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Biomedical subjects

Y Kohno

Publications and source records attributed to Y Kohno.

At least 253 records · Page 14Linked to original sources
PubMed1989

Comparative pharmacokinetics of clarithromycin (TE-031), a new macrolide antibiotic, and erythromycin in rats.

Clarithromycin (TE-031) is a newly synthesized macrolide with high stability in acidic conditions. In the present study, the pharmacokinetics of [N-methyl-14C]clarithromycin were compared with those of [N-methyl-14C]erythromycin in rats by radioassay and bioassay. Both radioactivity and bioactivity of [14C]clarithromycin in plasma and tissues were found to be significantly higher than those of [14C]erythromycin at the same oral dose of 20 mg/kg (body weight). Among the tissues, the peak level of [14C]clarithromycin in the lung was especially high. Levels of radioactivity and bioactivity amounted to 15 and 73 times the corresponding levels of [14C]erythromycin. In the urine, bioactivity recovered after administration of [14C]clarithromycin was sevenfold higher than that for [14C]erythromycin. This accounted for about 60 and 20% of the total radioactivity in the urine for [14C]clarithromycin and [14C]erythromycin, respectively. An examination of metabolites in the urine for [14C]clarithromycin revealed appreciable amounts of bioactive unchanged clarithromycin. These results indicate that clarithromycin has pharmacokinetic properties superior to those of erythromycin. The desirable properties of clarithromycin include high levels in plasma resulting from its high stability in gastric acid; a high tissue affinity, especially to the lung; and favorable urinary excretion.

Administration, Oral↗
PubMed1989

Stereochemical studies on the formation of melanin by monophenol monooxygenase.

The oxidation of tyrosine by monophenol monooxygenase (tyrosinase: EC 1.10.3.1) to melanin has been studied by a combination of ultraviolet, circular dichroism, and nuclear magnetic resonance techniques. It is demonstrated that the chiral intermediate (dopachrome) is generated stereoselectively in this enzymic reaction.

Catechol Oxidase↗
PubMed1989

[Penetration of clarithromycin to saliva and its effect on normal salivary bacterial flora].

Clarithromycin (TE-031, A-56268), a new macrolide antibiotic, was administered to rats, and the distribution of the drug in the submandibular gland was studied using microautoradiography. The study revealed good accumulation of 14C-TE-031 in both the acini and the excretory ducts. TE-031 was administered to each of 3 healthy male volunteers in a single dose of 300 mg, and its concentrations in the serum and saliva was detected. Mean values of various pharmacokinetic parameters were as follows for the serum and saliva, respectively. Cmax 1.49 micrograms/ml and 1.93 micrograms/ml; Tmax 2.91 hours and 2.66 hours; T 1/2 6.31 hours and 4.15 hours; AUC 18.58 micrograms.hr/ml and 17.70 micrograms.hr/ml. Regarding the salivary bacterial flora, the total bacterial count decreased as the salivary TE-031 concentration increased, but it recovered to the initial level in 12 hours after administration. During the 24-hour period following an administration of TE-031, the salivary bacteria did not acquire resistance to the drug. Therefore, TE-031 is an antibiotic which exerts little effect on the normal salivary bacterial flora in short-term administration. Although the results differed among the individuals, the penetration of TE-031 to saliva was superior to that to the serum. Thus, TDM of TE-031 using salivary samples is possible.

Animals↗
PubMed1989

Anti-thyroid peroxidase antibody activity in sera of patients with systemic lupus erythematosus.

Although patients with SLE have autoantibodies to thyroid peroxidase (TPO), IgG from sera of SLE patients does not inhibit TPO activities, in contrast with IgG from sera of patients with thyroid disorders. This finding suggests that the specificities of anti-TPO autoantibodies in SLE are different from those in cases of thyroid disorders. These autoantibodies to TPO should be considered when searching for associations between SLE and autoimmune thyroid disorders.

Adolescent↗
PubMed1988

Kinetic study of the reaction between vitamin E radical and alkyl hydroperoxides in solution.

