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Biomedical subjects

T Hayashi

Publications and source records attributed to T Hayashi.

At least 145 records · Page 8Linked to original sources

CpG oligodeoxynucleotides accelerate reovirus type 2-triggered insulitis in DBA/1 suckling mice.

We reported previously that reovirus type-2 (Reo-2) triggers T-helper (Th) 1-mediated autoimmune insulitis resulting in temporal impaired glucose tolerance (IGT) approximately 10 days post infection (d.p.i) in suckling DBA/1 mice. We hypothesized that CpG motifs in bacteria may enhance virus-induced insulitis through its content of unmethylated CpG motifs. In the infected mice, the intraperitoneal treatment of synthetic 20-base oligodeoxynucleotides with CpG motifs (CpG ODN) caused increase in cumulative incidence of insulitis with IGT, increased serum interferon (IFN)-gamma concentration, and high frequency of autoantibody against pancreatic islet cells, compared to the infected mice without CpG ODN at 17 d.p.i. Also CD4+ and CD8+ lymphocytes infiltrated in and/or around pancreatic islets in the CpG ODN-treated mice. This evidence suggests that CpG ODN may contribute to accelerate Reo-2-induced autoimmune reaction against pancreatic islet cells via additional effects of Th1 cytokines especially IFN-gamma.

Animals↗

Involvement of apoptosis in the control of Sertoli and pre-meiotic germ cell numbers in the developing rabbit testis.

The numbers of Sertoli and pre-meiotic germ cells in the developing rabbit testis were investigated as an initial step in determining the physiological meaning of the control of cell number in the testis by apoptosis. Sections were stained immunohistochemically for the detection of apoptotic cells and counterstained with haematoxylin. The number resulting from subtraction of the number of apoptotic cells from the total cell number was defined as the viable cell number. The number of viable premeiotic germ cells in the adluminal compartment of seminiferous tubules decreased during the pre-natal period, although neither apoptotic nor necrotic figures were detected. After birth, the numbers of total and apoptotic Sertoli and pre-meiotic germ cells increased, maintaining a stable ratio of their viable cell populations until the induction of meiosis. During induction of meiosis, the increase in the number of viable Sertoli cells was significantly accelerated because of the rapid decrease in the number of apoptotic Sertoli cells. Just after spermatids were formed the number of viable spermatogonia increased, reflecting an active supply of differentiated sper matogonia entering meiosis. In conclusion, apoptosis of Sertoli and pre-meiotic germ cells plays an important role in the acquisition of a suitable ratio of both cell types, and in providing intratubular environments for further progression of spermatogenesis, by controlling numbers of both cell types during the post-natal period.

Animals↗

Expression of T helper 1 and T helper 2 cytokine mRNAs in freshly isolated peripheral blood mononuclear cells from dogs with atopic dermatitis.

Using reverse transcription-polymerase chain reaction (RT-PCR) and semi-quantitative PCR techniques, mRNA expression for canine interferon (IFN)-gamma, interleukin (IL)-4, IL-5 and IL-10 in freshly isolated peripheral blood mononuclear cells (PBMCs) was examined in dogs with or without atopic dermatitis (AD). The expression of IFN-gamma mRNA in dogs with AD was lower than that in dogs without AD (healthy control). The expression of IL-5 mRNA was higher in dogs with AD than in control dogs, but there were no significant differences in IL-4 mRNA and IL-10 mRNA expression between the groups. The number of circulating eosinophils was higher in dogs with AD than in control dogs, although eosinophilia was found in only one dog with AD. These results suggest that there is a tendency for the PBMCs of atopic dogs to express a type 2 cytokine pattern that is similar to the pattern observed in human AD patients.

Animals↗

Promotion of lupus in NZB x NZWF1 mice by plasmids encoding interferon (IFN)-gamma but not by those encoding interleukin (IL)-4.

The present study extended our previous observation that interferon (IFN)-gamma may be responsible for the active disease that develops in NZB x NZWF1 mice and serves as a model for human systemic lupus erythematosus. Treatments with cytokine-encoding plasmids were delivered intraperitoneally every 4 weeks, starting at 3 months of age (i.e. before the onset of lupus). In comparison with the control plasmid and the IL-4-encoding plasmid, the IFN-gamma-encoding plasmid promoted increased blood urea nitrogen values and reduced the survival rate, and these changes were accompanied by the development of anti-nuclear antibody. There were no differences, however, between treatment with control plasmids and treatment with IL-4-encoding plasmids in terms of the development of lupus. The findings clearly indicated that IFN-gamma but not IL-4 contributed to the development of lupus in the NZB x NZWF1 mice.

Animals↗

Lactic dehydrogenase virus (LDV) infection inhibits allergic eosinophil reaction in the airway.

