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

E d i t o r s :

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)

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International Congress Series No. 796 ISBN 0 444 81054 4

Published by: Sole distributors for the U S A and C a n a d a : Elsevier Science Publishers B.V. Elsevier Science Publishing Company Inc. (Biomedical Division) 52 Vanderbilt Avenue P.O. Box 211 New York, NY 10017 1000 A E Amsterdam USA The Netherlands

L i b r a r y of Congress 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 : International Thyroid Symposium (6tk

Tokyo, Japan) The thyroid 1988.

1988 :

(International congress series ; no. 796) Includes index. 1. Thyroid gland—Physiology—Congresses. 2. Thyroid

gland—Immunology—Congresses. 3. Thyroid g l a n d — Diseases—Congresses. I. Nagataki, S. II. Torizuka, Kanji, 1926- . III. T i t l e . IV. Series. [DNLM: 1. Autoantibodies—immunology—congresses. 2. Hypothyroidism—congresses. 3. Thyroglobulin— 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 88-31069 ISBN 0-444-81054-4 (U.S.)

Bayerische Staatsbibliothek

München

Printed in The Netherlands

CONTENTS

D u e to unavoidable circwnstances the papers marked with a n * could not be presented at the meeting but have, nevertheless, been included in this volume.

SPECIAL LECTURE

Future trend in thyroidology S . H . I n g b a r

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 1 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 13

Thyrotropin and cyclic AMP 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 . N a g a t a k i 19

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 25 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 33 Coincident regulation of rat thyroid M H C Class II R T l . D a and R T l . D ^ transcripts

D . S . Neufeld and T.F. Davies 37 'Rehabilitation' of cytokines in thyroid autoimmunity: Are they only exerting negative effects?

U. Deuss, M . Buscema and G . F . Bottazzo 43 Antibody against c-erb A protein can interact with rat liver nuclear T 3

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 51

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 57

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 63

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 71 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 75 Intrathyroidal lymphocyte subpopulation study in Graves' disease

K L . L i a w , Y.C. T u , C.C. Yao and I J . Su 81 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 85

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 89

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 95

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 99 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 105 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 . G u z m a n 109

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 . N a k a g a w a , T. K u r o d a and M . Fujishima 115

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 . P i n c h e r a 121

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 125

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 129

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 133 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 137

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 141

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 145

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 149

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 155

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 159

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 . M a t s u d a , 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 163

Measurement of TSH receptor autoantibodies (TR Ab) in children with hyperthyroidism

F . P e t e r 167 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 171

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 I t o 175

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 181 Identification of antigens of abnormal thyroid stimulators by Western blotting

N . Kuzuya, Y. K a w a k a m i and K. Yamashita 185 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 189

Comparison of thyroid stimulating activities measured by cyclic AMP 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 193

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 197

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 203

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 209

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 213

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 217

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 223 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 229

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 233 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 237

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 241

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 245 Occurrence of Graves' hyperthyroidism preceded by silent thyroiditis

J. N o h , M . Yoshimoto, N . I s h i k a w a , N . M o m o t a n i , N . H a m a d a , H . M o r i i and K I t o 249

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 253

T3-predominant Graves' disease: Clinical characteristics and pathogenesis of T 3 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 257

Xll l

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 261

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 265

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 271 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 275 *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 279

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 283

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 289 The influence of humic substances on the thyrotropin receptor

T . C . C h a n g and F.J. L u 293 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 297

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 301

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 307

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 TBG 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 (T3) 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

XV

Mechanism of hormone action and metabolism Thyroid hormone induces gene expression of fibronectin in the rat liver

Y. M u r a t a , H . Seo and N . M a t s u i 381 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 385 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 . B r i g n o n e 389

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 393 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 397

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 403

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 407 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 411 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 415 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 419

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 423

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 431

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 435 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 439

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 443

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 447

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 451

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 455

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 459

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 465

*Functional Status of the thyroid gland in malnutrition /. C h a k r a v a r t y and D . Das 469

Thyroid hormones in protein energy malnutrition (PEM) Y. Sachdev 473

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 477 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 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 487

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 491

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 495

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 499

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 503 Thyroid functions in ankylostomiasis

R . S i n g h , D . K . H a z r a , A . R a j a n , A . K h a n n a , A . K . S h u k l a , R . K . A g a r w a l , 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 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 513 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 517 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 521

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 525

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 529 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 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 . I n g b a r 539

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 543

Human chorionic gonadotropin stimulates iodide uptake, adenylate cyclase, and DNA 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 547

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 . I t o h 551

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 555 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 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 565

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 569

Effect of estradiol (E2) on calcitonin (CT) secretion and the finding of E 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 573

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 579

Fine-needle biopsy (FNB) and the outcome of benign thyroid nodules S. Tseleni-Balafoutas, K. Katsouyanni, J. Kitsopanides and D . A . Koutras 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 595 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 601 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 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 611 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 615 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 619 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 623 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 627

