Biomedical subjects

K Kasagi

Publications and source records attributed to K Kasagi.

At least 37 records · Page 2Linked to original sources

PubMed1997

Assessment of thyroid growth stimulating activity of immunoglobulins from patients with autoimmune thyroid disease by cytokinesis arrest assay.

OBJECTIVE: To develop a novel bioassay for the assessment of thyroid cell growth stimulating activity using cytochalasin B (CB) and to test immunoglobulins (IgGs) from patients with autoimmune thyroid diseases. DESIGN: The assay is based on the principle that growing cells during incubation with CB show an increased number of nuclei in a cell (N/C index), since CB, at appropriate concentrations, is known to inhibit cytoplasmic cleavage without affecting nuclear mitosis. The N/C index represents potential DNA production while cells are incubated with CB. METHODS: FRTL-5 thyroid cells were incubated with various thyroid stimulators in TSH-free medium containing 2 mg/J CB for 3 days. After the incubation, the cells were harvested in trypsin/EDTA to obtain single cell suspension, fixed, dropped onto a glass slide, stained and observed under a microscope to determine the N/C index. RESULTS: Bovine TSH at 10(-3)-1.0 U/I, forskolin at 1x10(-7)-10(-5) mol/l, cholera toxin at 10x10(-5)-10(-3) mg/l, or (Bu)2cAMP at 1 x 10(-5)-10(-3) mol/l increased the N/C index up to approximately 2.0 in a dose-dependent manner. IgGs not only from 27 patients with untreated goitrous Graves' disease but also from 14 patients with goitrous Hashimoto's thyroiditis elicited an increase in the N/C index, which exceeded the mean + 2 S.D. of the values for 17 normal subjects (mean +/- S.D., 1.063 +/- 0.014). Four patients with primary myxedema displayed a normal N/C index. In Graves' disease, the N/C index did not correlate significantly with thyroid stimulating antibodies (TSAb) activities but did correlate significantly with estimated goiter size (P < 0.05). IgGs containing blocking-type TSH-receptor antibodies inhibited the TSH- or Graves IgG-stimulated increase in N/C index almost completely, but did not influence the stimulatory effect of IgG from two patients with Hashimoto's thyroiditis. CONCLUSIONS: We have developed a sensitive and simple assay for thyroid growth stimulating activity by using CB, and found that all tested patients with goitrous Graves' disease and goitrous Hashimoto's thyroiditis have thyroid growth stimulating immunoglobulins whose activity does not correlate with TSAb.

Animals↗

PubMed1997

Evaluation of technetium-99m-MIBI scintigraphy in metastatic differentiated thyroid carcinoma.

UNLABELLED: Technetium-99m-methoxyisobutyl isonitrile (99mTc-MIBI) was evaluated for its ability to detect metastases from thyroid carcinoma. METHODS: Twenty-seven thyroidectomized patients with metastatic differentiated thyroid carcinoma, of whom 20, 9 and 12 had lung, lymph node and bone metastases, respectively, were examined with 99mTc-MIBI. The scan results were compared with those of 201TI and 131I whole-body scans. RESULTS: Increased accumulation of 99mTc-MIBI was observed in lung metastases of 15 patients (75.0%), 12 lymph node metastases (100.0%) and 29 of 31 bone metastases (93.5%). Increased accumulations of 201TI and 131I scans were seen in, respectively, 16 (80.0%) and 17 (85.0%) of the 20 patients with lung metastases, 12 (100.0%) and 5 (41.7%) of the 12 lymph node metastases and 28 (90.3%) and 27 (85.1%) bone metastases. Because of its better image quality, 99mTc-MIBI detected more lesions in the lung (n = 38) than 201TI did (n = 17). CONCLUSION: Technetium-99m-MIBI is clinically useful for detecting metastases from differentiated thyroid carcinoma and deserves clinical application in the postoperative follow-up of such patients.

Adult↗

PubMed1996

Development of primary hypothyroidism with antithyroglobulin, antiperoxidase, and blocking-type thyrotropin receptor antibodies after radiation therapy for neuroblastoma.

