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Biomedical subjects

K Tadokoro

Publications and source records attributed to K Tadokoro.

At least 181 records · Page 10Linked to original sources

Myeloproliferative disorder due to abnormal production of hematopoietic stimulators.

A new kind of myeloproliferative disorder (L-8313) has been discovered. It was transplantable into syngeneic mice with spleen cells. The mice showed hepato-splenomegaly with a marked leukocytosis and anemia 3 weeks after transplantation of L-8313 cells. The number of GM-CFU and CFU-S per spleen increased to more than 40 times normal. The results of chromosomal and PGK analysis demonstrated that these increased stem cells were of host origin. Both the culture medium of the spleen cells and the serum from L-8313 bearing mice showed high levels of IL-3, BPA and CSF. Consequently, hematopoietic cells of the host mice underwent remarkable proliferation in response to these stimulating factors when L-8313 cells were transplanted. We also have been successful in establishing an in-vitro cell line and have maintained it for over one year. The phenotype of L-8313 cells was Thy 1.2 positive. Some L-8313 cells showed a positive acid phosphatase reaction but the cytochemical character of myeloid lineage was not observed. Therefore, L-8313 is considered to be a T-cell derived hematopoietic regulatory cell neoplasm with the ability to produce several hematopoietic stimulating factors.

Anemia↗

Diesel-exhaust particulates inoculated by the intranasal route have an adjuvant activity for IgE production in mice.

Our previous study indicated that the IgE antibody responses in mice immunized with intraperitoneal injection of the antigens mixed with diesel-exhaust particulates (DEP) were higher than those in the animals immunized with the antigens alone. We examined the adjuvant activity of DEP inoculated by the intranasal route, i.e., the natural entrance of DEP. In 3-week interval immunization, the IgE antibody responses in mice immunized with intranasal inoculation of ovalbumin (OA) mixed with DEP were higher than responses in the animals immunized with OA alone. DEP had an adjuvant activity for anti-OA IgE antibody production, even in a small dose such as 1 micrograms administered with a 3-week interval. Also in 1-week interval immunization, the enhancing effect of DEP on anti-OA IgE antibody production was demonstrated when mice were immunized with intranasal inoculation of OA and DEP. The possibility cannot be excluded that DEP, which are kept buoyant in the environmental atmosphere of urban districts, may exert an adjuvant activity for IgE antibody production after being inhaled into the human body and have some relation to the mechanism of the outbreak of allergic rhinitis caused by pollens in Japan.

Adjuvants, Immunologic↗

Characterization of leukotriene A4 synthase from murine mast cells: evidence for its identity to arachidonate 5-lipoxygenase.

Leukotriene A4 synthase was purified from the cytosolic fraction of murine mast cells. The enzyme converted 5-hydroperoxy-6-trans-8,11,14-cis-icosatetraenoic acid (5-HPETE) to leukotriene A4. This unstable product was identified by demonstration of two epimers of 6-transleukotriene B4, methanol trapping, as well as further transformation to leukotriene B4 by leukotriene A4 hydrolase. Leukotriene A4 synthase stereospecifically eliminated the D-hydrogen at C-10 (pro-R) in the synthesis of leukotriene A4 when incubated with [10D-3H;3-(14)C]5-HPETE. The purified enzyme also exhibited 5-lipoxygenase activity toward arachidonic acid and 8-lipoxygenase activity towards 8,11,14-cisicosatrienoic acid. All of these activities required Ca2+ and ATP for their maximal velocities. The effects of heat treatment and of several lipoxygenase inhibitors on these enzyme activities as well as coelution in various chromatographic systems strongly suggest that lipoxygenase and leukotriene A4 synthase activities reside in the same enzyme molecule.

Animals↗

IgE antibody-mediated shock reaction caused by topical application of chlorhexidine.

A case of an anaphylactic shock following topical application of chlorhexidine preparation is reported. Specific skin-sensitizing antibodies against chlorhexidine were demonstrated in the serum from the patient by a passive transfer test. IgE antibodies against chlorhexidine were also detected by radioallergosorbent technique (RAST). Paper discs conjugated with chlorhexidine-HSA (human serum albumin) significantly bound the IgE antibodies. Furthermore, all of the sera from seven other patients with shock reactions following the topical application of chlorhexidine preparation also showed high RAST counts. Both chlorhexidine gluconate and chlorguanide which represents approximately half a molecule of chlorhexidine inhibited the reaction in a dose-dependent fashion. It is suggested that the shock reactions following topical application of chlorhexidine are mediated by IgE antibodies against chlorhexidine and that chlorhexidine and chlorguanide share the same antigenic determinant.

Administration, Topical↗

Hypersensitivity caused by synthetic thyroid hormones in a hypothyroid patient with Hashimoto's thyroiditis.

A 63-year-old hypothyroid woman with Hashimoto's thyroiditis developed fever, eosinophilia, and liver dysfunction in response to replacement doses of triiodothyronine, or L-thyroxine. The symptoms disappeared on cessation of the replacement therapy. Lymphocyte stimulation tests showed high stimulation indexes for both hormones. After an interval of four months, when the patient became severely hypothyroid, treatment with triiodothyronine on a slowly increasing dose program was tried and resulted in a good control without ill response at this time. This observation indicates that, under certain pathologic conditions, hypersensitivity may be induced to thyroid hormones administered exogenously.

