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Biomedical subjects

S Sakata

Publications and source records attributed to S Sakata.

At least 145 records · Page 8Linked to original sources
PubMed1993

Autoimmune T-cell recognition sites of human thyrotropin receptor in Graves' disease.

Five overlapping synthetic peptides representing two regions of thyrotropin (TSH) binding sites of human thyrotropin receptor (TSHR) (peptides 12-30, 24-44, 308-328, 324-344 and 339-364) were investigated for their ability to cause proliferation of peripheral blood lymphocytes (PBL) from eight patients with Graves' disease. The same experiment was done using PBL from four cases with Hashimoto's thyroiditis, two cases with subacute thyroiditis, two cases with rheumatoid arthritis (RA) and eight normal volunteers. PBL obtained from each patient with Graves' disease responded to one or more of peptides 12-30, 24-44, 308-328 and 324-344, while peptide 339-364 had no stimulating activity. The level of stimulating activity of each of the four aforementioned TSHR peptides varied from patient to patient. None of the five TSHR peptides caused the proliferation of PBL from patients with Hashimoto's thyroiditis, subacute thyroiditis, or RA and from normal volunteers. The results indicate that the proliferation of PBL by TSHR peptides is specific in patients with Graves' disease and that the regions of TSHR which are involved in the binding to TSH are also the target of autoimmune T-cell recognition in Graves' disease. The difference in T-cell response from patient to patient could be explained by genetic regulation toward each autodeterminant.

Adolescent↗
PubMed1993

Case report: silent thyroiditis after adrenalectomy in a patient with Cushing's syndrome.

A case of silent thyroiditis after unilateral adrenalectomy for treatment of Cushing's syndrome is reported. The left adrenocortical adenoma was resected. Glucocorticoid was replaced after the operation and was gradually tapered. Thyrotoxic symptoms with painless goiter occurred 9 months after the adrenalectomy when a replacement dose of prednisolone was tapered to 5 mg/d. Plasma-free thyroid hormones increased and thyrotropin was suppressed. Thyroidal uptake of radioactive iodine was extremely low. Both titers of antimicrosomal and antithyroglobulin antibodies stayed at high levels throughout the observation period from the preoperative stage. Normalization of thyroid functions was obtained 3 months after the onset of thyrotoxicosis with beta-adrenergic blocker alone. It was speculated that exposure to a large amount of endogenous and supplementary exogenous glucocorticoid protected the patient's immune system from autoimmune attack of thyroid antigens and that tapering of the supplementary glucocorticoid caused exacerbation of immune responses, resulting in overt thyroid dysfunction even 9 months after adrenalectomy.

Adrenalectomy↗
PubMed1993

Case report: silent thyroiditis developed during alpha-interferon therapy.

Alpha-interferon (IFN-alpha) was used for the treatment of chronic active hepatitis C in a 30-year-old woman who was euthyroid but had low titers of antithyroid antibodies before treatment. Two months after the initiation of IFN-alpha therapy she became thyrotoxic. She had nontender diffuse goiter. A laboratory examination revealed elevated levels of serum free thyroid hormones and a suppressed concentration of serum thyrotropin. Titers of antimicrosomal antibodies increased. The anti-thyrotropin receptor antibody was negative. A 99mTcO- scintigram of the thyroid showed reduced uptake. During the IFN therapy free thyroid-hormone levels started to decline. The IFN-alpha therapy was completed 1 month after the onset of thyrotoxicosis. Two months after the completion of the therapy the patient became euthyroid and 99mTcO- uptake was normalized. It is likely that preexisting chronic thyroiditis was exacerbated to cause silent thyroiditis during IFN-alpha therapy. None of the other 11 patients with chronic hepatitis C who had had no anti-thyroid antibodies and were treated with IFN-alpha showed anti-thyroid antibodies and thyroid dysfunction after the therapy. It is advisable to assess anti-thyroid antibodies and thyroid function in patients who are going to receive IFN-alpha treatment.

Adult↗
PubMed1993

Aneurysm of the posterior cerebral artery: report of eleven cases--surgical approaches and procedures.

Eleven cases of an aneurysm of the posterior cerebral artery are reported. All 11 aneurysms were saccular, and 3 were either giant or large. The aneurysms arose from the P1 segment in three patients, the P1-P2 junction in three patients, the P2 segment in three patients, and from the P3 segment in two patients. In all, 10 patients underwent surgery. All P1 and P1-P2 junction aneurysms were treated with the pterional approach. Three P2 and two P3 aneurysms were managed by the subtemporal approach. Two small aneurysms in the series were treated by coating the aneurysmal dome, two by clipping the afferent artery, and all other saccular type aneurysms were treated by clipping the aneurysmal neck. Seven patients had either an excellent or good outcome; two had poor results; and one patient died. The operative approaches and procedures are also discussed in relation to the anatomy of posterior cerebral artery aneurysms.

