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Biomedical subjects

S Sakata

Publications and source records attributed to S Sakata.

At least 163 records · Page 9Linked to original sources
PubMed1992

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↗
PubMed1992

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↗
PubMed1992

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↗
PubMed1992

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↗
PubMed1992

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↗
PubMed1992

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↗
PubMed1992

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↗
PubMed1992

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↗
PubMed1992

[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↗
PubMed1991

Localization and synthesis of the hormone-binding regions of the human thyrotropin receptor.

Two regions of human thyrotropin (thyroid-stimulating hormone, TSH) receptor (TSHR) (residues 12-44 and 308-364) were selected on the basis that they exhibit no sequence resemblance to luteinizing hormone/chorionic gonadotropin receptor. Five synthetic overlapping peptides (12-30, 24-44, 308-328, 324-344, and 339-364) were studied for their ability to bind 125I-labeled human TSH (hTSH), its isolated alpha and beta subunits, bovine TSH, ovine TSH, human luteinizing hormone, and human follicle-stimulating hormone. The human TSHR peptides 12-30 and 324-344 exhibited remarkable binding activity to human, bovine, and ovine TSH and to the beta chain of hTSH. Lower binding activity resided in the adjacent overlapping peptides, probably due to the contribution of the shared overlap to the binding. The specificity of TSH binding to these peptides was confirmed by their inability to bind human luteinizing hormone, human follicle-stimulating hormone, and the alpha chain of hTSH. Thyrotropins did not bind to bovine serum albumin or to peptide controls unrelated to the TSHR system. Furthermore, the binding of hTSH to TSHR peptides 12-30 and 324-344 was almost completely (approximately 90%) inhibited by rabbit antibodies against hTSH but not by antisera against unrelated proteins. It is concluded that the binding of TSH to its receptor involves extensive contacts and that the TSHR peptides 12-30 and 324-344 contain specific binding regions for TSH that might be either independent sites or two faces (subsites) within a large binding site.

Amino Acid Sequence↗
PubMed1991

Antitumor activity of 2'-deoxy-2'-methylidenecytidine, a new 2'-deoxycytidine derivative.

The antitumor activity of 2'-deoxy-2'-methylidenecytidine (DMDC), an inhibitor of DNA synthesis, was examined and compared with that of 1-beta-D-arabinofuranosylcytosine (ara-C) against various murine tumors and human tumor xenografts. Against P388 murine leukemia, repeated treatments of DMDC were more effective than its single administration. Interestingly, DMDC was effective against colon 26 murine carcinoma, M5076 murine reticulum cell sarcoma, LX-1 human lung cancer xenograft, and SK-Mel-28 human melanoma xenograft, which are less sensitive or refractory to ara-C, while DMDC was not more potent against murine leukemias P388 and L1210 than ara-C. The in vitro cytotoxic effects of DMDC and ara-C against L1210 leukemia cells were prevented dose dependently by deoxycytidine, suggesting that DMDC, like ara-C, may require phosphorylation by deoxycytidine kinase for antitumor activity. DMDC was effective against human and murine experimental tumor models, especially nonleukemic tumors refractory to ara-C, suggesting that DMDC will be a promising agent for the treatment of cancer.

Animals↗
PubMed1991

Thyroid hormone metabolism and nuclear binding in Gunn rats.

We examined the serum concentrations of total, free thyroid hormones and TSH, activity of hepatic T4 5'-deiodinase, and T3 binding to hepatic nuclei in homozygous (j/j) and heterozygous (j/+) Gunn rats. Both total T3 and free T3 (FT3) concentrations in sera from j/j rats were significantly lower than those of j/+ rats on 5-10, 15-20, and 25-30 days after birth. Both total T4 and free T4 (FT4) concentrations in j/j and j/+ rat sera were not significantly different on 5-10 days. However, in j/j rats they were significantly higher than those of j/+ rats on days 15-20 and 25-30. Serum reverse T3 (rT3) concentrations were higher in j/j than in j/+ rats on days 5-10, 15-20, and 25-30. Serum TSH concentration in j/j and j/+ rats on 15 days post-natal were 1.42 +/- 1.28 and 1.65 +/- 1.24 micrograms/l (mean +/- SD), respectively, which were not significantly different from each other. T3 formation from T4 in hepatic microsomal fractions obtained 15 days after birth was significantly lower in homozygotes than in heterozygotes (4.89 +/- 1.18 vs 11.15 +/- 2.38 pmol/mg protein/min, p less than 0.005). Binding constants (Ka) as well as maximal binding capacities (MBC) for T3 of hepatic nuclei from 15 day-old j/j and j/+ rats were similar (ka; 3.58 x 10(9) vs 3.15 x 10(9) M-1, MBC; 0.316 vs 0.380 pmol/mg DNA). From these results we suggest that decreased conversion from T4 to T3 is one of the major reasons for high serum levels of T4 and rT3, and low levels of T3 in j/j rats, and that nuclear T3 binding and pituitary TSH secretion are unaltered in j/j rats.

