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Biomedical subjects

K Kasagi

Publications and source records attributed to K Kasagi.

At least 91 records · Page 5Linked to original sources
PubMed1989

The prediction of thyroid function in infants born to mothers with chronic thyroiditis.

To elucidate the relationship between the mother's TSH-receptor antibody activities and the status of thyroid dysfunction in their offspring, blood was taken from 5 mothers with chronic thyroiditis with potent thyrotropin (TSH)-receptor blocking activity, and the potency of TBII and TSBAb activity was assayed more quantitatively. In those mothers whose infants suffered from neonatal hypothyroidism, the 50% inhibition of binding of labeled TSH to its receptors was obtained at more than 30 to 50-fold dilution, while in those mothers whose infants had transiently increased TSH or were euthyroid, the titers were of less than 30-fold dilution. Similarly, in those mother whose infants suffered from neonatal hypothyroidism, the 50% inhibition of TSH-induced cAMP accumulation was obtained at approximately 400 to 3000-fold dilution, while in those mothers whose infants had transiently increased TSH or were euthyroid, the titers were of less than 50-fold dilution. On the other hand TBII activity was much less potent in serum from patients with Graves' disease. These results suggested that the titration of serum with dilution to obtain 50% inhibition of labelled TSH binding to its receptor may be the simplest way to predict thyroid dysfunction of the newborn infants born to mothers with chronic thyroiditis.

Adolescent↗
PubMed1989

Mechanisms of increased sensitivity for detection of thyroid stimulating antibodies by use of hypotonic medium.

We have attempted to clarify the mechanism whereby the sensitivity to detect thyroid stimulating antibodies by use of cultured thyroid cells is enhanced when sodium chloride is removed from isotonic medium. Preexposure of cultured porcine thyroid cells to 10(-4) mol/l cycloheximide increased the subsequent cAMP response to TSab stimulation in isotonic NaCl medium, but not in hypotonic NaCl-free medium. Crude membrane fractions from porcine thyroid tissues were incubated with 6 Graves' IgGs in NaCl or NaCl-free medium at 37 degrees C for 1 h, centrifuged, washed, added [125I]TSH, and incubated for another hour. The result of the 'residual TBII assay' indicated that all 6 IgGs exhibited greater inhibition of [125I]TSH binding to the membranes when pre-incubated under hypotonic than isotonic conditions. When cultured porcine thyroid cells were incubated with 7 TSab samples in NaCl or NaCl-free medium depleted with 3-isobutyl-1-methylxanthine at 37 degrees C for 1 h, washed, added the NaCl-free medium containing 3-isobutyl-1-methylxanthine, and incubated for another 2 h, the use of NaCl-free medium during the pre-incubation resulted in greater increase in cAMP elicited by all 7 samples. In summary, 1) an inhibitory mechanism upon adenylate cyclase seems to be involved under isotonic conditions and may require new protein synthesis; 2) the binding of TSH receptor antibodies to the TSH receptor increases when NaCl is removed from isotonic medium, and 3) these factors are considered responsible for the enhanced sensitivity under hypotonic conditions.

Animals↗
PubMed1989

[A case report of thyroid papillary cancer that manifested leukocytosis and hypercalcemia after radiotherapy in bone metastasis].

Bone metastasis from a thyroid papillary cancer of a 59-year-old woman had been successfully treated with radiotherapy (6,000 rad) and iodine-131 (120 mCi). One year later, the patient developed leukocytosis (maximum 143,000/mm3) and hypercalcemia (16.0 mg/dl). A colony stimulating factor (CSF) was detectable in her plasma, and nude mice that had been given metastatic tissues similarly developed leukocytosis and hypercalcemia. Leukocytosis and hypercalcemia seemed to have been caused by the CSF produced in the bone metastasized tissues of this thyroid cancer.

Bone Neoplasms↗
PubMed1988

Studies on thyrotrophin receptor antibodies in patients with euthyroid Graves' disease.

