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Biomedical subjects

Y Yanagi

Publications and source records attributed to Y Yanagi.

At least 73 records · Page 4Linked to original sources
PubMed1994

Measles virus infects mouse fibroblast cell lines, but its multiplication is severely restricted in the absence of CD46.

Mouse cell lines (L, NIH3T3, and RMA cells) infected with the Edmonston strain of measles virus (MV) did not exhibit cytopathic effects (CPE), consistent with the finding that mice are not susceptible to MV. Northern blot analysis, however, revealed that MV genes were transcribed in infected L and NIH3T3 cells, although expression levels were much lower than those in lytically infected Vero cells. Expression of MV genes was not detected in infected RMA cells. L and NIH3T3 cells were found to synthesize viral proteins and produce infectious virions after infection. These cell lines did not express on the surface the molecule detectable by antibodies directed against human CD46, the recently identified MV receptor. L cell transfectants expressing human CD46 exhibited CPE after MV infection, and produced 50 times more viral transcripts and 20 times more infectious virions than the parental L cells. The lowest titer of MV that induced viral multiplication in L cells as detected by cocultivation with Vero cells was larger than that in CD46+ L cells by two orders of magnitude. Our results indicate that MV can infect some mouse cells in the absence of CD46, yet the presence of CD46 facilitates multiplication and cytopathogenicity of MV in mouse cells.

3T3 Cells↗
PubMed1994

L cell clone developing plaques upon infection with measles virus (Edmonston strain).

An L cell clone developing cytopathic plaques upon infection with measles virus (Edmonston strain) was obtained. The sensitivity as measured by the newly devised UV-Vero assay was not significantly different between plaque-forming and non-plaque-forming L cell clones. Cytopathogenicity and sensitivity to the virus infection appear to be under different host cell regulations.

Animals↗
PubMed1994

T-cell receptors from virus-specific cytotoxic T lymphocytes recognizing a single immunodominant nine-amino-acid viral epitope show marked diversity.

Following infection of the H-2d mouse by lymphocytic choriomeningitis virus, the newly generated cytotoxic T lymphocyte (CTL) response is focused to a single 9-amino-acid peptide sequence (epitope) of the virus. More than 96% of the primary, secondary, and clonal CTL respond to this lymphocytic choriomeningitis virus nucleoprotein epitope. This unique system affords the opportunity to evaluate the T-cell response to a single viral CTL epitope in a case in which the outcome of infection, either viral clearance or host death, is mediated by the CTLs. Specifically, the molecular structure of the T-cell receptors (TCRs) of CTLs responding to this epitope was analyzed. By using an anchored polymerase chain reaction, the TCR chains of three CTL clones cDNAs were amplified, sequenced, and found to have unique V alpha of V beta chains relative to each other as well as to lack restriction to any particular variable chain. These data indicate that the highly diverse antiviral CTL response is pleomorphic and probably provides an advantage to the host as it limits the emergence of viral variants that could more easily arise if the TCR response were homogeneous.

Amino Acid Sequence↗
PubMed1992

Measles virus inhibits mitogen-induced T cell proliferation but does not directly perturb the T cell activation process inside the cell.

Measles virus (MV) inhibits lymphocyte function in patients, as well as in cells infected in vitro. The proliferation of phytohemagglutinin-stimulated T lymphocytes is suppressed by in vitro MV infection, as shown by the diminished incorporation of [3H]thymidine into DNA and the reduced frequency of cells in the S phase of the cell cycle, as compared with mock-infected cells. MV infection itself, however, does not completely block DNA synthesis in infected cells, because infected T cells expressing MV antigens on the cell surface, isolated by fluorescence-activated cell sorter, could still proliferate. Northern blot analysis indicated that the expression of genes induced during T cell activation, such as those encoding interleukin 2 (IL-2), c-myc, IL-2 receptor, IL-6, c-myb, and cdc-2, was not significantly suppressed in MV-infected cells, suggesting that MV does not interfere with the T cell activation process. When anti-MV serum or carbobenzoxy-D-Phe-L-Phe-Gly, a synthetic oligopeptide known to inhibit MV-induced fusion, was added 24 hr after infection, the inhibition of T cell proliferation was reversed in a dose-dependent manner. From these results we propose a model for the inhibition of T cell proliferation by MV; MV glycoproteins expressed on the cell surface of infected cells interact with the MV receptor or other molecules on the cell membrane of adjacent T cells, which in turn affects the proliferation of those T cells.

