Biomedical subjects

J Yodoi

Publications and source records attributed to J Yodoi.

At least 163 records · Page 9Linked to original sources

PubMed1993

Alternative transcripts of the human CD23/Fc epsilon RII. A possible novel mechanism of generating a soluble isoform in the type-II cell surface receptor.

Human CD23/Fc epsilon RII is a 45 kDa type-II membrane glycoprotein having two isoforms (a and b) that only differ in the structures of their intracytoplasmic tails. CD23/Fc epsilon RII has been demonstrated to have multiple roles in the immune system such as regulation of lymphocyte growth and differentiation and IgE-mediated immune responses. Here, we found that the human B-cell line RPMI8866, in addition to a and b transcripts, contained shorter transcripts (a' and b') that lack the entire third exon. These alternative transcripts were also detected in peripheral blood lymphocytes as well as other hematopoietic cell lines with CD23/Fc epsilon RII. Because exon 3 encodes all of the transmembrane segment and the anchoring region of the cytoplasmic tail, it is suggested that a' and b' transcripts encode secretory forms of CD23/Fc epsilon RII or they may function as regulatory transcripts involved in the control of CD23/Fc epsilon RII expression.

Alternative Splicing↗

PubMed1993

Regulation of eosinophil migration by adult T cell leukemia-derived factor.

Adult T cell leukemia-derived factor (ADF), originally defined as an IL-2 receptor alpha-chain (IL-2R alpha)/p55 (Tac) inducer, is a human thioredoxin homologue and has many cytokine-like activities. In this study, we examined the regulatory effect of ADF on eosinophil migration using human eosinophils and an eosinophilic subline of HL-60 human promyelocytic leukemia cells, YY-1. rADF induced migration of eosinophils from patients with hypereosinophilia, although rADF exhibited little activity on eosinophils from healthy donors. When human eosinophils were incubated with rADF (0.1-10 micrograms/ml) at 37 degrees C for 24 h, both chemotactic and chemokinetic activity of the complement anaphylatoxin peptide C5a on eosinophil migration was markedly enhanced in a dose-dependent manner. Similarly, this enhancing effect of rADF was observed in the migration assay using YY-1 cells. In contrast, rADF showed no modulation of migratory behavior of human eosinophils and YY-1 cells by IL-3, IL-5, nor granulocyte-macrophage colony-stimulating factor. Scatchard analysis of C5a receptors on YY-1 cells using 125I-C5a showed that rADF modulated neither the density nor the affinity of the cell membrane significantly. Furthermore, mutant ADF (mADF), which had no reducing activity, had no enhancing effect on C5a-induced eosinophil migration. These results indicate a possible involvement of ADF in the recruitment of eosinophils through redox regulation by a dithiol reductase activity.

Adult↗

PubMed1993

Astroglial expression of ATL-derived factor, a human thioredoxin homologue, in the gerbil brain after transient global ischemia.

Distribution of adult T cell leukemia derived factor (ADF/TRX), a human thioredoxin homologue, was studied by immunohistochemistry in gerbil brain during reperfusion after transient cerebral ischemia. In control brains, immunoreactivity was observed widely in the central nervous system, including the ependyma, tanycytes, endothelial cells as well as subcommisural organs, and weakly in the neuronal cell bodies. During reperfusion, ADF/TRX was expressed in glial cells in the CA1 and dentate hilus of the hippocampus, and in a few cases in the lateral portion of the caudateputamen. ADF/TRX positive glias first appeared after reperfusion for 24 h, and the intensity of staining peaked at 72 h and diminished after 7 days of reperfusion. They were concentrated around microvessels and identified to be astroglia by double labeling immunohistochemistry with glial fibrillary acidic protein as marker. Immunoblotting analysis demonstrated an increase of ADF/TRX in the postischemic hippocampus. Astroglial expression of ADF/TRX in postischemic injuries suggests a role in neuroprotection by hydrogen peroxide reducing and protein-refolding activities or in modulation of local immune responses.

Animals↗

PubMed1993

Enhancement of Fc epsilon RII/CD23 expression on U937 cells with opsonized zymosan: the requirement of a Fc gamma RI/CD64 mediated signal associated phagocytosis.