We describe a girl with hypothyroidism and blocking-type thyrotropin receptor antibodies that developed after chemotherapy and irradiation of the neck region for neuroblastoma. Results of thyroid studies before treatment were normal. Twenty months after completion of treatment, the girl had hypothyroidism with high titers of blocking-type thyrotropin receptor antibodies, antithyroglobulin, and antiperoxidase antibodies.

Antibodies↗

PubMed1996

Clinical significance of measurements of antithyroid antibodies in the diagnosis of Hashimoto's thyroiditis: comparison with histological findings.

Measurements of antithyroglobulin and antimicrosomal (antiperoxidase) antibodies have been performed widely for the clinical diagnosis of autoimmune thyroid diseases. The present study was designed to compare these antibody titers with histological findings of the thyroid in patients with diffuse goiter who were suspected of having Hashimoto's thyroiditis. One hundred and ten euthyroid or hypothyroid patients (10 males and 100 females; age 48 +/- 15 (SD) years old) with diffuse goiter were studied for the measurement of antithyroglobulin and antimicrosomal or antiperoxidase antibodies by a hemagglutination technique (TGHA and MCHA, respectively) and by a newly developed radioassay (TgAb and TPOAb, respectively). The antibody titers were compared with the histological findings obtained by needle biopsy. TgAb, TPOAb, TGHA, and MCHA were detected in 80 (96.4%), 61 (73.5%), 37 (44.6%), and 54 (65.1%) of 83 patients with histologically proven Hashimoto's thyroiditis, respectively, but in only one (3.7%) of 27 patients without any inflammatory changes in the biopsy specimen. In 55 patients with negative TGHA and MCHA, the TgAb positivity was more closely associated with the histological diagnosis of Hashimoto's thyroiditis than the TPOAb positivity was, the incidence of each antibody in Hashimoto's thyroiditis being 89.7% (26/29) and 27.6% (8/29), respectively. In conclusion, the histological diagnosis of Hashimoto's thyroiditis can most precisely be predicted by the newly developed radioassay for TgAb.

Adolescent↗

PubMed1996

Serial occurrence of two types of postpartum thyroid disorders. Usefulness of Tc-99m pertechnetate uptake.

A 32-year-old woman with a history of Graves' disease had an episode of thyrotoxicosis 2.5 months after her first childbirth. Because of low thyroidal uptake of Tc-99m pertechnetate, a diagnosis of postpartum painless thyroiditis was made and the patient was observed without medication. After the normalization of serum levels of thyroid hormones, a second wave of thyrotoxic symptoms emerged. This time, the Tc-99m uptake was slightly elevated and the patient was diagnosed to have a relapse of Graves' disease. This case underscores the previously reported notion that thyroidal uptake was indispensable to distinguish these two causes of postpartum thyrotoxicosis.

Adult↗

PubMed1996

Tumoricidal cytokines enhance radioiodine uptake in cultured thyroid cancer cells.

UNLABELLED: We explored whether the stimulation of iodine uptake by interferons seen in rat thyroid cell line is reproducible in human thyroid cancer and thus applicable to enhance the efficacy of radioiodine therapy. METHODS: Surgical specimens from 12 papillary and 2 follicular adenocarcinomas were minced and seeded in culture trays. After 14-16 days in a medium supplemented with 5% calf serum, we measured cellular uptake of 125I during a 40-min incubation period. RESULTS: In 8 of 12 papillary and all 2 follicular carcinomas, interferon-gamma significantly stimulated iodine incorporation. The four nonresponder tumors had lower basal iodine uptake and relatively less differentiation of histologic features. The effect was dose dependent (0-100 U/ml), and the average maximum increase in responding cases was 35.1% over basal values. Tumor necrosis factor-alpha alone did not alter uptake, but at 300 U/ml it further enhanced the effect of interferon-gamma in the two follicular tumors. In addition to the pure cytokines, supernatant from lymphocyte culture conditioned with a bacterial immunostimulator also boosted radioiodine trapping in thyroid cancer cells. CONCLUSION: These in vitro results warrant animal experiments to test potential usefulness of tumoricidal cytokines in radioiodine therapy.

