting CNS involvement. Although the SPECT findings did not correlate with the neuropsychiatric symptoms, early and delayed Tc-99m ECD SPECT seems to provide useful objective diagnostic information in SLE patients.

Adult↗

Characteristics of myocardial 18F-fluorodeoxyglucose positron emission computed tomography in dilated cardiomyopathy and ischemic cardiomyopathy.

Myocardial 18F-fluoro-2-deoxyglucose (FDG) positron emission tomography (PET) has been used to assess myocardial ischemia and viability, but few studies have conducted on FDG-PET for dilated cardiomyopathy (DCM). We investigated myocardial FDG uptake in patients with DCM in comparison with ischemic cardiomyopathy (ICM). Twenty-four patients with heart failure were included in this study. Fourteen of them were diagnosed as DCM and the other 10 were ICM. All of them underwent myocardial FDG-PET at fasting and after glucose loading the same day. FDG uptake was quantified by the ratio of the counts at the heart to those at the liver (H/L ratio). Left ventricular (LV) function was measured by echocardiography. We classified FDG distribution patterns in the myocardium in the fasting state into 3 types (faint uptake, regional uptake and diffuse uptake). In DCM patients, 5 had faint uptake, 7 had regional uptake, and the other 2 had diffuse uptake. On the other hand, all ICM patient had regional uptake (p < 0.05). In DCM, there were no significant relationships between the patterns and LV functions. On the other hand, there were close correlation between the H/L ratio after glucose loading and the left ventricular ejection fraction (r = 0.680, p < 0.01). The changes in PET images caused by glucose loading were classified into 2 types (non-reversing and reversing patterns). DCM significantly showed a non-reversing pattern (86%, 12 of 14 patients) whereas ICM showed mainly a reversing pattern (70%, 7 of 10 patients; p < 0.05). In conclusion, myocardial FDG uptake after glucose loading may indicate a myocardial viable mass although FDG uptake at fasting was not evidently related to LV function. The change in the pattern of the FDG image from fasting to glucose loading may be useful in differentiating DCM from ICM.

Adult↗

The critical role of Th1-dominant immunity in tumor immunology.

To investigate the precise role of antigen-specific Th1 and Th2 cells in tumor immunity, we developed a novel adoptive tumor-immunotherapy model using OVA-specific Th1 and Th2 cells and an OVA gene-transfected tumor. This therapeutic model demonstrated that both antigen-specific Th1 and Th2 cells had strong antitumor activity in vivo with distinct mechanisms. However, immunological memory suitable for the generation of tumor-specific cytotoxic T lymphocytes was induced only when tumor-bearing mice received Th1 cell therapy, but not Th2 cell therapy. Thus it was strongly suggested that Th1-dominant immunity is critically important for the induction of antitumor cellular immunity in vivo. We also proposed that several immunomodulating protocols using interleukin (IL)-12, IL-12 gene, the natural killer T cell ligand alpha-galactosylceramide, or Th1 cytokine-conditioned dendritic cells might be useful strategies for the induction of Th1-dominant immunity essential for the development of tumor-specific immunotherapy.

Animals↗