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Biomedical subjects

K Kuma

Publications and source records attributed to K Kuma.

At least 271 records · Page 15Linked to original sources

Gonadotropin response to luteinizing hormone releasing hormone in hyperthyroid patients with menstrual disturbances.

This study was designed to investigate the gonadotropin response to luteinizing hormone releasing hormone (LHRH) in patients with hyperthyroidism, as related to the presence or absence of menstrual disorders. Forty-one Japanese women with hyperthyroidism were separated into groups on the basis of the presence of a regular menstrual cycle, hypomenorrhea, or amenorrhea and further subdivided into the phase of the menstrual cycle at the time of testing. The findings in these groups were compared with those in normal subjects with respect to thyroid function, basal serum LH and FSH levels and serum LH and FSH responses to LHRH, and basal estradiol levels. Serum LH responses to LHRH were increased over normal subjects in those with hyperthyroidism regardless of the phase of the menstrual cycle and regardless of the presence or absence of menstrual disturbances. However, these augmented LH responses to LHRH were less marked in those with menstrual disorders than in those with regular menstruation. Both basal serum FSH and peak serum FSH response to LHRH were also increased in the follicular phase but not in the luteal phase of the cycle in hyperthyroid patients, regardless of menstrual function. These results suggest that high levels of circulating thyroid hormones augment the gonadotropin response to LHRH, and that increased LH and FSH secretion probably maintains the normal cyclic pituitary gonadal axis function in patients with hyperthyroidism.

Adult↗

Interaction between thyrotropin (TSH) binding inhibitor immunoglobulins (TBII) and soluble TSH receptors in fat cells.

To clarify whether TSH binding inhibitor immunoglobulins (TBII) are antibodies to the membrane site associated with the TSH receptor itself or its neighboring sites, the interactions of TSH and TBII with soluble TSH receptor were investigated with a TSH radioreceptor assay using labeled highly purified bovine TSH (bTSH) and Triton extracts from guinea pig crude fat cell membranes (800-10,000 x g fraction). Treatment of the crude fat cell membranes with 0.5% (vol/vol) Triton X-100 resulted in solubilization of membrane proteins with recoveries of 25-30%, whereas increasing the concentration of Triton X-100 in the assay medium caused a decrease of [125I]bTSH binding to the solubilized membranes. Thus, the solubilized membranes were found to retain the capacity to bind [125I]bTSH below the Triton X-100 concentration of 0.4% in the assay medium. Incubation of the solubilized membranes with [125I]bTSH for 24 h at 4 C led to a steady state of specific binding, while incubation at 37 C resulted in more rapid but less specific binding, with a shorter duration of the steady state. Maximum binding occurred within the physiological pH range. Both TSH and Graves' immunoglobulins (Igs) specifically inhibited [125I]bTSH binding to the solubilized membranes, as demonstrated by polyethylene glycol separation of the [125I]bTSH-solubilized membrane complex from unbound [125I]-bTSH. Scatchard analysis of [125I]bTSh displacement curves for both TSH and Graves' Igs indicated a single class of binding site for each, with an affinity constant of 1.8 x 10(9) M-1. In addition, Igs capable of inhibiting [125I]bTSH binding to the solubilized membranes were detected predominantly in the serum of patients with Graves' disease. These results strongly suggest that TBII are antibodies directed to the TSh receptor itself without strict organ and species specificity.

Adipose Tissue↗

Characterization of triton-solubilized TSH receptors from human thyroid plasma membranes.

The TSH receptor from human thyroid plasma membranes has been solubilized in 10 mM Tris/HCl, 50 mM NaCl, pH 7.4 containing 0.5% triton X-100. Binding of [125I]TSH to the soluble receptor showed rapid and reversible kinetics and reached a maximum within 30 min at 37 degrees C, by 1 h at 25 degrees C and by 24 h 4 degrees C. Optimal pH was 7.4. The soluble receptor retained specificity with cross-reactivity only to crude hCG (0.03%). Scatchard plots were curvilinear indicating the presence of at least two binding sites. The high affinity site showed an affinity content of 1.1 X 10(9) M-1 with binding capacity of 1.3 X 10(-10) M/mg protein. TSH-binding inhibitor immunoglobulins from patients with Graves' disease inhibited [125I]TSH binding to the soluble receptor in a dose-dependent manner. NaCl inhibited the TSh binding and this was ascribed to the decrease in the receptor capacity. Trypsin, neuraminidase and phospholipase C treatment of the solubilized receptor had no effect on TSH binding. The apparent molecular weight of the receptor, determined by gel filtration of Sepharose 6B, was approximately 300 000.

Cell Membrane↗

Changes in thyroid function in euthyroid subjects with a family history of Graves' disease: a follow-up study of 69 patients.

