Biomedical subjects

Y Yanagihara

Publications and source records attributed to Y Yanagihara.

At least 19 recordsLinked to original sources

PubMed2000

Possible involvement of Shc in IL-4-induced germline epsilon transcription in a human B cell line.

The IL-4Ralpha contains the I4R motif which binds to the phosphotyrosine binding domain of several adaptor proteins, including IRS-1/2 and Shc. Although the involvement of IRS-1/2 in IL-4-induced PI3-kinase activation is known, there is little information on the role of Shc in IL-4 signaling. In this study, we found the preferential utilization of Shc by the IL-4Ralpha in a human Burkitt's B lymphoma cell line, DND39. IL-4 induced the association of tyrosine-phosphorylated Shc with the IL-4Ralpha, whereas no detectable tyrosine phosphorylation of IRS-1 or IRS-2 was induced. IL-4-induced germline epsilon promoter activation was enhanced by overexpression of Shc and was inhibited by truncated Shc lacking the collagen-homologous domain. We further found the association of Shc with PLCgamma1. Although direct tyrosine phosphorylation of PLCgamma1 was not detectable, the amount of PLCgamma1 coprecipitable with anti-phosphotyrosine was increased after IL-4 stimulation. These results suggest that Shc can function as an adaptor protein of the IL-4Ralpha and mediate the germline epsilon transcription.

Adaptor Proteins, Signal Transducing↗

PubMed1999

Cutting edge: dominant effect of Ile50Val variant of the human IL-4 receptor alpha-chain in IgE synthesis.

Two variants of the IL-4R alpha-chain (IL-4Ralpha) gene have been recently identified in association with different atopic disorders. To clarify the etiological relationship between the two variants, we analyzed responsiveness to IL-4 of transfectants with four kinds of IL-4Ralpha carrying either Val or Ile at 50 and either Gln or Arg at 551. The substitution of Ile for Val augmented STAT6 activation, proliferation, and transcription activity of the Iepsilon promoter by IL-4, whereas that of Arg for Gln did not change these IL-4 signals. Arg551 was not associated with atopic asthma in the Japanese population. CD23 expression and IgE synthesis by IL-4 were augmented in Ile50-bearing PBMC, compared with those bearing Val50. Taken together, substitution of Arg551 does not enhance the IL-4 signal for generation of germline epsilon transcript, whereas the substitution of Ile50 contributes to enhancement of IgE synthesis.

Amino Acid Substitution↗

PubMed1999

Female mating strategy in an enclosed group of Japanese macaques.

Female Japanese macaques (Macaca fuscata) are noted for mating with multiple males and for their ability to exert mate choice. In a captive group of Japanese macaques housed at the Primate Research Institute of Kyoto University, Japan, behavioral and endocrine data were combined to examine female mating strategies. During one breeding season, daily behavioral observations were conducted on females who exhibited copulatory behavior. Blood was collected from females twice weekly and their ovulatory periods estimated by analyzing hormone profiles. Females began mating shortly before ovulation, peaked at ovulation, and continued receiving ejaculations for up to ten weeks after conception. Females were more responsible than males for inbreeding avoidance with matrilineal kin. Males sometimes approached females from their own matriline, but females avoided such males and expressed mate choice behavior preferentially toward non-matrilineal males. Over the entire mating season, females did not choose non-matrilineal males on the basis of displays, dominance rank, age, weight, or weight change during the mating season. When females were likely to conceive, however, they expressed mate choice behavior toward males who displayed most frequently. Female mating strategy may include both mate choice at ovulation and other, non-procreative functions.

Animals↗

PubMed1999

Production of IL-4 and expression of CD40 ligand by human CD8 T cells.

