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Biomedical subjects

N Kojima

Publications and source records attributed to N Kojima.

At least 235 records · Page 13Linked to original sources
PubMed1983

[Thyroid hormone autoantibodies in Hashimoto's disease and Graves' disease].

We previously reported the presence of thyroid hormone autoantibodies (THAA) in the sera from three (2 Hashimoto's thyroiditis, 1 Hashimoto's thyroiditis suspected) out of four sisters in a family and one patient with Graves' disease during treatment with methimazole (MMI). According to the investigations of the binding of labelled thyroid hormones, endogenous and/or therapeutic thyroid hormones interfered with their binding with THAA. This interference, however, was excluded when the sera were acidified with a 0.05M glycine-HCl buffer (pH 2.1) and all the liberated thyroid hormones were absorbed into dextrancoated charcoal. In this study, the specific binding of the tracer thyroid hormone to gamma-globulin was examined in hormone-stripped sera from patients with Hashimoto's disease (pretreatment n = 29; L-T4 treatment n = 9) and Graves' disease (pretreatment n = 21; MMI or propyl-thiouracil (PTU) treatment n = 22; MMI or PTU treatment after 131I therapy n = 8) under conditions in which the difference of the concentration of gamma-globulin in each case did not influence the binding. None of the patients examined had increased binding of 125I-T3 with their gamma-globulin. Elevated binding of 125I-T4 was found in sera obtained from 3 patients (2 pretreatment, 1 L-T4 treatment) with Hashimoto's disease and 7 patients (1 pretreatment, 4 MMI or PTU treatment, 2 MMI or PTU treatment after 131I therapy) with Graves disease. Seven (2 Hashimoto's disease, 5 Graves disease) out of these 10 patients with anti-T4 autoantibodies had antibodies against thyroglobulin (Tg) as measured by the hemagglutination method. Titers of anti-T4 autoantibodies and anti-Tg antibodies did not correlate. In Graves disease, anti-T4 autoantibodies were detected during the treatments in sera from 5 (3 MMI or PTU treatment, 2 MMI or PTU treatment after 131I therapy) out of 16 patients (10 MMI or PTU treatment, 6 MMI or PTU treatment after 131I therapy) who had anti-Tg antibodies. On the other hand, anti-T4 autoantibodies prior to the medication could not be found in sera from 5 patients with positive anti-Tg antibodies. From these results, it is suggested that antithyroid drugs and/or 131I therapy might induce the production of THAA in patients with Graves disease through the deterioration of immunological tolerance and/or through the modification of the Tg molecule.

Adult↗
PubMed1983

[Evaluation on the interaction between thyroxine binding globulin (TBG) and thyroxine (T4) in healthy subjects and pregnant women].

A very simple method for the evaluation of the interaction between thyroxine binding globulin (TBG) and thyroxine (T4) has been developed and evaluated in 6 healthy subjects and 5 pregnant women. Rabbit anti-human TBG antiserum was precipitated with 50% ammonium sulfate followed by passing a DEAE-cellulose column. Immunoglobulin G (IgG) fraction thus prepared was covalently attached on a Sepharose CL-4B and used as an immunoadsorbent of serum TBG. After treatment with charcoal to remove endogeneous thyroid hormones, 10 microliter of sera from 6 healthy subjects and 5 pregnant women were incubated with 125I-T4 and various concentrations of cold T4 followed by immunoadsorption with anti-TBG-Sepharose, and association constants (Ka) between TBG and T4 were calculated in each subject using Scatchard's plot. The Ka value thus obtained in 6 healthy subjects was 1.47 X 10(8) M-1 (SD = 0.24), and in 5 pregnant women it was 0.82 X 10(8) M-1 (SD = 0.21) which was significantly lower than that of healthy subjects (P less than 0.001). Our present method does not need purification of TBG from serum to investigate its functions, especially in relation to the binding with thyroid hormones. Also, only a very small amount (100 approximately 150 microliter) of serum is enough for the calculation of Ka between T4 and TBG. The whole procedure is very easy to perform and can be done in a relatively short time, and therefore we consider this method clinically relevant and useful.

Adult↗
PubMed1983

Structure of linkage region between ribitol teichoic acid and peptidoglycan in cell walls of Staphylococcus aureus H.