Effect of amiodarone on , 2 7 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 631

THYROGLOBULIN Structure and gene expression Intrathyroidal metabolism of 3 5 S-PTU and 3 5 S-MMI 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 641

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 645 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 649 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 653 Abnormal thyroglobulin in mice with inherited congenital goiter (cog/cog)

A . B . Schneider, M . Basche and W.G. Beamer 657 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 . T a r g o v n i k 661

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 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 673 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 677

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 681

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 685

Index of authors 691

© 1988 Elsevier Science Publishers B.V. (Biomedical Division) The thyroid 1988. S. Nagataki, K. Torizuka, editors. 105

SUPPRESSOR CELL FUNCTION IN THYROID AUTOIMMUNE DISEASE IS AFFECTED BY PLASMID ENCODED PROTEINS OF ENTEROPATHOCENIC YERSINIA

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 Lübeck* 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 s t r i k i n g c r o s s r e a c t i v i t i e s o f humoral and c e l l u l a r immunity ( 1 , 2 , 3 ) . S i n c e Y.e. a l s o has 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. might p l a y f o r the p a t h o g e n i s i s of AITD became a m a t t e r of i n t e r e s t . R e c e n t l y 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 4 2 - 4 6 MDa p l a s m i d which i s r a p i d l y l o s t a f t e r s u b c u l t i v a t i o n ( 4 ) . T h i s p l a s m i d mediates v i r u l e n c e f u n c t i o n s such as serum- and phago c y t o s i s r e s i s i t a n c e or c e l l a d h e r e n c e ( 5 ) • The p l a s m i d a l s o encodes f o r at l e a s t 6 p r o t e i n s a g a i n s t which humans and a n i m a l s produce a n t i b o d i e s a f t e r Y . e . - i n f e c t i o n s . In c a l c i u m d e f i c i e n t c u l t u r e medium thevSe immunogenic 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 q u a n t i t i e s ( 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 have h i g h f r e q u e n c i e s

of R P - a n t i b o d i e s of IgM,IgA and IgG c l a s s as w e l l as a n t i b o d i e s t o a 25 kDa RP.This 25 kDa RP shows a n t i g e n i c homologies w i t h the TSH-r e e e p t o r ( 7 ) • M o r o o v e r , i n G r a v e s v d i s e a s e ( G D ) a n t i b o d i e s t o the 25 kDa RP and a n t i b o d i e s of IgA c l a s s emerge e a r l y at the onset o f the 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 i n p a t i e n t s * b1o o d ( 8) . W i t h i n 12 mo nt h s t he re a f t e r t hes e a n t i bo di e s v a n i s h ( 9 ) • S i n c e b a c t e r i a c a r r y i n g the p l a s m i d äffect some p r o p e r t i e s o f

macrophages,i.c. c e l l adherence 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 i n v e s t i g a t e the f u n c t i o n a l e f f e c t the RPs and Y.e.-plasma membranes(YOP) might have on the immnune s u r v e i l l a n c e i n p a t i e n t s with AITD. In the p r e s e n t study we l o o k e d at the e f f e c t of RPs and of Y.e.-plasma membranes on lymphocyte S t i m u l a t i o n w i t h an im re 1a t ed an t i gen,t etanus toxo i d a n t i g e n ( T T A ) .

MATERIAL AND METHODS

P a t i e n t s p r o f i l e P a t i e n t s with G r a v e s " h y p e r t h y r o i d i s m and normal i n d i v i d u a l s who

p r e v i o u s l y had been s e n s i t i z o d t o TTA were a s s e s s e d f o r RP ant i 1)od i es. A l l GD pa t i e n t s ( n - 5 ) were R P an t ibody 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 y e a r s ago,tho i n d i v i d u a l s were r e - s e n s i t i z e d w i th t h e i r c o n sent.

Lvmphoeyle f r a c t i o n s H e p a r i n i z e d p e r i p h e r a l b l o o d was s u b m i t t e d t o F i c a l l d e n s i t y

c e n t r i f u g a t i o n . The lymphocyte f r a c t i o n (PBL) was suspended w i t h sheep red blood 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 the SRBC were l y s e d with water. One p a r t o f PBLs was p l a t e d f o r 2 hours i n p l a s t i c d i s h e s with complcte RPMI 1640 medium wi t h 2 0 % f e t a l c a l f serum(FCS). The adherent c e l l s and the non-adherent 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 the r e c o n s t i t u t i o n e x p e r i -

106

ments. The y i e l d of adherent macrophages (/)M) v a r i e d from 2-4% of the i n i t i a l PBLs.