Adenocarcinoma, Follicular↗

PubMed1996

[Effectiveness of the radioactive strontium (89Sr) chloride agent, SMS.2P for pain palliation in patients with metastatic bone tumor in phase III multicenter clinical trial].

The phase III clinical trial of strontium-89 chloride agent (SMS.2P) was performed in 90 patients with painful bone metastases secondary to prostate (53), breast (18) and other types of cancer (19). Some patients experienced a transient increase in pain or nausea and vomiting. However both symptoms subsided and serious side effects were not observed in any of the patients. As reported, we confirmed some abnormal changes in peripheral blood picture. A decrease in the number of white blood cells and platelets was considered to be partly a result of bone marrow suppression due to 89Sr irradiation. Pain was substantially improved after 89Sr therapy in 58% of the patients and there was some alleviation in 12%. The release from pain was accompanied by an improved quality of life for these patients including sleep patterns and morbidity. Some patients were able to resume their former life styles. Most of the improved patients experienced pain relief from days to one week following 89Sr therapy and in half cases, this remained effective for 2 or 3 months. There were even cases in which the pain relief continued over an observation period of time of clinical study.

Adult↗

PubMed1995

Augmentation of thyrotropin-induced iodide uptake in FRTL-5 cells by immunoglobulins containing blocking thyrotropin-receptor antibodies under NaCl-depleted conditions.

We have found recently that Graves' immunoglobulins (Igs) are more active under NaCl-free conditions to increase iodide uptake in FRTL-5 thyroid cells. The present study was designed to examine the effect of blocking-type thyrotropin (TSH)-receptor antibodies (TR-abs) in the same assay. FRTL-5 cells were incubated with crude Ig fractions from 13 patients with primary hypothyroidism having blocking TR-abs and 100 mU/l bovine TSH in NaCl-free Hanks' balanced salt solution (HBSS) supplemented with 274 mmol/l sucrose (HBSS(-)-sucrose) to keep isotonicity for 3 days, followed by the determination of 60 min of 125I uptake in the cells. Thyrotropin alone increased the uptake to 3.3- to 5.2-fold of the basal. When the highest concentration (250 ml serum equivalent (eq.)/l) of the Ig was used, the TSH-stimulated 125I uptake was decreased to 0-42% in 11 of the 13 cases. When the lower concentrations (0.4-50 ml serum eq./l) were used, however, 125I uptake was enhanced (1.4- to 11.4-fold) unexpectedly in all 13 cases. Such an enhancement was specific to blocking TR-abs, because the effect was duplicated by the purified IgG but not by Igs from 10 healthy control subjects or from three TR-ab-negative hypothyroid patients. When Graves' Igs, instead of TSH, were used as a stimulator, the similar stimulatory effect of the Ig with blocking activity was observed on the 125I uptake induced by three Graves' Igs but not on the response to one Graves' Ig. These Igs alone displayed no stimulating activity. When isotonic 5H medium was used instead of HBSS(-)-sucrose, effects of these 13 Igs were only inhibitory on the TSH-stimulated 125I uptake.(ABSTRACT TRUNCATED AT 250 WORDS)

Adult↗

PubMed1995

Myocardial oxidative metabolism in hyperthyroid patients assessed by PET with carbon-11-acetate.

UNLABELLED: Hyperthyroid patients often complain of cardiovascular symptoms because of increased metabolism. This study was designed to quantitatively evaluate myocardial oxidative metabolism in these patients. METHODS: Dynamic PET with 11C-acetate was performed in 19 patients who had not undergone treatment for hyperthyroidism. Eight were restudied 2 wk after oral administration of propranolol. The clearance rate constant of 11C-acetate (Kmono) was calculated with monoexponential fitting of tracer washout from the myocardium as a marker of myocardial oxidative metabolism. The results were compared with those in nine normal subjects both at rest and during dobutamine infusion. RESULTS: Kmono in our patients (0.109 +/- 0.028 min-1) was significantly increased compared to normal subjects (0.066 +/- 0.016 min-1) (p < 0.05). After propranolol treatment, Kmono decreased (0.082 +/- 0.014 min-1) but remained significantly higher in eight patients than normal subject levels (p < 0.05), while the rate pressure product decreased significantly (7500 +/- 1700) toward the normal range (7900 +/- 1500). CONCLUSION: These results suggest the possibility of excessive myocardial oxygen consumption in hyperthyroid patients. The clearance rate of 11C-acetate is a new and valuable index to assess myocardial oxidative metabolism not closely related to the pressure rate product or thyroid hormones in these patients.

