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Biomedical subjects

S Sakane

Publications and source records attributed to S Sakane.

At least 19 recordsLinked to original sources
PubMed1999

Differences between changes in serum thyrotropin-binding inhibitory antibodies and thyroid-stimulating antibodies in the course of antithyroid drug therapy for Graves' disease.

There has recently been controversy regarding whether the measurement of thyrotropin-binding inhibitory antibodies (TBIAb) is useful in the management of Graves' disease. Another method of assessing Graves' disease by measuring adenylate cyclase activity in thyroid cells, known as thyroid-stimulating antibodies (TSAb), differs from TBIAb not only in terms of assay but also in immunoglobulin type according to recent studies. In this study, the concentrations of TBIAb and TSAb were compared in serial serum samples collected from 29 patients with Graves' hyperthyroidism during 12 months of antithyroid drug therapy. Before therapy, there was a correlation between TBIAb and TSAb (r = 0.59). The radioactive iodine uptake (RAIU) was not significantly correlated with either TBIAb or TSAb (r = 0.20 and r = 0.29, respectively), and the serum free thyroxine (FT4) concentration was also not significantly correlated with either TBIAb or TSAb (r = 0.06 and r = 0.22, respectively). In patients with Graves' ophthalmopathy, TSAb levels were higher than in patients without ophthalmopathy (1015%+/-851% vs. 456%+/-323%, p<0.01), but the TBIAb levels were not significantly different. After antithyroid treatment, TBIAb did not decrease significantly (from 42.1%+/-20.8% to 20.5%+/-19.5%, p = 0.29). On the other hand, TSAb was significantly decreased after 12 months of treatment (from 649%+/-611% to 294%+/-205%, p< 0.05). These findings indicate that TBIAb and TSAb are not identical, and that TSAb has a closer relationship to thyroid function than TBIAb. In the clinical setting, determination of the serum TSAb level may provide a more accurate index of the thyroid status in Graves' disease patients receiving antithyroid therapy.

Adult↗
PubMed1999

Acute and early effects of triiodothyronine administration on serum markers of bone and mineral metabolism.

There have been few studies on acute changes of bone metabolism in humans by thyroid hormone. This study aimed to examine the effects of triiodothyronine on serum markers of bone and mineral metabolism during a 7-d course of daily 75 microg therapy in 14 normal volunteers by drawing blood on 1, 2, 3, 5, and 7 d of therapy. Serum calcium concentrations did not significantly change during the course of therapy, while serum phosphorus concentrations were significantly (p < 0.05) decreased from 3.21 +/- 0.43 mg/dL (mean +/- SD) to 2.85 +/- 0.46 mg/dL on the 7th d. Serum PTH concentrations were significantly decreased from 339 +/- 116 pg/mL to 316 +/- 29 pg/mL. Serum concentrations of alkali-phosphatase and bone-specific alkali-phosphatase were not significantly changed, but serum osteocalcin concentrations were significantly increased from 5.71 +/- 1.98 mg/dL to 6.73 +/- 2.24 mg/dL. Serum carboxy-terminal propeptide of type I collagen concentrations were significantly decreased from 137.8 +/- 33.7 microg/L to 119.2 +/- 33.6 microg/L. Serum pyridinoline cross-linked telopeptide domain of type I collagen concentrations, a bone resorption marker, were significantly increased from 3.40 +/- 0.77 to 3.87 +/- 1.05 microg/L, and such significant increase was obtained from the 3rd day. The results indicate that some of bone and mineral markers change rapidly in response to triiodothyronine-induced acute thyrotoxicosis, but the manner of change is not the same as that of chronic thyrotoxicosis.

Adult↗
PubMed1999

Estrogen supplementation for bone dematuration in young epileptic man treated with anticonvulsant therapy; a case report.

We encountered a young man treated with anticonvulsant therapy who had greatly reduced bone mineral density. An 18-year-old man was admitted to our hospital for shoulder pain and further evaluation of decreased bone mineral density. He had been treated with anticonvulsants, including phenytoin, phenobarbital, valproic acid and zonisamide for seizures. Although testosterone was found within the normal range for adult men, the serum estrogen concentration was below the detection limit (< 10 pg/ml) and his wrist epiphyses were not yet closed. After 10 months of treatment with the conjugated estrogen, both his height and weight showed improvement, while his bone mineral density and bone age were increased. These findings suggested that estrogen therapy had a significant effect on his skeletal growth and bone maturation in man. This is the first report showing the beneficial effect of estrogen supplementation in an epileptic man receiving treatment with anticonvulsants.