BACKGROUND: The role of CD8(+) T cells in IgE synthesis remains unclear. OBJECTIVE: The aim of this study was to investigate IL-4 production and CD40 ligand expression by human CD8(+) T cells. METHODS: We conducted functional and phenotypic analyses of human T cells in peritoneal washings from severe combined immunodeficiency mice reconstituted with PBMCs from normal and atopic human donors. We also examined the expression of IL-4 and CD40 ligand by CD8(+) T cells from a patient with adenosine deaminase deficiency who received autologous T cell-directed gene therapy. RESULTS: Transfer of atopic cells into the mice caused production of IgE and IgG with increased expression of IL-4 and CD40 ligand mRNA. In addition, both intracellular IL-4 and cell surface CD40 ligand were detected in CD8(+) and in CD4(+) T cells. CD8(+) T-cell lines generated from the patient's T cells carrying the adenosine deaminase gene expressed not only IL-4 mRNA and protein but also CD40 ligand mRNA and protein after being stimulated with an anti-CD3 mAb. After anti-CD3 stimulation and paraformaldehyde fixation, CD8(+) T cells induced IgE synthesis by normal human B cells in the presence of recombinant IL-4. CONCLUSION: Taken together, these results demonstrate that IL-4-producing and CD40 ligand-expressing CD8(+) cells are detectable among human T cells and suggest that such cells may promote IgE production by B cells under some conditions.

Adenosine Deaminase↗

PubMed1999

Natural killer (NK) T cells are significantly decreased in the peripheral blood of patients with rheumatoid arthritis (RA).

The number of NK T cells was measured in relation to the Th1/Th2 imbalance observed in RA. Peripheral blood samples of patients with RA (n = 60) and healthy controls (n = 36) were stained with anti-NK receptor 1A (anti-NKR-P1A), anti-CD56, and anti-CD3 MoAbs, and examined by three-colour flow cytometry. NK T (NKR-P1A+CD3+) cells in the peripheral blood were decreased in RA compared with the controls: 25 +/- 20/microl versus 143 +/- 53/microl (P < 0.0001). CD56+CD3+ cells were also decreased in RA: 60 +/- 46/microl versus 116 +/- 54/microl (P < 0.0001). The decrease was significant when adjusted to the number of total lymphocytes (P < 0.0001) or NK (CD56+CD3-) cells (P < 0.0001), and showed no correlation with age, sex, disease duration, disease activity, functional class, x-ray stage, drug treatment, joint score, grip strength, C-reactive protein, rheumatoid factor or erythrocyte sedimentation rate of the patients. The results show that the levels of NK T cells are depressed in the peripheral blood of patients with RA, suggesting that the measurement of NK T cells in peripheral blood may have clinical importance for a Th1-type autoimmune disease like RA.

Age Factors↗

PubMed1999

Determination of members of a Borrelia afzelii-related group isolated from Ixodes nipponensis in Korea as Borrelia valaisiana.

The 16S rRNA sequences of the Korean Borrelia strains 5MT and 9MT, isolated from Ixodes nipponensis, showed identities of 99.0-99.1% to that of B. afzelii. The strains were tentatively classified as belonging to the B. afzelii-related group. In this study, Korean isolates, including these strains, were characterized further and compared with recently described new species. These strains generated a RFLP pattern that has not been found previously in RFLP analysis of the 5S-23S rRNA intergenic spacer and the flagellin gene. When phylogenetic trees were constructed, based on the 5S-23S rRNA intergenic spacer, flagellin gene and 16S rRNA sequences, these Korean isolates formed a cluster with the Borrelia strain Am501 isolated from Ixodes columnae in Japan and Borrelia valaisiana strains VS116T and UK isolated from Ixodes ricinus in Europe and were distinguishable from the other species. However, these three groups of strains were divergent from each other in the molecular masses of the putative outer surface protein A (OspA) and in the sequences of the ospA gene. These findings suggest that these Korean isolates and one Japanese isolate are members of B. valaisiana and that OspA of this species is divergent, as is that of Borrelia garinii. This led to the speculation that B. valaisiana strains are adapted to the vector ticks found in each locality.

Animals↗

PubMed1999

International multicenter evaluation of the clinical utility of a dipstick assay for detection of Leptospira-specific immunoglobulin M antibodies in human serum specimens.

