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Biomedical subjects

S Sakata

Publications and source records attributed to S Sakata.

At least 181 records · Page 10Linked to original sources

A case of progressive systemic sclerosis (PSS) with silent thyroiditis and anti-bovine thyrotropin antibodies.

We have examined a patient with progressive systemic sclerosis (PSS) who had increased serum T3 (235 ng/dl) and T4 (13.2 micrograms/dl) and low 24-h thyroidal 123I-uptake (1.2%). A diagnosis of silent thyroiditis was made on the basis of the clinical course and laboratory and histopathologic findings. Simultaneous measurement of serum anti-thyrotropin receptor antibody (TRAb) showed a negative value (-49.0%) which suggested the presence of anti-TSH antibody. Further examination by immune precipitation with 125I-bovine TSH (bTSH) and also with 125I-human TSH (hTSH) revealed the presence of anti-bTSH antibody but not anti-hTSH antibody in his serum gamma-globulin. The significance of the association of PSS, silent thyroiditis, and anti-bTSH in one individual is discussed.

Animals↗

Oxygen consumption in resting dog gracilis muscle perfused at varying oxygen delivery.

The different response of O2 uptake (VO2) of resting skeletal muscle to the changes in blood flow has been thought to reflect a species difference. To scrutinize this notion, we investigated the relation between O2 delivery (arterial O2 content multiplied by blood flow) and VO2 in isolated dog gracilis muscle perfused solely with normal hematocrit (Ht) blood (n = 9), or alternately with normal and low Ht blood (n = 6), or alternately with normal and high Ht blood (n = 3) at varying perfusion rates. Eleven out of the 18 preparations showed an autoregulation of blood flow, and the others did not. But, in all preparations, the VO2 was delivery-independent above a critical O2 delivery (0.45 ml/(min.100 g muscle)) and showed the constant VO2 of 0.30 ml/(min.100 g), while below the critical level it turned out to be delivery-dependent. The maximal extraction ratio was 0.67. The same relationship was found with the low and high Ht perfusion. The pattern observed in dog gracilis muscle was essentially the same as that in rat gracilis muscle (KOLAR and JANSKY, 1984).

Animals↗

[Effects of hypocapnia on hemodynamics and myocardial metabolism in anesthetized dogs].

The authors previously reported that hypocapnia increased myocardial oxygen demand under droperidol-fentanyl (D-F) anesthesia. In this study, we observed myocardial oxygen tension, hemodynamics, and coronary arterial-venous blood content differences of oxygen and lactate before and after hyperventilation in dogs with and without a narrowed coronary artery under halothane anesthesia. We studied the functional and metabolic responses of the heart to hypocapnia under halothane in comparison with D-F anesthesia. In the intact heart, heart rate, LV dp/dt max and myocardial energy demand (heart rate x systolic aortic pressure x LV dp/dt max), which increased during hypocapnia under D-F anesthesia, were unchanged during hypocapnia under halothane anesthesia. Aortic pressure and coronary flow were unchanged under both types of anesthesia. Though subendocardial oxygen tension decreased significantly, myocardial lactate extraction was unchanged under both types of anesthesia. In the heart with a constricted coronary artery, subendocardial oxygen tension and lactate extraction ratio decreased significantly during hypocapnia under both types of anesthesia. Myocardial lactate production was observed in six of eleven dogs in which myocardial energy demand increased under D-F anesthesia. Myocardial lactate production was observed in one dog under halothane anesthesia. Coronary arterial-venous blood oxygen content difference increased under D-F anesthesia, but not under halothane anesthesia. In summary, hypocapnia increased myocardial oxygen demand under D-F anesthesia but not under halothane anesthesia. In the intact heart under both types of anesthesia, hypocapnia deteriorated myocardial oxygen supply-demand relations, but the evidence of myocardial anaerobic metabolism was not observed.(ABSTRACT TRUNCATED AT 250 WORDS)

Anesthesia↗

Thyroxine binding to human serum albumin immobilized on sepharose and effects of nonprotein albumin-binding plasma constituents.

