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Biomedical subjects

M Taniguchi

Publications and source records attributed to M Taniguchi.

At least 343 records · Page 19Linked to original sources

Absent myocardial iodine-123-BMIPP uptake and platelet/monocyte CD36 deficiency.

UNLABELLED: Global absence of myocardial 123I-15-(p-iodophenyl)-3-(R,S)-methyl pentadecanoic acid (BMIPP) uptake is occasionally noted, and it reflects myocardial long-chain fatty acid uptake abnormality. CD36, a membrane glycoprotein expressed on platelet, monocyte and endothelial cells, may contribute to myocardial fatty acid transport, and its deficiency has been reported in a small subset of the population. We hypothesized that CD36 deficiency may be related to absent myocardial BMIPP uptake. Thus, we investigated CD36 expression of platelet/monocyte in patients with absent myocardial BMIPP uptake. METHODS: Peripheral blood of 7 patients with global absence of myocardial BMIPP uptake (3 of 7 patients in one family) and 3 control subjects were examined in flow cytometric analysis. Platelet/monocyte surface CD36 was detected by using OKM5, an anti-CD36 mouse monoclonal antibody. RESULTS: There were no apparent relationships between specific clinical symptoms and absent myocardial BMIPP uptake. None of the blood samples of the 7 patients were stained with OKM5 on the platelet/monocyte cell surface, indicating that all of these patients were Type I CD36-deficient subjects. In contrast, all the control subjects showed normal staining. CONCLUSION: The fact that rare Type I CD36 deficiency was observed in all patients with absent myocardial BMIPP uptake suggests that CD36 plays a role in the myocardial long-chain fatty acid uptake process in humans.

Adult↗

Continuous and simultaneous cultivation of benthic food diatom Nitzschia sp. and abalone Haliotis sieboldii by using deep seawater.

By using low-temperature, clean, and nutrient-rich properties of deep seawater (DSW; seawater below the euphotic layer), a continuous and simultaneous cultivation system for a benthic food diatom, Nitzschia sp., and juvenile abalone was established. Cell suspension of Nitzschia sp. was added to a bioreactor made of acrylic pipe (7 cm diameter x 50 cm long) containing short vinyl tubes (2 cm diameter x 2 cm long) as substrata. DSW collected from 320 m depth at Muroto City, in Kochi Prefecture, Japan, was supplied to the reactor and incubated under natural light (ca. 6000 lux) with a continuous DSW flow rate of 40 turnovers per hour. After growing enough benthic diatoms in the reactor, juveniles of abalone, Haliotis sieboldii (shell length ca. 10-20 mm) were put into a reactor, and cultivated simultaneously with food diatoms in the continuous flow system. During the four-month incubation, 7-month-old abalone juveniles with a shell length of 12.4 (average) +/-0.2 (SD) mm were grown to 19.4 (+/-1.7) mm in the reactor. Daily growth rates of abalones were 50-110 µm/day. These results indicate that the continuous cultivation system with DSW supports the growth of juvenile abalone without any supply of seaweed until it grows to release size.

Journal Article↗

Improvement of systemic lupus erythematosus activity by the association of delayed onset Cushing's syndrome.

We describe a 43-year-old woman with systemic lupus erythematosus (SLE) who had complete resolution of all SLE symptoms as a result of hypercortisolemia induced by a glucocorticoid-producing adenoma of the left adrenal gland. After an adrenalectomy, she developed an SLE exacerbation, characterized by photosensitivity, polyarthralgia, and hemolytic anemia, which required intensive steroid therapy. This is the first report of a patient with SLE entering apparent remission due to excessive adrenal secretion of glucocorticoids.

Adult↗

A simple and sensitive bioassay for the detection of human interleukin-18/interferon-gamma-inducing factor using human myelomonocytic KG-1 cells.

Interleukin-18 (IL-18)/interferon-gamma-inducing factor (IGIF) is a novel cytokine which plays an important role in Th1 responses. Here we describe a simple, sensitive bioassay for human IL-18 using the human myelomonocytic cell line, KG-1, which produces IFN-gamma in response to human IL-18. IFN-gamma production induced by human IL-18 was completely blocked by an antibody against human IL-18. Human IL-18 could be measured in a concentration range from approximately 100 to 10,000 pg/ml, and intra- and inter-assay coefficient variations were both below 15%. It was possible to measure human IL-18 in human serum, cell lysate or culture supernatant by this bioassay. Thus, the human IL-18 bioassay can be expected to be useful in the investigation of the relationship between human IL-18 and various diseases or in analyzing the mechanisms of human IL-18 secretion from IL-18 producing cells.

Animals↗

Requirement for Valpha14 NKT cells in IL-12-mediated rejection of tumors.