The kinetics of surface Fc epsilon RII/CD23 was tested on monocytic cell line U937 stimulated with opsonized zymosan. Zymosan opsonized with human serum enhanced not only the expression of surface Fc epsilon RII/CD23 but also Fc epsilon RII/CD23 mRNA detected by Northern blot and in situ hybridization techniques. This stimulation showed a marked synergism with IL-4 in the induction of Fc epsilon RII/CD23. Heat-inactivation of serum did not affect the inducibility of Fc epsilon RII/CD23 by opsonized zymosan, suggesting the involvement of serum substances other than complement. Zymosan treated with human gamma-globulin also induced Fc epsilon RII/CD23, indicating the possible involvement of Fc gamma receptors. The Fc epsilon RII/CD23 inducing effect of opsonized zymosan was partially blocked by pretreatment with heat-aggregated human gamma-globulin or an anti-Fc gamma RI monoclonal antibody but not by the anti-Fc gamma RII or Fc gamma RIII antibody. Our results showed the involvement of signals from Fc gamma receptor associated phagocytosis in the induction of Fc epsilon RII/CD23.

Blotting, Northern↗

PubMed1993

Enhancing effect of 17 beta-estradiol on human NK cell activity.

The in vitro effect of 17 beta-estradiol on NK activity was studied. The proliferation and NK activity of YT-N17 (a human NK-like cell line) were enhanced by 17 beta-estradiol (E2), and the enhancement was blocked by tamoxifen (Tx), an antagonist of E2. On the contrary, other steroid hormones such as Tx, progesterone, and testosterone had no effect. YT-N17 contained 11.8 fmol/mg protein of estrogen receptor (mean of two independent assays), a value which was 5-10-fold higher than that of other hematopoietic cell lines. An enhancement of NK activity by E2 was also seen in large granular lymphocytes obtained from normal subjects, and it was again suppressed by Tx. These data suggest that E2 is one of the activating factors for NK/LGL cells.

Cell Division↗

PubMed1993

Soluble CD23 as a sensitive marker for Epstein-Barr virus-related disorders after liver transplantation.

Plasma levels of the soluble fragments of Fc epsilon RII/CD23 (sCD23/IgE-binding factor) were measured to assess the level of activation of B lymphocytes associated with Epstein-Barr virus infection in 28 patients who received living-related liver transplantation and were treated with FK506 and steroids. In 6 patients with symptoms of EBV infection (EBV-related disorders), the plasma concentration of sCD23 increased to more than 9.8 ng/ml at the onset of symptoms. In a patient with B cell lymphoma, the plasma levels of sCD23 increased significantly when peripheral lymphadenopathy was noticed, and remained more than 10 ng/ml during the terminal period. In 4 of 6 patients, the increase of plasma levels of sCD23 preceded the increase of anti-EBV capsid antigen IgM. In the other 2 of 6 patients, there was no significant increase of the antibody, despite the integration of EBV DNA in the mononuclear cells in their ascites. The plasma levels of sCD23 of the patients without symptoms of EBV infection did not exceed 7.5 ng/ml. In contrast, the proportion of CD20+/CD23+ B lymphocytes in peripheral blood mononuclear cells was not significantly different in the patients with EBV-related disorders and those with latent asymptomatic EBV infection. Therefore, the plasma level of sCD23 is a sensitive and useful marker of EBV-related polyclonal and/or monoclonal B cell proliferation in transplanted patients with immunosuppression.

Adolescent↗

PubMed1993

Cholera toxin inhibits lethal hit stage of natural killer cell-mediated cytotoxicity.

Cytolytic process which was affected by cholera toxin (CT) resulting in the loss of natural killer (NK) cell activity was analyzed. Conjugate formation assay, membrane phospholipid methylation assay and serine esterase (granzyme A) release assay were used to determine the stage of the CT-induced inhibition of NK cell-mediated cytotoxicity. A human NK cell line YT cell-mediated cytotoxicity was completely abolished by CT pretreatment or addition of CT to the assay system. The conjugate formation assay revealed that the binding between YT cells and target cells was not affected by CT. The defined triggering stage which is coupled with membrane phospholipid methylation was not affected by CT treatment, either. On the other hand, the lethal hit stage which is represented by serine esterase (SE) release was completely inhibited by CT treatment of YT cells. Therefore, CT inhibits the stage after binding and triggering--i.e., lethal hit stage of NK cell-mediated cytotoxicity. The results also suggest that there exists a CT-sensitive negative cytotoxic signal transduction pathway as well as usual positive signal transduction pathway and these pathways might cross talk each other in the NK cell cytotoxic process.