A n t i g e n s TTA was k i n d l y p r o v i d e d by BEHRING SA,Marburg.FRG. The S t a n d a r d

c o n c e n t r a t i o n used was 2Lf/ml TTA. Y.e.-RPs were s e p a r a t e d from the c a l c i u m 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 ) .RPs were resuspended by s o n i f i c a t i o n and passed through a 0 . 4 5 p s t e r i l e f i l t e r . The Y . e . - s e r o p t y p e s used were 0 : 3 and 0 : 9 s t r a i n s . In lymphocyte c u l t u r e s RPs were used at lOOng/ml f i n a l c o n c e n t r a t i o n . For the p r e p a r a t i o n of b a c t e r i a l o u t e r membrancs(YOP), membranes

were d i s r u p t e d by s o n i c l y s i s ( 1 0 ) . 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 passed t h r o u g h a 0 . 4 5 h f i l t e r . The p r o t e i n which passed the f i l t e r was used at lOng/ml f i n a l c o n c e n t r a t i o n . When i n d i c a t e d , indomethacin(IM) was a p p l i e d at l - 1 0 n g/ml.

Lymphocyte c u l t u r e s C e l l s 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

complete c u l t u r e medium c o n t a i n e d 10$ FCS. Lymphocytes were used at 1.5*10^ c e l l s / m l . When i n d i c a t e d , 2 % adherent </M were added. Lymphocytes were c u l t u r e d f o r 6 days w i t h TTA w i t h or w i t h o u t

a d d i n g : JjM, RPs , YOPs , IM. For the l a s t 24 hours 0 . 5 p C i/ml 3 h_thymidine ( 3 H - T d R ) . T h e r e a f t e r , c e l l s were c o l l e c t e d w i t h an automated c e l l h a r v e s t e r a p p l y i n g the sequence watcr,TCA 10%,et hano 1.Samples were counted i n a s c i n t i I I a t i o n c o u n t e r and c a l c u l a t e d as S t i m u l a ­t i o n i n d c x ( S I ) ± S t a n d a r d d e v i a t i o n ( S D ) . S t i m u l a t i o n or i n h i b i t i o n of the TTA response were e x p r e s s e d as % of the S t i m u l a t i o n w i th ITA al o n e (TTA= 1 0 0 % ) .

100%

50%

TTA PBL

F i g u r e 1 : I' f f e c t of Y . e . - p l a s m i d e n c o d e d a n t i g e n s on the TTA r e ­sponse of normal p e r i p h e r a l b l o o d lymphocytes. RP R e l e a s e Pro­t e i n s , M P YOP from Y . e . w i t \\ / M(f without p l a s m i d ,

mac rophage s, T T-1ymphocy t e s, T^ t e t a n u s t o \ o i d ant i gen.

RESULTS

F i g u r e 1 shows how the RPs are s u p p r e s s i n g the TTA response of normal PBLs( 7 0 % + 4,n-5,P < 0 . 05) • Y O P - f r a c t i o n s , h o w e v e r , d o not äffect the TTA S t i m u l a t i o n , r e g a r d l e s s l y of whether they d e r i v e from b a c t e r i a w i t h plasmid(M-P) or w i t h o u t ( M 0 ) . A s i m i l a r p a t t e r n i s

107

found w i t h T - c e l l s r e c o n s t i t u t e d w i t h macrophages(^M). In the absence of macrophages the RPs do not i n f l u e n c e the TTA response of T-lymphocytes. In c o n t r a s t , P B L s from p a t i e n t s w i t h GD are not a f f e c t e d by RPs which o n l y produce an i n s i g n i f i c a n t r e d u c t i o n of the TTA r e s p o n s e ( F i g u r e 2 ) . The YOPs,however, produce an excess S t i m u l a t i o n . F i g u r e 3 demonstrates t h a t t h e s u p p r e s s i v e potency of RPs i s

macrophage dependent. D e p l e t i o n of PBLs from macrophages or a d m i n i s t r a t i o n of indömethacin(IM) a b o l i s h e s the s u p p r e s s i o n of the TTA response w i t h normal PBLs.

