Biomedical subjects
Publications and source records attributed to R Takeuchi.
Buerger's disease or thromboangiitis obliterans with involvement of small arteries of the upper and lower extremities usually afflicts young male smokers, but this report presents a middle-age female nonsmoker with diabetes mellitus who satisfied clinical, angiographic and histologic criteria for the diagnosis of Buerger's disease.
The obstetric course and neonatal outcome were studied in 35 pregnant women with neuropsychiatric disorders who were admitted to Toho University Ohmori Hospital between 1981 and 1990. The rate of live births associated with psychiatric disease was 0.49% (40 of 8.191 deliveries). These were schizophrenia (N = 17), epilepsy (N = 12), depression (N = 2), neurosis (N = 3) and psychogenic response (N = 1). Iron deficiency anemia was observed in 8 of 16 epileptic women. Cesarean section or vacuum extraction were performed in 15 of 40 cases (37.5%). The indications for these procedures were uncontrollable psychotic symptoms in all of 6 schizophrenic women, while those in all 7 epileptic women were obstetrical. Symptoms of schizophrenia became worse in 33.3% and 50% of the patients during and after birth, respectively. The incidence of preterm delivery was 15%, and 25% of newborn infants were of low birthweight. Drug withdrawal symptoms were observed in 4 of 16 infants (25%) born to epileptic mothers. Three of 10 offspring of epileptic mothers were affected by febrile convulsions within 6 years of age. Although a relatively higher incidence of obstetric complications has recognized, there seem to be no specific complications in epileptic or psychiatric women. Our results also suggest the importance and need for close cooperation between the obstetrician and psychiatrist, and a follow-up program for offspring.
To evaluate noninvasive regional cerebral blood flow (CBF) measurements using technetium-99m-L, L-ethyl cysteinate dimer (99mTc-ECD), radionuclide angiography, resting- and acetazolamide-activating-SPECT studies were performed during about one hour. Forty-four cases with diagnosis of cerebral ischemic disorders were studied. For 36 cases (Group "Acz"), radionuclide angiography was performed immediately after intravenous bolus injection of 300 MBq of 99mTc-ECD, followed by the consecutive SPECT studies. In the midst of the first SPECT study, acetazolamide was administered. Just after the completion of the first SPECT study, another 300 MBq of 99mTc-ECD was added and the second SPECT study was started. For the remaining 8 cases (Group "Placebo"), physiological saline was administered instead of acetazolamide. Quantitative flow-mapping image was calculated from the qualitative SPECT image by the application of Patlak plot graphical analysis and Lassen's correction. Group "Placebo" showed no increase of mean CBF (mCBF) between the resting- and the placebo-challenged-SPECT image (2nd mCBF/1st mCBF; 98 +/- 5%). Group "Acz" showed 124 +/- 15% increase of mCBF under acetazolamide activation. By use of these quantitative flow-mapping images, acetazolamide-activated CBF increase was recognized clearly and easily. This noninvasive method is easy to perform and may be helpful to measure cerebral perfusion changes in the acetazolamide test.
The methylotrophic yeast, Candida boidinii, was investigated as a new efficient host for heterologous gene expression. The Saccharomyces cerevisiae adenylate kinase gene (ADK1) was used as the first example for heterologous enzyme production in C. boidinii. C. boidinii cells were transformed with plasmids harboring the S. cerevisiae ADK1 gene under the alcohol oxidase (C. boidinii AOD1) promoter. The chromosome-integrant strains produced adenylate kinase protein corresponding to 22%-28% of the total soluble proteins in an enzymatically active form. When the three-copy integrative transformant was grown for 60 h on methanol-glycerol medium in a 1.5-l jar fermentor, adenylate kinase was produced intracellularly with a yield of up to 2 milligrams culture medium. As the expression of the S. cerevisiae ADK1 in C. boidinii was under similar regulation to that of the C. boidinii AOD1, the previously cloned 1.7-kb AOD1 promoter fragment was proved to harbor sufficient cis elements for AOD1 regulation and found to be an efficient promoter for heterologous gene expression.
A 12 year old boy was admitted to our hospital because of short stature. From the age of 7, his growth velocity decreased and he manifested intolerance to low temperatures, hoarseness, dry skin, and slowness of thought and physical movement. On admission, his height was 129.8 cm (-3 s.d.) and his body weight was 43.2 kg (-0.5 s.d.). His clinical features also included relaxation phase of tendon reflexes, periorbital puffiness and cold skin but no struma. His bone age was 9 years. His serum thyroxine (T4), triiodothyronine (T3), free T4 and free T3 were low, while his thyrotropin was high. He was positive for antithyroglobulin antibodies, antimicrosomal antibodies, and TSH-binding inhibitor immunoglobulins. He was diagnosed as having atrophic thyroiditis. We also determined the HLA haplotypes of his family members. His father's HLA haplotypes were A2, BW61(a) and A24, BW52(b), while his mother's haplotypes were A24, BW52(c) and A30, BW60(d). The HLA haplotypes of both the patient and his younger brother showed a and d, while the patient's elder brother's HLA haplotypes showed b and c. His family members all had normal thyroid function, but his father was positive for antimicrosomal antibodies. In summary, we describe a rare case where the onset of hypothyroidism was prepubertal, where the pathogenesis may have involved TSH-receptor blocking antibodies, and where the inheritance of the disease may have been from the paternal side of the family.
