Growth Curve and Distribution of Rous Sarcoma Virus (Bryan) in Japanese Quail

On primary infection with the Bryan strain of Rous sarcoma virus (RSV), the growth curve of the virus in the brain of Japanese quail was similar to that observed in chicks and turkey poults. Infectious virus disappeared from the brain after inoculation. After an eclipse period during which no virus was detectable, infectious virus began to appear at 2 days and reached maximal titers in the brain samples at 7 days after inoculation. When Japanese quail were infected intracerebrally with RSV, relatively high titers of virus were recovered from brain tissue but not from liver, lung, kidney, or blood of moribund birds. Only tumors produced in the wing web of quail infected subcutaneously yielded high titers of virus. Other tissues yielded no virus, even though wing web tumors appeared as early as in chicks similarly infected. RSV could be propagated in the wing web of quail for at least 14 passages without any loss of infectivity. On the other hand, serial passage in quail brain resulted in a progressive loss of infectivity until virus was completely lost.     

Construction and packaging of pseudotype retrovirus containing human N—ras cDNA antisense sequence and its biological effects on human hepatoma cells

N-ras is one of the transforming genes in human hepatic cancer cells.It has been found that N-ras was overexpressed at the mRNA and protein level in hepatoma cells.In order to explore the biological roles of N-ras in human hepatic carcinogenesis and the potential application in control of cancer cell growth,a preudotype retrovirus containing antisense sequence of human N-ras was constructed and packaged.A recombinant retrovirus vector containing antisense or sense sequences of N-ras cDNA was constructed by pZIP-NeoSV(X)1.The pseudotype virus was packaged ang rescued by transfection and infection in PA317 and ψ 2 helper cells.It has been demonstrated that the pseudotype retrovirus containing antisense N-ras sequence did inhibit the growth of human PLC/PRF/5 hepatoma cells accompanied with inhibition of p21 expression,while the retrovirus containing sense sequence had none.The pseudotype virus had no effect on human diploid fibroblasts.     

Gene technology-based antimetabolite design: the use of an in vitro protein expression system to facilitate antimetabolite design for virally-induced human diseases and malignant conditions

A precondition for the chemotherapeutic treatment of a variety of virally-induced human diseases and malignant conditions is a highly selective interaction of the drug molecule to be used with it's biological target. To ensure the development of novel, effective drugs, it is essential that the biological target is well characterised with regard to it's structure and activity. Such characterisation relies upon adequate amounts of pure target being available. One of the most important enzymatic importers for antimetabolites is the enzyme thymidine kinase. In this article an in vitro protein expression system is described which facilitates the production of milligram amounts of pure and biologically active thymidine kinase, from a number of important biological sources. Results have shown that the in vitro produced enzyme has the exact biochemical propeties of the in vivo enzyme. Thus the in vitro protein expression system is an ideal vechicle to facilitate an in depth investigation of the enzyme's biological properties.     

Antisense EGFR sequence reverses the growth properties of human liver carcinoma cell line BEL-7404 in vitro

A recombinant plasmid containing a full length human epidermal growth factor receptor (EGFR) cDNA sequence in antisense orientation was transferred into cells of a human liver carcinoma cell line BEL-7404. Compared with the control cell clone JX-0 transferred with the vector plasmid and the parent BEL-7404 cells, the antisense EGFR transferred cell clone JX-1 showed a decreased EGFR gene expression and reduced significantly the growth potential either in anchorage-dependent or anchorage-independent growth. Furthermore, JX-1 cells appeared to be distinctly dependent on serum concentration for monolayer growth. The results suggested that antisense EGFR could partly block the EGFR gene expression and reverse the malignant growth properties of human liver carcinoma cells in vitro.     