Thyroid stimulating antibodies (TSAb) and TSH-binding inhibitor immunoglobulins (TBII) were assessed in 30 patients with euthyroid Graves' disease. TSAb were detected in 24 cases (80.0%), the incidence being not significantly different from that in hyperthyroid Graves' disease (29/30, 97.6%). On the other hand, the incidence of TBII in patients with euthyroid Graves' disease (12/30, 40.0%) was significantly lower than that in patients with hyperthyroid Graves' disease (30/30, 100.0%). The mean TSAb and TBII activities in the euthyroid patients were significantly lower than in the hyperthyroid patients (P less than 0.005 and P less than 0.001, respectively). Both TBII and, more closely, TSAb activities correlated with T3-nonsuppressibility and inhibition of serum TSH response to TRH stimulation. The findings supported the stimulation in vivo of the thyroid by these antibodies. Both antithyroglobulin and antimicrosomal antibody titres in euthyroid Graves' disease were significantly lower than in hyperthyroid Graves' disease (P less than 0.05, P less than 0.01, respectively). Goitre size was significantly smaller (P less than 0.001), and 99mTc thyroid uptake was significantly lower (P less than 0.001) in the euthyroid than in the hyperthyroid group. Thus, the reduced mass of thyroid tissues responding to the stimulators was considered to be one of the factors responsible for the euthyroidism despite the presence of TSAb. The high incidence of TSAb and relatively low incidence of TBII in euthyroid Graves' disease indicate that the presence of TSAb does not necessarily lead to hyperthyroidism and that the development of overt thyrotoxicosis may require augmentation of both TSAb and TBII.

Adolescent↗
PubMed1988

Development of hyperthyroidism following primary hypothyroidism: a case report with changes in thyroid-related antibodies.

We report a 48-year-old woman who developed hyperthyroidism following primary hypothyroidism. The serum T4 level was initially low and serum TSH level was high with clinical signs of hypothyroidism. The thyroid gland was not enlarged. Therapy with L-T4 was started. Three years later she developed hyperthyroidism; serum free T4 increased to 29.1 pmol/l after cessation of L-T4 therapy. The 123I thyroid uptake was increased with no suppression by exogenous T3. When she was hypothyroid, the activity of thyroid stimulating antibodies (TSAb) in serum measured by cyclic AMP production in cultured porcine thyroid cells were negative at 93.4% (normal less than 140%), while thyroid stimulation-blocking antibodies (TSBAb) determined by inhibition of TSH-induced cyclic AMP increase were positive at 96.1% (normal less than 40%). When hyperthyroidism subsequently occurred, TSBAb became negative (30.9%), while TSBAb became positive (163.3%). The findings indicate that hypothyroidism due to the potent TSBAb activity is not always persistent, but can be changed when various types of thyroid-relating antibodies change in the course of the disease.

Antibodies↗
PubMed1988

Transient neonatal hyperthyroidism and maternal thyroid stimulating immunoglobulins.

Serum thyroid stimulating hormone binding inhibitor immunoglobulins (TBII) and thyroid stimulating antibody (TSAb) concentrations were measured in three pregnant women with hyperthyroidism and then in their infants. The results suggested that TBII concentrations in infants in the neonatal period or from mothers during the third trimester of pregnancy showed a good correlation with the development of neonatal hyperthyroidism.

Adult↗
PubMed1988

Inhibition of thyrotropin-stimulated iodide uptake in FRTL-5 thyroid cells by crude immunoglobulin fractions from patients with goitrous and atrophic autoimmune thyroiditis.