Antiviral Agents↗
PubMed1992

Studies on the synthesis of sesquiterpene lactones, 14. Syntheses of (-)-arbusclin D and (+)-4-EPI-arbusclin D: the stereochemical assignment of arbusclin D.

Efficient syntheses of (-)-arbusclin D and (+)-4-epi-arbusclin D are reported. By these syntheses the C-4 stereochemistry of arbusclin D and the absolute configuration of (-)-arbusclin D have been determined to be a s shown in structure 1. The biological activities, such as cytotoxic activity toward P-388 lymphocytic leukemia, plant growth regulating activity, and antimicrobial activity of compounds 1, 3, 7, 9, 12, and 14 were also studied.

Animals↗
PubMed1992

Diversity of T-cell receptors in virus-specific cytotoxic T lymphocytes recognizing three distinct viral epitopes restricted by a single major histocompatibility complex molecule.

Cytotoxic T lymphocytes (CTL) recognize virus peptide fragments complexed with class I major histocompatibility complex (MHC) molecules on the surface of virus-infected cells. Recognition is mediated by a membrane-bound T-cell receptor (TCR) composed of alpha and beta chains. Studies of the CTL response to lymphocytic choriomeningitis virus (LCMV) in H-2b mice have revealed that three distinct viral epitopes are recognized by CTL of the H-2b haplotype and that all of the three epitopes are restricted by the Db MHC molecule. The immunodominant Db-restricted CTL epitope, located at LCMV glycoprotein amino acids 278 to 286, was earlier noted to be recognized by TCRs that consistently contained V alpha 4 segments but had heterogeneous V beta segments. Here we show that CTL clones recognizing the other two H-2Db-restricted epitopes, LCMV glycoprotein amino acids 34 to 40 and nucleoprotein amino acids 397 to 407 (defined in this study), utilize TCR alpha chains which do not belong to the V alpha 4 subfamily. Hence, usage of V alpha and V beta in the TCRs recognizing peptide fragments from one virus restricted by a single MHC molecule is not sufficiently homogeneous to allow manipulation of the anti-viral CTL response at the level of TCRs. The diversity of anti-viral CTL likely provides the host with a wider option for attacking virus-infected cells and prevents the emergence of virus escape mutants that might arise if TCRs specific for the virus were homogeneous.

Amino Acid Sequence↗
PubMed1991

T-cell receptor and T-cell-resistant virus variants.

Analysis of the T-cell receptor has revealed the molecular basis of antigen recognition by T cells specific for viral antigens. Studies using T-cell receptor transgenic mice have provided evidence for clonal deletion of virus-specific T cells in persistently infected hosts and for selection of T-cell-resistant virus variants in vivo.

Animals↗
PubMed1990

Restricted V-segment usage in T-cell receptors from cytotoxic T lymphocytes specific for a major epitope of lymphocytic choriomeningitis virus.

