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Biomedical subjects

M J Collins

Publications and source records attributed to M J Collins.

At least 91 records · Page 5Linked to original sources

Suppression of T cell-mediated immunity by tumor cells: immunogenicity versus immunosuppression and preliminary characterization of the suppressive factors.

In studying the immunogenicity of spleen cells and tumor cells in the generation, of cytotoxic T lymphocyte (CTL) in the allogeneic mixed lymphocyte culture (MLC) or mixed lymphocyte tumor cell culture (MLTC) reactions, we have found that the tumor cells not only appear to be poorly immunogenic, but are also immunosuppressive. This was shown by the ability of the tumor cells or their cell-free extracts to suppress standard MLC reactions. This suppression was acting mainly at the induction phase of the cytotoxic response. It could not interfere with the killing activity of the fully generated CTLs. In a Friend virus-induced leukemia FBL-3 system, at least two major components could be attributed to the cause of immunosuppression; one was of viral origin and the other was of non-viral origin. The viral component was sensitive to UV-irradiation and could be pelleted after ultracentrifugation at 100,000 g. The non-viral component was UV-resistant and was retained in the supernatant fraction after ultracentrifugation. Friend virus and 12 commonly found murine viruses have been excluded as the possible candidates causing the immunosuppression. The immunosuppressive viruses are very likely of endogenous origin and are defective in replication as shown by electromicroscopy, and by the virus focus-inducing and reverse transcriptase assays. These findings indicate that probably all tumor cells possess the immunosuppressive factor(s) which may account for their apparent lack of immunogenicity and the lack of proper immune responses in the tumor-bearing hosts.

Animals↗

Enzyme-linked immunosorbent assay for detection of antibodies to murine hepatitis virus.

An enzyme-linked immunosorbent assay was developed for the detection of antibodies to murine hepatitis virus. A high prevalence of antibody to murine hepatitis virus was found by the enzyme-linked immunosorbent assay in colonies with a low prevalence of complement-fixing antibodies. Murine hepatitis virus strain A59 was found to be broadly reactive as an enzyme-linked immunosorbent assay antigen.

Age Factors↗

Sensitivity of enzyme-linked immunosorbent assay, complement fixation, and hemagglutination inhibition serological tests for detection of Sendai virus antibody in laboratory mice.

The enzyme-linked immunosorbent assay technique for detection of Sendai virus antibody in mice was approximately 100- and 300-fold more sensitive than the complement fixation and hemagglutination inhibition tests, respectively. The assay also permitted direct quantitative measurement of the amount of antibody on a single serum dilution rather than by the more traditional serial titration.

Animals↗

Temporal integration of tone glides.

Temporal integration of rising and falling tone glides against a 50-2800-Hz background of noise at a sound pressure level of 60 dB re 20 micronPa was studied in two experiments. Glides were in the frequency ranges 200-700 Hz and 1200-1700 Hz for durations of 5-120 ms. Results indicate an asymmetry in the detectability of rising and falling glides of short duration, with rising glides detected at lower signal intensities in both frequency ranges. These effects are discussed in terms of differences in pattern of frequency analysis of identical, but temporally reversed, waveforms.

Acoustic Stimulation↗

Temporal integration of two-component tone glides.

Temporal integration of complex signals composed of two linearly combined tone glides was studied in a 60-dB SPL noise background. When both glide tones increased or decreased in frequency, integration functions differed for durations shorter than 50 ms in a manner similar to results obtained for single-component tone glides. That is, rising two-component glides were detected at lower thresholds than were falling two-component glides. However, when one component increased in frequency and the other decreased, thresholds were the same, regardless of which component increased and which decreased.

Acoustic Stimulation↗

Hepatic jaundice in a colony of nude mice.

A colony of nude mice was maintained under controlled standards of care for 12 months, at which time a rapidly escalating liver disease developed in the animals, characterized by jaundice, emaciation, and rapid death. Histologically, the livers had swollen, vacuolated hepatic cells and increased numbers of enlarged Kupffer cells. Mouse hepatitis virus was not isolated from the livers of sick mice. Although the nature of the lesions suggested toxicity, efforts to reproduce the lesions by increased exposure to chemical compounds used for colony husbandry were unsuccessful. A definitive determination of the causative agent was not made.

Animals↗

Naturally occurring mouse hepatitis virus infection in the nude mouse.

