Biomedical subjects
Publications and source records attributed to M Taniguchi.
A cDNA for a putative novel serine protease, TLSP, was cloned from human hippocampus cDNA with polymerase chain reaction based strategies. The putative amino acid sequence of TLSP is similar to the trypsin-type serine proteases. TLSP mRNA is expressed in keratinocytes. Overexpressed TLSP protein in neuro2a cells was detected in culture medium.
We genetically engineered human myelomonocytic KG-I cells by introducing cDNA of murine interleukin-18 receptor (MuIL-18R) and established human cells which were capable of responding to MuIL-18. These cells expressed larger number of MuIL-18R (> 13,000 sites/cell) than intrinsic human IL-18 receptor (HuIL-18R) (< 2,500 sites/cell). And the cells responded to MuIL-18 as well as to HuIL-18 in a dose-dependent manner, and produced large amounts of interferon-gamma (IFN-gamma). We could estimate the amount of murine IL-18 based on the amounts of IFN-gamma produced by these cells. The stoichiometry was observed up to 150 ng/ml of MuIL-18. By using these cells, a large amount of MuIL-18 (448 +/- 89.2 ng/ml) was detected in sera of Propionibacterium acnes (P. acnes)/lipopolysaccharide (LPS)-treated endotoxic mice (the same conditions in which IL-18 was first identified). These cells provide us with a useful tool for determining the bioactivity of MuIL-18.
We examined cytokinin and nitrate responsiveness in gene expression of five distinct response regulator homologs (ARR3-ARR7) in the leaves of nitrogen-starved Arabidopsis plants. The transcripts accumulated after spraying the shoots with t-zeatin. The induction of accumulation was highly specific for cytokinins. The transcripts also accumulated by supply of nitrate to the culture medium. These findings suggest that ARRs are involved in inorganic nitrogen signal transduction mediated by cytokinin as in the case of ZmCip1, a response regulator homolog recently identified in maize.
Neuropsin is a serine protease which is thought to function in a variety of tissues including the brain and skin. This protease has been shown to have important roles in neural plasticity in mice. Here we have cloned a cDNA and analyzed the gene for human neuropsin by polymerase chain reaction-based strategies. The cDNA had 72% identity to mouse neuropsin. The deduced amino acid sequence showed 72% identity to mouse neuropsin. Key amino acid residues for the enzyme activity and all cysteine residues were conserved between human and mouse neuropsin. The gene for human neuropsin had six exons and five introns, and the gene organization is similar to trypsin-type serine proteases. The mRNA was expressed in primary cultures of keratinocytes.
myo-Inositol is accumulated into cells by means of the Na+/myo-inositol cotransporter (SMIT), which is of interest because its activity is upregulated by hyperosmotic stress. We investigated the effects of hyperglycemia on the expression of SMIT mRNA mainly in rat hippocampus. In normal control rats, SMIT mRNA signals were predominantly located in the hippocampus, cerebellum and choroid plexus. Interestingly, massive induction in the hippocampus was observed on the acute stage of induced hyperglycemia in the CA3/CA4, the molecular layer of the dentate gyrus, and the hippocampal fissure. The perivascular cells along the hippocampal fissure also expressed prominent signals. In the cerebral cortex, heterogeneous induction was observed from layers 2 to 6. Furthermore, these changes immediately returned to baseline levels after normalization of glucose levels. These results suggest that regional specificity of permeability of the blood-brain barrier and/or cellular differences in sensitivity to hyperglycemic stress would exist in the brain.
We have recently identified alpha-galactosylceramide (alpha-GalCer) as a specific ligand for an invariant Valpha14/Vbeta8.2 T cell receptor exclusively expressed on the majority of Valpha14 NKT cells, a novel subset of lymphocytes. Here, we report that alpha-GalCer selectively activates Valpha14 NKT cells resulting in prevention of tumor metastasis. The effector mechanisms of the ligand-activated Valpha14 NKT cells seem to be mediated by natural killer (NK)-like nonspecific cytotoxicity. Indeed, the cytotoxic index obtained by alpha-GalCer-activated Valpha14 NKT cells was reduced by the addition of cold target tumor cells or by treatment with concanamycin A, which inhibits activation and secretion of perforin, but not by mAbs against molecules involved in the NKT cell recognition and conventional cytotoxicity, such as CD1d, Vbeta8, NK1. 1, Ly49C, Fas, or Fas ligand. These results suggest that the ligand-activated Valpha14 NKT cells kill tumor cells directly through a CD1d/Valpha14 T cell receptor-independent, NK-like mechanism.
