Biomedical subjects

M Matsui

Publications and source records attributed to M Matsui.

At least 37 records · Page 2Linked to original sources

PubMed2001

Induction of hepatitis C virus-specific cytotoxic T lymphocytes in mice by immunization with dendritic cells treated with an anthrax toxin fusion protein.

As a novel and safe vaccine strategy, the anthrax toxin-mediated antigen delivery system composed of lethal factor (LF) fusion protein and protective antigen (PA) has been studied to prime hepatitis C virus (HCV) core-specific cytotoxic T lymphocytes (CTLs) in vivo. The core epitope fused to LF (LF-core) together with PA induces a negligible core-specific CTL response in mice, whereas core-specific CTL are effectively primed in mice by injecting dendritic cells (DCs) treated in vitro with LF-core and PA. These findings imply that LF fusion protein plus PA in combination with dendritic cells may be useful for a novel T cell vaccine against HCV infection.

Animals↗

PubMed2001

Apolipoprotein E epsilon 4 and the pattern of regional brain atrophy in Alzheimer's disease.

BACKGROUND: Although the APOE epsilon 4 allele increases the risk of developing AD, the effects of the epsilon 4 allele on brain atrophy in clinical AD patients are controversial. OBJECTIVE: To investigate a possible relationship between the genetic variants of APOE and brain atrophy in patients with AD. METHODS: Using MRI-based volumetry techniques, the authors compared the volumes of the hippocampal formation, amygdaloid complex, and whole brain in probable AD patients (based on criteria of the National Institute for Neurological and Communicative Disorders and Stroke/Alzheimer's Disease and Related Disorders Association) with different APOE alleles. One group (n = 46) had the epsilon 3/3 allele, one group (n = 46) had the epsilon 3/4 allele, and one group (n = 46) had the epsilon 4/4 allele. The three groups were matched for age, sex, disease duration, education level, and severity of dementia represented by their score of the Mini-Mental State Examination. A possible difference in pattern of cognitive deficits with dose of the APOE epsilon 4 allele was also examined. RESULTS: The normalized hippocampal volume was correlated with the number of APOE epsilon 4 alleles (r = -0.285, p = 0.0007). The amygdalar volume was also correlated with the number of APOE epsilon 4 alleles (r = -0.178, p = 0.037). The number of APOE epsilon 4 alleles was positively correlated with the whole-brain volume (r = 0.185, p = 0.030). It was also correlated with Wechsler Adult Intelligence Scale-Revised performance IQ (r = 0.203, p = 0.017) and with Wechsler Memory Scale-Revised attention/concentration score (r = 0.191, p = 0.025). CONCLUSIONS: Different patterns of regional brain atrophy were found among patients of different APOE genotypes. The effect of APOE epsilon 4 allele on the brains of AD patients may have regional specificity.

Aged↗

PubMed2001

Decreased acetylcholine content and choline acetyltransferase mRNA expression in circulating mononuclear leukocytes and lymphoid organs of the spontaneously hypertensive rat.

It has been confirmed that the neurotransmitter acetylcholine (ACh) is present in blood; it is synthesized in T-lymphocytes by choline acetyltransferase (ChAT) and released upon T-lymphocyte activation. Both muscarinic and nicotinic ACh receptors have been identified on lymphocytes isolated from thymus, lymph node, spleen and blood, and their stimulation by muscarinic and nicotinic agonists elicits a variety of functional and biochemical effects, providing a strong argument that ACh synthesized and released from T-lymphocytes acts as an autocrine and/or paracrine factor regulating immune function. In the present study, we compared ACh levels in the blood, circulating mononuclear leukocytes (MNLs), thymus and spleen of spontaneously hypertensive rats (SHRs), which exhibit immune deficiencies related to the emergence of natural thymocytotoxic autoantibody, age-related decline of T-cell function and morphological changes in immune organs, with ACh levels in age-matched, normotensive Wistar Kyoto rats. In each case, ACh levels in 5-, 10- and 20-week-old SHRs were significantly lower than in WKYs. ChAT mRNA expression in MNLs was also significantly depressed in the SHRs. These results suggest that diminished synthesis and release of ACh from MNLs into blood and lymphoid organs likely reflects an immune deficiency related to T-cell dysfunction.

Acetylcholine↗

PubMed2001

Introduction of tapasin gene restores surface expression of HLA class I molecules, but not antigen presentation of an HIV envelope peptide in a hepatoma cell line.