Kinetic study of the reaction between vitamin E radical and alkyl hydroperoxides has been performed, as a model for the reactions of lipid hydroperoxides with vitamin E radical in biological systems. The rates of reaction of hydroperoxides (n-butyl hydroperoxide 1, sec-butyl hydroperoxide 2, and tert-butyl hydroperoxide 3) with vitamin E radical (5,7-diisopropyl-tocopheroxyl 4) in benzene solution have been determined spectrophotometrically. The second-order rate constants, k-1, obtained are 1.34 x 10(-1) M-1s-1 for 1, 2.42 x 10(-1) M-1s-1 for 2, and 3.65 x 10(-1) M-1s-1 for 3 at 25.0 degrees C. The result indicates that the rate constants increase as the total electron donating capacity of the alkyl substituents at alpha-carbon atom of hydroperoxides increases. The above rates, k-1, are about seven order of magnitude lower than those, k1, for the reaction of vitamin E with peroxyl radical.

Alkylation↗
PubMed1988

Autoimmune thyroiditis induced in mice depleted of particular T cell subsets. I. Requirement of Lyt-1 dull L3T4 bright normal T cells for the induction of thyroiditis.

T cell-depleted C3H/He or (C57BL/6xC3H/He)F1 (B6C3F1) mice were prepared by adult thymectomy and injection of antithymocyte serum, followed 3 wk later by lethal x-irradiation and bone marrow reconstitution. When these T cell-depleted mice were not injected or injected i.v. with normal spleen and lymph node cells treated with either anti-Thy-1, -L3T4 or -Lyt-2 antibody plus C or C alone, none of the groups of mice developed thyroiditis. In contrast, the adoptive transfer of normal cells treated with anti-Lyt-1 plus C resulted in high incidence of the production of antithyroglobulin antibody and the induction of typical thyroiditis lesion. The thyroid was the sole organ involved, because neither typical inflammatory lesion in other organs nor autoantibody such as anti-DNA antibody was detected in mice that exhibited thyroiditis. Analyses of surface phenotypes of cells required for inducing thyroiditis by the adoptive transfer revealed that an appreciable percentage of Lyt-1 dull T cells remained after the treatment of normal lymphoid cells with anti-Lyt-1 plus C. Almost all of these Lyt-1 dull T cells expressed magnitudes of L3T4 or Lyt-2 Ag comparable to those detected on Lyt-1 bright T cells. More important, the induction of thyroiditis was almost completely prevented by either in vitro or in vivo elimination of Lyt-1 dull L3T4+(bright) but not of Lyt-1 dull Lyt-2+(bright) T cells. These results indicate that Lyt-1 dull L3T4+ T cells existing in normal healthy individuals have potential to induce typical thyroiditis which is associated with the production of antithyroglobulin autoantibody, and that the activation and/or function of this T cell subset is regulated by the Lyt-1 bright T cell population coexisting in normal lymphoid cell population.

Animals↗
PubMed1988

[Characterization of thyroglobulin and thyroid peroxidase activity in patients with functioning thyroid benign tumors].

The content and chemical and immunological properties of thyroglobulin (Tg) and the activity of thyroid peroxidase (TPO) were studied in nodular and extranodular (periphery) thyroid tissue from patients with functioning thyroid tumors (hot nodules). From the present observations, the tumor extracts contained fairly large amounts of Tg, similar to that in the periphery tissue, while the content of Tg was markedly decreased in non-functioning thyroid tumors (cold nodules). The iodine content of Tg was significantly higher in nodular tissue compared with periphery tissue. These observations were in contrast to the results seen in the cold nodules in which hormone synthesis was defective. On the nature of carbohydrate moiety as compared with normal tissue, oligosaccharides of Tg from the periphery tissues changed in a manner similar to that of tumor oligosaccharides. That is, high-mannose type oligosaccharides were markedly decreased whereas multiantennary and unidentified oligosaccharides were increased. These observations were similar to those of non-functioning tumors. The content of sialic acid decreased markedly both in the tumor and periphery tissues. Immunologically, Tg preparations of the tumor and periphery tissue did not show the same affinity to the antibodies, depending on the content of iodine. Therefore, it seems that the contribution of the iodine content and iodo-amino acid has little or no significance in the heterogeneous nature of Tg-immunogenecity. Benign tumors and the periphery tissue were subjected to assay for thyroid peroxidase activity by the method employing guaiacol as the second substrate. The specific activities of the tumors were generally higher than those of periphery tissues, both in functioning and non-functioning benign tumors. In non-functioning carcinoma, on the other hand, TPO activities were lower in tumor portions than in periphery portions. This indicates that non-functioning thyroid carcinomas have a different characteristic.

