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Y Hidaka

Publications and source records attributed to Y Hidaka.

At least 19 recordsLinked to original sources
PubMed2001

Influence of breast-feeding on the production of cytokines.

PROBLEM: Recently, we reported increases in the production of interferon-gamma (IFN-gamma), interleukin-2 (IL-2), and IL-4 during the postpartum period. The present study was undertaken to investigate whether these increases might be explained by increased prolactin while breast-feeding. METHOD: Whole blood from 41 women who were breast-feeding, 13 women not breast-feeding, and 31 healthy non-pregnant women was stimulated with phorbol 12-myristate 13-acetate and ionomycin, and the levels of cytokines in the supernatant were measured by enzyme-linked immunosorbent assay. Their serum levels of prolactin were measured by enzyme immunoassay. RESULTS: Increases in IFN-gamma, IL-2, IL-4, and IL-10 production were observed in women who were breast-feeding but not in women who were not breast-feeding. Serum levels of prolactin correlated with the levels of IFN-gamma in culture supernatant. CONCLUSIONS: These results suggest that breast-feeding induces production of cytokines and that IFN-gamma production is enhanced by physiological concentrations of prolactin.

Breast Feeding↗
PubMed2000

Molecular cloning and characterization of a new human histamine receptor, HH4R.

A new histamine receptor, HH4R, was cloned from human leukocyte cDNA. The deduced amino acid sequence showed about 40% identity to that of the human histamine H3 receptor, HH3R. HH4R-expressing cells responded to histamine, inhibiting forskolin-induced cAMP accumulation. An H3 agonist, N-alpha-methylhistamine (NAMHA), bound specifically to HH4R, while another H3 agonist, R(-)-alpha-methylhistamine (RAMHA), and the H3 antagonist, thioperamide, competed with this binding. RAMHA, NAMHA, and imetit inhibited forskolin-induced cAMP accumulation in HH4R-expressing cells. However, the binding affinities and agonistic activities of H3 agonists to HH4R were weaker than those to HH3R. Low expression of HH4R was detected in a wide variety of peripheral tissues by RT-PCR; however, in contrast with HH3R, expression was not detected in the brain. These observations indicate that the clone is a distinct histamine receptor from HH3R, and thus is named HH4R.

Amino Acid Sequence↗
PubMed2000

Dual function of the propeptide of prouroguanylin in the folding of the mature peptide: disulfide-coupled folding and dimerization.

Guanylyl cyclase activating peptide II (GCAP-II), an endogenous ligand of guanylyl cyclase C, is produced via the processing of the precursor protein (prepro-GCAP-II). We have previously shown that the propeptide in pro-GCAP-II functions as an intramolecular chaperone in the proper folding of the mature peptide, GCAP-II (Hidaka, Y., Ohno, M., Hemmasi, B., Hill, O., Forssmann, W.-G., and Shimonishi, Y. (1998) Biochemistry 37, 8498-8507). Here, we report an essential region in pro-GCAP-II for the correct disulfide pairing of the mature peptide, GCAP-II. Five mutant proteins, in which amino acid residues were sequentially deleted from the N terminus, and three mutant proteins of pro-GCAP-II, in which N-terminal 6, 11, or 17 amino acid residues were deleted, were overproduced using Escherichia coli or human kidney 293T cells, respectively. Detailed analysis of in vivo or in vitro folding of these mutant proteins revealed that one or two amino acid residues at the N terminus of pro-GCAP-II are critical, not only for the chaperone function in the folding but also for the net stabilization of pro-GCAP-II. In addition, size exclusion chromatography revealed that pro-GCAP-II exists as a dimer in solution. These data indicate that the propeptide has two roles in proper folding: the disulfide-coupled folding of the mature region and the dimerization of pro-GCAP-II.

Amino Acid Sequence↗
PubMed2000

Enzyme-linked immunosorbent assay for anti-tropomyosin antibodies and its clinical application to various heart diseases.

