THE THYROID 1988 Proceedings of the International Thyroid Symposium, Tokyo, 13-15 July 1988

Editors: Shigenobu Nagataki First Department of Internal Medicine Nagasaki University School of Medicine Nagasaki, Japan Kanji Torizuka Fukui Medical School Fukui, Japan

EXCERPTA MEDICA, Amsterdam - New York - Oxford

© 1988 Elsevier Science Publishers B.V. (Biomedical Division) All rights reserved. No part of this publication may be reproduced, stored in a retrieval System or transmitted in any form or by any means, electronic, mechanical, photocopying, recording or otherwise without the prior written permission of the publisher, Elsevier Science Publishers B.V., Biomedical Division, P.O. Box 1527, 1000 BM Amsterdam, The Netherlands. No responsibility is assumed by the Publisher for any injury and/or damage to persons or property as a matter of products liability, negligence or otherwise, or from any use or Operation of any methods, products, instructions or ideas contained in the material herein. Because of rapid advances in the medical sciences, the Publisher recommends that independent verification of diagnoses and drug dosages should be made. Special regulations for readers in the USA - This publication has been registered with the Copyright Clearance Center Inc. (CCC), 27 Congress Street, Salem, M A 01970, USA. Information can be obtained from the C C C about conditions under which photocopies of parts of this publication may be made in the USA. All other Copyright questions, including photocopying outside the USA, should be referred to the Copyright owner, Elsevier Science Publishers B.V., unless otherwise specified. International Congress Series No. 796 ISBN 0 444 81054 4 Published by: Elsevier Science Publishers B.V. (Biomedical Division) P.O. Box 211 1000 A E Amsterdam The Netherlands L i b r a r y of Congress

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C a t a l o g i n g in P u b l i c a t i o n D a t a :

I n t e r n a t i o n a l Thyroid Symposium (6tk Tokyo, Japan) The thyroid 1988.

1988 :

( I n t e r n a t i o n a l congress s e r i e s ; no. 796) Includes index. 1. Thyroid g l a n d — P h y s i o l o g y — C o n g r e s s e s . 2. Thyroid gland—Immunology—Congresses. 3. Thyroid g l a n d — Diseases—Congresses. I . Nagataki, S. I I . T o r i z u k a , K a n j i , 1926. III. Title. IV. S e r i e s . [DNLM: 1. Autoantibodies—immunology—congresses. 2. Hypothyroidism—congresses. 3. T h y r o g l o b u l i n — immunology—congresses. 4. Thyroid Diseases—immunology —congresses. 5. Thyroid Hormones—immunology— congresses. 6. Thyroid Neoplasms—congresses. Library of Congress Cataloging-in-Publicalion Data W3 EX89 no.796 / WK 200 1595t 1988] QP188.T54I67 1988 612'.44 ISBN 0-444-81054-4 (U.S.)

Printed in The Netherlands

88-31069

Bayerische Staatsbibliothek München

CONTENTS

D u e to unavoidable circwnstances the papers marked with a n * could at the meeting but have, nevertheless, been included in this volume.

not be

presented

SPECIAL LECTURE Future trend in thyroidology S.H. Ingbar

PLENARY LECTURES In vitro TSH secretion-refractoriness: Interaction of T R H receptor-related phosphatidylinositol (PI) metabolism T. M i c h i m a t a , T. Iriuchijima and M . M o r i Endocrine and developmental regulation of thyrotropin (TSH) carbohydrate synthesis B . D . W e i n t r a u b , N . Gesundheit, P.W. Gyves, T. T a y l o r and G.S. DeCherney Thyrotropin and cyclic A M P analogue enhance thyroid peroxidase mRNA level through a regulatory protein in cultured human thyrocytes Y. N a g a y a m a , S. Y a m a s h i t a , K. Ashizawa, K. M a t s u o , T. Matsumoto, S. H a r a k a w a , S. I n o u e , H . H i r a y u , M . I z u m i , N . I s h i k a w a , K. I t o and S.Nagataki A pregolgi membrane-bound form of thyroglobulin (TG) contains mannose phosphate and tetraiodothyronine (T4) M . D e L u c a , P . Santisteban, S. Shifrin and L . D . K o h n Cellular origin of thyroid heterogeneity G. H u b e r , M . D e r w a h l , H . - J . Peter and H . Studer Coincident regulation of rat thyroid M H C Class II R T l . D and R T l . D ^ transcripts D . S . Neufeld and T.F. Davies 'Rehabilitation' of cytokines in thyroid autoimmunity: Are they only exerting negative effects? U. Deuss, M . Buscema and G . F . Bottazzo Antibody against c-erb A protein can interact with rat liver nuclear T receptors H . N a k a m u r a , K. M a s u d a , T. T a g a m i and H . I m u r a High-field surface-coil MR imaging in thyroid disease J. Konishi, S. N o m a , S. M i n a m i , T. Sago, Y. I i d a , K. Kasagi, Y. N a k a n o , H . höh and K. T o r i z u k a

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ix Europe: 'Between-country' diversity in the management of hyperthyroidism due to Graves' disease D . G l i n o e r , D . Hesch, P . L a u r b e r g , M . M a l i n s k y , B . H a a k , H . Fritzsche and R . Lagasse