125I-thyroxine (125I-T4) binding to human serum albumin (HSA) covalently attached onto CNBr-activated Sepharose (HSA-Sepharose) was studied. 125I-T4 binding to HSA-Sepharose was rapid and saturable. Nonlinear curve-fitting analysis of binding isotherms revealed two classes of binding sites. The values of dissociation constants of high and low affinity sites were 2.19 +/- 0.53 x 10(-6) M and 2.69 +/- 0.78 x 10(-5) M, respectively. The number of binding sites of the high and the low affinity sites were 1.28 +/- 0.46 mol/mol and 23.5 +/- 9.7 mol/mol of HSA, respectively. Fatty acids and bilirubin competitively inhibited the high-affinity binding of 125I-T4 to HSA-Sepharose without affecting the low-affinity binding. 8-anilino-1-naphthalene sulfonic acid (ANS) inhibited the high affinity T4 binding via reduction of the binding capacity. Unlabeled T4 showed little inhibition of ANS binding to HSA, as measured by fluorescence intensity. These results suggest that ANS allosterically inhibits the high-affinity T4 binding to HSA-Sepharose.

Anilino Naphthalenesulfonates↗

Binding of thyroid hormones to human hemoglobin and localization of the binding site.

Radiolabeled thyroid hormones were allowed to bind to erythrocyte cytosol and the complex was fractionated by Sephadex G-100 or by high-performance liquid chromatography (HPLC). On Sephadex G-100, four radioactive peaks (P1-P4) were obtained, whereas HPLC gave only three radioactive peaks (P1-P3). Chromatographic studies with human adult Hb and non-Hb cytosol protein fractions, which had been reacted with radiolabeled thyroid hormones, and immune precipitation with specific antisera for the hormones, confirmed that the first peak of Sephadex G-100 radioactivity was a mixture of Hb and non-Hb proteins, while the second peak was Hb. The third peak was free 125I and the fourth peak was unbound 125I-T3 or 125I-T4. The third peak of HPLC was confirmed to be a mixture of free 125I and unbound radiolabeled thyroid hormones. Scatchard analysis of the interaction between T4 and apo-Hb, and the alpha- and beta-chains of human Hb suggested the presence of the specific binding site(s) for the hormone. Interaction between T4 and synthesized peptides, which constitute the heme pocket of the beta-chain of Hb (beta 61-75, beta 71-85, beta 81-95), indicated that the T4 binding site of Hb resides within the heme-binding cavity. It is concluded that human erythrocyte cytosol does not contain "receptor" for thyroid hormones and cannot be a model for studying functions of cytosol "receptor" for the hormones; rather, it contains binding protein with large binding capacity, including Hb and non-Hb proteins, which possibly constitute a large reservoir for the hormone in blood.

Binding Sites↗

Localization and synthesis of an insulin-binding region on human insulin receptor.

Seven regions of the alpha subunit of human insulin receptor (HIR) were synthesized and examined for their ability to bind radioiodinated insulin. A peptide representing one of these regions (namely, residues alpha 655-670) exhibited a specific binding activity for insulin. In quantitative radiometric titrations, the binding curves of 125I-labeled insulin to adsorbents of peptide alpha 655-670 and of purified placental membrane were similar or superimposable. The binding of radioiodinated insulin to peptide or to membrane adsorbents was completely inhibited by unlabeled insulin, and the inhibition curves indicated that the peptide and the membrane on the adsorbents had similar affinities. Synthetic peptides that were shorter (peptide alpha 661-670) or longer (peptide alpha 651-670) than the region alpha 655-670 exhibited lower insulin-binding activity. It was concluded that an insulin-binding region in the HIR alpha subunit resides within residues alpha 655-670. The results do not rule out the possibility that other regions of the alpha subunit may also participate in binding of HIR to insulin, with the region described here forming a "face" within a larger binding site.

