Biomedical subjects
Publications and source records attributed to N Amino.
The effects of thyroid stimulating hormone (TSH) deficiency on thyroid development was examined using ultrasonography in a child with congenital isolated TSH deficiency. Ultrasound revealed the thyroid gland was one sixth normal volume, suggesting that TSH plays an important part in thyroid growth, but not a critical role in differentiation.
We reported that gestational thyrotoxicosis is induced by thyroid-stimulating activity (TSA) of circulating hCG. However, the serum immunological hCG concentration did not correlate to TSA. To elucidate this, we examined the relation of carbohydrate moieties of hCG to bioactivity in 79 early pregnant women, divided into 4 groups: no emesis, mild emesis, hyperemesis, and gestational thyrotoxicosis with hyperemesis. Serum free T4 (FT4) and free T3 (FT3) levels were significantly higher and TSH was lower in the hyperemesis (FT4, 23.42 +/- 5.02 pmol/L; FT3, 6.26 +/- 1.80 pmol/L; TSH, 0.30 +/- 0.44 mU/L) and in gestational thyrotoxicosis (FT4, 48.65 +/- 14.80 pmol/L; FT3, 14.71 +/- 3.47 pmol/L; TSH, < 0.04 mU/L) groups than in the no emesis group (FT4, 16.99 +/- 2.48 pmol/L; FT3, 5.51 +/- 0.75 pmol/L; TSH, 1.37 +/- 1.23 mU/L; P < 0.0005). TSA was also significantly higher in the hyperemesis (566 +/- 187%) and gestational thyrotoxicosis (832 +/- 168%) groups than in the no emesis group (321 +/- 135%). We found no significant difference among serum hCG concentrations measured by immunoassay in the four groups. To characterize the carbohydrate chains, serum hCG was fractionated by Concanavalin-A and ricin lectin affinity chromatography. The fraction firmly bound to Con-canavalin-A, which contains hCG with high mannose and hybrid-type carbohydrate chains, was significantly higher in the hyperemesis group (91.07 +/- 2.06%; n = 15) than in the no emesis group (89.61 +/- 2.38%; n = 24; P < 0.04). The fraction firmly bound to ricin column, which contains hCG with asialo-carbohydrate chains, was significantly increased in the gestational thyrotoxicosis group (3.44 +/- 1.70%; n = 5) compared with that in the no emesis group (1.77 +/- 0.49%; n = 24; P < 0.03). Serum FT4 positively correlated to the hCG fraction firmly bound to ricin column (r = 0.61; P < 0.001). We conclude that thyrotoxicosis with hyperemesis may be caused by circulating asialo-hCG with higher thyrotropic bioactivity.
PIT1 abnormality is defined as a genetic abnormality in the PIT1 gene that encodes a pituitary specific transcription factor, Pit-1/GHF-1. PIT1 abnormality indicates combined deficiency of thyrotropin (TSH), growth hormone (GH) and prolactin (PRL), and has been reported in several cases. We studied the PIT1 gene in a patient with combined deficiency of TSH, GH and PRL. A novel mutation substituting a termination codon for Glutamate at 250th codon (E250X) was identified in the homozygous state in the patient. Both of the healthy parents harbored this mutation in the heterozygous state. This nonsense mutation results in complete loss of helix 3 of the POU homeodomain of Pit-1/GHF-1. As helix 3 of the homeodomain is involved directly in DNA binding, the mutant Pit-1/GHF-1 may lose the DNA binding activity of the POU homeodomain and lose its transcriptional activation. The E250X mutation is therefore considered to be the cause of the combined deficiency of TSH, GH and PRL in this patient.