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THYROID AUTOIMMUNITY Cellular immunity and MHC Class 2 antigen M H C Class 2 antigen expression in high and low responders with interferon y injected mice Y. K a w a k a m i , N . Kuzuya and K. Yamashita Non-toxic nodular goitre and papillary Carcinoma of the thyroid are not autoimmune thyroid diseases J. Aguayo, Y. Sakatsume, C. Jamieson, V. V. Row and R . Volpe Intrathyroidal lymphocyte subpopulation study in Graves' disease K L . L i a w , Y.C. T u , C.C. Yao and I J . Su The cellular interaction in thyroid glands from patients with Graves' disease (immunohistochemical staining and phenotypic marker of thyroid infiltrating mononuclear cells) K. E g u c h i , K. M i g i t a , A . K a w a k a m i , Y. U e k i , H . T e z u k a , T. Otsubo, H . N a k a o , C. S h i m o m u r a , M . M a t s u n a g a , N . I s h i k a w a , K. I t o and S. N a g a t a k i TSH-binding inhibitor immunoglobulin (TBII) and lymphocyte subsets of thyroidal venous blood in patients with Graves' disease A . Sugenoya, Y. Kasuga, S. Kobayashi, H . M a s u d a and F. I i d a

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Cellular immunity and autoantibody +

Circulating T a l cells: A new index of immunological activities in patients with Graves' disease Y. U e k i , K. E g u c h i , C. S h i m o m u r a , T. Otsubo, H . N a k a o , K. M i g i t a , A . K a w a k a m i , N . I s h i k a w a , K. I t o and S. N a g a t a k i In vitro induction of anti-thyroid microsomal antibody secreting cells in peripheral lymphocytes from normal subjects M . I i t a k a , J. I s h i i and R . Volpe Suppressor cell function in thyroid autoimmune disease is affected by plasmid encoded proteins of enteropathogenic Yersinia B . E . Wenzel, J. Heesemann, S. G r a m m e r s t o r f and P . C . Scriba Immunogenetic factors in the pathogenesis of goiter and autoimmune thyroiditis in iodine-sufficient areas of Kentucky, USA, and Colombia, SA E . G a i t a n , J . M . Cruse, S.W. C h a p m a n , R . C . Cooksey, D . G a i t a n , E . F . M e y d r e c h , J . G . Adams, G.S. G a i t a n , T . M . Preuss, J. Astudillo and R.N. Guzman

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X Thyroid functional disorders with thyroid autoantibody manifested after habitual ingestion of excess iodide K. O k a m u r a , K. Sato, H . I k e n o u e , M . Yoshinari, M . Nakagawa, T. K u r o d a and M . Fujishima

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Antiperoxidase and antithyroglobulin antibodies New monoclonal antibody radioimmunoassay (RIA) of anti-thyroid peroxidase autoantibodies S. M a r i o t t i , S. A n e l l i , P . Piccolo, P . C a t u r e g l i , J. Ruf, P . C a r a y o n and A . Pinchera Studies on human thyroid peroxidase (TPO) autoantigenicity by cloned cDNA recombinant epitopes S. M a r i o t t i , M . Ludgate, F. L i b e r t , C. D i n s a r t , P . Piccolo, F. S a n t i n i , A . P i n c h e r a , P . C a r a y o n and G. Vassart 101 kDa thyroid microsomal antigen - Two forms? N . H a m a d a , K. Okamoto, A . H i n o t a n i , J. Y a m a k a w a , M . O h n o , K. I t o , L . J . Degroot and H . M o r i i Common antigenic determinants of thyroglobulin and thyroid peroxidase: Possible autoantigenic determinants related to the causes of thyroiditis Y. Kohno, N . N a i t o , K. Saito, O. T a r u t a n i , H . N a k a j i m a and T. Hosoya IgG subclasses of microsomal and thyroglobulin antibodies: Functional affinity and patterns of inheritance S . M . M c L a c h l a n , A . Stephenson, M . Devey, K. Bleasdale, S. Mojfitt, F. C l a r k , E . T . Young and B . Rees Smith Monoclonal antithyroglobulin autoantibody in Hashimoto's serum G. B . Salabe', A . O l i v i e r i , H . Lotz-Salabe' a n d G . Ravagnan Effect of MMI and PTU on the production of thyroglobulin (TG) and thyroid hormone antibodies in mice and rats immunized with T G T. Komaki, S. S a k a t a , H . S h i m a , M . M a t s u d a , N . K o j i m a , H . T a k u n o , S. N a k a m u r a and K. M i u r a Anti-thyroid hormone and anti-thyroglobulin autoantibodies in BB/W rat susceptible to spontaneous autoimmune thyroiditis Y. H a r a , K. K a w a k a m i , M . Yanagisawa, S. M i u r a , M . U r a b e , K. I n o u e , S. S a k u r a i , T. T a n i k a w a , K. Sato, M . I i t a k a , S. Kawazu, J. Ishii and KKomeda

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Antithyroid hormone antibody The role of thyroglobulin as an antigen of thyroid hormone antibodies S. S a k a t a , K. N a g a i , O. T a r u t a n i , Y. Kohno, K. Saito, T. Komaki, M . M a t s u d a , N . K o j i m a , H . T a k u n o , N . Tokimitsu and K. M i u r a Chronic amiodarone therapy is not associated with higher prevalence of serum autoantibodies to triiodothyronine and thyroxine L. B a r t a l e n a , A . Loviselli, S. B a l z a n o , L . B u r a t t i , V. Sica, G. Giannessi, M . Pilosu, F. A g h i n i - L o m b a r d i , L . P e t r i n i and E . M a r t i n o

