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Biomedical subjects

D Keast

Publications and source records attributed to D Keast.

At least 73 records · Page 4Linked to original sources

Biologic and immunologic studies on a murine model of regional lymph node metastasis.

Some biologic, hematologic, and immunologic aspects of the growth and metastasis of the MC-2 fibrosarcoma indicated its suitability as a model for the study of lymphogenous metastasis. The tumor was maintained in syngeneic female BALB/c mice by the serial sc passage of 10(5) viable tumor cells. It metastasized macroscopically in all mice to regional lymph nodes (RLN) and to the lungs. Both forward and retrograde node-to-node metastases were found. Tumor growth and metastasis were associated with splenomegaly, thymus atrophy, cachexia, neutrophilia, lymphopenia, and anemia. Tumor excision at various times after inoculation showed that all mice whose tumors were excised when there was histologic evidence of metastasis in all RLN (day 13; mean of tumor wt, 122 mg) died subsequently from metastases, whereas no animals died whose tumors were excised on or before day 8 (mean of tumor wt, 15 mg). The onset of metastasis was seen in some RLN on day 8. All survivors were immune to challenge with 10(5) viable tumor cells, which demonstrated the immunogenicity of the tumor. Concomitant tumor immunity could be demonstrated prior to the onset of metastasis (days 6 and 7) but not early (days 0--2) or late (days 15, 19, and 20) in primary-site tumor growth. The early immune response to the tumor demonstrable as concomitant tumor immunity appeared to be abrogated by the progressive growth and metastasis of the neoplasm. Tumor cells passaged in adult thymectomized, X-irradiated, syngeneic recipients produced larger RLN metastases and smaller primary tumors than those passaged in control mice.

Animals↗

Passage and Survival of Chlamydospores of Phytophthora cinnamomi Rands, the Causal Agent of Forest Dieback Disease, Through the Gastrointestinal Tracts of Termites and Wild Birds.

Chlamydospores of Phytophthora cinnamomi Rands have been shown to survive in the intestinal tracts of termites (Nasutitermes exitiosus) and two species of forest birds indigenous to West Australian jarrah forests. Viable chlamydospores were recovered from bird feces within the normal rate of passage time for food through the gut. The above factors would allow these creatures to function as vectors for the spores.

Journal Article↗

Cigarette smoke and phagocyte function: effect of chronic exposure in vivo and acute exposure in vitro.

Phagocytic function was studied in mice chronically exposed to cigarette smoke, and the effects of in vitro exposure to cigarette smoke on macrophage activity were also assessed. Cultures of radiolabeled Pseudomonas aeruginosa were employed to investigate phagocyte activity in vivo and in vitro. Mice were exposed on weekdays to fresh cigarette smoke for periods up to 37 weeks and the bactericidal and clearance activity of their lungs was measured. Both pulmonary clearance and bactericidal activity was impaired. The clearance of intravenously injected bacteria from the blood of smoke-exposed mice occurred at the same rate as in control mice, but the accumulation of radiolabel by the liver was decreased. In addition, the rate of elimination of radiolabel from the liver was less than the controls. Macrophages exposed to cigarette smoke in vitro initially had a depressed phagocytic rate, but if phagocytosis over a prolonged period was measured it was eventually enhanced over the rate of control macrophages. The vapor phase of cigarette smoke could also transiently inhibit and then enhance the phagocytic activity.

Animals↗

Erythrocyte autoantibodies induced in mice immunized with rat antigens.

Antibody reacting against syngeneic mouse erythrocytes could not be elicited (by rat erythrocytes) in athymic nude mice. Rat antigen preparations from heart, muscle testes, brain erythrocyte ghosts and foetal material failed to elicit detectable autoantibody reactivity against mouse erythrocytes, even though all these preparations (other than brain and foetal) induced a reduction in half life of syngeneic murine erythrocytes in vivo. We suggest that an unstable rat erythrocyte antigen is responsible for the induction of the autoimmune reactions, which in turn depend on T-cells for their generation.

Animals↗

Modification by soluble antigen of the immune response to mycobacterial infection.

After inoculation with viable BCG organisms, spleen cells from mice developed cellular immune reactivity to purified protein derivative antigen by day 10, which declined by day 25; after rechallenge on day 25, a vigorous secondary response rapidly developed (by day 29). The inclusion of autochthonous serum (from the BCG-infected mice) in the in vitro cellular immune reactivity tests altered this pattern considerably: the primary response was shortened, and the secondary response totally abated, suggesting the presence of blocking factors active against BCG-specific cellular immune reactivity in the sera of infected animals. Subsequent experiments indicated that BCG-specific serum blocking factor activity could be generated in the serum of control mice by the intravenous inoculation of purified protein derivative.

Animals↗

Serum modulation of in vitro cellular immune reactivity to Epstein-Barr virus-associated antigen.