Adenoma↗
PubMed1988

Retardation of the development of hypertension in DOCA salt rats by taurine supplement.

To study the antihypertensive effect of orally administered taurine in DOCA salt hypertension, urinary excretion of catecholamines, electrolytes, and arg-vasopressin was measured over four weeks in 20 taurine treated DOCA rats (group 1), 20 taurine untreated DOCA rats (group 2), and seven taurine untreated sham operated rats (group 3). Additional experiments were performed to determine whether or not the pressor and sympathetic responses to hypothalamic stimulation were altered after taurine treatment in DOCA rats. Systolic blood pressure decreased significantly in group 1 after the first week compared with that in group 2, and the differences became progressively more evident thereafter. At the fifth week the mean blood pressure was significantly lower in group 1 than in group 2, as was the heart rate. Although urinary excretion of adrenaline decreased significantly in group 1 at the first and fourth weeks, the difference in urinary excretion of noradrenaline between groups 1 and 2 was not significant. Urinary excretion of adrenaline and noradrenaline in group 3 was significantly lower than that in both hypertensive groups (groups 1 and 2). Urinary sodium excretion increased significantly in group 1 at the first and second week compared with group 2. With graded electrical stimulation of the ventromedial hypothalamus, resulting pressor and sympathetic responses were significantly smaller in group 1 than in group 2. These results suggest that the hypotensive effects of orally administered taurine in DOCA hypertensive rats are caused by suppression of the peripheral sympathetic nervous activity and by the resulting natriuresis.

Animals↗
PubMed1988

Enhanced thyroid iodine metabolism in patients with triiodothyronine-predominant Graves' disease.

Some patients with hyperthyroid Graves' disease have increased serum T3 and normal or even low serum T4 levels during treatment with antithyroid drugs. These patients with elevated serum T3 to T4 ratios rarely have a remission of their hyperthyroidism. The aim of this study was to investigate thyroid iodine metabolism in such patients, whom we termed T3-predominant Graves' disease. Mean thyroid radioactive iodine uptake was 51.0 +/- 18.1% ( +/- SD) at 3 h, and it decreased to 38.9 +/- 20.1% at 24 h in 31 patients with T3-predominant Graves' disease during treatment. It was 20.0 +/- 11.4% at 3 h and increased to 31.9 +/- 16.0% at 24 h in 17 other patients with hyperthyroid Graves' disease who had normal serum T3 and T4 levels and a normal serum T3 to T4 ratio during treatment (control Graves' disease). The activity of serum TSH receptor antibodies was significantly higher in the patients with T3-predominant Graves' disease than in control Graves' disease patients (60.5 +/- 19.2% vs. 20.4 +/- 18.2%; P less than 0.001). From in vitro studies of thyroid tissue obtained at surgery, both thyroglobulin content and iodine content in thyroglobulin were significantly lower in patients with T3-predominant Graves' disease than in the control Graves' disease patients. Thyroid peroxidase (TPO) activity determined by a guaiacol assay was 0.411 +/- 0.212 g.u./mg protein in the T3-predominant Graves' disease patients, significantly higher than that in the control Graves' disease patients (0.129 +/- 0.112 g.u./mg protein; P less than 0.01). Serum TPO autoantibody levels determined by immunoprecipitation also were greater in T3-predominant Graves' disease patients than in control Graves' disease patients (52.6 +/- 27.7% vs. 32.4 +/- 11.4%; P less than 0.05). Binding of this antibody to TPO slightly inhibited the enzyme activity of TPO, but this effect of the antibody was similar in the two groups of patients. The data suggest enhanced iodine metabolism in the thyroid gland of patients with T3-predominant Graves' disease, which may relate to the discordant T3 overproduction in patients with this type of Graves' disease.