CONCLUSIONS

Our e x p e r i m e n t s show f o r the f i r s t time t h a t the p l a s m i d of e n t e r o p a t h o g e n i c Y.e. does i n t e r f e r e through i t s p r o t e i n p r o d u c t s w i t h the immune s u r v e i l l a n c e i n normal i n d i v i d u a l s . The s u p p r e s s i v e e f f e c t of RPs on t h e TTA response i s e x e r t e d on the adherent macrophages. The e f f e c t on the T - c e l l p r o l i f e r a t i o n appears to be mediated by P r o s t a g l a n d i n s , s i n c e the c y c l o - o x y g e n a s e b l o c k e r , I M , a b o l i s h e s the s u p p r e s s i o n . A l t h o u g h p h a g o c y t o s i s r e s i s i t a n c e and c e l l adherence o f e n t e r o p a t h o g e n i c Y.e. are a t t r i b u t e d t o the p l a s m i d encoded Y0P1 a n t i g e n , o u r membrane f r a c t i o n s d i d not sup p r e s s the TTA r e s p o n s e . In c o n s t r a s t , b o t h ,membranes from Y.e. with or w i t h o u t p l a s m i d , s t i m u l a t e d lymphocytes from p a t i e n t s with GD,who were p r e - s e n s i t i z e d by Y.e.(RP-antibody p o s i t i v e ) . T h i s may i n d i c a t e t h a t the p l a s m i d dependent(YOP 1) s u p p r e s s i v e e f f e c t i s c o u n t e r a c t e d by the s t i m u l a t o r y p r o p e r t i e s of the membrane 1 i p o p r o t e i n s ( 1 0 ) . The macrophages i n GD appear not t o r e a c t t o the RPs,although p h a g o c y t o s i s r e s i s t a n c e i s p l a s m i d encoded(5)»

rfi

RP M-P M-*

T*0M n=5

RP M-P M »

T n=5

F i g u r e 2: E f f e c t of Y.e.-p1a sm i d encoded a n t i g e n s on the TTA r e ­sponse of PBLs from p a t i e n t s with GD. RP- Rele a s e Pro­t e i n s ,M-P -YOP from Y.e. wi t h /M-0 wit h o u t p l a s m i d ^M^macrophages; T= T-lymphocytes TTA- t e t a n u s

t o x o i d a n t i g e n

T h i s c o u l d mean t h a t macrophages are rendered i n a c t i v e by RPs.Hence, b a c t e r i a can not be e l i m i n a t e d t h r o u g h p h a g o c y t o s i s and a l a t e n t or c h r o n i c i n f e c t i o n might r e s u l t . T h i s s c e n a r i o would be r e f l e c t e d by the p e r s i s t i n g h i g h p r e v a l e n c e of Y . e . - a n t i b o d i e s i n GD-p a t i e n t s ( 8 ) . In g e n e t i c a l l y committed i n d i v i d u a l s a n t i g e n i c mimery

108

o f RPs with t h y r o i d a n t i g e n s ( 7 ) would l e a d t o the break of s e l f -t o l e r a n c e and the developement o f AITD. These a r e , o f c o u r s e , h y p o t h e t i c a l c o n s i d e r a t i o n s , s i n c e i n our System the Y.e.-RPs are s e c r e t e d under n o n - p h y s o i l o g i c a l c o n d i t i o n s , i . e . c a l c i u m d e f i c i e n c y . F u r t h e r i n v e s t i g a t i o n s w i l l show what s i g n i f i c a n c e RPs might have i n v i v o .

F i g u r e ?: E f f e c t of indömethacin on the RP mediated s u p p r e s s i o n of the TTA response w i t h normal PBLs. RP- R e l e a s e P r o t e i n s TTA= t e t a n u s t o x o i d antigen;oM- macrophages IM- indömethacin

TTA + R P * T-CELLS

REFERENCES

1. Bech K, L a r s e n JM, Hansen GM, Nerup J ( 1974) Lancet 11:551

2. Lidmann K, E r i k s o n U, Morberg A, F r a g r e u s A ( 1976) C l i n Exp Immunol 2 3 : 4 2 9

3 . Bech K,Clemmensen 0 , L a r s e n JH, Bendixen G ( 1977) Lancet II:1060

4 . Zink DL, F e e l e y JG, W e l l s JG, Vanderzant C, V i c k e r y JC, Roof W, 0 vDonnovan GA (1980 ) Nature 283 :224

5. Heesemann J , A l g e r m i s s e n B, L a u f s R (1984 ) I n f e c t Immun 4 6 : 1 0 5

6. Heesemann J , Gross U, Schmidt M, L a u f s R ( 19 8 6 ) I n f e c t Immun 54:561

7. Wenzel BE, Heesemann J ( 1987) Hormone & Metab Res 1 7(s ) : 7 7

8 . Wenzel BE, llcesemann J , Wenzel KW, S c r i b a PC ( 1988) Lance t 1 :56

9 . Wenzel BE, Heesemann J , Wenzel KW, S c r i b a PC (1988 ) J E n d o c r i n o l Inv 11/2:139

10. Pekkola-Heino K, V i l j a n e n MK, S t a h l b e r g TH, G r a n f o r s K, Toivanen A ( 1987 ) A c t a path m i c r o b i o l scand S e c t C 95*-27

Supported by "Deutsche F o r s c h u n g s g e m e i n s c h a f t " : S F B 232;He-1297/1-4

