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11 ·5·92 September-Oetober 1992 mmun •••••• •••• •••• •• •• •• ••••• ••• •• ....... . • •e •••••• •••• ••••• • S. Karger Medical and Scientific Publishers Basel· Freiburg Paris· London NewYork· NewDelhi Bangkok . Singapore Tokyo . Sydney Supplement Issue Included in subscription European Urology (ISSN 0302-28381, Vol. 21, Suppl. 1 (1992) Editor: C.C. Schul man, Brussels .Edito1r:. Franeo Di Silverio, Rome Proceedings of the 2nd Mediterranean Congress of Urology arkers in Urology Rome, July 3-6,199 An extensive survey of the diagnostic and prognostic roles of tumor markers. Beta-Human Chorionic Gonadotropin and AIpha-Fetoprotein in Central and Peripheral Venous Blood of Patients with Testicular Tumors Kidney Tumors Contents Bladder Tumors Javadpour, N.,' Guirguis, R: Tumor Collage- nase-Stimulating Factor and Tumor Autocrine Motility Factor as Tumor Markers in Bladder Cancer· An Update· Sanchez-Fernandez de Sevilla, C.; MorelI, L.; Gi/-Salam, M. et a/.: Morphometric and Immunohistochemical Characterization of Bladder Carcinoma in situ and Its Preneoplastic Lesions . Schmidt, A.;Bub, P.;Rüther, U. etal.:Tissue Polypeptide Antigen for Monitoring of Ad- vanced Bladder Cancer after MVEC Chemotherapy . Romero, J.; Ales, L.; Mal/offe, C. et a/: BlooderWash Cytology and Flow Cytometryfor the Diagnosis of Transitional Cell Carcinoma ofthe Urinary Bladder . Sanchez-Fernandez de Sevilla, M. c.; Gil-Salom, M.; PerezBacete, M. et al: DNA-Ploidy, MorphometricStereological and P-Glycoprotein Study of Superficiaf Bladder Carcinomas . Di Silverio, F.; von He/and, M.; Oe Berardinis, E. et a/: ~r!?gnostjc Role of Flow Cytometry in Superflclal BladderCancer· Saracino, G.A.;Ditonno, P.; Disabato, G. et al.: Prediction of Recurrence and Progression in Primary Superficial Bladder Cancer with DNA Flow Cytometry . Marandofa, P.; LardennOiS, B.; Pfoton, D. et af: A New MarkerforEarly Detection and Indicator of Progression of Cancer of the Bladder. Preliminary Results with Ag-NOR Index in 38 Cases of Superficial Bladder Cancer Testicular Tumors Javadpour, N.: Current Status of Tumor Markers in Testicular Cancer. A Practical Review . Zenico, T.; Zoli, M.; Fiori, M. et al.: Eighth International Natural Killer Cell Workshop and First Meeting of the Society for Naturallmmunity Uzard, G.; Roignot, P.; Dusserre-Guion, L er a/.:Characterization of Seven Kidney Tumors by Flow Cytometry: Analysis of Cell Cycle, DNA Content and P-Glycoprotein Expression . DiSilverio, F.;Gaffucci, M;Flammia, G.P. et al.:Biological and Clinicallmplication ofCellular DNA Content in Renal Cell Carcinomas . Corrado, F.; Mannini, 0.; Ferri, C. et a/.: The Prognostic Significance of DNA Ploidy Pattern in Transitional Cell Cancer of the Renal Pelvis and Ureter: Contil).uing Follow-Up Dönmez, T.; Ka/e, M; Ozyürek, Y. et al.: Erythrocyte Sedimentation Rates in Patients with Renal Cell Carcinoma . Trombetta, C.; Berretta, A.; Siracusano, S. et a/: Evaluation of Hematochemical Parameters and Renal Echography after ESWL Veneziano, L; D'Angefo, A.R.;Burrai, L eta!: DNA Markers in Diagnosis of Adult Dominant Polycystic Kidney Disease Prostatic Carcinoma Schalken, J.A.; Debruyne, F.MJ.: Identification of New Prostate Cancer Progression Markers by Differential Hybridization Analysis de Matteis, A.: Tissue Markers in the Diagnosis and Prognosis of Prostatic Carcinoma Marandofa, P.; Lardennois, 8.; Ploton, D. et al: Nucleolar Organizer Regions: Preliminary Results of the Clinical Use of a New Marker for Prostatic Carcinoma (40 Cases) . Cfar-Blanch, F.; Morell-Quadreny, L; Fenoffosa-Entrena, B. et a/.: Correlation between Serum Values of Prostatic Acid Phosphatase and Morphometric Analysis in the Cytologic Diagnosis