Tropomyosin is one of the key proteins for muscle contraction. We developed an enzyme-linked immunosorbent assay for antibodies to porcine muscle tropomyosin and measured serum anti-tropomyosin antibodies in patients with heart diseases and in normal controls. The mean values of absorbance in the ELISA assay of patients with ischemic heart disease (n=36, P<0.001), dilated cardiomyopathy (n=28, P<0.005), valvular heart disease (n=27, P<0.05), and collagen disease (n=38, P<0.05) were significantly higher than those of normal controls (n=53), but the value in patients with hypertrophic cardiomyopathy (n=19) was not significantly different from that of normal controls. When the cut-off value was fixed at the mean+2 SD of absorbance in normal controls, positive reactions were found in 19.4%, 7.1%, 18.5% and 15.8% of patients with ischemic heart disease, dilated cardiomyopathy, valvular heart disease, and collagen disease, respectively. An inhibition study revealed that anti-tropomyosin antibodies were different from anti-myosin antibodies, but there was a partial cross-reactivity between the two. Thus, there was a weak correlation of the titers of the two types of antibody within the group of heart diseases. These data indicate that measurement of anti-tropomyosin antibodies by ELISA is helpful for detecting autoimmune abnormalities in various heart diseases.

Adult↗
PubMed2000

A BASH/SLP-76-related adaptor protein MIST/Clnk involved in IgE receptor-mediated mast cell degranulation.

Cross-linking of the high-affinity IgE receptor (FcepsilonRI) on mast cells by IgE-antigen complex triggers signal transduction cascades leading to the release of inflammatory mediators and production of cytokines, which are critical for the development of allergic reactions. We have identified a novel member of the BASH/SLP-76 immunoreceptor-coupled adaptor family expressed in mast cells, termed MIST (for mast cell immunoreceptor signal transducer), which has later been found to be identical to a recently reported cytokine-dependent hemopoietic cell linker, Clnk. Upon FcepsilonRI cross-linking, MIST/Clnk is tyrosine phosphorylated and associates with signaling proteins, phospholipase Cgamma, Vav, Grb2 and linker for activation of T cells (LAT). Overexpression of a mutant form of MIST/Clnk inhibited FcepsilonRI-mediated degranulation, increase in intracellular Ca(2+), NF-AT activation and phosphorylation of LAT. As a crucial signaling component for FcepsilonRI-induced mast cell degranulation, MIST/Clnk might serve as a target for anti-allergic therapy.

Adaptor Proteins, Signal Transducing↗
PubMed2000

Changes in cytokine production during and after normal pregnancy.

PROBLEM: The systemic T helper 1/T helper 2 (Th1/Th2) cytokine balance during normal human pregnancy is controversial, and observations about the balance in the postpartum period have only been reported for up to 3 months. METHOD: Whole-blood, from 83 healthy pregnant women, 80 healthy postpartum women, and 31 healthy non-pregnant women was stimulated with phorbol 12-myristate 13-acetate (PMA) and ionomycin, and the levels of cytokines in the supernatant were measured by enzyme-linked immunosorbent assay (ELISA). RESULTS: The production of all measured cytokines decreased during pregnancy, especially in the second trimester. After delivery, interferon-gamma (IFN-gamma) and interleukin-2 (IL-2) increased from 2 to 11 months postpartum, and IL-4 increased from 6 to 11 months postpartum. CONCLUSIONS: These data indicate that 1) decreases in production of both Th1-and Th2-type cytokines during pregnancy may be related to the pregnancy-induced amelioration of autoimmune diseases: 2) increases in production of both Th1- and Th2-type cytokines in the postpartum period may be related to the postpartum aggravation of autoimmune diseases.

Adult↗
PubMed2000

Relationship between breast milk feeding and atopic dermatitis in children.

OBJECTIVE: To determine whether or not the breast milk feeding has a role in the prevalence of atopic dermatitis among children. METHODS: The target population of the study was all children participating in health check-up program for 3-year-old children in 60 municipalities locating 10 selected prefectures during designated 2 months between October and December 1997. Using a questionnaire, information on nutrition in infants (breast milk only, bottled milk only, or mixed), parity, mothers' age at birth, and a history of atopic dermatitis was obtained. Besides, data on potential confounding factors were obtained. RESULTS: Questionnaires from 3856 children (81.6% of those who were to participate in the programs, and 96.4% of children who participated them) were analyzed. After the adjustment for all potential confounding factors using unconditional logistic models, the risk of atopic dermatitis was slightly higher among children with breast milk (odds ratio [OR] = 1.16 with 95% confidence interval [CI] 0.96-1.40). Mothers' age at birth (OR for those who were more than 30 years or older in comparison with those who were younger than 30 years = 1.15; 95% CI, 0.96-1.37) and those with second or later parity orders (OR = 1.14, 95% CI; 0.95-1.35) showed odds ratios that were higher than unity without statistical significance. CONCLUSION: Breast milk elevates the risk of atopic dermatitis slightly without statistical significance; the risk may be, however, higher in children in second or later parity orders.