Drug Hypersensitivity↗

Evidence for the existence of isozymes of choline kinase and their selective induction in 3-methylcholanthrene- or carbon tetrachloride-treated rat liver.

New evidence is provided that rat liver choline kinase exists in several distinct forms (choline kinases I, II and III) which differ in isoelectric point, molecular size and antigenicity against anti-rat kidney choline kinase IgG. Remarkable and selective induction of the choline kinase II and choline kinase III forms of choline kinase was caused similarly by the administration of polycyclic aromatic hydrocarbon carcinogen, 3-methylcholanthrene or hepatotoxic carbon tetrachloride (CCl4). The immunochemical approach further indicated that the elevation in the activity of choline kinase in the 3-methylcholanthrene- or CCl4-treated rat liver was not accompanied by a parallel increase in the amount of choline kinase II enzyme protein, compatible with the induction of either a small amount of new enzyme protein(s) with very high specific activity or another enzyme which might catalyze post-translational modification of choline kinase.

Animals↗

Evidence for the existence of multiple forms of choline (ethanolamine) kinase in rat tissues.

In order to characterize the form of choline kinase in rat tissues, both electrophoretic and gel chromatographic patterns of choline kinase activity were compared in the liver, kidney, lung, whole intestine and carbon tetrachloride-induced liver cytosols. Kinetic parameters of the reaction were also compared for the main forms of choline kinase protein from these tissues. The overall results suggested strongly that choline kinase does not exist in one particular active form but exists in multiple forms in rat tissues. In the study present here, the electrophoretic patterns of both choline kinase and ethanolamine kinase activities were compared in rat liver, kidney, lung and intestinal cytosols. The results strongly supported the view that both kinase activities are represented on the same enzyme protein(s) in each of the rat tissues examined.

Animals↗

Distinction of the human basophil promoting activity from human interleukin-3.

Lectin-stimulated supernatants of human peripheral blood leukocytes (PBL) contained an activity that maintained the long-term growth of murine interleukin-3 (IL-3) dependent cell lines such as the 32 Dcl line. We compared this human IL-3 activity with the basophil promoting activity (BaPA) recently described by us. Besides lectin-stimulated PBL supernatants that contained both BaPa and IL-3, we found that BaPA was produced mainly by E rosette-positive T cells or the human Mo T cell line, while IL-3 was produced by human T hybridomas and, more interestingly, by human macrophage cell lines. Based on molecular weight (BaPA: 20-30 kilodaltons, IL-3: 15-19 kilodaltons) as well as on molecular charge (BaPA: pI = 6.1-7.5, IL-3: 4.9-6.2), we concluded that human IL-3 and BaPA are distinct factors.

Basophils↗

Clonal analysis of basophil differentiation in bone marrow cultures from a Down's syndrome patient with megakaryoblastic leukemia.

We present the in vitro differentiation of marrow cells from a patient with Down's syndrome accompanied by megakaryoblastic leukemia into basophils in the presence of phytohemagglutinin-stimulated leukocyte conditioned medium, using a liquid culture and methylcellulose culture system. Identification of basophils was established by metachromatic staining with toluidine blue, transmission electron microscopy, and the presence of histamine. However, these basophils did not release histamine in response to calcium ionophore or chemotactic peptide. Samples from suspension cultures that contained 90% basophils showed chromosomal markers characteristic of leukemic cells (48, XY, +11, +21, t(1;15)) in all examined mitoses. The cellular composition of leukemic colonies grown in methylcellulose culture from single cells was studied using the micromanipulation technique. High plating efficiency and extreme predominance of basophil colonies were observed. In a total 137 cultures, 79 revealed colony growth. Of 59 colonies that were analyzed by cytologic examination, 46 were pure basophil colonies. These basophil colonies showed disperse morphology, similar to that of a normal basophil colony. The clonality of the basophil colonies and skewing of lineage expression were documented from leukemic single-cell cultures. These data showed that leukemic cells have the capacity for differentiation into some lineages that are not expressed in vivo.

Basophils↗

Factor-dependent in vitro growth of human normal bone marrow-derived basophil-like cells.

A factor(s) present in supernatants from lectin-stimulated peripheral blood mononuclear cells promoted the production of basophil-like cells in liquid cultures of normal human bone marrow cells. The cultured basophil-like cells had lobulated or round nuclei, and the cytoplasmic granules stained metachromatically with toluidine blue and azurophilic with Giemsa. 20% of the metachromatically staining cells were peroxidase positive but not positive for nonspecific esterase. The histamine content was 0.5-2 pg/cell. The basophil-like cells released histamine upon challenge with calcium ionophore A23187 but not with compound 48/80. They also released histamine with anti-IgE when passively sensitized with human myeloma IgE. The development of basophil-like cells was promoted in a dose-dependent fashion by a factor(s) in the conditioned medium. Blocking of cell proliferation with hydroxyurea or X irradiation inhibited the development of basophil-like cells. The production of the factor was dependent on the presence of T cells. The factor was different from interleukin 2 and its molecular weight was estimated to be 25,000-40,000 by gel filtration on a Sephacryl S-200 column. Thus, human basophil-like cells derived from normal bone marrow cells can grow and differentiate in vitro under the regulation of T cells.

Basophils↗