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Biomedical subjects

H K Min

Publications and source records attributed to H K Min.

At least 55 records · Page 3Linked to original sources

Graves' hyperthyroidism following primary hypothyroidism: sequential changes in various activities of thyrotropin receptor antibodies.

A 40-year-old male who developed Graves' hyperthyroidism following primary hypothyroidism is reported. He presented with clinical signs of hypothyroidism and concomitant myasthenia gravis. The thyroid was not palpable. He was treated with T4, pyridostigmine and prednisolone. One year later he developed hyperthyroidism and goitre. His initial serum IgG had no intrinsic thyroid stimulating activity, but showed almost complete inhibition of TSH-stimulated cAMP generation (99.4%, normal less than 38%) and [3H]thymidine incorporation (99.5%, normal less than 40%) into rat thyroid cells, FRTL-5 cells, with very high activity (80.2%, normal less than 15%) of TSH binding inhibitor immunoglobulin. When he developed hyperthyroidism and goitre, his IgG showed a strong thyroid stimulation, both cAMP production (27-fold increase) and [3H]thymidine incorporation (5.5-fold increase). No inhibitory activities were noted. These findings suggest that clinical states of autoimmune thyroid diseases can be changed in accordance with changes of functional properties of TSH receptor antibodies.

Adult↗

RFLP analysis of HLA-DR beta and -DQ beta genes in the Korean patients with insulin-dependent diabetes mellitus.

Human genomic DNA samples from 19 Korean patients and 31 controls of known serological DR antigen specificity were studied for insulin-dependent diabetes mellitus (IDDM)-associated variation in HLA-DR beta and -DQ beta restriction fragment length polymorphisms (RFLPs). Genotyping allowed for accurate assignment of HLA-DR types. For HLA-DRw6, a 12kb/DR beta/Taq I fragment was decreased in Korean IDDM (p less than 0.05). However, we could not find an increased frequency of a 12kb/DQ beta/Bam HI fragment or decreased frequency of a 3.7kb/DQ beta/Bam HI fragment in Korean IDDM. These results suggest a possible protective role of the HLA-DRw6 specificity in IDDM, irrespective of ethnic background, the absence of a specific DQ beta RFLP pattern associated with IDDM in Koreans, and the difference of the Korean population in the genetic of IDDM, compared to the Caucasoid population.

Asian People↗

Role of blocking TSH receptor antibodies on the development of hypothyroidism and thyroid atrophy in primary myxedema.

We studied 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 IgG to inhibit TSH binding to its receptor, and to inhibit TSH-stimulated cAMP increases and 3H-thymidine incorporation in a rat thyroid cell line, FRTL-5. The incidences of TSH binding inhibitor immunoglobulin (TBII), thyroid stimulation blocking antibody (TSBAb) and thyroid growth blocking antibody (TGBAb) in patients with primary myxedema were 53.6%, 75% and 65.2%, respectively. However, in goitrous Hashimoto's thyroiditis, these were 14.3%, 0% and 17.7%, respectively. These antibodies inhibited the receptor binding of 125I-bTSH dose-dependently, and also inhibited dose-dependently not only TSH-stimulated but also Graves' IgG-stimulated cAMP increase and 3H-thymidine incorporation. TBII activities of patients with primary myxedema were significantly correlated with both their TSBAb (r = 0.665; p less than 0.01) and TGBAb (r = 0.618; p less than 0.01) activities. Thirteen patients whose TBII activities were more than 50% had both strong TSBAb (75.1-100%) and TGBAb (57.4-100%) activities. Transient neonatal hypothyroidism was found in an infant born to a mother having potent TBII activities. Serum of the baby also had potent TBII activities and the baby's IgG inhibited TSH-stimulated cAMP increase and 3H-thymidine incorporation. These data suggest that a significant proportion 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 inhibition of TSH-stimulated cAMP generation.

Adolescent↗

Pathogenetic role of thyrotropin receptor antibody in the development of hyperthyroidism following primary hypothyroidism.