Amino Acid Sequence↗

Two cases of Graves' disease with antithyroid hormone antibodies: implication on the role of thyroglobulin as an antigen.

We have experienced two cases of Graves' disease with antithyroid hormone autoantibodies (Case 1: anti-T4; Case 2: anti-T3) who finally underwent subtotal thyroidectomy after antithyroid drug treatment. Using serial sera obtained before and after operation, the correlation between titers of antithyroglobulin (anti-Tg) and anti-T4 or anti-T3 autoantibodies was examined in each case. There was a significant positive correlation between titers of anti-T4 (Case 1, r = 0.90, p less than 0.05), or anti-T3 (Case 2, r = 0.64, p less than 0.01) and anti-Tg antibodies. Using the homogenate of the thyroid tissue, it was found that the sole iodoprotein in the thyroid gland in each patient was 660 KDa Tg. In addition, Tg purified from the thyroid gland from Case 2 showed different immunological activity with normal Tg in two out of four murine monoclonal anti-Tg antibodies tested. On the other hand, Tg from Case 1 had identical immunological activity with normal Tg in every four monoclonal antibodies. These results are consistent with the view that the antigen responsible for the development of antithyroid hormone autoantibodies is Tg, at least in our two cases. The reason for the persistence of anti-T3 autoantibodies in Case 2, despite the subtotal thyroidectomy, could be due to some unidentified structural abnormalities of Tg which was detected only by the monoclonal anti-Tg antibodies.

Adenoma↗

Influences of propranolol and atenolol on the circadian rhythm of heart rate in elderly patients with essential hypertension.

1. The influence of long-acting propranolol and of atenolol on the circadian rhythm of heart rate was assessed using 24 h electrocardiographic recordings in elderly patients with essential hypertension. Eighteen elderly patients were investigated before treatment and after 12 weeks on 60 mg of long-acting propranolol once a day; 21 elderly patients were studied before treatment and after 12 weeks on 50 mg of atenolol once a day. The mean hourly heart rate in 24 h electrocardiographic recordings was used to fit cosine curves by the statistical technique of least squares, and the following parameters were estimated: mesor (rhythm-adjusted mean of the heart rate), amplitude (one-half of the total diurnal variation of the heart rate) and acrophase (the time when the heart rate was at its peak above the mean). 2. The cosine curves were fitted with a P value of 0.01 or less before and after treatment in all patients. 3. In the long-acting propranolol group, the mesor and amplitude were reduced significantly after treatment. The acrophase appeared significantly earlier after treatment than before treatment. 4. In the atenolol group, the mesor and amplitude decreased significantly after treatment. However, the acrophase did not change with treatment. 5. We conclude that both propranolol and atenolol decrease the mesor and amplitude through blocking cardiac beta 1-receptors, and that only propranolol may have some effects on the central nervous system, resulting in the circadian phase shift.

Aged↗

cDNA cloning of somatolactin, a pituitary protein related to growth hormone and prolactin.

From a flounder pituitary cDNA library, cDNA clones encoding a 28-kDa glycoprotein produced by the pars intermedia of the pituitary were isolated and characterized. Nucleotide sequencing demonstrated a precursor of the 28-kDa protein, which consisted of 231 amino acid residues, to be cleaved into a signal peptide (24 amino acids) and a mature protein (207 amino acids) containing one N-glycosylation site. By comparison of amino acid sequences, the 28-kDa protein was found to be distantly and similarly related to growth hormone and prolactin. Consequently, it was named somatolactin. Somatolactin mRNAs were specifically expressed as 1.2 and 1.8 kb poly(A)+ RNAs in flounder pituitary.

Amino Acid Sequence↗

Anti-thyroglobulin autoantibodies in sera from patients with chronic thyroiditis and from healthy subjects: differences in cross-reactivity with thyroid peroxidase.