We performed a multicenter evaluation of a robust and easily performed dipstick assay for the serodiagnosis of human leptospirosis. The assay is aimed at the detection of Leptospira-specific immunoglobulin M (IgM) antibodies. The study involved 2,665 serum samples collected from 2,057 patients with suspected leptospirosis in 12 countries on five continents with different levels of endemicity and different surveillance systems. The patients were grouped as laboratory-confirmed leptospirosis case patients and noncase patients based on the results of culturing and the microscopic agglutination test. Paired samples from 27.7% of the subjects were tested. Of the 485 case patients, 87.4% had a positive dipstick result for one or more samples. Of the 1,513 noncase patients, only 7.2% had a positive result. Whereas most (88.4%) of the positive samples from the case patients showed moderate to strong (2+ to 4+) staining in the dipstick assay, most (68.1%) of the positive samples from the noncase patients showed weak (1+) staining. The sensitivity of the dipstick assay increased from 60.1% for acute-phase serum samples to 87.4% for convalescent-phase samples. The specificities for these two groups of samples were 94.1 and 92.7%, respectively. The dipstick assay detected a broad variety of serogroups. The results of the dipstick assay were concordant (observed agreement, 93.2%; kappa value, 0.76) with the results of an enzyme-linked immunosorbent assay for the detection of specific IgM antibodies, a test which is often used in the laboratory diagnosis of current or recent leptospirosis. This study demonstrated that this easily performed dipstick assay is a valuable and useful test for the quick screening for leptospirosis; has a wide applicability in different countries with different degrees of endemicity; can be used at all levels of the health care system, including the field; and will be useful for detecting and monitoring outbreaks of leptospirosis.

Agglutination Tests↗

PubMed1999

Cord-blood-derived human cultured mast cells produce interleukin 13 in the presence of stem cell factor.

BACKGROUND: Mast cells have been regarded as a potential source of cytokines. Although the human mast cell line HMC-1 and human lung mast cells have been shown to produce interleukin (IL) 13, it still remains uncertain whether cord-blood-derived human cultured mast cells produce IL-13. METHODS: Human cultured mast cells were raised from cord blood cells in the presence of stem cell factor (SCF) and IL-6. Levels of IL-13 mRNA were examined by a semiquantitative reverse transcriptase-polymerase chain reaction. IL-13 levels in the supernatants were measured with an enzyme-linked immunosorbent assay. RESULTS: When the IgE-sensitized cultured mast cells were activated with anti-IgE, mRNA for IL-13 was amplified with a peak at 3 h after the stimulation. IL-13 was not detected in the supernatants of the activated mast cells in the absence of SCF, whereas the mast cells secreted significant amounts of IL-13 after the stimulation in the presence of SCF. Calcium ionophore A23187 also stimulated the mast cells to release IL-13 into the supernatant in the presence of SCF. CONCLUSIONS: These observations suggest that human mast cells can produce IL-13 under the condition with SCF. The cord-blood-derived human cultured mast cells will help in studying the functional properties of human mast cells in allergic diseases.

Calcimycin↗

PubMed1999

[Preparation of ketamine tablets for treatment of patients with neuropathic pain].

Ketamine is known to have distinguished analgesic effects without anesthetic when administered in a low dose. Since ketamine is not commercially available except injection forms, we prepared ketamine tablets for the home-care medication of patients with neuropathic pain. The direct compression or wet granulation method was employed to form 150 mg of tablets containing 50 mg of ketamine. The latter method was superior to the former one in terms of content uniformity, weight variation and disintegration tests of the tablets. Ketamine contents in the tablet prepared by the wet granulation method were unchanged for 12 weeks under the conditions of 25 degrees C and 75% relative humidity (RH). The Cmax and AUC0-3 h values for ketamine after administration of the tablet were slightly smaller than those of the syrup in a healthy volunteer. However, analgesic effects of the tablet was similar to that of the syrup in a patient with neuropathic pain. And the tablet was also effective for another four patients with neuropathic pain. These results indicate that ketamine tablets are useful for the home-care medication of patients with neuropathic pain.

Adult↗

PubMed1998

Vi-deficient and nonfimbriated mutants of Salmonella typhi agglutinate human blood type antigens and are hyperinvasive.

We generated nonfimbriated mutants from both Vi-positive and -negative Salmonella typhi to analyze the role of type 1 fimbriae and Vi-antigen in bacterial invasion. A Vi-defective mutant of S. typhi GIFU 10007-3 was more invasive than the wild-type strain GIFU 10007. The wild-type strain expressing Vi-antigen did not agglutinate both Saccharomyces cerevisiae and human erythrocytes but Vi-defective mutants were able to agglutinate S. cerevisiae and human erythrocytes. Nonfimbriated mutants from Vi-negative GIFU 10007-3 lost the ability to adhere to S. cerevisiae but still could agglutinate human erythrocytes. The Vi-negative mutant increased secreted proteins and became 5-fold more invasive than the wild-type strain. Nonfimbriated Vi mutants became 50-120-fold more invasive than the wild-type GIFU 10007. To determine why nonfimbriated Vi mutants still agglutinate human red blood cells, we searched bacterial proteins that could bind human blood-type antigens. We finally identified a candidate 37 kDa outer membrane protein that recognized fucosyl-galactose, a structure common to blood type A, B and H antigens.

