Biomedical subjects

H K Min

Publications and source records attributed to H K Min.

At least 37 records · Page 2Linked to original sources

PubMed1995

Differing frequency of autoantibodies to glutamic acid decarboxylase among Koreans, Thais, and Australians with diabetes mellitus.

The wide racial-geographic differences in the incidence and prevalence of insulin-dependent diabetes mellitus (IDDM) between Europids and Asian populations prompted us to compare frequencies of positivity of autoantibody to glutamic acid decarboxylase (GAD). The patients with IDDM included 41 Koreans, 30 Thais, and 45 Australian Europids; the Koreans included 14 cases regarded as atypical IDDM by reason of a delayed requirement for insulin treatment. Autoantibodies were measured by radioimmunoprecipitation using iodinated purified porcine brain GAD. The frequency of positive tests for anti-GAD of 30% (8/27) for Koreans and 51% (20/39) for Thais was significantly lower than the 84% (38/45) for Australian Europids, even after stratifying by age of onset. Correspondingly, the mean levels of anti-GAD among seropositive cases were significantly lower for Koreans than for Australian Europids. In contrast to Thais and Australians, more than half the Koreans were diagnosed at age > 20 years, but there was no significant difference in positivity for anti-GAD between those over or under the age of 20 at diagnosis. The different frequency of positivity in tests for anti-GAD among Koreans, Thais, and Australian Europids with IDDM suggests that there is a greater etiologic heterogeneity of IDDM among Asian than Europid populations, in whom autoimmune destruction of pancreatic islets predominates.

Adolescent↗

PubMed1995

Clinical heterogeneity of insulin dependent diabetes mellitus in Korea.

This study was undertaken to find out how many current Korean patients with insulin dependent diabetes mellitus (IDDM) had a previous history of non-insulin requiring phase. Fasting serum C-peptide levels were measured in the 2300 diabetic patients during the visit to the Asan Medical Center, Seoul, Korea. Fifty-nine patients showed fasting serum C-peptide levels below 0.13 nmol/l. These 59 patients were classified further into two groups according to their history of insulin requirement: group A who required insulin within 1 year after diagnosis or presented initially as diabetic ketoacidosis and group B who had non-insulin requiring phase at least for 1 year (median: 5 years; range: 1-23 years). Twenty-six patients (44%) were classified into group A and 27 patients (46%) into group B. Median age of onset was 26 years (range: 10-50 years) and 45 years (range: 23-73 years) in groups A and B, respectively (P < 0.001). While the two groups had similar values in the current and maximum body mass indices, sex ratio and the prevalence of islet cell antibodies, 58% of the group A and 7% of the group B patients had histories of diabetic ketoacidosis. These results suggest a clinical heterogeneity in patients with IDDM in Korea.

Adolescent↗

PubMed1995

Insulin restores fatty acid composition earlier in liver microsomes than erythrocyte membranes in streptozotocin-induced diabetic rats.

Alterations of fatty acid composition have been observed in a number of tissues in both experimental and human diabetes. Suppression of delta 6 desaturase in the liver, a key enzyme of fatty acid desaturation, has been reported to be responsible for these phenomena. We measured the fatty acid composition of the liver and the erythrocytes, and examined delta 6 desaturase activities to compare the effect of short-term insulin therapy on the tissues with and without delta 6 desaturase, ie., the liver and the erythrocytes using streptozotocin (STZ)-induced diabetic rats. Linoleic (P < 0.05), palmitic (P < 0.01) and docosahexaenoic (DHA) acid (P < 0.01) were higher and arachidonic (P < 0.01) and oleic acid (P < 0.01) were lower in the liver microsomes of diabetic rats when compared to those in control rats. These alterations were partly reversed with insulin treatment. In the erythrocyte membrane, linoleic (P < 0.01) and stearic acid (P < 0.05) were higher, and palmitic (P < 0.05), palmitoleic (P < 0.01), and arachidonic acid (P < 0.01) were lower in diabetic rats. In contrast to the case of the liver microsomes, however, these alterations were persistently observed after 48 h of insulin treatment. The activities of delta 6 desaturase in diabetic rats were 68% of those of controls (P < 0.05), and increased to 119% of controls after insulin treatment. These results show that insulin restores the fatty acid composition earlier in the liver microsome than in the erythrocyte membrane in STZ-induced diabetic rats. The erythrocyte membrane would not be suitable for the investigation dealing with rapid changes of fatty acid composition.