We studied the effects of crude immunoglobulin (Ig) fractions of serum from patients with goitrous and atrophic autoimmune thyroiditis on TSH-, thyroid-stimulating immunoglobulin (TSI)-, forskolin-, and dibutyryl cAMP-stimulated 125I uptake by FRTL-5 thyroid cells. TSH-stimulated 125I uptake was inhibited by the Ig fractions from 15 patients with atrophic thyroiditis who had serum TSH binding inhibitor Igs (TBII), 10 (62.5%) of 16 TBII-negative patients with atrophic thyroiditis, 7 (43.8%) of 16 hypothyroid patients with goitrous thyroiditis who had no TBII activity, and only 2 (15.4%) of 13 euthyroid patients with goitrous thyroiditis who were negative for TBII. The mean inhibition of TSH-stimulated 125I uptake produced by the crude Igs from the former 3 groups of hypothyroid patients was statistically significant (P less than 0.001, P less than 0.001, and P less than 0.01, respectively) and correlated closely with the ability of the Ig fractions to inhibit TSI-stimulated 125I uptake (r = 0.882) and TSH-stimulated cAMP accumulation (r = 0.929). The inhibition of TSH- or TSI-stimulated 125I uptake by Ig samples containing TBII correlated significantly with the TBII activities. On the other hand, in the presence of Igs from TBII-negative hypothyroid patients, the inhibition of TSH-stimulated 125I uptake correlated significantly with that of forskolin-stimulated 125I uptake (r = 0.685). Although 6 (12.8%) of 47 Ig samples from hypothyroid patients inhibited dibutyryl cAMP-stimulated 125I uptake, the activities were marginal. These findings suggest that at least 2 types of antibodies are involved in the inhibition of TSH- or TSI-stimulated 125I uptake: 1 being a competitive inhibitor of TSH binding to its receptors, and another exerting influence on a step subsequent to TSH or TSI binding, presumably through adenylate cyclase inhibition.

Bucladesine↗
PubMed1988

Evaluation of TSH-receptor antibodies as prognostic markers after cessation of antithyroid drug treatment in patients with Graves' disease.

Clinical usefulness of thyroid-stimulating antibodies (TSab) and TSH-binding inhibitor immunoglobulins (TBII) for predicting the prognosis in patients with Graves' disease after cessation of antithyroid drug treatment was evaluated, and compared with that of T3 suppression test and goitre size. Among 46 patients who had been euthyroid on a maintenance dose of antithyroid drugs for at least one year and had discontinued taking medicine, 16 relapsed within one year (group 1), 7 relapsed later than 1 year (group 2), and 23 patients remained in remission for more than 1 year (group 3). Incidence of TSab, TBII, T3 nonsuppressibility and large goitre (transverse diameter longer than means of the values for the 46 patients: greater than or equal to 4.36 cm in females; greater than or equal to 4.74 cm in males) determined at the time of discontinuation of treatment was 87.5% (14/16), 56.3% (9/16), 78.6% (11/14) and 81.3% (13/16) in group 1; 66.7% (4/6), 28.6% (2/7), 50.0% (3/6), and 57.1% (4/7) in group 2, and 56.5% (13/23), 24.1% (5/23), 35.7% (8/23), and 26.1% (6/23) in group 3, respectively. All relapsed patients showed remarkable increases in both TSab and TBII activities at the time of relapse. High incidence of TSab in patients remaining in remission suggests that a reduced functional reserve of the thyroid, probably owing to destructive changes and/or shrinkage of the gland, may cause impaired responses to TSab and is involved in the cause of remission. Development of blocking type of TBII was not considered to be a cause of remission. Remission was predictable in all patients with any two of the indices such as negative TSab, positive T3 suppressibility, and small goitre.

Adolescent↗
PubMed1988

Comparison of thyroid stimulating activities measured by cyclic AMP production, those by radioiodine uptake in FRTL-5 cells and TSH-binding inhibitory activities in patients with hyperthyroid and euthyroid Graves' diseases.

