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T Mukuta

Publications and source records attributed to T Mukuta.

At least 37 records · Page 2Linked to original sources
PubMed1994

Effect of FK-506 on xenografted human Graves' thyroid tissue is severe combined immunodeficient mice.

OBJECTIVE: We studied the macrolide antibiotic FK-506, an immunosuppressive agent, in an attempt to ameliorate the lesion of autoimmune thyroid disease in human thyroid tissue xenografted into severe combined immunodeficient (SCID) mice. It was not felt appropriate to employ this agent directly in patients with autoimmune thyroid disease because adequate therapeutic modalities are available and the introduction of new, experimental agents could not be justified. Moreover, the study of the tissue before and after treatment could not have been undertaken directly in patients. DESIGN: Human thyroid xenografts from four patients with Graves' disease and two normal persons were xenografted into SCID mice. Two weeks after xenografting, human immunoglobulin G (IgG) was detectable in all SCID mice xenografted with Graves' thyroid tissue. Mice were divided into two groups with human IgG levels similar to each other. Mice in the first group were treated with FK-506 daily for 6 weeks; mice in the second (similar) group were given phosphate-buffered saline (PBS) only (control group). MEASUREMENTS: Blood samples were taken every 2 weeks from the tail veins for human IgG, thyroid stimulating antibody, thyroperoxidase antibodies, thyroglobulin antibodies, and interferon-gamma (IFN-gamma). After 8 weeks treatment, animals were sacrificed; thyroid tissue was examined histologically and for thyrocyte HLA-DR expression. FK-506 was also added to thyrocytes in in-vitro tissue culture conditions. RESULTS: After 4-6 weeks of FK-506 therapy, human IgG, all thyroid antibodies and IFN-gamma were suppressed, while the levels remained elevated in the control group. Lymphocytic infiltration virtually disappeared in the human thyroid tissue of the FK-506-treated mice and thyrocyte HLA-DR expression markedly declined; in the control mice, lymphocytic infiltration remained heavy and HLA-DR expression remained high. On the other hand, FK-506 added directly to thyrocytes in vitro (without lymphocytes) did not reduce thyrocyte HLA-DR expression. CONCLUSIONS: FK-506 appears to suppress the activation of intrathyroidal lymphocytes, but not thyrocytes. From these observations, it is concluded that this agent, by its action on intrathyroidal lymphocytes, is able to ameliorate the immunologically mediated histological and serological disturbance in human autoimmune thyroid disease, at least under these circumstances.

Animals↗
PubMed1994

Effect of removing human Graves' thyroid xenografts after eight weeks in nude mice and rexenografting them into SCID mice.

Human thyroid xenografts from four patients with Graves' disease (GD) and two normal persons were initially xenografted into nude mice. Eight weeks after xenografting, the thyroid tissue appeared normal; indeed, thyroid infiltrating lymphocytes in the GD xenograft could no longer be identified when analyzed histologically. Thus, human immunoglobulin G (IgG), thyroperoxidase (TPO)-antibodies (Abs), thyroglobulin (Tg)-Abs, thyroid-stimulating antibodies (TSAb), and thyrocyte histocompatibility leucocyte antigen (HLA)-DR expression were undetectable. These same tissues were retrieved from the nude mouse and rexenografted into severe combined immunodeficient (SCID) mice (with no prior xenograft); autologous peripheral blood mononuclear cells (PBMC) or CD8-depleted PBMC (non-CD8 cells) were simultaneously injected into some of these SCID mice. Engraftment of a GD thyroid rexenograft (TH) alone did not cause IgG, TSAb, TPO-Ab, or Tg-Ab production, thyrocyte HLA-DR expression, or lymphocytic infiltration in thyroid grafts. Engraftment of GD PBMC or non-CD8 cells alone (i.e. without a thyroid xenograft) caused human IgG to rise, but only minimal titers of thyroid antibodies appeared. When TSAb, TPO-Ab, and Tg-Ab were quantified, GD TH plus PBMC-engrafted SCID mice showed significantly higher production of each antibody than that of GD PBMC alone, and this phenomenon was further enhanced by the removal of CD8+ cells. GD thyrocytes showed marked HLA-DR expression at human surgery; however, after 8 weeks' sojourn in nude mice, DR expression disappeared. After a further 8 weeks following rexenografting into SCID mice, TH plus PBMC resulted in a reappearance of DR expression only in GD but not in grafts from normal persons, and this was enhanced by the depletion of CD8 cells. These results were also in parallel with histological findings inasmuch as the normal tissue remained normal with no thyroid antibodies appearing with PBMC or CD8-depleted cells. In experiments from two GD patients, autologous skeletal muscle as well as thyroid tissue were xenografted into nude mice. Eight weeks after xenografting, these were rexenografted into SCID mice that contained prior autologous primary GD thyroid xenografts. Histological findings showed new lymphocytic infiltration in rexenografted thyroid tissues in the SCID mice but not in autologous skeletal muscle. This signifies that the immune assault in GD is specifically targeted to the thyroid tissue.(ABSTRACT TRUNCATED AT 400 WORDS)