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XI Clinical features of patients with thyroid hormone autoantibodies N . K o j i m a , S. S a k a t a , S. N a k a m u r a , K. N a g a i , T. Komaki, M . Matsuda, H . T a k u n o , J. T a k a m a t s u , N . Tokimitsu and K. M i u r a Measurement of TSH receptor autoantibodies (TR Ab) in children with hyperthyroidism F.Peter Thyroid stimulating Immunoglobulin assay by solubilized porcine thyroid membrane preparation H . U c h i m u r a , K. I n o u e , Y. F u k u e , T. M i t s u h a s h i , K. Kubota, N. Sasaki, F. T a k a k u , Y. M a n a b e and K. I t o Binding antibodies to affinity purified human TSH receptors in euthyroid Graves' disease T. Shinozawa, Y. M a t s u s h i t a , K. A r i k a w a , Y. I c h i k a w a , M . H o m m a and K Ito

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Thyroid stimulating antibody Anti-human IgG antibodies enhance the activity of thyroid stimulating antibodies in vitro T. Saito, H. S h i m u r a , T. Endo and T. O n a y a Identification of antigens of abnormal thyroid stimulators by Western blotting N . Kuzuya, Y. K a w a k a m i and K. Yamashita Anti-TSH antibodies in Graves' disease - Binding characteristics to intact TSH and porcine TSH subunits and interaction with TSH receptor antibodies Y. Ochi, M . I m o k a w a , T. N a g a m u n e , Y. N a k a j i m a , M . I s h i d a , Y. K a j i t a , T. H a c h i y a and H . O g u r a Comparison of thyroid stimulating activities measured by cyclic A M P production, those by radioiodine uptake in FRTL-5 cells and TSH-binding inhibitory activities in patients with hyperthyroid and euthyroid Graves' diseases K. Kasagi, A . H i d a k a , H . H a t a b u , Y. T o k u d a , T. M i s a k i , Y. I i d a and J.Konishi Glycosaminoglycan (GAG) synthesis in thyroid cells: Stimulation by thyrotropin (TSH), insulin-like growth factor-I (IGF-I), and IgG preparations from Graves' patients with pretibial myxedema F. V. Alvarez, C M . R o t e l l a , W . A . V a l e n t e , J. C h a n , O. Isozaki, R . Toccafondi, A . D . K o h n and L . D . K o h n Changes in thyroglobulin release-stimulating activity (Tg-RSA) in immunoglobulin G from patients with Graves' disease during therapy with thionamide drug Y. F u k u e , K. Kubota, N . Sasaki, F. T a k a k u , Y. K a n a j i and H . U c h i m u r a

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XU

Thyroid Stimulation blocking antibody Autoantibodies able to block thyroid adenylate cyclase inhibit TSH- and TSAb-stimulated growth of FRTL-5 cells P . V i t t i , L . Chiovato, C M a r c o c c i , F. S a n t i n i , P . Bassi, C. M a m m o l i , G. Lopez, M . Gryczynska, G. F e n z i and A . P i n c h e r a Role of blocking type TSH receptor antibodies in primary myxedema B . Y. C h o , Y.K. Shong, CS. Koh and H . K M i n Autoantibodies in patients with Graves' disease which block the thyroid stimulating activities of autoantibodies associated with Graves' dermopathy T. W. T a o , S . L . L e u and J . P . Kriss

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Clinical aspects High plasma concentrations of human atrial natriuretic peptide in hyperthryoidism L . D u n t a s , F . S . Keck, J. Rosenthal, U. Loos and E . F . Pfeiffer The elevated plasma levels of atrial natriuretic peptide (ANP) in patients with hyperthyroidism T. K u r o d a , M . Yoshinari, H . I k e n o u e , K. Sato, K. O k a m u r a and M . Fujishima TSH concentrations in amniotic fluid of pregnant women with blocking-type TSH receptor antibodies: Its usefulness in predicting neonatal hypothyroidism S. Sakane, J. T a k a m a t s u , H . K i t a o k a , K. O k u d a and K. Kasagi Relationship between pregnants and offsprings in thyroid dysfunction M . K a m b a r a , K. Sawada, M . M u r a t a , N . M o m o t a n i , K. O k a d a and M . Matsumoto Autoimmune thyroiditis and primary Sjögren's Syndrome U . - B . Ericsson, B . H a n s e n and R . M a n t h o r p e Long term prospective Observation of patients with silent thyroiditis: Close relationship with Graves' disease, and high prevalence of relapse of silent thyroiditis, and development of hypothyroidism Y. Ozawa and Y. Shishiba Occurrence of Graves' hyperthyroidism preceded by silent thyroiditis J. N o h , M . Yoshimoto, N . Ishikawa, N . Momotani, N . H a m a d a , H . M o r i i and K I t o Clinical significance of anterior pituitary cell surface antibodies (PCSA) in Graves' disease /. Kobayashi, T. I n u k a i , A . I s h i i , Y. Yamaguchi, T. Yamaguchi, S. Kobayashi, A . Hashimoto and M . S u g i u r a T -predominant Graves' disease: Clinical characteristics and pathogenesis of T overproduction J. T a k a m a t s u , T. Hosoya, Y. Kohno, O. T a r u t a n i , M . S u g a w a r a , S. Sakane, K. T a k e da, H . K i t a o k a and K. K u m a

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Xlll Long-term sodium ipodate treatment for Graves' disease: High rate of recurrent thyrotoxicosis E . M a r t i n o , S. B a i z a n o , A . Loviselli, V. Sica, L . P e t r i n i , L . Grasso, M . F a l c o n e and L . B a r t a l e n a A duration until normalization of serum TBII levels as a reliable marker to predict prognosis in hyperthyroid patients K. K a m i j o , M . Sato, K. Kawasaki and A . Y a c h i