The authors measured thyrotropin binding inhibitory immunoglobulin (TBII), thyroid stimulating antibody (TSAb), and thyroid stimulation blocking antibody (TSBAb) sequentially in patients who developed hyperthyroidism following primary hypothyroidism, and compared changes in these various functional parameters of thyrotropin receptor antibody (TRAb) with clinical manifestations, in order to investigate the role of TRAb in the development of hyperthyroidism following primary hypothyroidism. In a patient with goitrous chronic thyroiditis, TBII, TSAb and TSBAb were not detected at the initial hypothyroid phase. But with appearance of TBII and TSAb, the patient developed hyperthyroidism. In a patient with primary nongoitrous myxedema, initially high TBII and TSBAb were detected without TSAb activity. His TSBAb disappeared and TSAb appeared with development of goiter growth and hyperthyroidism. These two mechanisms, that is, appearance of previously absent TSAb and conversion of TSBAb to TSAb, might play a causative role in the development of hyperthyroidism following primary hypothyroidism. These phenomena might be evidence that Graves' disease, chronic thyroiditis, and primary nongoitrous myxedema are on a continuing spectrum of a common syndrome sharing similar pathophysiology, at least with respect to TRAb.

Adult↗

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 radioreceptor assay, stimulation of adenylate 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 12 months observation period, but in eight patients TSAb activities gradually decreased and were undetectable at the end of a 12 month observation period. Persistence of TSAb was not associated with clinical outcome. Eight patients developed hypothyroidism within 1 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↗

Anti-bovine TSH antibodies in patients with Graves' disease and primary myxedema.

Three patients with Graves' disease and one patients with primary myxedema had serum TSH-binding immunoglobulins of high affinity detected by the TSH binding inhibition immunoglobulin (TBII) assay. These IgGs bound 61%, 33%, 60% and 53% of radiolabeled TSH, respectively, higher than the maximal specific binding (25%) in the TBII assay. Such binding was detected even in the absence of TSH receptor with only small differences in the precipitable radioactivity (61%, 28%, 61%, 54%, respectively, in comparison with the assay non-specific binding 11.3%). The 125I-bTSH binding of IgGs was competitively inhibited by the addition of bTSH, but not inhibited by hTSH. Moreover IgG binding to bTSH was not inhibited by the addition of serial dilutions of TBII positive pooled Graves' IgG (0.1-10 mg/ml) from different untreated patients. The titers of these TSH binding antibodies were not changed during the treatment of Graves' disease. Following guinea pig fat cell membrane receptor purification, the IgG of one patient with Graves' disease revealed TBII activity of 43.7% inhibition of 125I-bTSH binding to the TSH receptor without binding activity of 125I-bTSH in the absence of the TSH receptor. These studies suggest that anti-TSH antibodies and TSH receptor antibodies are present independent of one another in sera of some patients with autoimmune thyroid diseases and anti-TSH antibodies result in false TBII assay results.

Adult↗

Effects of several simple sugars on serum glucose and serum fructose levels in normal and diabetic subjects.

Fructose has a reaction constant 7.5 times as high as that of glucose in its nonenzymatic reaction with protein in vitro. The effects of glucose, sucrose and fructose ingestion on serum fructose and glucose levels were studied to evaluate the overall biohazard, i.e., the probability of their altering proteins while circulating in the blood. Normal and diabetic subjects were given either 75 g glucose, 75 g fructose, 75 g sucrose, or 112.5 g fructose after fasting, and their serum levels of sugars were measured at 0, 1, 2 and 3 h. In normal subjects, fructose ingestion produced significantly lower serum glucose levels and significantly higher serum fructose levels than did glucose ingestion, while sucrose produced intermediate results. The glycemic effect was found to be lowest for fructose and highest for glucose. The calculated overall biohazard was, however, highest for fructose and lowest for glucose in normal subjects. Furthermore, the serum fructosemic index was directly proportional to the amount of fructose ingested. In diabetic subjects, blood fructose clearance was significantly more delayed than in the controls when the same amount of fructose was ingested. These results suggest that an evaluation of the effects of simple in the diabetic diet requires a closer examination of the overall biological effects of the sugars.

Adult↗

Artificial induction of intravascular lipolysis by lipid-heparin infusion leads to insulin resistance in man.

