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Biomedical subjects

Takeyuki Kohno

Publications and source records attributed to Takeyuki Kohno.

6 recordsLinked to original sources
PubMed2006

Preparation of antibodies against a novel immunosuppressant, FTY720, and development of an enzyme immunoassay for FTY720.

FTY720 (1) is a novel immunosuppressant (immunomodulator), derived from ISP-I (2: myriocin and thermozymocidin). To clarify the pharmacokinetic properties of 1, antibodies against 1 were prepared and a competitive enzyme immunoassay (EIA) was developed. Two kinds of haptens, 3 and 4, for 1 were synthesized and coupled to ovalbumin (OVA). Rabbits were immunized with 3-OVA or 4-OVA, and corresponding antibodies were obtained. Both antibodies recognized the 2-amino-2-(2-phenylethyl)propane-1,3-diol moiety in 1. Using the anti-3-OVA antibody, a competitive EIA for 1 was developed and evaluated. The range of quantification by the EIA was 0.06-10 ng/mL. The application of the EIA has enabled us to measure the FTY720 concentration in serum after oral administration of 1 (1mg/kg) to rats.

Administration, Oral↗
PubMed2005

A novel immunomodulator, FTY720, prevents development of experimental autoimmune myasthenia gravis in C57BL/6 mice.

Prophylactic oral administration of a novel immunomodulator (immunosuppressant), FTY720 (1 mg/kg, three times a week), completely prevented the development of experimental autoimmune myasthenia gravis (EAMG) in C57BL/6 mice. EAMG has been used as an animal model for human myasthenia gravis, and was established by immunizing the mice with acetylcholine receptor (AChR) from Torpedo californica. FTY720 also suppressed the production of both anti-Torpedo californica AChR antibody and anti-mouse AChR autoantibody by the mice, which were observed in mice in which EAMG had become established. These results strongly suggest that FTY720 is a promising candidate for treatment of human myasthenia gravis.

Animals↗
PubMed2004

A novel immunomodulator, FTY720, prevents spontaneous dermatitis in NC/Nga mice.

Oral administration of a novel immunomodulator, FTY720 (0.1 mg/kg, once a week), completely prevented the spontaneous development of dermatitis in NC/Nga mice. It also strongly suppressed hyper IgE production in serum, as well as hypertrophy of the epidermis and the degranulation of granulocytes in the skin, all of which were observed in mice in which the dermatitis had become established. These results strongly suggest that FTY720 is a promising candidate for treatment of human atopic dermatitis.

Animals↗
PubMed2002

Antibodies to food antigens in Japanese patients with type 1 diabetes mellitus.

To examine humoral and mucosal immune responses to food antigens and their relation to the pathophysiology of type 1 diabetes mellitus, IgA and IgG antibodies to cow's milk antigens (bovine serum albumin (BSA) and beta-lactoglobulin (BLG)) and another food antigen (ovalbumin, (OVA)) in human serum were assessed by enzyme-linked immunosorbent assay (ELISA). If anti-idiotype antibodies to the antibodies were present in serum, they might interfere with the ELISA assay, so suitable microtiter plates were employed to minimize such interference. The levels of IgA and IgG antibodies to the above antigens (P<0.001-P<0.01) and the prevalence of positive sera (P<0.001-P<0.05) in the patient group (n=52, aged 14.5+/-4.1 (S.D.) years) were significantly higher than those in the control group (n=41, aged 13.3+/-6.8 (S.D.) years). Interestingly, the levels of IgA antibodies to all the food antigens examined were elevated in 26 (50%) patients, while the elevation was seen in 3 (7%) healthy controls. The elevation of IgA antibodies in the patients was well correlated with increased concentrations of IgA and transforming growth factor (TGF)-beta, which induces IgA-producing B-cells, in serum. Although the cytokine TGF-beta is secreted from regulatory T-cells (Th3), and is related to oral tolerance, the interleukin-2 (IL-2, Th1)/IL-4 (Th2) ratio in the patient group was significantly elevated (P<0.001), which might indicate that the oral tolerance is impaired in patients. Thus, we demonstrated that both IgA and IgG antibodies to several food antigens are elevated in patients. We suggest that impairment of oral tolerance might be related to the pathogenesis of type 1 diabetes mellitus.

Adolescent↗
PubMed1995

A Bacillus subtilis spore coat polypeptide gene, cotS.

A gene, cotS, encoding a spore coat polypeptide of Bacillus subtilis, was isolated from an EcoRI fragment (5.4 kb) of the chromosome by using synthetic oligonucleotide probes corresponding to the NH2-terminal amino acid sequence of Cot40-2 previously purified from the spore coat of B. subtilis. The nucleotide sequence (2603 bp) was determined and sequence analysis suggested the presence of two contiguous ORFs, ORF X and cotS, followed by the 5'-region of an additional ORF, ORF Y, downstream of cotS. The cotS gene is 1053 nucleotides long and encodes a polypeptide of 351 amino acids with a predicted molecular mass of 41083 Da. The predicted amino acid sequence was in complete agreement with the NH2-terminal amino acid sequence of Cot40-2. The orfX gene is 1131 nucleotides long and encodes a polypeptide of 377 amino acids with a predicted molecular mass of 42911 Da. The gene product of cotS was confirmed to be identical to Cot40-2 by SDS-PAGE and immunoblotting from Escherichia coli transformed with a plasmid containing the cotS region. Northern hybridization analysis indicated that a transcript of cotS and orfX appeared at about 5 h after the onset of sporulation. The transcriptional start point determined by primer extension analysis suggested that -10 and -35 regions are present upstream of orfX and are very similar to the consensus sequence for the sigma k-dependent promoter. Terminator-like sequences were not found in the DNA fragment (2603 bp) sequenced in this paper, which suggested that the cotS locus may be part of a multicistronic operon. The cotS gene is located between dnaB and degQ at about 270-275 degrees on the genetic map. Insertional mutagenesis of the cotS gene by introducing an integrative plasmid resulted in no alteration of growth or sporulation, and had no effect on germination or resistance to chloroform.

Amino Acid Sequence↗