Animals↗
PubMed1991

Anti-bovine thyrotropin autoantibodies in patients with Hashimoto's thyroiditis, subacute thyroiditis, and systemic lupus erythematosus.

We report four cases found to have anti-bovine thyrotropin (bTSH) antibodies, two with Hashimoto's thyroiditis and the other two, each with subacute thyroiditis and systemic lupus erythematosus (SLE). The unusually high negative titers of anti-TSH receptor antibodies (Case no. 1, -43.1%; Case no. 2, -34.9%; Case no. 3, -55.2%; Case no. 4, -59.9%) led to the incidental finding of the presence of anti-bovine (bTSH) antibodies in each patient. Case no. 1 was diagnosed to have Hashimoto's thyroiditis and was treated with L-thyroxine (L-T4). With the treatment, serum free T4 (FT4)normalized with a decline in the serum TSH concentration. The other patient diagnosed to have Hashimoto's thyroiditis (Case no. 2) remained euthyroid even without supplemental thyroid hormone therapy and the serum concentrations of FT4 and TSH stayed within the normal range. The third is a case of subacute thyroiditis (Case no. 3) with a typical clinical course of the disease. She had the anti-bTSH antibodies on her first outpatient visit. Serial examination of her sera disclosed the antibody titers to be on the same range over the 28 months after the onset of the symptoms. The fourth is a patient with SLE who had been treated with steroid (alternative day therapy of 40 mg/day prednisolone). Titers of the anti-bTSH antibodies spontaneously declined to the negative level 5 months later. None of the four cases had antibodies against human TSH alpha-subunit of bovine LH and alpha-subunit of bovine FSH.(ABSTRACT TRUNCATED AT 250 WORDS)

Adolescent↗
PubMed1991

Immunogenetic study of thyroid hormone autoantibodies in a family.

Haplotypes of the human major histocompatibility complex (HLA) and immunoglobulin G heavy chain allotype (Gm) were determined in nine members of a family in which three sisters had thyroid hormone autoantibodies (THAA) in serum. Among three sisters with THAA, two of them were hypothyroid and treated with synthetic thyroid hormones (patients nos. 1 and 2). The other remaining sister (patient no. 3) was euthyroid. Light chain allotype (Km) in them was also examined. Three patients had the same two Gm haplotypes. Km (1) allotype was negative in these three patients. HLA haplotypes of patient no. 1 were the same as those of patient no. 2. However, HLA haplotypes of patient no. 3 were completely different from those of patients nos. 1 and 2. The same combination of Gm haplotypes and the absence of Km (1) allotype were not observed in the remaining members without THAA. These results suggest that genes linked to Gm and Km allotypes are associated with the production of THAA at least in our patients.

Autoantibodies↗
PubMed1991

Serum ferritin concentration in subacute thyroiditis.