Cytotoxic T lymphocytes (CTL) play an important role in recovery from a number of viral infections. They are also implicated in virus-induced immunopathology as best demonstrated in lymphocytic choriomeningitis virus (LCMV) infection of adult immunocompetent mice. In the present study, the structure of the T-cell receptor (TCR) in LCMV-specific CTL in C57BL/6 (B6) mice was investigated. Spleen T cells obtained from LCMV-infected mice were cultured in vitro with virus-infected stimulator cells and then stained with anti-TCR V beta antibodies. A skewing of V beta usage was noticeable in T cells enriched for their reactivity to LCMV, suggesting that particular V segments are important for the recognition of LCMV T-cell epitopes in B6 mice. To gain more detailed information on the structure of the TCR specific for LCMV epitopes, we studied CTL clones. It has been shown that approximately 90% of LCMV-reactive CTL clones generated in H-2b mice are specific for a short peptide fragment of the LCMV glycoprotein, residues 278 to 286, recognized in the context of the class I major histocompatibility complex molecule, Db. Four CTL clones possessing the specificity were randomly selected from a collection of clones, and their TCR genes were isolated by cDNA cloning or by the anchored polymerase chain reaction. All four clones were found to use V alpha gene segments belonging to the V alpha 4 subfamily. By RNA blot analysis, two more clones with the same specificity were also shown to express the V alpha 4 mRNA. In contrast, three different V beta gene segments were used among the four clones examined. J beta 2.1 was used by three of the clones. Although amino acid sequences in the V(D)J junctional regions were dissimilar, aspartic acid was found in the V alpha J alpha and/or V beta D beta J beta junctions of all four of these clones, suggesting that this residue is involved in binding the LCMV fragment. Restricted usage of V alpha and possibly J beta segments in the CTL response to a major T-cell epitope of LCMV raises the possibility that immunopathology in LCMV infection can be treated with antibodies directed against such TCR segments. Thus, similar analysis of the TCR in other virus infections is warranted and may lead to therapeutic strategies for immunopathology due to virus infections.

Amino Acid Sequence↗
PubMed1989

Polymorphism of T-cell receptor genes among laboratory and wild mice: diverse origins of laboratory mice.

Southern blots of genomic DNA from 23 strains of laboratory mice and 19 individual wild mice were examined for restriction fragment length polymorphisms in their loci encoding the T-cell receptors (Tcr): the constant regions of the alpha, beta, and gamma chains (C alpha, C beta, and C gamma) and a variable region family of the beta chain (V beta 8). Only a few polymorphisms were observed for each locus in the laboratory mice after using three restriction enzymes, Bam HI, Eco RI, and Hind III. All the laboratory mice examined fall into one of two types for the C alpha, C beta, and V beta 8 loci and one of three types for the C gamma. These types are found in some of the wild mice studied, indicating that they were already present in the founder mice of laboratory mouse strains. In contrast, the Tcr genes are highly polymorphic among wild mice. Analysis of the polymorphisms in these loci suggests that laboratory mice have inherited their genes not only from Mus musculus domesticus, but also from other subspecies, and much more than previously believed from Asian subspecies.

Animals↗
PubMed1989

Post-transcriptional allelic exclusion of two functionally rearranged T cell receptor alpha genes.

We cloned and sequenced T cell receptor (TCR) alpha and beta chain cDNA from a lambda gt10 library obtained from a murine I-Ak autoreactive helper T cell clone MS202. Two types of cDNA clones for the alpha chain and one for the beta chain were obtained. The two alpha chain transcripts used two different V alpha genes: V alpha 4, joined to J alpha 11.2; and V alpha 5, J alpha TA13. The four V alpha 4 cDNA clones obtained did not have a complete sequences, lacking the leader portion. The V alpha 4 genomic gene segment of MS202 was revealed to contain two exons corresponding to the V alpha 4.MD13 cDNA sequence, and the potential RNA splicing signals between the two exons were intact. Both of the alpha chain cDNA clones showed in-frame rearrangements. Immunoprecipitation of 125I-surface-labeled lysate of MS202 with anti-TCR antiserum and subsequent electrophonetic analyses indicated that only one of the alpha chain polypeptides was expressed on the cell surface. Thus, allelic exclusion of the alpha chain in MS202 is achieved by post-transcriptional regulation rather than rearrangements.

Alleles↗
PubMed1989

Antitumor activities of a novel 9-aminoanthracycline (SM-5887) against mouse experimental tumors and human tumor xenografts.