The effects of interferon (IFN)-gamma induced by virus infection on eosinophil reaction in allergic airway inflammation are not yet clear. We investigated the effects of lactic dehydrogenase virus (LDV) infection, which increases IFN -gamma production with no viral infection or replication in respiratory epithelium, on allergic airway hypersensitivity. LDV infection suppressed antigen-induced eosinophil recruitment into the airway in sensitized mice. IL -5 gene expression in bronchoalveolar lavage (BAL) cells was significantly suppressed in LDV -infected mice compared with uninfected controls. The numbers of total T cells and CD 4+ T cells were significantly reduced in LDV -infected mice compared with controls. The present results suggested that the increase in production of IFN -gamma by viral infection suppresses the eosinophil reaction, and this suppressive effect may be mediated by inhibition of the recruitment of CD 4+ T cell and IL -5 production.

Allergens↗

Molecular cloning and characterization of mouse calcitonin gene-related peptide receptor.

The calcitonin gene-related peptide (CGRP) plays important roles as a neurotransmitter/neuromodulator in the central nervous system, and as a potent vasodilator when secreted from peripheral, perivascular nerves through its specific receptors. In this study, we cloned mouse cDNA counterparts of the human CGRP receptor composed of calcitonin receptor-like receptor (CRLR) and receptor activity modifying protein 1 (RAMP1) and examined the signal transduction mechanism through the CGRP receptor. Mouse CRLR (mCRLR) is a 462-amino acid G protein-coupled heptahelical receptor, and mouse RAMP1 (mRAMP1) is a 148-amino acid single membrane-spanning protein with a short cytoplasmic portion. Specific binding of (125)I-CGRP was detected only when both mCRLR and mRAMP1 cDNAs were cotransfected to COS-7 cells, and the Kd value of the receptor was 2.2 x 10(-10) M. CGRP induced a marked elevation of the intracellular cAMP levels in COS-7 cells cotransfected with mCRLR and mRAMP1. CGRP signaling through the mCRLR/mRAMP1 receptor complex was found to increase the promoter activities of cyclic AMP responsive element and serum responsive element in the co-transfected HeLa cells. These results indicate that mCRLR and mRAMP1 constitute a functional mouse CGRP receptor for the transduction of CGRP signaling by PKA and extracellular signal-regulated kinase signal transduction pathways.

Amino Acid Sequence↗

Construction of a dense comparative map between human chromosome 1p36-->p35 and swine chromosome 6 by using human sequence-tagged sites.

Construction of a comprehensive comparative map between swine and human chromosomes is a prerequisite, in order to select candidate swine genes for traits from the human genome database as well as to understand the evolutionary process of the two species. The present study attempted to use 910 sequence-tagged sites (STSs) localized in human chromosome (HSA) 1p36-->p35 (35 Mbp) for radiation hybrid (RH) mapping to swine chromosomes (SSCs). Out of the 910 STSs subjected to amplification of swine orthologues, primer pairs for 13 STSs were found to amplify the respective orthologues and the STSs were assigned to SSCs. Eleven STSs were assigned to SSC6 in the same order as that in HSA1: SSC6cen-(SHGC-150)-(A006H31)-(X82877)-(A007E03)-(IB404)-(stGDB:371372)-(stSG31658)-(A009Q18)-(stSG14201/A009C01)-(H08335)-qter. One of the remaining two STSs, WI-20819, was assigned to SSCX, and the other, R91D18R, was not linked to any first-generation markers of the IMpRH map with a lod score greater than 3.

Animals↗

Tardive decrease of astrocytic glutamate transporter protein in transgenic mice with ALS-linked mutant SOD1.

The expressions of glutamate transporter proteins were immunocytochemically examined in the spinal cord of transgenic mice harboring a Gly93 --> Ala (G93A) mutant human SOD1 gene. Astroglial EAAT2 protein level was preserved in the ventral horn even after the beginning of paralysis, and finally decreased at terminal stage of the disease (35 weeks of age), when neuronal EAAT3 protein level was also decreased. In contrast, glial fibrillary acidic protein (GFAP) immunoreactivity progressively increased from 25 weeks of age in the ventral horn. The present results show interesting dissociative expressions of astroglial proteins EAAT2 and GFAP in the same ventral horn, but suggest not an early and primary role of EAAT2 in the motoneuronal death of this model.

Amino Acid Transport System X-AG↗

A case of paroxysmal kinesigenic dyskinesia with spastic paraparesis.