Serum concentration of ferritin was measured in 20 patients (19 women, one man) with untreated (thyrotoxic phase) subacute thyroiditis, 32 patients (21 women, 11 men) with untreated Graves' disease, 17 patients (all women) with euthyroid Hashimoto's thyroiditis, 12 patients (all women) with hepatitis A (HAV), eight patients (all women) with pneumonia, and 59 normal controls (30 women, 29 men). In female patients with subacute thyroiditis, the serum concentration of ferritin was 163.6 +/- 116.3 micrograms/L (after log transformation, 2.12 +/- 0.31 micrograms/L, mean +/- SD), which was significantly higher than values in female Graves' disease (P less than .05), Hashimoto's thyroiditis (P less than .001), pneumonia (P less than .05), and healthy subjects (P less than .001), being 97.9 +/- 71.9 micrograms/L (after log transformation, 1.85 +/- 0.42 micrograms/L), 51.6 +/- 53.0 micrograms/L (after log transformation, 1.48 +/- 0.50 micrograms/L), 88.2 +/- 56.3 micrograms/L (after log transformation, 1.86 +/- 0.30 micrograms/L), and 25.2 +/- 7.4 micrograms/L (after log transformation; 1.16 +/- 0.10 micrograms/L), respectively, but was not significantly different with HAV, being 368.3 +/- 514.0 micrograms/L (after log transformation, 2.32 +/- 0.47 micrograms/L). In a male with subacute thyroiditis, the serum concentration of ferritin was 521.8 micrograms/L (after log transformation, 2.72 micrograms/L), which was higher than +/- 3 SD and +/- 1 SD of the levels in healthy males (93.0 +/- 55.9 micrograms/L; after log transformation, 1.89 +/- 0.27 micrograms/L) and male Graves' disease patients (257.0 +/- 195.5 micrograms/L; after log transformation, 2.28 +/- 0.38 micrograms/L), respectively. Elevated serum ferritin concentration significantly declined with treatment by either aspirin or prednisolone (paired t test, P less than .001).(ABSTRACT TRUNCATED AT 250 WORDS)

Acute Disease↗
PubMed1991

Synthesis and examination of antigenicity of four hormonogenic sites and two non-hormonogenic sites of human thyroglobulin.

Four peptides (HTg-1, 1-10; HTg-2, 2547-2558; HTg-4, 2592-2603; HTg-6, 2737-2748) which contain hormonogenic acceptor tyrosine (Tyr) residues and two control peptides (HTg-3, 2582-2591; HTg-5, 2687-2694) of human thyroglobulin (Tg) were synthesized, radioiodinated and their binding with serial anti-human Tg antisera which had been raised in two rabbits (TG-1, TG-2) tested. Although increased binding of each of the six peptides was observed, HTg-4 and HTg-2 had higher binding whereas HTg-1 and HTg-6 showed lower binding with the immune gamma globulin from both rabbits. Each of the six peptides was iodinated with inorganic iodine (127I) using the chloramine-T method and the inhibitory activity of each peptide on the interaction between 125I-T4 and anti-Tg antibodies was tested. At the same time, Tg obtained from a normal thyroid tissue (NTg, iodine content 0.38%) and from a Hürthle cell adenoma (CTg, iodine content 0.000%) were also tested for inhibition of 125I-T4 binding. 125I-T4 binding with rabbit anti-Tg antisera was displaced not only by NTg and CTg but also by three out of four hormonogenic peptides. Among the three peptides, HTg-2 had the highest inhibitory activity, inhibiting 125I-T4 binding to the extent of 21.5% (TG-1) and 16.0% (TG-2). Two control peptides (HTg-3, HTg-5) did not inhibit 125I-T4 binding with anti-Tg antibodies.(ABSTRACT TRUNCATED AT 250 WORDS)

Amino Acid Sequence↗
PubMed1991

Postnatal transition of gamma-globin gene expression in normal Japanese population.

Temporal course of postnatal changes in the gamma isoform composition of human fetal haemoglobin (HbF) was studied in 259 cord, 272 infantile and 216 adult Japanese blood samples. Reversed phase high-performance liquid chromatography was used for determination of the three isoforms of the gamma chain (A gamma T, A gamma I and G gamma), and the adult samples, usually with less than 1% of Hb F, were enriched for Hb F by an alkali denaturation-salting out procedure. The results show that the G gamma gene expression, kept at a higher and strictly-controlled level in the neonatal period, undergoes a gradual change during 1 year, beginning 3-4 months after birth, to the adult stage which is characterized by a generally lower and loosely-controlled expression of the gene. Further change seems to occur after 1 year, settling to the final adult level. The A gamma T gene frequency is estimated as 0.139 in the present Japanese adult population, and is essentially identical to the value for the newborns in the same population (0.141).

Adult↗