Adult↗
PubMed1994

Effectiveness of chemotherapy for advanced adenocarcinoma of the pancreas in combined modality therapy.

Because it is difficult to diagnose at an early stage, pancreatic carcinoma is usually well advanced by the time it is diagnosed. The combined use of intraoperative radiotherapy, gastrointestinal and/or biliary tract bypass operation, celiac plexus nerve block, and chemotherapy is widely applied in treatment, with favorable results reported in some patients with advanced disease. To evaluate the efficacy of chemotherapy in such combinations, we compared the effect of 5-fluorouracil, its analogues, and mitomycin C on the survival of patients with advanced stage pancreatic cancer. We found no significant difference between the patients treated or not treated with these drugs. Clearly, there is a need for new agents having greater efficacy against pancreatic carcinoma.

Adenocarcinoma↗
PubMed1993

Rapidly progressive thyroid failure in Graves' disease after painful attack in the thyroid gland.

We studied a new type of Graves' disease: rapidly progressive thyroid failure after painful attack in the thyroid gland. Four women with the mean (+/- SD) age of 51 +/- 3.2 years had newly diagnosed hyperthyroid Graves' disease. A severe painful episode developed in the thyroid glands of two patients and permanent hypothyroidism occurred spontaneously within 2 or 3 months thereafter. Two to three episodes of pain developed in the thyroid glands of the other two patients during antithyroid drug therapy. There was a transient rise in serum thyrotropin level after each painful episode and permanent hypothyroidism developed 6 to 8 months after the initial painful attack. The clinical picture is characterized by moderate to severe pain in the thyroid gland with tenderness. Patients responded to steroid or anti-inflammatory therapy. During painful attack, increased or normal thyroid radioiodine uptake, elevated levels of C-reactive protein, and an elevated erythrocyte sedimentation rate were found, but there was no cytological evidence of subacute thyroiditis. After painful attack, serum thyroid stimulation antibody began to decrease in three of the patients while thyroid stimulation blocking antibody developed in one patient. This is a rapid and self-destructive process of the Graves' thyroid gland, which appears to be associated with painful attack in the thyroid gland.

Autoantibodies↗
PubMed1993

New animal models for human autoimmune thyroid disease. Xenografts of human thyroid tissue in severe combined immunodeficient (SCID) and nude mice.

