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control. This variability for U-937, when induced to differentiate, has been noted before by Koren et al. (1979) using MLC supernatants to induce differentiation and concomitant increase in Fc receptor expression and activity in ADCC. A similar variability has been found also in differentiation experiments with the K-562 and HL-60 lines (Andersson, personal cummunication; Nilsson, unpublished work). The functional assays alway gave reproducible results and leave room for no other interpretation than that the U-937 cells, after exposure to TP A or MLC supernatant, acquire the presumed typieal functional features of mature monocytesmacrophages (increased capacity for phagocytosis, lysozyme secretion, and activity as effector cell in ADCC). We therefore suggest that the surface changes simultaneously recorded are associated with a change in the stage of monocytic differentiation of U-937 cells and therefore useful markers in studies of monoblast-macrophage differentiation. Of partieular interest seems to be the possibility of using some of the major SGP, as detected by tritiated sodum borohydride labeling, as differentiation markers. The major SGP hallmarks for mature monocytie cells seems to be the 180K, 140K, and 85K SGP. All these are strongly labeled both in blood monocytes and TPA stimulated U-937 cells. Specific changes in the SGP compositions have previously been found in the HL-60 (Gahmberg et al. 1979) and in the K-562 cell lines (Nilsson et al. 1980a) during induced differentiation and thus further strenthens the usefulness of certain SGP as differentiation markers. It is not yet c1ear whether "terimal" differentiation occurs at all in the U -937. Neither is the concomitant change in growth and DNA synthesis fully analyzed. Our studies so far indicate that at least partial inhibition of growth and DNA synthesis accompany TPA treatment and the induced phenotypic alterations. It is thus possible that TP A may induce a cell cyc1e block similar to what has been described by Rovera et al. (1979) for HL-60 cells. D. Concluding Remarks We conc1ude that the human histiocytic lymphoma cellline U -937 may be induced by TP A or MLC supernatant to undergo morphologie and functional differentiation in vitro which resembles the stepwise maturation events described for normal monocytie cells. The cellline may, therefore, be useful as a model for controlled in vitro studies of various aspects of monocytic differentiation. The observed specific changes in the composition of the major SGP suggest that such GP might be useful differentiation markers. Acknowledgements This study was supported by the Swedish Cancer Society and the Fortia Fund. The skillful technical assistance of Mrs. Ingela Stadenberg is gratefully acknowledged. References Andersson LC, Jokinen M, Gahmberg CG (1979) Induction of erythroid differentiation in the human leukaemia cell line K-562. Nature 278:364-365 - Collins SJ, Gallo RC, Gallagher RE (1977) Continuous growth and differentiation of human myeloid leukemie cells in suspension culture. Nature 270:347-349 - Collins SJ, Ruscetti FW, Gallagher RE, Gallo RC (1978) Terminal differentiation of human promyelocytic leukemia cells induced by dimethyl sulfoxide and other polar compounds. Proc Natl Acad Sci USA 75:2458-2462-ForsbeckK(to be published) - Gahmberg CG, Hakomori S (1973) External labeling of cell surface galactose and galactosamine in glycolipid and glycoprotein of human erythrocytes. J Biol Chem 248: 4311-4317 - Gahmberg CG, Nilsson K, Andersson LC (1979) Specifie changes in the surface glycoprotein pattern of human promyelocytic leukemic cell line HL-60 during morphologie and functional differentiation. ProcNatl AcadSciUSA 76:4087-4091-Gallagher R, Collins S, Trujillo J, McCredie K, Ahearn M, Tsai S, Metzgar R, Aulakh G, Ting R, Ruscetti F, Gallo F (1979) Characterization of the continuous differentiating myeloid cell line (HL-60) from a patient with acute promyelocytic leukemia. Blood 54:713-733 - Gidlund M. Örn A, Pattengale P, Wigzell H, Jansson M, Nil~"'lll1 K (to be published) Induction of differentiation in two human tumor cell lines is paralleled by a decrease in NK susceptibility. Nature - Huber C, Sundström CC, Nilsson K, Wigzell H (1976) Surface receptors on human haematopoietie cell lines. Clin Exp Immunol 25:367-376 - Huberman E, Callaham MF (1979) Induction of terminal differentiation in human promyelocytic leukemia cells by tumor-promoting agents. Proc Natl Acad Sei USA 76:1293-1296 - Klareskog L, Trägärdh L, Lindhlom JB, Peterson 220