Animals↗

PubMed1994

The effect of obesity on fibrinolytic activity and plasma lipoprotein (a) levels in patients with type 2 diabetes mellitus in Korea.

To determine whether previously reported abnormalities in fibrinolytic activity and plasma lipoprotein (a) levels could reflect obesity rather than diabetes per se, plasma concentrations of tissue-type plasminogen activator (t-PA), type 1 plasminogen activator inhibitor (PAI-1), and lipoprotein (a) (Lp (a)) were investigated in sixty-four type 2 diabetic patients (56.1 +/- 9.5 years; body mass index, 24.6 +/- 3.3 kg/m2) and thirty-two control subjects (57.9 +/- 8.9 years; body mass index, 24.6 +/- 3.4 kg/m2). Both the plasma t-PA and PAI-1 antigen levels were similar between the diabetic group (10.6 +/- 3.8 ng/ml; 27.7 +/- 11.6 ng/ml) and the control group (12.2 +/- 3.5 ng/ml; 27.7 +/- 9.6 ng/ml). The PAI-1 levels were evenly distributed from 5.93 to 52.7 ng/ml in diabetic patients. The difference of Lp (a) levels between the two groups was negligible (the diabetic group, median 11 mg/dl (range 0-72 mg/dl); the control group, median 13 mg/dl (range 0-55 mg/dl)). Significant correlations between PAI-1 levels and body mass index (BMI) were observed in both groups. In the diabetic group, PAI-1 levels also correlated with fasting C-peptide levels (r = 0.54, P < 0.01) and serum triglyceride levels (r = 0.28, P < 0.05). However, we could not find a significant association between either t-PA or PAI-1 levels and Lp (a) levels in the diabetic and control groups.(ABSTRACT TRUNCATED AT 250 WORDS)

Adult↗

PubMed1993

Excimer laser photorefractive keratectomy for astigmatism.

The effectiveness of excimer laser photorefractive keratectomy (PRK) for astigmatism was evaluated. We treated 136 eyes of naturally occurring myopic astigmatism using the 193-nm excimer laser with an expanding slit and an iris diaphragm, and followed for a minimum of 6 months. At 6 months after operation, the mean refractive cylinder decreased from 1.62 +/- 0.88 D preoperatively to 0.48 +/- 0.48 D. For detailed analysis of the results, the surgically induced refractive change (SIRC) was determined from the preoperative and postoperative refractions by vector analysis of astigmatism. When we compared the cylinder of the SIRC with the preoperative refractive cylinder, the effect of the cylindrical ablation was 93.9 +/- 36.7% at 6 months. The axial error of the cylinder of the SIRC to the preoperative cylindrical axis was 5.9 +/- 10.2 degrees at 6 months. These results suggest that excimer laser PRK with an expanding slit appears to have a significant effect for the correction of astigmatism.

Adult↗

PubMed1993

Negative correlation between the conversion of thyrotropin receptor-bound blocking type thyrotropin receptor antibody to the stimulating type by anti-human IgG antibodies and the biological activity of blocking type thyrotropin receptor antibody.

