Incidence of postpartum onset of disease among patients with rheumatoid arthritis.
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Abortion, Induced↗
Biomedical subjects
N Amino
Publications and source records attributed to N Amino.
Platelet activation induced by combined effects of anticardiolipin and lupus anticoagulant IgG antibodies in patients with systemic lupus erythematosus--possible association with thrombotic and thrombocytopenic complications.
Antiphospholipid antibodies (aPL) are well known to be associated with arterial and venous thrombosis. In a series of 180 patients with systemic lupus erythematosus (SLE), the prevalence of arterial thrombosis was obviously higher in the patients who had both anticardiolipin antibodies (aCL) and lupus anticoagulant (LA) (17/35, 48.6%, p<0.05) (Table 1) than in the other patients bearing aCL or LA alone or neither of them (2/145, 1.4%). Since a substantial fraction of the former group of patients with arterial thrombosis also had thrombocytopenia (12/17, 70.6%), there was a possibility that aCL and LA might have enhanced platelet activation and aggregation. To test this possibility, we studied the in vitro effects of aCL and LA on the enhancement of platelet activation by flow cytometric analysis using anti-CD62P and anti-CD41 monoclonal antibodies directed against platelet activation-dependent granule-external membrane (PADGEM) protein and platelet glycoprotein IIb (GPIIb), respectively. Platelet activation defined by the surface expression of CD62P was not induced by aCL+ x LA+ plasma only, but was significantly augmented by aCL+ x LA+ plasma in combination with adenosine diphosphate (ADP) at a low concentration that had only a modest effect on platelet activation. In contrast, aCL+ x LA-, aCL- x LA+ and aCL- x LA- plasma samples were incapable of enhancing platelet activation in the presence or absence of ADP stimulation. In addition to plasma samples, the purified IgG from aCL+ x LA+ plasma (aCL+ x LA+-IgG) also yielded apparent enhancement of platelet activation induced by ADP. Furthermore, platelet activation was generated by the mixture of aCL+ x LA--IgG and aCL- x LA+-IgG fractions prepared from individual patients, but not by each fraction alone. These results suggest that aCL and LA may cooperate to promote platelet activation, and may be involved, at least partially, in the pathogenesis of arterial thrombosis and thrombocytopenia in patients with SLE.
Adolescent↗
[From a diagnostic test to discovery of a new syndrome].
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Autoantibodies↗
[Organ-specific autoimmune diseases and cytokines].
Changes in serum levels of cytokines in organ-specific autoimmune diseases were reviewed. Serum levels of IL-12, critical for the development of Th1 cells, were increased in thyrotoxic patients with Hashimoto's thyroiditis and Graves' disease. Serum levels of IL-5, secreted from Th2 cells, were increased in thyrotoxic patients with Graves' disease, but not in thyrotoxic patients with Hashimoto's thyroiditis. In patients with IDDM, serum levels of Th1 cytokines (IFN-gamma and IL-2) were increased but serum levels of Th2 cytokines (IL-4 and IL-10) were not increased. These findings suggest that measuring the serum concentration of various cytokines is useful to analyze Th1/Th2 balance in autoimmune diseases.
Cytokines↗
[Postpartum autoimmune thyroid syndrome].
Thyroid dysfunction frequently (around 5%) occurs after delivery through immune rebound mechanism. More than half of the patients suffer from postpartum thyroiditis. Initially, patients have a thyrotoxic phase, later passing through euthyroidism to hypothyroidism and, finally, return to euthyroidism. After delivery, other forms of autoimmune thyroid dysfunction also occur, including Graves' disease, transient hypothyroidism without preceding destructive thyrotoxicosis, and persistent hypothyroidism. To include all these conditions, the term postpartum autoimmune thyroid syndrome is often used. To predict who will develop postpartum thyroid dysfunction, the measurement of anti-thyroid microsomal antibody (MCAb) during pregnancy is useful because 62% of subjects with positive MCAb show thyroid dysfunction after delivery.
Autoimmune Diseases↗
[Serum TSH measurement].