The reactivity of peripheral blood leukocytes to Epstein-Barr virus-associated antigen was assessed employing two in vitro tests, leukocyte adherence inhibition (LAI) and leukocyte migration inhibition (LMI). In both tests, autologous serum from some normal subjects was shown to confer strong reactivity on weak or non-responder cells. Reactivity to purified protein derivative of tuberculin (PPD) assessed in parallel was shown to be unaffected by autologous serum. Employing the LAI system, variations in the effects of autologous serum samples collected on consecutive days was shown to be dependent on the reactivity of the leukocytes themselves, rather than changes in the activity or concentration of factors present in the serum.

Antigens, Viral↗

Cell-mediated immune response to influenza virus infections in mice.

The local and systemic cell-mediated immune (CMI) responses to influenza virus infection in mice were examined by leukocyte migration inhibition and lymphocyte-mediated cytotoxicity tests. Mice were inoculated intranasally with 5 50% lethal doses of the A/WSN (H0N1) strain of influenza virus. Cells from the lymph nodes draining the upper and lower respiratory tract were used to measure the local response, and the spleen was the source of cells used for systemic determinations. The local response by pulmonary lymph node cells was greater and appeared earlier than was observed systemically in the spleen. The specificity of the CMI response was investigated by using a heterologous virus strain, A/Jap (H2N2), and recombinants A/Jap-NWS (H2N1) and A/NWS-Jap (H0N1), obtained from a cross between A/Jap (H2N2) and a virus, A/NWS (H0N1), with surface antigenic specificity similar to that of the inoculated virus. From the results of both tests used as correlates of CMI, it appeared that the response was specific against the hemagglutinin component of the inoculated virus. No reactivity was observed against the heterologous virus A/Jap (H2N2) nor against the recombinant A/Jap-NWS (H2N1) bearing the same neuradminidase as that of the inoculated virus.

Animals↗

Dissociation of correlates of cellular immunity in man: functional heterogeneity within the antigen-reactive cell population?

Cellular immune responsiveness (CMI) to ubiquitous bacterial antigens was assessed in serial peripheral blood samples collected from normal subjects, employing three in vitro correlates of CMI in parallel. Delayed cutaneous hypersensitivity (DCH) was also assessed on a number of occasions in these subjects. These experiments showed that the reactivity of peripheral blood leukocytes from normal individuals as measured in each of the in vitro tests fluctuated from day to day, and that the reactivity of cells functioning in each of the tests fluctuated independently of one another. In contrast, DCH reactivity in these individuals was not subject to such fluctuations. The results are discussed in terms of the periodic appearance of functionally distinct subpopulations of T lymphocytes in the peripheral circulation.

Antigens, Bacterial↗

The in vitro response to phytomitogens of marsupial leukocytes.

Leukocytes from two macropod marsupials, the quokka (Setonix brachyuras) and the tammar (Macropus eugenii) were separated from whole blood by dextran sedimentation and established in culture with either phytohemagglutinin-P, concanavalin A, or pokeweed mitogen. The leukocyte response to each mitogen, as measured by the incorporation of tritiated thymidine into DNA, was similar to that described in other experimental systems. These results suggest that the functional elements of the cellular immune response in marsupials may have evolved along very similar lines to those in the eutherian mammals.

Animals↗

Early onset of serum blocking in a murine melanoma model.

The early onset of serum blocking of host cell-mediated immunity was investigated in a transplantable murine melanoma employing two in vitro assays. One of these was based on the Takasugi and Klein cytotoxicity test; the other was a new test based on the inhibition of adherence of leukocytes to a plastic surface in the presence of tumor antigen. Both tests yielded similar results, and the adherence inhibition test was more sensitive. Blocking could be detected as early as 1 h after the inoculation of 1 times 10(7) melanoma cells. Early onset of serum blocking was also demonstrable if homogenized of tissue-cultured tumor cells were inoculated. Serum blocking under these circumstances was initially transient, declining at 24 to 48 h, but reappearing by the 4th day after inoculation. Furthermore, a functional immune system was not required for blocking factor development in this system, as evidenced by the onset of a similar pattern of blocking activity in heavily irradiated animals.

Animals↗

The L.A.I. microtest: a rapid and sensitive precedure for the demonstration of cell-mediated immunity in vitro.

A new microtest for cell-mediated immunity is described, which is based on the elaboration of a diffusible factor from sensitized lymphocytes following contact with specific antigen. The factor inhibits the adherence of neighbouring leucocytes to plastic surfaces. Production of the factor is ablated by pretreatment of lymphocytes with Theta-antiserum. It is suggested that the factor may be a new lymphokine, leucocyte adherence inhibition factor (LAIF).

Animals↗

Changes in host immunity following excision of a murine melanoma.

Changes in cell mediated and humoral immunity following the excision of a transplantable melanoma growing in the footpad of its syngeneic host, as measured by an in vitro cytotoxicity test, were assessed. Spleen cell cytotoxicity did not change significantly. Cells from the regional lymph nodes stimulated tumour growth before tumour excision. Three days following tumour excision this stimulatory effect was undetectable. Loss of serum factors capable of blocking the cytotoxicity of spleen cells occurred 24 h after tumour excision. Serum cytotoxicity increased after tumour excision to a maximum of the third day. Following tumour excision the rise in serum cytotoxicity and loss of regional lymph node tumour stimulation were concomitant with the loss of blocking activity.

Animals↗