Adolescent↗
PubMed1988

Antigenic determinants on thyroglobulin: comparison of the reactivities of different thyroglobulin preparations with serum antibodies and T cells of patients with chronic thyroiditis.

To delineate the antigenic determinants on thyroglobulin (Tg) recognized by serum autoantibodies and peripheral blood T cells from patients with chronic thyroiditis, we studied the reactivities of three different Tg preparations, i.e. enzyme-digested Tg fragments, physically or chemically denatured Tg, or Tg with differing iodine contents. Human Tg was digested with staphylococcal V8 protease, and the fragments were separated by high performance liquid chromatography. The autoantibodies reacted with the larger fragments, but their ability to bind to small fragments was limited. On the other hand, T cells reacted similarly with all fragments, regardless of mol wt. The autoantibodies bound little to denatured Tg after its disulfide bonds were destroyed with dithiothreitol or 2-mercaptoethanol, while the reactivity of heat-denatured Tg was partially decreased, and that of Tg denatured with sodium dodecyl sulfate was conserved. Conversely, T cells reacted with Tg denatured by heating or dithiothreitol treatment. These results indicate that autoantibodies recognize mainly a conformational structure of Tg, presumably containing disulfide bonds, whereas T cells recognize the primary structure of Tg. Variations in the iodine content of Tg were not associated with altered reactivity with autoantibodies or T cells. We propose that variations in Tg conformation related to iodination of the molecule do not contribute significantly to its reactivity with autoantibodies and T cells. In addition, T cells reacted with the smaller Tg fragments containing few T3 or T4 residues to a greater extent than they did with larger Tg fragments with the same amount of T3 or T4 as native Tg. Therefore, it appears that the Tg-reactive T cells predominantly recognize determinants on the Tg molecule that are unrelated to hormone-containing sites.

Adolescent↗
PubMed1988

Thyroglobulin and thyroid peroxidase share common epitopes recognized by autoantibodies in patients with chronic autoimmune thyroiditis.

Monoclonal antibodies specific for human thyroid peroxidase (TPO) were prepared by the hybridoma technique using hyperimmune spleen cells from mice immunized with TPO purified from thyroid glands from patients with Graves' disease. Use of the microenzyme-linked immunosorbent assay method revealed that some of the monoclonal antibodies cross-reacted strongly with human thyroglobulin (Tg). Conversely, monoclonal anti-Tg antibodies cross-reacted with TPO, albeit to a lesser degree. Some anti-Tg autoantibodies in serum from patients with chronic autoimmune thyroiditis purified by Tg affinity chromatography bound TPO, and such binding was completely inhibited by Tg. Western blotting experiments revealed that thyroid microsomal 103K proteins recognized by mouse monoclonal and polyclonal anti-TPO antibodies were recognized by some monoclonal anti-Tg antibodies and anti-Tg autoantibodies, and conversely, that 19S Tg was recognized by some monoclonal anti-TPO antibodies. TPO was immunoprecipitated by anti-Tg autoantibodies isolated by Tg affinity chromatography. On the other hand, the specificity for TPO of the anti-Tg autoantibodies was not identical with that of anti-TPO autoantibodies. These cross-reactivities were not due to contamination of TPO with Tg or vice versa, or to contamination of the anti-Tg autoantibody preparations with anti-TPO autoantibodies. Taken together, these data indicate that Tg and TPO share common antigenic determinants and that some of those determinants are recognized by autoantibodies in the serum of patients with chronic autoimmune thyroiditis.

Adolescent↗
PubMed1988

[Bone marrow scintigraphy with 111In-chloride--a clinical value for the hematological diseases].