Serum TSH (thyrotropin) measurement is the first-line test to evaluate the thyroid function. Recent sensitive serum TSH assays are based on immunometric assays (IMAs) that use two or more antibodies. Electrochemiluminescent immunoassay expanded both the functional sensitivity potential and the range of serum TSH measurement. It is usually combined with serum free T4 measurement to evaluate the thyroid function, but can be used alone when the pituitary function is normal. Serum TSH levels do not reflect the thyroid function, i) when thyroid function is changing widely, ii) in low T4-T3 states, iii) in central hyperthyroidism or hypothyroidism, and iv) when antibodies such as heterophile antibodies, rheumatoid factors, and rarely anti-TSH antibodies are present.
Humans↗
Accurate and objective preoperative diagnosis of thyroid papillary carcinomas by reverse transcription-PCR detection of oncofetal fibronectin messenger RNA in fine-needle aspiration biopsies.
Recently, the restricted expression of oncofetal fibronectin mRNA was reported in thyroid papillary and anaplastic carcinomas. In this study, by extracting RNA from the leftover cells inside the needles used for fine-needle aspiration biopsy, we establish a new method for gene diagnosis of these carcinomas without further invasiveness to the patient (aspiration biopsy-reverse transcription-PCR, ABRP). RNA was extracted from 177 fine-needle aspiration biopsies of thyroid nodules that were suspicious for malignancy, and then the gene diagnoses made by reverse transciption-PCR detection of oncofetal fibronectin mRNA were compared with cytological diagnoses. Thirty-five (94.6%) of 37 samples that were diagnosed as papillary or anaplastic carcinomas by cytological examination showed a positive result by gene diagnosis, whereas only 4 (3.7%) of 109 samples that were cytologically diagnosed negative for both carcinomas showed a positive result. Among all of the cases, 50 patients underwent surgery, and a histological diagnosis was consequently made. The sensitivity and specificity of this method were 96.9 and 100%, respectively. A combined examination using both genetic and cytological approaches may contribute to a more precise preoperative diagnosis of papillary and anaplastic carcinomas.
Adolescent↗
Effect of solubilization of porcine thyrotropin (TSH) receptor on TSH binding and on radio-receptor assay for anti-TSH receptor antibodies.
The effect of solubilization of porcine thyrotropin receptor (TSHR) on TSH binding and on the radio-receptor assay for anti-TSHR antibodies was examined. After TSHR solubilization with 1% dodecylpolyethy-leneglycoether, TSH binding affinity was increased, from Kd = 1.15 nM to 0.45 nM, and TSH binding capacity was slightly increased, from 0.15 nM to 0.19 nM. With a particulate membrane suspension from thyroid cells, blocking of TSH binding to the membrane suspension by anti-thyrotropin receptor antibody was observed only for thyroid stimulation blocking antibody (TSBAb), not for thyroid-stimulating antibody (TSAb). After the solubilization of TSHR, both TSBAb and TSAb blocked TSH-binding to the solubilized TSHR. We speculate that TSAb interacts with the TSHR in the native conformation without interfering with TSH binding, and that after the solubilization, any anti-TSHR antibody interferes with TSH-binding due to the conformational change in TSHR. With these particulate thyroid cell membrane preparations, we can detect only TSBAb by the radio-receptor assay.
Animals↗
High prevalence of thrombocytopenia in SLE patients with a high level of anticardiolipin antibodies combined with lupus anticoagulant.