Search for the possible role of ‘immunotherapy’ in operable bronchial non-small cell carcinoma (stage I and II): A phase I study with Corynebacterium parvum intrapleurally

Summary The possibility of giving C. parvum intrapleurally (i.p.) was investigated. C. parvum was given post-operatively either i.p. only or i.p. and intravenously (i.v.) simultaneously. The dose varied from 0.1–10 mg i.p. All patients had been operated for a bronchial carcinoma. Results: (1) Subjective complaints of either dyspnoea, thoracic pain, chills or nausea occured in 31 of 63 patients. No clear dose relation was found. A feeling of discomfort and fever could occur for another 3–4 days after the above more acute symptoms had disappeared. (2) Increased fever (0.5° C) occurred in 71% of the patients injected i.p. only. (3) No anaphylactic reaction was observed. (4) Increased total white blood cell counts (<20%) occurred in 38 patients. The WBC increase was mainly due to higher number of neutrocytes and granulocytes. Total lymphocyte, monocyte, eosinophilic, and basophilic granulocytes values per mm³ circulating blood remained unchanged, except at the dose of 7 mg C. parvum i.p. when monocyte values were increased significantly from 576±247 to 1100±578/mm³. (5) Moderate to severe effusions were observed radiologically in three patients after C. parvum intrapleurally.The study group is: M. Kaufmann, J. Stjernswärd (Ludwig Institut for Cancer Research, Lausanne Branch, Switzerland), M. Zelen, K. Stanley (Frontier Science and Technology Research Foundation, Inc. Amherst, New York, USA), D. S. Freestone, R. Bomford, M. T. Scott, T. Priestman (The Wellcome Research Laboratory, Beckenham, England), C. Mouritzen, G. Ahlbom (Dept. of Thoracic and Cardiovascular Surgery, Aarhus Kommunehospital, Aarhus, Denmark), N. Konietzko, D. Greschuchna (Ruhrland Klinic, Essen-Haidhausen, Germany), P. Hilgard (Innere Klinik und Poliklinik [Tumorforschung] Essen, Germany), J. Vogt-Moykopf, D. Zeidler, H. Toomes (Thoraxchirurgische Spezial-Klinik, Heidelberg-Rohrbach, Germany), F. Krause, R. Rios (Thoraxchirurgische Abt., Fachkrankenhaus für Lungen- und Bronchialerkrankungen, Löwenstein, Germany), J. Orel, M. Benedik, B. Hrabar (Clinical Center, Dept. of Thoracic Surgery, Ljubljana, Yugoslavia), S. Plesnicar (The Institute of Oncology, Ljubljana, Yugoslavia), H. A. Rostad, J. R. Vale (Rikshospital, Oslo, Norway), S. Hagen, S. Birkeland, (Ulleval Hospital, Oslo, Norway), T. Harbitz, R. Nissen-Meyer (Aker Hospital, Oslo, Norway), L. Rodriguez, V. O. Björk, K. Böök (Karolinska Sjukhuset, Thoracic Clinic, Stockholm, Sweden), E. Gradel, J. Hasse, P. Holbro (Kantonsspital, Thoraxchirurgische Klinik, Basel, Switzerland), L. Eckmann (Tiefenauspital, Chir. Univ.-Klinik, Bern, Switzerland), B. Nachbur, T. Liechti (Inselspital, Dept. of Thoracic and Cardiovascular Surgery, Bern, Switzerland), H. Cottier (Inst. of Pathology, Inselspital, Bern, Switzerland), W. Maurer, M. Kaufmann, P. Froelicher (Bürgerspital, Surgical Dept., Solothurn, Switzerland), H. Denck, N. Pridun (Krankenhaus der Stadt Wien-Lainz, Chir. Abt., Vienna, Austria), K. Karrer (Institute for Cancer Research, University of Vienna, Austria) Reprint requests should be addressed to any of the members listed above, or to the Ludwig Lung Cancer Trial, Operation Office, LICR, CH-1066 Epalinges, Switzerland. (For Current Contents, etc., please use above address)     

