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WD Jr, de Noronha F, Cotter SM (1978) Feline oncornavirus associated cell membrane antigen: a tumor specific cell surface marker. In: Bentvelzen P, Hilgers J, Yohn DS (eds) Advances in comparative leukemia research 1977. Elsevier/North Holland Biomedical Press, Amsterdam, pp 337-340 - Franeis DP, Essex M, Hardy WD Jr (1977) Excretion of feline leukemia virus by naturally infected pet cats. Nature 269:252-254 - Franeis DP, Cotter SM, Hardy WD Jr, Essex M (1979a) Comparison of virus-positive and virus-negative cases of feline leukemia and lymphoma. Cancer Res 39:3866-3870 - Francis DP, Essex M, Cotter SM, Jakowski RM, Hardy WD Jr (1979b) Feline leukemia virus infections: the significance of chronic viremia. Leuk Res 3 :435-441 - Franeis DP, Essex M, Gayzagian D (1979c) Feline leukemia virus: survival under horne and laboratory conditions. J Clin Microbiol9: 154-156 - Francis DP, Essex M, Jakowski RM, Cotter SM, Lerer TJ, Hardy WD Jr (1980) Feline lymphoma: descriptive epidemiology of a virally-induced malignancy in a c10sed cat population. Am J Epidemiol 111: 337-346 - Frankel AE, Gilbert JH, Porzig KJ, Scolnick EM, Aaronson SA (1979) Nature and distribution of feline sarcoma virus nucleotide sequences. J Virol 30:821-827 - Grant CK, De Boer DJ, Essex M, Worley MB, Higgins J (1977) Antibodies from healthy cats exposed to feHne leukemia virus lyse feline lymphoma cells slowly with cat complement. J Immunol 119:401-406 - Grant CK, Essex M, Pedersen NC, Hardy WD Jr, Cotter SM, Theilen GH (1978) Cat complement and cat anti sera lyse feline lymphoblastoid cells: Correlation of lysis with detection of antibodies to FOCMA. J Natl Cancer Inst 60:161-166 - Grant CK, Ramaika C, MadeweIl BR, Pickard DK, Essex M (1979) Complement and tumor antibody levels in cats, and changes associated with natural feline leukemia virus infection and maHgnant disease. Cancer Res 39:75-81 - Grant CK, Essex M, Gardner MB, Hardy WD Jr (1980) Natural feline leukemia virus infection and the immune response of cats of different ages. Cancer Res 40:825-829 - Hardy WD Jr, Old LJ, Hess PW, Essex M, Cotter SM (1973) Horizontal transmission of feline leukemia virus in cats. Nature 244: 266-269 - Hardy WD Jr, McClelland AJ, Zuckerman EE, Hess PW, Essex M, Cotter SM, MacEwen EG, Hayes AA (1976) Prevention of the infectious spread of the feHne leukemia virus in pet cats. Nature 263:326-328 - Hardy WD Jr, Zuckerman EE, MacEwen EG, Hayes AA, Essex M (1977) A feline leukemia and sarcoma virus induced tumor specific antigen. Nature 270:249-251 - Hardy WD Jr, Zuckerman EE, McClelland AJ, Snyder HW Jr, Essex M, Francis DP (1980) The immunology and epidemiology of FeLV non producer feline lymphosarcoma. Cold Spring Harbor Conf Cell Prolif 7: 677-697 - Hoover EA, Olsen RG, Hardy WD Jr, Schaller JP, Mathes LE (1976) Feline leukemia virus infecton: age-related variation in response of cats to experimental infection. J Natl Cancer Inst 57: 365-370 - Mackey L, Jarrett W, Jarrett 0, Laird H (1975) Anemia assoeiated with feline leukemia virus infection in cats. J Natl Cancer Inst 54: 209-218 - Niederkorn JY, Shadduck JA, Albert D, Essex M (1980) FOCMA antibodies in cats with FeSV -induced ocular melanomas. In: Hardy WD Jr, Essex M, McClelland J (eds) FeHne leukemia and sarcoma viruses. Elsevier, New York pp 181-186 - Noronha F de, Grant CK, Essex M, Bolognesi DP (to be published) Passive immune serotherapy protects cats from disseminated FeSV -induced fibrosarcomas. In: Hardy WD Jr, Essex M, McClelland J (eds) Feline leukemia and sarcoma viruses. EIsevieriNorth Holland, New York - Porzig KJ, Barbacid M, Aaronson SA (1979) Biological properties and translation al products of three independent isolates of feline sarcoma virus. Virology 92: 91-107 - Rosenberg ZF, Pedersen FS, Haseltine WA (1980) Comparative analysis of the genome of feline leukemia viruses. J Virol 35: 542-546 - Russell PH, Jarrett 0 (1978) The occurrence of feline leukemia virus neutralizing antibodies in cats. Int J Cancer 22:351-357 - Sarma PS, Log T (1973) Subgroup c1assification of feline leukemia and sarcoma viruses