Acetates↗

PubMed1995

[Phase II clinical trial of the radioactive strontium (89Sr) chloride agent, SMS. 2P for pain palliation in patients with prostate cancer with bone metastases].

The phase II clinical trial of a strontium (89Sr) chloride agent (SMS. 2P) was performed in 9 patients with painful bone metastases secondary to prostate cancer. After an intravenous administration, 89Sr circulated in the plasma and was rapidly cleared. Urinary excretion varied widely among the patients. No serious acute side effects were observed. A mild transient increase in pain was reported by 4 patients 2-4 days after administration, two of whom complained of mild nausea or vomiting. All symptoms improved and never became a clinical problem. There were some abnormal hematological parameters. In particular, a decrease in the platelet level seemed to be a marrow suppression due to 89Sr irradiation. It is difficult to discriminate between the effects of 89Sr and the progress of the disease using tumor markers. The pain level improved within 2 weeks after administration and the effect continued for at least 8 weeks, which improved the quality of life for these patients.

Aged↗

PubMed1994

Scintigraphic findings of the thyroid in hypothyroid patients with blocking-type TSH-receptor antibodies.

The present study was designed to analyse the scintigraphic appearance of the thyroid in hypothyroid patients with blocking-type TSH receptor antibodies (TRAbs). Eleven hypothyroid patients with autoimmune thyroiditis positive for TSH binding inhibitor immunoglobulins (TBII) [80% +/- 12 (SD)%; normal < 11%] and for thyroid stimulation-blocking antibodies (TSBAbs) (90% +/- 9%: normal < 32%) were studied. Thyroid scanning was performed using technetium-99m or iodine-123, when the patients were hypothyroid. Analysis of the scan images revealed the presence of localized functioning areas in six patients (group 1), and no visualization of the thyroid in the remaining five patients (group 2). Patients in group 1 showed significantly higher uptake of 99mTc than those in group 2 (P < 0.05). Interestingly, three patients in group 1 were positive for thyroid-stimulating antibodies (TSAbs) (249% +/- 17%; normal < 145%), which were not detected in the remaining eight patients. Antibodies against thyroglobulin and microsomal antigens were detected in nine nine (81.8%) and 11 (100%) patients, respectively, but neither of these titres correlated with the scan image. Three patients in group 1 underwent scintigraphy again after treatment with thyroxine, at which time the functioning lesion was not noted. Fourteen hypothyroid patients with negative TBII displayed no such scintigraphic findings. Chronic stimulation of the thyroid by TSAbs and/or TSH might be responsible for the presence of the functioning lesion, but clarification of the mechanism requires further studies. In summary (1) TSAbs were detected in three (27.3%) of 11 hypothyroid patients with blocking TRAbs; (2) thyroid scintigraphy revealed the presence of localized functioning area(s) in approximately half of these cases.

Adolescent↗

PubMed1994

Stimulated iodide uptake in FRTL-5 cells preincubated with Graves' immunoglobulins in NaCl-free medium: a sensitive assay for thyroid-stimulating antibodies.

The present study was designed to increase the sensitivity of iodide uptake assay for detecting thyroid-stimulating antibodies (TSAb). Based on the previous observations that TSAb are more active to increase cAMP levels in the NaCl-free condition, we improved the assay procedure and defined the optimum conditions: FRTL-5 cells were incubated with immunoglobulin (IgG) in NaCl-free medium for 3 days, and then 125I uptake in the cells was determined after 60 min. The sensitivity of iodide uptake assay for TSAb increased 3-fold by the modification, when assessed by the IgG concentration required to elicit the same response. The described assay is as sensitive as that using cAMP measurement in NaCl-free buffer. Thus, it could detect TSAb in all 21 patients with active Graves' disease and in 7 of 8 with ophthalmic Graves' disease but not in 29 of 30 control subjects. Thyroid stimulating activities assessed by these two assays correlated with each other (n = 29, r = 0.707, p < 0.001). False positive results obtained in 4 hypothyroid patients with Hashimoto's thyroiditis (serum TSH concentrations, 11-171 mU/L) could be prevented using anti-TSH antibodies. In summary, the described assay allows evaluation of stimulated thyroid function directly without affecting the detection of TSAb.