Adolescent↗
PubMed1993

Thyroid hormone autoantibodies in patients with untreated Graves' disease: with special reference to age.

We examined thyroid hormone autoantibodies (THAA) in 170 patients with untreated Graves' disease (145 women and 25 men, aged 8-74 yr). THAA were found in 28 patients (16.5%, group I), but not detected in the remaining 142 patients (83.5%, group II). Neither the male/female ratio nor prevalence of antithyroid antibodies (Ab) (thyroglobulin Ab and/or microsomal Ab) differed between the 2 groups. The mean age of group I was significantly lower than that of group II. Furthermore, prevalence in group I decreased progressively with age. In addition, there was a negative correlation between T4 Ab titers (but not T3 Ab titers) and age in group I. These results indicate that the production of THAA, especially T4 Ab, is influenced by age in untreated Graves' patients. The present study also indicates that the age of the patients is one of the important factors causing different results concerning the prevalence of THAA in Graves' disease.

Adolescent↗
PubMed1993

Immune recognition of hormonogenic sites of human thyroglobulin: studies of Graves' sera and a murine monoclonal antibody with thyroid hormone antibody activity.

We synthesized four peptides (HTg-1, 1-10; HTg-2, 2547-2558; HTg-4, 2592-2603 and HTg-6, 2737-2748) and two peptides (HTg-3, 2582-2591 and HTg-5, 2687-2694) with or without hormonogenic acceptor tyrosine of human thyroglobulin (hTg). They were iodinated with 127I or 125I. 127I-labeled peptides were tested for their ability to displace 125I-T4 binding to thyroid hormone autoantibodies (THAA) in two cases of Graves' disease and to a murine anti-hTg monoclonal antibody with anti-T4 activity (mAb). 125I-labeled peptides were tested for the direct binding to the aforementioned antibodies. None of the peptides displaced 125I-T4 binding to THAA or to a mAb, or exhibited increased binding to THAA and to a mAb. 125I-T4 binding to a mAb was equally displaced by hTgs obtained from a normal thyroid gland (NTg) and a case of Hürthle cell adenoma with undetectable iodine content (CTg). 125I-T4 binding to serum gamma globulin in each patient's serum was completely displaced by NTg, but CTg displaced 125I-T4 binding 2% and 5% in Case 1 and Case 2, respectively. It was speculated that the mAb recognizes a topological epitope around the hormonogenic site of hTg, while that of THAA in our two cases recognizes only T4 or an iodine dependent topological epitope(s) of hTg.

Animals↗
PubMed1993

Biological activities of rat antisera raised against synthetic peptides of human thyrotropin receptor.

Twenty three male Wistar rats were divided into five groups and were immunized with five overlapping synthetic peptides (Group I (n = 5), peptide 12-30; Group II (n = 5), 24-44; Group III (n = 4), 308-328; Group IV (n = 5), 324-344; and Group V (n = 4), 339-364) of human thyrotropin receptor (TSHR), which had been conjugated with rabbit serum albumin. Sera obtained 34 days after the first immunization were investigated for their ability to displace 125I-TSH binding to thyrotropin receptor (thyrotropin binding inhibitor immunoglobulins (TBII)). In addition, biological activity, namely thyroid stimulating (TSAb) or blocking (TSBAb) activities in them were tested with cultured porcine thyroid cells. TBII activities in Group I, II, III, IV, and V rats were 12.6 +/- 4.1% (range 9.2-17.2%), 16.3 +/- 4.0% (range 11.7-22.0%), 16.7 +/- 4.9% (range 13.2-20.1%), 14.5 +/- 5.7% (range 8.1-19.0%), and 13.8 +/- 6.3% (range 8.1-14.3%), respectively, which were not significantly different from control rat sera (12.3 +/- 6.7%, range 1.2-20.1%). TSAb activities in Group I, II, III, IV, and V rats were 608 +/- 675% (range 275-1813%), 234 +/- 26% (range 209-265%), 313 +/- 175% (range 187-568%), 190 +/- 63% (range 145-301%), and 134 +/- 24% (range 107-158%), respectively. TSAb activities in Group I, II, III, and IV rats were significantly higher than those from control rat sera (P < 0.01) while those of Group V were not significantly different from control rat sera. None of the rats in each group exhibited TSBAb activity.(ABSTRACT TRUNCATED AT 250 WORDS)

Amino Acid Sequence↗
PubMed1993

Autoimmune hepatitis and hypothyroidism associated with anti-thyroid hormone autoantibodies.

