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T Taga

Publications and source records attributed to T Taga.

At least 181 records · Page 10Linked to original sources
PubMed1990

Analysis of very long-chain fatty acids and plasmalogen in the erythrocyte membrane: a simple method for the detection of peroxisomal disorders and discrimination between adrenoleukodystrophy and Zellweger syndrome.

We analyzed the sphingomyelin very long-chain fatty acids (VLCFAs) and phosphatidylethanolamine (PE) plasmalogen contents of the erythrocyte membrane in patients suffering from peroxisomal disorders. In a patient with Zellweger syndrome, both a decrease in the PE plasmalogen content and an increase in the sphingomyelin VLCFAs content of the erythrocyte membrane were noted. In patients with adrenoleukodystrophy, however, there was no decrease in PE plasmalogen, although the sphingomyelin VLCFAs content of the membrane was significantly increased in comparison with control values. Analyses of both sphingomyelin VLCFAs and PE plasmalogen were carried out simultaneously, using both the same process and the same sample.

Adrenoleukodystrophy↗
PubMed1990

AIDS Kaposi sarcoma-derived cells produce and respond to interleukin 6.

Cell lines derived from Kaposi sarcoma lesions of patients with AIDS (AIDS-KS cells) produce several cytokines, including an endothelial cell growth factor, interleukin 1 beta, and basic fibroblast growth factor. Since exposure to human immunodeficiency virus increases interleukin 6 (IL-6) production in monocytes and endothelial cells produce IL-6, we examined IL-6 expression and response in AIDS-KS cell lines and IL-6 expression in AIDS Kaposi sarcoma tissue. The AIDS-KS cell lines (N521J and EKS3) secreted large amounts of immunoreactive and biologically active IL-6. We found both IL-6 and IL-6 receptor (IL-6-R) RNA by slot blot hybridization analysis of AIDS-KS cells. The IL-6-R was functional, as [3H]thymidine incorporation by AIDS-KS cells increased significantly after exposure to human recombinant IL-6 (hrIL-6) at greater than 10 units/ml. When AIDS-KS cells (EKS3) were exposed to IL-6 antisense oligonucleotide, cellular proliferation decreased by nearly two-thirds, with a corresponding decrease in the production of IL-6. The decrease from IL-6 antisense in AIDS-KS cell proliferation was reversed by the addition of hrIL-6. We confirmed that AIDS-KS cells produced IL-6 in vivo by preparing RNA and tissue sections from involved and uninvolved skin from a patient with AIDS Kaposi sarcoma. We detected immunoreactive IL-6 in the involved tumor areas and to a lesser extent in the surrounding normal epidermis. Slot blot hybridization showed a great excess of IL-6 and IL-6-R RNA in involved skin compared to uninvolved skin. These results show that both IL-6 and IL-6-R are produced by AIDS-KS cells and that IL-6 is required for optimal AIDS-KS cell proliferation, and they suggest that IL-6 is an autocrine growth factor for AIDS-KS cells.

Acquired Immunodeficiency Syndrome↗
PubMed1990

Flowcytometric analysis of DNA pattern of cells derived from xeroderma pigmentosum A--hypersensitivity to vincristine, etoposide and methotrexate.

Xeroderma pigmentosum complementation group A (XPA) is one of the DNA repair deficient syndromes. The cell biological features of XPA were examined by flowcytometry using Epstein Barr (EB) virus-transformed lymphoblastoid cells. Cellular sensitivity to vincristine (VCR), etoposide (VP-16) and methotrexate (MTX) were assayed by DNA pattern changes by flowcytometry. Recently, ataxia-telangiectasia (AT), one of the same kind of disorder, has been reported to have an increased sensitivity to VCR and VP-16. However, AT showed some resistance to MTX according to other reports. Our results showed that XPA had an increased sensitivity to VCR and also to VP-16. Moreover, different from AT, XPA showed some sensitivity to MTX. Thus there is some cell biological similarity between XPA and AT, as well as some difference of the abnormality in the DNA repair pathway.