A hepatoma cell line, Hep G2, reveals the diminished HLA class I surface expression and the reduced expression of LMP2, LMP7, and tapasin transcripts, suggesting that the reduced expression of these transcripts may be associated with the low expression of HLA class I molecules. Introduction of tapasin gene dramatically up-regulates the surface expression of HLA class I molecules on Hep G2 cells, and unexpectedly, enhances the expression of LMP2 and LMP7 transcripts as well. Unlike Hep G2, these tapasin-transfected Hep G2 cells are recognized by allo-specific CTL. However, the transfectant is unable to endogenously present an HIV envelope peptide to an HIV-specific CTL clone, suggesting that a proteasome-independent antigen processing pathway exists and still remains defective in the transfectant. These data may provide significant evidence that the nonproteasomal antigen processing pathway as well as the proteasomal pathway may be impaired in tumor cells to escape immune surveillance performed by CTL.

Antigen Presentation↗

PubMed2001

Analysis of Tag1-like elements in Arabidopsis thaliana and their distribution in other plants.

Analysis of genomic DNA of Arabidopsis Columbia (Col.) ecotype using a transposon Tag1-specific primer showed the presence of Tag1 homologues which was confirmed by Southern hybridization with a Tag1 probe. Further analysis showed that the homologue, 0.75 kb in length, had inverted repeats at both ends, 8-bp duplicated sequences at the site at which it is located and about 80% homology with Tag1, and was randomly distributed in the Arabidopsis genome. Based on these results, we concluded that these elements are non-autonomous variants of Tag1 and we termed this element sTag1. Using the polymerase chain reaction fragment hybridization technique, we found the distribution of such homologues in other plant species.

Arabidopsis↗

PubMed2001

The effect of tandospirone, a serotonin(1A) agonist, on memory function in schizophrenia.

BACKGROUND: The purpose of this study was to test the hypothesis that the addition of tandospirone, a 5-HT(1A) partial agonist, to ongoing treatment with typical antipsychotic drugs, would improve memory function in patients with schizophrenia. METHODS: Eleven outpatients (male/female = 7/4) with schizophrenia who had been on stable doses of haloperidol and biperiden were given tandospirone, 30 mg/day, for 4 weeks. The Wechsler Memory Scale-Revised (WMS-R) was administered at baseline and 4 weeks after the addition of tandospirone. The Brief Psychiatric Rating Scale (BPRS; Total, Positive, and Negative subscale scores) and the Simpson-Angus Scale for Extrapyramidal Symptoms (SAS) were also completed on the two occasions. To exclude the possibility of a practice effect on the WMS-R test, 11 age-matched patients with schizophrenia (M/F = 7/4) were tested at baseline and after a 4-week interval. RESULTS: Repeated measures analysis of variance revealed a significant time by group (patients with or without tandospirone) effect for the Verbal-, but not the Visual Memory composite scores of the WMS-R test; no significant change was observed in patients without tandospirone, whereas improvement in the Verbal Memory score was noted in patients receiving tandospirone. Moreover, there was improvement in the Inclusion score, an index of memory organization as measured by the Logical Memory subtest of WMS-R, only in patients with tandospirone. Scores on the BPRS and SAS were improved during treatment with tandospirone, but the effects did not reach statistical significance. CONCLUSIONS: The results suggest that adjunctive treatment with 5-HT(1A) agonists may improve some types of memory function in schizophrenia.

Adult↗

PubMed2001

Cloning and functional expression of a chitinase cDNA from the common cutworm, Spodoptera litura, using a recombinant baculovirus lacking the virus-encoded chitinase gene.

A Chitinase cDNA named Slchi was cloned from the epidermis of the common cutworm, Spodoptera litura, and the enzymatic properties of its recombinant proteins were characterized. The Slchi cDNA encodes 552 amino-acid residues (aa) including a 19 aa putative signal peptide, with the calculated molecular mass of the putative mature protein 60,152 Da. A major transcript of Slchi about 2.8 kb was detected in the epidermis only during molting in the last instar larvae, suggesting its involvement in the digestive system for old cuticle. The E. coli-produced recombinant Slchi exhibited weak chitinolytic activity against 4MU-(GlcNAc)(3)>4MU-(GlcNAc)(2)>4MU-(GlcNAc)(4), in this order, but not against 4MU-(GlcNAc)(1). A recombinant Slchi with higher specific activity was obtained using recombinant Hyphantria cunea NPV (HycuNPV), which expresses Slchi under polyhedrin promoter. To discriminate chitinase activity of recombinant Slchi from an active chitinase encoded in HycuNPV genome (chiA), we further knocked out the chiA gene from the recombinant virus. The recombinant Slchi expressed in insect cell culture showed a similar substrate specificity against 4MU-(GlcNAc)(n) (n=1-4) to that produced in E. coli, while the viral chitinase showed the highest activity against 4MU-(GlcNAc)(2). The recombinant Slchi was secreted rapidly into the culture medium from the infected cells, whereas the viral chitinase retained predominantly in the cells.