Animals↗

PubMed1994

Induction in vitro of 72-kD heat shock protein in a continuous culture of rat thyroid cells, FRTL5.

In Graves' disease and Hashimoto's thyroiditis, the presence of 72-kD heat shock protein (hsp-72) on thyrocytes has been reported. To clarify the significance of this phenomenon, we induced the antigen in thyroid cell culture in vitro. In the FRTL5 rat cell line, which had been heated at 42.5 degrees C or treated with sodium arsenite, expression of hsp-72 was examined with immunoperoxidase staining and immunoprecipitation of the metabolically labelled protein using a specific MoAb. In the cells cultured either with or without thyrotropin (TSH), heat and chemical stresses reproducibly and dose-dependently induced hsp-72 antigen, whereas unstimulated controls had no significant immunoreactivity. Unlike in Graves' retrocular fibroblasts, hydrogen peroxide was not an effective stress in FRTL5, and the induction was not suppressed by methylmercaptoimmidazole and propylthiouracil, nor enhanced by interferon-gamma (IFN-gamma) and tumour necrosis factor-alpha (TNF-alpha). These data could not support the hypotheses that suppression of thyroid autoimmunity by thionamides is due to their modulatory action on hsp-72 expression, or that presence of that antigen in the thyroid tissues affected by autoimmunity is secondary to cytokine secretion from infiltrating immunocytes. On the other hand, coculture experiments of stressed FRTL5 cells and syngeneic Fisher rat splenocytes suggest that aberrantly expressed hsp may activate part of the thyroid-infiltrating lymphocytes and thereby aggravate autoimmune processes. The induction and detection systems of hsp-72 using FRTL5 cells would facilitate future studies, possibly utilizing human materials as well, to explore possible relations between stress proteins and thyroid autoimmunity.

Animals↗

PubMed1994

Metastatic thyroid cancer presenting as thyrotoxicosis: report of three cases.

Three patients with metastatic thyroid follicular carcinoma developed thyrotoxicosis. Two had mild T3 toxicosis without detectable TSH binding inhibitor immunoglobulins (TBII) or thyroid stimulating antibodies (TSAb). Considerable concentration of 131I by tumours occurred, although serum TSH was undetectable. The third patient developed thyrotoxicosis several months after treatment with 131I had commenced and this was associated with concurrent increase in both TBII (90%; normal, less than 11%) and TSAb (2100%). We conclude that thyrotoxicosis in patients with metastatic thyroid carcinoma may result from a large bulk of tumour functioning either autonomously or after stimulation by TSH receptor antibodies.

Adenocarcinoma, Follicular↗

PubMed1994

[A new one-step, labeled-antibody assay for measuring free thyroid hormone concentrations].

We describe one-step labeled-antibody assays for measuring free T4 and free T3 concentrations in serum, based on a novel principle (Amerlex-MAB). Free T4 or free T3 in the sample competes with a molar excess of a cross-reactant (T3 or T2, respectively), chemically coupled to magnetizable polymer particles, for binding to 125I-labeled monoclonal anti-T4 or anti-T3 antibody, respectively. 125I radioactivity bound to the solid phase is inversely proportional to the serum free T4 or free T3 concentration. This one-step assay apparently proceeds to equilibrium after 30 min at 37 degrees C. Within- and between-assay precision (CV) was < 5.7% for free T4 or 6.2% for free T3. The reference range was between 0.98 and 1.77 ng/100 ml for free T4 and between 2.8 and 4.6 pg/ml for free T3. The measurement of free T4 and free T3 concentrations could clearly discriminate hyperthyroid and hypothyroid patients from euthyroid subjects. These values correlated closely to those obtained by an analog radioimmunoassay (Amerlex-M). This method is free from interference by major T4-binding proteins in serum, showing improved performance, compared to the analog radioimmunoassay, with sera from NTI patients with low serum albumin concentrations or anti-thyroid hormone antibodies. We expect these assays to be clinically useful for the evaluation of thyroid functions.