Cell Line↗
PubMed1990

Multiple binding of inhibitors in the complex formed by bovine trypsin and fragments of a synthetic inhibitor, 4-[4-(N,N- dimethylcarbamoxylmethoxycarbonylmethyl)phenoxycarbonylphenyl+ ++] guanidinium methanesulfonate (FOY-305).

The crystal of bovine trypsin complexed with a potent inhibitor, 4-[4-(N,N- dimethylcarbamoylmethoxycarbonylmethyl)phenoxycarbonylphenyl ]guanidinium (FOY-305) in the novel orthorhombic from with a low molecular packing density was studied by the X-ray diffraction method. Using synchrotron radiation, the intensity data were collected to 1.8 A resolution. The structure was solved by molecular replacement methods, and refined to an R-factor = 18.0% for 14364 reflections by the restrained least-squares method. The final difference Fourier maps revealed that hydrolyzed inhibitor fragments bind with the protein at multiple sites around the active center of trypsin. The structural feature in the crystalline state probably corresponds to a statistical average of several complexes which would be formed between the inhibitor and trypsin during the binding and releasing process in solution.

Animals↗
PubMed1990

Biology of multifunctional cytokines: IL 6 and related molecules (IL 1 and TNF).

Interleukin 1 (IL 1), IL 6, and tumor necrosis factor (TNF) are typical examples of multifunctional cytokines involved in the regulation of the immune response, hematopoiesis, and inflammation. Their functions are widely overlapping but each shows its own characteristic properties. IL 6 was originally identified as a B cell differentiation factor, and thus one of the major functions of IL 6 is antibody induction. Transgenic mice have provided much needed information on the pathophysiological role of cytokines. With IL 6 transgenic mice, deregulation of the IL 6 expression was suggested to be involved in the generation of plasmacytoma/myeloma and mesangium proliferative glomerulonephritis. The cis-regulatory elements and trans-acting nuclear factor (or factors) for the IL 6 expression (NF-IL 6) have been identified. NF-IL 6 was shown to be a member of a C/EBP family, and the possible involvement of NF-IL 6 not only in the IL 6 regulation but also in the induction of various acute phase proteins was also observed. The findings suggest the presence of a positive regulatory loop in acute-phase reaction. IL 1 receptor belongs to an Ig superfamily, but the IL 6 receptor is a member of a newly identified cytokine receptor family. The IL 6 receptor system was shown to be composed of a ligand binding chain and a signal-transducing molecule. IL 6 was found to trigger the association of these two polypeptide chains. This unique mechanism may be applied to other cytokine receptor systems.

Animals↗
PubMed1989

Regulation of interleukin 6 receptor expression in human monocytes and monocyte-derived macrophages. Comparison with the expression in human hepatocytes.

IL-6 is a cytokine with pleiotropic biological functions, including induction of the hepatic acute phase response and differentiation of activated B cells into Ig-secreting plasma cells. We found that human peripheral blood monocytes express the IL-6-R, which is undetectable on the large majority of lymphocytes of healthy individuals. Stimulation of monocytes by endotoxin or IL-1 causes a rapid downregulation of IL-6-R mRNA levels and a concomitant enhancement of IL-6 mRNA expression. IL-6 itself was found to suppress the IL-6-R at high concentrations. A gradual decrease of IL-6-R mRNA levels was observed along in vitro maturation of monocytes into macrophages. We show that downregulation of IL-6-R mRNA levels by IL-1 and IL-6 is monocyte specific, since IL-6-R expression is stimulated by both IL-1 and IL-6 in cultured human primary hepatocytes. Our data indicate that under noninflammatory conditions, monocytes may play a role in binding of trace amounts of circulating IL-6. Repression of monocytic IL-6-R and stimulation of hepatocytic IL-6-R synthesis may represent a shift of the IL-6 tissue targets under inflammatory conditions.