ABO Blood-Group System↗

PubMed1998

Elevation of serum IgE level and peripheral eosinophil count during T lymphocyte-directed gene therapy for ADA deficiency: implication of Tc2-like cells after gene transduction procedure.

We have successfully carried out T-cell-directed gene therapy for a boy with severe combined immunodeficiency due to adenosine deaminase deficiency (ADA SCID) and unexpectedly found an elevation of serum IgE level and peripheral eosinophil count during the course. More than 90% of transduced cells cultured for 7-11 days before infusion into the patient were positive for CD8 and expressed Th2-type cytokine genes such as IL-4, IL-5 and IL-13. Furthermore, CD4(+) T-depleted PBMC (peripheral blood mononuclear cells) from the patient synthesized IgE in vitro by stimulation with IL-4. Collectively, these results suggested that Tc2-like cells in the transduced cells have distinct immunological functions to help IgE synthesis and activate eosinophils.

Adenosine Deaminase↗

PubMed1998

Cultured basophils but not cultured mast cells induce human IgE synthesis in B cells after immunologic stimulation.

By generating human mast cells and basophils from umbilical cord blood mononuclear cells cultured in the presence of appropriate cytokines, we investigated whether these two cultured cells could provide the cytokine and cell contact signals that are required to induce IgE synthesis in B cells. To activate cultured mast cells and basophils, cross-linking of cell surface high-affinity IgE receptor (Fc epsilonRI) was performed with specific antigen after sensitization with murine IgE. Upon Fc epsilonRI stimulation, basophils, but not mast cells, secreted significant amounts of immunoreactive IL-4 and IL-13 and expressed detectable CD40 ligand (CD40L) and a very low level of Fas ligand (FasL). These observations at the protein level were consistent with the data obtained at the gene transcriptional level, except for the faint expression of only IL-13 mRNA in mast cells. When added to normal human B cells, activated basophils induced IgE and IgG4 synthesis as well as soluble CD23 release. In contrast, neither IgE nor IgG4 synthesis could be induced by the interaction of B cells with activated mast cells, even in the presence of recombinant IL-4. The induction of IgE synthesis by activated basophils was completely abrogated by two neutralizing MoAbs against IL-4 and IL-13 and by a soluble form of CD40. This abrogation was accompanied by abolished mature C epsilon transcription in both cases. Addition of anti-FasL MoAb, however, did not significantly affect IgE induction mediated by activated basophils. These results demonstrate that unlike cultured mast cells, cultured basophils produce biologically active IL-4 and IL-13 and express functional CD40L after Fc epsilonRI stimulation, thereby contributing to IgE production by B cells, and suggest that relatively weak expression of FasL by cultured basophils is not involved in IgE regulation.

B-Lymphocytes↗

PubMed1998

Infectivity and arthritis induction of Borrelia japonica on SCID mice and immune competent mice: possible role of galactosylceramide binding activity on initiation of infection.

We investigated the relationship between the binding activity to galactosylceramide (GalCer) and the arthritis induction activity of Borrelia japonica. The B. japonica strains maintained the ability to induce arthritis in inbred C3H/HeN and immunodeficient SCID mice, but the ability was lower than that of Borrelia burgdorferi sensu stricto virulent strain 297. Histopathological changes were restricted to the joints, and a marked effusion of polymorphonuclear neutrophils into the joint space was found. The binding activity of B. japonica strains to GalCer was lower than that of the virulent strain 297 but higher than that of the high-passage strain 297. The lower infectivity and virulence of B. japonica may explain its lower binding ability to GalCer.

Animals↗

PubMed1998

Lyme disease Borrelia species in northeastern China resemble those isolated from far eastern Russia and Japan.