PA (1978) Reactivity of a rabbit antiserum against highly purified HLA-DR antigens. Scand J Immunol 7: 199-208 - Koren HS, Anderson SJ, Larrick JW (1979) In vitro activation of a human macrophagelike cell line. Nature 279:328-331 - Minowada J, Sgawa K, Lok MS, Kubonishi I, Nakazawa S, Tatsumi E, Ohnuma T, Goldblum N (1980) A model of lymphoid-myeloid cell differentiation based on the study of marker profiles of 50 human leukemia celliines. In: Serrou B, Rosenfeld C (eds) International Symposium on new trends in human immunology and cancer immunotherapy. Doin editeurs, Paris pp 180-199 - Nilsson K (1978) Established human lymphoid celliines as models for B-Imyphocyte differentiation. Human lymphocyte differentiation. Its application to cancer. In: Serrou B, Rosenfeld C (eds) INSERM Symposium No 8. Eisevieri North Holland Biomedical Press, pp 307-317 - Nilsson K (1979) The nature oflymphoid celllines and their relationship to EB virus. In: Epstein MA, Achong BG (eds) The Epstein-Barr-virus. Springer, Heidelberg - Nilsson K, Evrin PE, Welsh KI (1974) Production of B 2 -microglobulin by normal and malignant human cell lines and peripherallymphocytes. Transplant Rev 21: 53-84 - Nilsson K, Andersson C, Gahmberg CG, Wigzell H (1977) Surface glycoprotein patterns of normal and malignant human lymphoid cells. H. B-cells, B-blasts and Epstein-Barr virus (EBV) positive and negative B-Iymphoid cell lines. Int J Cancer 20:708-718 - Nilsson K, Andersson LC, Gahmberg CG, Forsbeck K (1980a) Differentiation in vitro of human leukemia and lymphoma cell lines. In: Serrou B, Rosenfeld C (eds) International Symposium on new trends in human immunology and cancer immunotherapy. Doin editeurs, Paris pp 271-282 - Nilsson K, Andersson LC, Gahmberg CG (1980b) Cell surface characteristics of human histiocytic lymphoma lines. 1. Surface glycoprotein patterns. Leuk Res 4:271-277 - Nilsson K, Kimura A, Klareskog L, Andersson LC, Gahmberg CG, Hammarström S, Wigzell H (to be published) Cell surface characteristics of histiocytic lymphoma cell lines. H. Expression of Helix Pomatia A-hemagglutinin binding surface glycoproteins and Ia-like antigens. Leuk Res - Pertoft H, Johnsson A, Wärmegard B, Seljelid R (1980) Separation of human monocytes on density gradients of Percoll R • J Immunol Methods 33:221-229 - Ralph P, Moore MAS, Nilsson K (1976) Lysozyme synthesis by established human and murine histiocytic lymphoma cell lines. J Exp Med 143: 1528-1533 - Rovera G, Santoli D, Damsky C (1979) Human promyelocytic leukemia cells in culture differentiate into macrophage-like cells when treated with a phorbol diester. Proc Natl Acad Sei USA 76:2779-2783 - Rutherford TR, Clegg JB, Weatherall DJ (1979) K-562 human leukemic cells synthesize embryonic haemoglobin in response to haemin. Nature 280: 164-165 - Sjöberg 0, Inganäs M (1979) Detection of Fc receptor-bearing lymphocytes by using IgG-coated latex particles. Scand J Immunol 9:547-552 - Sundström C, Nilsson K (1976) Establishment and characterization of a human histiocytic lymphoma cell line (U-937). Int J Cancer 17:565-577 - Sundström C, Nilsson K (1977) Cytochemical profile of human haematopoietic biopsy cells and derived celllines. Br J Haematol 37:489-501 - Venge P, Hällgren R, Stalenheim G, Olsson I (1979) Effect of serum and cations on the selective release of granular proteins from human neutrofils during phagocytosis Scand J Haematol 22: 317-326 - Zech L, Haglund U, Nilsson K3 Klein G (1976) Characteristic chromosomal abnormalities in biopsies and lymphoid cell lines from patients with Burkitt and non-Burkitt lymphomas. Int J Cancer 17:47-56 221
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Haematology and Blood Transfusion 2
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Dr. Rolf Neth, Universitäts-Kinder
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Participants of the Meeting Aaronso
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Kurth, R, Friedrich-Miescher-Labora
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Wilsede Scholarship Holders (Grante
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Preface Gut ist eine Lehrart, wo ma
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Personal and scientific discussion
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Acknowledgement We should like to t
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Wilsede, June 21 1978 Memorial Trib
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limiting benign lymphoproliferative
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this most unlikely, however (for re
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longer subject to the same control
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Bregula U, Wiener F, Harris H (1971
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fresh lymph node biopsies from ten
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Fig. 3. Binucleate mitosis in an ob
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y Fig. 4. Schematic diagram of post
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than that among patients with Stage
Page 35 and 36:
Tests of binding affinity, agglutin
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N Engl J Med 297: 963-968 - Green I
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Clinical Aspects
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"ring chromosome". "Mar" is marker,
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191 chromosomally abnormal patients
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tumors of both African and non-Afri
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Haematology and Blood Transfusion V
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Retrospective group 26/93 evolved l
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Treatment
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advantage in terms of duration of f
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leukaemia. An analysis of 168 patie
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11. Treatment Program Chemotherapy