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IODINE AND THYROID Iodine and thyroid function *Observations on the placental permeability to maternal thyroxine in the rat X . L . L i u , Z . P . C h e n , B . Z . H o u and T. M a Thyroiditis in BB/W rats bred with excessive iodine intake M . L i , R . A . Osborn, D . W u , G . F . M a b e r l y and C J . Eastman *Effect of drinking water of iodine excess on function of pituitary thyroid axis in the inhabitants X . C h e n , X . Z h a n g , Y. T a o , S. Yang, Y. C h e n , J. Z h a o , Q. L i u , C. Wei, S. W a n g , Z . Z h a n g and J. F e n g Iodine intake and thyroid function in normal individuals D . S . M o u l o p o u l o u , D . A . Koutras, J. Mantzos, A. Souvatzoglou, G . D . Piperingos, K . S . Karaiskos, D . M a k r i y a n n i s , J. Sfontouris and S . D . Moulopoulos

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Thyroid diseases in various areas The role of nutritional factors in etiopathogenesis of simple goiter B . K r i s h n a R a m , P . Shah and A . K . S h a r m a The influence of humic substances on the thyrotropin receptor T . C . C h a n g and F.J. L u Goitre survey in a North Indian village P . N . S i n g h , B . H a s a n , J. Ahmed, O. C h a n d r a , S. Kulshreshtha and V. K u m a r Profile of thyroid diseases. A hospital experience in India (Delhi and Agra), Libya and Iran V. K u m a r , D . K . H a z r a , A . K . G u p t a , A . G u p t a , R . S i n g h , L . G u p t a , S. Kachlas, V. S u r i , P . G . G o p i n a t h a n N a i r , S. Kulshreshtha and S. Singh

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Thyroiditis and hypothyroidism Incidence of thyroiditis among euthyroid goitres J.K. A g r a w a l , H . S . Bajpai, A . K . G u p t a , A . H a t w o l , M . K u m a r , S.K. Srivastava, S.K. Singh and R . P . B h a t t

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xiv Features of endemic cretinism in Qinghai, China S.C. Boyages, G . F . M a b e r l y , C J . E a s t m a n , J . - P . H a l p e r n , J. C o l l i n s , J. Jupp, Y.C. Yi, Z . - H . Wong and C. Jin A high prevalence of pituitary tumour in myxedematous endemic cretins S.C. Boyages, J . - P . H a l p e r n , G . F . M a b e r l y , C.J. E a s t m a n , C. You, C. J i n and Z . - H . Wong Evaluation of an iodization Programme in central Java, Indonesia. A preliminary report F. Yasin, G. M a , G. M a b e r l y , C. E a s t m a n , D . E n g l i s h and B . Armstrong

Prevention of IDD Goitre, iodine deficiency (ID) and goitre prevention in the German Democratic Republic (GDR) W. M e n g , K. B a u c h , G. Knappe, G. Kirsch and F . E . U l r i c h Iodized oil injections fail to benefit myxedematous cretins, from Qinghai, China S.C. Boyages, J . - P . H a l p e r n , G . F . M a b e r l y , C.J. E a s t m a n , D . Yu, C. You, C. Jin and Z . - H . Wong Thyroid function of subjects with goitre and cretinism in an endemic goitre area of rural China after use of iodized salt A . Ouyang, X . P . F a n g , T.S. Su and J . M . H e r s h m a n

THYROID HORMONE ACTIONS AND METABOLISM Thyroid hormone binding proteins Cloning of thyroxine-binding globulin (TBG) cDNA and analysis of T B G mRNA F. Kambe, H . Seo, Y. M u r a t a and N . M a t s u i Human apolipoproteins A-I and C are novel thyroxine-binding proteins S. Benvenga, H J . C a h n m a n n and J. Robbins Drug effects of serum thyroid hormone binding J . R . Stockigt, C . F . L i m , J.W. B a r l o w , Y. B a i and D J . Topliss Cellular uptake of circulating triiodothyronine (T ) and the hormonal effect in peripheral tissues of the rat K. Yamamoto, K. Saito, I. N a g a y a m a , T. Saito and T. Kuzuya Conformational transition of human c-erb A protein upon thyroid hormone binding K. I c h i k a w a , K. H a s h i z u m e , S. F u r u t a , Y. N i s h i i , T. M i y a m o t o , T. Osumi, K. Y a m a u c h i , H . Otsuka, T. Y a m a d a and L J . Degroot The mitochondrial pathway of thyroid hormone action K. Sterling Thyroid hormone binding to hemoglobin S. S a k a t a , S. N a k a m u r a , N . Yoshioka, M . Z o u h a i r Atassi and K. M i u r a 3

XV

Mechanism of hormone action and metabolism Thyroid hormone induces gene expression offibronectinin the rat liver Y. M u r a t a , H . Seo and N . M a t s u i Thyroid hormone modulates the synthesis of proteoglycans by human skin fibroblasts in culture Y. Shishiba, Y. T a k e u c h i , N . Yokoi, Y. Ozawa and T. Shimizu Decreased respiration and a-glycerophosphate dehydrogenase activity in heart mitochondria from cold-exposed, triiodothyronine-treated hypothyroid rats A . A . Z a n i n o v i c h , J . A . B r i g n o n e , L R . M i g n o n e , C R . Ricci and C M . Brignone Non-GSH, NADPH-dependent cytosolic thiol cofactor for iodothyronine deiodination K. hvase, B . C . W. H u m m e l and P . G . Walfish Possible idiotypic differences among the 5'-deiodinating isoenzymes of iodothyronines CS.

