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Biomedical subjects

K Kasagi

Publications and source records attributed to K Kasagi.

At least 109 records · Page 6Linked to original sources
PubMed1987

Optimization and clinical assessment of a radioreceptor assay for thyrotropin-binding inhibitor immunoglobulins.

We tried to improve the sensitivity of a radioreceptor assay for thyrotropin-binding inhibitor immunoglobulins (TBII) by modifying assay conditions. About a twofold increase in sensitivity without a loss of reproducibility was obtained by prolonging the incubation of the receptors with test serum from 15 to 120 min before the addition of 125I-labeled thyrotropin. In 20 untreated, 49 treated patients with Graves' disease and 19 patients with euthyroid Graves' disease, TBII activities obtained using 120 min preincubation were significantly higher than those obtained using 15 min preincubation (p less than 0.005). No significant increase in TBII activities was observed in the presence of sera from patients with primary hypothyroidism (n = 17), simple goiter (n = 7), adenomatous goiter (n = 11), thyroid adenoma (n = 11) or cancer (n = 12). TBII were detectable in 15 (47%) of 32 triiodothyronine-nonsuppressible Graves' patients who were receiving maintenance antithyroid drug therapy using 120 min preincubation, while they were positive in only 6 patients (19%) using 15 min preincubation. The assay using a longer preincubation period was found to be sensitive, specific and useful for diagnosis and follow-up of Graves' disease.

Adenoma↗
PubMed1987

Disappearance of blocking type thyrotropin binding inhibitor immunoglobulin (TBII) during thyroid and steroid medication in a patient with autoimmune thyroiditis.

A 55 year-old female had suffered from 3 consecutive diseases for a year. The diseases were ulcerative colitis, primary hypothyroidism and idiopathic thrombocytopenic purpura, and had been treated with L-thyroxine (50 micrograms daily) and betamethasone (0.5 to 1.5 mg daily). On examination, the thyroid gland was not palpable at all, thyroid 99 mTc pertechnetate uptake was 0%, and an echogram revealed the existence of an atrophic gland. Thyrotropin binding inhibitor immunoglobulin (TBII) in the serum was elevated to 58.0% and her IgG almost completely inhibited the in vitro cAMP increase due to bTSH. After 5 months TBII turned out to be negative and the inhibitory IgG activity was reduced significantly. The thyroid gland also became visible scintigraphically. Thyroid medication was then stopped. Four months after the cessation of thyroxine, she felt quite well and her thyroid functions remained within the normal ranges. Antibody to Yersinia enterocolitica was positive at a low titer (X20) in the early stages, but elevated reciprocally with the fall in TBII and finally reached X320. In conclusion, evidence of the disappearance of blocking type TBII from the serum was demonstrated for the first time. Steroid might have caused some favorable effects, and this clinical report indicates the possibility that remission of hypothyroidism due to blocking type TBII can be expected.

Antibodies, Bacterial↗
PubMed1987

HLA-DR antigen expression on intrathyroidal lymphocytes and thyrocytes in Hashimoto's thyroiditis and Graves' disease: an immunohistological study.

In frozen sections of thyroid glands with Hashimoto's thyroiditis (HT) and Graves' disease (GD), infiltrating lymphocytes were tested for their expression of HLA-DR antigens as a marker of in situ activation. In a combination of indirect immunoperoxidase and direct immunofluorescence staining, most of the immunoglobulin D positive mature B cells were found to be DR positive (DR+) in both diseases. In HT, sizable portions of both helper/inducer T (Leu3+) and suppressor/cytotoxic T (Leu2+) cells were DR+ in interfollicular regions as well as in lymphocyte clusters and lymphoid follicles. In GD, the proportion of DR+ cells in the interfollicular Leu2+ population was significantly lower than that of HT. DR+ thyrocytes were seen in all 14 cases of HT and in 14 out of 16 cases of GD, especially in the vicinity of lymphocyte aggregates. The extent of their DR expression was not correlated with the percentage of DR+ cells in either T subset. These results indicate that a significant portion of infiltrating T cells are activated in autoimmune thyroid diseases, and there may be bidirectional interaction between DR+ thyrocytes and DR+ T cells. The difference in frequency of Leu2+ DR+ cells may account for the difference between the immunopathological features of HT and GD.

Adolescent↗
PubMed1987

A sensitive and practical assay for thyroid-stimulating antibodies using FRTL-5 thyroid cells.