Amino Acid Sequence↗

PubMed2001

Selective adsorption of biopolymers on zeolites.

Zeolites adsorb biopolymers on their surface and may be suitable as a new type of chromatographic carrier material for proteins, nucleic acids, and their conjugates. We report here various parameters that influence the adsorption of biopolymers on synthesized zeolites with regard to the Si/Al2 ratio and three-dimensional structure. There are three physicochemical principles that may underly the adsorption: 1) below the isoelectric point (pI), mainly Coulombic attraction similar to ion-exchange chromatography; 2) at pI, hydrophobic interactions (a kind of van der Waals attraction) plus the three-dimensional mesopore structure; and 3) above pI, the sum of the Coulombic repulsion and attraction forces, such as the hydrophobic interaction, and also substitution reaction of water on the Al molecule with a protein amino-base. At high Si/Al2 ratio in the presence of a small amount of Al and with mesopores between the zeolite particles, maximal adsorption was seen at pI and was suggested to be dependent on the number of hydrophobic interaction points on the mesopores, and their morphology. The application of zeolites to biochemistry and biotechnology is also discussed.

Journal Article↗

PubMed2001

Technetium-99m-ECD SPECT in antiphospholipid antibody syndrome: a drastic improvement in brain perfusion by antiplatelet therapy.

We present a case of antiphospholipid antibody syndrome (APS) with repeated transient ischemic attacks (TIAs). Magnetic resonance imaging showed multiple cerebral infarcts and ischemic changes in the cerebral white matter. Cerebral angiographies showed no abnormalities. Technetium-99m-ethyl cysteinate dimer (Tc-99m-ECD) brain SPECT showed multiple decreased perfusion areas, which were more extensive than the lesions demonstrated on MRI. After treatment with an antiplatelet agent, the patient subsequently recovered from the TIAs. Although no interval changes were observed by MRI after therapy, follow-up Tc-99m-ECD SPECT revealed a marked improvement in brain perfusion. This is the first imaging report of remarkable post-therapy improvement in brain perfusion in APS cases.

Antiphospholipid Syndrome↗

PubMed2001

Identification of a novel inhibitor of LPS-induced TNF-alpha production with antiproliferative activity in monocyte/macrophages.

An isoquinoline derivative, 5-methyl-7,8-dimethoxy-1-phenylpyrazolo[5,4-c]isoquinoline (compound 1), was identified as a novel inhibitor of LPS-induced TNF-alpha production by cell-based screening. Compound 1 suppressed LPS-induced TNF-alpha production in RAW264.7 cells and murine peritoneal macrophages in a dose-dependent manner similar to SB203580, known as a specific inhibitor of p38 MAPK. It also inhibited an LPS-induced increase in serum TNF-alpha in a mouse endotoxic shock model with an ED(50) of approximately 10 mg/kg. Compound 1 had little effect on the incorporation of [3H]-leucine into the cells, while it suppressed LPS-induced TNF-alpha mRNA levels in RAW264.7 cells. The results indicate that suppression of TNF-alpha production was not a result of nonspecific inhibition of de novo translation but was based on the decreased TNF-alpha mRNA levels. The in vitro kinase assay revealed that compound 1 did not strongly inhibit p38 MAPK activity, its potency being much lower than that of SB203580, suggesting that the TNF-alpha-suppressive action of compound 1 cannot be attributed to the inhibition of p38 MAPK. Furthermore, in contrast to SB203580, it significantly inhibited the growth of RAW264.7 and THP-1 cells in a cytostatic manner. Compound 1 is likely to have antiinflammatory and antiproliferative effects by acting on some molecule other than p38 MAPK that contributes to both LPS-induced TNF-alpha production and the cell growth of monocyte/macrophages.

Activating Transcription Factor 2↗

PubMed2001

Expression of thioredoxin in bleomycin-injured airway epithelium: possible role of protection against bleomycin induced epithelial injury.