Cholera Toxin↗

PubMed1993

Elevated serum levels of IL-8 in patients with HIV infection.

Serum levels of IL-8 were determined in HIV-infected individuals and the results were compared with those for HIV- controls. The IL-8 levels were measured by an ELISA with a MoAb and a polyclonal antibody to recombinant IL-8. The means and 95% confidence intervals of IL-8 in sera of 36 HIV-infected individuals and 32 matched controls were 275 and 216-349 pg/ml, and 8 and 4-14 pg/ml, respectively, showing a 34-fold increase in IL-8 in the circulation of HIV-infected individuals. This increase does not appear to be related to the disease state, infection or systemic medical agents. This finding suggests the possible involvement of IL-8 in the pathogenesis of HIV-induced disease.

Adult↗

PubMed1993

Redox regulation of a src family protein tyrosine kinase p56lck in T cells.

Protein tyrosine phosphorylation was examined after T cells were exposed to oxidative stress in vitro to investigate the possible involvement of redox regulation in T-cell signaling. Oxidative reagents such as hydrogen peroxide (H2O2) and diamide, which oxidize the free sulfhydryl groups in the cells, markedly induced tyrosine phosphorylation of multiple cellular proteins, especially a 55-kDa protein, of cultured peripheral blood T lymphocytes (PBL blasts). The 55-kDa molecule phosphorylated by diamide turned out to be a src family protein tyrosine kinase, p56lck. The immune complex kinase assay showed that the kinase activity of p56lck of diamide-treated PBL blasts was enhanced. The tryptic peptide mapping of p56lck demonstrated that diamide induced the phosphorylation both at Tyr-394 (autophosphorylation site) and at Tyr-505 (negative regulatory site). Taken together, the tyrosine phosphorylation and presumably kinase activity of p56lck were swiftly enhanced by oxidative stress, indicating that T cells have a redox-sensitive signaling mechanism, which is partly mediated by the lymphocyte-specific protein tyrosine kinase p56lck.

Cells, Cultured↗

PubMed1992

Expression of calpain II gene in human hematopoietic system cells infected with human T-cell leukemia virus type I.

We examined the distribution of calpains I and II in human hematopoietic system cell lines by Western and Northern blot analyses and enzyme activity assay. Expression of calpain I, a low Ca(2+)-requiring cysteine protease, was observed in all human T-cell lines tested. By contrast, expression of calpain II, a high Ca(2+)-requiring form, in human T-cells was closely correlated with human T-cell leukemia virus type I (HTLV-I) infection, which is known to result in the expression of adult T-cell leukemia-associated antigens, interleukin-2 (IL-2) receptor alpha, and Ca(2+)-dependent cell proliferation. Specific expression of calpain II in HTLV-I-infected cells occurred at the mRNA level. Furthermore, expression of calpain II in human natural killer-like cells was augmented by HTLV-I pX gene transfection. In HTLV-I-infected cells, the trans-acting transcriptional activation of the long terminal repeat and control elements for the IL-2 receptor alpha, c-fos, and granulocyte-macrophage colony-stimulating factor genes by the Tax from the pX gene is already known. Our results suggest that the similar trans-activation occurs to the calpain II gene in HTLV-I-infected hematopoietic system cells.

Blotting, Western↗

PubMed1992

Report of a patient with POEMS/Takatsuki/Crow-Fukase syndrome associated with focal spinal pachymeningeal amyloidosis.

The authors present the results of an autopsy of a 67-year-old Japanese man with POEMS/Takatsuki/Crow-Fukase syndrome (P/T/CFS) diagnosed in 1972. Each component of the syndrome was gradually recognized after the resection of lumbar vertebral solitary plasmacytoma in 1967. The patient died in 1989 of generalized infection and renal failure. Autopsy revealed in the vertebral canal between the fifth and seventh thoracic vertebrae dorsal pachymeningeal fibrosis, with prominent amyloid deposition that oppressed the spinal cord. This condition was consistent with the final neurologic manifestation of the patient, bilateral motor and sensory disturbance below the sixth thoracic level. Myelopathy remained clinically unnoticed because neurologic disturbance had begun as peripheral polyneuropathy. Normocellular marrow with heterogeneously scattered lambda light chain-positive plasma cells and degeneration of the myelinated fibers of sciatic nerve also were observed. This is the first report of focal spinal amyloidosis associated with P/T/CFS.