Blotting, Northern↗
PubMed1989

Characterization of IL-6 receptor expression by monoclonal and polyclonal antibodies.

mAb and polyclonal antibodies against human IL-6R were prepared by using a murine transfectant cell line expressing the human IL-6R and a synthetic oligopeptide made on the basis of the deduced amino acid sequence as immunogens. Immunoprecipitation of radiolabeled IL-6R with these antibodies showed that the Mr of a mature IL-6R was 80 kDa and its value was reduced to 50K after treatment with O- and N-glycanase and neuraminidase, indicating that IL-6R is a glycoprotein. Two mAb recognizing different epitopes were prepared. One, PM1 inhibited the binding of 125I-IL-6 to the receptor and blocked the IL-6-dependent growth of a T lymphoma line, KT3. PM1 could not bind to IL-6R when it was saturated with IL-6, indicating that this antibody recognizes the IL-6 binding or the adjacent site on IL-6R. The other, MT18 was not inhibited by IL-6 for its recognition of IL-6R, therefore, this could be used for cytofluorometric staining of normal cells. Nonstimulated B cells expressed undetectable amount of IL-6R regardless of the expression of surface IgD. However, after the stimulation with PWM, IL-6R was observed on IgD- B cells with a relatively large size, but subtly on IgD- small B cells and not on IgD+ B cells, fitting the function of IL-6 which acts on activated B cells to induce Ig production. In contrast, IL-6R was detected on non-stimulated CD4+/CD8- and CD4-/CD8+ T cells. The level of IL-6R on both T cell subpopulations was not significantly changed after stimulation with phytohemagglutinin.

Antibodies, Monoclonal↗
PubMed1989

Interleukin-6 triggers the association of its receptor with a possible signal transducer, gp130.

Interleukin-6 mediates pleiotropic functions in various types of cells through its specific receptor (IL-6-R), the cDNA of which has already been cloned. We report here that an 80 kd single polypeptide chain (IL-6-R) is involved in IL-6 binding and that IL-6 triggers the association of this receptor with a non-ligand-binding membrane glycoprotein, gp130. The association takes place at 37 degrees C within 5 min and is stable for at least 40 min in the presence of IL-6, but does not occur at 0 degree C. Human IL-6-R can associate with a murine gp130 homolog and is functional in murine cells. Mutant IL-6-R lacking the intracytoplasmic portion is functional, suggesting that the two polypeptide chains interact to involve their extracellular portion. In fact, a soluble IL-6-R lacking the transmembrane and intracytoplasmic domains can associate with gp130 in the presence of IL-6 and mediate its function. These findings indicate that the complex of IL-6 and IL-6-R can interact with a non-ligand-binding membrane glycoprotein, gp130, extracellularly and can provide the IL-6 signal.

Animals↗
PubMed1989

Restriction fragment length polymorphisms on the q24-q28 region of X chromosome among Japanese population.

Restriction fragment length polymorphisms were studied among the Japanese population using 12 polymorphic DNA probes on the q24-q28 region of X chromosome. The frequency distribution for probes p22-33, p482.6a, p43-15, 52A, pPM101, cX33.2 and cpx234, was the same as that for Caucasians, and that for probes 4D-8 and St14-1 (MspI) was slightly different (p less than 0.05). However, it was quite different (p less than 0.01) for probes p114.12, St14-1 (TaqI), 36B-2 and MN12. Probe p114.12 showed no HindIII polymorphism for the Japanese people. On the contrary, probe MN12, which has a low PIC value (0.15) for Caucasians, was found to be useful for Japanese (PIC value = 0.50). These results suggest that 7 DNA probes (p482.6a, p43-15, 52A, St14-1, p114.12 (BclI), 36B-2 and MN12) are useful (PIC greater than 0.42) for linkage analysis of X-linked disease in Japan.

Blotting, Southern↗
PubMed1989

Restriction fragment length polymorphisms of X chromosome among Japanese population.