Adult↗
PubMed1997

Incomplete thyrotroph suppression determined by third generation thyrotropin assay in subacute thyroiditis compared to silent thyroiditis or hyperthyroid Graves' disease.

Serum TSH concentrations were determined by both second and third generation assays in three types of thyrotoxicosis associated with subacute thyroiditis, silent thyroiditis, and hyperthyroid Graves' disease at the time of each patient's initial visit to the clinic. Serum TSH concentrations as measured by the second generation assay with an analytical sensitivity of 0.04 mU/L were below the detection limit in every patient. In contrast, serum TSH concentrations as measured by the third generation assay with an analytical sensitivity of 0.009 mU/L were below the detection limit in 18 of 21 (86%) patients with Graves' disease, 18 of 20 (90%) with silent thyroiditis, but only 4 of 18 (22%) with subacute thyroiditis. Changes in serum TSH concentrations were studied in healthy volunteers given daily 75 micrograms of T3; their serum TSH concentrations on the second generation assay fell below the detection limit within 3 days in every subject. However, the TSH concentration measured by the third generation assay remained above the detection limit in 6 of 8 normal subjects even on the 14th day of therapy. The reason for incomplete TSH suppression in most subacute thyroiditis patients may be that these patients had notable neck pain, and their initial visit to the clinic may have occurred earlier after the onset of disease than with patients who have had silent thyroiditis or Graves' disease. Thus, the serum TSH concentration had not decreased sufficiently below the detection limit at the time blood was drawn. The data suggest also that the highly sensitive TSH assay, if the level is above the detection limit, can be used to suppose that the short duration of the initiation of thyrotoxicosis indicates a case of subacute thyroiditis.

Acute Disease↗
PubMed1997

Cryofibrinogenemia with polyarthralgia, Raynaud's phenomenon and acral ulcer in a patient with Graves' disease treated with methimazole.

Cryofibrinogenemia is a cryopathy in which hypersensitivity to cold is a prominent feature. Cryofibrinogenemia developed in an 18-year-old Japanese female patient during methimazole therapy for Graves' disease. She developed cryopathy (livedo reticularis, Raynaud's phenomenon and acral ulcer) and polyarthralgia during methimazole therapy, and we detected cryofibrinogen in her plasma. Her symptoms resolved after administration of prostaglandins and anticoagulants. Several reports indicate that methimazole therapy induces autoantibody-related disease. In the present case, we cannot exclude the possibility that methimazole therapy contributed to the cryofibrinogenemia.

Adolescent↗
PubMed1996

A variant of adenomatous goiter with characteristic histology and possible hereditary thyroglobulin abnormality.

A variant type of adenomatous goiter was identified in 24 of 2160 patients with adenomatous goiter who underwent thyroidectomy. The characteristics of the thyroid gland in these 24 patients included large goiter, small follicles, scant colloid, and columnar follicular cells containing yellow-green granules on hematoxylin-eosin staining. The thyroid gland was slightly orange-red, and electron microscopic examination showed abundant lysosomes with colloid droplets. When comparing the features of this group with those of 24 patients with common adenomatous goiter, the incidence of familial predisposition to thyroid diseases in the former group was higher. The age at the time of detection of goiter was lower, i.e. 17 +/- 15 vs. 44 +/- 17 yr (P < 0.001, variant type vs. common type), the serum total T4 concentrations were lower (84 +/- 21 vs. 103 +/- 18 nmol/L; P < 0.01), and the serum TSH concentrations were higher (2.4 +/- 2.1 vs. 1.0 +/- 0.9 mU/L; P < 0.01). Thyroid radioiodine uptake was remarkably increased (49 +/- 22 vs. 16 +/- 9%; P < 0.001), and lower levels of serum thyroglobulin were noted (33 +/- 51 vs. 484 +/- 603 micrograms/L; P < 0.01). The thyroglobulin content was low in the thyroid gland studied. The data suggest that the etiology of this variant type of goiter is a hereditary abnormality in thyroglobulin synthesis, and this type of goiter may be distinguished from common adenomatous goiter by the characteristic morphology of the thyroid gland in addition to clinical findings.

