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Biomedical subjects

J H Ransom

Publications and source records attributed to J H Ransom.

9 recordsLinked to original sources

Expression of class II major histocompatibility complex molecules correlates with human colon tumor vaccine efficacy.

Vaccination of colon cancer patients with X-irradiated autologous tumor cells and Bacillus Calmette-Guérin results in a significant reduction in tumor recurrence. A study was undertaken to determine whether the expression of tumor-associated antigens, expression of major histocompatibility complex molecules, or the cellular composition of the vaccine cells correlates with vaccine efficacy. A significant increase in the percentage of histocompatibility leukocyte antigen (HLA) class II molecule-expressing tumor cells was the only marker with a positive correlation. Because HLA class II molecule expression is not a prognostic marker in control patients, it was hypothesized that HLA class II molecules are involved in the induction of tumor immunity in patients treated with the autologous colon tumor vaccine. Enhancement of HLA class II molecule-expressing cells could be induced in X-irradiated colon tumor cells injected into the skin of mice when the cells were mixed with gamma-interferon. Therefore, addition of gamma-interferon to the colon tumor vaccine, resulting in increased numbers of HLA class II molecule-expressing cells, could potentiate the generation of tumor immunity.

Antigens, Neoplasm

Acarex test correlates with monoclonal antibody test for dust mites.

Forty-two dust samples from the homes of patients having positive mite skin tests were tested by both monoclonal antibody and Acarex techniques. A Spearman's correlation coefficient of 0.85 (p = 0.0001) was found. The Acarex test is simple to use and is much less expensive than the monoclonal antibody method. The use of either method may enhance patient compliance with mite-control instructions and may prove crucial to the effective use of miticides in infested homes.

Animals

Dust mite assays in clinical allergy practice: mite antigen exposures among skin test positive patients in Kansas.

We have attempted to determine whether sensitive monoclonal antibody assays for Dermatophagoides mite antigens Der p I and Der f I can be carried out in a private clinical allergy practice laboratory, to ascertain incidence of significant home mite exposure in dust samples from patient homes in Kansas, and to consider whether such information impacts on patient management. We analyzed 152 dust samples from 62 patient homes. All patients were skin prick test positive for one or both common mite species available for skin testing, and had potentially relevant histories. Der p I and Der f I antigen levels were added together, and levels above 2 micrograms/g of dust were considered "positive." By this definition, elevated levels were found in at least one sample from 48 of 62 homes tested (77%); however, 61% of mattress samples tested, 41% of carpet samples, and 54.5% of furniture samples had levels below those considered likely to cause symptoms. Only 13 of 152 samples yielded Der p I levels above 2 micrograms/g. We conclude that monoclonal antibody assays for Der p I and Der f I antigens can be performed in a well-equipped office laboratory staffed by trained medical technologists, that Der f I is the predominant mite species in Kansas, and that data derived from mite assays may be important in treatment planning for patients suspected of having mite-related allergy symptoms.

Allergens

Flow cytometric evaluation of leukoregulin as an intrinsic molecular mediator of natural killer lymphocyte cytotoxicity.

The action of leukoregulin, a dominant tumor inhibitory lymphokine in native nonfractionated lymphokine preparations, was studied at the target cell level to ascertain its role as a molecular mediator in natural killer lymphocyte cytotoxicity. Leukoregulin was isolated from lymphokines produced by phytohemagglutinin stimulated human peripheral blood mononuclear leukocytes. Thirty minute leukoregulin treatment increased the sensitivity of human K562 leukemia cells to natural killer cell cytotoxicity. Maximum target cell sensitization to natural killer cytotoxicity was achieved within two hours. Measurement of K562 cell surface conformation by narrow angle forward light scatter and plasma membrane permeability by fluorescein diacetate fluorochromasia with a FACS IV flow cytometer demonstrated leukoregulin specific bio-membrane changes as early as five minutes with a maximum being attained within two hours of target cell exposure to leukoregulin. Analysis of K562 cells during development of a natural killer cell cytotoxicity reaction showed identical flow cytometric cell surface membrane changes to those developing in K562 cells exposed to leukoregulin alone. These observations suggest that leukoregulin is an intrinsic element in natural killer cell cytotoxicity and that the modulation of natural killer cell cytotoxicity may result from the early alteration in target cell surface membrane integrity induced by leukoregulin.

Cell Line

Analysis of a cytostatic lymphokine produced by incubation of lymphocytes with tumor cells: relationship to leukoregulin and distinction from recombinant lymphotoxin, recombinant tumor necrosis factor, and natural killer cytotoxic factor.

Supernatants from the coculture of peripheral blood lymphocytes and the NK-susceptible cell line K562 were highly growth inhibitory for a variety of tumor cell lines. No correlation was observed between the susceptibility of the target cell lines to growth inhibition and to lysis by NK cells. Rather, the spectrum of cytostatic activity and the characteristics of the soluble factor were similar to those of leukoregulin, a recently described lymphokine. The supernatants of tumor-lymphocyte cultures contained only low levels of IFN-alpha and IFN-gamma, and antibodies to interferons did not affect the observed growth inhibition. The pattern of target cell susceptibility to growth inhibition by this factor was also quite distinct from that seen with purified recombinant LT or TNF. Furthermore, monoclonal antibodies to these cytokines also had no effect on the cytostasis, arguing against a requirement for, or synergistic interaction with, low levels of these cytokines. Some of the targets susceptible to the factor were only growth inhibited but not lysed, thereby distinguishing it from NKCF. Furthermore, the cytostasis was not inhibited by mannose-6-PO4 or rabbit antibodies to granule cytolysin, both of which have been reported to block NKCF. Therefore, the results show that a cytostatic factor is released in tumor-lymphocyte incubation that is quite distinct from interferons, LT, and TNF but has characteristics that resemble those of leukoregulin.

Adult

Immunological monitoring in a controlled trial of immunotherapy in stage IIB malignant melanoma.

Fifteen patients undergoing surgery for Stage IIb malignant melanoma were randomly allocated either to a group who received a vaccine of BCG mixed with irradiated autologous melanoma cells, or a control group who received no further treatment. All patients were monitored sequentially for immunological competence and tumour-directed immunity, using a wide range of techniques, and the results were compared retrospectively with their clinical course. Three months after surgery, there was a trend towards inhibition of PHA-induced lymphocyte transformation by autologous serum in patients who developed recurrent tumour within 12 months after treatment. Serum from patients who remained tumour-free for 12 months did not inhibit stimulation of autologous lymphocytes by PHA. Apart from this test, no other immunological parameters correlated either with clinical course or with the type of treatment received.

Antibody Formation

Vox dox.

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Asthma