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Biomedical subjects

H Hiratani

Publications and source records attributed to H Hiratani.

13 recordsLinked to original sources
PubMed2002

Drug-induced neutropenia associated with anti-neutrophil cytoplasmic antibodies (ANCA): possible involvement of complement in granulocyte cytotoxicity.

Although antineutrophil antibodies are thought to be involved in drug-induced neutropenia, neither the precise mechanisms nor the particular antigens on the neutrophil surface have yet been clarified. Recently, we examined a patient with Graves' disease who developed antineutrophil cytoplasmic antibodies (ANCA) after propylthiouracil treatment and exhibited neutropenia. Because several target antigens of ANCA are expressed on the surface of neutrophils, it was suggested that ANCA might contribute to neutropenia. The patient's serum bound specifically to neutrophils and HL-60 cells differentiated into granulocytes, and lysed the HL-60 cells via a complement-mediated mechanism. Furthermore, two representative ANCA antigens, proteinase 3 and myeloperoxidase, significantly inhibited both the binding and cytotoxicity of the serum. Finally, tumour necrosis factor-alpha, which is known to up-regulate cell surface expression of several ANCA antigens, enhanced both the binding and cytotoxicity of the serum. These findings suggest that ANCA induced by propylthiouracil contributed to leucopenia through a complement-mediated mechanism.

Antibodies, Antineutrophil Cytoplasmic↗
PubMed2001

[Association study on candidate loci of susceptible genes of autoimmune thyroid diseases in a Japanese population].

Autoimmune thyroid diseases(AITD), which include Graves' disease(GD), Hashimoto's thyroiditis(HT), primary hypothyroidism with blocking-type anti-thyrotropin receptor antibody and idiopathic myxedema, are believed to be a multifactorial disease with a significant genetic and environmental component. Several genetic factors associated with AITD susceptibility have been tentatively identified, including the HLA genes and the cytotoxic T lymphocyte associated-4(CTLA-4) gene. More recently, as part of a genome scan, five additional chromosomal locations, i.e., chromosome 5, 8, 9, 15 and X, have recently been reported in a Japanese population. In the present study, in order to confirm evidence obtained by the genome scan, we performed an association study regarding these five candidate loci identified as regions where susceptible genes of AITD exist. Five microsatellite markers, which are located in these loci, were genotyped in a set of 487 unrelated Japanese AITD patients and 218 Japanese controls. Markers located in chromosome 5, 15 and X showed association in AITD patients with significant increase in particular alleles (p < 0.01), while markers in chromosome 8 and 9 did not consistently show significant association. These findings partly support evidence by the previous genome scan that attempted to identify loci of susceptible genes of AITD in a Japanese population; presence of an AITD susceptibility locus at 5q31-33 was suggested. Genotyping using other markers located in these loci would be helpful not only to confirm regions of AITD susceptible genes but also to narrow the regions.

Adolescent↗
PubMed2000

Association of autoimmune thyroid disease with microsatellite markers for the thyrotropin receptor gene and CTLA-4 in Japanese patients.

In a previous study we identified a microsatellite marker near the thyrotropin receptor (TSHR) gene. Studies with this marker, TSHR-CA, revealed a significant association between autoimmune thyroid disease (AITD) in Japanese patients and one specific allele (allele 1; 180 base pair [bp]) of the microsatellite sequence. In addition, weak evidence for association of AITD with two alleles of the CTLA-4 gene was observed. In the present study, TSHR-CA has been mapped to approximately 600 kb of the TSHR gene using radiation hybrid mapping. TSHR-CA and another TSHR microsatellite marker, TSHR-AT, which is located in intron 2 of TSHR gene, were genotyped in a set of 349 unrelated Japanese AITD patients and 218 Japanese controls. The TSHR-AT marker showed association in this Japanese AITD population with a significant increase in allele 5 (294 bp; p < 0.05) and a significant decrease in allele 7 (298 bp; p < 0.05). The association of allele 5 of TSHR-AT was also significant in hypothyroid patients (thyrotropin-binding inhibitory immunoglobulin-positive [TBII+], P < 0.01; thyrotropin-binding inhibitory immunoglobulin-negative [TBII-], p < 0.05). The association of allele 7 of TSHR-AT were also significant for the hypothyroid TBII+ patients (p < 0.05). The CTLA-4 gene was also genotyped in this expanded set of Japanese AITD patients and controls. Association between AITD susceptibility and allele 2 (102 bp; p < 0.01) and allele 4 (106 bp; p < 0.01) were observed. These associations were also observed with GD patients (allele 2, p < 0.01; allele 4, p < 0.01). Associations with TSHR-CA were observed for Hashimoto's thyroiditis (HT) patients with respect to alleles 3 (179 bp; p < 0.05) and 5 (175 bp; p < 0.05) and with hypothyroid TBII- patients for allele 4 (177 bp; p < 0.05). The presence of specific alleles of TSHR-CA, TSHR-AT, and CTLA-4 contribute significant increase in risk of development of AITD. These results confirm and expand on our previous study suggesting that alleles of the TSHR and CTLA-4 genes, or genes near them contribute to AITD susceptibility and set the stage for future studies of interactions between these genes and AITD.

