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T Yamamura

Publications and source records attributed to T Yamamura.

At least 19 recordsLinked to original sources
PubMed1996

T-T cellular interaction between CD4-CD8- regulatory T cells and T cell clones presenting TCR peptide. Its implication for TCR vaccination against experimental autoimmune encephalomyelitis.

Regulatory T cells recognizing TCR determinants presumably play a critical role in the control of experimental autoimmune encephalomyelitis, a prototype tissue-specific autoimmune disease. This study was initiated to determine whether regulatory T cells can be induced against a V beta 17a CDR2 peptide (residues 50-68) in SJL/J mice. Although the TCR peptide showed regulatory effects in vivo, the presence of T cells specific for the peptide could not be proven with conventional proliferation assays. Unexpectedly, in the presence of myelin basic protein-specific T clone cells (Tcc), the sensitized spleen cells vigorously proliferated in response to the TCR peptide. The subsequent experiment showed that this was due to the outstanding capability of the Tcc as APC for the exogenous TCR peptide. Using the Tcc as APC, we were able to establish V beta 17a50-68-specific T cell lines from in vivo primed spleen cells. The line cells were MHC class I restricted and dominated by T cells with a distinct surface phenotype (CD4-CD8-V beta 17a+). Presentation of the peptide by the Tcc was inhibited by treatment with gelonin that could block a MHC class I presentation pathway. The ability of T cells to present the TCR peptide was not related to their Ag specificity, but correlated with the expression levels of MHC class I molecules and adhesion molecules such as intercellular adhesion molecule-1 and B7-1 on their surface. The TCR peptide-specific T cells produced a soluble mediator(s) that is inhibitory for T cell activation and were protective against actively induced experimental autoimmune encephalomyelitis. These results show that V beta 17a50-68 vaccination induces regulatory CD4-CD8- T cells that could interact with T cells presenting relevant TCR fragments.

Amino Acid Sequence↗
PubMed1996

Human CAAF1 gene--molecular cloning, gene structure, and chromosome mapping.

We have isolated and characterized a cDNA and the gene of the human homologue of CAAF1, a novel member of the S100 calcium-binding protein family. The 276-bp open reading frame encoded a 92-amino acid polypeptide with a predicted molecular mass of 10,575 Da. The deduced amino acid sequence of human CAAF1 showed 66% homology to bovine CAAF1. The human CAAF1 gene consisted of three exons, with the two EF hand motifs of the CAAF1 protein separately encoded by exons 2 and 3. This gene was expressed at a high level in polymorphonuclear leukocytes and at an intermediate level in esophageal mucosa. The tissue distribution of CAAF1 mRNA was different from that of other S100 proteins. Direct R-banding fluorescence in situ hybridization revealed that the human CAAF1 gene was mapped to chromosome 1q21.2-q22, where most of the S100 genes form a cluster.

Amino Acid Sequence↗
PubMed1996

Use of transrectal ultrasonography to select type of surgery for villous tumors in the lower two thirds of the rectum.

OBJECTIVE: To determine the accuracy of transrectal ultrasonographic (TRUS) staging of rectal villous tumors when used to select a surgical procedure. DESIGN: Case series. SETTING: College hospital, Hyogo, Japan. PATIENTS: From 1988 to 1995, 24 patients were treated for villous tumors after diagnosis by TRUS, and were followed up for 0.5 to 7.5 years. MAIN OUTCOME MEASURES: Ultrasonographic tumor stage (u-T), pathologic tumor stage (p-T), biopsy findings, and surgical procedures were studied. RESULTS: Overall, 71% of the tumors were accurately staged by TRUS. However, 4 u-T1 and 3 u-T2 tumors were overstaged, with pathological examination showing 2 adenomas and 5 p-Tis tumors. Three of these 7 patients were overtreated surgically. The results of a biopsy predicted adenoma in 2 of the u-T1 tumors and 2 of the u-T2 tumors that were overstaged by TRUS. Pathological examination revealed that an enlarged lymphoid follicle in the mucosa had deformed the thin muscle layer of the rectal wall and abolished its continuity on TRUS imaging. The weakness of TRUS would seem to be in the accuracy of p-Tis staging. CONCLUSIONS: Transrectal ultrasonography had the advantage of predicting malignant infiltration in rectal villous tumors. The surgeon should know the limitations of TRUS diagnosis to select the most appropriate operation for each patient.