We examined 13 patients with euthyroid Graves' disease suspected ophthalmologically, by comparing them with 20 patients with untreated Graves' disease and by following them up for 5 to 10 years. They had Graves' ophthalmopathy (NOSPECS class II-IV) without other ocular diseases, normal levels of serum thyroid hormones, and no previous history of Graves' disease. Proptosis in euthyroid Graves' disease was not significantly different from that in untreated Graves' disease. In 3 patients with euthyroid Graves' disease, TSH was suppressed. There was either no TSH response to TRH or it was low in 7 of 12 patients examined. The result of a T3-suppression test was abnormal in 8 of 11 patients examined. Titers of serum TGHA, MCHA, TSH-binding inhibitory immunoglobulin (TBII), and thyroid stimulating antibody (TSAb) were significantly lower in patients with euthyroid Graves' disease compared than in patients with untreated Graves' disease. TSAb, however, was positive in 12 of 13 (92%) patients. In spite of positive TSAb, 9 of 13 patients with euthyroid Graves' disease had normal radioactive iodine uptake (RAIU). During the observation period, various abnormalities in thyroid function developed: persistent hyperthyroidism in 5 patients (38%), transient thyrotoxicosis in 2 (15%) and transient hypothyroidism in 1 (8%). We conclude that euthyroid Graves' disease is a subtype of Graves' disease that minimally develops thyrotoxicosis in spite of the existence of TSAb due to some mechanism inhibiting thyroid growth or stimulation, and that the measurement of TSAb provides a useful marker for the diagnosis of this disease.
We examined the effects of the long-term administration to mice of thyroid hormone or propylthiouracil (PTU) on lymphocyte subsets in spleens, and thymuses to clarify whether hyperthyroxinemia itself causes the changes in lymphocyte subsets, such as the marked increase in CD5+ B cells and decrease in natural killer (NK) cells, observed in hyperthyroid Graves' disease. Both the number and proportion of splenic NK (Thy-1+ asialo GM1+) cells were increased in hyperthyroxinemic mice treated with thyroxine (T4) for both short and long terms (8 and 32 weeks, respectively), those of splenic and thymic T (CD5+ sIgM-) cells and CD5-B cells were increased only in hypothyroxinemic mice treated with PTU for 32 weeks, compared with those in euthyroid mice. These data indicate that 1) long-term hyperthyroxinemia increases splenic and thymic T cells and splenic NK cells, but not CD5+ B cells, in mice, 2) long-term hypothyroxinemia induced by PTU treatment increases splenic B cells and CD5- B cells, and 3) hyperthyroxinemia itself does not cause the changes in CD5+ B cells and NK cells, which are observed in hyperthyroid Graves' disease, in mice.
A fifty-year-old woman was admitted to our hospital because of palpitation and general fatigue. She had received hemithyroidectomy for thyroid papillary adenocarcinoma at 28 years of age. She had experienced episodes of repeated painless thyroiditis five times over the last 12 years. At her sixth episode of thyrotoxicosis, she was suspected to have Graves' disease and admitted to our hospital. Laboratory findings revealed thyrotoxicosis with positive thyroid stimulating antibody and high radioactive iodine uptake, i.e. Graves' disease. Painless thyroiditis often relapses but rarely develops into Graves' disease. This is a rare case in which repeated painless thyroiditis was followed by Graves' disease. The relation between painless thyroiditis and Graves' disease is discussed.
Five types of immunoassay, enzyme immunoassay (EIA), radioimmunoassay (RIA), fluoroimmunoassay (FIA), chemiluminescent immunoassay (CLIA) and counting immunoassay (CIA), are generally used. Radioimmunoassay was first developed but it needs specific facilities and the half life of radioisotope is not long. Enzyme immunoassay is at present most popular in Japan. The goal of development of immunoassay is improvement of sensitivity and automation. In order to improve sensitivity of an assay, immunoenzymometric assay (IEMA), which is a non-competitive method, was developed and fluorescent materials and chemiluminescent materials are used for the detection of enzyme activity. Automation of immunoenzymometric assay could be done with solid phase antibody method.
Although various hematological disorders have been considered to be etiologic factors in deep vein thrombosis (DVT), the involvement of dysplasminogenemia (DPG) in DVT has not been studied in detail. In 72 consecutive DVT patients, the presence of DVT was suspected based on a history of lower limb swelling and tenderness with acute onset, and was confirmed by duplex scanning, radioisotope venography, or contrast venography. DPG was identified by the observation of dissociation between the activity and antigenicity of plasminogen. Of the 72 patients, 9 (12.5%) were diagnosed as having DPG, and several antithrombin-III deficiency and protein C and S deficiency were identified. The mean age of the genetically normal and DPG patients was 52 +/- 15 and 40 +/- 15 years, respectively (p < 0.05). Thus, these findings suggest that DPG is deeply related to the development of DVT, and that abnormality of the fibrinolytic system is one of the major etiologic factors in DVT.