Adult↗
PubMed2000

Enzyme immunoassay for autoantibodies to human liver-type arginase and its clinical application.

BACKGROUND: Arginase is an enzyme of the urea cycle, and one of the two isoenzymes is the liver-type enzyme. We examined serum autoantibodies to this liver-type enzyme in patients with hepatitis. METHODS: Antibodies to recombinant human liver-type arginase were measured by ELISA in 95 patients and 55 healthy controls. RESULTS: The mean absorbance values in the ELISA assays of patients with definite autoimmune hepatitis (n = 11; P <0.0001), probable autoimmune hepatitis (n = 31; P <0.0001), and hepatitis C (HCV; n = 20; P <0.01) were significantly different from those of healthy controls, but the values in patients with hepatitis B (HBV; n = 23) and other autoimmune diseases (n = 10) were not significantly different from those of healthy controls. When the cutoff was fixed at the upper 95th percentile of the absorbance value in healthy controls, positive reactions were found in 18.2%, 32.3%, 20.0%, 13. 0%, and 10.0% of patients with definite autoimmune hepatitis, probable autoimmune hepatitis, HCV hepatitis, HBV hepatitis, and other autoimmune diseases, respectively. All of these positive reactions were abolished by inhibition of serum with recombinant antigen. The specificity and sensitivity of this ELISA were 96% and 29%, respectively. The intraassay and interassay coefficients of variation were 2.3-7.5% and 9.8-11%, respectively. There was no relationship between these antibodies and anti-nuclear, anti-smooth muscle, or anti-cytochrome P450IID6 antibodies. CONCLUSIONS: The ELISA for anti-liver-type arginase autoantibody improved the detectability of autoimmune hepatitis when compared with established assays for liver-specific autoantibodies.

Arginase↗
PubMed1999

Determination of the binding site on the extracellular domain of guanylyl cyclase C to heat-stable enterotoxin.

Guanylyl cyclase C, one of the family of membrane-bound guanylyl cyclases, consists of an extracellular domain and an intracellular domain, which are connected by a single transmembrane polypeptide. The extracellular domain binds unique small polypeptides with high specificity, which include the endogenous peptide hormones, guanylin and uroguanylin, as well as an exogenous enterotoxigenic peptide, heat-stable enterotoxin, secreted by pathogenic Escherichia coli. Information on this specific binding is propagated into the intracellular domain, followed by the synthesis of cGMP, a second messenger that regulates a variety of intracellular physiological processes. This study reports the design of a photoaffinity labeled analog of heat-stable enterotoxin (biotinyl-(AC(5))(2)-[Gly(4), Pap(11)]STp(4-17)), which incorporates a Pap residue (p-azidophenylalanine) at position 11 and a biotin moiety at the N terminus, and the use of this analog to determine the ligand-binding region of the extracellular domain of guanylyl cyclase C. The endoproteinase Lys-C digestion of the extracellular domain, which was covalently labeled by this ligand, and mass spectrometric analyses of the digest revealed that the ligand specifically binds to the region (residue 387 to residue 393) of guanylyl cyclase C. This region is localized close to the transmembrane portion of guanylyl cyclase C on the external cellular surface. This result was further confirmed by characterization of site-directed mutants of guanylyl cyclase C in which each amino acid residue was substituted by an Ala residue instead of residues normally located in the region. This experiment provides the first direct demonstration of the ligand-binding site of guanylyl cyclase C and will contribute toward an understanding of the receptor recognition of a ligand and the modeling of the interaction of the receptor and its ligand at the molecular level.

Animals↗
PubMed1999

Histopathological and immunohistochemical studies of membranes of deacetylated chitin derivatives implanted over rat calvaria.