Adenocarcinoma↗
PubMed1996

TCR repertoire to proteolipid protein (PLP) in multiple sclerosis (MS): homologies between PLP-specific T cells and MS-associated T cells in TCR junctional sequences.

In the pathogenesis of multiple sclerosis (MS), autoimmune T cells reactive with proteolipid protein (PLP) may play a crucial role. We determined 23 TCR beta-chain sequences of limiting dilution T cel lines (TCL) selected against a synthetic peptide, PLP 95-116, 105-124 or 139-155, from the peripheral blood of three Japanese MS patients with the DR2,w15 haplotype (TI, SK and OK). Fourteen sequences were originated from TI, seven from SK and two from OK. The PLP-reactive TCL utilized various Vbeta and Jbeta gene segments, but there was significant bias in the Vbeta and Jbeta usage. Overutilization of the Vbeta2 family and dominant usage of the Jbeta2.5 subfamily was seen in PLP 105-124-reactive and 95-116-reactive TCL respectively. More remarkably, a majority of the TCL were found to express beta-chain CDR3 motifs that appear to be unique to MS brain infiltrates. In contrast, these motifs were only rarely seen in control TCR sequences from peripheral blood or from a TCL selected against tetanus toxoid. In several cases, the betaCDR3 homologies between the PLP-reactive T cells and MS brain T cells were extensive, owing to the shared motifs in combination with the surrounding amino acid identities. These results indicate that PLP-specific T cells may be involved in the immunopathology of MS.

Adult↗
PubMed1996

[Techniques for measurement of nitric oxide in biological systems: principles and practice].

Despite being small and simple in structure the nitric oxide free radical (NO.) is now proving to be of vital physiological significance, and it has been shown to play important roles in complex processes such as vasodilatation, inflammation, thrombosis, immunity and neurotransmission. To conduct meaningful research into the role of NO., it is necessary to accurately determine its concentration. Its direct and quantitative measurement, however, has been little discussed inspite of the abundance of studies on this compound. Generally most authors refer to indirect qualitative measurements, such as employment of NO-synthase inhibitors, measurement of cGMP or citrulline, and the detection of NO.-induced physiological effects such as vascular relaxation. The primary difficulties in the direct measurement of NO stem from its short lifetime and very low concentrations. Notwithstanding these problems, several quantitative methods for measuring NO. have been established. The most commonly used techniques are as follows: 1) UV-visible spectrophotometry of the diazotization product of the nitrite, NO-hemoglobin or methemoglobin, 2) fluorometry of the fluorescent product of the nitrite, 3) detection of chemiluminescence by its reaction with ozone or luminol/H2O2, 4) amperometric microelectrode assay, and 5) electron spin resonance spectrometry. All the aforementioned techniques have certain limitations that should be considered carefully prior to each application.

Animals↗
PubMed1996

[Effects of halothane, isoflurane, enflurane, and sevoflurane on the monosynaptic reflex response in the isolated spinal cord of newborn rats].