Bleomycin (BLM) is an anticancer drug, administration of which leads to severe lung injury, in which the generation of intracellular reactive oxygen species (ROS) is thought to participate in that. Thioredoxin (TRX) has been found to function as a powerful antioxidant by reducing ROS, and thus protecting against ROS-mediated cytotoxicity. However, a protective role of TRX in BLM-induced lung injury has not been determined. In the present study, we therefore attempted to clarify this issue. Human TRX-transfected L929 murine fibrosarcoma cells were more resistant to BLM-induced cytotoxicity than the parental and the control transfected cells, indicating that TRX plays the protective role in BLM-induced cytotoxicity. Next, we examined TRX expression in the lung of in vivo model of BLM-induced lung injury and BLM-stimulated bronchial epithelial cells in vitro to clarify the role of TRX in BLM-induced lung injury. In the lungs of BLM-treated mice, the expression of TRX was strongly induced in bronchial epithelial cells. TRX expression was also up-regulated at both the mRNA and protein levels in cultured BEC with the treatment with BLM. However, the expression of other major antioxidants, such as Cu/Zn-SOD, Mn-SOD, catalase and glutathione peroxidase, was not affected by BLM. These observations suggest that the cellular reduction and oxidation (redox) state modified by TRX is involved in the BLM resistancy and the induction of TRX in bronchial epithelial cells might play a protective role in BLM-induced lung injury.

Animals↗

PubMed2001

High expression of HLA-A2 on an oral squamous cell carcinoma with down-regulated transporter for antigen presentation.

Using the reverse transcription PCR, we evaluated expression levels of various antigen presentation-related genes, including LMP2, LMP7, MECL-1, PA28alpha, PA28beta, TAP1, TAP2, and tapasin, in two oral squamous cell carcinoma cell lines, HSC5 and HSC7. Expression levels of LMP2, MECL-1, TAP1, and TAP2 transcripts are reduced in both cell lines in comparison with a normal epithelial cell line. Further, HSC5 and HSC7 show diminished expression of LMP7/tapasin, and PA28alpha/beta, respectively. Surface expression of HLA-B alleles is down-regulated in both lines presumably due to low expression of TAP1/2. However, HLA-A2 surface expression is not significantly down-regulated in HSC5 cells, suggesting an involvement of signal-sequence derived peptides in the TAP-independent pathway. The current study would contribute to our understanding of significance of abnormalities in the antigen presentation machinery of oral squamous cell carcinoma, and provide meaningful information in the design of CTL-based tumor vaccines by intra-cellular delivery system.

Antigen Presentation↗

PubMed2001

Interaction of hnRNP A2/B1 isoforms with telomeric ssDNA and the in vitro function.

Overexpression of heterogeneous nuclear ribonucleoprotein (hnRNP) A2/B1, especially of B1 has been reported as a useful marker to detect cancers in early stage, although the biological reason is not clear. A2/B1 proteins were previously reported to bind telomeric DNA repeats. Alternative splicing of A2/B1 gene produces abundant A2, less abundant B1, and testis-specific minor isoforms B0a and B0b. In this study, B1 and B0b that have the N-terminal 12 amino acid insertion were suggested to have higher affinities to telomeric single-stranded DNA (ssDNA) than A2 and B0a. Kinetic analyses using purified B1 and B0b indicated that they interact dynamically with a single array of telomeric repeats. Furthermore, functional assays demonstrated that B1 and B0b bind with telomeric repeats in a tandem fashion and protect them from a nuclease and promote telomerase activity. A2/B1 proteins, especially B1 and B0b, may function as telomeric ssDNA-binding proteins in cancer and reproductive cells.

Alternative Splicing↗

PubMed2001

The subunit 1 of the COP9 signalosome suppresses gene expression through its N-terminal domain and incorporates into the complex through the PCI domain.

The COP9 signalosome is a conserved protein complex composed of eight subunits. Individual subunits of the complex have been linked to various signal transduction pathways leading to gene expression and cell cycle control. However, it is not understood how each subunit executes these activities as part of a large protein complex. In this study, we dissected structure and function of the subunit 1 (CSN1 or GPS1) of the COP9 signalosome relative to the complex. We demonstrated that the C-terminal half of CSN1 encompassing the PCI domain is responsible for interaction with CSN2, CSN3, and CSN4 subunits and is required for incorporation of the subunit into the complex. The N-terminal fragment of CSN1 cannot stably associate with the complex but can translocate to the nucleus on its own. We further show that CSN1 or the N-terminal fragment of CSN1 (CSN1-N) can inhibit c-fos expression from either a transfected template or a chromosomal transgene ( fos-lacZ). Moreover, CSN1 as well as CSN1-N can potently suppress signal activation of a AP-1 promoter and moderately suppress serum activation of a SRE promoter, but is unable to inhibit PKA-induced CRE promoter activity. We conclude that the N-terminal half of CSN1 harbors the activity domain that confers most of the repression functions of CSN1 while the C-terminal half allows integration of the protein into the COP9 signalosome.

Active Transport, Cell Nucleus↗

PubMed2001

Phytochrome-mediated control of COP1 gene expression in rice plants.