It has been reported that receptor-bound blocking type TSH receptor antibody (TRAb) can be converted to the stimulating type by anti-human IgG antibodies. To evaluate the relationship between the conversion of receptor-bound blocking type TRAb to the stimulating type and the biological activity of blocking type TRAb, we compared converting activities of blocking type TRAb from 10 patients with primary nongoitrous hypothyroidism with both the doses of blocking type TRAb which show 50% inhibition of 125I-bTSH binding to the TSH receptor and those which show 50% inhibition of TSH-stimulated cAMP production in cultured rat thyroid cells (FRTL-5). The additions of anti-human IgG antibody to FRTL-5 cell-bound blocking IgGs resulted in the increase in cAMP production in a dose-dependent manner and the converting activities (percent increase of cAMP production) also depended on the doses of blocking IgGs. The converting activities were significantly correlated with the doses of blocking IgGs which showed 50% inhibition of 125I-bTSH binding to the TSH receptor (r = 0.71, p = 0.011). And these converting activities were also significantly correlated with the doses of blocking IgGs which showed 50% inhibition of TSH-stimulated cAMP increase (r = 0.81, p = 0.002), and were negatively correlated with thyroid stimulation blocking antibody activities (r = 0.58, p = 0.02). We have demonstrated that all cell-bound blocking type TRAb were converted to the stimulating type by anti-human IgG antibody and the degree of conversion was negatively correlated with the biological activity of blocking type TRAb.(ABSTRACT TRUNCATED AT 250 WORDS)

Adult↗

PubMed1993

Direct relationship between elevated free testosterone and insulin resistance in hyperprolactinemic women.

Women with hyperprolactinemia have been reported to have hyperandrogenemia and/or insulin resistance. However, little is known about the association of hyperandrogenemia and insulin resistance in these women. To investigate whether hyperandrogenemia and/or insulin resistance occur in hyperprolactinemic women, and to assess the relationship between them, we measured basal androgen level and both glucose and insulin levels after oral glucose administration in 20 hyperprolactinemic women and 7 female control subjects. Free testosterone level was higher and estradiol level lower in hyperprolactinemic women than in control subjects (p < 0.05), whereas dehydroepiandrosterone sulfate (DHEAS) and total testosterone levels were similar (p > 0.05). Both fasting glucose and insulin levels didn't differ in the two groups (p > 0.05). However, both serum glucose and insulin levels, after a 75 g glucose load, were significantly increased in hyperprolactinemic women, (p = 0.001, p < 0.001, respectively). In simple linear regression analysis in hyperprolactinemic women, only free testosterone level had a positive correlation with the incremental area under the insulin curve (insulin-IAU) (r = 0.47, p < 0.05). In multiple stepwise regression analysis, free testosterone level, mean blood pressure and DHEAS level were associated significantly with insulin-IAU (beta = 0.98, p < 0.0001; beta = 0.58, p = 0.002; beta = -0.67, p < 0.003, respectively). These results suggest that insulin resistance is closely related to elevated free testosterone level in hyperprolactinemic women.

Adult↗

PubMed1992

Inhibition of CD3-linked phospholipase C by phorbol ester and by cAMP is associated with decreased phosphotyrosine and increased phosphoserine contents of PLC-gamma 1.

The mechanisms by which phorbol 12-myristate 13-acetate (PMA) and cAMP attenuate the hydrolysis of phosphatidylinositol 4,5-bisphosphate (PtdIns 4,5-P2) induced by ligation of the T-cell antigen receptor complex (TCR) was studied in the human Jurkat T-cell line. It has previously been shown that stimulation of Jurkat cells with antibodies to CD3, components of the TCR, elicits a rapid and transient phosphorylation of phospholipase C (PLC)-gamma 1, the predominant PLC isozyme in Jurkat cells, at multiple tyrosine residues and that such tyrosine phosphorylation leads to activation of PLC-gamma 1. Prior incubation of Jurkat cells with PMA or forskolin, which increases intracellular cAMP concentrations, prevented tyrosine phosphorylation of PLC-gamma 1 as well as the hydrolysis of PtdIns 4,5-P2 induced by ligation of CD3. Dose-response curves of PMA and of forskolin for the inhibition of PLC-gamma 1 tyrosine phosphorylation and of PtdIns 4,5-P2 hydrolysis were similar. These results suggest that the inhibition of PtdIns 4,5-P2 hydrolysis by PMA and cAMP is attributable to reduced tyrosine phosphorylation of PLC-gamma 1. Treatment of Jurkat cells with PMA or forskolin stimulated the phosphorylation of PLC-gamma 1 at serine 1248. PMA treatment also elicited the phosphorylation of PLC-gamma 1 at an unidentified serine site. Phosphopeptide map analysis indicated that the sites of PLC-gamma 1 phosphorylated in Jurkat cells treated with PMA and forskolin are the same as those phosphorylated in vitro by protein kinase C (PKC) and cAMP-dependent protein kinase (PKA), respectively. Stimulation of Jurkat cells with antibodies to CD3 also elicited phosphorylation of PLC-gamma 1 at serine 1248 and at the unidentified serine site phosphorylated in PLC-gamma 1 from PMA-treated cells. Thus, phosphorylation of PLC-gamma 1 by PKC or PKA at serine 1248 may modulate the interaction of PLC-gamma 1 with the protein tyrosine kinase or the protein tyrosine phosphatase; this altered interaction may, at least in part, be responsible for the decreased tyrosine phosphorylation of PLC-gamma 1 seen in PMA- and forskolin-treated Jurkat cells. Furthermore, in the absence of PMA, activation of PKC by diacylglycerol provides a negative feedback signal responsible for reducing the phosphotyrosine contents of PLC-gamma 1.