A significant portion (about 12.7%) of healthy subjects was found to contain anti-thyroglobulin (anti-Tg) antibodies in their sera. We compared the binding activities of these antibodies and of anti-Tg autoantibodies from sera of patients with chronic thyroiditis with human thyroid peroxidase (TPO). The results obtained by ELISA indicated that out of 10 healthy subjects with anti-Tg antibodies, only four had anti-Tg antibodies capable of binding to TPO, whereas anti-Tg autoantibodies from almost all patients with chronic thyroiditis possessed high binding activities to TPO. By use of the immunoprecipitation method, it was also shown that although all anti-Tg autoantibodies from patients precipitated TPO, a majority of anti-Tg antibodies from healthy subjects could not precipitate TPO. Such findings cannot be ascribed to the differences in levels of anti-Tg autoantibodies and anti-TPO autoantibodies in sera and the differences in avidities of anti-Tg antibodies in sera between healthy subjects and patients with chronic thyroiditis. Thus, it can be concluded that anti-Tg antibodies from healthy subjects differ from those of patients with chronic thyroiditis with respect to TPO binding, probably due to difference in fine specificities of these anti-Tg antibodies.

Adolescent↗

Antibodies to Yersinia enterocolitica serotype 3 in autoimmune thyroid diseases.

The prevalence of increased titres of antibodies to Yersinia enterocolitica (serotype 3) has been studied in sera from patients with various thyroid diseases. In contrast to the low prevalences of the antibodies in healty subject (24.3%), titres (greater than 10) of anti-Yersinia enterocolitica (anti-Yersinia) were found more frequently in patients with thyroidal disorders, especially in Graves' disease (70.0%). Furthermore, high titres of the antibodies (greater than or equal to 160) were found only in patients with Graves' disease. There was no significant correlation between the titers of anti-Yersinia antibodies and those of anti-TSH receptor antibodies in sera from patients with Graves' disease. In seven individual samples of sera, the anti-Yersinia antibody titer was high before treatment, but the decrease in the anti-TSH receptor antibody titer following treatment was associated with a simultaneous decline in anti-Yersinia antibodies in all of them. A highly positive and significant correlation between the titers of anti-TSH receptor antibodies and anti-Yersinia antibodies was obtained in each of them. These findings could be merely a reflection of the measurement of the cross-reaction of anti-Yersinia antibodies with anti-TSH receptor antibodies but the possibility of an association between Yersinia infection and the production of anti-TSH receptor antibodies in at least some patients with Graves' disease cannot be ruled out.

Adult↗

Japanese dietary intake of salt and protein--relating to the strategy of salt restriction.

The high level of Japanese salt intake, which has been the major risk factor for cerebrovascular disease and hypertension, has decreased since World War II, and reached a steady level. In the present study, the dietary salt intake in Tohoku (once the district of highest sodium intake) and that in Kyushu (once the district of median or low sodium intake) were studied in relation to nutritional status by the analysis of sodium and urea-nitrogen excretion in 24-hr urine samples collected from 305 healthy Japanese. When the amount of urinary creatinine and urea-nitrogen were adjusted, the mean value of urinary sodium in females was significantly larger in Tohoku than in Kyushu, but not significantly in males. The regional difference of salt intake still remains, although it seems to be disappearing. Traditionally, Japanese high intake of salt was accompanied by poor nutritional status. In the present study, however, a significant positive correlation was observed between sodium and urea-nitrogen. The excess of protein intake would cause the excess of salt intake. Therefore, the strategy of further salt restriction should be directed to not only traditional salty foods but also nutritional status such as protein intake.

Age Factors↗

A simple procedure for determination of the dead time of a stopped-flow instrument.

The reducing reaction of 2,6-dichlorophenolindophenol by L-ascorbic acid was used to determine the dead time of a stopped-flow instrument. Because this reaction is irreversible, the dead time could be determined by a simple graphical analysis. The dead time values determined by the present method were comparable to those by other methods previously reported.