of Prostatic Carcinoma . Di Si/verio, F.; D'Eramo, G.; Flammia, GP. et al.: New Ultrasensitive Assay Development by Using Monoclonal Antibodies for Detecting Prostate-Specific Antigen . Romics, f.; Ga/amb, L.: Changes in Prostate-Specific Antigen and Prostatic Acid Phosphatase Concentration following Prostatic Examination in Benign Prostatic Hypertrophy and Prostate Cancer Patients . Puppo, P.; Perachino, M; Ricciotti, G. et a/.: Comparison between Digital Rectal Examination, Prostate-Speciflc Antigen and Transrectal Ultrasound in Symptomatic Patients. Results on 141 Cases . Di Silverio, F.; D'Eramo, G.; Caponera, Met al.:The Prognostic Value of DNA Content in Patients with Prostatic Carcinoma . Zanetti, G.; Trinchieri, A.; Dei Nero, A. et al: Prognostic Significance of ProstateSpecific Antigen in Endocrine Treatment for Prostatic Carcinoma . Zatton;, F.; Piazza, R.; V~anello, R. ~taf.:Preoperativeand Postoperative Evaluation of Prostate-Specific Antigen i~ Localized Prostatic Cancer Treated by Radlcal Pros!atectomy . Marcelfini, M.; DeCarli, P.;Abbollto,MR. et al.:Serum Osteocalcin in Monitoring Bone Metastases in Advanced Prostatic Cancer . Curatofo, c.; Ludovico, G.M; Correa!e, M et al.: Advanced Prostate Cancer Follow-Up with Prostate-Specific Antigen, Prostatic Acid Phosphatase, Osteocalcin and Bone Isoenzyme of Alkaline Phosphatase ..................................... I I I I Molecular and Cellular Aspects of Natural Killer Cell T riggering and Signalling October 4-6, 1992 St. Petersburg Beach, FL,USA I Benign Prostatic Hypertrophy Omacini, S.; Mione, R.; Barichelfo, M et al.: Relationship between Prostatic Acid Phosphatase and Prostate-Specific Antigen Serum Levels and Prostatic Volume in Benign Prostate Hyperplasia. Pitfall on Tumor Markers Assessrnent in Primary Prostatic Cancer? . ~im~ek, U.; Kutlu, S.; Yava.~9aoglu I. et al.: Seasonal Variation of Prostatic Acid Phosphate and Prostate-Specific Antigen in Patients without Prostatic Malignancy Fields oi Interest Urology,Oncology Markers in Urology Proceedings ofthe 2nd Mediterranean Congress of Urology Rome, July 3-6, 1991 'European Urology', Vol. 21, Suppl. 1 (1992) Editor: Di Silverio, F. (Rome) IV + 116 p., 62 fig., 54 tab., soft cover, 1992 SFe. 42.- f DM 50.- f f 18.30 f US$ 33.75 Prices subject to change US $ price for USA, f price for UK, DM price for FRG only ISBN 3-8055-5612-8 KARGER KAR.GER. Abstract Editors Eva Lotzova, Hauston, TX, USA Julie Y Djeu, Tampa, FL, USA John C Ruckdeschel, Tampa, FL, USA Q Contents Eighth International Natural Killer Cell Workshop and First Meeting of the Society for Naturallmmunity .............................................................................. Generously supported by .. .................. .. ................................................................................................. H. Lee Moffitt Cancer Center & Research Institute U niversity of South Florida ••••••••••.•••••••••• .................................................................................................. Session I Abstracts Genetics Institute Hoffmann-La-Roche Inc. Abstracts No. 1-34 (Invited Speakers: 1-5) Sandoz Corporation ............... NK Cells in Infectious Disease and Cancer 241 ....................................................................................................... . Session 11 ~~------------------------------~258 35-63 (lnvited Speakers: 35-40) NK-Related Genes: Expression and Function ·········································S~~~i·~~·III· 64-76 (Invited Speakers: 64-66) .............................................................. NK Cells and Integrin/Adhesion Molecules 273 ............................................................................................................ :........ .. Session IV ..................................... S. Karger Medical and Scientific Publishers Basel· Freiburg . Paris. London NewYork· New Delhi· Bangkok Singapore . Tokyo . Sydney .................................... . .................................... . Drug Dosage The authors and the publisher have exerted every cffon. to enSUTe that drug selection and dosage set forth in this text are in aeeord with eurrent recommeudations and praetiee at the time of publicatioll. However, in view of ongoing research, changes in government regulations, and thc eonstant fiow of info=ation relating to drug therapy and drug reaction5, the reader i5 urged to check the paekage insert for eaeh drug for any change in indications and dosage and for added warnings and precautiOllS. This is partieularly impOitant when the recommended agent is a new and/or infrequently employed drug. All rights reserved. No part of this publieation may be translated iuto other languages, reproduced or utiJized in any fonn or by any means, electronic or mechanieal, inc1uding photocopying, recording, microcopying, or by any infonnation storage and retrieval system, without pennission in writing from the publisher or, in the case of phOlocopying, direet payment of a speeified fee to the Copyright Clcaranee Center (sec 'Infor_ mation for Readers and Subscribers'). © Copyright 1992 by S. Karger AG, P.O. Box, CH-4009 Basel (Switlerland) Printed in Switzerland on acid-free paper by Thür AG Offsetdruck, Pratteln ISBN 3-8055-5690-X 77-107 (Invited Speakers: 77-80) NK Cells and Signal Transduction 279 ....................................................................................................................... Session V 108-138 (Invited Speakers: 108-110) NK Cells and Cytokines '" ................................................................................................................ 295 ~';3 Author Index 238 VIIIth Tut. NK Cell Workshop 239 Q Contents Eighth International Natural Killer Cell Workshop and First Meeting of the Society for Naturallmmunity .............................................................................. Generously supported by .. .................. .. ................................................................................................. H. Lee Moffitt Cancer Center & Research Institute U niversity of South Florida ••••••••••.•••••••••• .................................................................................................. Session I Abstracts Genetics Institute Hoffmann-La-Roche Inc. Abstracts No. 1-34 (Invited Speakers: 1-5) Sandoz Corporation ............... NK Cells in Infectious Disease and Cancer 241 ....................................................................................................... . Session 11 ~~------------------------------~258 35-63 (lnvited Speakers: 35-40) NK-Related Genes: Expression and Function ·········································S~~~i·~~·III· 64-76 (Invited Speakers: 64-66) .............................................................. NK Cells and Integrin/Adhesion Molecules 273 ............................................................................................................ :........ .. Session IV ..................................... S. Karger Medical and Scientific Publishers Basel· Freiburg . Paris. London NewYork· New Delhi· Bangkok Singapore . Tokyo . Sydney .................................... . .................................... . Drug Dosage The authors and the publisher have exerted every cffon. to enSUTe that drug selection and dosage set forth in this text are in aeeord with eurrent recommeudations and praetiee at the time of publicatioll. However, in view of ongoing research, changes in government regulations, and thc eonstant fiow of info=ation relating to drug therapy and drug reaction5, the reader i5 urged to check the paekage insert for eaeh drug for any change in indications and dosage and for added warnings and precautiOllS. This is partieularly impOitant when the recommended agent is a new and/or infrequently employed drug. All rights reserved. No part of this publieation may be translated iuto other languages, reproduced or utiJized in any fonn or by any means, electronic or mechanieal, inc1uding photocopying, recording, microcopying, or by any infonnation storage and retrieval system, without pennission in writing from the publisher or, in the case of phOlocopying, direet payment of a speeified fee to the Copyright Clcaranee Center (sec 'Infor_ mation for Readers and Subscribers'). © Copyright 1992 by S. Karger AG, P.O. Box, CH-4009 Basel (Switlerland) Printed in Switzerland on acid-free paper by Thür AG Offsetdruck, Pratteln ISBN 3-8055-5690-X 77-107 (Invited Speakers: 77-80) NK Cells and Signal Transduction 279 ....................................................................................................................... Session V 108-138 (Invited Speakers: 108-110) NK Cells and Cytokines '" ................................................................................................................ 295 ~';3 Author Index 238 VIIIth Tut. NK Cell Workshop 239 Abstracts ..................................... Symposium Chairpersons Julie Y. Djeu, Tampa, FL, USA lohn C. Ruckdeschel, Tampa, FL, USA i~~·i~~ds~~~k~~~~~d·ci.~i;~~;~~~~······················ ......... . Session I Paolo Allavena, MD Hugh F. Pross, MD, PhD Milan, ltaIy Paul l. Anderson, MD, PhD Boston, MA, USA D. Kay Blanchard, PhD Tampa, FL, USA Ronald B. Herberman, MD Benjamin Bonavida, PhD Los Angeles, CA, USA Sidney Golub, PhD 1erome Ritz, MD Rika Ishikawa, Helen C Su, Christine A. Biron Boston, MA, USA Division of Biology and Medicine, Brown University, Providence, R.I., USA John C. Ruckdeschel, MD Rome, Italy Julie Y. Djeu, PhD Tampa, FL, USA Los Angeles, CA, USA Perugia, Italy Angela Santoni, PhD Ocnver, CO, USA Prcsident 1 Regulation of Splenie Natural Killer Cell Responses During Virallnfections Tampa, FL, USA lames L. Cook, MD Eva Lotzova, PhD ................. David Raulet, PhD Carlo Riccardi, MD, PhD Providence, RI, USA International Society for Naturallmmunity Kingston, Ont., Canada Berkeley, CA, USA Christine Biron, PhD Öffi~~~~~f·ih~·················· .. ....................................................... . William E. Seaman, MD San Francisco, CA, USA Paul M. Sondel, MD. PhD Vice President Ronald B. Herberman MD Tuomo Timonen, MD Pittsburgh, PA, USA Secretary leffrey P. Houchins, PhO ' Minneapolis, MI, USA Klas Karre, MD, PhD Stockholm, Sweden Ralf Kiessling, MD, PhD Stockholm, Sweden Eva Klein, MD, PhD StockhoIm, Sweden Vinay Kumar, MD Madison, WI, USA Walter Storkus, PhD Durharn, N C, USA Tuomo Timonen, MD Helsinki, Finland Giorgio Trinchieri, MD Philadelphia, PA, USA Rayrnond M. Welsh, PhD Worchester, MA, USA Stanley Wolf, PhD Cambridge, MA, USA DaUas, TX, USA Lewis L. Lanier, PhD I .1 I PaIo Alto, CA, USA Paul l. Leibson, MD, PhD Rochester, MN, USA Eva Lotzova, PhO Houston, TX, USA Albert Mantovani, MD Milan, Italy Lorenzo Moretta, MD, PhD Genova, Italy John R. Ortaldo, PhD Frederick, MD, USA Eckhard R. Podack, MD, PhD Miami, FL, USA Natural killer (NK) cell activation and pro1ifera~ tion peak on day 3 and subside by day 5-7 post-infection of mice with either lymphocytic choriomeningitis virus (LCMV) or murine cytomegaloviurs (MCMV). Our laboratory has been characterizing the positive and negative regulation of these NK ceIl responses. Cytokine studies have demonstrated