Fifty-nine Borrelia burgdorferi sensu lato culture isolates collected from northeastern China were characterized by 5S-23S rRNA intergenic spacer restriction fragment length polymorphism (RFLP) analysis and reactivity with monoclonal antibodies (MAbs). Among 59 culture isolates, 30 (50.8%) were Borrelia garinii and 17 (28.8%) were Borrelia afzelii, 2 were mixtures composed of B. garinii with RFLP pattern B and B. garinii with pattern C, and 9 were mixtures composed of B. garinii and B. afzelii. One isolate, ChY13p, produced a unique pattern and was identified as B. garinii based on analyses of 16S rRNA gene sequence, flagellin PCR-RFLP typing, and MAb reactivities. No Borrelia burgdorferi sensu stricto or Borrelia japonica isolates were detected. The results indicate that Lyme disease Borrelia species in northeastern China resemble those of Borrelia isolates from far eastern Russia and Japan.

Base Sequence↗

PubMed1997

Relationship between pathogenicity of Coxiella burnetii isolates and gene sequences of the macrophage infectivity potentiator (Cbmip) and sensor-like protein (qrsA).

Coxiella burnetii, the Q fever agent, is an obligate intracellular bacterium and survival in phagolysosomes is an important virulence factor. The present study was performed to determine the relationship between its pathogenicity and genes related to its survival in macrophages, i.e. macrophage infectivity potentiator and Q fever agent regulatory sensor-like protein. The sequence similarity was more than 99% among Japanese, European and American strains, and no relationship was found between pathogenicity in guinea pigs and these genes.

Bacterial Proteins↗

PubMed1997

Characterization of Borrelia garinii isolated from Lyme disease patients in Hokkaido, Japan, by sequence analysis of OspA and OspB genes.

The outer surface proteins OspA and OspB genes of clinical Borrelia garinii isolates (JEM1-8) from Hokkaido, Japan were sequenced. One strain, JEM4, has a single ospA gene which is similar to European B. garinii strains PBr (sequence homology value: 94.1%) and T25 (91.2%). Five of the other seven strains exhibit a homologous C-terminus (300 bp) on both ospA and ospB genes (88.7-97.3%). The other two strains seem to be derived from the five strains by ospA or ospB alterations. In a phylogenetic analysis based on ospA, these strains could be classified into B. garinii, but formed independent branches and separated from the typical B. garinii isolates from Europe and Russia.

Amino Acid Sequence↗

PubMed1997

Homogeneity of Borrelia japonica and heterogeneity of Borrelia afzelii and 'Borrelia tanukii' isolated in Japan, determined from ospC gene sequences.

Borrelia afzelii, B. japonica, and 'B. tanukii' isolated from various sources and geographical origins in Japan were characterized by restriction fragment length polymorphism (RFLP) analysis and sequencing analysis of the outer surface protein C (OspC) amplicon. B. afzelii and 'B. tanukii' generated variable RFLP patterns and differences in ospC gene sequence were confirmed. In contrast, 26 isolates of B. japonica generated one OspC RFLP type, and sequence similarity between B. japonica ranged from 96.4 to 99.7%. These finding suggests that B. japonica is unique in comparison with other members of B. burgdorferi sensu lato species with respect to homogeneity of the ospC gene.

Animals↗

PubMed1997

Possible role of nuclear factor-kappa B activity in germline C epsilon transcription in a human Burkitt lymphoma B cell line.

Nuclear factor-kappa B (NF-kappa B) plays a broad role in gene regulation, but it is not evident whether NF-kappa B acts as a messenger system for germline C epsilon transcription. We report here that the signaling cascade triggered by interleukin-4 (IL-4) or anti-CD40 monoclonal antibody (mAb) participates in NF-kappa B activation responsible for germline C epsilon transcription in a human Burkitt lymphoma B cell line, DND39. Both IL-4 and anti-CD40 mAb induced activation of phosphatidylinositol 3-kinase (PI3-kinase), translocation of a zeta isoform of protein kinase C, and nuclear expression of NF-kappa B. All such events were abrogated by treatment with LY294002, a specific inhibitor of PI3-kinase. In addition, N-acetyl-L-cysteine (NAC), a potent antioxidant, decreased NF-kappa B activation caused by IL-4, anti-CD40 mAb, or their combination. NAC was also effective in diminishing germline C epsilon transcription, and its potency was higher in cultures costimulated with IL-4 and anti-CD40 mAb than in those stimulated with IL-4 alone. These results indicate that IL-4 and ligation of CD40 induce NF-kappa B expression via at least a mechanism dependent on the PI3-kinase pathway and suggest that NF-kappa B sensitive to NAC may play a role in regulating germline C epsilon transcription.

Acetylcysteine↗