Although extensive evidence indicates that free fatty acids can decrease glucose utilization in vitro, it is still controversial how an increase in lipolysis affects glucose metabolism in man. To test the hypothesis that an increase in lipolysis is related to insulin resistance, we examined the effect of lipid-heparin infusion on glucose metabolism in ten normal subjects by the euglycaemic glucose clamp technique and isotopic determination of glucose turnover. In the control euglycaemic clamp studies with insulin infusion at 0.2 and 1.0 mU.kg-1.min-1, endogenous glucose production was suppressed from the basal rate of 2.0 +/- 0.3 mg.kg-1min-1 to 1.1 +/- 0.7 mg.kg-1.min-1 and -0.4 +/- 0.7 mg.kg-1min-1 respectively. Glucose utilization increased from the basal rate of 2.0 +/- 0.3 mg.kg-1min-1 to 2.3 +/- 0.5 mg.kg-1min-1 and 5.9 +/- 1.8 mg.kg-1min-1 respectively. When the euglycaemic clamp studies were coupled with lipid-heparin infusion at comparable low and high rates of insulin infusion, endogenous glucose production increased (1.8 +/- 0.7 mg.kg-1.min-1, p less than 0.001, and 0.3 +/- 0.6 mg.kg-1.min-1, p less than 0.05, respectively), and glucose utilization decreased (2.1 +/- 0.3 mg.kg-1.min-1, not significant, and 3.2 +/- 0.7 mg.kg-1.min-1, p less than 0.001 respectively). These data suggest that the artificial induction of intravascular lipolysis by lipid-heparin infusion leads to a state of insulin resistance in man.

Adult↗

Transient neonatal hypothyroidism due to transplacental transfer of maternal immunoglobulins that inhibit TSH binding, TSH-induced cAMP increase and cell growth.

Transient neonatal hypothyroidism due to transplacental transfer of maternal blocking type TSH receptor antibodies (TRAb) was found in a baby born to a 27-yr-old mother, who had been receiving thyroxine medication for primary myxedema. Maternal IgG inhibited radiolabelled TSH binding to its receptor (TBII), TSH-stimulated thyroid adenylate cyclase (AC) activation (TSII) and TSH-stimulated 3H-thymidine uptake (TGII) in cultured rat thyroid cells (FRTL-5). At birth, the baby's IgG showed similar activities to maternal IgG but all these activities decreased gradually, and disappeared from her serum within 12 weeks of age. In the baby, initially nonvisualized thyroid was clearly visualized on 99 m-Tc thyroid scintigraphy when all these blocking activities disappeared, TSII and TGII being decreased more slowly than TBII, and the baby remained euthyroid after discontinuation of thyroxine. This study suggests that such IgGs induced hypothyroidism and thyroid atrophy in the mother and were responsible for transient neonatal hypothyroidism in the baby.

Adult↗

HLA and Graves' disease in Koreans.

The HLA-A, B, C and DR antigen distribution in 128 Korean patients with Graves' disease was compared with that in 220 controls. The frequency of HLA-B13, DR5 and DRw8 (relative risk 3.8, 4.4, and 2.3, respectively) was significantly increased in patients with Graves' disease. There was no significant correlation between the presence of these HLA antigens and the clinical features.

Female↗

Separation of physiological factors influencing glucose-insulin kinetics in diabetic patients.

A new quantitative method was developed for separation of physiological factors influencing glucose intolerance in diabetes mellitus using a three-compartmental model and the intravenous glucose tolerance test (IVGTT) in humans. The present model includes the physiologic factors of the hepatic glucose balance function, the peripheral tissue's glucose utilization rate, and the insulin secretion rate. The insulin sensitivity parameter and hepatic glucose sensitivity parameter were estimated in optimal fitting of the model-based data of glucose and insulin concentrations to the measured IVGTT data in 9 normal and 11 diabetic subjects. The results show that these sensitivity parameters are important for separation of the effects of the interactive physiologic factors, and, also useful in evaluating different glucose-insulin kinetics in 3 clinical groups of normal and diabetic subjects.

Adult↗