Membranes made of 65, 70, 80, 94, and 100% deacetylated chitin (chitosan) were implanted subperiosteally over the calvaria of 100 rats. Reactions were studied at 1, 2, 4, and 8 weeks after implantation. Membranes prepared with 65, 70, and 80% deacetylated chitin initially elicited marked inflammatory reactions that subsided in time with granulation tissue formation and osteogenesis. Osteocalcin-positive cells were detected immunohistochemically in the granulation tissue. On the other hand, membranes made of 94% deacetylated chitin and chitosan showed mild inflammation and minimal osteogenesis. The results indicate that membranes made of 65, 70, and 80% deacetylated chitin enhance osteogenesis at the site of their implantation. However, the initially severe inflammatory reaction associated with these materials needs to be controlled before the materials would be suitable for clinical application.

Acetylation↗
PubMed1999

Effect of hydroxyapatite content on physical properties and connective tissue reactions to a chitosan-hydroxyapatite composite membrane.

The present study investigated the effect on certain physical properties of adding various amounts of hydroxyapatite (HAP) to chitosan sol. Also investigated were connective tissue reactions to a composite membrane that is being developed for possible use in guided tissue regeneration and for the limitation of HA particle migration at sites of implantation. The physical properties evaluated were shrinkage, tensile strength, hardness, calcium ion release, and morphology. Assessment of physical properties indicated that a ratio of HA to chitosan sol of 4/11 by weight is optimal in the preparation of the composite membrane. Subperiosteal implantation of the membranes over rat calvaria revealed that the membranes were well tolerated, with fibrous encapsulation and occasional areas of osteogenesis. Increasing the hydroxyapatite content seems to enhance membrane degradation.

Animals↗
PubMed1999

Molecular cloning of homologs of RAS and RHO1 genes from Cryptococcus neoformans.

We cloned and sequenced homologs of RAS(CnRAS) and RHO1(CnRHO1) genes from Cryptococcus neoformans. The proteins encoded by the CnRAS and CnRHO1 genes contained 216 and 197 amino acids, respectively. The deduced amino acid sequence of the CnRAS gene shared a high degree of sequence identity with the Ras proteins in other fungal species: Coprinus cinereus(76%), Lentinula edodes(74%), Saccharomyces cerevisiae RAS2(72%), and Schizosaccharomyces pombe(68%). The deduced amino acid sequence of the CnRHO1 gene shared a high degree of sequence identity with the Rho1 proteins in other fungal species: Candida albicans(78%), S. pombe(77%) and S. cerevisiae(76%). The deduced proteins contained GTP-binding and GTP-hydrolysis domains, and the prenylation site that are conserved among the small G protein superfamily. The synthetic peptides that contained the C-terminal amino acid sequence of the CnRas and CnRho1 proteins were geranylgeranylated.

Amino Acid Sequence↗
PubMed1999

Expression and characterization of the extracellular domain of guanylyl cyclase C from a baculovirus and Sf21 insect cells.

Guanylyl cyclase (GC)-C, a single-transmembrane receptor protein for heat-stable enterotoxin, guanylin, and uroguanylin, and its N-terminal extracellular domain were prepared at a high level of expression from a system constructed of Sf21 insect cells and recombinant baculovirus. The recombinant GC-C, containing the complete sequence, retained its binding affinity to heat-stable enterotoxin with a KD value (6.2 x 10(-10) M) and cyclase catalytic activity at a level similar to those of GC-C expressed in mammalian cell lines, such as COS-7. The N-terminal extracellular domain was prepared in a form which contained the hexahistidine tail at its C-terminus and was purified as a homogenous protein by Con A and Ni-chelating affinity chromatography from the culture medium of the insect cells. The purified N-terminal extracellular domain of GC-C exhibited the high (KD = 4 x 10(-10) M) and low (KD = 7 x 10(-8) M) affinity sites in binding to heat-stable enterotoxin. These results clearly indicate that the N-terminal extracellular domain of GC-C possesses the same biochemical characteristics as the complete GC-C protein even in the membrane-free form. Moreover, the extracellular domain is able to form an oligomer in a ligand-dependent manner, suggesting that the N-terminal extracellular domains interact with one another in binding to ligands.

Animals↗
PubMed1999

Postpartum onset of acute heart failure possibly due to postpartum autoimmune myocarditis. A report of three cases.