P i t t m a n , R . R . C a v a l i e r i and L . A . G a v i n

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Biological actions Effect of hyperthyroid sera on rat embryogenesis S. H a r a k a w a , S. A k a z a w a , M . A k a z a w a , M . H a s h i m o t o , Y. N a g a y a m a , H . H i r a y u , S. Y a m a s h i t a , M . I z u m i and S. N a g a t a k i The consecutive Observation on learning capacity in the lst-3rd generations of iodine deficiency rat Z . P . C h e n , L . D o n g and T. M a Evoked potential abnormalities in thyroid disorders T.S. H u a n g , Y.C C h a n g , S . H . Lee and F. W. C h e n Effects of thyroid hormone on the latency of evoked potentials by photic and electrical stimulations observed in the lateral geniculate nucleus and the visual cortex M . T a k e d a , M . Suzuki and M . Kato The effect of thyroid Status on isoniazid acetylation D . P h i l l i p s , J. L a z a r u s , M . Littley, A . H u t c h i n g s , B . Spragg and P.Routledge Hypothyroidism-induced hypothermia in the rat: Role of the brain cholinergic mechanism M . M o r i , M . A k u z a w a , M . Yamaguchi, T. M i c h i m a t a , T. I r i u c h i j i m a , K. M i y a s h i t a , T. Sato, M . M u r a k a m i and S. Kobayashi

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Thyroid diseases Radioimmunoassays for free thyroxine and free triiodothyronine in serum, with magnetic Separation of the solid phase W. M a y , K. W a i t e and C.J. Eastman

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xvi Clinical study on decreased serum thyroxine binding globulin due to radiofrequency hyperthermia T. H a s h i m o t o , H . H i s a z u m i , K. N a k a j i m a and F. M a t s u b a r a Studies on thyroid indicators during the relapse of Graves' disease following discontinuation of antithyroid drug therapy H. A k i y a m a , I. Kobayashi, T. Yamaguchi, Y. Shoda, K. O h s h i m a , M . M o r i , Y. S h i m o m u r a and S. Kobayashi Erythrocyte zinc concentration in patients with hyperthyroidism Y. Kiso, K. Yoshida, T. W a t a n a b e , M . Yamamoto, K. Kaise, N . Kaise, Y. I t a g a k i , T. A r a i , T. S a k u r a d a , S. Saito and K. Yoshinaga Serum ferritin concentration in patients with hyperthyroidism, hypothyroidism and thyroid hormone autoantibodies H. T a k u n o , S. S a k a t a , T. Komaki, M . M a t s u d a , N . K o j i m a , S. N a k a m u r a , K. N a g a i , N . Tokimitsu and K. M i u r a Studies on the remission of Graves' disease: Role of thyroid stimulators on overshoot of thyroidal radioiodine uptake in Graves' disease following discontinuation of antithyroid drug T. Yamaguchi, I. Kobayashi, T. I n u k a i , A . I w a s h i t a , Y. Shoda, H . A k i y a m a , S. Kobayashi and Y. Kondo The effects of aminophylline on thyrotoxic tremor D . Buss, D . P h i l l i p s , M . Littley, R . M a r s h a l l , P . Routledge and J. Lazarus Thyroid State and serum angiotensin-converting enzyme during acute starvation G. Komaki, H . T a m a i , S. Matsubayashi, N . Kobayashi, S. M o r i and T. N a k a g a w a

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Non thyroidal illness Changes in thyroidal secretion of T3 to T R H in patients with anorexia nervosa: Before and after weight recovery H . T a m a i , K. K i y o h a r a , N . Kobayashi, G. Komaki, T. N a k a g a w a and S. N a g a t a k i *Functional Status of the thyroid gland in malnutrition /. C h a k r a v a r t y and D . Das Thyroid hormones in protein energy malnutrition (PEM) Y. Sachdev Studies on the pituitary and thyroid functions in patients with nonthyroidal illnesses: Assessment of bioactivity for serum TSH in patients with chronic renal failure on hemodialysis M . H o r i m o t o , M . N i s h i k a w a , N . Yoshikawa and M . I n a d a No lymphocyte production of immunoreactive thyrotropin (IR-TSH) in thyroid diseases L . D u n t a s , F . S . Keck, L M e r k l , H . Schrezenmeier, U. Loos and E . F.Pfeiffer

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481

xvii

THYROID DISEASES Hypothyroidism High incidence of primary non autoimmune hypothyroidism in adult thalassemia major patients M . E . L a i , S. B a l z a n o , M . L . M u r t a s , A . F i g u s , V. Sica, S. J a n n e l l i , P . F a r c i , A . B a l e s t r i e r i and E . M a r t i n o Study of water excretion in patients with hypothyroidism J.K. T o r n g , J . H . C h e n , Y.J. Lee, S.J. S h i n , P . J . H s i a o and J H . Tsai The influence of thyroid Status on serum lipid parameters of athyreotic patients F . S . Keck, U. Loos, J . G . Wechsler, L . D u n t a s , S. Wieshammer and E . F . Pfeiffer Thyroid function following head and neck radiotherapy D . K H a z r a , A . K . S h u k l a , V.K. Rohatgi, R . S i n g h , S. Kulshreshtha, L . G u p t a , S.S. Kachlas, R . N . L . Srivastava and V. K u m a r Sensitive TSH measurement on triiodothyronine therapy in the diagnosis of thyroid hormone resistance J. T a k a m a t s u , M . M a j i m a , T. M a j i m a and S. U e d a Thyroid functions in ankylostomiasis R. Singh, D . K . H a z r a , A . Rajan, A . Khanna, A.K. Shukla, R.K. Agarwal, R . K . S i n g h , V. M i s h r a , V.K. K h u r a n a , S. S i n g h , S. Kulshreshtha and V. K u m a r