We isolated a COP1 cDNA from rice and found that it could complement the Arabidopsis cop1-4 mutant. The putative rice COP1 protein has the Ring-finger, coiled-coil. and WD-40 repeat domains, which are also conserved in pea, tomato, and mammalian COP1 proteins. The degree of overall identity between rice COP1 and Arabidopsis COP1 is 73%, and the similarity value is 83%. Expression of rice COP1 was detected in almost all plant tissues, with the level being relatively higher in calli and very low in etiolated leaves. The expression level was positively controlled by light in etiolated and green leaves. At the end of the light period, expression of the gene in green leaves could be down-regulated by far-red light. This far-red light effect could be prevented by subsequent irradiation with red light. These results indicate that phytochrome regulates rice COP1 expression.

Amino Acid Sequence↗

PubMed2001

Biosynthesis and release of methylarsenic compounds during the growth of freshwater algae.

Arsenic transformations by freshwater algae have been studied under laboratory conditions. By the use of a new analytical method, we identified methylarsenic(III) species in the growth medium of green-alga Closterium aciculare incubated under axenic conditions. The arsenate concentration in the experimental medium began to decrease just after inoculation, and the levels of arsenite and methylarsenicals increased with the growth of C. aciculare. Initially, most of the arsenate was converted into arsenite, which peaked in concentration during the exponential phase. Methylarsenicals accumulated rapidly in the stationary phase. DMAA(V) production was enhanced when the ratio of phosphate to arsenate decreased in the culture medium. The levels of DMAA(V) increased continuously toward the end of the experiment. On the other hand, methylarsenic(III) species remained relatively steady during the stationary phase. Methylarsenic(III) species accounted for 0-35% of methylarsenicals. These results suggest that arsenite and methylarsenicals (containing methylarsenic(III) species) are supplied by phytoplankton, and serve as evidence of the origin of methylarsenic(III) species in natural waters.

Arsenates↗

PubMed2001

Assessment of air pollution in Nagasaki City: determination of polycyclic aromatic hydrocarbons and their nitrated derivatives, and some metals.

Air pollutants such as polycyclic aromatic hydrocarbons (PAHs), their nitrated derivatives (NPAHs), and some metals on airborne particles in Nagasaki city, Japan were determined over a period of 12 months by high-performance liquid chromatography with chemiluminescence, fluorescence and flameless atomic absorption spectrometry. The average concentrations (range) were 18.24 (4.07-41.54) ng/m3 for total PAHs, 0.91 (0.23-4.10) pg/m3 for NPAHs, 7.95 (1.71-16.31) ng/m3 for Pb, 11.56 (3.35-24.96) ng/m3 for Mn and 3.79 (0.97-14.71) ng/m3 for Ni (n = 136). The toxic equivalency factors adjusted concentration of total PAHs determined in Nagasaki city area was 2.33 ng/m3. Concentrations of total PAHs and NPAHs in winter were higher than those in summer. In a weekly variations study, total PAHs and NPAHs concentrations, as well as traffic volume showed a similar tendency with all values higher during weekdays and lower at the weekend. The correlation coefficients between total PAHs or NPAHs and traffic volume were 0.781 and 0.818, respectively. These results suggested that one of the main sources for NPAHs and PAHs in a city area might be motor vehicles.

Air Pollutants↗

PubMed2001

Effect of high population density environment on skin barrier function in mice.

Previous reports have demonstrated that stressful stimuli markedly influenced physiological conditions and homeostasis. In this study, we examined the influence of high population density environment on barrier function and water retention property of skin in mice. Overcrowding stress induced dramatic body weight reduction and significant increase in adrenal gland weight. Macroscopic skin appearance showed moderate exfoliation and slight wrinkle formation in the stress group. Moreover epidermis hyperplasia not concomitant with inflammatory reactions such as infiltration of immunocytes and vasodilation was observed in the skin from the stress group. Skin surface conductance in the stress group was significantly lower than in the control group. On the other hand, transepidermal water loss in the stress group increased significantly, compared to the control group. Moreover, transdermal penetration of indomethacin and nicotinic acid amide was enhanced significantly. These results suggest that overcrowding stress induced impairment of barrier function and water retention property. To elucidate the mechanism of overcrowding stress-induce dry skin, contents of ceramide and pyrrolidone carboxylic acid, which are the important compounds contributing to those functions were evaluated. Both of them in stratum corneum declined significantly in the stress group. Taken together, these results demonstrate that overcrowding stress induced dry skin, and that the impairment of barrier function and water retention property correlated with decrease in ceramide and pyrrolidone carboxylic acid.

Adrenal Glands↗