A 40-year-old hypothyroid female who had been treated with synthetic thyroxine was admitted to our hospital in October 1988 due to abnormal liver function tests. She had low serum free triiodothyronine (T3; 2.3 pg/ml) and high serum thyrotropin (TSH; 20.8 microU/ml) concentrations. On the other hand, the serum free thyroxine (FT4) level was inappropriately high, being 2.46 ng/dl. Immune precipitation of radiolabeled thyroid hormones with her serum disclosed the binding of 125I-T3 and 125I-T4 to the extent of 9.5% and 11.3%, respectively (normal ranges for 125I-T3 and 125I-T4 binding are less than 6.3% and 5.9%, respectively). 125I-T4 binding to the patient's serum gamma globulin was completely displaced with the addition of unlabeled T4. Further examination disclosed that anti-T4 antibodies in her serum belong to IgG kappa class immunoglobulin.

Adult↗
PubMed1993

Synthesis and biological activity of 1-(2-deoxy-2-C-fluoromethyl- and 2-C-hydroxymethylarabinofuranosyl)-cytosines.

We newly synthesized 1-(2-deoxy-2-C-fluoromethyl- and 2-C-hydroxymethyl-arabinofuranosyl)cytosines and evaluated their biological activities. The syntheses of these compounds were achieved by radical deoxygenation of tert-alcohol of 2'-position of the corresponding fluorohydrine and acetoxymethyl derivative. 1-(2-Deoxy-2-C-fluoromethylarabinofuranosyl)cytosine (5) showed potent antileukemic and anticytomegalovirus activities.

Antineoplastic Agents↗
PubMed1992

Biological activities of rabbit antibodies against synthetic human thyrotropin receptor peptides representing thyrotropin binding regions.

Recently, we have shown that the thyrotropin (TSH) binding regions of human thyrotropin receptor (TSHR) reside in two areas within residues 12-44 and 308-344. Serial antisera were raised against four overlapping synthetic peptides representing these two regions of TSHR (peptides 12-30, 24-44, 308-328, and 324-344) and were investigated for their ability to stimulate or block the cultured porcine thyroid cells. In addition, serum concentrations of triiodothyronine (T3) and thyroxine (T4) in serial sera obtained from each rabbit were examined. It was shown that residues of 12-30 and 324-344 of TSHR, respectively, are the site (at least a part of the site) where stimulating (TSAb) and blocking type (TSBAb) immunoglobulins are directed.

Amino Acid Sequence↗
PubMed1992

Improved microbioassay for plasma erythropoietin based on CFU-E colony formation.

We examined the conditions necessary for performing a reliable erythropoietin (EPO) assay based on CFU-E colony formation in fetal mouse liver cell (FMLC) microcultures using 96-well microtiter plates. Both linearity of colony numbers with the number of cells plated and comparison among the colony ratios at various densities of seeding cells indicated that the colonies originated from a single progenitor cell when 7500 or fewer cells were plated into individual microtiter wells. About a twofold CFU-E enrichment in 12- to 13-day FMLC was achieved by Ficoll-Paque centrifugation. Plasma treated with acid-boiling stimulated the colony formation most and contained no colony inhibitor. Dose-response curve for the plasma was parallel to the EPO standard curve. The "erythroid colony-stimulating activity" in the plasma was additive to that in the standard EPO, and was completely neutralized by a monoclonal antibody against recombinant human EPO. Using the assay procedure thus established, plasma EPO titer was determined in normal subjects, in patients with nonuremic anemia and polycythemia vera, and in dialysis patients with chronic renal failure. The use of different preparations of standard EPO resulted in a significant difference in the titers because their dose-response curves differed from one another. An inverse relationship was found between EPO titers and hemoglobin concentrations in the nonuremic anemic patients, but not in the dialysis patients with about one half the normal EPO level.

Anemia↗
PubMed1992

A case of rheumatoid arthritis associated with silent thyroiditis.

A 41-year-old female with rheumatoid arthritis had nontender enlarged thyroid gland. Thyroid function tests revealed increased concentrations of serum free T3 (FT3, 10.8 pmol/L) and free T4 (FT4, 31.1 pmol/L) with suppressed concentration of thyrotropin (TSH, lower than 0.1 mU/L) and low 24-hour thyroidal radioactive iodine uptake (1.6%). Serum thyrotropin receptor antibody (TRAb) was negative (0%) and she had positive anti-thyroglobulin and anti-microsomal antibodies. A diagnosis of silent thyroiditis was made based on laboratory findings. Serum concentrations of FT3 and FT4 normalized one month later without treatment. The causal relationship between the two diseases is discussed.