Adult↗
PubMed1996

Changes in thyroid volume in response to radioactive iodine for Graves' hyperthyroidism correlated with activity of thyroid-stimulating antibody and treatment outcome.

This study investigated 1) the relationship between thyroid volume and thyroid function in radioactive iodine (RAI) treatment for Graves' disease, and 2) the activity of thyroid-related Ig in serum on the responsiveness of thyroid tissue to RAI. The changes in thyroid volume per megabecquerel (MBq) of 131I retained in thyroid tissue was calculated by ultrasonography as a quantitative indicator of the effect of RAI on thyroid volume. Of the 52 patients treated with 131I (3.7 MBq retained/g thyroid tissue), 26 patients showed thyrotoxicosis, 20 patients became euthyroid, and 6 patients developed hypothyroidism 6 months after therapy. The change in thyroid volume per MBq 131I was lower (P < 0.01) in the hyperthyroid patients than in the euthyroid or hypothyroid patients. The activity of thyroid-stimulating antibody in serum immediately before the therapy was greater (P < 0.01) in the hyperthyroid patients than in the euthyroid patients and was greater (P < 0.05) in the euthyroid patients than in the hypothyroid patients; it was inversely correlated with the changes in thyroid volume per MBq 131I (r = -0.667; P < 0.01). Accurate measurement of changes in thyroid volume during the course of RAI treatment provides evidence of the responsiveness of Graves' disease thyroid tissue to RAI, which is related to the outcome of thyroid function. Thyroid-stimulating antibody determination may be useful in deciding the appropriate dose of RAI to obtain euthyroidism instead of hyperthyroidism.

Adult↗
PubMed1995

Serum concentrations of granulocyte colony-stimulating factor (G-CSF) determined by a highly-sensitive chemiluminescent immunoassay during the clinical course of subacute thyroiditis.

Granulocyte colony-stimulating factor (G-CSF) concentrations in serum were determined for the first time by a newly developed and highly sensitive chemiluminescent immunoassay (the limitation of detection, 0.5 pg/ml) in ten patients with subacute thyroiditis, during treatment with glucocorticoid or indomethacin. Before therapy, circulating neurophil counts significantly increased to 5.15 +/- 2.07 x 10(3)/microliters compared with the convalescent phase (2.94 +/- 1.07 x 10(3)/microliters), and the data were correlated with individual serum G-CSF levels (r = 0.854, P < 0.01). Serum concentrations of interleukin-3 (IL-3) and granulocyte-macrophage colony-stimulating factor (GM-CSF) were less than the detectable threshold of ELISA. During two weeks of glucocorticoid therapy, although the circulating neutrophil counts increased from 5.15 +/- 2.46 x 10(3)/microliters to 7.73 +/- 1.64 x 10(3)/microliters (P < 0.01), serum G-CSF levels were depressed from 25.1 +/- 15.3 pg/ml to 13.8 +/- 13.9 pg/ml (P < 0.01). These data indicate that G-CSF is one of the mediators of the increase of neutrophils in subacute thyroiditis, while it does not contribute to steroid-induced neutrophilia.

Adult↗
PubMed1994

[A case of primary thyroid T-cell lymphoma with infiltration of lymphoma cells in peripheral blood: diagnosed by DNA analysis].

A 57-year-old woman came to our hospital with complaints of neck swelling and headache in 1991. She was diagnosed as having chronic thyroiditis in euthyroidism because she had a diffuse goiter with both antithyroglobulin antibody (TGHA) and antimicrosomal antibody (MCHA). In 1992, she complained of the rapid growth of her thyroid gland and a swallowing disturbance. Atypical lymphocytes were observed in 16.5% of leukocytes in peripheral blood and similar atypical cells were found in bone marrow. Although an ultrasound scan of the thyroid gland revealed a symmetrical enlargement without a pseudocystic appearance, cytological study with fine needle aspiration biopsy of the thyroid gland demonstrated an abundance of atypical lymphoid cells. A whole body scintigram with 67gallium citrate showed no significant accumulation except in the thyroid gland. With a diagnosis of suspected primary thyroid lymphoma, total thyroidectomy was performed. However the diagnosis of malignant lymphoma was not confirmed histologically. A study of lymphocytes subset with two-color flow cytometry, which was performed for both lymphocytes in peripheral blood and infiltrating lymphocytes in the resected thyroid gland, revealed abnormal increased CD4 positive T cells and decreased HLA-DR expression. Additionally, southern blot DNA analysis for abnormal lymphocytes using restriction enzymes, EcoRI and BamHI, demonstrated rearrangement of the T-cell antigen receptor, which indicates a monoclonal proliferation of lymphocytes. After total thyroidectomy, atypical lymphocytes in peripheral blood decreased, and circulating autoantibodies including TGHA and MCHA disappeared. From these data, this patient was finally diagnosed as having a primary T-cell lymphoma of the thyroid gland, which is a very rare type of thyroid lymphoma.(ABSTRACT TRUNCATED AT 250 WORDS)