Monosynaptic reflex responses (MSRs) in the isolated spinal cord of newborn rats were elicited in the ventral root by stimulation of the ipsilateral dorsal root. MSRs were considered to be mediated by non-NMDA class glutamate receptors. We studied the depressant effects of halothane, isoflurane, enflurane, and sevoflurane on MSR amplitudes as a function of anesthetic concentration comparing with MAC value of each anesthetics. The spinal cord of newborn rats were rapidly dissected out, and placed in a chamber superfused with artificial cerebrospinal fluid (ACSF, pH 7.4, 34 degrees C) equilibrated with 95% O2 - 5% CO2. Anesthetic gases were delivered with specific vaporizers and bubbled in the ACSF. Each anesthetic concentration was determined by gas chromatography. Either of the anesthetics reversibly depressed MSR amplitudes in a concentration dependent fashion. Concentration-response curves for MSR amplitudes were constructed and the concentrations which produced a half-maximum inhibition (IC50) were 0.56, 0.65, 0.97 and 1.18 mM for halothane, isoflurane, enflurane, and sevoflurane, respectively. These IC50 values correlated well with those of MAC values (r = 0.999, P < 0.001) obtained from adult rats in an in vivo condition. The MSR response in the isolated spinal cord of newborn rats is considered as a useful model for analysis of potency of volatile anesthetics.

Anesthetics, Inhalation↗
PubMed1995

Long-term effects of small bowel transplantation on intestinal motility.

We previously found that the contractile motility of the jejunum was increased 4 weeks after transplantation, and that the dominant intrinsic neural component was changed from cholinergic to nonadrenergic, noncholinergic (NANC). The present study investigated the long-term effects of transplantation on jejunal motility using rats that survived for 2 years after surgery. Jejunal strips were harvested from various groups of rats, and intestinal motility was assessed by electrical transmural stimulation. Stimulation produced a similar increase of contraction at 4 weeks and 2 years after grafting. Pretreatment with atropine showed that the cholinergic component of contraction was 45%, 24%, 32%, and 24% in controls, rats 4 weeks after transplantation, 2-year-old controls, and rats 2 years after transplantation, respectively. The NANC component (obtained with atropine and guanethidine) in each group was, respectively, 56%, 73%, 60%, and 69%. The actual value of the tetrodotoxin-insensitive myogenic component was significantly increased at 2 years after transplantation. A substance P antagonist ([Arg6, D-Trp7,9, Mephe8], substance P 6-11), inhibited most of the NANC contraction after transplantation. These results suggested that substance P has a key role in the motility of transplanted small bowel throughout the life of the grafts.

Analgesics↗
PubMed1995

Demonstration of interleukin-3 receptor-associated antigen in the central nervous system.

We previously reported that interleukin-3 (IL-3) acts as a neurotrophic factor for cholinergic neurons. However, it has not yet been determined whether the action is derived from the interaction of IL-3 with IL-3 receptors. As the first step to study IL-3 receptors in the central nervous system, we examined the presence and localization of IL-3 receptor-associated antigen (IL-3RAA) in mouse and rat brain. Immunohistochemically, IL-3RAA, which is closely involved both in the IL-3 binding to IL-3 receptors and the tyrosine phosphorylation in the signal transduction for IL-3 in hematopoietic cells, was demonstrated in neurons throughout the brain. This was confirmed in primary cultured neurons and neuronal cell lines by immunocytochemistry and flow cytometry. The staining intensity varied among regions and the most intense immunoreactivity for IL-3RAA was found in large neurons in the magnocellular basal nuclei, pyramidal cells in the cerebral cortex, and neuronal cells in some nuclei of the brainstem. Not only cholinergic cell lines derived from the septal region but also other neuronal cell lines exhibited IL-3RAA immunoreactivity by flow cytometry. Therefore, we conclude that IL-3RAA is present in a wide variety of neurons in the brain including cholinergic neurons of the basal forebrain. Western blot analysis revealed that the candidates for IL-3RAA are 145, 100, and 50 kDa proteins both in neuronal and IL-3-dependent cell lines.

Animals↗
PubMed1995

Subtypes of endothelin ETA and ETB receptors mediating tracheal smooth muscle contraction.