Movement-related magnetic fields were recorded with a whole-head magnetoencephalographic system in three dextrals and three sinistrals during right or left index finger extension. The motor field (MF) demonstrated an asymmetrical isofield map pattern with larger field reversal over the contralateral hemisphere for dominant hand movement and an almost symmetrical pattern for non-dominant hand movement in each subject. The equivalent current dipole moment of the MF for the contralateral hemisphere was significantly larger than the ipsilateral hemisphere for dominant hand movement, and almost equal for both hemispheres for non-dominant hand movement. These results were congruent for both dextrals and sinistrals, suggesting a more important role of the hemisphere contralateral to the dominant hand in unilateral voluntary movement, regardless of handedness.
Anti-idiotypic antibodies are a new type of useful tools for the possible treatment of cancer patients, since some act as antigen specific immunomodulators. Anti-idiotypic monoclonal antibody (anti-Id MAb) D704 (Ab2) was established which bore the internal image of the determinant defined by MAb M2590 (Ab1) against a sialic acid residue on GM3 ganglioside. In an in vivo syngeneic tumor system, anti-Id MAb D704 was more effective in preventing tumor progression, as compared with anti-GM3 MAb or no treatment. Significant suppression of tumor growth and prolongation of survival by administration of anti-Id MAb D704 in an animal group inoculated with 1 x 10(4)/mouse melanoma cells were seen, but not in a group inoculated with 5 x 10(4) cells/mouse. In an active specific immunotherapy protocol utilizing Ab2, the activity of anti-anti-Id antibodies (Ab3) specific for GM3 (antigen) which has a weak immunogenicity only, was maintained for more than 3 months. Ab2 generated cellular anti-tumor immune responses, including delayed type hypersensitivity (DTH) reaction. Immunohistological analysis indicated a marked infiltration of CD4 and CD8 positive cells into the DTH sites. Our results suggest that internal image bearing anti-Id MAbs have a therapeutic potential against tumors if the number of melanoma cells is relatively low or if hosts are at an early stage of melanoma progression.
A UV emission spectrometer using a non-periodic spherical grating has been designed, which can be attached to the linear or helical undulator beamlines of the HiSOR light source at the Hiroshima Synchrotron Radiation Centre. The useful range of emitted photons from 10 to 100 eV is covered by two gratings with nominal groove spacings of 1/600 and 1/1200 mm. The energy resolution with a 100 micro m entrance slit width and the 1/600 mm grating is better than 0.2 eV below 50 eV.
A compact racetrack-type 700 MeV storage ring (HiSOR) has been constructed at Hiroshima Synchrotron Radiation Center (HSRC). As the ring was planned for synchrotron radiation research on science and technology using VUV to X-rays up to 5 keV with limited size and cost, the ring was designed (i) to realize a high magnetic field (2.7 T) using conventional dipole magnets for higher critical energy, and (ii) to include two straight sections for insertion devices. A linear undulator (25-300 eV) and a new-type helical/linear undulator were installed at the two straight sections. The latter undulator consists of upper and lower jaws, as in a planar undulator; each jaw consists of one fixed magnet array at the centre and two magnet arrays on both sides. By longitudinal displacement of the side magnet arrays, the phase between the vertical and horizontal magnetic fields, and therefore the polarization (right- or left-circular, elliptical, linear) can be selected. The helical/linear undulator gives almost perfect circular polarization at 4-40 eV in the helical configuration without changing the phase of the magnet arrays, as well as linearly polarized light at 3-300 eV in the linear configuration.
The history of HSRC is briefly sketched, going back to the early HiSOR project. The present status of this 0.7 GeV compact storage ring is described and an outline of the future of the facility is given in the context of western Japan.
