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RC, Mannweiler K, Moloney W (eds) In: Modern trends in human leukemia II. Lehmann, Munich pp 169-176 - GrafT, AdeN, BeugH (1978) Temperature-sensitive mutant of avian erythroblastosis virus suggests a block of differentiation as mechanism of leukaemogenesis. Nature 257: 496-501 - Graf T, v. Kirchbach A, Beug H (1979) Mechanism of target cell specificity by defective avian leukemia viruses: a hypothesis. Neth R, Gallo RC, Hofschneider PH, Mannweiler K (eds) In: Modern trends in human leukemia IH. Springer, Berlin Heidelberg New York, pp 429-438 - Graf T, Beug H, Hayman MJ (1980) Target ce11 specificity of defective avian leukemia viruses: hematopoietic target ce11s for a given virus type can be infected but not transformed by strains of a different type. Proc Natl Acad Sei USA 77:389-393 - Graf T, v. Kirchbach A, Beug H (1981) Characterization of the hematopoietic target ce11s of AEV, MC29 and AMV avian leukemia viruses. Exp Ce11 Res 131 :331-343 - Hanafusa H (1977) Cell transformation by RNA tumor viruses. In: Wagner RR, Fraenkel-Conrat H (eds) Comprehensive virology vol 10, Viral gene expression and integration. Plenum, New York, pp 401-483 - Miller RG, Phillips RH (1969) Separation of cells by veloeity sedimentation. J Cell Physiol 73: 191-202 - PertoftH, Laurent TC (1977) Isopycnic separation of cells and organelles by centrifugation in modified silica gradients. In: Catsimpolas N (ed) Methods of ce11 separation. Plenum, New York, pp 25-65 - Roussel M, Saule S, Lagrou C, Rommens C, Beug H, Graf T, Stehelin, D (1979) Defective avian leukemia viruses: three new types of viral oncogenes of ce11ular origin specific for haematopietic ce11 transformation. Nature 281 :452-455 - Stehelin D, Graf T (1978) Avian myelocytomatosis and erythroblastosis viruses lack the transforming gene src of avian sarcoma viruses Cel113:745-750 423
Haematology and Blood 'fransfusion Vol. 26 Modern Trends in Human Leukemia IV Edited by Neth, Gallo, Graf, Mannweiler, Winkler © Springer-Verlag Berlin Heidelberg 1981 PRCII, a Representative of a New Class of A vian Sarcoma Viruses P. K. Vogt, J. C. Neil, C. Moscovici, andM. L. Breitman A. Abstract The Poultry Research Center Virus 1I (PRC II) is a replication-defective avian sarcoma virus with envelope determinants of the A and B subgroups. In nonproducing cells transformed by PRClI the products of the replicative genes gag, pol, and env are not demonstrable, but a single polyprotein of Mr 105,000 (p105) can be detected. P105 contains peptides of the gagproteins p19 and p27 plus transformationspecific sequences. It does not contain peptides of gPr95 env of Pr180gag-pol (with the possible exception of one pol peptide). The transformation-specific sequences of p 1 05 are distinct form those of p100 of avian carcinoma virus MH2, of pllO coded for by avian myelocytoma virus MC29, and of p75 or p40 of avian erythroblastosis virus AEV. They also show no resemblance to p60 src of Rous sarcoma virus. P105 is phosphorylated on a tyrosine residue and has an associated phosphokinase activity. P105 appears to be capable of autophosphorylation and of phosphorylating homologous immunoglobulin. B. Introduction Until recently aB avian sarcoma viruses were thought to have fundamentally the same genetic structure. The investigated strains, chiefly Rous sarcoma virus (RSV) and its relatives, contain an about 1.8-kilobase (kb) insertion at the juncture of the env gene and the C region (Duesberg and Vogt 1970; Wang et al. 1975). This transformation-specific insertion, termed src, was found to be of cellular origin and to code for a protein kin ase of Mr 60,000 with preference for tyrosine as a phosphoacceptor (Stehelin et al. 1976; Spector et al. 1978; Brugge and Erikson 1977 ; Collett and Erikson 1978; Levinson et al. 1978; Hunter and Sefton 1980). In contrast to RSV, avian acute leukemia virus es code for polyproteins that are derived from a gene in which gag sequences at the 5' tenninal part of the genome are fused to transformation-specific, cell-derived sequences in the middle of the genome. The cell-derived sequences form a substitution for replicative information of the gag, pol, and env genes (Bister et al. 1977; Hu et al. 1979; Lai et al. 1979; Sheiness and Bishop 1979; Roussel et al. 1979; Sheiness et al. 1980). As a consequence of this missing information, the acute avian leukemia viruses are replication defective (Ishizaki and Shimizu 1970; Graf 1975; Bister and Vogt 1978; Hu and Vogt 1979). A genome organization similar to that of avian acute leukemia viruses has also been found in Abelson and radiation leukemia virus of mice and in feline sarcoma virus (Witte et al. 1978; Manteuil-Brutlag et al. 1980; Barbacid et al. 1980; Sherr et al. 1980; Van de Yen et al. 1980). Recently a new dass of avian sarcoma virus es has been described which lack src and have a genetic structure related to the avian acute leukemia viruses (Breitman et al. 1981; Hanafusa et al. 1980; Kawai et al. 1980; Lee et al. 1980; Neil et al. 1981). The viruses belonging to this group are Fujinami sarcoma virus (FSV) , Y73, which is arecent field isolate, and PRelL Even though these viruses have transformation-specific sequences which are different from the src of RSV, their transformation-specific proteins bear some intriguing functional resemblance to p60 src • This functional similarity suggests possible common elements in the mechanism of trans- 424
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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
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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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F. Transformation of Mouse Bone Mar
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were carried out with 3H-MTX in the
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the lysozyme cDNA prepared from ovi
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et al. 1976). The BJAB cellline in
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dalton bands corresponding to light
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1979). The EBV-carrying cell lines
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producer lines (DAUDI and P3HR-1),
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G, Giovanella B, Westman A, Stehlin
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Dc;bt CT + i J.I9 Raji; 1. i .. 100
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c. Discussion During infectious mon
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C. Nonepisomal Viral DNA We have us
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A 260 3.0 A B 1670 70 N2 2.0 c: E .