Adult↗

PubMed1992

Reactive oxygen-reducing and protein-refolding activities of adult T cell leukemia-derived factor/human thioredoxin.

Reducing and protein-refolding activities of adult T cell leukemia-derived factor (ADF)/human thioredoxin were studied. Recombinant ADF/human thioredoxin produced by E. coli, which has an insulin-reducing activity as efficient as that of E. coli thioredoxin, also reduced some reactive oxygen species, such as hydrogen peroxide. Furthermore, recombinant ADF/human thioredoxin was found to have protein-refolding activity for scrambled (mispaired disulfide-containing) RNase A. Cys-31 at the active site of ADF/human thioredoxin proved essential for reducing activity, and loss of Cys-31 in ADF/human thioredoxin attenuated the protein-refolding activity. These data suggest a physiological role of ADF/human thioredoxin in protecting living cells from proteotoxicity caused by reactive oxygens in vivo.

Amino Acid Sequence↗

PubMed1992

Thioredoxin regulates the DNA binding activity of NF-kappa B by reduction of a disulphide bond involving cysteine 62.

A role for redox regulation in activation of the NF-kappa B transcription factor was suggested by the observation that DNA binding activity of free protein, but not preformed DNA-protein complex, is inhibited by -SH modifying agents but enhanced by reducing agents. Mutagenesis of conserved cysteine residues in the p50 subunit identified amino acid 62 as being important for DNA binding, as a serine substitution at this position reduces DNA binding affinity, but renders the protein insensitive to -SH modifying agents. DNA binding activity of the wild type protein but not the amino acid 62 mutant was also stimulated by thioredoxin while detection of disulphide cross linked dimers in p50 but not the amino acid 62 mutant suggests that thioredoxin stimulates DNA binding by reduction of a disulphide bond involving cysteine 62. The physiological relevance of these findings was supported by the observation that cotransfection of a plasmid expressing human thioredoxin and an HIV LTR driven reporter construct resulted in an NF-kappa B dependent increase in expression of the reporter gene. Thus modification of p50 by thioredoxin, a gene induced by stimulation of T-lymphocytes in parallel with NF-kappa B translocation, is a likely step in the cascade of events leading to full NF-kappa B activation.

Amino Acid Sequence↗

PubMed1992

Expression cloning of beta 1,4 N-acetylgalactosaminyltransferase cDNAs that determine the expression of GM2 and GD2 gangliosides.

GM2 and GD2 gangliosides are sialic acid-containing glycosphingolipids expressed in some normal tissues such as brain and in various tumors such as neuroblastomas, astrocytomas, and malignant melanomas. We used a eukaryotic cell transient expression system to isolate cDNA clones that determine GM2 expression. We developed a new cell line from murine melanoma line B16 by transfecting with the polyoma T antigen gene that was suitable for this purpose. Two cDNA clones, both of which have a continuous open reading frame of 1683 base pairs, were isolated. Although the cloned cDNAs had no primary sequence similarity to reported glycosyltransferases, the deduced amino acid sequence predicted a type II transmembrane protein with an overall structure similar to other glycosyltransferases. The cDNA clones, when stably transfected, determined the expression of GM2 in B16 cells and GM2 and GD2 in the human melanoma line MeWo. Northern blot analysis revealed two transcripts in all cells that expressed either GM2 or GD2 or both. These findings indicate that the cDNAs catalyze the transfer of GalNAc onto GM3 and GD3 by a beta 1,4 linkage, resulting in the synthesis of GM2 and GD2, respectively. Namely they suggest that these cDNAs derive from the UDP-GalNAc: GM3/GD3 beta 1,4 N-acetylgalactosaminyltransferase (EC 2.4.1.92) gene.

Amino Acid Sequence↗

PubMed1992

Expression and growth-promoting effect of adult T-cell leukemia-derived factor. A human thioredoxin homologue in hepatocellular carcinoma.

Adult T-cell leukemia-derived factor (ADF), originally defined as an interleukin-2 receptor inducer, is a human thioredoxin homologue. ADF is detected in many malignant tissues and has a growth-promoting effect on transformed cells. In this study, ADF expression was examined immunohistochemically in human liver cell lines and liver tissues, and its growth-promoting effect was tested on human hepatoma cells. On three liver cell line--PLC/PRF/5, HepG2, and Chang liver cells--ADF stained positively and also was detected by immunoblotting. ADF had strong staining in the fetal liver (n = 8), although it was faint in the normal adult liver (n = 6). In hepatocellular carcinoma (n = 25), ADF expression generally was enhanced and was very strong in 52% (13 of 25) of the cases, although it was moderate in cases of chronic hepatitis or cirrhosis. ADF augmented the growth of PLC/PRF/5 cells and showed an additive effect with epidermal growth factor. These results indicate possible involvement of ADF in cell activation and growth of hepatocytes, as is the case with lymphocytes.