Autoantibodies↗
PubMed1992

Peroxidase and coupling activities of thyroid peroxidase in benign and malignant thyroid tumor tissues.

The coupling activity of thyroid peroxidase (TPO) in thyroid glands from patients with benign adenoma, papillary carcinoma, and diffuse goiter (Graves' disease) was measured for the first time, in addition to the peroxidase activity of these tissues. The peroxidase activity of TPO in the mitochondria-microsomes fraction was measured with guaiacol or iodide as the second substrate. In the case of papillary carcinoma, the mean protein-based specific activity obtained by the guaiacol assay was about 1/7 of that of diffuse goiter. The iodide oxidation activity of carcinoma was very low, about 1/25 [corrected] of that in diffuse goiter and 1/70 of that in adenoma. The peroxidase activity in adenoma was almost similar in the guaiacol oxidation assay and approximately one half in the iodide oxidation assay as compared with that in diffuse goiter. There was a close correlation between the guaiacol and iodide oxidation assays in individual patients with adenoma and diffuse goiter, but not in patients with papillary carcinoma. The coupling activity of TPO was measured with thyroglobulin purified from pooled toxic diffuse goiters and chemically iodinated to contain little additional T3 and T4. The specific coupling activity of TPO in mitochondria-microsomes from carcinoma was significantly lower (about 1/5) than that of diffuse goiter, and the activity in adenoma was not significantly different (about 1/2) from that of diffuse goiter. The data of coupling activities has a close correlation with that of peroxidase activities in individual patients with adenoma but not in patients with carcinoma. Based on these findings, the qualitative abnormality of TPO and its relation to the cold 123I scintigram in thyroid tumors are discussed.

Adenoma↗
PubMed1992

Epithelial hyperplasia and decreased colloid content of the thyroid gland in triiodothyronine-predominant Graves' disease.

Patients with T3-predominant Graves' disease have an increased serum T3 level despite a normal or even lower level of serum T4 caused by antithyroid drug treatment. This study investigated the morphological characteristics of the thyroid gland in this type of hyperthyroidism. Ultrasound showed a similar thyroid echogenicity in both T3-predominant and ordinary Graves' disease, but thyroid weight was significantly greater in T3-predominant Graves' disease than in the controls [91 +/- 37 g vs. 48 +/- 17 g (mean +/- SD); P < 0.01]. The height of thyroid follicular epithelial cells were significantly greater in T3-predominant Graves' disease than in the controls (9.6 +/- 1.0 vs. 6.4 +/- 1.1 microns), but the epithelial height did not correlate significantly with the serum TSH receptor antibody titers. Epithelial cells occupied 26.4 +/- 10.9% of the total thyroid tissue in T3-predominant Graves' disease, while they occupied only 14.5 +/- 6.8% in the controls. Intracolloidal vacuoles also occupied a significantly greater area in the T3-predominant group (6.6 +/- 3.9% vs. 1.9 +/- 1.0% for controls). These findings suggest that the thyroid gland is more active in T3-predominant Graves' disease and has a more rapid turnover of intrathyroidal iodine than in the ordinary type of Graves' disease.

Adolescent↗
PubMed1992

Biochemical studies of the relationship between iodothyronine 5'-monodeiodinase and protein disulphide isomerase in rat liver.