487 491

495

499

503

507

Nodule, thyroiditis and hyperthyroidism Scintigraphic and Sonographie studies in thyroid diseases C.C. W u , J.K. T o r n g and Y . H . H o Effects of inhalational anesthesia and abdominal surgery on thyroid functions in man A . M a t s u k i and T. O y a m a Subacute thyroiditis as a systemic multi-organ disease S. H a m a d a , T. Y a g u r a , H . Ishii, T. Yoshimasa, T. Oonishi, H . I s h i d a and K. T a n a k a A case of painless thyroiditis associated with periodic paralysis K. W a t a n a b e , T. F u j i h i r a , K. Z e k i , K. Y a h a t a , S. Yamamoto, M . K a n a t a n i , H . Suzuki, S. O d a and S. E t o Results of drug treatment in Graves' disease and non-immunogenic hyperthyroidism (disseminated autonomy) W. M e n g , S. M e n g , R . H a m p e l , M . Ventz, E . Männchen and G. Kirsch Drug treatment of thyrotoxicosis: Rapid response in iodine deficiency T. Jones, A . M i t h a i , N . K o c h u p i l l a i , B . V . B a b u , M . Y a m i n , P . G . S u n d a r a - R a m a n and M . M . S . A h u j a

513

517

521

525

529

533

xviii

THYROID GROWTH AND CANCER Growth factors Mitogenic efTect of human serum on rat FRTL5 cell line and its relationship to serum concentration of insulin-like growth factor-I T. M i s a k i , R . M . B . M a c i e l , D . T r a m o n t a n o , A . C . Moses, A . L o m b a r d i and S.H. Ingbar Growth stimulating activity secreted by cultured human thyrocytes K. Kubota, Y. F u k u e , N . Sasaki, F. T a k a k u and H . U c h i m u r a Human chorionic gonadotropin stimulates iodide uptake, adenylate cyclase, and D N A synthesis in cultured rat thyroid cells J . M . H e r s h m a n , H . Y . Lee, M . S u g a w a r a , C.J. M i r e l l , X . P . Pang, M . Yanagisawa and A . E . Pekary Iodide potentiates a growth-promoting activity of epidermal growth factor in human thyroid cells in monolayer culture T. O k u g a w a , N . O g a w a , Y. Goto, S. E n d o , H . Ohashi, M . H a k a m a t a and M.Itoh The role of TSH in mediating compensatory changes in the remaining thyroid lobe after hemithyroidectomy G . A . Hedge, M . M i c h a l k i e w i c z , J . M . Connors and L . J . Huffman Malignant transformation of benign nodules of rat thyroid gland induced by diisopropanolnitrosamine (DIPN) an immunohistochemical study A . Kawaoi, H . U s h i y a m a , Y. K a t o h , H . Matsumoto and S. M o r i y a m a

539 543

547

551

555

559

Thyroid tumor Effects of castration before and after treatment with N-bis(2-hydroxypropyl)-nitrosamine (DHPN) on the development of thyroid tumors in rats treated with DHPN followed by phenobarbital Y. H i a s a , Y. K i t a h o r i , H . M a t u k i , M . O h s h i m a , N . Konishi, T. Shimoyama, Y. Sakaguchi, H . H a s h i m o t o , S. M i n a m i , S. Okamoto and T. Tsujii Human leucocyte antigens and immunoglobulin heavy-chain allotype in malignant iymphoma of the thyroid S. Matsubayashi, H . T a m a i , T. M o r i t a , F. M a t s u z u k a , K. K u m a , T. M i y a z a k i , H . Matsumoto and S. N a g a t a k i Effect of estradiol (E ) on calcitonin (CT) secretion and the finding of E 2

565

569

2

receptors in medullary thyroid Carcinoma (MCT)

W. de l a T o r r e , E . Rose II, J. Rodriguez, F. R i b e r a and A . G a r c i a Ameijeiras Anaplastic thyroid Carcinoma. An immunohistological study of 48 cases S. T a m a i , Y. Hosoda, K. Y a k u m a r u and K. I t o Fine-needle biopsy (FNB) and the outcome of benign thyroid nodules S. Tseleni-Balafoutas, K. Katsouyanni, J. Kitsopanides and D . A . Koutras

573 579 583

XIX

Chromosomal pattern of offsprings of patients with differentiated thyroid Cancer treated with radioiodine C. Ceccarelli, F. P a c i n i , F. Lippi, E . T a r a n t i n o , N . F o r m i c a , G. Cesaretti, F. Perpoli and A . P i n c h e r a

587

Treatment of thyroid tumor Treatment of thyroid adenocarcinoma with natural interferon (IFN)-gamma N . Aoki, Y. O h n o , H . H i r a m a t s u and I. N a g a t a Mortality from papillary thyroid Carcinoma: A case-matched control study of 56 lethal cases treated at one institution during a 25 year period I . D . H a y , S . A . S m i t h , J . R . Goellner, J.J. Ryan and W . M . McConahey Natural course of benign solitary thyroid nodules and the effect of thyroxine therapy P . S . Y. Cheung,