Antigens, CD↗

PubMed1992

Evaluation of serum basal thyrotrophin levels and thyrotrophin receptor antibody activities as prognostic markers for discontinuation of antithyroid drug treatment in patients with Graves' disease.

OBJECTIVE: We evaluated whether antithyroid drug treatment could be terminated more appropriately when both the serum basal thyrotrophin (TSH) level and TSH receptor antibody activity have become normal. DESIGN: This was a prospective randomized study of patients with Graves' disease followed for a mean of 28 months after the withdrawal of antithyroid drug treatment. PATIENTS AND INTERVENTIONS: A total of 174 patients with hyperthyroid Graves' disease were entered consecutively into this study, 11 of whom were subsequently excluded. One hundred and sixty-three patients were divided randomly into two groups having different criteria for the discontinuation of the antithyroid drug. Group 1 consisted of 79 patients whose antithyroid drug treatment was discontinued if both their serum TSH level and thyrotrophin binding inhibitor immunoglobulin (TBII) activity normalized. Group 2 consisted of 84 patients who were treated for 24 months irrespective of their serum TSH level and TBII activity. All patients were treated initially with 400 mg/day of propylthiouracil followed by decreasing doses that maintained a euthyroid state. MEASUREMENTS: Serum basal TSH levels and TBII activities were measured using a radioimmunometric assay and a radioreceptor assay, respectively, every 2 months during the antithyroid drug treatment. RESULTS: The remission rate of Group 1 (51.9%) was not significantly different from that (63.1%) of Group 2. The mean duration of treatment in Group 1 was 10.2 +/- 4.5 months (range 5-24, median 10). Median duration of treatment in Group 1 was 14 months shorter than in Group 2. In Group 1, the relapse rate was independent of the duration of the treatment. Further, the mean duration of treatment in the relapsed patients was not significantly different from that for patients who went into remission (9.9 +/- 3.8 vs 10.7 +/- 5.7 months; P greater than 0.1). In Group 2, the relapse rate was dependent on the time when both the serum TSH level and TBII activity were normalized (chi 2 = 27.0, d.f. = 4; P less than 0.001). When both the serum TSH level and TBII activity were normalized, the relapse rate of Group 2 was not significantly different from that of Group I for treatment periods of 6-12 months (25 vs 24.2%, P greater than 0.1), 12-18 months (33.3 vs 40%, P greater than 0.1), and 18-24 months (46.2 vs 50%, P greater than 0.1). However, the relapse rate of Group 2 was significantly lower than that of Group 1 when there was only a 6-month treatment period (5.6 vs 42.9%, P less than 0.05). Of the clinical and laboratory parameters measured, male sex, change of goitre size during treatment, and TSH levels and TBII values at the end of treatment, were of prognostic significance in predicting a relapse. CONCLUSION: The present study suggests that antithyroid drugs treatment can be terminated more appropriately when both the serum TSH level and TBII activity are made normal, thus avoiding prolonged and unnecessary drug treatment.

Adult↗

PubMed1991

IgE-induced tyrosine phosphorylation of phospholipase C-gamma 1 in rat basophilic leukemia cells.