The cell walls of Staphylococcus aureus H were found to contain mannosamine in an amount (28.1 nmol/mg) comparable to the content of muramic acid 6-phosphate. The acidic polymer fraction obtained by heating the cell walls at pH 2.5 was shown to contain mannosamine and glycerol in addition to the components of ribitol teichoic acid. Mild alkali treatment of this polymer fraction followed by gel filtration resulted in separation of a disaccharide N-acetylmannosaminyl(1 leads to 4)N-acetylglucosamine and the ribitol teichoic acid moiety that contained glycerol. Smith degradation of the reduction product from the same polymer fraction gave a fragment characterized as (1,2-ethylene-diol phosphate)-(glycerol phosphate)3-N-acetylmannosaminyl(1 leads to 4)N-acetylxylosaminitol. Thus, the ribitol teichoic acid chain in the cell walls is probably linked to peptidoglycan through a linkage unit, (glycerol phosphate)3-N-acetylmannosaminyl(1 leads to 4)N-acetylglucosamine.

Carbohydrate Conformation↗
PubMed1983

[Studies on anti-T3 and anti-T4 autoantibodies found in 2 sisters with juvenile hypothyroidism due to Hashimoto's thyroiditis. III. Anti-rT3 autoantibodies].

We previously reported that two sisters with juvenile hypothyroidism due to Hashimoto's thyroiditis (case 1: 13 years old, case 2: 10 years old) had antibodies against T3 and T4, and that the titers of these antibodies decreased but remained above normal levels even in the euthyroid state during L-T4 treatment. In our further investigations we found the binding of 125I-rT3 to serum gamma-globulin in both cases in the pre-treatment period. This binding was completely inhibited by the addition of unlabelled rT3. In addition to these findings, we also found the presence of anti-rT3 antibodies in two rabbits (TG-1, TG-2) immunized with human thyroglobulin. Since it has been suggested that autoantibodies against thyroglobulin cross-react with T3 and T4, we examined the specificities of anti-rT3 antibodies which were found in both cases and in the two rabbits in order to clarify the role of thyroglobulin in rT3 antibody production. The association constants and binding capacities of rT3 antibodies in cases 1 and 2 were 2.9 X 10(8) M -1 and 50 ng/ml serum, and 2.2 X 10(9) M -1 and 1.5 ng/ml serum, respectively. Cross reactivities of these anti-rT3 antibodies with T3 and T4 were 1.8% and 276% in case 1, and 0.24% and 38% in case 2, respectively. These results suggest that anti-rT3 antibodies in case 1 are anti-T4 antibodies interacting with rT3, and those in case 2 are antibodies against rT3 which have a high cross reactivity with T4. In both cases, however, cross reactivities with T3 were very small. Cross reactivities of anti-rT3 antibodies with T3 and T4 in TG-1 and TG-2 were 4.0% and 53%, and 53% and 182%, respectively. These data were compatible with those obtained from both cases. The observation that anti-rT3 antibodies found in two sisters and two rabbits immunized with human thyroglobulin had similar characteristics in terms of cross reactivities with T3 and T4 suggests the role of thyroglobulin as an antigen in rT3 antibody production in both patients.

Adolescent↗
PubMed1983

Paramagnetic centers in the nickel-containing, deazaflavin-reducing hydrogenase from Methanobacterium thermoautotrophicum.