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efractory congestive heart failure
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period (Sequence II) was gene rally
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children with a multiple drug proto
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DAYS 1 5 10 15 20 25 30 35 , I I I
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Biologically Drug Outcome fit" sens
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may counterbalance the potential be
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Ht (0--0) 50 40 30 20 10 0 Platelet
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10 7 ,-----------------------------
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11. Haematological and Biochemical
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0\ 0\ INTERFERON ... 10 3 rl E "'
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("pre-B" phenotype) has been descri
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human bone marrow cells exhibit the
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10 9.,0 MBKCC .. .,4 B prot:oool 1'
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demann W, Büehner T, Arlin Z, Gee
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-...l 00 a-tLDRENS CAt«:ER S TU>Y
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prognostic characteristics under in
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significantly higher in HR} (14.5%,
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normal or elevated immunoglobulin l
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References Andreeff M, Darzynkiewic
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R GROUP 1 ( 1970 - 1971 ) 17 PTS. R
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Table 3. Influence of initial featu
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LIJ (f) a.. < -1 LIJ Q: u. 0 >- I-
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me nt indicated that additional the
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42:2123-2134 - Chessells JM, Cornbl
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Baum et al. 1979). This study was b
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1. 0 '--'1--" 0.9 e: o .- VI VI E C
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e: o e: 1. 0 ,.--...-- 1'"'\ ......
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In conclusion, we can state that th
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Haematology and Blood Transfnsion V
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INDUCTION VCR + PRED + ASNASE (wk 3
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SCHED.INT 1 MTX • ! Adria MTX •
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~ looh---------ooooc>----o---c>----
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Consoll- Irra .tlon t) .tlon Indu
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Highrisk Standard risk Table 1. Cli
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Cumulo/ive comp/el9 remission 1.0 .
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10° 8 = 6 ö 4 Non T Cell .~ :ö
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% SURVIVAL 100 ~ ~II 0 80 60 40 - -
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a) Percentage of donor cell mitoses
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Table 5. Results of bone marrow tra
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...... w N Table 7. Clinical result
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agent had to be added and that in t
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C. Chronic Myelogenous Leukemia The
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Patients with a suitable donor rece
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No. Recurrent Leukaemia Other death
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followed by dialysis against isoton
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HS, HL- Heme >_ 40 0 HS I ;:. =====
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knowing at present. These genes may
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esistance to antifolates. In Vitro
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a DNA probe specific for the gene t
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translocation between chromosomes 9
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Table 1. Subdivision of 1827 Myelo-
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NORMAL CELL ®
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some change of the primary type, in
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Page 181 and 182: F. Transformation of Mouse Bone Mar
Page 183 and 184: Haematology and Blood Transfusion V
Page 185 and 186: were carried out with 3H-MTX in the
Page 189 and 190: the lysozyme cDNA prepared from ovi
Page 193 and 194: et al. 1976). The BJAB cellline in
Page 195 and 196: dalton bands corresponding to light
Page 197 and 198: 1979). The EBV-carrying cell lines
Page 199 and 200: producer lines (DAUDI and P3HR-1),
Page 201 and 202: G, Giovanella B, Westman A, Stehlin
Page 205 and 206: Dc;bt CT + i J.I9 Raji; 1. i .. 100
Page 207 and 208: c. Discussion During infectious mon
Page 211 and 212: C. Nonepisomal Viral DNA We have us
Page 213 and 214: A 260 3.0 A B 1670 70 N2 2.0 c: E .