We report the first case of paroxysmal kinesigenic dyskinesia (PKD) with spastic paraparesis. A 17-year-old male began to show a dystonic posture in both his upper limbs when walking at age 12 years. Neurological examination revealed bilateral talipes cavus, spasticity in all extremities with general hyperreflexia and pathological reflexes. On starting to walk, he showed a dystonic posture in bilateral maniphalanx, wrists, elbows, and toes. Magnetic resonance imaging (MRI) revealed high T2-weighted signal intensity in bilateral pyramidal tract. Although the combination of pyramidal and the basal ganglia disorders is very rare, the present case suggests an inter-relation of the pyramidal and the basal ganglia systems.

Adolescent↗

Alterations in lipid metabolism induced by recombinant bovine tumor necrosis factor-alpha administration to dairy heifers.

Endotoxin induces marked changes in lipid metabolism via its effects on cytokines. To evaluate the role of tumor necrosis factor-alpha (TNF) in mediating changes of lipid metabolism in ruminants, we performed a crossover saline-controlled study in Holstein heifers (n = 8; 394.0 kg average BW), investigating the metabolic effects of a single intravenous administration of recombinant bovine TNF (rbTNF, 5.0 microg/kg). Blood samples were taken from a jugular vein at 0 (1100, just before injection), 0.5, 6, 12, and 24 h after each treatment. Dry matter intake in the heifers was not affected by single administration of the rbTNF. The rbTNF produced early as well as later hypertriglyceridemia (P < 0.05) in dairy heifers. The rbTNF also induced an early and sustained rise (P < 0.05) in the plasma NEFA concentration. Plasma retinol concentration was decreased (P < 0.05) at 24 h after rbTNF injection, whereas the a-tocopherol concentration was not significantly affected by rbTNF treatment. At 0.5 and 24 h, there was an increase (P < 0.05) in the plasma concentration of the very-low-density lipoprotein (VLDL) fraction in rbTNF-treated heifers. Between 6 and 24 h after rbTNF treatment, concentration of the low-density lipoprotein fraction declined (P < 0.05) but the high-density lipoprotein fraction was not altered in the rbTNF-treated heifers. These results indicate that TNF produces a hypertriglyceridemic response associated with an increase of the VLDL fraction and a disturbance of retinol metabolism in dairy heifers.

Animals↗

Acute myocardial infarction associated with myocardial bridge and coronary artery vasospasm.

A 65-year-old man was admitted to our hospital with acute myocardial infarction (MI). Emergency coronary angiography showed no significant organic lesions, but a myocardial bridge was found at the mid-left anterior descending artery An acetylcholine provocation test revealed 90% spastic stenosis just proximal to the myocardial bridge. His acute MI could have been caused by both a coronary spasm and the myocardial bridge.

Acetylcholine↗

Preparation of enantiomerically pure 2'-substituted 2-diphenylphosphino-1,1'-binaphthyls by reductive cleavage of the carbon-phosphorus bond in a borane complex of 2-diphenylphosphino-2'-diphenylphosphinyl-1,1'-binaphthyl.

Reaction of (S)-2'-boranatodiphenylphosphino-2-diphenylphosphinyl-1,1'-binaphthyl (3, borane complex of BINAP monoxide) with an excess of n-butyllithium in THF at -78 degrees C brought about a selective cleavage of the carbon-phosphorus bond between the binaphthyl and diphenylphosphinyl groups to generate the binaphthyllithium 14, the treatment of which with electrophiles MeOD, I(2), and ClSnMe(3) gave, after removal of the borane, the corresponding 2'-substituted 2-diphenylphosphino-1,1'-binaphthyls (E-MOP 9: E = D, I, SnMe(3)), without loss of the enantiomeric purity.

Journal Article↗

Overexpression of MUC1 reconfigures the binding properties of tumor cells.

Although it is known that adhesion and antiadhesion are essential to the metastatic spread of tumor cells, little is known about the molecules that regulate these processes. MUC1 is overexpressed and aberrantly glycosylated by a variety of tumor cells. Studies described here examined whether tumor-associated MUC1 conferred new binding properties on tumor cell lines. Flow cytometry analysis with soluble P-, E- and L-selectin/IgM chimeric proteins was performed on human pancreatic (S2-013 and Panc-1) and colon (Caco-2) tumor cells. S2-013 cells bound E- and P-selectin and Caco-2 cells bound P-selectin. Epitope-tagged MUC1 (MUC1F) expressed by S2-013, Panc-1 and Caco-2 tumor cells did not bind to P-, E- or L-selectin. Overexpression of MUC1F on the surface of S2-013 cells blocked the interactions of E-selectin to tumor-associated ligand(s) but did not affect accessibility of monoclonal antibodies to other cell surface glycoproteins (CD9, CD44). Cell aggregation assays revealed that MUC1F expressed by S2-013 cells was able to bind to intracellular adhesion molecule-1 expressed on B cells. Overexpression of MUC1F containing a targeted mutation (the tandem repeat domain entirely or partially deleted) did not block the binding of E-selectin to its S2-013-associated ligand. These results demonstrate for the first time that the heavily O-glycosylated tandem repeat domain of MUC1 can simultaneously mediate and block binding to adhesion molecules with some molecular specificity and further support the hypothesis that MUC1 plays a dual role in the metastatic spread of tumor cells.