Immunotherapy for remission maintenance in acute myeloblastic leukemia

Summary Forty-eight patients with acute myeloblastic leukemia in remission were treated with immunotherapy in addition to remission-maintenance chemotherapy. The first 16 patients were treated with weekly BCG and a leukemia cell vaccine (group 1). The next 32 patients were randomly allocated to receive BCG and a leukemia cell vaccine given once monthly (group 2) or BCG given monthly with no leukemia cell vaccine (group 3). There was no significant difference in remission duration or survival between the randomly allocated groups (2 and 3).Comparisons with group 1 are limited by the non-random allocation to this group, but selection bias was unlikely and clinical features were similar in the three patient groups. No significant difference in remission duration or survival was seen amongst the three groups studied. There was no advantage in the addition of leukemia cell vaccine (groups 1 and 2) to BCG alone (group 3) and no advantage to weekly (group 1) versus monthly immunotherapy (groups 2 and 3). Only 7 of the 48 patients achieved a second remission, and 4 of these were short-term partial remissions.The following are contributing members of the Toronto Leukemia Study Group: Doctor's Hospital, Harvey Silver MD; Humber Memorial Hospital, Alan Seidenfeld MD; Mississauga Hospital, Michael King MD; Mount Sinai Hospital, Dominic Amato MD; Northwestern Hospital, Wilhelm Kwant MD; Oshawa General Hospital, Hak Chiu MD; St Michael's Hospital, Bernadette Garvey MD, Kenneth Butler MD; St Joseph's Hospital, H. James Watt MD, Murray Davidson MD; Toronto General Hospital, Gerald Scott MD, William Francombe MD, Kenneth Shumak MD; John Crookston MD, PhD; Toronto Western Hospital, James G. Watt MD, David Sutton MD; Michael Baker MD; Domenic Pantalony MD; Wellesley Hospital, Dale Dotten MD; Women's College Hospital, George Kutas MD; York Finch Hospital, Sam Berger MD     

Delayed hypersensitivity and Ig level in 210 patients with chronic myeloid leukemia

Summary Serum immunoglobulin concentration and skin reactivity to at least three recall antigens were determined in 210 patients with chronic myeloid leukemia (CML). Immunoglobulin concentration was normal in the great majority of the patients. Skin tests were negative in 50 of 210 cases (24%). No relationship could be demonstrated between skin reactivity, age, time since diagnosis, WBC, lymphocyte count, and splenectomy. Prior antileukemic therapy was a major factor in determining the response to skin tests.S. Tura (Chairman) and M. Baccarani (Secretary), Cattedra di Ematologia dell'Università e Servizio di Ematologia dell'Ospedale S. Orsola, Bologna; G. de Sandre, G. Perona, G. Cetto, G. Pizzolo, Istituto di Patologia Medica e Cattedra di Ematologia dell'Università, Verona; P. Rambotti, B. Falini, Clinica Medica dell'Università, Perugia; T. Chisesi, G. Capnist, Divisione di Ematologia, Ospedale Civile, Vicenza; A. Cajozzo, P. Citarella, Cattedra di Ematologia dell'Università, Palermo; G. Broccia, Sezione di Ematologia, Ospedale Armando Businco, Cagliari; V. Liso, G. Troccoli, Clinica Medica II dell'Università, Bari; L. Bruzzese, G. Nappi, A. Abbadessa, Clinica Medica (I Facoltà) dell'Università, Napoli; A. Porcellini, C. Delfini, Divisione di Ematologia, Ospedali Riuniti, Pesaro; E. Cacciola, R. Giustolisi, R. Musso, V. Raimondi, Cattedra di Ematologia dell'Università, Catania; G. Torlontano, L. Geraci, Cattedra di Ematologia dell'Università, Chieti, e Divisione di Ematologia, Ospedale Civile, Pescara; F. Mandelli, G. Mariani, B. Monarca, N. Petti, Cattedra di Ematologia dell'Università, Roma; R. di Guglielmo, A. Miliani, Clinica Medica dell'Università, Firenze; C. Bernasconi, M. Lazzarino, G. Castelli, Divisione di Ematologia, Ospedale S. Matteo, Pavia; A. Alberti, S. Magro, Servizio di Ematologia, Ospedale Generale Regionale, Catanzaro; A. Neri, P. Iacopino, Divisione di Ematologia, Ospedali Riuniti, Reggio Calabria; R. Delsignore, M. C. Baroni, Istituto di Patologia Medica dell'Universita, Parma; E. Bajetta, S. Monfardini, Istituto Nazionale per lo Studio e la Cura dei Tumori, Milano; S. Tognella, Istituto Scientifico di Medicina Interna, Cattedra di Clinica Medica 2R, Università, Genova.