A case of Hashimoto's thyroiditis with antibodies to thyroid hormone analogues.
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Adolescent↗
Biomedical subjects
S Sakata
Publications and source records attributed to S Sakata.
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↗
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↗
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↗
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↗
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↗
Relationship between erythropoietin and erythroid colony-stimulating activity in mouse plasma.
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Animals↗
Inverse relationship between erythroid colony-stimulating and inhibiting activities in plasma from non-uremic anemic patients.
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Anemia↗
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↗
Neutralization and immunoaffinity chromatography of erythroid colony-stimulating activity in mouse plasma by an anti-erythropoietin monoclonal antibody.
A relationship between erythropoietin (EPO) and erythroid colony-stimulating activity (ECSA) in mouse plasma was examined in fetal mouse liver cell (FMLC) cultures using a monoclonal antibody (MoAb) R2 raised against recombinant human EPO. Most of the ECSA in plasma from normal, anemic, and hypoxic mice was neutralized by MoAb. This neutralization could be reversed by addition of excess of anemic plasma or by preincubation of MoAb with goat anti-mouse IgG antibody. Most of the plasma ECSA was bound to an immunoadsorbent column containing the immobilized MoAb, and the retained ECSA was completely neutralized by MoAb. The plasma ECSA and standard EPO showed parallel dose-response curves and additive effect on CFU-E stimulation. Based on these findings, we conclude that mouse plasma ECSA detected by CFU-E assay using FMLCs is mainly due to EPO.
Anemia↗
Novel uracil derivatives: newly synthesized centrally acting agents.
A series of 1-amino-5-substituted uracils and their 4-thio or 2,4-dithio substituted analogues were synthesized and assayed for anti-conflict activity in rats and anesthetic activity in mice. 1-Amino-5-halogenouracils 3b-e, 1-amino-4-thiouracil (9a), and 1-amino-5-halogeno-4-thiouracils 9c, d showed both anti-conflict and anesthetic activities. The most active compound was 1-amino-5-chloro-4-thiouracil (9d) which showed anxiolytic activity at 2 mg/kg of oral administration (p.o.) on a modified Geller-Seifter conflict schedule. Its minimum effective dose (MED) was lower than that of diazepam. The 50 percent effective dose (ED50) for anesthetic activity in mice of the compound (9d) was 32.9 mg/kg, p.o.
Anesthetics↗
A case of hypothyroidism with simultaneous presence of stimulating type anti-thyrotropin (TSH) receptor antibodies and anti-thyroxine (T4) autoantibodies.
We have examined a hypothyroid patient with stimulating type anti-thyrotropin (TSH) receptor antibodies and without blocking type anti-TSH receptor antibodies. Although she had high serum TSH (240 microU/ml) and low free triiodothyronine (FT3, 0.49 pg/ml) concentrations, which agree with physical findings of hypothyroidism, she had an unusually high free thyroxine (FT4) concentration (3.56 ng/dl). Incubation of her serum with 125I-T4, followed by precipitation with 12.5% polyethylene glycol (PEG) disclosed a higher binding of 125I-T4 (34.4%) than in normal controls, being 5-7%. In addition, binding of 125I-T4 to her serum gamma-globulin was completely displaced by the addition of unlabelled T4. From these results it was concluded that her serum contained anti-T4 autoantibodies. Treatment with synthetic T4 was begun and her thyroid function was monitored by sensitive TSH radioimmunoassay (RIA) and RIA of FT4 after PEG treatment. Since both sensitive TSH RIA and FT4 RIA results after PEG treatment give results concordant with the physical findings, it was concluded that both of the RIA results are useful for the evaluation of thyroid function in patients with thyroid hormone autoantibodies.
Aged↗
Thyrotropin-secreting pituitary adenoma: a case report.
We report a 44-year-old male with a thyrotropin (TSH)-secreting pituitary adenoma. Based serum free triiodothyronine (FT3, 12.1 pmol/l) and free thyroxine (FT4, 28 pmol/l) were increased with normal basal TSH (3.1 mU/l). There was impaired TSH response to thyrotropin releasing hormone (TRH) test. Serum TSH was suppressed to 59% of the basal level after oral administration of 1.4 mg 3,3'-5-triiodothyroacetic acid (triac), whereas no suppression was observed after 75 micrograms daily administration of triiodothyronine (T3). Serum concentrations of alpha-subunit of TSH (TSH-alpha) and TSH-alpha/TSH molar ratio were high, being 1.95 micrograms/l, and 4.4, respectively. Pituitary CT and MRI scan showed the presence of a macroadenoma in the anterior lobe of the pituitary gland. Histopathology of the excised pituitary confirmed the diagnosis of a TSH-producing adenoma. A positive correlation between TSH and FT3 (r = 0.66, P less than 0.01) or FT4 (r = 0.54, P less than 0.01) was observed in serial sera obtained before and after operation.
Adult↗
Non-suppressed thyroidal radioactive iodine uptake (RAIU) in thyrotoxic phase in a case of subacute thyroiditis with thyroid-stimulating antibodies (TSAb).