The relationship between type I iodothyronine 5'-monodeiodinase (5'-MD) and protein disulphide isomerase (PDI) was investigated by using a synthetic 18-amino acid peptide (LAP475c), which corresponds to the sequence of amino acids at position 373-390 of PDI including its active site, and anti-LAP475c antibody. Western blot analysis revealed that our anti-LAP475c antibody was highly specific for 57K protein in solubilized rat liver microsomal protein (SRLMP) that corresponded to PDI. Anti-LAP475c IgG (1:100 dilution) precipitated 46% of 5'-MD. These data suggest that PDI may play a regulatory role in the 5'-monodeiodination reaction.

Amino Acid Sequence↗
PubMed1991

Insulin-dependent diabetes mellitus in which glycemic control was improved during pregnancy but deteriorated after delivery with the occurrence of postpartum thyrotoxicosis: a case report.

We report a patient, a twin, with diabetes mellitus whose hyperglycemic state fluctuated during the course of the pregnancy and the subsequent delivery. She was diagnosed as having slowly progressive IDDM because of her clinical course and the findings of serum positive ICA/CF, positive HLA-DR4 and disconcordance of diabetes mellitus with her identical twin. Insulin therapy was not initially needed in the first two years because the endogenous insulin secretion was not completely reduced. After two years of insulin therapy the patient became pregnant. Her glycemic control was remarkably improved without changes in dietary intake and insulin dosage. After delivery glycemic control deteriorated after delivery with the occurrence of postpartum thyroiditis. Urinary excretion of CPR was increased during pregnancy but decreased after delivery. ICA/CF in serum were persistently detected in the whole observation period. It seems that the improved glycemic control during pregnancy was caused by the reduction in the autoimmune reaction and the deterioration in glycemic control during the postpartum period was induced by the acceleration of the autoimmune reaction by the same mechanism of postpartum autoimmune thyroiditis.

Adult↗
PubMed1991

A study of the serum concentration of tumor necrosis factor-alpha in thyroidal and nonthyroidal illnesses.

We have studied serum concentrations of immunoassayable tumor necrosis factor-alpha (TNF alpha) and iodothyronines (T4, T3, and rT3) in normal subjects (n = 16) and patients with nonthyroidal illnesses (NTI; n = 13), hyperthyroidism (n = 10), and hypothyroidism (n = 9). The mean (+/- SEM; femtomoles per mL) serum concentration of TNF alpha was 45 +/- 4.3 in normal subjects, 84 +/- 38 in NTI, 54 +/- 6.0 in hyperthyroidism, and 50 +/- 10 in hypothyroidism; the various values did not differ significantly from one another. Serum TNF alpha was well within the normal range in all NTI patients, except one patient with a brain glioma and infection in whom it was elevated (540 fmol/mL). There was no significant correlation between serum TNF alpha and serum T4, T3, or rT3 levels in NTI patients. Similarly, there was no correlation between serum TNF alpha and serum thyroid hormone (T3 or T4) levels when data in normal subjects were combined with those in NTI patients. The dialyzable fraction of T3 and the free T3 concentration did not correlate with serum TNF alpha levels. However, there was a tendency toward a positive correlation between dialyzable fraction of T4 and the serum concentration of TNF alpha in NTI (r = 0.54; n = 11; 0.05 greater than P less than 0.1). The relationship between these two parameters became more clear when data in normal subjects and NTI patients were combined for statistical analysis (r = 0.59; n = 22; P less than 0.005). The free T4 concentration correlated positively with serum TNF alpha levels whether the data in NTI patients were analyzed alone (r = 0.93; P less than 0.001) or in combination with data from normal subjects (r = 0.85; P less than 0.001). Our data suggest that circulating TNF alpha may contribute to elevated free T4 in NTI. However, it is not a universal or common factor in the pathogenesis of other alterations in serum thyroid hormone levels in NTI (euthyroid sickness syndrome).

Adolescent↗
PubMed1990

[The prognostic application of thyroid volume determination in patients with Graves' disease].