A group of athymic nude mice developed an unusual chronic wasting disease within 1-3 months after their arrival into the laboratory. Affected nude mice had severe, acute-to-chronic, active hepatitis with multinucleated giant hepatocytes and fibrosis. Vascular and central nervous system lesions were frequently present, giant cell peritonitis, ascites, and multinucleated giant cells in the intestinal epithelial villi were less frequently observed. Mouse hepatitis virus was isolated from the livers of three mice with lesions. The virus, when inoculated into nude mice, produced lesions similar to those observed in the natural outbreak.

Animals↗

Immunosuppressive activity of a subline of the mouse EL-4 lymphoma. Evidence for minute virus of mice causing the inhibition.

Filtered culture fluids from the early in vitro passages of a subline of the C57BL/6 mouse EL-4 lymphoma, EL-4(G-), were strongly inhibitory for BABL/c vs. C57BL/6 mixed lymphocyte cultures (MLC). The inhibitory activity could be preserved by storage at -75 degrees C or 4 degrees C, thus allowing its further characterization. The inhibitory factor was particulate (nondialyzable, sedimentable at 100,000 g for 1 h), very small (recovered after 0.10 mum filtration), sensitive to UV irradiation, but heat stable (56 degrees C, 1 h) and resistant to chloroform. It was infectious, since later, noninhibitory passages of EL-4(G-) tissue culture cells became strongly inhibitory upon inoculation with the culture fluid. This data was consistent with the inhibitory factor being an infectious virus. Virus analysis by mouse antibody production tests revealed that viruses were indeed present in EL-4(G-) ascites cells and in the culture fluid, and not in a late passage of EL-4(G-) tissue culture cells which were not inhibitory. Neutralization of the inhibitory factor was achieved by pretreatment with ascitic fluid or with the sera raised against those (EL-4(G-)-derived materials which contained viruses. Mouse reference immune sera against minute virus of mice (MVM) completely neutralized the inhibitory factor in the culture fluid or in EL-4(G-) ascites cells. Two prototype MVM strains, and one Kilham rat virus preparation, did not inhibit the mouse MLC. Thus, the possibility exists that a variant of MVM, or an unidentified virus, has been grown and selected for in EL-4(G-) cells and recognized, due to its immunosuppressive characteristics. In any event, immunosuppression by EL-4(G-) cells was not mediated by the tumor cells, their metabolic products, or associated endogenous type C viruses, but by an exogenous virus, most likely a variant MVM with immunosuppressive characteristics. This adds weight to a parallel observation from our laboratory on the immunosuppressive effects of Kilham rat virus in rat lymphocyte cultures.

Animals↗

Naturally-occurring Sendai virus infection of athymic nude mice.

Nude (nu/nu) mice, Balb/c-derived, responded to a naturally-occurring Sendai virus infection in a different manner than conventional mice. They developed a chronic debilitating disease and a persistent viral infection of the respiratory tract with intranuclear inclusion bodies in tracheal, bronchial and bronchiolar epithelial cells, laryngeal and tracheal glandular epithelium and in type I and II alveolar cells. The infection was identified by serologic and tissue culture studies, the mouse antibody production test and ultrastructural examination of pulmonary lesions. Phlebitis of pulmonary veins, suppurative rhinitis and otitis media accompanied the viral infection while some mice developed a secondary bronchopneumonia.

Animals↗

Effects of high exposure concentrations of inhaled low-toxicity dust on pulmonary function in guinea pigs.

The acute pulmonary function response to graded levels of a low toxicity dust was studied in guinea pigs. Four groups of five male guinea pigs each were exposed to mean concentrations of 0, 0.25, 1.01 and 5.39 mg Foundry Hill Clay l-1 air with mass median aerodynamic diameters of 2.6, 4.6 and 6.7 microns, respectively. There was a 15-min pre-exposure period to clean air, a 1-h exposure to the test atmosphere and then a 1-h recovery period with exposure to clean air. Concentration-related changes, compared to the pre-exposure period, occurred with a rapid onset in a number of parameters. Generally, the severity of observed effects increased with exposure time and, therefore, with inhaled dose. Statistically significant changes (P < 0.05) were observed in tidal volume, dynamic compliance, dynamic resistance, flow, pressure and minute volume during the last 15 min of exposure. The observed changes were consistent with acute bronchoconstriction. These effects reversed rapidly and there were no significant changes 1 h post-exposure. These results suggest that adverse physiological responses of short duration can occur when animals are exposed via inhalation to low-toxicity materials in the concentration range 0.25-5 mg l-1.

Administration, Inhalation↗