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vivo. Nature 260:302-306 - Kirk JTO
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Fig. 1. a Polyacrylamide gelelectro
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1979). The lymphocyte subpopulation
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lysin 0 antigens are found, and mix
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Pope JH (1978) Long-term T cell-med
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Haematology and Blood Transfnsion V
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Charaeteristie Morphologie maturati
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after TPA-induction (Table 3). The
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PA (1978) Reactivity of a rabbit an
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Blood Monocyte. B lood Monocytes 1-
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and nonhistone proteins can serve a
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The findings of the evaluation of s
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Fig. 3. Tumor grawth of L 428 cells
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Cell biological and Immunological A
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consideration. Sanel (1973) obtaine
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endotoxin serum, were used. A parti
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monocytic leukemia cell line in cul
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B. Isolation, Characterization and
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don al hemopathies generally displa
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nitors. Blood Cells 6:595-607 - Min
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\I) ....I ....I IU Jl 200 r 100 90
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their haemopoietic cells' ability t
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normal normal ALL ALL ALL persons p
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64.5 { V)
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References Biermann E, Neth R, Gros
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ehambers, the growth pattern observ
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References Anderssen LC, 10kinen M,
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REH CELL UNE TO CALLb~Ö ~q~ V.M. c
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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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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
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l1J ~ 100 ~ Q. ::) l1J Z 0 ~ z >- .
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Table 2. Growth inhibition of S49 e
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Reverse Infectious ASC/2X1Q6 transc
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Page 381 and 382: munized animals to 1316 tumor cells
Page 383 and 384: 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
Page 399 and 400: zed in infected cells argue that th
Page 401 and 402: a specific viral transforming prote
Page 403 and 404: 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: Haematology and Blood Transfusion V
Page 413 and 414: Fig. 2. Photomicrographs of NY68 in
Page 415 and 416: 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
Page 421 and 422: 85,- 66- -27 - -66 40- 27- -1'9 19-
Page 425 and 426: = 0.5 o E Q. o ILI 0.4 (J) « ILI .
Page 427 and 428: Table 1. Oncogenic potential of avi
Page 429 and 430: 100 III GI c: o "8 80 > w
Page 431: Expt. No. Infecting virus Proportio
Page 435 and 436: sequences, provided its gag portion
Page 437 and 438: 77:3009-3013 - Hu SSF, Moscoviei C,
Page 439 and 440: RI 2.2 md and Hind III 2.6 md leuke
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
Page 453 and 454: ~ ..................... ~ Cell 3' 5
Page 455 and 456: a :Sa,C! + . ~ 111 i' ( " '~ .J. b
Page 457 and 458: Table 1 Sampie Tissue TS fragment"
Page 459 and 460: a b Sac I / rep ._-_.-_ K J nl rep
Page 461 and 462: Haematology and Blood 'fiansfusion
Page 463 and 464: Osteopetrosis and osteosarcomas occ
Page 465 and 466: Lymphoma cellline Table 1. T and B
Page 467 and 468: Table 2. In vivo growth and oneogen
Page 471 and 472: Table 1. Transforming aetivity of c
Page 473 and 474: Table 3. Transformation aetivity of
Page 475 and 476: - Shoemaker C, Goff S, Gilboa E, Pa
Page 477 and 478: indieate a shifting of target eell
Page 479 and 480: Table 2. Expression of Jl and Sourc
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~ i ,..1---------,,':::::::::::::::
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fragment of pBR322 DNA, a 3.0-kbp S
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Mak TW (1979) Proc Natl Acad Sci US
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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
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contains antigens which react with
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le of reacting in sensitive radioim
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gic approach. In: Hiatt HH, Watson
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12 Eco R [ Fig. 1. Hybridization pa
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10 - '1~ )( -~ S:! E A U I o 1 2
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Haematology and Blood 'fransfusion
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cultures. These cells did not conta
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indication of malignant T-cells in
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Fig. 3. Thin-section electron micro
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Table 3. Lack of detectable related
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J. HTLV Was Present in the Primary
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specific signals into nonspecific s
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Table 2. Distribution of HTLV-relat
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u 10 ~ 20 ~ :c 30 a 40 o Fig. 1. Ki
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SSV TrS-gp labeled effectively with
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60 HFF/SSV cDNA CELL RNAs: 0 HF/SSV
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Antisera a Table 1. Immunofluoresce
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Haematology and Blood 'ftansfusion
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y competition RIA yielded virtually
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SiS'V' gp70: ANTIGEN, ANTI BODY, IM
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type-C virus p30 antigen in cells f
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c. Results The fractionated whole-b
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induced antibodies as well as exper
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- Fig. la-f. Retravirus particles p
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eplication of infecting murine leuk
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immunodeficiency, multic10nal lymph
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Bovine leukemia --, proteins of 499
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Human T- cell - -, characterization
Page 563 and 564:
RNA -, of tumor virus 439 Rous sarc
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Haematology andBlood Transfusion Su
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