The relationship between thrombocytopenia and the level of anticardiolipin antibodies (aCL) and/or the existence of lupus anticoagulant (LA) ware studied in 146 patients with systemic lupus erythematosus (SLE). These patients were divided into six groups: A, those LA positive with a high level of aCL (>10 U/ml) (10 cases); B, those LA positive with a low level of aCL (3-10 U/ml) (15 cases); C, those LA positive but aCL negative (<3 U/ml) (12 cases); D, LA negatives with a high level of aCL (12 cases); E, LA negatives with a low level of aCL (16 cases); and F, aCL and LA double negatives (81 cases). The prevalence of thrombocytopenia (platelet count < or = 100 x 10(9)L) was by far the highest in group A (9/10 cases, 90.0%, P < 0.005, Fisher's exact probability test) as compared with group B (4/15 cases, 26.7%), group C (4/12 cases, 33.3%), group D (1/12 cases, 8.3%), group E (4/16 cases, 25.5%), and group F (9/81 cases, 11.1%). When the relationship between moderate thrombocytopenia and arterial or venous thrombosis was studied in these patients with SLE, thrombocytopenia was detected in 10 (83.3%, P < 0.005, Fisher's exact probability test) of 12 patients with arterial thrombosis; however, it was present in only 4 (23.5%) of 17 patients with venous thrombosis and in 14 (12.3%) of 114 patients without thrombosis. These findings suggest that a high aCL activity combined with LA positively reflects a high risk for both thrombocytopenia and arterial thrombosis.
Adolescent↗
Restricted expression of oncofetal fibronectin mRNA in thyroid papillary and anaplastic carcinoma: an in situ hybridization study.
Restricted expression of oncofetal fibronectin mRNA in the tissues of thyroid papillary and anaplastic carcinoma has recently been shown by both Northern blot analysis and reverse transcriptase polymerase chain reaction (RT-PCR). Oncofetal fibronectin mRNA can be a target of gene diagnosis and targeted gene therapy, provided it is expressed in all cancer cells in the tissues. To investigate this criterion in thyroid cancer tissues, we measured their expression of oncofetal fibronectin mRNA using in situ hybridization. An abundant expression of oncofetal fibronectin mRNA was found in all the observed cancer cells of six papillary carcinomas and an anaplastic carcinoma, but not in the tissues of normal thyroid, Graves' disease, adenomatous goitre, follicular adenoma, follicular carcinoma or medullary carcinoma. This result encourages us to establish gene diagnosis of thyroid papillary and anaplastic carcinomas by detecting oncofetal fibronectin mRNA in biopsies.
Antigens, Neoplasm↗
Increased serum concentration of interleukin-5 in patients with Graves' disease and Hashimoto's thyroiditis.
We investigated serum levels of interleukin-5 (IL-5) in order to examine the role of T-helper 2 (Th2)-type immune response in the pathogenesis of autoimmune thyroid diseases. Serum levels of IL-5 were determined by a highly sensitive sandwich enzyme-linked immunosorbent assay in 42 patients with Graves' disease, 32 patients with Hashimoto's thyroiditis, 12 patients with silent thyroiditis, and 21 normal controls. Compared with serum levels in normal subjects (5.8 +/- 4.2 pg/mL), IL-5 was increased in patients with Graves' disease (16.4 +/- 16.7 pg/mL, p < .01), and in patients with Hashimoto's thyroiditis (10.0 +/- 7.6 pg/mL, p < .05), but not in patients with silent thyroiditis. There was no correlation between serum free thyroxine (FT4) and IL-5 levels. These data suggest an important role of the Th2-type immune response in the pathogenesis of Graves' disease and Hashimoto's thyroiditis.
Adult↗
Serum concentration of soluble Fas in patients with autoimmune thyroid diseases.
