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Endogenous murine leukemia virus (MuLV) proviral copies were analyzed in thymomas induced in normal BALB/c (Fv-1b) and in Fv-1n congenic mice by X-irradiation. Both strains of mice developed leukemia with similar kinetics, indicating that N-tropism of endogenous MuLV was not a rate-limiting factor in development of disease. Southern blot analysis, using a probe specific for ecotropic virus and for ecotropic-specific sequences retained in pathogenic, env-recombinant viruses, showed that the majority of radiation leukemias lacked newly acquired, clonally integrated, proviruses. This was in contrast to virus-induced leukemias, which routinely exhibited several new proviral integration sites. When an internal proviral DNA restriction fragment was monitored, some radiation leukemias showed evidence of nonclonal infection, accounting for more frequent isolation of infectious virus from such leukemias. Differences in expression of T-cell surface antigens were found in X-ray-induced and virus-induced leukemias. All radiation leukemias were TL positive, whereas virus-induced leukemias were primarily negative for TL. Some differences were also found in Lyt-1 and Lyt-2 expression. The data as a whole suggest that, in the majority of cases, radiation leukemogenesis is not initiated by a viral route--that is, the sort of viral mechanism for which exogenous infection by known pathogenic MuLV is the paradigm.

Interleukin 2 (IL-2) production was studied in a subclone of the murine thymoma EL 4. Phenotypic characterization revealed the EL 4-17-2 line to be Thy-1.2+, Lyt-1.2+, and Lyt-2.2-. Costimulation with 500 ng 12-O-tetradecanoylphorbol 13-acetate (TPA)/ml and 5 micrograms concanavalin A (Con A)/ml induced optimal levels of IL-2. Three related phorbol esters stimulated comparable levels of IL-2 when used in conjunction with Con A. Kinetic experiments indicated that IL-2 first became detectable at 2 hours in TPA-treated cultures, whereas in cultures stimulated with Con A alone IL-2 production was not evident until 8 hours. Flow cytometry indicated that TPA and its related phorbol esters cause a perturbation in the cycling of the cell which may be related to increased IL-2 production. Under the conditions examined, no interferon-gamma (IFN-gamma) was detectable. Conversely, both granulocyte-macrophage colony-stimulating factor (CSF-GM) and interleukin-3 (IL-3) were found under conditions that led to stimulation of IL-2 synthesis. CSF-GM was produced in cultures treated singly with 500 ng TPA/ml or with Con A. IL-3 production was similar to IL-2 production, because optimal levels were found in cultures after combined treatment with phorbol ester and mitogen.

Morphologic, cytochemical and immunocytochemical studies of pericardial fluid from a 30-year-old man presenting with cardiac tamponade are described. Based on the results of the immunocytochemical studies and the histologic examination of excised pericardium, a diagnosis of malignant thymoma was made. This is the first documented case in which malignant cells were found in the pericardial effusion in a patient with invasive thymoma. The significance of using a multidisciplinary approach to the study of body fluids is discussed.

Changes of the activity potentials of motor units and muscular fibres registered with the aid of needle electrodes are compared with the results of morphological examinations of biopsy specimens of 1,096 muscles taken from 137 patients with myasthenia, combinations of myasthenia with thymoma and polymyositis, as well as from patients with terminal polyneuropathy with the myasthenic syndrome. It has been shown that characteristic of myasthenia are differentiated changes of the motor unit activity potentials: in half of the muscles examined the parameters of those potentials were found to be normal, no polyphasic or protracted potentials were observed. In the patient with combinations of myasthenia with thymoma, polymyositis, and in terminal polyneuropathy with the myasthenic syndrome pronounced changes of all the activity potentials of the motor units were observed in the form of both a sharp shortening and a prolongation of their duration; a great number of polyphasic potentials was registered and spontaneous activity of various degree was observed. Morphological examinations of 55 biopsy specimens of the muscles of the same patients revealed a correlation between the degree of the dystrophic and atrophic changes of the muscular fibres and depth of the affection as determined on the basis of electromyographic findings.

Two cases of a neuromuscular hyperactivity syndrome associated with a proliferative thymoma and high serum titres of acetylcholine receptor (AChR) antibody with no signs of myasthenia are reported. The clinical and electrodiagnostic findings indicated generalized cholinergic hyperactivity at the neuromuscular junction and in the autonomic and central nervous system, resulting in generalized myokymia, excessive sweating and intermittent psychotic behaviour. The association with thymoma and raised AChR antibody suggests that this syndrome represents a unique type of autoimmune disease, in which antibodies against the AChR facilitate rather than inhibit cholinergic action. This conclusion is supported by the remission of symptoms after thymectomy and with immunosuppressive therapy in one case.