By using an assay measuring cAMP production in FRTL-5 thyroid cells, thyroid stimulating antibodies (TSab) were detected in all of 15 patients with euthyroid Graves' disease (EG) and of 26 patients with hyperthyroid Graves' disease (HG). There was no significant difference between TSab activities in EG and in HG. In an effort to elucidate why EG patients remain euthyroid in spite of having TSab, we investigated the effect of the patient's crude immunoglobulin fractions on 125I uptake in FRTL-5 thyroid cells, one of the indices of stimulation subsequent to cAMP production. The 125I uptake stimulating (IUS) activity was positive in 46.7% (7/15) of EG patients and 88.5% (23/26) of HG patients, being significantly lower in the former than in the latter (P less than 0.02). Although the IUS activities significantly correlated with TSab activities in 41 patients with EG and HG (r = 0.784, P less than 0.001), the ratio of IUS to TSab in EG tended to be lower than that in HG. TSH-binding inhibitor immunoglobulins (TBII) activities in EG patients were negative or weakly positive, being significantly lower than those in HG patients (P less than 0.001). Thus, the ratios of TBII to both TSab and IUS activities were significantly higher in HG than in EG (P less than 0.01, P less than 0.001, respectively). The in vitro IUS activities also correlated with TBII activities (r = 0.441, P less than 0.001) and in vivo 99mTc thyroid uptake (r = 0.401, P less than 0.001) in both EG and HG patients.(ABSTRACT TRUNCATED AT 250 WORDS)

Adult↗
PubMed1988

Antibody-dependent cell-mediated growth inhibition of rat thyroid cells, FRTL-5, in patients with autoimmune thyroid diseases.

We studied antibody-dependent mononuclear cell-mediated growth inhibition of thyroid cells in 18 untreated patients with Graves' disease, 18 patients with chronic thyroiditis, and 15 normal subjects by measuring the ability of their sera to inhibit [3H]thymidine incorporation into DNA in a rat thyroid cell line, FRTL-5, in the presence of normal mononuclear cells. [3H]thymidine incorporation was significantly inhibited in the presence of sera from patients with Graves' disease and chronic thyroiditis (P less than 0.001), whereas it was not affected in normal subjects. A significant correlation was observed between the inhibition of [3H]thymidine incorporation and the titre of anti-microsomal antibodies (P less than 0.05). The inhibitory effect on [3H]thymidine incorporation was significantly abolished when serum pre-absorbed with human thyroid membranes was used (P less than 0.005). These inhibitory effects on [3H]thymidine incorporation significantly correlated with those obtained by using IgG fractions (P less than 0.01). These data indicate that antibody-dependent mononuclear cell-mediated growth inhibition may play a role in thyroid cell growth regulation in patients with autoimmune thyroid disease.

Adolescent↗
PubMed1988

Sensitive, practical bioassay of thyrotropin, with use of FRTL-5 thyroid cells and magnetizable solid-phase-bound antibodies.

We have developed a new method for assessing the bioactivity of thyrotropin (TSH) in human serum by measuring cAMP production in FRTL-5 thyroid cells as an index of stimulation. To eliminate serum inhibitors of the cAMP response to TSH, we purified samples by mixing them with anti-TSH antibodies coupled to magnetizable particles. This method of immunoaffinity purification was simple and suitable for the measurement of a large number of samples. The detection limit of the bioassay was 3.13 milli-int. units of human TSH per liter. Intra-assay and interassay coefficients of variation ranged from 5.4 to 8.6% and from 12.6 to 21.5%, respectively. The concentrations of bioassayable TSH closely correlated with those of immunoassayable TSH, both in the immunoaffinity-purified samples (r = 0.946, P less than 0.001) and in the serum samples (r = 0.945, P less than 0.001) from 14 euthyroid subjects and 53 hypothyroid patients with Hashimoto's thyroiditis. The bioactivity-to-immunoactivity ratio was almost constant (0.84 +/- 0.30; mean +/- SD) over the range of concentrations of immunoassayable TSH in serum, 6.3 to 177 milli-int. units/L. We also demonstrate that the technique is applicable to measurements of bioactivities of circulating forms of immunoreactive TSH in different pathophysiological conditions.