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)
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.
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.
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.
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.
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.
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.
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.
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.
The transcription initiation signals in retroviruses lie within the long terminal repeat (LTR) sequences. We have found a new transcriptional promoter in a central portion of the genome of human T-cell leukaemia virus type I (HTLV-I). The transcription start site is located just upstream to the ATG codon of the transcriptional trans-activator molecule, tax protein (Tax). The internal promoter may provide a new insight into gene expression of HTLV-I. The mechanism of leukaemogenesis by the defective HTLV-I is also discussed. Furthermore, we have identified two repeats of a novel enhancer sequence AGTTCT, which are located around the initiation site. We call the sequence HIRE (HTLV-I Internal Regulatory Element).
BACKGROUND: In an attempt to determine possible factors affecting the efficacy of iodine-131 (I-131) treatment for metastatic thyroid carcinoma, the authors focused their efforts on thyroid functions after total thyroidectomy. METHODS: Between 1980 and 1991, 47 patients with lung metastases of differentiated thyroid carcinoma were treated with I-131. Relationships of the images on post-therapy scans with various clinical features were studied. RESULTS: Among them, 28 (59.6%) showed I-131 uptake in the metastases on post-therapy scans. Younger patients had lesions that concentrated more radioactive iodine than did those of older patients. The amount of I-131 concentrated in the metastatic lesions correlated with serum triiodothyronine (T3), thyroxine (T4), and thyroglobulin levels and inversely with serum thyroid-stimulating hormone (TSH) levels determined at the time of therapy. Serum T3 and T4 levels were significantly higher in 28 patients with positive scans than in 19 patients with negative scans. Most patients who had metastases with markedly increased radioactivity were euthyroid or mildly hypothyroid, suggesting that thyroid hormones produced by tumor masses compensated for severe hypothyroidism after total thyroidectomy, and showed favorable responses to the treatment. In three patients successfully treated, decreases in serum thyroglobulin levels and the size of metastatic lesions were accompanied by the development of severe hypothyroidism. CONCLUSIONS: The presence of a large amount of metastatic functioning thyroid tissues responsive to I-131 treatment can be suspected in patients with less severe hypothyroidism after total thyroidectomy.
A 41-year-old hyperthyroid woman visited the hospital in April 1989. She spontaneously developed hypothyroidism in August 1989 and recurrent hyperthyroidism in November 1991. TSH binding inhibitor immunoglobulins (TBII) and thyroid-stimulating antibodies (TSAb) activities were 34.7% (normal range, < 11.0%) and 295.0% (normal range, < 145.0%), respectively, at her first visit. When she was hypothyroid, TBII were 85.9-90.0%, TSAb were 75-190%, and thyroid stimulation-blocking antibodies (TSBAb) activities were 80.0-96.6% (normal range, < 32.2%). When she became hyperthyroid again, TSAb activities were markedly increased to 1108% with TBII and TSBAb activities being 82.2 and 62.8%, respectively. The results indicate that both stimulating and blocking types of TSH receptor antibodies were present in her serum and that her fluctuating thyroid function could be explained by alterations in the balance between the activities of these two types of antibodies.
To clarify the relation of TSH receptor antibody (TRAb) to Graves' ophthalmopathy and thyroid function, the activities of TSH binding inhibitor immunoglobulins, thyroid-stimulating antibodies, and thyroid stimulation-blocking antibodies were measured in five patients with hypothyroid Graves' disease. The diagnosis was based on the presence of Graves' ophthalmopathy and either permanent or transient hypothyroidism without a history of treatment for hyperthyroid Graves' disease. TSH binding inhibitor immunoglobulins and thyroid-stimulating antibodies were detected in all five patients. Thyroid stimulation-blocking antibodies results indicated that a blocking type of TRAb was not a cause of hypothyroidism. Destructive changes in the thyroid were probably responsible for hypothyroidism, since 1) high antibody titers against thyroglobulin and thyroid microsomal antigen, 2) diffuse hypoechogenicity of the thyroid on ultrasonography, 3) absent or impaired responses of serum T3 after TRH or TSH stimulation, and 4) histological findings similar to those in Hashimoto's thyroiditis were observed. In all patients except one, thyroid function was changeable, with euthyroid and even subclinical hyperthyroid episodes occurring during the course of the illness. It is conceivable that such unstable thyroid function may be attributable to subtle changes in the balance between the effects of destructive changes in the thyroid and the stimulatory effects of TRAb. In conclusion, all patients had TRAb, suggesting a possible relationship between such antibodies and Graves' ophthalmopathy. Patients develop euthyroidism or subclinical hyperthyroidism during the course of the illness with high frequency.