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normal individuals under steady state conditions appear to be quiescent. This contrasts with results obtained for the proliferative state of CFU-GEMM during regeneration and for patients with various clon al hemopathies. It was feasible to study patients with PV and CML prior to and subsequent to therapeutic interventions without demonstrating changes in the proliferative state. The increased proliferative rate of CFU-GEMM may adequately explain the increased number of cells observed in these disorders. The active proliferation of leukemic blast colony forming cells is consistent with the interpretation of a growth advantage of blast cells observed under these clinical conditions. This was further documented by assessing the rec10ning ability of blast colony forming cells. In addition, it becomes apparent that chemotherapeutic intervention in patients with acute myeloid leukemia is complex and may include, beside cytoreduction, changes in the recloning ability of blast colony forming cells. It is thus conceivable to select drugs with differing biological effects for patients with specific cell culture prognostics. Our studies thus far have not succeeded in identifying the relationship of pluripotent hemopoietic progenitors and blast-forming cells. One of the main difficulties is related to the low frequency of mixed colonies observed during phases of relapse and the greatly reduced number of blast cell colonies at the time of remission. The observation that CFU-GEMM as weIl as blast cell colonies can be recloned may provide a powerful tool to be employed in the future, particularly if specific fractions of PHA-LCM become available to facilitate selective cloning. References Adamson JW, Fialkow PJ, Murphy S, Prchal JF, Steinmann E (1976) Polycythemia vera: Stern cell and probable clonal origin of the disease. N Engl J Med 295 :913-916 - Aye MT, Niho Y, Till JE, McCulloch EA (1974) Studies of leukemic cell populations in culture. Blood 2/205:219 - Becker AJ, McCulloch EA, Siminovitch L, Till JE (1965) The effect of differing demands for blood cell production on DNA synthesis by hemopoietic colony forming cells of mice. Blood 26: 296-308 - Buick RN, Chang LJ-A, Messner HA, Curtis JE, McCulloch (1981) Self-renewal capacity of leukemia blast progenitor cells. Cancer, in press - Buick RN, Till JE, McCulloch EA (1977) Colony assay for proliferative blast cells circulating in myeloblastic leukemia. Lancet 1:862-863 - Buick RN, Minden MD, McCulioch EA (1979) Self renewal in culture of proliferative blast progenitor cells in acute myeloblastic leukemia. Blood 54:95-104 - Chang U-A, McCulloch EA (1979) A tumor promotor increases the self renewal of blast progenitors in acute myeloblastic leukemia. Blood [Supp I] 54/5: p 169a - Dicke KA, Spitzer G, Ahearn MJ (1976) Colony formation in vitro by leukemic cells in acute myelogenous leukaemia with phytohaemagglutinin as stimulating factor. Nature 259: 129-130 - Fauser AA, Messner HA (1978) Granuloerythropoieticcolonies in human bone marrow, peripheral blood and cord blood. Blood 52: 1243 - Fauser AA, Messner HA (1979a) Identification of megakaryocytes, macrophages and eosinophils in colonies of human bone marrow containing neutrophilic granulocytes and erythroblasts. Blood 53: 1023 - Fauser AA, Messner HA (1979b) Separation of stimulating activity in PHA -LCM by isoelectric focusing for leukemic blast cell colonies and colonies of normal hemopoietic progenitors. Blood [Supp I] 54: p 107 - Fauser AA, Messner HA (1979c) Proliferative state of human pluripotent hemopoietic progenitors (CFU GEMM) in normal individuals and under regenerative conditions after bone marrow transplantation. Blood 54/5: 1197 - Fauser AA, Messner HA (1979d) Pluripotent hemopoietic progenitors in peripher al blood of patients with polycythemia rubra vera. Blood [Supp I] 54: p 138 - Fauser AA, Messner HA (submitted to Blood) Pluripotent hemopoietic progenitors (CFU-GEMM) in polycythemia vera: Analysis of erythropoietin requirement and proliferative activity - Fialkow PJ, Gartier SM, Yoshida A (1967) Clon al origin of chronic myelogenous leukemia in man. Proc Natl Acad Sci USA 58:1468-1471 - Fialkow PJ, Jacobson RJ, Papayannopoulou TH (1977) Chronic myelocytic leukemia: Clonal origin in astern cell common to the granulocyte erythrocyte, platelet and monocyte/macrophage. Am J Med 63: 125-130 - Izaguirre CA, McCulloch EA (1978) Cytogenetic analysis of leukemic clones. Blood [Supp 1] 52: 287 - McCulloch EA (1979) Abnormal myelopoietic clones in man. J Natl Cancer Inst 63: 883-891 - McCulloch EA, Till JE (1977) Stern cells in normal early hemopoiesis and certain clon al hemopathies. In: Hoffbrant AV, Brain M, Hersh J (eds) Recent advances in hematology, vol 2. Churchill-Livingston, London, pp 85-110 - Messner HA, Fauser AA (1978) Distribution of fetal hemoglobin in individual colonies by RIA: A lead towards human stern cells. In: Stamatoyannopoulos, Nienhuis (eds) Cellular and molecular regulation of hemoglobin switching. Grune & Stratton, pp 379 - Messner HA, Fauser AA (1979) Human pluripotent hemopoietic progenitors (CFU-GEMM) in culture. In: NIH Conference on Aplastic Anemia, San Francisco. - Messner HA, Fauser AA, Lepine J, Martin M (1980) Properties of human pluripotent hemopoietic proge- 249
nitors. Blood Cells 6:595-607 - Minden MD, Till JE, McCulloch EA (1978) Proliferative state ofblast cell progenitors in acute myeloblastic leukemia. Blood 52:592-600 - Park C, Savin MA, Hoogstrated B, et al. (1977) Improved growth of the in vitro colonies in human acute leukemia with the feeding culture method. Cancer Res 37: 4594-4601 - Scandurra R, Cannella C, Elli R (1969) Use of isoelectric focusing in the purification of L-glutamate - phenylpyruvate aminotransferase. Sei Tools 16: 17 - Senn JS, Pinkerton PH, Messner HA, McCulloch EA (1979) Detection of blast cell colonies in preleukemic states. Blood [Suppl I] 54/5: p 175a - Taetle R, Buick RN, McCulloch EA (1980) Effect ofInterferon on colony formation in culture by blast cell progenitors in acute myeloblastic leukemia. Blood 56:549-552 - Wiggans RG, Jacobson AJ, Fialkow PJ, et al. (1978) Probable donal origin of acute myeloblastic leukemia following radiation and chemotherapy of colon cancer. Blood 52:659-663 250