Niemann-Pick disease type C (NP-C) is an autosomal recessive disorder characterized by the sequestration and trapping of endocytosed cholesterol in lysosomes. The NPC1 gene on chromosome 18 was recently identified but its physiological function remains unknown. We have studied the lipid compositions of cultured human NP-C fibroblasts and mouse SPM-3T3 cell line derived from the C57BL/KsJ NP-C model mouse, which belongs to the same complementation group. Fibroblasts derived from apparently normal age-matched individuals and a subline of SPM-3T3 cells which restores cholesterol metabolism by transfer of human chromosome 18 were used as controls. Levels of free cholesterol in whole cell homogenates increased about 1.5-fold in human NP-C fibroblasts and mouse SPM-3T3 cells, while in the plasma membrane, cholesterol content did not significantly change in NP-C fibroblasts but rather decreased in SPM-3T3 cells. The total phospholipid content did not significantly change; however, among phospholipid head groups, increases in sphingomyelin and decreases in other classes were observed in human NP-C fibroblasts and mouse SPM-3T3 cells. The ratios of saturated fatty acids to unsaturated fatty acids increased in both human and mouse cells. The increase was also confirmed in the plasma membrane fraction of SPM-3T3 cells. Membrane fluidity was examined using a 1,6-diphenyl-1,3,5-hexatriene (DPH) fluorescent probe. The DPH anisotropy values were markedly increased in NP-C fibroblasts and in SPM-3T3 cells. The results suggest that a NP-C mutation causes complex alterations in cellular lipid contents and biophysical properties of the membrane.
Two patients presented with a tumor involving mainly the supplementary motor area or the premotor cortex. Shortly after tumor resection, each developed transient impairment of voluntary movements. An electromyogram, with the skin electrodes placed over the muscles of the upper arms and forearms, demonstrated aberrant ipsilateral, contralateral or bilateral muscle activation during unilateral motor tasks in both patients. The bilateral activation was more prominent in the patient who had an intact dominant hemisphere. The present study suggests for the first time the importance of non-primary motor areas of the human brain in activating the proper set of muscles on the proper side of the body.
To clarify the cellular origin of de novo CD5+ diffuse large B-cell lymphoma (CD5+ DLBL), particularly in comparison with other CD5+ B-cell neoplasms such as chronic lymphocytic leukemia (CLL) and mantle cell lymphoma (MCL), we analyzed the nucleotide sequence of the Ig heavy chain variable region (IgVH) genes of de novo CD5+ DLBL cases. All 4 cases examined had extensive somatic mutations in contrast with CLL or MCL. The VH gene sequences of de novo CD5+ DLBL displayed 86.9% to 95.2% homology with the corresponding germlines, whereas those of simultaneously analyzed CLL and MCL displayed 97.6% to 100% homology. The VH family used was VH3 in 1 case, VH4 in 2 cases, and VH5 in 1 case. In 2 of 4 examined cases, the distribution of replacement and silent mutations over the complementarity determining region and framework region in the VH genes was compatible with the pattern resulting from the antigen selection. Clinically, CD5+ DLBL frequently involved a variety of extranodal sites (12/13) and lymph node (11/13). Immunophenotypically, CD5+ DLBL scarcely expressed CD21 and CD23 (3/13 and 2/13, respectively). These findings indicate that de novo CD5+ DLBL cells are derived from a B-1 subset distinct from those of CLL or MCL.
Gene targeting in embryonic stem (ES) cells is a powerful tool for generating mice carrying specifically designed mutations in the germline. Puromycin can completely kill ES cells within 24 to 48 h whereas G418 and hygromycin cannot. We have, therefore, proposed that the puromycin N-acetyltransferase ( pac ) gene, may be utilized as a transient gene-integration marker. Using a circular expression vector of cre and pac genes, Cre-mediated mutant cells were effectively enriched by pulse treatment of puromycin without stable integration of their genes. We have thus demonstrated the first application of pac as a transient gene-integration marker for ES cells.
Explore the source record for details and available documents.
Although Tc-99m HMPAO uptakes in various brain tumors have been reported, SPECT images of neurocytoma have not been described. The authors report a patient with intraventricular neurocytoma (IN) who demonstrated significant uptake of Tc-99m HMPAO and Tl-201 Cl before brain biopsy. Residual tumor after biopsy showed significant uptake of I-123 IMP on early SPECT images, but this uptake was decreased on delayed images. The three radionuclides seem to have different uptake mechanisms.
We present a case of primary renal lymphoma, which is a rare entity and poses diagnostic challenge. Ultrasound and CT scan demonstrated a nonspecific solid tumor in the left kidney. 67Ga-citrate scintigraphy demonstrated an intense uptake in the tumor, which led to a correct diagnosis, so that we could spare unnecessary laparotomy and possible nephrectomy.