We have been employing two mouse models for the study of human thyroid xenografts from patients with autoimmune thyroid disease (AITD). The first mouse strain is that of the athymic "nude" mouse which accepts human thyroid xenografts, but the passenger lymphocytes are lysed in this model over several weeks; in the second model, the severe combined immunodeficient (SCID) mouse, both the xenograft and its lymphocytes survive. The AITD thyroid xenograft returns to normal function and morphology in the nude mouse over several weeks whereas the same AITD thyroid xenografts undergo aggravation of their lesions in the SCID mouse. Normalized ("cleansed") thyroid tissue in the nude mouse, now bereft of the passenger lymphocytes, can be removed and then re-xenografted into SCID mice. There it will remain normal unless autologous peripheral blood mononuclear cells are added, whereupon the AITD lesion will be reproduced. Autologous "irrelevant" muscle tissue having undergone the same process will not show such lesions. There is thus no evidence for a primary thyroid cell disturbance in AITD, the abnormality appearing to be only in the immune system. Moreover peripheral blood mononuclear cells appear to contain sufficient memory cells to be able to mount an immune assault on the autologous normalized thyroid tissue (to which they had been previously sensitized) but not on irrelevant autologous (muscle) tissue.

Animals↗
PubMed1993

A long-term follow-up study of patients with non-toxic diffuse goitre in Japan.

OBJECTIVE: Although non-toxic diffuse goitre is a common disorder, little is known of the clinical course of patients. We therefore decided to investigate the long-term clinical outcome of patients with non-toxic diffuse goitre. DESIGN: A retrospective study. PATIENTS: Of 850 patients with non-toxic diffuse goitre who met our criteria and were seen in our thyroid clinic between 1977 and 1985, 108 who had been followed for from 5 to 14 years (mean 8 years) were entered in this study. All patients fulfilled our criteria having soft diffuse goitres, normal serum TSH and T4 concentrations, and undetectable antithyroglobulin and antithyroid microsomal antibodies. MEASUREMENTS: A family history of thyroid disease was obtained and the occurrence of Graves' ophthalmopathy was noted. Serum TSH and T4 concentrations, and antithyroglobulin and antithyroid microsomal antibodies were measured during the follow-up period. Thyroidal radioactive iodine uptake (RAIU), serum free T4 and free T3 concentrations, and TSH binding inhibitory immunoglobulin (TBII) activities were determined in all patients who were subsequently found to have abnormal serum TSH or T4 concentrations or signs of Graves' ophthalmopathy. RESULTS: Thirty-six of the 108 patients (33%) had a family history of autoimmune thyroid disease. Elevated serum T4 or free T4 concentrations and depressed serum TSH concentrations were found in six patients during the follow-up period. Hyperthyroid Graves' disease was diagnosed in four of the six patients, subacute thyroiditis in one, and transient post-partum thyrotoxicosis in one. Hypothyroidism was found in one patient who was diagnosed as having transient post-partum hypothyroidism. Euthyroid Graves' disease was diagnosed in one patient. Furthermore, six of these eight patients had a family history of autoimmune thyroid disease in first-degree relatives. CONCLUSION: During a prolonged follow-up period of patients with non-toxic diffuse goitre, Graves' disease was found in five of 108 patients (four hyperthyroid Graves' and one euthyroid Graves'), post-partum thyroid dysfunction in two, and subacute thyroiditis in one. Six of these eight patients had a family history of autoimmune thyroid disease in first-degree relatives. Long-term follow-up is necessary for patients with non-toxic diffuse goitre, especially those who have a family history of autoimmune thyroid disease.

Adolescent↗
PubMed1993

Treatment of methimazole-induced agranulocytosis using recombinant human granulocyte colony-stimulating factor (rhG-CSF).