by viral interference and neutralization tests. Virology 54: 160-170 - Sherr CJ, Sen A, Todaro GJ, Sliski AH, Essex M (1978) Pseudotypes of feHne sarcoma virus contain an 85,000 dalton protein with feHne oncornavirus-associated cell membrane antigen (FOCMA) activity. Proc Natl Acad Sei USA 75: 1505-1509 - Sliski AH, Essex M, Meyer C, Todaro GJ (1977) Feline oncornavirus associated cell membrane antigen (FOCMA): expression on feline sarcoma virus transformed nonproducer mink cells. <strong>Science</strong> 196: 1336-1339 - Snyder HW Jr, Hardy WD Jr, Zuckerman EE, Fleissner E (1978) Characterization of a tumour-specific antigen on the surface of feHne lymphosarcoma cells. Nature 175:656-657 - Snyder HW Jr, Phillips KJ, Hardy WD Jr, Zuckerman EE, Essex M, SHski AH, Rhim J (1980) Isolation and characterization of proteins carrying the feline oncornavirus-associated cell membrane antigen (FOCMA). Cold Spring Harbor Symp Quant Biol 44: 878-899 - Stephenson JR, Essex M, Hino S, Aaronson SA, Hardy WD Jr (1977a) Feline oncornavirus-associated cell membrane antigen. VII. Relationship between FOCMA and virion glycoprotein gp70. Proc Natl Acad Sei USA 74:1219-1223 - Stephenson JR, Khan AS, SHski AR, Essex M (1977b) Feline oncornavirus-associated cell membrane antigen (FOCMA): identification of an immunologically cross-reactive feline sarcoma virus coded protein. Proc Natl Acad Sci USA 74:5608-5612 - Worley M, Essex M (1980) Identification of membrane proteins assoeiated with transformation-related antigens shared by feline lymphoma cells and feline sarcoma virus transformed fibroblasts. In: Hardy WD Jr, Essex M, McClelland J (eds) Feline leukemia and sarcoma viruses. Elsevier, New York pp 431-440 487
Haematology and Blood Transfusion Val. 26 <strong>Modern</strong> Trends in Human Leukemia IV Edited by Neth, Gallo, Graf, Mannweiler, Winkler © Springer-Verlag Berlin Heidelberg 1981 Relationship 01 the Feline Oncornavirus Associated Cell Membrane Antigen to a Feline Sarcoma Virus Encoded Polyprotein H. W. Snyder Jr., M. Dutta-Choudhury, and W. D. Hardy Jr. A. Introduction The feline oncornavirus associated cell membrane antigen (FOCMA) is expressed on the membranes of cells transformed by infection with the feline leukemia virus (FOCMA-L) or feline sarcoma virus (FOCMA-S) (Hardy et al. 1977; Essex et al. 1977). Expression of FOCMA is transformation-specific and not dependent upon concomitant expression of antigens associated with feline leukemia virus (FeLV) or the endogenous virus RD114 (reviewed in Snyder et al., to be published a). In the natural environment FOCMA is the target for an effective immunosurveillance response: complement-dependent lytic antibodies directed to FOCMA reverse or prevent tumor development (Essex et al. 1975; Grant et al. 1977). FOCMA-L has been isolated from feline lymphosarcoma (LSA) cell membranes and has been shown to reside on a 70,000 dalton pro tein which is neither glycosylated nor phosphorylated (Snyder et al. 1978, to be published a). The nature of FOCMA-S is a subject of intense investigation at the present time. The observation that FOCMA is induced on FeSV -transformed nonproducer fibroblasts of nonfeline as weIl as feline origin has been interpreted as evidence that FOCMA-S may actually be encoded by FeSV (Essex et al. 1979). Present evidence suggests that in the derivation of the defective FeSV genome sequences from the pol and the 3' end of the gag and env genes were deleted and the gag-pol deletion was substituted with cat cellular DNA sequences which contain information for transformation (Frankel et al. 1979; Sherr et al. 1980). The translation products of FeSV genomes in nonproducer fibroblasts are "fusion" proteins comprised of covalently linked FeLV p15, p12, a portion of p30, and nonstructural ("x") components of differing sizes depending on the particular strain of FeSV (Khan and Stephenson 1977; Sherr et al. 1978a; Barbacid et al. 1980; Van de Yen et al. 1980; Ruscetti et al., to be published). These proteins have generally been referred to as "gag-x" polyproteins. The question of FOCMA association with the "x" portion of these fusion pro teins