Swelling of the thyroid gland is a common symptom in patients with Graves' disease. However, until recently there were no adequate means of measuring the thyroid volume. In this study, thyroid volume (in Graves' disease patients on antithyroid drug (ATD) therapy) was measured serially by a new ultrasound technique involving the use of a specifically programmed computer. The relationships between thyroid volume and prognosis, and between thyroid volume and serum thyroglobulin (Tg) concentration were examined. Sixty untreated patients with Graves' disease and 62 healthy subjects were included in the study. Twenty of the 60 patients with Graves' disease who had no anti-Tg antibodies underwent serial measurement of thyroid volume and serum Tg concentration during long term (18-42 months) ATD therapy. Thyroid volume in normal subjects ranged from 5.6 ml to 20.2 ml, with a mean of 12.0 +/- 4.0 ml. In patients with untreated Graves' disease, the volume ranged from 13.3 to 190.7 ml with a mean of 40.2 +/- 27.8 ml (n = 60). Thyroid volume was significantly correlated with both serum Tg concentration (n = 20, r = 0.678, p less than 0.01) and serum TSH receptor antibody activity (n = 18, r = 0.590, p less than 0.01). During ATD therapy, the thyroid volume decreased gradually in most patients. Eleven of 20 treated patients experienced remission after therapy was discontinued, and in these patients, thyroid volume was significantly smaller (p less than 0.01) than before treatment. Four patients developed hypothyroidism due to over dosage of ATD at which time thyroid volume increased in all four. In the course of therapy, even during episodes of hypothyroidism changes in serum Tg concentrations paralleled changes in thyroid volume. After 12 months of therapy, thyroid volume expressed as a percentage of the pretreatment value was significantly smaller in patients in remission (77.6 +/- 8.9%) than in those who did not show remission (92.4 +/- 11.6%). These data suggest that serial ultrasonographic measurement of thyroid volume is useful in predicting the course of hyperthyroidism in ATD-treated patients with Graves' disease.

Adolescent↗
PubMed1990

Isolation of a hepatic iodothyronine 5'-monodeiodinase by nondenaturing agarose gel electrophoresis.

We have examined the application of nondenaturing agarose gel electrophoresis for isolation of the catalytically active iodothyronine 5'-monodeiodinase (5'-MD) in rat liver microsomes. Preliminary studies showed that most ingredients of conventional sodium dodecyl sulfate (SDS)-polyacrylamide gel electrophoresis, including acrylamide, SDS, and bromophenol blue, markedly inhibited 5'-MD activity in solubilized rat liver microsomal proteins (SRLMP). We replaced these inhibitory components with those that had little or no inhibitory effect on the 5'-MD and devised conditions for nondenaturing agarose gel electrophoresis for isolation of a 5'-MD protein. SRLMP (up to 120 micrograms protein/well), prepared by preincubation with 5 mM 3-[(3-cholamidopropyl)dimethylammonio 1-propanesulfonate] (CHAPS) and 1% 2-mercaptoethanol, were subjected to electrophoresis in 0.35% agarose gel in 20 mM Tris-HCl, 10 mM EDTA, pH 6.6 buffer containing 2 mM CHAPS and 1 mM thioglycolic acid. Electrophoresis was carried out for 14 h at 4 C using 2.5 V/cm. After phoresis, the gel was sliced into 16 fractions, and homogenates of each fraction were tested for 5'-MD activity by incubation with 0.6 nM [125I]rT3 for 30 min at 37 C in the presence of 10 mM dithiothreitol. The peak 5'-MD activity was detected in fraction 6 (Rf, 0.375). This fraction accounted for about 30% of total 5'-MD activity and only 6% of protein in the gel. The gel slice containing the peak 5'-MD activity was next subjected to a second electrophoresis at pH 7.6 for 4 h in a 90 degrees different direction. The most 5'-MD activity was demonstrated in the third of 8 gel fractions. SDS-polyacrylamide gel electrophoresis of this fraction demonstrated only one 55 K protein in most experiments and occasionally an additional 35 K protein. The specific activity of 5'-MD in this fraction of greater than 11 pmol I-/mg protein.h was at least 2.3-fold that in SRLMP. Rabbits were immunized with agarose gel containing the peak 5'-MD activity. Immunized rabbit immunoglobulin G bound up to 70% of 5'-MD activity in SRLMP, and the binding effect varied in a dose-dependent manner. Western blot analysis revealed that the anti-5'-MD antibody bound only one 55 K protein among innumerable proteins in SRLMP. A specific antiprotein disulfide isomerase antibody bound a slightly larger, 57 K protein in SRLMP.(ABSTRACT TRUNCATED AT 400 WORDS)

Acrylamide↗