Animals↗
PubMed1987

Anti-TSH antibody with high specificity to human TSH in sera from a patient with Graves' disease: its isolation from, and interaction with, TSH receptor antibodies.

A patient with thyrotoxic Graves' disease had an apparent measurable level of serum TSH (2.5 microU/ml) by double-antibody radioimmunoassay (RIA). The serum IgG bound with both [125I]human(h)TSH and [125I]bovine(b)TSH. The [125I]hTSH binding was more effectively displaced by human than bovine TSH, whereas [125I]bTSH binding was displaced exclusively by bTSH. Scatchard analyses revealed that [125I]hTSH binding showed two components, whereas [125I]bTSH binding had only one component. Serum TSH determined by RIA became undetectable 21 months after antithyroid drug treatment with a parallel decrease of [125I]hTSH binding IgG activity. Four thyrotrophin binding inhibitory immunoglobulins (TBII) from other patients did not interfere with the binding of the patient's serum to [125I]h- or bTSH. Furthermore, the in-vitro thyroid stimulating activities of three thyroid stimulating antibodies (TSAb) were not affected by the addition of this patient's IgG. On the other hand, this patient's Ig (3 mg/ml) abolished the in-vitro thyroid stimulation by bTSH (100 microU/ml), but did not affect that by hTSH (100 microU/ml). The anti-hTSH antibody, TSH receptor antibody and anti-bTSH antibody in the serum, which contains TSAb as well as anti-TSH antibodies, could be partially purified by hTSH-agarose and subsequently by guinea pig fat cell membrane affinity absorptions. However, the anti-hTSH antibody fraction obtained had both hTSH binding activity and thyroid stimulating activity, and this fraction did not show any inhibitory effect on the in-vitro thyroid stimulation of autologous TSH receptor antibody or hTSH. The possible significance of anti-TSH antibodies is discussed.

Adult↗
PubMed1987

Thyroid gland: MR imaging.

Magnetic resonance (MR) imaging was performed in eight healthy volunteers and 30 patients with histologically and endocrinologically proved thyroid diseases. The use of a surface coil greatly improved spatial resolution, and normal anatomic structures were well demonstrated. In thyroid tumors, the margin, pseudocapsule, and lymph nodes were easily detected. Smooth margins, lobulated margins, and pseudocapsules were found in both adenoma and papillary carcinoma, whereas unclear margins were found only in papillary carcinoma. An unclear margin between the tumor and adjacent normal thyroid tissue seemed to reflect an ill-defined tumor border on gross pathologic examination. Metastatic lymph nodes as small as 3 mm were seen. Identification of small vessels enabled detection of dilated vessels in thyroid parenchyma in patients with Graves disease. Hemorrhage (hemorrhagic degeneration) was often found in adenoma, papillary carcinoma, and adenomatous goiter, resulting in variable signal intensity.

Adenoma↗
PubMed1987

The role of subunit sialic acid in the thyrotropic and gonadotropic activities of human chorionic gonadotropin.

The present studies were undertaken to delineate the role of sialic acid residues in the two subunits of hCG in relation to its hormonal activity. Sialic acid was removed by treatment of the individual subunits or intact hCG with insolubilized neuraminidase. Desialylated variants of hCG were obtained by combining an asialo subunit (as alpha or as beta) with its complementary intact or desialylated subunit. When tested in the hCG receptor assay using a rat testis fraction, none of the hCG variants exhibited any loss of activity compared with that of intact purified hCG. In in vitro bioassays that employed cAMP and testosterone generation in rat Leydig cells as indices of response, intact hCG and as alpha in combination with intact beta (as alpha-beta) were equipotent. In contrast, intact alpha-subunit combined with as beta (alpha-as beta) and desialylated intact hCG (asialo-hCG) showed activity that at the highest concentration of each tested (20 ng/ml) was no more than half of that evoked by intact hCG. In a TSH receptor assay in human thyroid membranes, loss of sialic acid from either one or both hCG subunits resulted in enhancement of binding affinity; the rank order of decreasing potency was asialo-hCG, alpha-as beta, as alpha-beta. However, despite their enhanced binding affinity, and like intact hCG itself, none of the variants elicited a cAMP response in either human thyroid membranes or cultured human thyroid cells. Rather, asialo-hCG and alpha-as beta, but not intact hCG and as alpha-beta, were effective antagonists of the stimulatory response induced by bovine TSH in thyroid cells. These findings indicate that desialylation of hCG enhances its binding affinity for hCG receptors in testis and, much more so, for TSH receptors in human thyroid. Desialylation also changes hCG from a full agonist to a partial agonist in testis and from a nonagonist to an antagonist in human thyroid. In all cases, sialic acid in the beta-subunit of hCG appears to have a predominant role in these effects.