In the isolated rabbit trachea, endothelin (ET)-1, ET-3 and the selective ETB receptor agonists, IRL 1620 and sarafotoxin S6c (STXc), induced contraction with EC50 of 2-9 nM. An ETA1 receptor antagonist, BQ-123, was ineffective whereas desensitization of the ETB receptor strongly antagonized the effect of ET-3, IRL 1620 and STXc. An ETB1 receptor antagonist, RES-701-1, antagonized the effects of ET-3 and IRL 1620 whereas the effect of STXc was antagonized by an ETB2 receptor antagonist, BQ-788. In the ETB-desensitized trachea, only ET-1 induced large contraction that was partially antagonized by BQ-123. These results suggest that ET induces tracheal contraction by activating multiple ET receptors: the ET-1-selective ETA (BQ-123-sensitive ETA1 and insensitive ETA2 subtypes) and the isopeptide-nonselective ETB receptors (RES-701-1-sensitive ETB1 and insensitive ETB2 subtypes).

Animals↗
PubMed1995

Polymorphic reticulosis is a neoplasm of large granular lymphocytes with CD3+ phenotype.

BACKGROUND: Polymorphic reticulosis, a type of lethal midline granuloma (LMG), has been referred to as nasal T-cell lymphoma (NTL) because of its proliferating cells' positive reactivity to anti-T-lymphocyte antibodies. Recently, several studies have suggested that proliferating cells in NTL may be natural killer (NK) in nature. NK cells and human nonmajor histocompatibility-restricted cytotoxic T-lymphocytes have the morphology of large granular lymphocytes (LGL) (i.e., a high cytoplasmic:nuclear ratio and cytoplasmic granules). Whether NTL-LMG possesses an LGL morphology is examined in this study. METHODS: Two lymph node smears, peripheral blood showing a leukemic picture, and an electron microscope (EM) examination of a cutaneous lesion, respectively, were obtained from four patients with NTL-LMG. Immunohistochemical examination of the proliferating cells and of the Epstein-Barr virus (EBV) genome by both polymerase chain reaction and in situ hybridization also were performed. RESULTS: All patients presented with necrotic and granulomatous lesions in the upper respiratory tract. Histology showed polymorphous cellular infiltrates containing large atypical cells with positive reaction to CD3 (three patients), CD43 (two patients), CD45RO (two patients), and OPD4 (one patient). Imprint smears revealed azurophilic large membrane-delimited granules in an ample cytoplasm, which was confirmed by EM. The presence of the EBV genome in the tumor cells was observed in one patient. CONCLUSION: The current findings showed that NTL-LMG or polymorphic reticulosis is a proliferation of LGL with a CD3+ phenotype.

Adult↗
PubMed1995

Water and electrolyte balance after ileal J pouch-anal anastomosis in ulcerative colitis and familial adenomatous polyposis.

The water and electrolyte balance was studied in 31 patients with ulcerative colitis (UC) and 22 with familial adenomatous polyposis (FAP) who underwent staged surgery involving colectomy and ileal J pouch-anal anastomosis (IAA), preoperatively, after terminal ileostomy, after high ileostomy, and after ileostomy closure. Serum electrolytes did not differ between each surgical stage. After terminal or high ileostomy, daily urine volume and urinary sodium loss was significantly lower, and daily fecal weight and fecal sodium loss was significantly higher than preoperatively. After ileostomy closure, urinary and fecal sodium loss became closer to preoperative value. Daily urinary potassium loss was significantly higher and fecal loss was lower after terminal and high ileostomy than preoperatively and did not show a significant change after ileostomy closure. The urinary sodium to potassium ratio after ileostomy closure was lower than preoperatively, but was higher than that after terminal and high ileostomy. Plasma aldosterone and renin levels were only significantly increased after high ileostomy. These findings indicate that high or terminal ileostomy caused chronic dehydration, which was compensated for by activation of the renin-aldosterone axis, while the water and electrolyte balance became closer to normal after ileostomy closure following ileoanal anastomosis.

Adenomatous Polyposis Coli↗
PubMed1995

Genetic but not diet-induced hypercholesterolemia causes low apolipoprotein A-IV level in rabbit sera.