Bone marrow scintigraphy with indium chloride (111In) was performed in fifty-one patients with the hematological diseases. The results of the investigation were that 1. in all patients, as well as in patients with aplastic anemia, no correlation was there between the degree of the indium chloride accumulation and peripheral blood counts, 2. in patients with aplastic anemia and pure red cell aplasia (PRCA) a tendency to reduction in uptake of indium chloride in bone marrow, 3. in patients with these two good correlation between the degree of indium chloride accumulation and histology of the erythroid bone marrow, but in patients with chronic myelocytic leukemia (CML) and atypical leukemia no correlation between the two, so it seemed unlikely that indium chloride should reflect the effective production of erythrocytes, 4. four patients with leukemia were studied with indium chloride bone marrow imaging two times to evaluate their responses to chemotherapy, and peripheral expansion was no change or reduced in two patients with acute myelocytic leukemia (AML) and one patient with acute lymphocytic leukemia (ALL) who obtained complete remission, but on the other hand, it enlarged in one patient with acute myelocytic leukemia who obtained partial remission, and 5. in two patients with chronic myelocytic leukemia it enlarged up to the ankle joints, which was considerably specific.

Acute Disease↗
PubMed1988

[An analysis of regional ventilation in pulmonary sarcoidosis by inspired 133Xe washout test].

Xenon-133 ventilation study were used to measure regional ventilation in seven patients with pulmonary sarcoidosis and in four normal subjects. For the purpose of analyzing the washout curves on the whole lungs, two ventilation indexes were calculated, which were TA/H and T1/2. TA/H is that the area under the curve divided by the difference in mean count rate during equilibrium and at 120 s after washout started. T1/2 value represents the time required to 50% of the mean count rate during equilibrium. The average time of TA/H on the whole lung was 13.5 +/- 1.1 s in normal subjects (n = 4), 13.0 +/- 4.3 s in stage I (bilateral hilar lymphadenopathy without lung involvement on chest X-ray) sarcoidosis (n = 3), 21.3 +/- 1.8 s in stages I, II (lung involvement) sarcoidosis (n = 4). The average time of T1/2 on the whole lung was 43.7 +/- 4.7 s in normal subjects, 42.3 +/- 16.0 s in stagel sarcoidosis, 72.5 +/- 28.6 s stages II, III sarcoidosis. The ventilation indexes on the regional lungs showed almost a similar tendency to that on the whole lung. The ventilation indexes in patients with stage II, III sarcoidosis were significantly longer than in normal subjects and in patients with stage I sarcoidosis. It was suggested that 133Xe washout test might detect regional ventilation abnormalities which were not recognized on chest X-ray in pulmonary sarcoidosis.

Aged↗
PubMed1987

Imbalance among T-cell subsets in patients with coronary arterial aneurysms in Kawasaki disease.

The populations of T cells were studied in 46 patients with Kawasaki disease, separated into 2 groups: group I--11 patients with coronary aneurysms; and group II--35 patients with normal coronary arteries. Patients from both groups with early acute illness, before day 5, had a significant reduction in the population of OKT3+ (p less than 0.001), OKT4+ (p less than 0.02) and OKT8+ cells (p less than 0.002), but normal OKT4/OKT8 ratios compared with age-matched control subjects. These abnormal values quickly returned to normal levels during week 2 in patients with normal coronary arteries. In contrast, patients in whom coronary aneurysms developed within 3 weeks of the onset had an imbalance between OKT4 and OKT8 during week 2, characterized by a decrease in the number of OKT8+ cells and an increase in the number of OKT4+ cells, resulting in a high OKT4/OKT8 ratio (p less than 0.01). Three patients in whom large coronary aneurysms developed had ratios higher than 4.50. Follow-up analysis of T-cell subsets from individual patients with coronary aneurysms showed that the OKT4/OKT8 ratio during the acute stage was reduced during the convalescent stage (p less than 0.005). In contrast, the ratio in patients with normal coronary arteries was normal during the course of the illness. These observations suggest that an immune regulatory process operating in coronary aneurysm formation is present.

Antibodies, Monoclonal↗