Restriction fragment length polymorphisms were studied among the Japanese using 13 polymorphic DNA probes on the X chromosome. For 6 probes (pPA4B, cpX203, p58-1, pHPGK-7e, cpX289 and 7b) the allelic frequencies were the same as those for Caucasians, but they were quite different (p less than 0.01) for 4 probes (dic56, pOTC (MspI), pTAK8B and pXG-16 (HindIII)). No polymorphisms were observed for 4 probes (pG95 alpha 1-7dIII/RI (n (chromosome number studied) = 54), pXG-16 (TaqI) (n = 50, p8 (n = 108), and pXG-17 (n = 76). These results suggest that not a small number of DNA probes currently available are useless for linkage analysis in Japan.

DNA Probes↗
PubMed1989

Restriction fragment length polymorphism analysis in healthy Japanese individuals and Japanese families with Gaucher disease.

We analysed the restriction fragment length polymorphism (RFLP) of 30 unrelated, healthy Japanese individuals and the members of seven Japanese families with Gaucher disease (5 Type I, 2 Type III) with the cDNA for human glucocerebrosidase, to investigate the frequency of the RFLP among healthy Japanese individuals and to determine the feasibility of the use of this probe DNA for carrier detection and prenatal diagnosis in Japanese families with Gaucher disease. In the Pvu II polymorphism, the common allele reported by Sorge et al was the rare allele for healthy Japanese individuals. The frequency of the common allele (+) in Japanese was 0.75 and the rare allele (-) was 0.25. The RFLP study was informative for carrier detection in the family in which both parents were heterozygous for the Pvu II polymorphism. Even in the family in which only one parent was heterozygous, carrier detection was feasible by combining the clinical history and the RFLP, although prenatal diagnosis was not feasible. The Kpn I polymorphism was not detected. It is necessary for precise carrier detection and prenatal diagnosis to investigate other restriction endonucleases which reveal the RFLP.

DNA↗
PubMed1989

A multifunctional cytokine (IL-6/BSF-2) and its receptor.

Interleukin 6 (IL-6)/B cell stimulatory factor 2 is a multifunctional cytokine produced by both lymphoid and nonlymphoid cells. IL-6 regulates immune response, acute phase reaction, and hematopoiesis. It was found that IL-6 production by T cells is dependent on macrophages, and IL-6 is one of essential factors for pokeweed mitogen induced immunoglobulin production. Both high- and low-affinity IL-6 receptors were identified. The molecular cloning of IL-6 receptors demonstrated that this receptor is a member of the immunoglobulin superfamily. The deregulated production of IL-6 is suggested to be involved in the pathogenesis of autoimmune diseases and in the development of multiple myeloma.

Animals↗
PubMed1989

Current concepts of B cell modulation.

Three interleukins with distinct functions, IL-4, IL-5 and IL-6, are involved in the regulation of B cell response into antibody producing cells. The studies with recombinant interleukins, however, demonstrated that the activities of these interleukins were not restricted to B lineage cells but showed a wide variety of biological functions on various tissues and cells. One of the most typical example of multifunctional interleukins is IL-6. It acts not only on B cells as B cell differentiation factor but also on T cells, hematopoietic stem cells, hepatocytes, nerve cells and myeloma cells. Deregulation of the expression of these interleukins was shown to be responsible for various diseases, such as i) IL-4 vs. immediate type hypersensitivity and ii) IL-6 vs. autoimmunity and multiple myelomas.

Animals↗
PubMed1988

Cloning and expression of the human interleukin-6 (BSF-2/IFN beta 2) receptor.

Interleukin-6 (IL-6/BSF-2/IFN beta 2) is a multifunctional cytokine that regulates the growth and differentiation of various tissues, and is known particularly for its role in the immune response and acute phase reactions. A complementary DNA encoding the human IL-6 receptor (IL-6-R) has now been isolated. The IL-6-R consists of 468 amino acids, including a signal peptide of approximately 19 amino acids and a domain of approximately 90 amino acids that is similar to a domain in the immunoglobulin (Ig) superfamily. The cytoplasmic domain of approximately 82 amino acids lacks a tyrosine/kinase domain, unlike other growth factor receptors.

Amino Acid Sequence↗