Index of authors

Adachi, M., 673 Adams, J.G., 109 Agarwal, R.K., 507 Aghini-Lombardi, F., 159 Agrawal, J.K., 307 Aguayo, J., 75 Ahmed, J., 297 Ahuja, M.M.S., 533 Akazawa, M., 403 Akazawa, S., 403 Akiyama, H., 439, 451 Akuzawa, M., 423 Alkimin, M., 661 Alvarez, F.V., 197 A n e l l i , S., 121 Aoki, N., 595 Arai, M., 627 Arai, T., 443 Arikawa, K., 175 Armstrong, B., 319 Ashizawa, K., 19 As t u d i l l o , J ., 109

Babu, B.V., 533 Bai, Y., 349 Bajpai, H.S., 307 B a l e s t r i e r i , A., 487 Balzano, S. , 159, 261, 487 Banga, J.P., 667 Barbosa, S., 661 Barlow, J.W., 349 Bartalena, L., 159, 261 Basche, M., 657 Bassi, P., 209 Bauch, K., 325 Beamer, W.G., 657 Benvenga, S . , 343 Bhatt, R.P., 307 Bleasdale, K., 137 Boey, J.H., 605 Bottazzo, G.F., 43 Boyages, S.C., 311, 315, 329 Briancon, C., 631 Brignone, CM. , 389 Brignone, J.A., 389 Buratti, L., 159 Buscema, M., 43 Buss, D., 455

Cahnmann, H.J., 343

691

Carayon, P., 121, 125 Caturegli, P., 121 Cav a l i e r i , R.R., 397 Ce c c a r e l l i , C., 587, 685 Cesaretti, G., 587 Chakravarty, I., 469 Chan, J., 197 Chandra, 0., 297 Chang, T.C., 293 Chang, Y.C., 411 Chapman, S.W., 109 Chen, F.W., 411 Chen, J.H., 491 Chen, X., 279 Chen, Y., 279 Chen, Z.P., 271, 407 Cheung, P.S.Y., 605 Chiovato, L., 209 Cho, B.Y., 213 Clark, F., 137 Col l i n s , J., 311 Collison, K., 667 Connors, J .M. , 555 Cooksey, R.C., 109 Cruse, J.M., 109

D'Abronzo, F.H., 661 Das, D., 469 Davies, T.F., 37 De l a Torre, W., 573 DeCherney, G.S., 13 Degroot, L.J., 129, 357 DeLuca, M., 25 Derwahl, M., 33 Deuss, U., 43 Devey, M., 137 Dinsart, C., 125, 649 Dong, L., 407 Dong, Q., 649 Dorris, M., 637 Duntas, L., 223, 481, 495

Eastman, C , 275, 311, 315, 319, 329, 431

Eguchi, K., 85, 95 E l i s e i , R., 685 Endo, S., 551 Endo, T., 181 English, D., 319 Ericsson, U.-B., 241

692

Eto, S., 525 Hesch, D., 63 Hiasa, Y., 565

Falcone, M., 261 Hidaka, A., 193 Fa r c i , P., 487 Hinotani, A., 129 Feng, J., 279 Hiramatsu, H., 595 Fenzi, G., 209 Hirayu, H., 19, 403 Figus, A., 487 Hisazumi, H., 435 Formica, N., 587 Ho, Y.H., 513 Fragu, P., 631 Homma, M., 175 Fritzsche, H. , 63 Horimoto, M., 477 F u j i h i r a , T., 525 Hosoda, Y., 579 Fuj ishima, M., 115, 229 Hosoya, T., 133, 257 Fukue, Y., 171, 203, 543 Hou, B.Z., 271 Furuta, S., 357 Hsiao, P.J., 491

Huang, T.S., 411 Gaitan, D., 109 Huber, G., 33 Gaitan, E., 109 Huffman, L.J., 555 Gaitan, G.S., 109 Hummel, B.C.W., 393 Garcia Ameijeiras, A., 573 Hutchings, A., 419 Gavin, L.A., 397 Gesundheit, N. , 13 Ichikawa, K., 357 Giannessi, G., 159 Ichikawa, Y., 175 Giganti, G., 641 Iida, F., 89 Glinoer, D., 63 Iida, Y., 57, 193 Goellner, J.R., 601 Iitaka, M., 99, 149, 677 Gopinathan Nair, P.G., 301 Ikenoue, H., 115, 229 Goto, Y., 551 Imokawa, M., 189 Grammerstorf, S., 105 Imura, H., 51, 611, 619 Grasso, L., 261, 685 Inada, M., 477 Grimaldi, S., 641 Inagaki, A., 681 Gryczynska, M., 209 Inagaki, M., 681 Gupta, A., 301, 307 Ingbar, S.H., 1, 539 Gupta, L., 301, 499 Inoue, K., 149, 171, 677 Guzman, R.N., 109 Inoue, S., 19 Gyves, P.W., 13 Inukai, T., 253, 451