Two hydrogenases from the methanogenic bacterium Methanobacterium thermoautotrophicum strain DeltaH have been purified and contain tightly bound nickel as well as the anticipated iron/sulfur atoms with a fixed ratio of 15-20 iron atoms per nickel. One hydrogenase reduces the 8-hydroxy-5-deazaflavin coenzyme factor 420 (F(420)), whereas the other has been purified as a methyl viologen-reducing hydrogenase. Both enzymes possess an EPR signal attributed to paramagnetic nickel as demonstrated by hyperfine coupling in (61)Ni-containing hydrogenases. Comparison to model compounds suggests a nickel(III) oxidation state in the inactive forms of these aerobically purified enzymes. Loss of the nickel(III) signal accompanies reductive activation but is not kinetically correlated with regain of high specific activity. On replacement of H(2) by argon in the gas phase over reduced, active, F(420)-reducing enzyme, several EPR signals appear, including a signal at g = 2.004 that is probably enzyme-bound FADH semiquinone, two signals at g = 2.140 and 2.196 that reflect a new form of paramagnetic nickel(III), and also a signal at g = 2.036 that may be an iron signal. The F(420)-reducing hydrogenase in the second paramagnetic nickel form is either itself active or in facile equilibrium with active enzyme. The size of the signal at g = 2.036 may correlate with the degree of activation of the enzyme. In contrast to the hydrogenase of Clostridium pasteurianum [Erbes, D. L., Burris, R. H. & Orme-Johnson, W. H. (1975) Proc. Natl. Acad. Sci. USA 72, 4795-4799], which appears to use only iron/sulfur prosthetic groups and which reacts with one-electron-transfer agents, this methanogen hydrogenase seems to utilize iron, nickel, and flavin redox sites and to reduce obligate one-electron (viologen) and two-electron (deazaflavin) oxidants.

Coenzymes↗
PubMed1983

Age- and sex-related differences of serum thyroxine binding globulin (TBG) in healthy subjects.

Serum concentrations of thyroxine binding globulin (TBG) were measured in healthy adult subjects aged 20-79 years (152 males and 148 females) by radioimmunoassay. In contrast to previous reports, there were no significant age-related differences in either sex. Significant sex-related differences were observed only in the fourth decade, being higher in females than males (P less than 0.01).

Adult↗
PubMed1982

The exchange of Fe3+ between acetohydroxamic acid and transferrin. Spectrophotometric evidence for a mixed ligand complex.

Transferrin, the serum iron transport protein, provides an excellent model for studying biological metal ion exchange reactions. A curious problem is that while a mixed ligand species of chelate-Fe3+-protein is anticipated from theoretical considerations and supported by kinetic results, no clear spectrophotometric evidence for such an intermediate has heretofore been obtained. In this study of the exchange of Fe3+ between acetohydroxamic acid and transferrin such evidence has been found. The reaction of Fe2+-acetohydroxamic acid with apotransferrin-CO3(2-) is distinctly biphasic when examined by stopped flow spectrophotometry. The first phase is complete within approximately 4 s and results in the formation of a transient species with a distinct spectral maximum at 432 nm. The second phase requires approximately 2 min and results in the formation of Fe3+-transferrin-CO3(2-). We suggest that the transient species is a mixed ligand complex. The reaction rate-concentration relationship for the formation of the intermediate is linear for Fe3+-acetohydroxamic acid and hyperbolic for apotransferrin-CO3(2-). This suggests a rate-limiting labilization of Fe3+-(acetohydroxamic acid)3 preceding attack by the apotransferrin-CO3(2-). The reverse reaction, the removal of Fe3+ from the Fe3+-transferrin-CO3(2-) by acetohydroxamic acid, does not provide spectral evidence for the intermediate. The velocity-concentration relationship shows a hyperbolic dependence on acetohydroxamic acid concentration and a linear dependence of Fe3+-transferrin-CO3(2-), suggesting a rate-limiting labilization of the Fe3+ of Fe3+-transferrin-CO3(2-) resulting from a conformational change.

Carbonates↗
PubMed1982

Regulation of immune response by preadministration of cells briefly pulsed with antigen in vitro. I. Suppression of IgE antibody response by antigen pulsed spleen cells.

The intravenous administration of syngeneic spleen cells (SPCs) briefly pulsed with antigen in vitro, results in a profound state of IgE antibody unresponsiveness. In Balb/c mice, the primary response of anti-DNP, anti-beef insulin and anti-ovalbumin IgE antibody is completely suppressed by the administration of antigen-pulsed spleen cells, 1 X 10(7), 5 X 10(7) and 1 X 10(8), respectively. This suppression is antigen specific and effects both primary and secondary immune responses. Furthermore, the immune response to dinitrophenylated Keyhole limpet hemocyanin (DNP-KLH) is most extensively suppressed by DNP-KLH pulsed SPCs, intermediately suppressed by KLH-pulsed SPCs and minimally suppressed by dinitrophenylated mouse gamma globulin or dinitrophenylated mouse serum albumin pulsed SPCs. Suppressing directly cells specific for hapten and carrier, hapten carrier protein pulsed SPCs would caused the additive suppressive effect. The suppression is induced strongly by the intravenous administration of antigen pulsed spleen cells, slightly by the subcutaneous administration and is not induced by the intravenous administration of antigen solution in phosphate buffer saline. This suppression may be mediated by either of two different mechanisms: one of them is responsible for the immediate tolerance which is induced without any suppressor cells 1 day after the administration of antigen pulsed SPCs, and the other is responsible for the suppression transferred by suppressor cells or factors to normal mice 7 days after the administration of antigen pulsed SPCs. This method in which IgE antibody response is suppressed by the administration of cells briefly pulsed in vitro with antigen, provides a powerful tool to analyze the first step of antigen specific suppression developed in vivo by conventional antigens.

