Incidence of postpartum onset of disease among patients with rheumatoid arthritis.
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Abortion, Induced↗
Biomedical subjects
Y Hidaka
Publications and source records attributed to Y Hidaka.
[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↗
[Cystic fibrosis lung disease and its management].
The function of the cystic fibrosis (CF) gene product, cystic fibrosis transmembrane conductance regulator (CFTR) is critical to normal lung defense. CFTR not only acts as a cAMP-dependent Cl-channel, but regulates other ion channels and several cellular functions. This article describes the current understanding of the clinical pathophysiology and the management of cystic fibrosis lung disease, particularly the CFTR-related bacterial colonization of the airways. Since chronic lung infection remains the major cause of early death, it is important to interrupt the cycle of infection and inflammation that leads to bronchiectasis and respiratory failure. Only a few cases have been reported in Japanese with no mutations including delta F508 identified. Those cases seem to be caused by unknown factors yet to be found.
Anti-Bacterial Agents↗
[Monoclonal RF immune complex].
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Antibodies, Monoclonal↗
Contribution of proline residue for efficient production of MHC class I ligands by proteasomes.
Proteasomes are processing enzymes capable of generating major histocompatibility complex (MHC) class I ligands, but the mechanism of how they excise ligands without destroying them is largely unknown. Previously, we reported that most products of ornithine decarboxylase degraded in vitro by the 26 S ATP-dependent proteasome, which contained one or two Pro residues (Tokunaga, F., Goto, T., Koide, T., Murakami, Y., Hayashi, S., Tamura, T., Tanaka, K., and Ichihara, A. (1994) J. Biol. Chem. 269,17382-17385), which implied that the Pro residue has a role in the escape from random cleavage by proteasomes. Here, we examine the role of the Pro residue in producing MHC class I ligands in vitro. Proteasomes generated two cytotoxic T lymphocyte-epitopic precursor peptides, SIIPGLPLSL and DMYPHFMPTNL, from the 29-mer and 25-mer peptides harboring these sequences, which are derived from the c-akt proto-oncogene and the pp89 protein of mouse cytomagalovirus, respectively. Replacement of the first or second Pro residue within these epitopes by Ala resulted in a marked reduction of this epitope-derived production or their random cleavage by proteasomes, irrespective of the presence of PA28, which greatly accelerates the generation of unmodified ligands. Moreover, replacement of a single amino acid residue other than Pro in both epitopic and flanking regions by Ala or Leu had no or little appreciable effect on the SIIPGLPLSL or its derivative production. Thus, Pro residue(s) within these epitopic sequences presumably contributes to efficient production of MHC class I ligands through prevention of their random cleavage by proteasomes.
Amino Acid Sequence↗
Incidence of congenital rubella syndrome and influence of the rubella vaccination program for schoolgirls in Japan, 1981-1989.
In 1984, the authors first conducted a nationwide survey of deaf children with a history of maternal rubella (HMR) in special schools for the deaf in Japan. The survey showed that the incidence of congenital rubella syndrome in the Japanese mainlands was similar to those in the United States and Europe. In 1993, a second nationwide survey by the authors evaluated the efficacy of the vaccination program for schoolgirls begun in 1977. This second survey yielded 272 deaf children with HMR born between 1981 and 1989. Per 100,000 annual livebirths, the incidence rates were 1.56-9.95 in the epidemic years 1981-1982 and 1987-1988 and 0.20-0.72 in the interepidemic years. During the 1987-1988 epidemic, the incidence rates per 100,000 livebirths were 1.52 among mothers eligible for the vaccination program and 5.52-7.44 among mothers not eligible, and the difference was significant. However, only 21.7% of the women who delivered children during the 1987-1988 rubella epidemic were eligible for the vaccination program, and because the majority of deaf children with HMR were born to mothers not eligible, a decrease in the birth rate of deaf children with HMR was not observed. These data suggested the need to introduce a new vaccine program to suppress rubella epidemics.
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↗
In vitro disulfide-coupled folding of guanylyl cyclase-activating peptide and its precursor protein.
Guanylyl cyclase-activating peptide II (GCAP-II), an endogenous ligand of particulate guanylyl cyclase C (GC-C), is processed from the precursor protein and circulates in human blood. GCAP-II consists of 24 amino acid residues and contains two disulfide bridges. The correct disulfide paring of GCAP-II is an absolute requirement for its biological activity. This study shows that the folding of the peptide from the reduced form yields a peptide with the native disulfide paring as a minor product and with non-native ones as major products, regardless of the presence or absence of reduced and oxidized glutathione. The results suggest that GCAP-II does not possess sufficient information to permit the adoption of the native conformation and to effectively form the correct disulfide pairing and, as a result, that GCAP-II is correctly folded by assistance of a factor(s) such as an intra- or intermolecular chaperone. We studied whether a peptide in the pro-leader sequence of the precursor protein (proGCAP-II) contains sufficient information to facilitate the folding of GCAP-II. For this purpose, we prepared proGCAP-II in Escherichia coli by a recombinant technique and examined the disulfide-coupled folding of proGCAP-II from the reduced form. proGCAP-II was quantitatively recovered with the correctly folded structure from the reduced form both in the presence and in the absence of reduced and oxidized glutathione. The protein contains only disulfide linkages at the same positions as the mature form of proGCAP-II, GCAP-II, and the biologically active isomer of GCAP-II in the molecule. These results provide evidence that the propeptide of proGCAP-II is a critical factor in the formation of the correct disulfide paring in the folding of the protein.
Amino Acid Sequence↗
A case of atypical aortic coarctation with refractory congestive heart failure--treatment with axillo-iliac artery bypass.
Coarctation of the aorta is rare. We present a case of atypical coarctation due to aortitis syndrome with congestive heart failure refractory to conventional medical treatment. Although indications for surgical treatment are not well established and, in general, treatment of choice is an aorto-aortic bypass, we selected axillo-iliac bypass with subcutaneous tunnel because of severe heart failure. Postoperatively, the pressure gradient disappeared and heart failure was improved.
Aged↗
Progressive patterns of degenerative arthritis in scaphoid nonunion demonstrated by three-dimensional computed tomography.
Degenerative arthritis following scaphoid nonunion was studied in 28 patients (29 wrists) using X-ray computed tomography and three-dimensional computed tomography (3-DCT). Degenerative changes were observed in 18 wrists with plain radiography and 27 wrists with 3-DCT. 3-DCT imaging more readily revealed osteophyte formation in osteoarthritis than plain radiography. 3-DCT images showed degenerative changes in the distal fragment of the scaphoid earlier than plain radiography. We found three stages of osteophyte formation in the radioscaphoid joint using 3-DCT. In the first stage, a linear osteophyte formed along the most radial portion of the distal fragment of the scaphoid. In the second stage, the radial styloid became pointed. In the third stage, the osteophyte on the distal fragment enlarged and lay over the dorsum of the radioscaphoid joint and other intercarpal joints.
Adolescent↗
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↗