Adult↗
PubMed1992

Striatal dysfunction in Rolling mouse Nagoya: an electrophysiological study.

To elucidate the neuronal mechanism of the motor disturbances of the Rolling mouse Nagoya (rolling, genotype rol/rol), an experimental neurologic mutant mouse, we studied the physiological characteristics of neurons of the globus pallidus (GP) in rolling, comparing them with those of the behaviorally normal heterozygotes (+/rol) and normal controls (+/+). Forty-nine units in rolling, 41 in heterozygotes and 48 in controls were recorded under urethane anesthesia. The group mean of the interspike interval (ISI) of the spontaneous unit discharges was significantly shorter in rolling (42.2 +/- 2.6 msec, mean +/- SEM) than that of controls and of heterozygotes (55.4 +/- 2.4 msec, P < 0.001 and 50.4 +/- 2.6 msec, P < 0.05, respectively), indicating a significantly higher rate of spontaneous unit activity in the GP of rolling. In the controls and heterozygotes, about 60% of the GP neurons responded to striatal (ST) electrical stimulation with a predominantly inhibitory response, whereas a significantly smaller number of the GP neurons (22%, P < 0.001) exhibited inhibitory responses in rolling. The positive field potentials recorded in the GP evoked by ST stimulation were significantly smaller in amplitude in rolling (1.04 +/- 0.10 mV, mean +/- SEM) than that of the controls and heterozygotes (1.78 +/- 0.15 mV, P < 0.001 and 1.97 +/- 0.17 mV, P < 0.001, respectively). These results are in agreement with our previously reported findings of increased glucose metabolism and reduced concentration of GABA in the GP and substantia nigra pars reticula (SNr) in rolling.(ABSTRACT TRUNCATED AT 250 WORDS)

Animals↗
PubMed1992

Increased oxidized form of human serum albumin in patients with diabetes mellitus.

High-performance liquid chromatographic (HPLC) analysis of human serum albumin (HSA) on Asahipak GS-520H columns at neutral pH (6.87) showed a clear resolution of human mercaptalbumin (HMA) and nonmercaptalbumin (HNA), which are reduced and oxidized form of HSA, respectively. We studied the conversion of HMA to HNA (mercapt-nonmercapt conversion) as an index of oxidative change of the tissues and organs in 28 normal subjects and in a total of 47 patients with non-insulin dependent diabetes mellitus (NIDDM). Mean (+/- SD) values of the HMA fraction of HSA, f(HMA), [HMA/(HMA + HNA)], was significantly lower in NIDDM patients than in normal subjects (0.63 +/- 0.067 vs 0.75 +/- 0.028, P < 0.001). It was lower in poorly controlled NIDDM patients (0.63 +/- 0.058, n = 20) than in well controlled NIDDM patients (0.67 +/- 0.032, n = 9) (P < 0.05). Plasma glucose values sampled on occasions including overnight fasting and postprandial ones (r = -0.441, n = 47, P < 0.01), but not plasma glucose values sampled on overnight fasting (r = -0.345, n = 29) or postprandial (r = -0.467, n = 18) conditions and HbA1c (r = -0.211, n = 34), negatively correlated with the f(HMA) values, indicating that mercapt-nonmercapt conversion may not be due to cumulative hyperglycemia over a month, but due to short-term alteration in blood glucose level. The presence or absence of diabetic complications including nephropathy, retinopathy and neuropathy did not affect the f(HMA) values. In conclusion, decreased f(HMA) values in the diabetic patients suggested the presence of a rapidly altered oxidative change of albumin due to hyperglycemia.

Adult↗
PubMed1992

In vitro drug combination of 1-beta-D-arabinofuranosyl-E-5-(2-bromovinyl)uracil with anti-human immunodeficiency virus or anticancer nucleosides.

1-beta-D-Arabinofuranosyl-E-5-(2-bromovinyl)uracil (BV-araU) and E-5-(2-bromovinyl)uracil, a metabolite of BV-araU, did not affect either the anti-human immunodeficiency virus activity or the cytotoxicity of azidothymidine in MT-4 and MOLT-4 cells. Similarly, the bromovinyl compounds did not affect the in vitro antitumor activities of arabinosylcytosine, 5-fluorouracil, and 5-fluoro-2'-deoxyuridine. The anti-varicella-zoster virus activity of BV-araU was not influenced by azidothymidine, 2',3'-didehydro-2',3'-dideoxythymidine, or arabinosylcytosine, whereas relatively high concentrations of fluorinated antitumor agents enhanced the anti-varicella-zoster virus activity.

Antiviral Agents↗