Amino Acid Sequence↗

Nocturnal blood pressure dip in CADASIL.

The influence of a nocturnal blood pressure dip on cerebral autosomal dominant arteriopathy with subcortical infarcts and leukoencephalopathy (CADASIL) has not yet been clarified. We attempted to examine a correlation with the nocturnal blood pressure dip and CADASIL. We monitored circadian blood pressure patterns by the use of a portable blood pressure monitoring device in five patients with CADASIL and 10 age- and sex-matched control subjects. Based on nocturnal fall in mean arterial blood pressure (MABP), we classified patients into extreme dippers (nocturnal reduction of MABP > or =20%), dippers (> or =10% but <20%), nondippers (<10% but > or =0%), and inverted dippers (<0%). Three patients revealed non-dipper and two inverted dipper. Nighttime MABP fall was significantly lower in patients compared with control subjects (P<0.01). This study suggests that a lower nocturnal blood pressure fall may be partly associated with incidence and/or worsening of deep white matter lesions in CADASIL.

Brain↗

Temporal and spatial differences of PSA-NCAM expression between young-adult and aged rats in normal and ischemic brains.

Highly polysialylated neural cell adhesion molecule (PSA-NCAM) is transiently expressed specifically in newly generated cells, and is important for migration and neurite outgrowth. To investigate the effect of aging on the migration of neural stem cell (NSC) after brain ischemia, the spatiotemporal expressions of immunoreactive PSA-NCAM were examined at 4 h or 1, 3 or 7 days after 90 min of middle cerebral artery occlusion (MCAO) in the young-adult or aged rats. In the sham control brain, PSA-NCAM staining was slightly observed both in dorsal and ventral parts of subventricular zone (SVZ) in the aged brain, but only in the dorsal part of SVZ in the young brain. After transient MCAO, immunoreactivity for PSA-NCAM increased in the number and the intensity in SVZ ipsilateral to MCAO in the young-adult brains and became the peak at 1 day, while that was at 3 days in the aged brains. These findings suggest that PSA-NCAM was located in different spatial distribution in normal condition between young and old rats. PSA-NCAM was induced after ischemia, and the temporal expression was also different after transient MCAO between young and older rats.

Aging↗

Opposing effects of anti-activation-inducible lymphocyte-immunomodulatory molecule/inducible costimulator antibody on the development of acute versus chronic graft-versus-host disease.

The functional role of inducible costimulator (ICOS)-mediated costimulation was examined in an in vivo model of alloantigen-driven Th1 or Th2 cytokine responses, the parent-into-F(1) model of acute or chronic graft-vs-host disease (GVHD), respectively. When the Ab specific for mouse ICOS was injected into chronic GVHD-induced mice, activation of B cells, production of autoantibody, and development of glomerulonephritis were strongly suppressed. In contrast, the same treatment enhanced donor T cell chimerism and host B cell depletion in acute GVHD induced host mice. Blocking of B7-CD28 interaction by injection of anti-B7-1 and anti-B7-2 Abs inhibited both acute and chronic GVHD. These observations clearly indicate that the costimulatory signal mediated by CD28 caused the initial allorecognition resulting in the clonal expansion of alloreactive T cells, whereas the costimulatory signal mediated by ICOS played a critical role in the functional differentiation and manifestation of alloreactive T cells. Furthermore, treatment with anti-ICOS Ab selectively suppresses Th2-dominant autoimmune disease.

Acute Disease↗

Rhodium-catalyzed asymmetric 1,4-addition of organoboron reagents to 5,6-dihydro-2(1H)-pyridinones. Asymmetric synthesis of 4-aryl-2-piperidinones.

Catalytic asymmetric synthesis of 4-aryl-2-piperidinones was realized for the first time by asymmetric 1,4-addition of arylboron reagents to 5,6-dihydro-2(1H)-pyridinones in the presence of a chiral bisphosphine-rhodium catalyst. In the reaction introducing 4-fluorophenyl group, the use of 4-fluorophenylboroxine and 1 equiv (to boron) of water at 40 degrees C gave the highest yield of the arylation product with high enantioselectivity (98% ee). The (R)-4-(4-fluorophenyl)-2-piperidinone obtained here is a key intermediate for the synthesis of (-)-Paroxetine.

Boron Compounds↗