Agranulocytosis, although extremely infrequent, is a serious complication of antithyroidal drug therapy in patients with hyperthyroidism. Presently, there is no specific therapy for this life-threatening complication, and recovery time is highly variable. Recently, recombinant human granulocyte colony-stimulating factor (rhG-CSF) was reported to be effective in shortening the recovery time of the neutropenia in patients undergoing chemotherapy. The present study was undertaken to determine the efficacy of rhG-CSF administration in patients with methimazole-induced (MMI) agranulocytosis. Thirty-four patients (7 males and 27 females, ages 16-68 yr) with MMI agranulocytosis were divided into 3 groups: group A (n = 11) was treated with antibiotics only; group B (n = 11) received antibiotics and dexamethasone, 8 mg/day; and group C (n = 12) was treated with antibiotics and im injections of rhG-CSF, 75 micrograms/day. Patients in groups A and B were studied retrospectively. When rhG-CSF became available, patients in group C were studied prospectively. Bone marrow sternal punctures were performed in all group C patients who were then divided into 2 subgroups according to the granulocyte to erythrocyte count ratio (G:E). Group C1 (n = 6) had a G:E ratio of less than 0.5, and group C2 (n = 6) had a ratio of more than or equal to 0.5. Recovery time in all groups was defined as the number of days required for the peripheral granulocyte count to be greater than 1.0 x 10(9)/L. There was no significant difference in recovery time between groups A and B: 10.1 +/- 2.2 and 12.3 +/- 1.9 days (mean +/- SE), respectively. P was not significant; the administration of dexamethasone proved to be ineffective in shortening the time for recovery from peripheral granulocytes. On the other hand, recovery time was significantly shorter in group C (6.8 +/- 1.2 days mean +/- SE) compared with groups A and B (P < 0.05). Group C2 recovered in 2.2 +/- 0.6 days whereas group C1 took much longer, 9.8 +/- 1.3 days (P < 0.001). There was a direct correlation between the G:E ratio and the peripheral leucocyte count, r = 0.806, P < 0.01. Furthermore, rhG-CSF significantly shortened recovery time when the peripheral granulocyte count was greater than 0.1 x 10(9)/L (group C2) compared with patients whose counts were less than 0.1 x 10(9)/L (group C1), 2.2 +/- 0.4 vs. 8.6 +/- 1.3 days, respectively (P < 0.001). These data indicate that administration of steroids is ineffective in shortening the duration of recovery in patients with MMI agranulocytosis.(ABSTRACT TRUNCATED AT 400 WORDS)

Adult↗
PubMed1992

Alterations in endothelium-associated proteins and serum thyroid hormone concentrations in anorexia nervosa.

Plasma concentrations of endothelium-associated proteins (EAP) (plasma fibronectin (PFN), angiotensin-converting enzyme, factor VIII-related antigen (F VIII-R:Ag)) and tissue plasminogen activator and serum thyroid hormone concentrations were studied in nine patients with anorexia nervosa (AN), before and after weight gain. Before weight gain (-35.9 (SE 2.3)% of standard body-weight) PFN was significantly reduced and F VIII-R:Ag was significantly increased in AN patients compared with the concentrations in control subjects (211.5 (SE 14.9) v. 274.7 (SE 16.6) micrograms/ml, P < 0.05; 129.2 (SE 14.1) v. 88.2 (SE 9.7) %, P < 0.05 respectively). Serum triiodothyronine (T3) and free T3 levels were also significantly lower before weight gain in AN patients (0.85 (SE 0.07) v. 1.53 (SE 0.08) nmol/l, P < 0.001; 2.57 (SE 0.23) v. 5.31 (SE 0.34) pmol/l, P < 0.001 respectively), although serum thyroxine (T4), free T4, and thyrotropin concentrations were within the normal range throughout the study periods. Following weight gain, PFN and F VIII-R:Ag concentrations normalized as did the thyroid hormone levels. The incremental changes in PFN levels correlated significantly with those in serum thyroid hormone concentrations (T3, r 0.79, P < 0.01; free T3, r 0.84, P < 0.01). These findings suggest that PFN levels may be directly related to serum T3 concentrations in AN patients.

Adult↗
PubMed1992

The role of thyroid stimulating antibody (TSAb) in the thyroid function of patients with post-partum hypothyroidism.