A lymphocyte subpopulation, the Valpha14 natural killer T (NKT) cells, expresses both NK1.1 and a single invariant T cell receptor encoded by the Valpha14 and Jalpha281 gene segments. Mice with a deletion of the Jalpha281 gene segment were found to exclusively lack this subpopulation. The Valpha14 NKT cell-deficient mice could no longer mediate the interleukin-12 (IL-12)-induced rejection of tumors. Although the antitumor effect of IL-12 was thought to be mediated through natural killer cells and T cells, Valpha14 NKT cells were found to be an essential target of IL-12, and they mediated their cytotoxicity by an NK-like effector mechanism after activation with IL-12.

Animals↗

CD1d-restricted and TCR-mediated activation of valpha14 NKT cells by glycosylceramides.

Natural killer T (NKT) lymphocytes express an invariant T cell antigen receptor (TCR) encoded by the Valpha14 and Jalpha281 gene segments. A glycosylceramide-containing alpha-anomeric sugar with a longer fatty acyl chain (C26) and sphingosine base (C18) was identified as a ligand for this TCR. Glycosylceramide-mediated proliferative responses of Valpha14 NKT cells were abrogated by treatment with chloroquine-concanamycin A or by monoclonal antibodies against CD1d/Vbeta8, CD40/CD40L, or B7/CTLA-4/CD28, but not by interference with the function of a transporter-associated protein. Thus, this lymphocyte shares distinct recognition systems with either T or NK cells.

Animals↗

A novel pathogenesis of megacolon in Ncx/Hox11L.1 deficient mice.

The Ncx/Hox11L.1 gene, a member of the Hox11 homeobox gene family, is mainly expressed in neural crest-derived tissues. To elucidate the role of Ncx/Hox11L.1, the gene has been inactivated in embryonic stem cells by homologous recombination. The homozygous mutant mice were viable. These mice developed megacolon with enteric ganglia by age 3-5 wk. Histochemical analysis of the ganglia revealed that the enteric neurons hyperinnervated in the narrow segment of megacolon. Some of these neuronal cells degenerated and neuronal cell death occurred in later stages. We propose that Ncx/Hox11L.1 is required for maintenance of proper functions of the enteric nervous system. These mutant mice can be used to elucidate a novel pathogenesis for human neuronal intestinal dysplasia.

Animals↗

Characterization of anti-human interleukin-18 (IL-18)/interferon-gamma-inducing factor (IGIF) monoclonal antibodies and their application in the measurement of human IL-18 by ELISA.

Interleukin-18 (IL-18)/interferon-gamma-inducing factor (IGIF) is a novel cytokine, which is a potent inducer of IFN-gamma production and plays an important role in Th1 responses. In order to develop a specific ELISA for the measurement of human IL-18, we established 13 anti-human IL-18 monoclonal antibodies and characterized them. 7 murine anti-human IL-18 mAbs and 6 rat anti-human IL-18 mAbs were obtained by fusion of splenocytes from mice or rats immunized with human IL-18, with SP2/0 myeloma cells. These antibodies were classified into 4 groups according to competitive binding ELISAs to the human IL-18 molecule. 1 murine mAb and all 6 rat mAbs neutralized IFN-gamma production induced by IL-18. A specific human IL-18 ELISA was developed using two neutralizing mAbs (#125-2H and #159-12B). This ELISA detects human IL-18 with a minimum detection limit of 10 pg/ml, but does not react with heat-denatured human IL-18. The ELISA does not show any cross-reactivity with other cytokines. Using this assay, human IL-18 was measurable in the plasma of leukemia patients. This ELISA would become a powerful tool for investigating the relationship between IL-18 and various diseases or analyzing the control mechanisms of IL-18 production from IL-18 producing cells.

Adult↗

Disruption of the Bcl6 gene results in an impaired germinal center formation.

The Bcl6 gene has been identified from the chromosomal translocation breakpoint in B cell lymphomas, and its products are expressed highly in germinal center (GC) B cells. To investigate the function of Bcl6 in lymphocytes, we have generated RAG1-deficient mice reconstituted with bone marrow cells from Bcl6-deficient mice (Bcl6(-/-)RM). Lymphogenesis in primary lymphoid tissues of Bcl6(-/-)RM is normal, and Bcl6(-/-)RM produced control levels of primary IgG1 antibodies specific to T cell-dependent antigens. However, GCs were not found in these mice. This defect was mainly due to the abnormalities of B cells. Therefore, Bcl6 is essential for the differentiation of GC B cells.

Animals↗

Expression of the proliferation-related Ki-67 mRNA in the early development of murine embryo.