Abatacept↗
PubMed2000

Hashimoto's thyroiditis with heterogeneous antithyrotropin receptor antibodies: unique epitopes may contribute to the regulation of thyroid function by the antibodies.

Blocking-type TSH-binding inhibitor Igs (TBIIs) are known to cause hypothyroidism and an atrophic thyroid gland in patients with primary myxedema. They can block the activity of thyroid-stimulating antibodies (TSAbs) in Graves' patients as well as the activity of TSH. The majority of the epitopes for these blocking-type TBIIs have been, and are shown herein, to be present on the C-terminal region of the extracellular domain of the human TSH receptor (TSHR), whereas those for Graves' TSAbs are on the N-terminus. We report on a patient with Hashimoto's thyroiditis who suffered from mild hypothyroidism and a moderately sized goiter. Her serum had a potent blocking-type TBII and a weak TSAb in human and porcine TSHR systems. Using human TSHR/lutropin-CG receptor chimeras, we determined that the functional epitope of her blocking-type TBII was uniquely present on the N-terminal, rather than the C-terminal, region of the extracellular domain of the TSHR, unlike the case for blocking-type TBIIs in primary myxedema patients. The epitope of her TSAb was also unusual. Although the functional epitopes of most TSAbs are known to involve the N-terminal region of the receptor, her TSAb epitope did not seem to be present solely on the N- or C-terminus of the extracellular domain of the receptor. Blocking-type TBIIs from patients with primary myxedema blocked her TSAb activity as well as stimulation by TSH; her blocking-type TBII was able to only partially block her TSAb. In contrast, her blocking-type TBII almost completely blocked TSAbs from Graves' patients. Thus, we suggest that the unique epitopes of this patient's heterogeneous population of TSH receptor antibodies, at least in part, contribute to regulation of her thyroid function.

Animals↗
PubMed1993

Charge isomers of urinary bikunin (trypsin inhibitor).

It was observed that the purified urinary bikunin (trypsin inhibitor) consisted of four major isomers with different electric charges which could be separated by HPLC using a Mono Q column. These isomers revealed the same antitrypsin activity and did not show any differences in the apparent molecular weight by SDS-PAGE, amino-acid composition, N-terminal amino-acid sequence (1-40) and C-terminal amino acid (Leu). The contents of sialic acid and uronic acid were also identical among these isomers. However, analysis of chondroitin sulfate revealed all the glycosaminoglycan chains of these isomers were undersulfated, comprising nonsulfated and 4-sulfated disaccharide units, and 4-sulfated disaccharide unit ratio varied among these isomers. After the chondroitin ABC lyase digestion, all the isomers were eluted at the same position on a Mono Q column chromatography. These results indicated that charge isomers of urinary bikunin was attributed to the difference on sulfation ratio in a glycosaminoglycan chain.

Amino Acids↗
PubMed1990

Existence and unique N-terminal sequence of alpha II (omega) interferon in natural leukocyte interferon preparation.