J . M . H . Lee and J . H . Boey

595

601

605

THYROID CELL BIOLOGY Establishment of azaguanine resistant clones from FRTL5 and their application to hybridization with Graves' thyroid cells and human fibroblast H . Sugawa, T. M o r i and H. I m u r a Polarized thyroid cells in monolayers cultured on Collagen gel: Their cytoskeleton Organization, iodine uptake and resting membrane potentials N . T a k a s u , S. O h n o and T. Y a m a d a Mechanism of action and presence in patients' sera of anti-fucosyl GM1 ganglioside antibody S. Kosugi, T. M o r i , M . I w a m o r i , Y. N a g a i and H . I m u r a Calcium dependent NADPH-oxidase in thyroid plasma membrane fraction produces Superoxide anion as detected by diacetyldeuteroheme-substituted horseradish peroxidase Y. N a k a m u r a , S. O h t a k i , R . M a k i n o and Y. I s h i m u r a Thyroid stimulating antibody assayed by iodothyronine release into medium using porcine thyroid cells M . Saß, T. Toshio, M . A r a i , Y. Tsuchiya, M . M i y a g a w a , O. Isozaki, K. Sato and K. Shizume Effect of amiodarone on I mapping of mice thyroid follicle: Relative quantitation by analytical ion microscope (AIM) P . F r a g u , C. B r i a n c o n and S. H a l p e r n

611

615

619

623

627

,27

631

THYROGLOBULIN Structure and gene expression 35

35

Intrathyroidal metabolism of S-PTU and S - M M I in rats A . T a u r o g and M . D o r r i s

637

XX Fluorescence, hydrodynamic and immunological studies on human deglycosylated thyroglobulin (dTg) S. G r i m a l d i , D . Pozzi, R . V e r n a , S. L i o , G. N a p o l i t a n o , G. G i g a n t i and F. M o n a c o Active but inefficient hormone formation in a very highly iodinated and glycosylated protein(s) in hagfish thyroid Y. O h m i y a , S. Suzuki and Y. Kondo Epitopes common to thyroglobulin and acetylcholinesterase demonstrated at the molecular level M . Ludgate, Q. D o n g , C. D i n s a r t , P . T a y l o r and G. Vassart Physicochemical and immunological properties of serum thyroglobulin from serum of healthy individuals K. Saito, Y. Kohno, O. T a r u t a n i , T. I s h i k i t a , S. Sakata and H . N a k a j i m a Abnormal thyroglobulin in mice with inherited congenital goiter (cog/cog) A . B . Schneider, M . Basche and W.G. Beamer Defective expression of the thyroglobulin gene in familial congenital goiter G. Medeiros-Neto, M . Knobel, F. Propato, F . H . D ' A b r o n z o , V. V a r e l a , M . A l k i m i n , S. Barbosa, B . Wajchenberg a n d H . Targovnik Activation of thyroglobulin gene by Graves* IgG in cultured human thyroid cells A . W . C . K u n g , J . P . B a n g a , K Collison

and A . M . M c G r e g o r

641

645

649

653 657

661

667

Serum level and measurement Advantage of monoclonal antibody in determination of serum thyroglobulin enzyme immunoassay and histochemical staining S. Noguchi, R . K a l o , M . Adachi, N . M u r a k a m i and M . T o d a Serial determination of serum thyroglobulin concentrations in Graves' disease T. T a n i k a w a , Y. H a r a , K. Sato, Y. Sakatsume, S. M i u r a , K. I n o u e , M . U r a b e , Y. K a w a k a m i , S. S a k u r a i , M . Yanagisawa, M . I i t a k a and J. Ishii Tumor marker antigens relating to thyroid follicular and parafollicular cell in various thyroid disorders S. O h t a n i , K. Iwase, A . N a g a s a k a , K. Kato, I. Nagatsu, S. Shinoda, M . I n a g a k i , T. T s u j i m u r a , A . I n a g a k i , S. M i y a k a w a , K. Kawase, T. Kawabe, T. O h y a m a , R . M a s u n a g a and K. M i u r a Serum thyroglobulin determination in thyroid Cancer. A ten year experience F. P a c i n i , C. Ceccarelli, R . Elisei, L . Grasso a n d A . P i n c h e r a

Index of authors

673

677

681 685 691

© 1988 Elsevier Science Publishers B.V. (Biomedical Division) The thyroid 1988. S. Nagataki, K. Torizuka, editors.

105

SUPPRESSOR C E L L FUNCTION IN THYROID AUTOIMMUNE D I S E A S E IS AFFECTED BY PLASMID ENCODED PROTEINS OF ENTEROPATHOCENIC Y E R S I N I A

B.E. WENZEL-; J . HE ES EM ANN-** ; S . GRAMMERSTORF * ; P.C. SCRIBA* D e p t . I n t e r n a l M e d i c i n e , M e d . U n i v e r s i t y L ü b e c k * and I n s t . M i e r o b i o l . & Immunol., U n i v e r s i t y Hamburg, FR Germany