Stimulation of rat basophilic leukemia (RBL-2H3) cells with oligomeric IgE elicited a rapid and transient phosphorylation of phospholipase C (PLC)-gamma 1 on tyrosine residues. Prior incubation of RBL-2H3 cells with a protein tyrosine kinase inhibitor, herbimycin A, prevented the tyrosine phosphorylation of PLC-gamma 1 as well as the hydrolysis of phosphatidylinositol 4,5-bisphosphate induced by oligomeric IgE. However, 5'-(N-ethyl)carboxamidoadenosine, which is known to activate PLC through a G protein, did not elicit tyrosine phosphorylation of PLC-gamma 1. These results, together with previous findings showing that tyrosine phosphorylation of PLC-gamma 1 enhances its catalytic activity, indicate that phosphorylation of PLC-gamma 1 by a nonreceptor tyrosine kinase is the mechanism by which IgE receptor aggregation triggers PLC activation.

Animals↗

PubMed1991

Intra-abdominal fat is associated with decreased insulin sensitivity in healthy young men.

To distinguish the relative role of intra-abdominal and subcutaneous abdominal fat in metabolic aberrations in upper body fat localization, we measured the relationship between regional fat distribution and insulin sensitivity in nine young men (28.6 +/- 0.7 years; body mass index [BMI], 24.7 +/- 1.3 kg/m2). Regional fat distribution was measured by anthropometric measurement and computed tomography (CT). Insulin sensitivity was measured by euglycemic hyperinsulinemic glucose clamp. Insulin sensitivity, expressed as the ratio of rate of glucose utilization to the mean plasma insulin concentration during the second hour of glucose clamp (M/I) was negatively correlated with BMI (r = -.91, P less than .001), waist to hip girth ratio (WHR) (r = -.80, P less than .01), subcutaneous abdominal fat area (r = -.90, P less than .001), and intra-abdominal fat area (r = -.88, P less than .01). Stepwise forward regression analysis showed that in addition to BMI, intra-abdominal fat area was a significant correlate of decrease in insulin sensitivity. These findings suggest that intra-abdominal fat play an important role in decreasing insulin sensitivity, even in healthy young men.

Abdomen↗

PubMed1991

Cycloheximide inhibits interferon-gamma-induced class II major histocompatibility complex antigen expression in cultured rat thyroid cells.

The effects of the agents that are related to intracellular events on interferon-gamma-induced class II major histocompatibility complex antigen expression were studied using the technique of immunocytochemistry. Rat class II major histocompatibility complex antigen (RT1.B) was expressed in 88.3 +/- 3.3% (n = 3) of the functioning rat thyroid cells (FRTL-5) cultured in a medium containing 100 U/ml recombinant rat interferon-gamma (IFN gamma). Deprivation of bovine TSH had no effect on the expression of RT1.B antigen by IFN gamma. A23187 (1 nM to 2 microM) and/or 10 nM to 10 microM phorbol 12-myristate 13-acetate did not induce the expression of RT1.B antigen. IFN gamma-induced RT1.B expression was not inhibited by either 10 nM to 100 microM 1-(5-isoquinolysulfonyl)-2-methylpiperazine or 200 nM to 200 microM 8-(N,N-dimethylamino)octyl-3,4,5-trimethoxybenzoate hydrochloride. It was also not inhibited by either 5-200 microM verapamil or 500 nM to 20 microM trifluoperazine. However, 0.01-10 micrograms/ml cycloheximide inhibited IFN gamma-induced RT1.B antigen expression in a dose-dependent manner. These results suggest that IFN gamma induces RT1.B antigen expression in FRTL-5 cells via de novo protein synthesis independent of the cAMP system, phosphatidylinositide system, and voltage-dependent calcium channel.

Animals↗

PubMed1990

Hyperglycemia per se can reduce plasma free fatty acid and glycerol levels in the acutely insulin-deficient dog.