2,6-Dichloroindophenol↗

[Two cases of bronchiolitis obliterans organizing pneumonia, showing multiple infiltrative shadows, diagnosed by open lung biopsy, and a report of their BAL findings].

Two cases of bronchiolitis obliterans organizing pneumonia (BOOP) were diagnosed by clinical features and pathological findings of open lung biopsy specimens. Findings of repeated (bronchoalveolar lavage (BAL) fluid analysis were also reported. Case 1 was a 54 year-old woman complaining of dry cough and low grade fever. Multiple infiltrative shadows in both lung fields were pointed out on her chest roentgenogram. Case 2 was a 68 year-old woman with symptoms of cough, sputum and low grade fever. Her chest X-ray films also showed multiple infiltrative shadows bilaterally. Although various antibiotics were given to both patients, new shadows appeared on their chest films without any improvement of clinical symptoms or inflammatory findings. TBLB specimens obtained from the two cases showed the findings of organizing pneumonia. In each case, open lung biopsy was performed, and the pathological diagnosis was consistent with BOOP. However, exclusion of the possibility of eosinophilic pneumonia and lymphoproliferative disorders of the lung was somewhat difficult in case 1. BALF analysis showed an increased number of lymphocytes in both cases, 75% and 37% respectively. The inverted ratio of OKT4/OKT8 (0.71) in BALF of case 1 was similar to that of hypersensitivity pneumonitis. In spite of clinical and roentgenological improvement after steroid therapy, the abnormal BAL findings still remained. Therefore it is suggested that BAL may be a useful tool for monitoring the steroid treatment of patients with BOOP.

Aged↗

[Difference in the effect of halothane on regional oxygen demand-supply relationship depending on the severity of coronary artery stenosis].

We examined the effect of halothane on myocardial oxygen balance and hemodynamics in three groups of canine heart. We measured regional subendocardial oxygen tension before and after 30 minute inhalation of 0.8% and 1.5% halothane in the mixture of nitrogen and oxygen (FIO2 not equal to 0.5). In moderate and severe stenosis group, left circumflex coronary artery flow was reduced to 66% and 31% respectively, at buprenorphine-anesthetized basal condition. In occlusion group, left circumflex coronary artery was ligated at its origin. Both concentrations of halothane decreased heart rate, aortic pressure and LV dp/dt max in all groups. Subendocardial oxygen tension increased in moderate stenosis group. But it was unchanged in severe stenosis group, and it rather decreased in occlusion group with 1.5% halothane inhalation. Halothane might improve endocardial oxygen demand-supply relation in the myocardium with mild to moderate coronary stenosis, while it will possibly deteriorate endocardial oxygen demand-supply balance in ischemic myocardium after coronary artery occlusion.

Animals↗

[Two cases of Graves' disease with anti-thyroid hormone autoantibodies: the effect of subtotal thyroidectomy on the titers of anti-thyroid hormone autoantibodies and anti-Tg antibodies].

We experienced two cases of Graves' disease associated with anti-thyroid hormone autoantibodies (Case 1: anti-T4, Case 2: anti-T3). Both cases underwent subtotal thyroidectomy, and titers of anti-thyroid hormone antibodies and anti-Tg antibodies were compared before and after operation. In case 1, titers of both anti-T4 and anti-Tg antibodies decreased after operation, whereas in Case 2, titers of both anti-T3 and anti-Tg were unchanged before and after operation. There was a significant positive correlation between titers of anti-T4 and anti-Tg antibodies in Case 1 (r = 0.90, P less than 0.01), and anti-T3 and anti-Tg antibodies in Case 2 (r = 0.64, P less than 0.01). These results strengthen the possibility that the antigen of anti-thyroid hormone autoantibodies in both cases is the Tg molecule.

Autoantibodies↗