A sensitive, precise and practical assay for thyroid stimulating antibodies was developed in which poorly differentiated rat thyroid cells (FRTL-5) were exposed to crude immunoglobulin fractions precipitated from serum with 15% polyethylene glycol under hypotonic conditions. After the incubation at 37 degrees C for 2 h, cAMP released into Hank's medium without NaCl was determined by radioimmunoassay. The removal of NaCl from the isotonic Hank's medium greatly enhanced cAMP production in response to both TSH and thyroid stimulating antibodies. The assay was sensitive enough to elicit an approximately 30-fold increase in cAMP at 10 mU/l bovine TSH. Thyroid stimulating activities measured using FRTL-5 cells significantly correlated with those measured using cultured porcine (r = 0.918, N = 72) or human (r = 0.830, N = 23) thyroid cells. Thyroid stimulating activities were detected in all of the 50 patients with hyperthyroid Graves' disease, the 14 patients with recurrent hyperthyroid Graves' disease, and the 25 patients with ophthalmic Graves' disease. Thyroid stimulating activity was also detected in some patients (9/24, 37.5%) with Hashimoto's thyroiditis whose serum TSH concentrations were higher than 30 mU/l. However, it was completely abolished by pre-treatment of the sera with anti-TSH antibodies. Although thyroid stimulating activities were detected in one of the patients with simple goitre (N = 10) and in one with thyroid cancer (N = 10), none of the patients with silent thyroiditis (N = 7), adenomatous goitre (N = 11), and thyroid adenoma (N = 9) were positive for thyroid stimulating antibodies.

Animals↗
PubMed1987

Autoantibody against diiodinated tyrosine-gastrin in a patient with Graves' disease.

We describe autoantibodies against iodinated gastrin in a patient with Graves' disease. Values for serum gastrin differed in this case, depending on which of two different radioimmunoassay (RIA) kits was used. RIA with the dextran-coated charcoal method for separation of free tracer gastrin gave a value less than 9.5 pmol/L, whereas the value by a RIA kit by the double-antibody method was 318 pmol/L. The patient's serum contained a binding protein for 125I-labeled gastrin, as detected by Sephadex G-200 column chromatography. The IgG fraction was responsible for the ability of serum to bind 125I-labeled gastrin. Interestingly, of the two possible forms of iodinated gastrins, monoiodinated (MIT) and diiodinated (DIT) tyrosine-125I-labeled gastrin, only the latter bound to patient's IgG. Furthermore, DIT-gastrin, but not gastrin or MIT-gastrin, inhibited the binding of DIT-125I-labeled gastrin. The patient's serum evidently contains autoantibodies against DIT-gastrin that interfere with RIA of gastrin.

Adult↗
PubMed1986

Sonography of Hashimoto's thyroiditis.

Fifty-three untreated patients with histologically confirmed Hashimoto's thyroiditis were divided into two groups according to the echogenicity of the thyroid. In 25 cases, the echogenicity of the thyroid was almost the same as or less than that of the adjacent muscles. Such cases were classified as group A. The other 28 cases were classified as group B. Mean T4 levels in group A were significantly lower than those in group B. In addition, the cases in group A had abnormally low T4 and abnormally high TSH more frequently than those in group B. In all cases in group A, there was severe degeneration and disappearance of thyroid follicles, whereas in most of the cases in group B, follicles of normal size were generally seen. Hypoechogenicity of the thyroid is a sign suggesting hypothyroidism and severe follicular degeneration.

Female↗
PubMed1986

Changes in thyroid-stimulating and TSH-binding inhibitory activities in a patient who developed hyperthyroidism due to Graves' disease following primary hypothyroidism.

A 23-year-old female who developed thyrotoxic Graves' disease following primary hypothyroidism was reported. She presented with symptoms of hypothyroidism and slight exophthalmos. After primary hypothyroidism was confirmed, she was treated with T4 in a dose of 50 micrograms/d. Two months after delivery, 1 year after the initial diagnosis of hypothyroidism, hyperthyroidism developed while she was taking T4. Graves' disease was confirmed by persistent thyrotoxicosis, high 99mTc thyroidal uptake, negative T3 suppressibility and detection of TSH-receptor antibodies. During the hypothyroid phase, TSH-binding inhibitory immunoglobulins (TBII) could not be detected, while thyroid stimulating antibodies (TSAb) were positive showing between 5.8 and 9.0 fold increases in the amount of cAMP produced in cultured porcine thyroid cells. Her IgG did not inhibit TSH-induced cAMP increase in vitro. When she developed hyperthyroidism, TSAb activity became more potent (31.7 fold increase in cAMP) and TBII became positive (+61.3%).