is addressed below. B. Results We have previously reported the isolation of 70,000 dalton proteins from lysates of feline LSA cells by immunoaffinity chromatography on a column of Sepharose containing bound IgG from cat anti-FOCMA serum (Snyder et al., to be published a; Fig.1A). Usingthe same affinity column we isolated a similarly sized protein from lysates of mink cells transformed by the Gardner-Arnstein strain of FeSV (GA FeSV) (Fig. 1, B). This result was unanticipated since published evidence suggested an association between FOCMA and the much larger (95,000 daltons) gag-x fusion protein in these cells (Stephenson et al. 1977; Sherr et al. 1978a,b; Snyder et al. 1978). In addition tothe p70 it was possible to isolate the Ga-FeSV fusion protein (termed P95 gag - x ) from the transformed mink cells by virtue of its binding to anti-FeLV antibodies on a different affinity column (Fig. 1, C). These purified proteins as well as those directly immunoprecipitated from detergentlysed cultured cells were analyzed for (1) associated FeLV antigens by radioimmunopre- 488
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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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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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munized animals to 1316 tumor cells
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Fig. 3. Expression of retroviral gp
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pg70. J Exp Med 143: 151-166 - McGr
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Table 1. Expression of tumor antige
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Virological and Molecularbiological
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Table 1. Oncogenic properties of re
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also Fig. 1). It followed that the
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whether this sequence is related to
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zed in infected cells argue that th
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a specific viral transforming prote
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detect viral RNA as the only charac
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Eisen H (1980) Myeloproliferate vir
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p,60- -34K - 1 2 3 4 Fig. 1. In vit
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.. p - • a'T ... I .t'l Fig. 4. D
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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
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vity was deterrnined. For endogenou
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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
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Expt. No. Infecting virus Proportio
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Haematology and Blood 'fransfusion
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sequences, provided its gag portion
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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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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: Haematology and Blood Transfusion V
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 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: contains antigens which react with
Page 499 and 500: le of reacting in sensitive radioim
Page 503 and 504: gic approach. In: Hiatt HH, Watson
Page 505 and 506: 12 Eco R [ Fig. 1. Hybridization pa
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 531 and 532: SSV TrS-gp labeled effectively with
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
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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
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RNA -, of tumor virus 439 Rous sarc
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Haematology andBlood Transfusion Su
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