Animals↗
PubMed1987

Inhibition of thyrotropin-induced growth of rat thyroid cells, FRTL-5, by immunoglobulin G from patients with primary myxedema.

We studied thyroid growth-blocking activity in immunoglobulin G (IgG) fractions of serum from 24 patients with primary myxedema, 24 patients with goitrous Hashimoto's thyroiditis, and 18 normal subjects by measuring the ability of their IgG to inhibit TSH-induced [3H]thymidine incorporation into DNA in a rat thyroid cell line, FRTL-5. Both groups of patients were receiving T4 when studied. [3H]Thymidine incorporation induced by 0.1 mU/ml bovine TSH was significantly inhibited by the addition of 2 mg/ml IgG from patients with primary myxedema (P less than 0.01), while it was not affected by IgG from the normal subjects or 23 of the 24 patients with goitrous Hashimoto's thyroiditis. IgG from patients with primary myxedema also inhibited the [3H]thymidine incorporation induced by Graves' IgG, but not that induced by forskolin, cholera toxin, (Bu)2cAMP or phorbol-12-myristate-13-acetate. The inhibition of TSH-induced [3H]thymidine incorporation by IgGs from patients with primary myxedema was significantly correlated with their inhibitory activities against both TSH-induced cAMP generation and TSH binding (P less than 0.001). These data indicate that these growth-blocking antibodies are directed against the TSH receptor and might be one of the causes of the thyroid atrophy in patients with primary myxedema.

Adolescent↗
PubMed1987

The mechanism of spontaneous hypothyroidism in patients with Graves' disease after antithyroid drug treatment.

The natural course of Graves' disease results in hypothyroidism in up to 20% of patients previously treated with antithyroid drugs. The precise mechanisms are not known, although autoimmune destruction of thyroid tissue has been proposed. We studied sequentially obtained serum samples from three patients with hyperthyroid Graves' disease previously treated with an antithyroid drug who became hypothyroid to determine possible causes of their hypothyroidism. Antithyroglobulin and antithyroid microsomal autoantibodies, TSH binding inhibitory immunoglobulin (TBII), thyroid-stimulating antibody (TSAb), and thyroid stimulation-blocking activity were measured. Autoantibodies were markedly elevated throughout the clinical course in all three patients. Patient 1 had no TBII and blocking activity and extremely high TSAb when she was euthyroid as well as hypothyroid. Hypothyroidism was probably the result of autoimmune thyroid destruction. In patient 2, TSAb disappeared, and TBII and blocking activity increased markedly when she developed hypothyroidism, which thus appeared to result from blocking antibodies. Patient 3 had intermittent periods of hyper- and hypothyroidism before becoming and remaining euthyroid. While initially hypothyroid, TBII was weakly positive, and TSAb was strongly positive; subsequently, when hyperthyroidism recurred, TBII and TSAb were strongly positive. Hypothyroidism appeared to result from focal autoimmune thyroiditis. Patients with hyperthyroid Graves' disease may develop hypothyroidism later by different means. Autoimmune thyroiditis, diffuse or focal, with thyroid destruction is one mechanism. The appearance of antibodies that block TSH stimulation may be another.

Adult↗