The antitumor effects of SM-5887, a totally synthetic 9-aminoanthracycline derivative, were evaluated in six murine experimental tumor systems (P388, Ehrlich carcinoma, sarcoma 180, Lewis lung carcinoma, B16 melanoma and colon 38) and nine human tumor-nude mouse systems (one breast cancer, two lung cancers and six gastric cancers). Characteristically SM-5887 showed excellent antitumor activities, superior to adriamycin (ADR), against human tumor xenografts, although its activities against murine experimental tumors were almost equal to those of ADR. When the human tumors were implanted sc in female athymic mice (BALB/c, nu/nu) and their volume reached 100-300 mm3, SM-5887 and ADR were injected iv. All nine human tumors tested showed statistically significant responses to SM-5887, and 7 of them were strongly suppressed in their growth by SM-5887 so that minimum T/C values were less than 30% at the maximum tolerated dose (MTD, 25 mg/kg) with a single iv injection. Compared with ADR, SM-5887 was statistically more effective in five tumors (one breast, one lung and three gastric), equal in two tumors (two gastric), and less potent in two tumors (one lung and one gastric). In addition, the 10-day-interval repeated iv treatments with SM-5887 at the MTD (25 mg/kg) resulted in remarkably potent antitumor effects (including complete regression) against human gastric cancer, 4-1ST, implanted in nude mice without enhancement of toxic effects. SM-5887 was also effective against ip-inoculated P388 by oral administration as well as iv injection.

Administration, Oral↗
PubMed1989

Toxicological aspects of a novel 9-aminoanthracycline, SM-5887.

The toxicological characteristics of SM-5887 were evaluated in mice after a bolus intravenous injection, and compared with those of adriamycin (ADR). The acute toxic signs observed after SM-5887 administration were body weight decrease, ataxia, hair loss, and myelosuppression. They were qualitatively comparable to those induced by ADR. The 50% lethal dose values determined by 14-day observation after drug administration were in the range of 32 to 50 mg/kg for SM-5887 and 16 to more than 20 mg/kg for ADR in four strains of mice. The maximum tolerated doses (MTD) were estimated to be 25 mg/kg for SM-5887 and 12.5 mg/kg for ADR (no death or body weight loss of more than 3 g occurred). When 14-day survivors were further observed until 90 days after drug administration, ADR frequently and dose-independently showed delayed-type lethal toxicity at doses of more than 10 mg/kg, whereas SM-5887 did not. The myelosuppression of SM-5887 was more severe even at a half of the MTD than that of ADR at the MTD, but its recovery was more rapid than that after ADR. In addition, when the drugs were injected into the subplantar region of mouse hind paws, ADR induced a severe inflammatory reaction, whereas SM-5887 yielded only a slight one. The data suggest that toxic effects of SM-5887 are more reversible and more controllable than those of ADR.

Animals↗
PubMed1989

CD4/Leu7 and CD8/Leu7 large granular lymphocytosis: comparative studies between NK cells and T cells.

Lymphocytes, co-expressing CD4/Leu7 and CD8/Leu7 markers respectively, taken from two patients having large granular lymphocytosis taking an indolent clinical course have been comparatively studied for function as NK cells and T cells. Both large granular lymphocytes (LGLs) were acid phosphatase positive and showed a beta-glucuronidase reaction in their cytoplasmic granules. Studies on case 1 indicated that the CD4/Leu7 lymphocytosis with LGL morphology takes a benign clinical course with mild neutropenia as well as those of CD8/Leu7 LG lymphocytosis. Both CD4/Leu7 and CD8/Leu7 LGLs behave similarly in their lack of NK activity, and manifest decreased IL-2 production in vitro and show a low IL-2 receptor expression unrelated to their T cell phenotype, but behave differently in influencing the immunoglobulin production in vitro and the ADCC activity, depending on their T cell phenotype and on the expression of Fc receptor, respectively. Furthermore, the altered Fc receptors which were undetectable by the Leul 1 antibody but were still effective for ADCC activity might be present in case 2 LGLs.

Aged↗
PubMed1989

[Studies on the development and growth of the human maxilla--special references to the anterolateral, infratemporal and orbital surfaces].