OBJECTIVE: We investigated the association between thyroid function and the biological activities of thyroid stimulating antibodies (TSAb) and thyroid stimulation blocking antibodies (TSBAb) in patients with post-partum hypothyroidism. DESIGN: A prospective study. PATIENTS: We studied 25 patients with post-partum hypothyroidism who visited our thyroid clinic during the period from 1985 to 1990. MEASUREMENTS: We measured TSH binding inhibitory immunoglobulin (TBII) and TSAb activity at the initial presentation of each of the 25 patients. Women found to have elevated TSAb activity were followed up. Upon finding negative TSAb activity along with positive TBII activity in the serum at the initial presentation, we measured TSBAb activity. Women found to have elevated levels of TSBAb at the initial presentation were also followed up. RESULTS: Elevated TBII activity was found in six of the 25 patients, as was high TSAb activity (205-2651%, normal 55.0-145.0%) in five of these six and in one other patient at the initial presentation. Markedly elevated TSBAb activity (89%) was found in one TBII positive patient. We were able to follow up serially five TSAb positive patients and the TSBAb positive patient over periods ranging from 11.5 to 26.5 months post-partum. The maximal value of TSAb activity was observed at the initial presentation in all TSAb positive patients, following which the activities gradually decreased. One of these patients developed Graves' hyperthyroidism associated with high TSAb activity (1223%) at 10.5 months post-partum. One of the other patients was restored to euthyroid with elevated TSAb activity (279%), but thereafter developed hypothyroidism in conjunction with the disappearance of TSAb activity at 26.5 months post-partum. In the other two patients, normalization of thyroid function was observed with elevated TSAb activity. Thereafter, thyroid function remained within the normal range even with the disappearance of TSAb activity. In the other patient, normalization of thyroid function was observed at 11.5 months post-partum, 3 months after the disappearance of TSAb activity. In the TSBAb positive patient, TSBAb activity decreased to 21% by 17.5 months post-partum associated with normalization of thyroid function. CONCLUSION: The present study demonstrates the presence of elevated levels of TSAb activity in some patients with post-partum hypothyroidism. In these patients, Graves' hyperthyroidism may be induced by TSAb activity, and hypothyroidism may reoccur with the disappearance of the TSAb activity. Furthermore, post-partum hypothyroidism may be due to increased TSBAb activity in some patients.

Antibodies↗
PubMed1991

Responses of growth hormone and cortisol to intravenous glucose loading test in patients with anorexia nervosa.

The hypothalamic satiety and hunger centers appear to be affected by changes in circulating blood glucose concentrations. The response of the centers, in turn, is reflected by alterations in growth hormone (GH) and cortisol levels. There are no studies attempting to relate blood glucose and GH and cortisol changes in patients with anorexia nervosa (AN) during an intravenous glucose tolerance test (IVGTT). In the present inquiry, IVGTT (10 g) were performed on AN patients to characterize the satiety and hunger centers' responses to changes in glucose and insulin levels as reflected by GH and cortisol levels. Study participants were 15 female AN patients and eight healthy female volunteers. No significant differences in blood glucose levels were observed between the two groups. However, immunoreactive insulin (IRI) levels in AN patients were significantly lower than those in the control group. Although GH and cortisol concentrations were significantly suppressed after the infusion in the control group, the AN patients' GH levels paradoxically increased, and cortisol levels did not change. Moreover, a negative correlation was observed between delta GH and delta IRI in all individuals in this study (r = -.61, P less than .01). In conclusion, abnormal GH and cortisol responses to a 10-g IVGTT were found in patients with AN. delta GH levels correlated negatively with delta IRI levels. These data suggest that hypothalamic satiety and hunger centers in AN respond abnormally to change in blood glucose levels.

Adolescent↗
PubMed1991

A follow-up study of 85 patients with Graves' disease in remission who developed undetectable serum thyroid-stimulating hormone concentrations using sensitive TSH assays.