Adult↗
PubMed1986

A sensitive and practical assay for thyroid-stimulating antibodies using crude immunoglobulin fractions precipitated with polyethylene glycol.

A simple, sensitive, and practical assay for thyroid-stimulating autoantibodies (TSAb) was developed in which cryopreserved porcine thyroid cells were incubated with crude immunoglobulin fractions sedimented from serum with polyethylene glycol. In the assay, 1.4- to 2.0-fold and 6- to 12-fold increases in cAMP released into Hank's medium without NaCl were found at 1 and 10 microU/ml bovine TSH, respectively. TSAb were detected in 41 (97.6%) of 42 patients with untreated hyperthyroid Graves' disease, 29 (55.8%) of 52 patients with hyperthyroid Graves' disease who were euthyroid while taking antithyroid drugs, 22 (78.6%) of 28 patients with euthyroid Graves' disease, and none of the patients with simple goiter, adenomatous goiter, thyroid adenoma, or thyroid cancer tested. TSAb activities measured using porcine thyroid cells significantly correlated with those measured using human thyroid adenoma cells (r = 0.908; n = 46; P less than 0.001). Thyroid-stimulating activity was also detected in 11 (28.9%) of 38 patients with Hashimoto's thyroiditis. However, the activity was considered to be due to TSH in the patients' sera, because it was completely abolished by pretreatment with anti-TSH antibodies. Serum TSH concentrations lower than 50 microU/ml did not affect the assay result. In Graves' disease after cessation of antithyroid drugs, 85.7% (12 of 14) of TSAb-positive patients relapsed, while 77.8% (14 of 18) of TSAb-negative patients remained in remission. Thus, the assessment of TSAb was useful as an index to predict prognosis.

Adenoma↗
PubMed1986

Binding of immunoglobulin G from patients with autoimmune thyroid diseases to solubilized guinea pig fat cell membranes crosslinked with 125I-TSH.

Binding of immunoglobulin G (IgG) to Triton-solubilized fat cell membranes crosslinked with 125I-TSH was studied by an indirect immunoprecipitation method. Guinea pig fat cell membranes (FCM) containing TSH receptors with an association constant of 1.92 X 10(9) M-1 were first reacted with 125I-TSH, then treated with a crosslinker, dissuccinimidyl suberate. The dissociation of 125I-TSH from the crosslinked 125I-TSH-FCM complexes due to the addition of 100 mU/ml unlabeled TSH was 9.0%, while it was 33% without the treatment. To the Triton-solubilized FCM crosslinked with 125I-TSH, 50 micrograms each of IgG from 20 normal controls, 20 patients with Graves' disease and 20 with Hashimoto's disease was added and precipitation was effected by adding anti-human IgG. In patients with Graves' disease, 125I-TSH-FCM complexes immunoprecipitated ranged from 1.10 to 4.18% with an average of 2.4 +/- 0.99 (S. D.) % which was significantly higher than those in normal controls (1.6 +/- 0.29%). The values in the patients with Hashimoto's disease averaged 1.7 +/- 0.53 (S. D.) which did not differ significantly from those of controls. The value did not correlate with either TSH-binding inhibiting activities or titers of anti-microsomal antibodies. These data suggest the presence of TSH-receptor antibodies which react with antigens other than TSH-binding sites in the patients with Graves' disease.

Adipose Tissue↗
PubMed1986

Clinical evaluation of radiotherapy for Graves' ophthalmopathy.

Seventeen patients with moderately severe ophthalmopathy due to Graves' disease were treated by cobalt or supervoltage radiotherapy. All patients complained of diplopia. The mean proptosis value was 21.4 mm. Three patients (18%) showed good response, 7 (41%) moderate and 7 minimal or no response. Improvement was noted mainly in soft tissue changes and diplopia, while proptosis decreased in only 5 patients. All except one patient who had marked extraocular muscle involvement revealed by computed tomography responded to treatment. These data indicate that radiotherapy may be indicated in patients with progressive ophthalmopathy, especially in those who are associated with extraocular muscle enlargement.

Adult↗
PubMed1986

Paired determination of thyroid-stimulating and TSH-binding inhibitory activities in patients with Graves' disease during antithyroid drug treatment.