In this paper, we report a 49-year-old female with subacute thyroiditis who had thyroid-stimulating antibodies (TSAb) and thyroid-stimulation-blocking antibodies (TSBAb) in serum. Although she was in the thyrotoxic phase and TSH was suppressed in May, 1990, her radioactive iodine uptake (RAIU) was not suppressed (35.5%) and a thyroid scan disclosed a diffuse goiter with no defect. Serum assays revealed the presence of TSAb, but TSBAb were negative. In August, 1990, the right lobe became undetectable by thyroid scan when the RAIU was 20.7% with the TSH level remaining suppressed. At that time, TSAb were negative, while TSBAb were positive. When the RAIU was 31.1% in October, 1990, both thyroid lobes became visible and the TSH level was normalized. TSBAb became negative, and although TSAb reappeared it later became undetectable. These results indicate that the changes in the patient's thyroid scan and RAIU were attributable to the presence of TSAb.
Autoantibodies↗
A case of papillary carcinoma of the thyroid associated with parathyroid adenoma without hyperparathyroidism.
A rare occurrence of the association of parathyroid adenoma in a case of thyroid papillary carcinoma is described. The patient was incidentally found to have parathyroid adenoma which was preoperatively diagnosed to be a metastatic lymph node. Analysis of her serum obtained before operation showed an elevation of serum parathyroid hormone (PTH) concentration without hypercalcemia. Since the association of hyperparathyroidism is high in patients with thyroid diseases, examination of not only serum levels of calcium and PTH but also careful interpretation of computed tomography (CT) and/or nuclear magnetic imaging (MRI) is necessary in the diagnosis of co-existing asymptomatic hyperparathyroidism.
Adenoma↗
Two cases of Hashimoto's thyroiditis with transient hypothyroidism.
Two cases of Hashimoto's thyroiditis are presented: a woman who suffered twice from transient hypothyroidism (Case 1), and a woman with polycystic ovary syndrome who had transient hypothyroidism which was inferred to have been caused by exacerbation of Hashimoto's disease (Case 2). In both cases, fluctuation in titers of both anti-thyroglobulin (TGHA) and antimicrosomal antibodies (MCHA) was observed. Although an increased serum thyroid stimulating hormone (TSH) concentration in Case 2 was associated with the increased titer of MCHA, this was not true of Case 1. Measurement of serum iodine concentration in Case 1 disclosed no correlation between serum TSH and iodine concentrations, suggesting that episodes of hypothyroidism in this patient are not due to iodine-induced hypothyroidism. The transient hypothyroidism in Case 2 was considered to be due to fluctuations in immune mechanism(s), but the reason in Case 1 was not clear in the present study.
Adult↗
Developmental changes in plasma erythroid colony-stimulating activity in mice: cyclic erythropoiesis associated with rapid growth.
To establish a role of erythropoietin (Epo) in regulation of fetal and neonatal erythropoiesis, plasma erythroid colony-stimulating activity (ECSA) in developing mice was measured by an erythroid colony-forming assay using fetal mouse liver cells. The ECSA in fetal and neonatal plasmas showed dose-response curves parallel to standard Epo curve and additive effects with standard Epo on the colony formation. Most of the plasma ECSA was neutralized by an anti-Epo monoclonal antibody. These results suggest that the plasma ECSA detected by the present bioassay is predominantly due to Epo. On day 12-14 of gestation, the plasma ECSA levels were at the highest values; thereafter the levels oscillated up to the age of 4 weeks. The packed cell volume (PCV) also oscillated, but with the reverse phase. Oscillation in PCV was associated with the growth. There was an inverse relationship between plasma ECSA and PCV levels throughout the prenatal and early postnatal periods. The results indicate that erythropoiesis in fetal and neonatal mice is regulated mainly on the basis of PCV-ECSA feedback control mechanism.
Animals↗
[Visualization of the female breast in bone scintigraphy].
Breast cancer incidence rates in Japan have more than doubled in the decade between 1975 and 1985 due to a well-established and affluent Western life-style. One hundred patients having breast cancer, 107 patients having mastectomies, and 243 patients having no breast cancer were reviewed for whole body and spot views of bone scintigraphy with 99mTc-MDP. The frequency of positive breast uptake in patients with no breast cancer showed a maximum in those patients between the ages of 30 and 40, with a progressive rise and fall before and after the peak, respectively. Patients between the ages of 50 and 60 with breast cancer showed a maximum uptake of 83%, while those patients between the ages of 70 and 80 with breast cancer showed an uptake higher than 50%. There was a markedly higher breast uptake ratio in the breast cancer group compared to the breast cancer free group. Although this scanning agent was of no value in recognition of tumor localization from breast uptake, we have to suspect a high incidence of cancer existence whenever there was unilateral increased breast activity. Even though the mechanism of 99mTc-MDP uptake by breast tissue is unknown, breast concentration of 99mTc-MDP appears to be influenced by hormones, especially estrogen.
Adolescent↗