INTRODUCTION Autoimmune t h y r o i d d i s e a s e ( A I T D ) and Y e r s i n i a e n t e r o e o l i t i c a ( Y . e . ) show striking c r o s s r e a c t i v i t i e s o f h u m o r a l and c e l l u l a r immunity ( 1 , 2 , 3 ) . S i n c e Y.e. a l s o h a s b i n d i n g s i t e s f o r t h y r o t r o p h i n T S H ) . t h e r o l e Y.e. m i g h t p l a y f o r t h e p a t h o g e n i s i s o f AITD became a matter of interest. Recently i t became e v i d e n t t h a t a p r e - r e q u i s i t e of v i r u l e n c e i n e n t e r o p a t h o g e n i c Y . e . - i n f e c t i o n s i s the presence o f a 42-46 MDa plasmid which i s r a p i d l y l o s t a f t e r subcultivation(4 ) . T h i s p l a s m i d m e d i a t e s v i r u l e n c e f u n c t i o n s s u c h a s s e r u m - and p h a g o c y t o s i s r e s i s i t a n c e or c e l l adherence(5)• The p l a s m i d a l s o e n c o d e s for a t l e a s t 6 p r o t e i n s a g a i n s t w h i c h humans and animals produce antibodies a f t e r Y . e . - i n f e c t i o n s . In calcium deficient culture medium thevSe i m m u n o g e n i c r e l e a s e - p r o t e i n s (RPs) a r e s e c r e t e d i n h i g h quantities(6). We r e c e n t l y r e p o r t e d t h a t p a t i e n t s w i t h AITD h a v e h i g h f r e q u e n c i e s o f R P - a n t i b o d i e s o f IgM,IgA and IgG c l a s s a s w e l l a s a n t i b o d i e s to a 25 kDa R P . T h i s 25 kDa RP shows a n t i g e n i c h o m o l o g i e s w i t h t h e TSHreeeptor(7)• Moroover,in Graves disease(GD) a n t i b o d i e s to the 25 kDa RP and a n t i b o d i e s o f IgA c l a s s emerge e a r l y a t t h e o n s e t o f t h e d i s e a s e but l a t e r than the T S H - r e c e p t o r a n t i b o d i e s are d e t e c t e d in p a t i e n t s * b1o o d ( 8) . W i t h i n 12 mo n t h s t he r e a f t e r t hes e a n t i bo d i e s vanish(9 )• Since bacteria carrying t h e p l a s m i d äffect some properties of macrophages,i.c. cell a d h e r e n c e and p a g o c y t o s i s r e s i s t a n c e ( 5 ) 5 we now investigate the functional effect the RPs and Y.e.plasma membranes(YOP) m i g h t h a v e on t h e immnune surveillance in patients w i t h AITD. I n t h e p r e s e n t s t u d y we l o o k e d a t t h e e f f e c t of RPs and o f Y . e . - p l a s m a membranes on l y m p h o c y t e S t i m u l a t i o n w i t h an im r e 1 a t ed an t i g e n , t e t a n u s t o x o i d a n t i g e n ( T T A ) . v

MATERIAL

AND

METHODS

Patients

profile

Patients with G r a v e s " h y p e r t h y r o i d i s m and n o r m a l i n d i v i d u a l s who previously had been sensitizod to TTA were assessed for RP ant i 1)od i e s . A l l GD pa t i e n t s ( n - 5 ) w e r e R P an t i b o d y p o s i t i vo and had TSH-receptor a n t i b o d i e s . I f t h e i r l a s t TIA v a c c i n a t i o n was more than 2 years a g o , t h o i n d i v i d u a l s were r e - s e n s i t i z e d with their consent. Lvmphoeyle f r a c t i o n s Heparinized peripheral blood was s u b m i t t e d to Ficall density c e n t r i f u g a t i o n . The l y m p h o c y t e f r a c t i o n (PBL) was suspended with s h e e p r e d b l o o d c e l l s ( S R B C ) . The s p o n t a n e o u s l y formecl r o s e t t e s ( S R B C R) were s e p a r a t e d from n o n . T - c e l l s on F i c o l l and f i n a l l y t h e SRBC were l y s e d w i t h w a t e r . One p a r t o f PBLs was p l a t e d f o r 2 h o u r s in plastic d i s h e s w i t h c o m p l c t e RPMI 1640 medium w i t h 2 0 % f e t a l calf serum(FCS). The adherent c e l l s and t h e n o n - a d h e r e n t lymphocytes were c o l l e c t e d , c o u n t e d and s t o r e d f o r t h e reconstitution experi-

106

ments. The the initial

yield PBLs.

of adherent

m a c r o p h a g e s (/)M) v a r i e d

from

2-4%

of

Antigens TTA was k i n d l y p r o v i d e d by BEHRING S A , M a r b u r g . F R G . The Standard c o n c e n t r a t i o n u s e d was 2 L f / m l T T A . Y . e . - R P s were s e p a r a t e d f r o m t h e calcium d e f i c i e n t medium by u l t r a f i l t r a t i o n ( A M I C O N , P M 1 0 ) . R P s were resuspended by s o n i f i c a t i o n and p a s s e d t h r o u g h a 0.45p sterile filter. The Y.e.-seroptypes used were 0 : 3 and 0:9 s t r a i n s . In l y m p h o c y t e c u l t u r e s RPs were u s e d a t lOOng/ml f i n a l c o n c e n t r a t i o n . For the preparation of b a c t e r i a l outer m e m b r a n c s ( Y O P ) , membranes were disrupted by sonic lysis(10). The membranes were w a s h e d , e x t e n s i v e l y s o n i c a t e d and p a s s e d t h r o u g h a 0 . 4 5 h f i l t e r . The protein which passed the filter was used at lOng/ml final concentration. When i n d i c a t e d , i n d o m e t h a c i n ( I M ) was a p p l i e d a t l - 1 0 n g / m l . Lymphocyte c u l t u r e s Cells were c u l t u r e d i n 96 w e l l p l a t e s , 5 w q e l l per sample. The c o m p l e t e c u l t u r e medium c o n t a i n e d 10$ F C S . L y m p h o c y t e s were u s e d at 1 . 5 * 1 0 ^ c e l l s / m l . When i n d i c a t e d , 2 % a d h e r e n t