Sequential changes in thyroid-stimulating antibodies (TSAb) and TSH-binding inhibitor immunoglobulins (TBII) during antithyroid drug treatment were studied in 17 patients with Graves' disease. Before treatment, TSAb and TBII were detected in 17 (100%) and 13 (76.5%) patients, respectively, with a significant correlation between the two activities (r = 0.600, n = 17, P less than 0.02). In 9 patients who became euthyroid as early as after 1-4 months of treatment, the TSAb and TBII activities both gradually decreased, and there was a good correlation between the changes of these activities during treatment. Among the 7 patients in whom small changes in TSAb and TBII activities were observed, 4 showed poor control of the thyrotoxicosis during the whole observation period (7 months-2 years). One patient who showed a marked dissociation between the changes in TSAb and TBII activities developed hypothyroidism, when his TBII became remarkably high. These potent TBII inhibited cAMP production induced by bTSH. These findings indicate that 1) changes in TSAb and TBII activities reflect the clinical course of hyperthyroidism in most patients with Graves' disease, and 2) development of a blocking-type of TBII may induce hypothyroidism in some patients after the treatment.

Adolescent↗
PubMed1985

Polyphloretin phosphate, an antagonist of thyrotropin action: evidence for an interaction with the hormone rather than the receptor.

Polyphloretin phosphate (PPP) is known to be an inhibitor of bovine TSH (bTSH)-induced stimulation of the thyroid in both in vivo and in vitro assays. The present studies were undertaken to delineate the mechanism of these effects. A high molecular weight PPP preparation strongly inhibited both the binding of 125I-labeled bTSH [( 125I]bTSH) to human thyroid membranes and the stimulation of adenylate cyclase evoked by bTSH therein. Inhibition of bTSH-induced adenylate cyclase activity by PPP was evident both in the absence and the presence of NaCl (150 mM) in the incubation medium. Incubation of membranes with PPP, followed by its removal, did not affect subsequent binding of [125I]bTSH, indicating that PPP did not bind firmly to or damage the TSH receptor. Gel chromatography on Sephadex G-100 revealed that [125I]bTSH incubated with PPP eluted earlier than [125I]bTSH alone, indicating that PPP had formed a higher molecular weight complex with [125I]bTSH. This effect could be prevented by the addition of an excess of unlabeled bTSH to the incubation mixture. Binding of [125I] bTSH in the higher molecular weight peak generated by incubation with PPP was less than half that in control specimens of [125I]bTSH. Studies with PPP were also conducted in a highly sensitive assay that employs cultured porcine thyroid cells and measures the cAMP response induced by bTSH. The inhibitory effect of PPP on bTSH-induced cAMP accumulation was also evident in this assay. However, the presence of divalent cations Ca++ and Mg++ in the assay medium greatly diminished the inhibitory effect of PPP. Similarly, addition of Ca++ and Mg++ to the incubation medium greatly reduced or abolished the inhibitory effect of PPP on [125I]bTSH binding. Both effects of these salts to lessen the inhibitory response to PPP were overcome by increasing the PPP concentration. Gel chromatographic studies revealed that Ca++ and Mg++ acted by inhibiting the formation of the high molecular weight complex of bTSH and PPP. From these findings, we conclude that PPP exerts its inhibitory effect on TSH-induced stimulatory responses in the thyroid, in vivo as well as in vitro, by forming a complex with the hormone. The complex either does not bind to TSH receptors or does so with much lower affinity.

Adenylyl Cyclases↗
PubMed1985

Primary myxedema with thyrotrophin-binding inhibitor immunoglobulins. Clinical and laboratory findings in 15 patients.

In a screening of 43 patients with primary myxedema, 9 patients were found to have IgG that inhibits the binding of 125I-thyrotrophin to its receptor (thyrotrophin-binding inhibitor immunoglobulins). Preparations of IgG from these patients did not stimulate thyroidal cyclic adenosine monophosphate generation and blocked thyroid stimulation by thyrotrophin in vitro. Clinical and laboratory features of 15 patients with this inhibitor, including 6 who were previously known, were compared with those of patients without the inhibitor. The patients with inhibitor, 2 men and 13 women, had onset of their hypothyroidism from age 2 to 49 years, and thyroid uptake in these patients was significantly lower than that in patients without inhibitor. Transient hypothyroidism was seen in all 5 infants born to 4 mothers having potent inhibitor immunoglobulins. These clinical findings indicate that thyrotrophin-receptor-blocking antibodies play a pathogenic role in a group of patients with primary myxedema.

Adolescent↗