Search PubMed⌕ Search

Biomedical subjects

S Sakata

Publications and source records attributed to S Sakata.

At least 289 records · Page 16Linked to original sources

Effect of nicardipine in a hypertensive patient with diabetes mellitus.

Nicardipine, a new calcium antagonist, was given to an insulin-treated diabetic patient with severe hypertension that had resisted ordinary antihypertensive treatment. After substitution of treatment with nicardipine, his blood pressure decreased from 210/110 to 142/76 mmHg. Despite this significant decrease in blood pressure, the patient's renal blood flow, as estimated by endogenous creatinine clearance, increased. His daily requirement of insulin and his degree of proteinuria remained unchanged by the use of nicardipine.

Blood Pressure↗

[Production of antithyroid hormone antibodies. 2. Genetic control of the production of anti-human thyroglobulin and antithyroid hormone antibodies in mice immunized with human thyroglobulin].

Recently anti-thyroid hormone antibodies have been found in many cases of thyroidal and non-thyroidal disorders. However, the exact mechanism(s) of production of anti-thyroid hormone antibodies in these patients is so far obscure. Thyroxine (T4) and triiodothyronine (T3) are haptens and are not immunogenic in free form. In this respect, human thyroglobulin (HTg) has long been suggested as an antigen of the anti-thyroid hormone antibodies observed in them because it carries thyroid hormones on its surface. In our previous communication, we reported the production of anti-HTg antibodies and anti-thyroid hormone antibodies in two rabbits and various strains of mice immunized with HTg. In order to elucidate the gene(s) which controls the production of anti-HTg and anti-thyroid hormone antibodies, various strains of mice which have different H-2 and Igh allotypes were immunized with HTg. The titers of anti-HTg and anti-thyroid hormone antibodies were measured, and the locus (loci) which controls the immune response against them was determined. Our present investigation has revealed that the Ir-gene(s) which controls the production of anti-HTg and anti-T4 antibodies is located in the I-A subregion. Concerning the production of anti-T4 antibodies in mice, the presence of Ir-gene(s) outside of H-2 is also suggested. The significance of the genetic mechanisms controlling the immune response against thyroid hormones in various thyroidal disorders is discussed.

Animals↗

[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↗

[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↗

[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↗

Preparation of native alpha and beta subunits from canine hemoglobin.

Preparation of native alpha and beta subunits from non-primate hemoglobins has never been successful using the procedure of Bucci, E. and Fronticelli, C. ((1965) J. Biol. Chem. 240, PC551-552). We describe a method for isolating the constituent subunits from canine hemoglobin. Human-canine hybrid hemoglobins (alpha 2Can beta 2A and alpha 2A beta 2Can) were prepared by acid hybridization techniques and DEAE-Sephadex chromatography. The hybrids were then reacted with an excess of p-chloromercuribenzoate under slightly acid conditions and the resultant alpha Can and beta Can subunits were isolated by either anion- or cation-exchange chromatography. Identifications of the subunits were made by gel electrophoresis and amino acid analysis. After removal of the bound mercurials with beta-mercaptoethanol, both subunits exhibited two reactive sulfhydryl groups per chain and were found to be fully in the native form, as judged by spectroscopy. By ultracentrifugal analysis, the alpha subunit was shown to be in a dimer-monomer equilibrium while the beta subunit was largely in a tetrameric form.

Amino Acids↗

Genetic control of mouse antibody production to human thyroglobulin.

Genetic control of immune responses in mice against human thyroglobulin was studied using the enzyme-linked immunosorbent assay and passive haemagglutination test. Our results revealed that mice of H-2a, H-2d, H-2q, H-2k and H-2r haplotypes were high responders for antibody production to human thyroglobulin, while mice of H-2b and H-2s haplotypes were low responders. High responsiveness to human thyroglobulin was transmitted to F1 mice in a dominant fashion. Study of the genetic mapping of the immune responses to human thyroglobulin using various congenic mice showed that I-A subregion gene(s) control the immune response to human thyroglobulin.