The present report describes a competitive enzyme immunoassay for rabbit apolipoprotein A-IV (apo A-IV). This assay was applied to the determination of its concentration and distribution in sera from normolipidemic and hyperlipidemic rabbits. The assay was sufficiently sensitive to study this 42-kDa protein in lipoproteins fractionated from 200 microliters of serum by FPLC gel filtration. In normolipidemic sera (n = 8), apo A-IV concentration was 5.32 +/- 0.76 mg/dl. A diet rich in cholesterol (0.5%), which induced an 18-fold increase in serum cholesterol, did not significantly alter apo A-IV concentration (6.65 +/- 1.52 mg/dl, n = 8). By contrast, genetically induced hypercholesterolemia (Watanabe heritable hyperlipidemia, WHHL mutation) caused a significantly reduced level of apo A-IV (3.8 +/- 1.14 mg/dl, n = 7). In each of the groups studied, apo A-IV was distributed in two distinct pools; a high-density lipoprotein-(HDL) associated pool and a lipoprotein-free pool. However, compared to normal, the distribution of apo A-IV in WHHL rabbit sera was shifted towards the lipoprotein-free pool. Consistent with previously reported observations on apo A-I, these results are compatible with the hypothesis of an impaired reverse transport of cholesterol in WHHL rabbits, an animal model for familial hypercholesterolemia.

Amino Acid Sequence↗
PubMed1995

Exogenous supply of artificial lipoproteins does not decrease susceptibility to atherosclerosis in cholesterol-fed rabbits.

We investigated the effects of reconstituted apo A-I-containing high-density lipoprotein (r-HDL, homologous to small pre-beta-migrating HDL) and reconstituted triglyceride-rich lipoprotein (r-TRL, a mixture of Intralipid and apo E) on atherogenesis in rabbits fed a 0.5% cholesterol diet for 8 weeks. Male Japanese white rabbits (n = 17) were divided into three groups: the control group (n = 7) received a placebo and 2.5 ml of Intralipid 20 h later; the second group (n = 6) received r-HDL containing 18 mg of apo A-I followed by 2.5 ml of Intralipid; and the third group (n = 4) received 18 mg of r-HDL and 2.5 ml of r-TRL containing 4 mg of apo E. Rabbits were injected with the agents weekly and the same interval (20 h) was maintained between the two injections. Three minutes after the injection of r-HDL, a sharp increase in the pre-beta-migrating fraction was observed. The cholesterol-rich diet similarly increased serum lipids in the three groups. No significant changes of the HDL cholesterol and apo A-I concentrations were observed in the three groups. Conversely, there was a 12-fold increase of apo E which correlated positively with the total cholesterol level. Injection of r-HDL and r-TRL caused slight inhibition of fatty streak development and lipid deposition in the aortic wall, but neither change was statistically significant. Lipid accumulation in the liver was similar in all three groups. These results suggest that the physiological properties of artificial and native lipoproteins may differ.

Animals↗
PubMed1995

Analysis of proteolipid protein (PLP)-specific T cells in multiple sclerosis: identification of PLP 95-116 as an HLA-DR2,w15-associated determinant.

Multiple sclerosis (MS) is a putative autoimmune disease that is linked with HLA-DR2,w15. Proteolipid protein (PLP) is a candidate autoantigen in MS, but the disease-associated epitopes have not been determined. Using overlapping and non-overlapping PLP peptides, we have studied the T cell response to the major hydrophilic domain PLP 85-159 in the peripheral blood of MS and healthy subjects (HS). Short-term T cell lines (TCL) were selected against each peptide using microwell plates and the frequency of peptide-specific TCL was estimated. PLP 95-116-specific TCL were most efficiently generated and the frequency was significantly higher in MS compared with HS (P < 0.05). When compared between DR2,w15+ and DR2,w15- MS, TCL frequency to PLP 95-116 was significantly higher in DR2,w15+ MS (P < 0.005) and TCL reactive to the overlapping peptide 105-124 were also increased in DR2,w15+ MS (P < 0.025). Using DR gene-transfected L cells, we could show that the DRB1*1501 product of the DR2 haplotype presents PLP 95-116 to TCL selected against the peptide. These results imply that PLP 95-116 represents a major epitope for the DR2,w15+ MS.