In a search for early lymphoid-specific genes, we isolated a cDNA clone (LL7) encoding a murine homologue of Ki-67 protein, a proliferation-related nuclear antigen. LL7 transcript appears preferentially in lymphoid organs as the bone marrow, spleen, and the thymus. Here, we studied the expression of murine Ki-67 (mKi-67) mRNA among various organs or tissues during the early development of fetus. In fetus, mKi-67 mRNA appears developmentally as early as day 11 and is expressed maximally at day 15. In situ hybridization on the section revealed that the expression of mKi-67 mRNA is preferential in the area of active organ formation such as neurological system and the fetal liver. These results suggest that mKi-67 plays an important role in the proliferation of early embryonic precursor cells of neurological and immune systems.

Animals↗

Effects of N-nitrosodimethylamine on glutathione levels during development of chick-embryo.

Glutathione content in the liver, kidney and eye of chick embryo increased during development, having the maximum at day 17 after incubation of eggs. Activity of enzymes involved in glutathione metabolism changed during development. gamma-Glutamyltransferase activity increased gradually until day 17 in the liver and eye, but decreased thereafter, while the enzyme activity increased continuously in the kidney. Glutathione reductase and glutathione peroxidase activities did not change significantly during development. Administration of N-nitrosodimethylamine (NDMA) to the fertile eggs 2 days after incubation resulted in an increase of glutathione levels in the liver and kidney at a dose of 0.01 mmol NDMA/egg, but the effect was not significant for glutathione levels by increasing the dose of NDMA. Decrease in viability and increase in formation of thiobarbituric acid (TBA) reactive substance were observed in the liver and kidney by administration of NDMA at 0.1 mmol/egg. By administration of buthionine sulfoximine (BSO) alone, viability and glutathione levels were decreased and TBA reactive substance was increased in the liver. Fatal toxicity of NDMA was observed especially when BSO was administered together with NDMA. These results indicate that glutathione plays an important role in protecting chick embryos against toxic effects induced by administration of NDMA.

Animals↗

CYP1A1, CYP2E1 and GSTM1 polymorphisms are not associated with susceptibility to squamous-cell carcinoma of the esophagus.

We investigated the genetic polymorphisms of CYP1A1, CYP2E1 and GSTM1 in Japanese esophageal cancer patients (n = 53) with a histological diagnosis of squamous-cell carcinoma, to determine whether susceptibility to esophageal cancer is associated with these polymorphisms. There were no significant differences in the frequency distribution of any one of the 3 polymorphisms between esophageal cancer patients and 132 healthy Japanese controls. The genotype distributions in tobacco smokers or alcohol drinkers were also quite similar for male patients and male controls. The age at onset of esophageal cancer was also similar for patients with any genotype of the 3 polymorphisms. We conclude that the 3 polymorphisms are unlikely to be associated with esophageal cancer susceptibility.

Adult↗

Phenotypes and invariant alpha beta TCR expression of peripheral V alpha 14+ NK T cells.

A novel subset of peripheral T cells, peripheral NK T cells, is found to be a major population comprising 5% of splenic T and 40% of bone marrow T cells. The majority of peripheral NK T cells are characterized by the expression of an invariant TCR-alpha encoded by V alpha 14/J alpha 281 with a one nucleotide N region. Moreover, a specific reduction of V alpha 14+ NK T cells has been demonstrated to be tightly associated with various autoimmune diseases, indicating their decisive role in autoimmune disease development. In this study, we investigated the phenotypes of peripheral V alpha 14+ NK T cells and their TCR-beta repertoire. Peripheral V alpha 14+ NK T cells, comprise two populations, i.e., small and large sized cells, at an equal frequency, belonged to the CD4- CD8- fraction, and are heat stable antigen(bright), macrophage-1bright, B220bright, CD45RBdim, and Mel-14dim, but CD5-, distinct from thymic NK T cells. TCR-beta analysis clearly showed that peripheral V alpha 14+ NK T cells utilized two to three dominant invariant TCR-beta, such as V beta 8.2 D beta J beta 2.5/V beta 7 D beta J beta 2.1 in the spleen and liver, V beta 8.2 D beta J beta 2.5/V beta 8.3 D beta J beta 2.2/V beta 7 D beta J beta 2.6 in the bone marrow, and V beta 7 D beta J beta 2.1/V beta 3 D beta J beta 1.2 in intestinal intraepithelial lymphocytes. Judging from the unusual surface phenotypes, such as heat stable antigen, macrophage-1, B220, CD45RBdim, and Mel-14dim, which are known to be T cell activation markers, peripheral V alpha 14+ NK T cells may always be activated under physiologic conditions, resulting in the oligoclonal expansion of V alpha 14+ NK T cells with different invariant TCR-beta in different peripheral organs. The unique features of V alpha 14+ NK T cells are discussed.

Amino Acid Sequence↗

Inhibitory effects of nucleoside 5'-alkylphosphates on sexual agglutination in Saccharomyces cerevisiae.