Iriuchijima, T., 7, 423 Haak, B., 63 Ishida, H., 521 Hachiya, T., 189 Ishida, M., 189 Hakamata, M., 551 I s h i i , A., 253 Halpern, J.-P., 311, 315, 329 I s h i i , H., 521 Halpern, S., 631 I s h i i , J., 99, 149, 677 Hamada, N., 129, 249 Ishikawa, N., 19, 85, 95 Hamada, S., 521 Is h i k i t a , T., 653 Hampel, R., 529 Ishimura, Y., 623 Hansen, B., 241 Isozaki, 0., 197, 627 Hara, Y., 149, 677 Itagaki, Y., 443 Harakawa, S., 19, 403 Ito, K., 19, 85, 95, 129 Hasan, B., 297 249, 579 Hashimoto, A., 253 Itoh, H., 57 Hashimoto, H., 565 Itoh, M., 551 Hashimoto, M., 403 Iwamori, M., 619 Hashimoto, T., 435 Iwase, K., 393, 681 Hashizume, K., 357 Iwashita, A., 451 Hatabu, H., 193 Izumi, M., 19, 403 Hatwal, A., 307 Hay, I.D., 601 Jamieson, C., 75 Hazra, D.K., 301, 499, 507 J a n n e l l i , S., 487 Hedge, G.A., 555 J i n , C., 311, 315, 329 Heesemann, J., 105 Jones, T., 533 Hershman, J.M., 333, 547 Jupp, J., 311

693

Kachlas, S. , 301, 499 Kaise, K., 443 Kaise, N., 443 Ka j i t a , Y., 189 Kambara, M., 237 Kambe, F., 339 Kamijo, K., 265 Kanaji, Y., 203 Kanatani, M., 525 Karaiskos, K.S., 283 Kasagi, K., 57, 193, 233 Kasuga, Y., 89 Kato, K., 681 Kato, M., 415 Kato, R., 673 Katoh, Y., 559 Katsouyanni, K., 583 Kawabe, T., 681 Kawakami, A., 85, 95 Kawakami, K., 149 Kawakami, Y., 71, 185, 677 Kawaoi, A., 559 Kawasaki, K., 265 Kawase, K., 681 Kawazu, S., 149 Keck, F.S., 223, 481, 495 Khanna, A., 507 Khurana, V.K., 507 Kirsch, G., 325, 529 Kiso, Y., 443 Kitahori, Y., 565 Kitaoka, H., 233, 257 Kitsopanides, J., 583 Kiyohara, K., 465 Knappe, G., 325 Knobel, M., 661 Kobayashi, I., 253, 439, 451 Kobayashi, N., 459, 465 Kobayashi, S., 89, 253, 423, 439,

451 Kochupillai, N., 53^ Koh, C S . , 213 Kohn, A.D., 197 Kohn, L.D., 25, 197 Kohno, Y., 133, 155, 257, 653 Kojima, N., 145, 155, 163, 447 Komaki, G., 459, 465 Komaki, T., 145, 155, 163, 447 Komeda, K., 149 Kondo, Y., 451, 645 Konishi, J . , 57, 193 Konishi, N. , 565 Kosugi, S., 619 Koutras, D.A., 283, 583 Krishna Ram, B., 289 Kriss, J.P., 217 Kubota, K., 171, 203, 543 Kulshreshtha, S., 297, 301, 499, 507 Kuma, K., 257, 569 Kumar, M., 307

Kumar, V., 297, 301, 499, 507 Kung, A.W.C , 667 Kuroda, T., 115, 229 Kuzuya, N., 71, 185 Kuzuya, T., 353

Lagasse, R., 63 Lai, M.E., 487 Laurberg, P., 63 Lazarus, J., 419, 455 Lee, H.Y., 547 Lee, J.M.H., 605 Lee, S.H., 411 Lee, Y.J., 491 Leu, S.L., 217 L i , M., 275 Liaw, K.L., 81 Libert, F., 125 Lim, C F . , 349 Lio, S., 641 Lip p i , F., 587 L i t t l e y , M., 419, 455 Liu, Q., 279 Liu, X.L., 271 Lombardi, A., 539 Loos, U., 223, 481, 495 Lopez, G., 209 Lotz-Salabe', H., 141 L o v i s e l l i , A., 159, 261 Lu, F.J., 293 Ludgate, M., 125, 649

Ma, G., 319 Ma, T., 271, 407 Maberly, C , 275, 311, 315, 319, 329 Maciel, R.M.B., 539 Maj ima, M., 503 Majima, T., 503 Makino, R., 623 Makriyannis, D., 283 Malinsky, M., 63 Mammoli, C., 209 Manabe, Y., 171 Männchen, E., 529 Manthorpe, R., 241 Mantzos, J., 283 Marcocci, C , 209 Mariotti, S., 121, 125 Marshall, R., 455 Martino, E., 159, 261, 487 Masuda, H., 8° Masuda, K., 51 Masunaga, R., 681 Matsubara, F., 435 Matsubayashi, S., 459, 569 Matsuda, M., 145, 155, 163, 447 Matsui, N., 339, 381 Matsuki, A., 517 Matsumoto, H., 559, 569 Matsumoto, M., 237