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Immunoreactive digoxin-like activity was found in the Chinese medicine, KYUSHIN tablet, taken popularly in Japan without prescription. The antibodies used in the assays of digoxin reacted with Ch'an-su, the major effective component of KYUSHIN, which contained cardiotonic steroids with a chemical structure similar to that of digoxin. One tablet of KYUSHIN had digoxin-like immunoreactivity equivalent to 1.9 micrograms. (TDx analyzer), 1.5 micrograms (Du Pont aca analyzer) and 72 micrograms digoxin (Enzymun-Test, Boehringer). These different equivalencies may be attributed to differences in cross-reactivity of the antibody used in the immunoassays. Two healthy volunteers took two KYUSHIN tablets three times a day, a typical dose, and digoxin-like immunoreactivity reached almost 0.4 microgram/l in 0.5 day. Recently, a competitive digoxin chemiluminescent immunoassay has been developed by Ciba Corning ACS 180. The assay utilizes an acridinium-ester labelled mouse monoclonal digoxin antibody as the tracer. In the extracted solution of KYUSHIN and serum after administration of two tablets, the digoxin-like immunoreactivity value on the Ciba Corning ACS 180 digoxin assay was < 0.10 microgram/l (off-range low). Therapeutic drug monitoring should be interpreted carefully in patients taking Chinese medicines, many of which contain the Ch'an-su component.
Various diseases often occur after delivery but the systemic examinations have not been studied before. Thyroid dysfunction frequently (4.4%) occurs after delivery through an immune rebound mechanism. If postpartum women complain of the symptoms caused by thyrotoxicosis (palpitation, weight loss, increased sweating, finger tremor, fatigue) or hypothyroidism (edema, cold intolerance, hoarseness, sleepiness, fatigue), it is essential to examine thyroid hormones, thyroid stimulating hormone, anti-thyroid microsomal antibody (MCHA) and anti-TSH receptor antibody. To predict who will develop postpartum thyroid dysfunction, the measurement of MCHA during pregnancy is useful because 62% of the subjects with positive MCHA show thyroid dysfunction after delivery. The individuals at high risk of postpartum onset of Graves' thyrotoxicosis can be found early in their pregnancy by the detection of thyroid stimulating antibody (TSAb). Other autoimmune diseases, such as rheumatoid arthritis, systemic lupus erythematosus, autoimmune hypophysitis and so on, also could develop after delivery. These findings indicate that laboratory tests in the postpartum period are essential to diagnose postpartum onset of autoimmune diseases and the measurement of autoantibodies in early pregnancy is useful for prediction of their onset in the postpartum period.
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On 1 September 1993, we left our old hospital and moved to our brand new establishment, and at that time we adopted the order-entry and reporting system. In this paper we report on our new laboratory computer system that has been developed to manage a lot of information and to analyze rapidly many test tubes (4000 samples per day) and to elevate the service for our patients. We developed the automated clinical laboratory system and this new system was named as the Clinical Laboratory Supervised System (CLASSY). We used the NEC system 3500 Model 10, NEC N5200 Model 03 sx and NEC PC9821 Ae as a laboratory host computer, an interface unit and a terminal for routine work, respectively. CLASSY covers the automated analysis not only for clinical chemistry, but also for hematology, urinalysis and microbiology. As the ordering and reporting system is applied to the hospital information system, order information for clinical test is transferred to our laboratory host computer when the bar-code label is printed out from the automatic bar-code labeller. Then it is transferred from the laboratory host computer to some subsystems or automatically to an analyzer through the interface units or modems.
IGF-I, when added to TSH-primed FRTL-5 cells, can induce a long lasting Ca2+ influx followed by the DNA synthesis. BAY K8644, a Ca2+ channel agonist, can also induce the DNA synthesis in TSH-treated cells. Staurosporine, which is known to be a potent inhibitor of protein kinase C(PKC) strongly inhibited the DNA synthesis caused by these two reagents. However, in PKC-down regulated cells, IGF-I and BAY K8644 could also evoke the DNA synthesis and the inhibitory effect of staurosporine persisted. These inhibitory effects did not relay on inhibition of the Ca2+ influx induced by BAY K8644. Thus these results demonstrate that staurosporine acts at a point distal to Ca2+ influx to inhibit G1-S transition and this staurosporine-sensitive pathway possibly mediates the mitogenic signal in PKC-independent manner.