To evaluate the in vivo effect of hyperglycemia per se on plasma free fatty acid (FFA) and glycerol concentrations, euglycemic and hyperglycemic clamp studies were performed in six overnight fasted dogs in the state of insulin deficiency produced by somatostatin (SRIF) infusion. The mean blood glucose concentrations during the steady-state (the second hour of each study) averaged 4.65 +/- 0.10 mmol/L in euglycemic clamp and 14.11 +/- 0.10 mmol/L in hyperglycemic clamp. During the SRIF infusion, plasma FFA concentrations increased from 0.32 +/- 0.05 mumol/mL at the basal state to 0.76 +/- 0.04 mumol/mL at the steady-state in euglycemic clamp and from 0.26 +/- 0.04 mumol/mL to 0.43 +/- 0.02 mumol/mL in hyperglycemic clamp. Plasma glycerol concentrations increased from the basal value of 0.07 +/- 0.01 mumol/mL to 0.15 +/- 0.01 mumol/mL during the steady-state in euglycemic clamp and from 0.06 +/- 0.01 mumol/mL to 0.08 +/- 0.01 mumol/mL in hyperglycemic clamp. The steady-state concentrations of plasma FFA and glycerol in hyperglycemic clamp were significantly lower than those in euglycemic clamp (P less than .001; respectively). These results suggest that hyperglycemia per se might decrease plasma FFA and glycerol concentrations at least in part by decreasing lipolysis in the acutely insulin-deficient dog.

Acute Disease↗

PubMed1990

Initial role of macrophage in the development of anti-beta-cell cellular autoimmunity in multiple low-dose streptozotocin-induced diabetes in mice.

Multiple injections of low doses of streptozotocin to susceptible strains of mice produce an experimental autoimmune diabetes mellitus. To investigate the possible initial role of macrophages in the development of insulitis, we studied the effect of macrophage-toxic silica administration on the development of in vitro cellular cytotoxic immune response against pancreatic beta-cells. Multiple streptozotocin-treated mice developed hyperglycemia at day 12 and their splenocytes showed cytotoxicity against cultured rat insulinoma cells. Mice given silica and streptozotocin together remained normoglycemic and their splenocytes showed no cytotoxicity. In contrast, in vitro depletion of macrophages from the splenocytes of mice given multiple streptozotocin alone did not abolish the cytotoxicity. These results show that macrophages themselves contribute little to the cellular cytotoxicity, but are necessary for the development of cytotoxic cells. From these results we suggest that there are at least two different steps in the development of insulitis; the presentation of beta-cell autoantigen by macrophages to helper-T cells, followed by the development of beta-cell-specific cytotoxic cells.

Animals↗

PubMed1990

Negative correlation between the change in bone mineral density and serum osteocalcin in patients with hyperthyroidism.

To assess the changes in bone mineral density and osteoblastic activity in patients with hyperthyroidism and to investigate the relationship between those changes, we measured bone mineral density and serum osteocalcin in 109 patients with Graves' disease, comprising 75 untreated patients and 34 patients under treatment, and 200 normal controls. The degree of change in bone mineral density was quantified with Z transformation, in which we used means and SDs of bone mineral densities obtained in the process of age- and sex-matched 1:1 pairing developed by ourselves. Bone mineral density was low in female patients with hyperthyroidism in the spine, femur neck, trochanter, and Ward's triangle, but was not low in male patients. Serum osteocalcin was elevated in patients with untreated Graves' disease and correlated negatively with the Z values of bone mineral densities of the spine, femur neck, and trochanter. In conclusion, indices of osteoblastic activity were elevated in patients with hyperthyroidism, probably secondary to a thyroid hormone-induced increase in bone resorption which resulted in reduced bone mineral density. Quantification of the change in bone mineral density by using the parameters derived in the process of age- and sex-matched pairing seems to be an efficient method for statistical analyses.

Adolescent↗

PubMed1990

Changes in thyrotropin receptor antibody after subtotal thyroidectomy in Graves' disease: comparison with the degree of lymphocytic infiltration in the thyroid.