Fas is an apoptosis-signaling receptor molecule found on the surface of a number of cell types. Malfunction of the Fas system accelerates autoimmune diseases, whereas its exacerbation may cause tissue destruction. Soluble Fas (sFas) molecule lacks the transmembrane domain due to alternative splicing and blocks Fas-mediated apoptosis. This study investigated serum levels of sFas in autoimmune thyroid diseases. Serum levels of sFas were determined by enzyme-linked immunosorbent assay in 46 patients with Graves' disease, 32 patients with Hashimoto's thyroiditis, 14 patients with silent thyroiditis, and 24 normal controls. Compared with normal subjects (1.43+/-0.37 ng/mL), sFas was increased in thyrotoxic patients with Graves' disease (1.89+/-0.47 ng/mL, p < 0.001), and was decreased in patients with Graves' disease in remission (1.02+/-0.41 ng/mL, p < 0.001) and in euthyroid patients with Hashimoto's thyroiditis (0.97+/-0.25 ng/mL, p < 0.0001), but was normal in hypothyroid patients with Hashimoto's thyroiditis and in thyrotoxic patients with silent thyroiditis. Thus, changes in serum levels of sFas could not be explained by changes in serum thyroid hormones, although sFas concentration correlated with free thyroxine (r = 0.692, p < 0.0001). Also, the levels of sFas significantly correlated with the activities of TSH receptor antibody in Graves' disease (r = 0.671, p < 0.0001). Increased sFas in Graves' disease suggests increased expression of alternatively spliced Fas mRNA variant that produces sFas protein and decreased of cell surface expression of Fas, and may induce thyroid cell growth and production of TSH receptor antibody by protecting against apoptosis of thyroid cells and autoreactive B cells. Decreased sFas in Hashimoto's thyroiditis suggests decreased Fas mRNA variant and increased full-length Fas mRNA and membrane Fas, and may induce destruction of thyroid cells by promoting apoptosis of thyroid cells.
Adult↗
Low response of the thyroid gland to endogenous thyrotropin increased by thyrotropin-releasing hormone in patients with euthyroid Graves' disease.
Euthyroid Graves' disease is defined as Graves' ophthalmopathy without hyperthyroidism, and the thyroid-stimulating antibody (TSAb) has been known to be a good marker for diagnosis. However, the question of why TSAb does not cause hyperthyroidism arises. To settle this, we examined thyroid responsiveness to endogenous thyrotropin (TSH) increased by thyrotropin-releasing hormone (TRH) in 23 patients with euthyroid Graves' disease. Nineteen patients (83%) had positive TSAb and 21 (91%) had at least one of the autoantibodies to the thyroid gland. Only one patient (4%) had positive thyroid-stimulation blocking antibody (TSBAb). Basal levels of free thyroxine (FT4), free triiodothyronine (FT3), and thyrotropin (TSH) in patients were not different from those in age- and sex-matched normal controls (n = 25). Response of TSH to TRH was normal; however, an increase of FT3, either absolute or as a multiple of baseline, in the TRH test in these patients (0.46+/-0.23 pg/mL, P < 0.001; 1.14+/-0.09 fold, p < 0.001) was significantly lower than that in controls (0.86+/-0.19 pg/ml; 1.26+/-0.07 fold). There was no correlation between the deltaFT3/deltaTSH ratio and TSAb activity. It is concluded that thyroid responsiveness in euthyroid Graves' disease is lower than in normal controls and this explains the euthyroid function in the patients even in the presence of TSAb.
Adolescent↗
Prediction of postpartum onset of rheumatoid arthritis.
OBJECTIVE: To investigate the prediction of the postpartum onset of rheumatoid arthritis (RA). METHODS: Two thousand five hundred and forty seven healthy pregnant subjects were examined prospectively and the relation between serum rheumatoid factors (RF) and postpartum onset of RA was observed. Rheumatoid factors were measured in early pregnancy by the antihuman IgG latex agglutination test (Latex test) and antirabbit IgG haemagglutination test (RAHA test). RESULTS: Latex test and RAHA test were positive in 26 (1.0%) and 64 (2.5%) pregnant subjects, respectively. Four hundred and ten subjects of 2547 pregnant women could be followed up for one year after delivery. None of 401 subjects without RF, or with only one RF on either Latex test or RAHA test, developed RA after delivery. Two (22.2%) of nine subjects with both RFs developed RA at one and three months postpartum, respectively. Transient arthralgia was found within 12 months postpartum in three of nine (33.3%) subjects with both RFs and this prevalence was significantly higher than that in RF negative subjects (8.1%). CONCLUSION: Postpartum onset of RA was found in at least 2 of 2547 healthy subjects (0.08%) and onset was predicted by positive test for rheumatoid factors.
Adult↗
Recurrent T354P mutation of the Na+/I- symporter in patients with iodide transport defect.