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Haematology and Blood Transfusion 2
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Dr. Rolf Neth, Universitäts-Kinder
Page 5 and 6:
Participants of the Meeting Aaronso
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Kurth, R, Friedrich-Miescher-Labora
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Wilsede Scholarship Holders (Grante
Page 11 and 12:
Preface Gut ist eine Lehrart, wo ma
Page 13 and 14:
Personal and scientific discussion
Page 15 and 16:
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
Page 25 and 26:
Bregula U, Wiener F, Harris H (1971
Page 27 and 28:
fresh lymph node biopsies from ten
Page 29 and 30:
Fig. 3. Binucleate mitosis in an ob
Page 31 and 32:
y Fig. 4. Schematic diagram of post
Page 33 and 34:
than that among patients with Stage
Page 35 and 36:
Tests of binding affinity, agglutin
Page 37 and 38:
N Engl J Med 297: 963-968 - Green I
Page 39 and 40:
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
Page 47 and 48:
Haematology and Blood Transfusion V
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Retrospective group 26/93 evolved l
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Page 53 and 54:
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 ,-----------------------------
Page 77 and 78:
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%,
Page 97 and 98:
normal or elevated immunoglobulin l
Page 99 and 100:
References Andreeff M, Darzynkiewic
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R GROUP 1 ( 1970 - 1971 ) 17 PTS. R
Page 103 and 104:
Table 3. Influence of initial featu
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LIJ (f) a.. < -1 LIJ Q: u. 0 >- I-
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Page 109 and 110:
me nt indicated that additional the
Page 111 and 112:
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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Page 205 and 206:
Dc;bt CT + i J.I9 Raji; 1. i .. 100
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c. Discussion During infectious mon
Page 209 and 210: Haematology and Blood Transfusion V
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 and 232: after TPA-induction (Table 3). The
Page 233 and 234: PA (1978) Reactivity of a rabbit an
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: don al hemopathies generally displa
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
Page 285 and 286: Table 1. Production of factor depen
Page 289 and 290: Table 1. Characteristics of the adh
Page 291 and 292: Fig. 3. A human marrow culture at 6
Page 293 and 294: 300 250 • HYPERPROLIFERATIVE PATT
Page 295 and 296: Fig. 9. Nonadherent population from
Page 297 and 298: The cobblestone areas were often no
Page 299 and 300: L (1976) Induction of colony format
Page 301 and 302: B. Materials and Methods J. Tissue
Page 303 and 304: Fig. 2. Ultrastructural appearance
Page 309 and 310: Table 1. Monoclonal antibody reacti
Page 311 and 312:
al. 1979; Janossy et al. 1979) is e
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to which this is an exact replica o
Page 315 and 316:
inger JL (1976) Distribution of la-
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I region antigens were found to be
Page 319 and 320:
have been reported to be present on
Page 321 and 322:
V. FunctionalAssays Assays for PHA
Page 323 and 324:
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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Page 333 and 334:
can be dissected by cloning. Utiliz
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Table 1. Origin and marker profile
Page 337 and 338:
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complete identity of gp 100 from no
Page 341 and 342:
Table 1. Reaction of single anti se
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Page 345 and 346:
media. Following 24-h incubation, c
Page 347 and 348:
nonleukemic eells (Greaves 1979). L
Page 349 and 350:
Page 351 and 352:
Fig. 2. Cytocentrifuged smears of b
Page 353 and 354:
Modification of amino-groups of hum
Page 355 and 356:
disturb this balance in the directi
Page 357 and 358:
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:
Page 363 and 364:
" K 10 • j ~ ALL RNlL AL wtfh les
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tion akuter Leukämiezellen in "spo
Page 367 and 368:
D. Results and Discussion J. Acute
Page 369 and 370:
selectively responsive to different
Page 371 and 372:
Page 373 and 374:
l1J ~ 100 ~ Q. ::) l1J Z 0 ~ z >- .
Page 375 and 376:
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
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:
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
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85,- 66- -27 - -66 40- 27- -1'9 19-
Page 423 and 424:
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 and 432:
Expt. No. Infecting virus Proportio
Page 433 and 434:
Haematology and Blood 'fransfusion
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 441 and 442:
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 469 and 470:
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
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
Page 491 and 492:
inserts in the genome of rapidly tr
Page 493 and 494:
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
Page 501 and 502:
Page 503 and 504:
gic approach. In: Hiatt HH, Watson
Page 505 and 506:
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
Page 517 and 518:
Fig. 3. Thin-section electron micro
Page 519 and 520:
Table 3. Lack of detectable related
Page 521 and 522:
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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