Autoimmune diseases, especially autoimmune thyroid disease, frequently develop after delivery due to the immune rebound mechanism. Most cases have transient dysfunction of affected organs. Cardiac dysfunction developed after delivery is called postpartum or peripartum cardiomyopathy. However, the aetiology of the disease is not clarified yet. Here we report three cases that developed acute heart failure in the postpartum period. One was complicated with an atrioventricular block and postpartum autoimmune thyroiditis. All patients recovered to normal cardiac function or pre-attack condition after 1 month of therapy with conventional drugs and bed rest. All three had positive antiheart antibody detected by indirect immunofluorescence assay, and one had antibody to heart myosin detected by enzyme-linked immunosorbent assay. Moreover, one of two patients examined revealed lymphocytic infiltration by endomyocardial biopsy. Antibodies to 26 viruses were not elevated significantly during the first 2 weeks after admission in any case. It is strongly suggested that heart failure is induced by postpartum autoimmune myocarditis, and thus clinicians should be aware of this disease.

Acute Disease↗
PubMed1999

The relevance of N-linked glycosylation to the binding of a ligand to guanylate cyclase C.

The role of carbohydrate moieties at the N-linked glycosylation sites of guanylate cyclase C (GC-C), a receptor protein for guanylin, uroguanylin and heat-stable enterotoxin, in ligand binding and structural stability was examined using site-directed mutagenesis of the putative N-linked glycosylation sites in the extracellular domain (ECD) of porcine GC-C. For this purpose, eight mutant proteins of ECD (N9A, N20A, N56A, N172A, N261A, N284A, N334A and N379A) and six mutant proteins of the complete GC-C (N9A, S11A, N172A, T174A, N379A and T381A) were prepared, in which Ala replaced Asn, Ser and Thr at the N-linked glycosylation consensus sites. All the mutant proteins showed a ligand-binding affinity (K(d)) similar to those of the wild-type proteins, although the deletion of a carbohydrate moiety at each of the N-linked glycosylation sites affected the ligand-binding ability of ECD or GC-C to some degree. However, the mutant proteins of ECD (N379A) and GC-C (N379A and T381A) showed considerably decreased binding ability in the context of maximum capacity (B(max)) to a ligand, despite the fact that the expression levels of these mutant proteins were nearly the same as the wild-type proteins. Moreover, the mutant protein of ECD (N379A) was considerably less stable to a denaturant. These results clearly indicate a crucial role for the carbohydrate moiety at N379, which is located near the transmembrane region, in structural stability, the ability to bind to a ligand and the cyclase catalytic activity of GC-C, and provide a route for the elucidation of the mechanism of the interaction between GC-C and a ligand.

Amino Acid Sequence↗
PubMed1999

Increased serum concentration of interleukin-12 in patients with silent thyroiditis and Graves' disease.

We previously reported that interleukin-5 (IL-5), secreted from Th2 cells, was increased in patients with Graves' disease, but not in patients with silent thyroiditis. In this study, we investigated serum levels of interleukin-12 (IL-12) in order to examine the role of Th1-type immune response in the pathogenesis of autoimmune thyroid diseases. Serum levels of IL-12 were determined by a highly sensitive sandwich enzyme-linked immunosorbent assay in 68 patients with Hashimoto's thyroiditis (26 of whom had silent thyroiditis), 74 patients with Graves' disease, 8 patients with subacute thyroiditis, and 27 normal controls. Serum levels of IL-12 in thyrotoxic patients with silent thyroiditis (385.2 +/- 164.5 pg/mL, mean +/- SD), and in thyrotoxic patients with Graves' disease (343.6 +/- 163.8 pg/mL) were significantly increased compared with serum levels in normal subjects (163.9 +/- 66.8 pg/mL, p < 0.0001, p < 0.0001, respectively) or in thyrotoxic patients with subacute thyroiditis (241.9 +/- 46.5 pg/mL, p < 0.01, < 0.05, respectively). The ratio of IL-12 to IL-5 in thyrotoxic patients with silent thyroiditis (64.2 +/- 39.7) was significantly higher than that in normal controls (33.7 +/- 13.3, p < 0.01) or in thyrotoxic patients with Graves' disease (40.6 +/- 36.0, p < 0.05). These data suggest that Th1-type immune response is predominant in silent thyroiditis, and that not only Th2-type immune response but also Th1-type immune response is important in the pathogenesis of Graves' disease.

Adult↗