Adult↗
PubMed1995

Evaluation of lens transparency changes through photographed images during a 13-month observation period.

Since the development of the anterior eye segment analysis system, several new types of anterior eye segment biometry have been performed. The main aim of this study was to evaluate whether changes in cataractous progression or an increase in lens transparency loss are detectable during a relatively short period of 13 months by measuring the intrapupillary opaque shadow area through retroillumination images or by calculating the light scattering intensity at the deepest cortical layer of the lens through Scheimpflug slit images. Secondly, the relationship between maximally dilated pupil sizes and patients' ages and that between cases with and without diabetes were studied. Thirty-one eyes (49.2%) of sixty-three cataractous lenses showed more than 5% increase in the opaque shadow area. Forty-five eyes (60.0%) showed more than a 5% increase in light scattering intensity. 92.5% of diabetic eyes and 92.3% of nondiabetic eyes showed pupil sizes over 6.5 mm after an instillation of mydriatica. In our study the applied method guaranteed a high reproducibility; thus is might be possible to detect an increase in cataractous changes and lens transparancy in around 50% of examined subjects in a period as short a 1 year. For the evaluation of cataract progression through a retroillumination image, the recommendable pupil size is > or = 6.5 mm.

Aged↗
PubMed1995

Common mutations in the low-density-lipoprotein-receptor gene causing familial hypercholesterolemia in the Japanese population.

Familial hypercholesterolemia (FH) is a common genetic disorder caused by mutations of the LDL-receptor gene. In the present study, we investigated four Japanese FH homozygotes and identified five point mutations: a splice site mutation in intron 12 (the 1845 + 2 T-->C mutation), a missense mutation in exon 7 (the C317S mutation), a nonsense mutation in exon 17 (the K790X mutation), a missense mutation in exon 14 (the P664L mutation), and a missense mutation in exon 4 (the E119K mutation). We developed simple methods for detecting these mutations. When we examined the presence of these mutations in 24 unrelated FH homozygotes, the 1845 + 2 T-->C mutation was found in 7 of them, and the other four mutations were unique for each proband. We also screened 120 unrelated FH heterozygotes for these mutations and found that the frequencies of the 1845 + 2 T-->C, C317S, K790X, P664L, and E119K mutations were 13.3% (16/120), 6.7% (8/120), 6.7% (8/120), 3.3% (4/120), and 1.7% (2/120), respectively. These mutations were found in more than 30% of unrelated Japanese FH patients. By using the detection methods developed in this study, the diagnosis of more than 30% of the genetic bases of Japanese FH heterozygotes is expected.

Adult↗
PubMed1995

Effects of adriamycin, an anticancer drug showing testicular toxicity, on fertility in male rats.

Adriamycin (ADR), an anticancer drug,was intravenously administered to Slc:SD male rats at doses of 0, 1 and 2 mg/kg once a week for 4 or 9 weeks before pairing, and the treatment period and parameters suitable for detection of male fertility disorder were examined. No adverse effects were observed on the copulation index, fertility index and spermatozoa, but testicular weights were low in the 1 and 2 mg/kg groups after 4-week treatment. In the 2 mg/kg group after 9-week treatment, 11 of 12 males had died or became moribund, and no successful pregnancies were observed. The males in the 1 and 2 mg/kg groups after 9-week treatment had decreased weights of the genital organs, an extremely decreased number of sperm and low sperm motility as well as a low implantation rate and a decreased number of live fetuses. Microscopically, the numbers of spermatogonia were decreased in the 1 and 2 mg/kg groups after 4-week treatment, whereas the numbers of even spermatozoa were diminished and genital organs showed atrophy after 9-week treatment. These results indicate that 4-week treatment before pairing is sufficient to detect effects of ADR on the testis, especially on spermatogonia, and that microscopic findings and testis weight are appropriate parameters for detection of male fertility disorders.

Animals↗