694

Matsumoto, T., 19 Matsunaga, M., 85 Matsuo, K., 19 Matsushita, Y., 175 Matsuzuka, F., 569 Matuki, H., 565 May, W., 431 McConahey, W.M., 601 McGregor, A.M., 667 McLachlan, S.M., 137 Medeiros-Neto, G., 661 Meng, S., 529 Meng, W., 325, 529 Merkl, I., 481 Meydrech, E.F., 109 Michalkiewicz, M., 555 Michimata, T., 7, 423 Migita, K., 85, 95 Mignone, I.R., 389 Min, H.K., 213 Minami, S., 57, 565 M i r e l l , C.J., 547 Misaki, T., 193, 539 Mishra, V., 507 Mithai, A., 533 Mitsuhashi, T., 171 Miura, K., 145, 155, 163, 375, 447, 681

Miura, S., 149, 677 Miyagawa, M., 627 Miyakawa, S., 681 Miyamoto, T., 357 Miyashita, K., 423 Miyazaki, T., 569 Mo f f i t t , S., 137 Momotani, N. , 237, 249 Monaco, F., 641 Mori, M., 7, 423, 439 Mori, S., 459 Mori, T., 611, 619 Morii, H., 129, 249 Morita, T., 569 Moriyama, S., 559 Moses, A.C., 539 Moulopoulos, S.D., 283 Moulopoulou, D.S., 283 Murakami, M., 423 Murakami, N., 673 Murata, M., 237 Murata, Y., 339, 381 Murtas, M.L., 487

Nagayama, I., 353 Nagayama, Y., 19, 403 Naito, N., 133 Nakagawa, M., 115 Nakagawa, T., 459, 465 Nakajima, H., 133, 653 Nakajima, K., 435 Nakajima, Y., 189 Nakamura, H., 51 Nakamura, S., 145, Nakamura, Y., 623 Nakano, Y., 57 Nakao, H., 85, 95 Napolitano, G., 641 Neufeld, D.S., 37 N i s h i i , Y., 357 Nishikawa, M., 477 Noguchi, S., 673 Noh, J., 249 Noma, S., 57

Ochi, Y., 189 Oda, S., 525 Ogawa, N., 551 Ogura, H., 189 Ohashi, H., 551 Ohmiya, Y., 645 Ohno, M., 129 Ohno, S., 615 Ohno, Y., 595 Ohshima, K., 439 Ohshima, M., 565 Ohtaki, S., 623 Ohtani, S., 681 Ohyama, T., 681 Okada, K., 237 Okamoto, K., 129 Okamoto, S., 565 Okamura, K., 115, 229 Okuda, K., 233 Okugawa, T., 551 O l i v i e r i , A., 141 Onaya, T., 181 Oonishi, T., 521 Osborn, R.A., 275 Osumi, T., 357 Otsubo, T., 85, 95 Otsuka, H., 357 Ouyang, A., 333 Oyama, T., 517 Ozawa, Y., 245, 385

163, 375, 447

Nagai, K., 155, 163, 447 Nagai, Y., 619 Nagamune, T., 189 Nagasaka, A., 681 Nagata, I., 595 Nagataki, S., 19, 85, 95, 403, 465, 569

Nagatsu, I., 681

Pacini, F., 587, 685 Pang, X.P., 333, 547 Pekary, A.E., 547 Perpoli, F., 587 Peter, F., 167 Peter, H.-J., 33 P e t r i n i , L., 159, 261 P f e i f f e r , E.F., 223, 481, 495

695

P h i l l i p s , D., 419, 455 Piccolo, P., 121, 125 Pilosu, M., 159 Pinchera, A., 121, 125, 209, 587, 685

Piperingos, CD., 283 Pittman, CS., 397 Pozzi, D., 641 Preuss, T.M., 109 Propato, F., 661

Rajan, A., 507 Ravagnan, G., 141 Rees Smith, B., 137 Ribera, F., 573 R i c c i , CR. , 389 Robbins, J., 343 Rodriguez, J., 573 Rohatgi, V.K., 499 Rosell, E., 573 Rosenthal, J., 223 Rotella, CM. , 197 Routledge, P., 419, 455 Row, V.V., 75 Ruf, J., 121 Ryan, J . J., 601

Sachdev, Y., 473 Sago, T., 57 Saito, K., 133, 155, 353, 653 Saito, S., 443 Saito, T., 181, 353 S a j i , M. , 627 Sakaguchi, Y., 565 Sakane, S., 233, 257 Sakata, S., 145, 155, 163, 375, 447, 653