Iodide transport defect (ITD) is a rare disorder causing congenital hypothyroidism. We previously reported that homozygous T354P mutation in the sodium/iodide symporter (NIS) gene caused ITD. To clarify the prevalence of this mutation, artificial substitution introducing PCR followed by restriction enzyme analysis was developed as a rapid screening method to detect the T354P mutation. Three apparently unrelated families with ITD, one patient with low thyroidal 99mTc pertechnetate (99mTcO4-) uptake and 52 healthy controls (104 alleles) were analyzed for this mutation. All families with ITD harbored the mutation, suggesting that T354P is a recurrent mutation and a major cause of ITD. This was not a widespread mutation, because it was not detected in the 52 unrelated normal controls. Because two cases with homozygous T354P mutation developed multinodular goiters within their second decade of life though they had been maintained in euthyroid state, homozygous T354P mutation alone and/or low intrathyroidal iodide and high serum TSH level in early life might account for tumorigenesis. The patient with low thyroidal 99mTcO4- uptake did not harbor the T354P mutation. Because familial hypocalciuric hypercalcemia was also present in this family, a possibility of the combined abnormality of TSH receptor and calcium functions, which includes an abnormality around the G protein, may be examined further.
Carrier Proteins↗
Genetic basis of congenital hypothyroidism: abnormalities in the TSHbeta gene, the PIT1 gene, and the NIS gene.
We have elucidated the molecular pathology of three types of congenital hypothyroidism. Thyrotropin (TSH) is the major regulator of thyroid function. In cases of isolated congenital TSH deficiency, we found that they are caused by a missense mutation in the conserved CAGYC region of the TSHbeta gene. Pit-1/GHF-1 is a pituitary specific POU-domain DNA binding factor, which transactivates the growth hormone (GH), prolactin (PRL), TSHbeta genes, and the PIT1 gene itself. In cases of combined deficiency of GH, PRL, and TSH, we found that they are caused by abnormalities in the PIT1 gene, either recessively or dominantly. Sodium dependent iodide symporter (NIS) actively transports iodide into the thyroid cells to produce thyroid hormones. In cases of iodide transport defect, we elucidated that a missense mutation in the transmembrane region of the NIS gene caused them.
Carrier Proteins↗
[Anti-receptor antibody and autoimmune disease].
Many receptors are located on the cell surface, and accessible by anti-receptor autoantibodies. After binding to the receptor, anti-receptor autoantibodies may activate the receptor, mimicking the effect of its genuine ligand, or inhibiting activation by ligands. Therefore, anti-receptor autoantibodies have pathogenic importance in several autoimmune diseases, such as Graves' disease, myasthenia gravis, Type B insulin resistance syndrome, and so on. The measurement of anti-receptor autoantibodies is often essential in the diagnosis of these diseases. There are two kinds of measurement procedures. One measures only binding or inhibition of ligand binding to the receptors. That test is simple and available in many laboratories, but cannot distinguish the function--stimulation or inhibition--of autoantibodies. However, procedures that can measure function are rather complicated and may not be available in some laboratories. Not only important for diagnosis, anti-receptor autoantibodies can also be utilized to study receptor-ligand interactions and receptor activation. Recently, there are many studies wherein genetically modified receptors are used for analysis. Here, we will present some our results, as examples.
Autoantibodies↗
[Stress, endocrine, and immune system; stress induces the onset of autoimmune diseases].
Stress can affect endocrine and immune function. In this paper, we reviewed the interaction between stress and Graves disease, which is induced by thyroid-stimulating autoantibodies. Psychological stress was reported to be a risk factor for Graves' disease, although the mechanism by which stress induces autoimmune disease remains unknown. Moreover, we found that other stress, such as delivery and allergic rhinitis can induce the onset of Graves' disease. Immune rebound after delivery and the overproduction of Th 2 (type 2 helper T cells)-derived cytokines after an attack of allergic rhinitis might help produce thyroid-stimulating autoantibodies.
Autoimmune Diseases↗