Page 215 and 216: vivo. Nature 260:302-306 - Kirk JTO
Page 217 and 218: Fig. 1. a Polyacrylamide gelelectro
Page 221 and 222: 1979). The lymphocyte subpopulation
Page 223 and 224: lysin 0 antigens are found, and mix
Page 225 and 226: Pope JH (1978) Long-term T cell-med
Page 227 and 228: Haematology and Blood Transfnsion V
Page 229 and 230: Charaeteristie Morphologie maturati
Page 231: after TPA-induction (Table 3). The
Page 235 and 236: Blood Monocyte. B lood Monocytes 1-
Page 239 and 240: and nonhistone proteins can serve a
Page 243 and 244: The findings of the evaluation of s
Page 245 and 246: Fig. 3. Tumor grawth of L 428 cells
Page 247 and 248: Cell biological and Immunological A
Page 249 and 250: consideration. Sanel (1973) obtaine
Page 251 and 252: endotoxin serum, were used. A parti
Page 253 and 254: monocytic leukemia cell line in cul
Page 255 and 256: B. Isolation, Characterization and
Page 259 and 260: don al hemopathies generally displa
Page 261 and 262: nitors. Blood Cells 6:595-607 - Min
Page 263 and 264: \I) ....I ....I IU Jl 200 r 100 90
Page 265 and 266: their haemopoietic cells' ability t
Page 267 and 268: normal normal ALL ALL ALL persons p
Page 269 and 270: 64.5 { V)
Page 271 and 272: References Biermann E, Neth R, Gros
Page 273 and 274: ehambers, the growth pattern observ
Page 275 and 276: References Anderssen LC, 10kinen M,
Page 277 and 278: REH CELL UNE TO CALLb~Ö ~q~ V.M. c
Page 281 and 282: the macrophage series in which the
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Table 1. Production of factor depen
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Table 1. Characteristics of the adh
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Fig. 3. A human marrow culture at 6
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300 250 • HYPERPROLIFERATIVE PATT
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Fig. 9. Nonadherent population from
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The cobblestone areas were often no
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L (1976) Induction of colony format
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B. Materials and Methods J. Tissue
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Fig. 2. Ultrastructural appearance
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Page 307 and 308:
Page 309 and 310:
Table 1. Monoclonal antibody reacti
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al. 1979; Janossy et al. 1979) is e
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to which this is an exact replica o
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inger JL (1976) Distribution of la-
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I region antigens were found to be
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have been reported to be present on
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V. FunctionalAssays Assays for PHA
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Functional studies of UCHT1 separat
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40 ,...... (5 L.. C o u 30 .9 ~ .~
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with immunohistochemieal methods (L
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can be dissected by cloning. Utiliz
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Table 1. Origin and marker profile
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complete identity of gp 100 from no
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Table 1. Reaction of single anti se
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media. Following 24-h incubation, c
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nonleukemic eells (Greaves 1979). L
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Fig. 2. Cytocentrifuged smears of b
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Modification of amino-groups of hum
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disturb this balance in the directi
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The majority of human blood lymphoc
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of the EBV infected B cells. Howeve
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and immunoglobulins. J Immunol 120:
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" K 10 • j ~ ALL RNlL AL wtfh les
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tion akuter Leukämiezellen in "spo
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D. Results and Discussion J. Acute
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selectively responsive to different
Page 371 and 372:
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l1J ~ 100 ~ Q. ::) l1J Z 0 ~ z >- .
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Table 2. Growth inhibition of S49 e
Page 377 and 378:
Reverse Infectious ASC/2X1Q6 transc
Page 379 and 380:
Page 381 and 382:
munized animals to 1316 tumor cells
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Haematology and Blood Transfnsion V
Page 385 and 386:
Fig. 3. Expression of retroviral gp
Page 387 and 388:
pg70. J Exp Med 143: 151-166 - McGr
Page 389 and 390:
Table 1. Expression of tumor antige
Page 391 and 392:
Virological and Molecularbiological
Page 393 and 394:
Table 1. Oncogenic properties of re
Page 395 and 396:
also Fig. 1). It followed that the
Page 397 and 398:
whether this sequence is related to
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zed in infected cells argue that th
Page 401 and 402:
a specific viral transforming prote
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detect viral RNA as the only charac
Page 405 and 406:
Eisen H (1980) Myeloproliferate vir
Page 407 and 408:
p,60- -34K - 1 2 3 4 Fig. 1. In vit
Page 409 and 410:
.. p - • a'T ... I .t'l Fig. 4. D
Page 411 and 412:
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Fig. 2. Photomicrographs of NY68 in
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DEAE (o(lJmn 'liI GI -2 2 o e s 1
Page 417 and 418:
vity was deterrnined. For endogenou
Page 419 and 420:
pr 180 - - - P 12/15 - A B c D E F
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85,- 66- -27 - -66 40- 27- -1'9 19-
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= 0.5 o E Q. o ILI 0.4 (J) « ILI .