Sakatsume, Y., 75, 677 Sakurada, T., 443 Sakurai, S., 149, 677 Salabe', G.B., 141 Santini, F., 125. 209 Santisteban, P., 25 Sasaki, N., 171, 203, 543 Sato, K., 115, 149, 229, 627, 677 Sato, M., 265 Sato, T., 423 Sawada, K., 237 Schneider, A.B., 657 Schrezenmeier, H., 481 Scriba, P.C., 105 Seo, H., 339, 381 Sfontouris, J., 283 Shah, P., 289 Sharma, A.K., 289 S h i f r i n , S., 25 Shima, H., 145 Shimizu, T., 385 Shimomura, C., 85, 95 Shimomura, Y., 439

Shimoyama, T., 565 Shimura, H., 181 Shin, S.J., 491 Shinoda, S., 681 Shinozawa, T., 175 Shishiba, Y., 245, 385 Shizume, K., 627 Shoda, Y., 439, 451 Shong, Y.K., 213 Shukla, A.K., 499, 507 Sica, V., 159, 261, 487 Singh, P.N., 297 Singh, R., 301, 499, 507 Singh, S., 301, 507 Singh, S.K., 307 Smith, S.A., 601 Souvatzoglou, A., 283 Spragg, B., 419 Srivastava, R.N.L., 499 Srivastava, S.K., 307 Stephenson, A., 137 Sterling, K., 361 Stockigt, J.R., 349 Studer, H., 33 Su, I.J., 81 Su, T.S., 333 Sugawa, H., 611 Sugawara, M., 257, 547 Sugenoya, A., 89 Sugiura, M., 253 Sundara-Raman, P.G., 533 Suri, V., 301 Suzuki, H., 525 Suzuki, M., 415 Suzuki, S., 645

Tagami, T., 51 Takaku, F., 171, 203, 543 Takamatsu, J., 163, 233, 257, 503 Takasu, N., 615 Takeda, K., 257 Takeda, M., 415 Takeuchi, Y., 385 Takuno, H., 145, 155, 163, 447 Tamai, H., 459, 465, 569 Tamai, S., 579 Tanaka, K., 521 Tanikawa, T., 149, 677 Tao, T.W., 217 Tao, Y., 279 Tarantino, E., 587 Targovnik, H., 661 Tarutani, 0., 133, 155, 257, 653 Taurog, A., 637 Taylor, P., 649 Taylor, T., 13 Tezuka, H., 85 Toccafondi, R., 197 Toda, M., 673 Tokimitsu, N., 155, 163, 447

696

Tokuda, Y., 193 Topliss, D.J., 349 Torizuka, K., 57 Torng, J.K., 491, 513 Toshio, T., 627 Tramontano, D., 539 Tsai, J.H., 491 Tseleni-Balafoutas, S., 583 Tsuchiya, Y., 627 Tsuj i i , T., 565 Tsuj imura, T., 681 Tu, Y.C., 81

Uchimura, H., 171, 203, 543 Ueda, S., 503 Ueki, Y., 85, 95 Ul r i c h , F.E., 325 Urabe, M., 149, 677 Ushiyama, H., 559

Valente, W.A., 197 Varela, V., 661 Vassart, G., 125, 649 Ventz, M., 529 Verna, R., 641 V i t t i , P., 209 Volpe, R., 75, 99

Waite, K., 431 Wajchenberg, B., 661 Walfish, P.G., 393 Wang, S., 279 Watanabe, K., 525 Watanabe, T., 443 Wechsler, J.G., 495 Wei, C., 279 Weintraub, B.D., 13 Wenzel, B.E., 105 Wieshammer, S., 495 Wong, Z.-H., 311, 315, 329 Wu, C.C., 513

Wu, D., 275

Yachi, A., 265 Yagura, T., 521 Yahata, K., 525 Yakumaru, K., 579 Yamada, T., 357, 615 Yamaguchi, M., 423 Yamaguchi, T., 253, 439, 451 Yamaguchi, Y., 253 Yamakawa, J., 129 Yamamoto, K., 353 Yamamoto, M., 443 Yamamoto, S., 525 Yamashita, K., 71, 185 Yamashita, S., 19, 403 Yamauchi, K., 357 Yamin, M., 533 Yanagisawa, M., 149, 547, 677 Yang, S., 279 Yao, C.C., 81 Yasin, F., 319 Yi , Y.C., 311 Yokoi, N., 385 Yoshida, K., 443 Yoshikawa, N., 477 Yoshimasa, T., 521 Yoshimoto, M., 249 Yoshinaga, K., 443 Yoshinari, M., 115, 229 Yoshioka, N., 375 You, C., 315, 329 Young, E.T., 137 Yu, D., 329

Zaninovich, A.A., 389 Zeki, K., 525 Zhang, X., 279 Zhang, Z., 279 Zhao, J., 279 Zouhair Atassi, M., 375

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