Human alpha interferon produced in Sendai virus-stimulated leukocytes was purified by immunosorbent affinity chromatography and subjected to subtype analysis. All subtypes in leukocyte culture supernatant were confirmed in purified preparation. One of these subtypes was reactive in Western blotting with antibody specific to alpha II (omega). N-terminal amino acid sequence analysis of this particular subtype showed addition of two amino acids to the N-terminus of alpha II predicted through cDNA studies. The apparent cleavage site for leader sequence of alpha II was different from the site common to all other alpha subtypes. This is the first report on the isolation of natural alpha II and its unique N-terminal amino acid sequence.

Amino Acid Sequence↗
PubMed1990

Enhancement of the fibrinolytic activity in plasma by oral administration of nattokinase.

The existence of a potent fibrinolytic enzyme (nattokinase, NK) in the traditional fermented food called 'natto', was reported by us previously. It was confirmed that oral administration of NK (or natto) produced a mild and frequent enhancement of the fibrinolytic activity in the plasma, as indicated by the fibrinolytic parameters, and the production of tissue plasminogen activator. NK capsules were also administered orally to dogs with experimentally induced thrombosis, and lysis of the thrombi was observed by angiography. The results obtained suggest that NK represents a possible drug for use not only in the treatment of embolism but also in the prevention of the disease, since NK has a proven safety and can be massproduced.

Administration, Oral↗
PubMed1989

Variant human neuroblastoma cell lines resistant to the differentiation-inducing effect of interferon-gamma.

Human recombinant interferon, (rIFN)-gamma, induced a human neuroblastoma cell line GOTO to differentiate, but neither rIFN-alpha A nor -beta did. To elucidate the mechanism of this rIFN-gamma-specific differentiation-inducing effect, we established two rIFN-gamma-resistant variant GOTO clones. They were insensitive to the growth-inhibitory and differentiation-inducing effect of 1 X 10(3) IU/ml rIFN-gamma. They were slightly sensitive to the growth-inhibitory effect of rIFN-gamma (2 X 10(4) IU/ml). Parental GOTO cells were very insensitive to the antivesicular stomatitis virus (VSV) effect of all three types of rIFNs and even 2 X 10(4) IU/ml rIFN-gamma could not inhibit the cytopathic effect of 5 TCID50 VSV by 50%. The degree of this insensitivity was the same in the variant GOTO cells as in the parental GOTO cells.

Cell Line↗
PubMed1987

[Morphological changes of human neuroblastoma cells induced by human gamma interferon].

The treatment of GOTO cells, originated from human neuroblastoma, with recombinant human interferon-gamma (rHuIFN-gamma) induced the morphological changes: the extension and bifurcation of neurites and the multinucleated giant cell formation. The treatment of KP-N-RT cells, originated from human neuroblastoma, with rHuIFN-gamma also induced the similar morphological changes. The treatment of these cells with natural HuIFN-gamma also induced the same morphological changes, but those with recombinant human leukocyte interferon (rHuIFN-alpha A), recombinant human fibroblast interferon (rHuIFN-beta) and recombinant murine interferon-gamma (rMuIFN-gamma) did not induce it. The rHuIFN-gamma and the rHuIFN-beta inhibited more strongly the growth of GOTO and KP-N-RT cells than the rHuIFN-alpha A. This suggests that the morphological changes of these neuroblastoma cells are not simply due to the cell growth inhibition, but due to the property which only the rHuIFN-gamma possesses.

Cells, Cultured↗
PubMed1985

A sensitive two-site enzyme immunoassay for human epidermal growth factor (urogastrone).

A sensitive enzyme immunoassay (EIA) was developed for human epidermal growth factor (hEGF) or urogastrone, which was isolated from human urine. Our EIA system is based on the sandwiching of an antigen between anti-hEGF IgG coated on a polystyrene tube and anti-hEGF antibody Fab'-linked beta-D-galactosidase (beta-D-galactosidase, EC 3.2.1.23). This method has the advantages that the procedures are simple and rapid and that the antibody Fab'-beta-D-galactosidase complex is more stable than radioisotope-labeled IgG. Purified hEGF is detectable at as low as 100 pg/ml, which is very sensitive compared to the radioimmuno-assays or radioreceptor assays already reported. Using this new EIA system, hEGF levels in human urine were examined. The values for normal males and females were 48.4 and 83.5 ng/mg creatinine, respectively, which shows that females excrete 1.7 times more hEGF than males.

Electrophoresis, Polyacrylamide Gel↗