Animals↗

A solid phase radioimmunoassay for the detection of anti-insulin antibodies.

A solid phase radioimmunoassay for the detection of anti-insulin antibodies has been developed and evaluated. After coating round-bottomed wells of polyvinyl chloride with porcine monocomponent insulin, 50 microliters of serum from either insulin-treated diabetics or non diabetic controls was added to the wells, followed by the addition of 125I-protein A, and then the radioactivity of the bound 125I-protein A on the wells was counted. This solid phase radioimmunoassay is very simple, does not require centrifugal steps and the results correlated well with those of previously published immune precipitation methods (r = 0.68, p less than 0.01). Our present method requires only 50 microliters of serum and 4 hours for the assay, if the wells are coated with insulin in advance. Therefore, this procedure is thought to be suitable for clinical use.

Chemical Precipitation↗

Kinetics of hepatic thyroxine 5'-deiodinase.

The enzymatic kinetic constants of 5'-deiodination of thyroxine in the rat liver were determined by studying the enzymatic activity at several sets of concentrations of thyroxine and dithiothreitol. Parallel increases in apparent Vmax and Km for thyroxine were observed by increasing the concentration of dithiothreitol. Double-reciprocal replots of these apparent values vs the dithiothreitol concentration gave straight lines. These results provide further evidence for a ping-pong mechanism of the enzymatic process. The 'true' Km values for thyroxine and dithiothreitol were computed to be 16 +/- 5 microM and 1.2 +/- 0.4 mM, respectively. The Vmax was 126 +/- 23 pmol/mg protein/min.

Animals↗

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↗

A simple microtonometric method for whole blood oxygen dissociation curve and a critical evaluation of the "single point" procedure for blood P50.

We devised a rapid and simple method to obtain oxygen dissociation curve (ODC) for a small amount of blood with simple equipment. This system achieved the gas-blood equilibrium within 3 min. Oxygen saturation of the equilibrated blood was measured spectrophotometrically while the pH, PCO2, and PO2 was measured with a Radiometer blood gas analyzer system. Whole procedures to construct ODC from the 6 point measurements could be performed within 1 hr. The standard ODC for 25 normal Japanese adults showed a mean P50 of 27.6 +/- 1.1 Torr (pH 7.40, PCO2 40 Torr, 37 degrees C), a slightly higher value than previously reported. The discrepancy, however, can be eliminated when corrected for a slightly lower SO2 by the present procedure. The standard curves for the adult blood at pH 7.20 and 7.60 and for the cord blood at pH 7.40 were also described. The "single point" procedure, a much quicker approach to measure the P50 (Aberman et al., 1975), was scrutinized by comparing with the "whole curve" method. The P50's by the two methods were not significantly different, mean +/- S.D. of the differences being 0.4 +/- 2.5 Torr (n = 126) for the adult blood at pH 7.40, PCO2 40 Torr and 37 degrees C. Similar results were obtained for the adult blood at pH 7.20 and 7.60 and for the cord blood at 7.40. We concluded that the "single point" method was sufficiently accurate and reliable.

Adult↗

[Quantitative study of single photon radionuclide computed tomography--delineation of body contours].

Several methods to obtain the body contour which is necessary to reconstruct the quantitative images with single photon radionuclide computed tomography (SPRCT) are described in this paper. A multipurpose gamma camera system which is composed of 2 detectors, data processor and others were used to collect the data of SPRCT and body contour. An iterative reconstruction technique was implemented to reconstruct the image. Three methods for obtaining the body contour were tested. The first method utilizes X-ray CT data. The data which are obtained by GE CT/T are transferred to the data processor of SPRCT through the off-line magnetic tape and delineate the body contour. The second method uses a transmission source which was attached on the opposite side to detector. The third method uses gamma-rays which are generated by Compton scatter in the tissue of patient. The first and the second methods were able to use to obtain the body contour, but the contour obtained by third method was not accurate.

Gamma Rays↗