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Table 1. Oncogenic potential of avi
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100 III GI c: o "8 80 > w
Page 431 and 432:
Expt. No. Infecting virus Proportio
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Haematology and Blood 'fransfusion
Page 435 and 436:
sequences, provided its gag portion
Page 437 and 438:
77:3009-3013 - Hu SSF, Moscoviei C,
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RI 2.2 md and Hind III 2.6 md leuke
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Page 443 and 444:
RELATIONSHIP OF ENDOGENOUS AND EXOG
Page 445 and 446:
E ........ E Cl. U E :::l .... Q) (
Page 447 and 448:
References Astrin S (1978) Endogeno
Page 449 and 450:
the same animal were examined (e.g.
Page 451 and 452:
I) 'IQ a \0 - CL -- Fig. 2. Restrie
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~ ..................... ~ Cell 3' 5
Page 455 and 456:
a :Sa,C! + . ~ 111 i' ( " '~ .J. b
Page 457 and 458:
Table 1 Sampie Tissue TS fragment"
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a b Sac I / rep ._-_.-_ K J nl rep
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Haematology and Blood 'fiansfusion
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Osteopetrosis and osteosarcomas occ
Page 465 and 466:
Lymphoma cellline Table 1. T and B
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Table 2. In vivo growth and oneogen
Page 469 and 470:
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Table 1. Transforming aetivity of c
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Table 3. Transformation aetivity of
Page 475 and 476:
- Shoemaker C, Goff S, Gilboa E, Pa
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indieate a shifting of target eell
Page 479 and 480:
Table 2. Expression of Jl and Sourc
Page 481 and 482:
Page 483 and 484:
~ i ,..1---------,,':::::::::::::::
Page 485 and 486:
fragment of pBR322 DNA, a 3.0-kbp S
Page 487 and 488:
Mak TW (1979) Proc Natl Acad Sci US
Page 489 and 490:
Table 1. Transformation of 3T3 cell
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inserts in the genome of rapidly tr
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pulations, it seemed likely that th
Page 495 and 496:
contains antigens which react with
Page 497 and 498:
Page 499 and 500:
le of reacting in sensitive radioim
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Page 503 and 504:
gic approach. In: Hiatt HH, Watson
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12 Eco R [ Fig. 1. Hybridization pa
Page 507 and 508:
Page 509 and 510:
10 - '1~ )( -~ S:! E A U I o 1 2
Page 511 and 512:
Haematology and Blood 'fransfusion
Page 513 and 514:
cultures. These cells did not conta
Page 515 and 516:
indication of malignant T-cells in
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Fig. 3. Thin-section electron micro
Page 519 and 520:
Table 3. Lack of detectable related
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J. HTLV Was Present in the Primary
Page 523 and 524:
specific signals into nonspecific s
Page 525 and 526:
Table 2. Distribution of HTLV-relat
Page 527 and 528:
u 10 ~ 20 ~ :c 30 a 40 o Fig. 1. Ki
Page 529 and 530:
Page 531 and 532:
SSV TrS-gp labeled effectively with
Page 533 and 534:
Page 535 and 536:
60 HFF/SSV cDNA CELL RNAs: 0 HF/SSV
Page 537 and 538:
Antisera a Table 1. Immunofluoresce
Page 539 and 540:
Haematology and Blood 'ftansfusion
Page 541 and 542:
y competition RIA yielded virtually
Page 543 and 544:
SiS'V' gp70: ANTIGEN, ANTI BODY, IM
Page 545 and 546:
type-C virus p30 antigen in cells f
Page 547 and 548:
c. Results The fractionated whole-b
Page 549 and 550:
induced antibodies as well as exper
Page 551 and 552:
- Fig. la-f. Retravirus particles p
Page 553 and 554:
eplication of infecting murine leuk
Page 555 and 556:
Page 557 and 558:
immunodeficiency, multic10nal lymph
Page 559 and 560:
Bovine leukemia --, proteins of 499
Page 561 and 562:
Human T- cell - -, characterization
Page 563 and 564:
RNA -, of tumor virus 439 Rous sarc
Page 565 and 566:
Haematology andBlood Transfusion Su
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