Eighty-five patients with Graves' disease in clinical remission after treatment for over 1 year by methimazole therapy (36 patients, group A) or subtotal thyroidectomy (49 patients, group B) who became undetectable for serum thyrotropin levels (TSH less than 0.05 mU/l), were further followed for 1 year or more. Eight patients in group A (22%) and 7 patients in group B (14%) relapsed. Eleven patients in group A (30%) and 5 patients in group B (10%) had fluctuating patterns of free T4 in the upper normal to slightly supranormal range indicative of subclinical hyperthyroidism. The remaining patients continued to have undetectable TSH levels or restored normal TSH levels and normal thyroid hormone concentrations in sera. The results of the present study indicate that the occurrence of undetectable serum TSH concentrations in Graves' disease patients previously treated with methimazole or surgery are not necessarily predictive of clinical relapse because the eventual outcome is variable.

Adult↗
PubMed1991

The incidence of thyroid stimulating blocking antibodies during the hypothyroid phase in patients with subacute thyroiditis.

The etiology of subacute (de Quervain's) thyroiditis (SAT) is uncertain, although it probably represents a nonspecific inflammatory response by the thyroid to a variety of viruses. It has been suggested that nonimmune processes are involved in SAT patients who have negative autoantibody titers. The disease has a variable course; although it is self-limited in most cases, some patients develop transient hypothyroidism, and others do not during the recovery period. The present study was performed to evaluate the occurrence of TSH receptor antibody (TRAb), measured by RRA (TSH binding inhibitor), TRAb measured by stimulation assay (thyroid-stimulating antibody), and TRAb measured by blocking assay [TSH-blocking antibody (TSH-BAb)] activity in 68 patients with SAT who had negative autoantibody titers. The patients were divided into 2 groups: group I, 31 patients who developed hypothyroidism during the recovery period; and group II, 37 patients who remained euthyroid during recovery. Positive immunoglobulin activity occurred in about 20% of group I patients during follow-up, but in only 3% of group II patients. About 20% of group I patients developed positive TSH-BAb activity and were hypothyroid, requiring exogenous hormone therapy for 1.2-3.5 yr, whereas hypothyroidism was relatively transient in group I patients who had negative TSH-BAb activity (2-6 months). Although increased TSH-BAb activity may account for hypothyroidism in some patients with SAT, the precise mechanism for the development of transient hypothyroidism in SAT remains enigmatic.

Adult↗
PubMed1990

The occurrence of thyrotropin binding-inhibiting immunoglobulins and thyroid-stimulating antibodies in patients with silent thyroiditis.

Silent (painless) thyroiditis has been recognized as a clinical entity for over a decade and is characterized by spontaneously resolving thyrotoxicosis. Its etiology is uncertain; however, a few reports have indicated the occurrence of TSH binding-inhibiting immunoglobulins (TBII) and thyroid-stimulating antibodies (TSAb) in some of the patients. The present study was undertaken to evaluate thyroid function and the occurrence of TBII and TSAb and thyroid autoantibodies (antithyroglobulin and antimicrosomal) in 53 patients with silent thyroiditis during the course of their disease. The patients were divided into 2 major groups: I) those who developed transient hypothyroidism and II) those who did not. All patients initially had significantly increased concentrations of serum T4, free T4, and free T3, suppressed TSH levels, and decreased thyroid radioiodine uptake. TBII and TSAb were initially positive in 8 (15.1%) and 10 patients (18.9%), respectively. Forty patients were available for follow-up. TBII was positive in 6 of 24 (25.0%), and TSAb was positive in 8 of 24 (33.3%) of the patients who developed transient hypothyroidism during the course of their disease. Among the patients who did not become hypothyroid at any time, TBII was positive in only 2 of 16 (12.5%), and none of the patients became TSAb positive. The findings indicate that increased TSAb and TBII activity may be detected in patients with silent thyroiditis and, when present, are associated with transient hypothyroidism during the course of the disease.

Adolescent↗