Intrapleural and intravenous Corynebacterium parvum in patients with resected stage I and II non-small cell carcinoma of the lung

Summary A prospective randomized trial compared the administration of intrapleural plus intravenous Corynebacterium parvum (C. parvum) versus placebo in patients with resected Stage I and Stage II non-small cell bronchogenic carcinoma. Treatment consisted of 7 mg C. parvum injected into the pleural space and 7 mg C. parvum intravenously once between days 6 and 12 postoperatively and 7 mg intravenously every 3rd month during the 1st year. Intrapleural administration of 35 cc of saline served as the placebo and the flush after intrapleural C. parvum.Of the 303 patients entered into this study, 286 were evaluable, with an average follow-up time of 3.5 years. More complications, especially fever, were observed in patients receiving C. parvum. A fever greater than 38 °C was observed in 9% of the patients assigned to placebo and 76% of the patients assigned to C. parvum. There was no significant difference between the treatments with respect to disease-free interval or survival.M. Kaufmann, J. Stjernswärd**, A. Zimmermann (Ludwig Institute for Cancer Research, Bern Branch); K. Stanley**, M. Isley, M. Zelen (Frontier Science & Tech. Research Foundation, Brookline, MA, USA); C. Mouritzen, P. Paulsen, U. Henriques (Dept. of Thoracic and Cardiovascular Surgery and Institute of Pathology, Kommunehospital, Aarhus, Denmark); N. Konietzko, W. Maassen, W. Hartung, W. Wierich (Ruhrland Clinic, Essen-Heidhausen, and Pathology Institute, Ruhr-University, Bochum, FRG); P. Oehl (Innere Klinik und Poliklinik Tumorforschung, Essen, FRG); J. Vogt-Moykopf, H. Toomes, W. Hofmann (Rohrbach Hospital, Clinic for Thoracic Medicine and Pathology Institute, Heidelberg, FRG); F. Krause, R. Rios, R. Spanel (Klinik Löwenstein, Löwenstein, and Pathology Institute, Ulm, FRG); J. Orel, B. Hrabar, D. Ferluga, T. Rott (University Medical Center, Thoracic Surgery and Pathology, Ljubljana, Yugoslavia); H. A. Rostad, J. R. Vale, P. Lexow (Rikshospital, Oslo, Norway); S. Hagen, S. Birkeland (Ulleval Hospital, Oslo, Norway); T. Harbitz, R. Nissen-Meyer (Aker Hospital, Oslo, Norway); E. Aspevik, H. Engedal, A. Mykin (Haukeland Hospital, Bergen, Norway); V. O. Björk, L. Rodriguez, K. Böök, J. Willems (Karolinska Sjukhuset, Thoracic Surgical Clinic and Pathology Department, Stockholm, Sweden); E. Grädel, J. Hasse, P. Dalquen (Kantonsspital, Dept of Surgery, Div. of Cardiac & Thoracic Surgery & Pathology Institute, Basel, Switzerland); L. Eckmann, K. Hänni, K. Zimmermann (Tiefenauspital Surg. Clinic, Univ. of Bern, Switzerland); B. Nachbur, H. U. Würsten, H. Cottier, A. Zimmermann (Inselspital Dept. of Thoracic and Cardiovascular Surg. and Pathology Institute, Bern, Switzerland); W. Maurer, M. Kaufmann (Bürgerspital, Surgical Department, Solothurn, Switzerland); H. Denck, E. Zwintz, St. Wuketich (Krankenhaus der Stadt Wien-Lainz, I. Chir. Dept., and Path. Inst., Vienna, Austria); N. Pridun, H. Hackl (Pulmonologisches Zentrum der Stadt Wien, and Path. Inst., Vienna, Austria); E. Moritz, W. Schlick, H. Holzner (II. Chir. University Clinic and Path. Inst., Vienna, Austria); K. Karrer (Institute for Cancer Research, Vienna, Austria); R. G. Crispen (ITR-Biomedical Research, University of Illinois, Chicago, USA); D. S. Freestone, R. Bomford, M. T. Scott, T. Priestman, L. Toy (The Wellcome Research Laboratories, Beckenham, England)** Present address: Cancer Unit, World Health Organization, Geneva, Switzerland Offprint requests to: K. Stanley, Ludwig Institute for Cancer Research, Inselspital, CH-3010 Bern, SwitzerlandLudwig Lung Cancer Study Group:     

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.     

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.     

Large E1B proteins of adenovirus types 5 and 12 have different effects on p53 and distinct roles in cell transformation.

The formation of complexes between oncoproteins of DNA tumor viruses and the cellular protein p53 is thought to result in inactivation of the growth suppressor function of p53. In cells transformed by nononcogenic human adenovirus type 5 (Ad5), the 55-kDa protein encoded by E1B forms a stable complex with p53 and sequesters it in the cytoplasm. However, the homologous 54-kDa protein of highly oncogenic Ad12 does not detectably associate with p53. Yet in Ad12-transformed cells, p53 is metabolically stable, is present at high levels in the nucleus, and contributes to the oncogenicity of the cells. Such properties have previously been described for mutant forms of p53. Here, we show that stable p53 in Ad12-transformed cells is wild type rather than mutant and that stabilization of p53 is a direct consequence of the expression of the Ad12 E1B protein. We also compared the effects of the E1B proteins on transformation of rodent cells by different combinations of oncogenes. A synergistic interaction was observed for the gene encoding the 54-kDa E1B protein of Ad12 with myc plus ras oncogenes, resembling the effect of mutant p53 on myc plus ras. In contrast, the Ad5 55-kDa E1B protein strongly inhibited transformation by myc plus ras but stimulated transformation by E1A plus ras. The data are explained in terms of different interactions of the two E1B proteins with endogenous p53. The results suggest that in cultured rat cells, endogenous wild-type p53 plays an essential role in cell proliferation, even in the presence of myc plus ras. The dependence on p53 is lost, however, when the adenovirus E1A oncogene is present.     

大鼠血小板中的神经肽Y及其对血管收缩的影响

特异性放射免疫分析显示大鼠血小板与富血小板血浆(PRP)分别含NPY免疫活性物质90±16ng/10~7血小板与93±19ng/ml,大大高于普通血浆(1.2±0.1ng/ml)与贫血小板血浆(PPP)(1.7±0.3 ng/ml)中的含量(P<0.001)。血小板样品HPLC各馏分的NPY放免活性峰位与标准NPY的峰位相符。PRP经胶原最大程度聚集后,血小板内的NPY浓度降为34±5 ng/10~7血小板,而PPP中的NPY浓度则升高到26±4 ng/ml。1.6 ml PRP经胶原作用产生最大程度聚集,由此分离所得的PPP引起离体灌流大鼠尾动脉收缩,张力上升380±80 mg;上述PPP经NPY抗血清处理后引起尾动脉收缩的幅度显著减小(190±40 mg,P<0.001)。而1 nmol/L人工合成NPY并不引起血管收缩。结果表明大鼠血小板中含有大量NPY,在不可逆聚集时可以释放,释放的NPY可能参与血小板聚集时释放物质的缩血管效应。     

显微高速摄影技术及其在血液微流变学研究中的应用

本文选用金黄地鼠的微血管,利用显微高速摄影技术,放大微观流场和血细胞,连续地“冻结”短瞬间的变化状态,把物理图象呈现在胶片上,经图像分析和数据处理,从定性及定量方面研究血液微流变学,为生命科学和医学研究提供了又一种新的方法。     

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.