Morphological and macroscopical studies were made on the lateral surface of the human maxilla. The materials consist of 128 cases of human fetuses ranging from the fourth to the tenth month and 306 cases of human juveniles and adults. The earliest month in which the loci with the scientific name (Nomina Anatomica) of the maxilla was observed was as follows; the frontal process, zygomatic process, anterior nasal spine and the nasal notch were first observed on the fourth fetal month. The infraorbital foramen and anterior lacrimal crest were first observed in some cases on the fourth fetal month and in all cases on the fifth fetal month. The infraorbital suture, lacrimal notch and alveolar process were first observed on the fifth to the sixth fetal month. The infraorbital sulcus and infraorbital canal were first formed on the fifth to the seventh fetal month. The following loci on the lateral surface of the maxilla which are related to the development of the maxillary teeth were first observed after birth as follows; the alveolar foramina were first observed in 3 to 7 years after birth and the maxillary tuberosity was first observed in 6 to 7 years after birth. The canine fossa was first observed in 6 years after birth. As far as the development of the maxilla is concerned, the frontal process and infraorbital margin were first observed and secondly the alveolar part was observed and finally the maxilla body which involved the maxillary sinus was formed.

Adolescent↗
PubMed1988

GHRH-induced GH response in patients with senile dementia of the Alzheimer type.

To clarify the functional state of the somatotropinergic system at the hypothalamo-hypophyseal level in senile dementia of the Alzheimer type, the GHRH test was performed in three groups of subjects: a) healthy elderly subjects; b) early onset senile dementia patients; and c) late onset senile dementia patients. Intravenous administration of GHRH(1-44)NH2 (100 micrograms) elicited a marked plasma GH response with a maximum peak (709.54 +/- 259.0 pmol/l; P less than 0.005) 60 min after injection in patients with early onset senile dementia, but no significant response was detected in the other two groups. Electroencephalographic recording showed that GHRH modifies brain bioelectrical activity, decreasing frequency (0.52 +/- 0.15 Hz) and increasing amplitude (8.25 +/- 4.5 microV) of the electroencephalogram basic rhythm. The evaluation of mental performance and behaviour with a battery of different tests for mental assessment revealed that GHRH induces transient clinical changes in psychomotor behaviour. According to these results, it seems likely that the somatostatin deficiency reported in senile dementia of the Alzheimer type may account for the enhanced GHRH-induced GH response observed in patients with early onset senile dementia. In consequence, the GHRH test might constitute a useful antemortem marker for senile dementia of the Alzheimer type if the present results can be replicated in early stages of the disease.

Aged↗
PubMed1988

[Functions of large granular lymphocytes--a case of large granular lymphocytosis with characteristic cell surface antigens].

A 58-year-old male visited the hematological clinic of Surugadai Nihon University Hospital, Tokyo, complaining of numbness around both elbows. The peripheral leukocyte count was 12,400/microliters, and large granular lymphocytes (LGL) occupied 79% of the leukocytes. The cell surface antigen studied by flow cytometry were the positive CD 2, 3, 5, 8, 11, and Leu-7, and the negative CD1, 4, 10, 16 (Leu-11), 19, 20, and OKTIa1. IgG-FCR checked by mean of the EA-rosette formation was positive. The LGL showed the negative NK cell activity and the positive ADCC and LAK cell activities. It was interesting that LGL was negative for CD16 (Leu-11) while they had ADCC activity. Since the rearrangement of the receptor gene in T-cells was demonstrated by the southern blot analysis, the proliferation of LGL was considered to be a clonal one. LGL did not inhibit the colony formation of granulocyte and erythrocyte precursors in the plasma clot culture. It was thus considered that this might partially explain the fact that the patient's neutrophil, Hb and platelet levels remained normal.

Antibody-Dependent Cell Cytotoxicity↗
PubMed1986

Does the deletion within T cell receptor beta-chain gene of NZW mice contribute to autoimmunity in (NZB X NZW)F1 mice?

To determine the transacting genetic factors of NZW contributing to the development of autoimmune disease in (NZB X NZW)F1 (B/W F1) mice, we examined the relationship between the T cell receptor beta chain gene deletion and the severity of autoimmune manifestations in 76 B/W F1 X NZB backcross mice. Very high association between the T cell receptor beta chain gene deletion and the development of autoimmune manifestations including the production of IgG anti-DNA antibodies and circulating retroviral gp70 immune complexes was observed, indicating that a defect in the NZW T cell receptor beta chain gene or a locus closely linked to it contributes to the autoantibody formation in B/W F1.

Animals↗