Animals↗
PubMed1982

Fibronectin in human hepatocellular carcinoma.

Human liver specimens with hepatocellular carcinoma were studied for distribution of fibronectin by immunofluorescence staining. Fibronectin was detected in the cytoplasm and/or on the cell surface in certain cases, which is in contrast to the observations in vivo for hepatocytes of normal and other fibrotic livers. The present finding is also in contrast to those for various other carcinomas so far reported.

Carcinoma, Hepatocellular↗
PubMed1981

The formation of Fe3+-transferrin-CO3(2-) via the binding and oxidation of Fe2+.

This paper examines the reaction pathway in which Fe2+ is bound by apotransferrin and subsequently oxidized by O2 to yield Fe3+-transferrin-CO3(2-). The time course of the reaction follows a curved first order function suggesting somewhat different reactivities of the two transferrin binding sites. The initial velocity of the oxidation reaction follows saturation kinetics with regard to apotransferrin, Fe2+, and NaHCO3. We suggest an equilibrium between these components and Fe2+-transferrin-CO3(2-). The initial velocity is a linear function of O2 concentration. This is consistent with the rate-limiting step of the overall reaction being the oxidation of the Fe2+-transferrin-CO3(2-). A second order rate constant of approximately 4 X 10(3) M-1 s-1 was estimated for the oxidation of Fe2+-transferrin-CO3(2-) by O2. Oxidation by H2O2 is about 30 times faster. The reaction velocity increases with increasing pH between pH 6.0 and 7.5 Fe3+-transferrin-anion complexes are formed by the binding and oxidation of Fe2+ iun the presence of O2 and synergistic anions. The anion is found to have a strong effect on the reaction rate and provides additional evidence for the proposed reaction route. The presence of chelating agents also strongly affects the rate of Fe3+-transferrin-CO3(2-) formation. EDTA and N-(2-hydroxyethyl)ethylenediaminetriacetic acid severely depress the rate, while other chelating reagents have a moderately inhibiting effect. Thioglycolate is found to enhance the reaction by a factor of 9. The formation of a quaternary complex consisting of thioglycolate-Fe2+-transferrin-CO3(2-) is suggested. The results are correlated with an earlier study on the reductive release of iron from transferrin (Kojima, N., and Bates, G. W. (1979) J. Biol. Chem. 254, 8847-8854).

Carbonates↗
PubMed1981

The effect of chemical agents, beverages, and spinach on the in vitro solubilization of iron from cooked pinto beans.

The solubilization of iron from cooked pinto beans was examined using an improved in vitro methodology. The iron content of the beans was found to exist in three populations: 1) that which is spontaneously soluble upon incubation; 2) that which can be mobilized by chelating or reducing agents; and 3) that which is more firmly bound to the insoluble bean residue. These fractions constitute approximately 25, 45, and 30%, respectively, of the bean iron content when using consecutive 30-min incubations at pH 2 and 6. Ascorbic acid is maximally effective in iron mobilization under acidic conditions and acts via iron reduction. Citric acid is maximally effective near pH 6. The combination of ascorbic acid and citric acid leads to the solubilization of 70% of the iron content of the beans. Orange juice also leads to maximal soluble iron, predominantly in the Fe2+ state. Tea severely decreases iron solubility in the system. Only 3% of the iron content of spinach is solubilized by 10 mM ascorbic acid. Whole spinach suspension and the insoluble spinach residue are able to remove iron from solution that was previously solubilized from beans.

Beverages↗