Y Nakajima

University of Wales, Cardiff, Wales, United Kingdom

Are you Y Nakajima?

Claim your profile

Publications (6)14.09 Total impact

  • Source
    [Show abstract] [Hide abstract]
    ABSTRACT: Animal models of autoimmune thyroid disease are associated with thyroglobulin (Tg) as autoantigen whereas in man the autoimmune response to microsomal antigen/thyroid peroxidase (TPO) appears to play a major role in thyroiditis. Consequently, we have compared the ability of TPO and Tg to induce thyroid autoantibodies and thyroid damage in mice known to be susceptible (CBA/J) or resistant (BALB/c) to thyroiditis induced using murine Tg. Groups of three to five mice were immunized twice using Freund's complete adjuvant with 80-100 micrograms highly purified porcine (p) TPO, pTg, rat (r) Tg, human Tg, bovine serum albumin (BSA) or BSA + 0.2 micrograms pTg (the level of Tg contamination of TPO). Four weeks after immunization with TPO, plasma from CBA/J (but not BALB/c) mice contained IgG class antibodies which bound to TPO-coated tubes in the presence or absence of excess Tg (and could therefore be clearly distinguished from Tg antibodies) but there was no evidence of thyroiditis in either strain of mice. In contrast, in CBA/J mice immunized with rTg and, to a lesser extent in mice that had received pTg, thyroid tissue was infiltrated with lymphoid cells and/or neutrophils and antibodies to pTg (but not pTPO) were present. Our observations demonstrate that induction of TPO antibody alone is insufficient to lead to thyroiditis in CBA/J mice. Further, these studies emphasize the complex interactions between MHC and different thyroid antigens in the processes leading to thyroid destruction.
    Preview · Article · Mar 1990 · Clinical & Experimental Immunology
  • [Show abstract] [Hide abstract]
    ABSTRACT: Affinity labelling with a 125I-labelled photoactive derivative of TSH (HSAB-TSH) was used to analyse TSH receptor size in the following specimens of human thyroid tissue: (1) cold nodules; (2) autonomous nodules; (3) papillary carcinoma; (4) medullary carcinoma; (5) metastasis of papillary carcinoma to lymph node; (6) anaplastic carcinoma, and (7) Graves' thyroid. In addition, a sample of histologically normal thyroid tissue surrounding specimens 1-4 was analysed in each case. Thyroid microsomes were also prepared from the tissue samples, solubilized using 1% deoxycholate and labelled with 125I. The preparations were immunoprecipitated using microsomal autoantibodies and protein A and analysed by SDS-PAGE and autoradiography. These studies indicated that no differences in the characteristics of the TSH receptor or of microsomal antigen were observed in the tissue samples 1-3 and 7. Neither protein was detected in tissue specimens 4-6.
    No preview · Article · Jul 1988 · Clinical Endocrinology
  • [Show abstract] [Hide abstract]
    ABSTRACT: The interaction between thyroid microsomal autoantibodies and thyroid microsomal antigen/thyroid peroxidase (TPO) has been studied using both intact antigen preparations and their water-soluble trypsin fragments. In an analysis of sera from 30 patients with Graves' or Hashimoto's diseases, microsomal antibodies showed similar reactivity towards trypsin fragments (with TPO activity) and intact detergent (sodium deoxycholate, DOC)-solubilized human microsomal antigen preparations (r = 0.96). This raised the possibility that both the peroxidase-active site and the major autoantigenic site(s) of microsomal antigen were present on the same trypsin fragments. Studies with porcine TPO showed that only a few sera contained microsomal antibodies which cross-reacted strongly with the porcine preparations. Further analysis was carried out by immunoprecipitation of 125I-labelled microsomal antigen followed by SDS-PAGE and autoradiography. These studies suggest that intact human microsomal antigen (a single-chain protein with Mr = 110,000) contains an intrachain loop of amino acids formed by a disulphide bridge. Trypsin treatment cleaves the antigen close to its transmembrane section and releases a water-soluble fragment (Mr = 100,000), containing the intact disulphide-linked loop of amino acids. Further trypsin action causes cleavage of the peptide bonds within the loop in some preparations. Consequently, three major water-soluble trypsin fragments (Mr = 100,000, 73,000 and 68,000) are formed all of which contain an intact disulphide bridge and have microsomal antibody binding activities. The integrity of the disulphide bridge in intact antigen/TPO preparations and their trypsin fragments is essential for autoantibody binding activity.
    No preview · Article · Oct 1987 · Molecular and Cellular Endocrinology

  • No preview · Article · Mar 1987 · Biochemical Society Transactions
  • [Show abstract] [Hide abstract]
    ABSTRACT: Studies of the TSH receptor using affinity labelling with photoactive derivatives of TSH and analysis by SDS-PAGE have shown that the receptor contains 2 subunits (A and B), linked by a disulphide bridge. Similar results are obtained with TSH receptors from human, porcine and guinea pig thyroid tissue and from guinea pig fat. Analysis of affinity labelled receptors under non-denaturing conditions suggest that subunits additional to the A and B subunits are not present. Hydrodynamic measurements indicate that the receptor A subunit has an approximately spherical structure (Stokes' radius 70 A) and when this interacts with TSH (an elongated structure with Stokes' radius 56A) a very elongated complex (Stokes' radius 104A) is formed. Isoelectric focusing studies of the TSH receptor A subunit, TSH and TSH receptor antibodies indicate that charge-charge interactions are of considerable importance in the binding of hormone and antibody to the receptor.
    No preview · Article · Feb 1987 · Acta endocrinologica. Supplementum
  • J. Furmaniak · Y. Nakajima · F.A. Hashim

    No preview · Article · Jan 1987