that interferons (IFN) are potent positive regulators whereas transforrning growth factors-ß (TGF-ß) are potent negative regulators of tbe in vivo NK cell responses. Tbe work presented hefe was undertaken to evaluate cellular interactions contributing to in vivo NK cell regulation. Histological examination of seetions isolated from LCMV-infected mice revealed dramatic changes in splenie architecture at firnes coinciding with IFN production and NK cell activation and proliferation; white pulp areas were increased but leukocyte concentrations in red pulp areas were decreased. To evaluate IFN expression and tbe contribution of IFN to the induction of the observed morphological changes, C57BLl6 mice were treated with the chemical inducer ofIFN, poly-inosinic-cytidylic cid (poly I:C). As early as 3 h after poly I:C administration, biologically active IFN was present in spleen and serum. Neutralization studies and Northern blot analyses demonstrated that IFN-ß was preferentially induced. Histological examination revealed poly I:C-induced splenic changes com~ parable to those observed during infection, i.e. dramatic increases in splenic white pulp area and de~ creases in red pulp leukocytes. The changes were observed at 6-36 h post-treatment. Spleen weights and splenic leukocyte yields remained relatively constant. Cell transfer experiments with Dil~labeled ceHs dem~ onstrated that poly I:C enhanced the accumulation of ceHs migrating from blood to white pulp regions. The changes in splenie leukocyte distribution were shown to be a result of IFN induction as: (1) treatment with anti-IFN antibodies inhibited the poly I:C~induced changes, and (2) administration of purified IFN~ß induced similar changes. In situ hybridization and immunohistochernical staining demonstrated that, at early times post~treatment, cells expressing high levels of IFN~ß were found in vasculature and dispersed in red pulp regions. By later times post~treatment, the intensely positive ceHs were localized deep within white pulp regions and in perivascular spaces. The results indicate that IFN induces a profound migration ofleukocytes into white pulp regions ofthe spleen. The data also suggest that a rninor sub~population ofleuko~ cytes is an especially potent and early producer ofIFN~ ß. Studies are underway to characterize the spienic dis~ tribution ofNK cells during the IFN-induced redistri~ bution and to determine how the architectural changes may contribute to the regulation ofNK cell responses during viral infections. 2 Natural Killer CelljNeutrophil Interactions for Resistance against Opportunistic Fungi Julie Y. Djeu, Sheng Wei, Carla Palma, ~ Antonio Cassone, D. Kay Blanchard Department of Medical Microbiology and Immunology, H. Lee Moffitt Cancer Center and Research Institute, University of South Florida College ofMedicine, Tampa, Fla., USA Candida albicans is an opportunistic fungal patho~ gen that causes persistent infection in immunocomprised hosts. To define if normal resistance might be controlled by natural killer cells in concert with neutro~ phils, we isolated large granular lymphocytes (LGL) from human peripheral blood by Percon gradients and neutrophils after separation from mononuclear cells with Ficoll-Hypaque gradients. Human LGL were found not to be able 10 inhibit Candida growth in a 240 VIIIth Int. NK Cell Workshop 241 NatImmun ISSN [0[8-89[6 NAIMEL [[(5) 237-3[6 (1992) Naturatyl •mmunl Eighth International Natural Killer Cell Workshop and First Meeting of the Society for Naturallmmunity MOlecular and Cellular Aspecls 01 Natural Killer Cell Triggering and Signalling ........... ........... ........... ........... ........... ........... ........... ........... ........... Abstracts 241 Author Index 313 11