Destruction-induced thyrotoxicosis and Graves' thyrotoxicosis must be differentiated, since they are treated differently. To find a useful marker, we examined serial changes in serum thyroglobulin (Tg) concentrations in 20 patients with postpartum thyroid disease (9, euthyroid Hashimoto's disease; 11, Graves' disease in remission in early pregnancy). Serum Tg was measured by a new multisite immunoradiometric assay that allows little influence of anti-Tg autoantibodies. Eight women developed destruction-induced thyrotoxicosis 1 to 4 months postpartum, 6 had relapse of Graves' thyrotoxicosis 2 to 4 months postpartum, and 6 remained euthyroid. In destruction-induced thyrotoxicosis, serum Tg 2 months before the onset was 13.3 +/- 11.4 micrograms/L, then clearly increased 1 month before (34.5 +/- 31.9 micrograms/L) and was even higher at the onset of thyrotoxicosis (116.5 +/- 137.1 micrograms/L). In contrast, serum Tg increased only at the onset in Graves' thyrotoxicosis (from 25.9 +/- 25.2 micrograms/L 1 month before to 76.1 +/- 75.3 micrograms/L at the onset, p < 0.05). There was no difference in serum Tg level at the onset between the two disorders. However, when data were expressed as the percent increase from the level one month before, and the cut-off value were taken at 150%, all 7 patients above the cut-off developed destruction-induced thyrotoxicosis, and 6 of 7 below had recurrent Graves' thyrotoxicosis. Thus, serial measurement of serum Tg is useful for the differentiation of destruction-induced thyrotoxicosis from Graves' thyrotoxicosis after delivery.
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OBJECTIVE: Autoimmune thyroid diseases often occur after delivery. However, it has been difficult to predict who will develop Graves' thyrotoxicosis after delivery. We tried to establish a systematic method for predicting post-partum onset of Graves' thyrotoxicosis. DESIGN: We followed up the pregnant women with antithyroid microsomal antibody (MCAb) from early pregnancy to the post-partum period and analysed the relation between the activities of thyroid stimulating antibodies (TSAb) in early pregnancy and post-partum occurrence of Graves' disease. PATIENTS: Seventy-one women with positive MCAb in early pregnancy were studied. They were randomly selected from 262 MCAb-positive subjects found in 3405 consecutive early pregnant women who attended our maternity clinic during the last ten years. MEASUREMENTS: MCAb was measured with a commercially available agglutination kit. For 71 MCAb-positive subjects, TSH-binding inhibitory immunoglobulin (TBII) and TSAb were measured in early pregnancy, and serially until 6 months after delivery for the subjects with either positive TBII or TSAb. Thyroid function and goitre size were recorded at every observation. RESULTS: Among the 71 subjects, 7 showed positive TSAb in early pregnancy without any thyroid dysfunction; all 7 developed thyroid dysfunction in the post-partum period. Five of them (70% of TSAb-positive subjects) developed Graves' disease, two showing persistence and three transiently. None of 64 TSAb-negative subjects developed Graves' thyrotoxicosis, though 44 developed various types of thyroid dysfunction as a result of post-partum autoimmune thyroiditis. CONCLUSION: The individuals at high risk of post-partum onset of Graves' thyrotoxicosis can be found early in their pregnancy by the detection of TSAb. Overall occurrence of post-partum Graves' disease in the general population is estimated above 0.54%, that is, one in 200 post-partum women may develop Graves' thyrotoxicosis, although thyrotoxicosis may be transient in half of the patients.
To assess the prevalence of postpartum onset of disease among the patients with Graves' disease, we performed a retrospective examination of 289 consecutive female patients with Graves' disease who attended our thyroid clinic. Of these patients, 92 were female of child-bearing age (20-39 y.o.) who have had one or more deliveries, and at least 37 patients revealed clear evidences of postpartum onset of the disease. That is, at least 40% of Graves' patients of 20-39 y.o. developed their disease during the postpartum period.