TRH tests were performed in 206 clinically and biochemically euthyroid relatives of patients with Graves' disease. In 117 of the 206, T3 suppression tests were performed. Results revealed that 56 of the 206 (27.1%) showed abnormal responses to TRH. Twenty-nine of these (14.1%) revealed absent or decreased responses, and 27 (13.1%) revealed augmented responses to TRH. Eight of the 117 (6.8%) were T3 nonsuppressible. These eight subjects consisted of 4 subjects out of 17 hyperesponders and 4 subjects out of 90 normal responders. The majority of suppressible subjects (86 among 109) demonstrated normal responses to TRH. Sixty-nine of the 206 subjects were followed for 6 months to 5 yr to observe changes in their thyroid functions. Among all 69 subjects 3 became clinically thyrotoxic 12, 12, and 18 months after their initial visit, respectively, and 2 became clinically hypothyroid 2 yr after their initial visit. Since 69 subjects were clinically and biochemically euthyroid and had no goiter or exophthalmos at their initial visit, the incidence of thyrotoxicosis or hypothyroidism in these subjects could be considered to be remarkably high. It is of interest that the 3 thyrotoxic patients were TRH hyporesponders at their first visit. One patient was T3 suppressible; T3 suppression tests were not performed in the other 2 patients at their initial visit. There was no abnormality in the first TRH test in 2 relatives who became hypothyroid. It is suggested that 1) among euthyroid relatives with a family history of Graves' disease, there are many with abnormalities in TRH responsiveness and T3 suppressibility, 2) nonsuppressible subjects are more likely to be TRH hyporesponders and vice versa, 3) hyperthyroidism or hypothyroidism occurs frequently in euthyroid relatives with a family history of Graves' disease, and 4) thyrotoxicosis occurs frequently in TRH-hyporesponders, and hypothyroidism occurs in the others.

Adolescent↗

Postpartum recurrence of hyperthyroidism and changes of thyroid-stimulating immunoglobulins in Graves' disease.

The changes of circulating thyroid-stimulating antibody (TSAb) in three patients with Graves' disease with relapsed hyperthyroidism after delivery were examined. All three patients were in clinical remission before and during pregnancy, but hyperthyroidism, with high radioactive iodine uptake, recurred 3--5 months post partum. TSAb activity, measured serially, was not detected at the time of the postpartum relapse, although it was detectable during pregnancy and in the euthyroid state after therapy. In two cases, the titer of antithyroid microsomal antibody increased concomitantly with an increase in the free T4 index. These data suggest that TSAb may not be a pathological thyroid stimulator in patients with recurrent hyperthyroidism after delivery in Graves' disease.

Adult↗

Blood pressure response to an angiotensin II antagonist in thyrotoxic patients with and without high blood pressure.

An angiotensin II antagonist, [sacrosine1, isoleucine8] angiotensin II, was infused into thyrotoxic patients. Blood pressure was monitored before and during the infusions to investigate whether the renin-angiotensin-aldosterone system was involved in the maintenance of blood pressure in normotensive and hypertensive thyrotoxic patients. Five out of 17 normotensive patients with hyperthyroidism showed more than a 10 mmHg decrease in mean blood pressure in response to the infusion (responders), while the remaining 12 patients showed no substantial change in blood pressure (non-responders). The infusion caused little change in blood pressure in 8 hyperthyroid patients with systolic hypertension. The mean levels of serum thyroxine, triiodothyronine, plasma renin activity and plasma aldosterone concentration in the normotensive responders were significantly higher than the values in the normotensive non-responders. There were no significant differences in these laboratory values between the hypertensive patients and the normotensive non-responders except that serum triiodothyronine levels were significantly higher in the hypertensive patients. The present study indicates that increased activity of the renin-angiotensin-aldosterone system is involved in the maintenance of blood pressure in most normotensive patients with severe hyperthyroidism, while hypertension in patients with hyperthyroidism is not angiotensin II dependent.

1-Sarcosine-8-Isoleucine Angiotensin II↗

Effect of beta-adrenergic blockade on plasma dopamine-beta-hydroxylase activity and triiodothyronine in hyperthyroidism.

The effect of propranolol on plasma dopamine-beta-hydroxylase activity and triiodothyronine was investigated in twelve subjects with Graves' disease. Plasma DBH activity, serum triiodothyronine and thyroxine were determined beforehand and electrocardiograms were recorded on the same days as the blood samples were taken. Propranolol administration was associated with clinical amelioration in blood pressure and ECG. There was a positive and significant correlation between changes in DBH activity and triiodothyronine caused by propranolol. These data offer evidence that there may be an interaction between plasma DBH activity and triiodothyronine during propranolol administration in hyperthyroidism.

Adolescent↗

Clinical and pathological significance of sibling Graves' disease.