Antibodies, Monoclonal↗

PubMed1994

[Basic and clinical evaluation of a novel immunoradiometric assay kit for free thyroxine].

We have evaluated a new immunoradiometric assay for free thyroxine (T4) utilizing thyroxine-coated particles and radioiodinated monoclonal anti-T4 antibodies. The assay results were reproducible with coefficients of variation no more than 3.1% for intraassay and no more than 6.7% for interassay. Serum free T4 values for 48 healthy subjects distributed at 1.13 +/- 0.19 ng/dl (mean +/- SD). In various thyroid diseases, the results with the new kit compared well with two other measurements (T4-analog RIA and equilibrium dialysis RIA). Altered concentration of thyroxine binding globulin did not significantly affect this assay, while anti-thyroxine autoantibodies caused factitiously elevated free T4 values in some cases. In pregnancy, free T4 concentration tended to decline mildly in late stages. About 20% of hypoalbuminemic samples from patients with nonthyroidal illnesses had free T4 concentration more than 2.00 ng/dl, probably due to renal failure or to the use of diuretics, heparin, or other drugs which may increase serum free T4 fraction in vivo. In conclusion, this new free T4 IRMA kit is convenient and reproducible, and suitable for routine measurement of clinical material.

Animals↗

PubMed1994

Radioiodine uptake by squamous-cell carcinoma of the lung.

A patient with a history of total thyroidectomy for papillary carcinoma showed a solitary hot spot in the chest on post-therapy radioiodine imaging. Subsequent evaluation demonstrated that this lesion was a primary squamous-cell lung cancer. Our case illustrates a rare but important differential diagnosis from lung metastasis of thyroid cancer in 131I scintigraphy. Alternatively, this "aberrant uptake" might be a rather common phenomenon for lung neoplasms, although the underlying mechanism is not yet known. Future experimental studies might lead to a new application of radioiodine imaging in pulmonary oncology.

Adenocarcinoma, Papillary↗

PubMed1994

Scintigraphic findings of the thyroid in euthyroid ophthalmic Graves' disease.

UNLABELLED: The scintigraphic findings of the thyroid were analyzed in patients with euthyroid ophthalmic Graves' disease known to have some thyroid-related abnormalities. METHODS: Technetium-99m-pertechnetate images of the thyroid from 38 euthyroid ophthalmic Graves' disease patients with small, soft or nonpalpable goiter were analyzed. RESULTS: Scan images showed homogeneous (even) and nonhomogeneous (uneven) 99mTc uptake in 20 and 16 patients respectively. Poor images due to low uptake were observed in two patients. Six patients displayed alterations in scintigraphic appearance from even to uneven patterns after T3 suppression test. Statistical analysis revealed that the uneven pattern was more frequently observed in euthyroid ophthalmic Graves' disease patients than in 26 patients with hyperthyroid Graves' disease who were euthyroid during antithyroid drug therapy (p < 0.005). The scintigraphic heterogeneity was correlated with reduced uptake as well as a higher ratio of the uptake values after T3 treatment to the pretreatment values. Scintigraphically, hot or warm lesions were observed in most cases showing the uneven pattern (16/22; 73%). Rather low titers of antithyroglobulin, antimicrosomal antibodies and TSH-binding inhibitor immunoglobulins were detected in only 4 (10.5%), 7 (18.4%) and 12 (31.6%) patients respectively, while the prevalence of thyroid-stimulating antibodies (TSAb) was as high as 86.8% (33/38). The scintigraphic heterogeneity did not correlate with the detection of these antibodies but did correlated with the severity and duration of ophthalmopathy. CONCLUSIONS: The presence of functioning follicular cells with some autonomy that were heterogeneously distributed in the thyroid was observed in about half the euthyroid ophthalmic Graves' disease patients. Chronic stimulation by TSAb may be the underlying mechanism for these findings.

Adolescent↗