Among various nucleoside 5'-alkylphosphates, uridine 5'-hexadecylphosphate (UMPC16) and adenosine 5'-hexadecylphosphate (AMPC16) inhibited the sexual agglutination between a and alpha haploid cells of Saccharomyces cerevisiae. The effect of AMPC16 accompanied severe growth inhibition of the yeast cells but it was not observed with UMPC16. Sexual agglutination was not inhibited by the presence of UMPC16 or AMPC16 when the yeast cells had been pretreated with the mating pheromone. UMPC16 was characterized as a specific inhibitor of sexual agglutination without direct influence on the agglutinin function, being distinguishable from any of those ever known.

Adenine Nucleotides↗

Accumulation of somatic hypermutation and antigen-driven selection in rapidly cycling surface Ig+ germinal center (GC) B cells which occupy GC at a high frequency during the primary anti-hapten response in mice.

Well-developed germinal centers (GC) contain rapidly dividing surface immunoglobulin-negative (sIg-) B cells (centroblasts), and most of their progeny are sIg+ B cells (centrocytes) in a resting state. It has been predicted that somatic hypermutation occurs in centroblasts, whereas antigen-driven selection takes place in centrocytes. The present analysis indicates that murine GC B cells bearing sIg with specificity for an immunizing antigen are in a rapidly cycling state and increase exponentially in number to occupy spleen GC at high frequency during the 1st week after primary immunization; however, the number of these cells is significantly reduced in the 2nd week of immunization. During that period, these proliferating sIg+ GC B cells accumulate somatic hypermutations with nucleotide exchanges indicative of affinity maturation. These sIg+ GC B cells co-express B7-2, ICAM-1, and LFA-1, and have potent antigen-presenting activity which results in T cell activation in vitro. These observations indicate that the sIg+ GC B cells accumulate somatic hypermutations and undergo antigen-driven selection through proliferation, probably upon activation by T cells. This sIg+ GC B cell population may represent cell cycling centrocytes; however, the possibility that these may represent centroblasts undergoing re-expression of sIg could not be excluded.

Amino Acid Sequence↗

Crystallization and preliminary X-ray analysis of human D-dopachrome tautomerase.

D-Dopachrome tautomerase catalyzes the conversion of D-dopachrome to 5,6-dihydroxyindole. This protein has amino acid sequence homology with that of macrophage migration inhibitory factor (MIF), suggesting a pathophysiological role of this protein in inflammatory and immunological events. We previously determined the tertiary structure of MIF and revealed the functional and evolutional relationships of this protein to isomerase. However, the reaction mechanism of both proteins associated with the inflammatory response, immune system, or tautomerase activities in vitro have not yet been clarified. The tertiary structure of D-dopachrome tautomerase would provide insight into the molecular function and the mechanism of these proteins. In this study, we crystallized human D-dopachrome tautomerase by a hanging-drop vapor diffusion method. The crystals belong to the trigonal space group P3, with unit cell dimensions a = b = 84.2 A and c = 41.0 A. They contain three (or two) monomers in the asymmetric unit, corresponding to a VM value of 2.21 (or 3.32) A3 Da-1. The best crystals diffract X-ray to 1.6 A resolution using a synchrotron radiation source. Crystallization of the selenomethionyl derivative of the protein for applying the multiwavelength anomalous diffraction method was also successful.

Chromatography, Gel↗

Establishment of internal-image anti-idiotype monoclonal antibodies to a human antibody to lung cancer.

Internal-image anti-idiotype antibodies are expected to enhance anticancer effector mechanisms in vivo. The objective of this study was to establish hybridomas producing anti-idiotype monoclonal antibodies against a human monoclonal antibody (hmAb) 4G12 that reacts strongly with lung squamous cell carcinomas. BALB/c female mice 6 weeks old were immunized with 4G12. Splenocytes were hybridized with P3U1 cells and hybrid cells secreting anti-4G12 hmAb were cloned. Two clones reacted with 4G12 hmAb but not with 3H12 IgM hmAb, human IgM, human serum or fetal calf serum. These two Ab2 antibodies (IgG1 kappa) 2B12 and 2H1 demonstrated 91.5% and 90.3% inhibition in their reactivity with radiolabelled 4G12 on PC10 cells, indicating that 2B12 and 2H1 antibodies were of the Ab2 beta type. In criss-cross inhibition assays, the binding of 2B12 or 2H1 to 4G12 was not inhibited by 2H1 or 2B12. Thus 2B12 and 2H1 were thought to recognize the different epitopes on the antigen-binding sites. Antisera against 2B12 and 2H1 demonstrated specific reactivity to PC10 cells. The two Ab2 beta antibodies, 2B12 and 2H1, express internal images of lung squamous cell carcinoma recognized by the 4G12 antibody and may be useful for cancer immunotherapy.

Animals↗