Carcinoma, Hepatocellular↗

PubMed1992

ADF (adult T cell leukemia-derived factor)/human thioredoxin and viral infection: possible new therapeutic approach.

ADF (adult T-cell leukemia-derived factor), originally defined as an inducer of interleukin 2 receptor/alpha (IL-2R/alpha), is a homologue of thioredoxin. ADF is constitutively produced by human lymphoid cell lines transformed by human T-lymphotropic virus type I (HTLV-I) or Epstein-Barr virus (EBV). ADF augments the proliferation of HTLV-I and EBV transformed cells as an autocrine growth factor. These data are indicative of the possible involvement of ADF in virus-related transformation of cells and their autocrine growth. On the other hand, thioredoxin contains a redox active disulfide and has a reducing activity in the presence of thioredoxin reductase and NADPH. To clarify the role of ADF/thioredoxin system in the viral transformation, we tested the effect of 13-cis-retinoic acid (RA), which is a competitive inhibitor of thioredoxin reductase, on the growth of ADF high producing cells. The expression of IL-2R/alpha on HTLV-I (+) cells was suppressed by RA. RA dose-dependently reduced the cell number and viability of ADF high producing lymphoid cells. Moreover, it had a suppressive effect on the proliferation of ADF high producing cells. It is suggested that RA has an inhibitory effect on the activation and the growth of cells producing ADF and that inhibition of the ADF/thioredoxin system may be a new therapeutic approach for retrovirus-related disorders.

Amino Acid Sequence↗

PubMed1992

Expression of adult T-cell leukaemia-derived factor, a human thioredoxin homologue, in the human ovary throughout the menstrual cycle.

An immunohistochemical study of the expression of adult T-cell leukaemia-derived factor (ADF), a human thioredoxin homologue, was performed in the normal human ovary throughout the menstrual cycle. Primordial follicles were negative for ADF. Both granulosa cells and theca interna cells at the stages of preantral and antral follicles contained ADF. The staining intensity of these cells was very strong in the preovulatory dominant follicle. After ovulation, both granulo-lutein and theca-lutein cells were positive for ADF. During pregnancy, the theca-lutein cells revealed very intense ADF staining. The theca interna cells of the atretic follicles showed ADF staining, while the granulosa cells of such follicles did not. These results suggest that ADF localizes in the ovarian steroidogenic cells which have the binding sites of either luteinizing hormone or follicle-stimulating hormone, and that ADF expression is closely associated with the activity of the ovarian steroidogenic cells.

Adult↗

PubMed1992

Lymphocyte transformation and thiol compounds; the role of ADF/thioredoxin as an endogenous reducing agent.

ADF (adult T-cell leukemia-derived factor), an inducer of IL-2R with growth promoting activity, is a homologue of thioredoxin which is involved in many thiol-dependent reducing reactions. ADF is constitutively produced and released by human lymphoid cell lines transformed by lymphocyte-tropic viruses, such as human T-lymphotropic virus type I (HTLV-I) and Epstein-Barr virus (EBV). We found that the viability and growth of these ADF high-producer cell lines (ATL-2, HUT102, MT-2, 3B6 and RPM18866) were highly dependent on L-cystine in the culture. In contrast to the relative cystine independency of ADF low-producer cells (Jurkat, Jijoye, U937 and K562), the growth of ADF high-producer cells was almost completely suppressed in L-cystine-free condition. Their viability and growth in L-cystine-free medium were markedly improved by 5 x 10(-5) M L-cysteine, 5 x 10(-5) M 2-ME or 10(-3) M GSH and partially by 10(-3) M DTT. The results demonstrate the requirement of reducing condition involving thiol compounds for the optimal growth of the virally transformed lymphoid cells. Furthermore, recombinant ADF (rADF) and suboptimal dose of 2-ME additively enhanced the growth of ATL-2 cells in L-cystine-free medium, implying the possible involvement of endogenous reducing agents such as ADF/thioredoxin homologue in the process of lymphocyte transformation/activation.

Cell Line↗