To evaluate changes in TSH receptor antibody after surgery in Graves' disease and its relationship with the degree of lymphocytic infiltration, serial serum levels of TSH receptor antibody were measured before and after the subtotal thyroidectomy in 50 patients with Graves' disease. In 22 (44%) out of 50 patients, thyrotropin binding inhibitor immunoglobulin (TBII) levels gradually decreased and disappeared completely within 12 months after surgery (TBII disappearing group). Twenty-eight (56%) patients showed persistent TBII activity and their levels were not changed until 12 months after surgery (TBII persistent group). The changes of thyroid stimulating antibody (TSab) levels were very similar to those of TBII in both groups. The thyroidal lymphocytic infiltration was more prominent in the TBII disappearing group. The degree of the decrease of TBII levels after surgery correlated with the grade of thyroidal lymphocytic infiltration. There was no significant difference of TSH receptor antibody (both TBII and TSab) levels between the thyroid and peripheral venous blood. These data suggest that the persistence or disappearance of TSH receptor antibody after surgery may reflect the difference between patients in whom the thyroid is the major site of TSH receptor antibody and those in whom additional sites of TSH receptor antibody synthesis exist.

Adolescent↗

PubMed1990

Changes in the properties of the thyrotropin receptor antibody in patients with Graves' disease after radioiodine treatment.

We investigated the effect of a single dose of 131I upon thyrotropin receptor antibodies (TRAb) in 21 patients with Graves' disease. The thyrotropin receptor antibodies were assessed by parallel measurements of thyrotropin binding inhibitor immunoglobulin (TBII), thyroid stimulating antibody (TSAb) and thyroid stimulation blocking antibody (TSBAb) in serum by radoreceptor assay, stimulation of adenlate cyclase and inhibition of TSH-stimulated adenylate cyclase activation in FRTL-5 cells, respectively. Prior to radioiodine treatment, TBII was detected in all 21 patients and TSAb in 19 patients. After radioiodine treatment, TBII activities did not change during the 12-months observation period, but in eight patients TSAb activities gradually decreased and were undetectable at the end of the 12-month observation period. Persistence of TSAb was not associated with the clinical outcome. Eight patients developed hypothyroidism within one year after radioiodine treatment. Three of the hypothyroid patients developed TSBAb, and the appearance of TSBAb coincided with the development of hypothyroidism. These results suggest that TSBAb might develop after radioiodine treatment in a minority of patients with Graves' disease and that the appearance of TSBAb, in addition to radiation-induced thyroid destruction, might be involved in the development of hypothyroidism following radioiodine treatment.

Adolescent↗

PubMed1989

Inhibition of thyrotropin-stimulated adenylate cyclase activation and growth of rat thyroid cells, FRTL-5, by immunoglobulin G from patients with primary myxedema: comparison with activities of thyrotropin-binding inhibitor immunoglobulins.

We studied the blocking type TSH receptor antibodies in 28 patients with primary myxedema and 21 patients with goitrous Hashimoto's thyroiditis by measuring the ability of their IgGs to inhibit TSH binding to its receptor, and to inhibit TSH-stimulated cAMP increase and [3H]thymidine incorporation in a rat thyroid cell line, FRTL-5. The incidences of TSH binding inhibitor immunoglobulin, thyroid stimulation inhibiting immunoglobulin and thyroid growth inhibiting immunoglobulin in patients with primary myxedema were 54.6, 75 and 65.2%, respectively, against 14.3, 0 and 17.7%, respectively, in goitrous Hashimoto's thyroiditis. The antibodies inhibited dose-dependently not only TSH stimulated but also Graves' IgG-stimulated cAMP increase and [3H]thymidine incorporation. The TSH binding inhibitor immunoglobulin activities in patients with primary myxedema were significantly correlated with both the thyroid stimulation inhibiting immunoglobulin (r = 0.665; P less than 0.01) and the thyroid growth inhibiting immunoglobulin (r = 0.618; P less than 0.01) activity. Thirteen patients whose TSH binding inhibitor immunoglobulin activities were more than 50% had both strong thyroid stimulation inhibiting immunoglobulin (75.1-100%) and thyroid growth inhibiting immunoglobulin (57.4-100%) activities. These data suggest that the vast majority of patients with primary myxedema have potent blocking type TSH receptor antibodies. These might play a role in primary myxedema causing hypothyroidism and thyroid atrophy through inhibiting TSH-stimulated cAMP generation.

Adenylyl Cyclases↗