The clinical picture and serum antithyroid antibodies in 16 pairs of siblings with Graves' disease were compared with an age and sex matched group of 32 patients with Graves' disease who did not have a family history of any thyroid disease (control patients). There was a significant difference in frequency and mean titres of antibodies to thyroglobulin between sibling patients. (positive 76.0%) and control patients (positive 40.0 %), but not in microsomal antibodies (sibling; positive 92.0%, control; 92.0%). There were no significant differences in the mean values of 24 h 131I-thyroidal uptake, serum T3U, serum T4 and T3 concentrations before treatment between the two groups. Lymphoid follicles and degeneration of the epithelia were more often found in the thyroid glands of sibling patients than in those of the control patients, when 32 (16 sibling, 16 control) thyroid glands from the same groups in the clinical study, including antibody series, were examined pathologically after subtotal thyroidectomy for Graves' disease. Moreover, there was a strong tendency to increased lymphocyte and plasma cell infiltration in the thyroid glands of sibling patients with Grave's disease. The findings might indicate that Graves' disease is closely related to Hashimoto's thyroiditis, especially in sibling patients with Graves' disease.

Adult↗

Thionamide therapy in Graves' disease: relation of relapse rate to duration of therapy.

The present study was undertaken to investigate whether there is a rational basis for the usual long periods of thionamide therapy in patients with hyperthyroid Graves' disease. Eighty untreated patients were given the minimum dose of thionamide drug needed to maintain serum thyroxine, triiodothyronine, and thyrotropin (TSH) concentrations within their normal ranges. Thyrotropin-releasing hormone (TRH) tests were done at 6 monthly intervals for 2 years. Among patients who had positive responses of TSH to TRH, approximately 10 patients every 6 months were asked to stop thionamide therapy and were followed up for at least 1 year after discontinuation of drugs. In the groups treated for 6, 12, 18, and 24 months, relapses occurred in nine of 13, five of nine, three of 12, and two of 11 patients, respectively. Values for thyroid function tests before and at the end of treatment were not different among these four groups of patients. The overall remission rates were not ascertained. However, a minimum of 1 year's treatment is recommended, at least in Japan.

Adolescent↗

Internal fistula as a route of infection in acute suppurative thyroiditis.

Seven cases of acute suppurative thyroiditis are described. Six patients had a recurrent painful swelling of the left anterior neck and one was seen at her first episode of the disease. A barium meal revealed a fistula originating from the apex of the left pyriform sinus in all cases. The fistula, a remnant of the fourth pharyngeal pouch, thus seems to be a common route of infection in acute suppurative thyroiditis, allowing bacterial infection to begin in the perithyroidal space and spread to the thyroid gland. Complete extirpation of the fistula is required for a permanent cure.

Acute Disease↗

Plasma dopamine-beta-hydroxylase activity and thyroid suppressibility in Graves' disease.

Plasma dopamine-beta-hydroxylase (DBH) activity, serum T4, T3, T3U, and the 24-hr thyroid uptake before triiodothyronine suppression testing were studied in 34 patients with treated Graves' disease. Although all of them were in the euthyroid state, there was a statistically significant difference in presuppression plasma DBH activity between those patients who showed suppression of their RAI uptake with triidothyronine and those who did not. This suggests a relationship between plasma DBH activity and thyroid suppressibility.

Dopamine beta-Hydroxylase↗

C cell carcinoma of the thyroid--papillary type.

Two cases of papillary type of C cell carcinoma of the thyroid were reported. They showed papillary arrangement with fibrovascular stalk in properly fixed tissues. Histochemically argyrophil reaction was positive in the cytoplasm and amyloid deposited in the stroma. Ultrastructurally secretory granules were found in their cytoplasm. The papillary type is not an artifact but one of the histologic variations of this carcinoma.

Adult↗

Interaction between thyroid-stimulating immunoglobulins and thyrotropin receptors in fat cell membranes.

In the TSH radioreceptor assay to study the interaction between Graves' immunoglobulins (Ig) and TSH receptors in guinea pig fat cell membranes, Graves' Ig were found to inhibit [125I]TSH binding to fat cell membranes in a dose-dependent manner. Scatchard analysis of [125I]TSH displacement curves by Graves' Ig indicated a single population of the binding sites in fat cell membranes, in contrast to two populations of TSH-binding sites in the membranes. Displacement of [125I]TSH bound to fat cell membranes by both Graves' Ig and unlabeled TSH were time and temperature dependent, with similar dissociation curves, suggesting a specific binding of Graves' Ig to the membrane sites related to the TSH receptor in the fat cells. Such Ig are referred to as fat cell-binding Ig, to be distinguished from the thyroid-stimulating Ig (TSI) detected by TSH radioreceptor assay using human thyroid membranes. Both fat cell-binding Ig and TSI were detected in the sera of a great majority of untreated patients with Graves' disease. A significant correlation was found between both values (r = 0.80; n = 19; P less than 0.001). According to these results, TSI might represent an autoantibody to the membranes associated with the TSH receptor of the target tissues without a strict organ specificity.

Adipose Tissue↗