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Biomedical subjects

V Ramakrishna

Publications and source records attributed to V Ramakrishna.

28 records · Page 2Linked to original sources
PubMed1993

Increased projection of MHC and tumor antigens in murine B16-BL6 melanoma induced by hydrostatic pressure and chemical crosslinking.

The B16-BL6 melanoma, like most spontaneously arising tumors, is poorly immunogenic and expresses low levels of major histocompatibility complex (MHC) antigens. Treatment of cells of this tumor in vitro by hydrostatic pressure in the presence of adenosine 2',3'-dialdehyde (oxAdo), a membrane-impermeant crosslinker, caused elevated projection of MHC and a specific tumor antigen as demonstrated by flow-cytometric analysis. Maximum projection of both the MHC and the tumor antigens could be reached by application of 1200 atm for 15 min in the presence of 20 mM oxAdo. It is not yet clear whether this passive increase in availability of antigens on the cell surface originated from a dormant pool of antigens in the plasma membrane or from pressure-induced fusion of antigen-rich intracellular organelles (e.g. the endoplasmic reticulum). The immunogenic properties of the antigen-enriched B16-BL6 cells are described in the following paper.

Animals↗
PubMed1993

Induction of cell-mediated immunity against B16-BL6 melanoma in mice vaccinated with cells modified by hydrostatic pressure and chemical crosslinking.

In the preceding paper we have demonstrated an increase in presentation of both major histocompatibility complex antigens (MHC) and a tumor-associated antigen of the weakly immunogenic B16 melanoma by a straight-forward technique. The method consists in modulating the tumor cell membrane by hydrostatic pressure and simultaneous chemical crosslinking of the cell-surface proteins. In B16-BL6 melanoma, the induced antigenic modulation was found to persist for over 48 h, which permitted the evaluation of the ability of modified B16-BL6 cells to induce immunity against unmodified B16-BL6 cells. In the present study, we have shown that a significant systemic immunity was induced only in mice that were immunized with modified B16-BL6 melanoma cells, whereas immunization with unmodified B16-BL6 cells had only a marginal effect when compared to the results in control sham-immunized mice. The induced immunity was specific since a single immunization affected the growth of B16-BL6 tumors but had no effect on MCA 106, an antigenically unrelated tumor. The addition of interleukin-2 to the immunization regimen had no effect on the antitumor responses induced by the modified B16-BL6 cells. The cell-mediated immunity conferred by immunization with treated B16-BL6 cells was confirmed in experiments in vitro where splenocytes from immunized mice could be sensitized to proliferate by the presence of B16-BL6 cells. In addition, the altered antigenicity of these melanoma cells appeared to correlate with their increased susceptibility to specific effectors. Thus, 51Cr-labeled B16-BL6 target cells, modified by pressure and crosslinking, in comparison to control labeled target cells, were lysed in much greater numbers by effectors such as lymphokine-activated killer cells and allogeneic cytotoxic lymphocytes (anti-H-2b), while such cells remained resistant to lysis by natural killer cells. Our findings indicate that the physical and chemical modifications of the tumor cells that are described here may be considered as a simple yet effective method for the preparation of tumor vaccines, which could be applied in tumor-bearing hosts.

Animals↗
PubMed1993

Antitumor effects of recombinant interleukin-6 expressed in eukaryotic cells.

In the present study we evaluate the antitumor efficacy of a glycosylated molecule of interleukin-6 (IL-6), which was cloned and expressed in Chinese hamster ovary cells. When tested with two syngeneic murine tumors, the MC38 adenocarcinoma and the MCA106 fibrosarcoma, recombinant IL-6 (rIL-6) significantly reduced the number of day-3 established MC38 lung metastases, but had no effect on MCA106 lung metastases. A similar effect of rIL-6 was seen on day-3 MC38 liver metastases. The antitumor activity mediated by rIL-6 was achieved at doses of the cytokine ranging from 6 micrograms to 150 micrograms/day. There was no correlation between the responsiveness to rIL-6 of these two tumors and their susceptibility, in vitro, to a direct cytostatic effect of the cytokine or the increase in the expression of major histocompatibility complex (MHC) antigens after exposure to rIL-6. However, a correlation was seen between the antitumor response to rIL-6 and the initial number of tumor cells expressing MHC antigens. The possible role of MHC antigens expressed on tumor cells, the generation of MHC-restricted cytotoxic cells and the responsiveness to IL-6 are discussed.

Animals↗
PubMed1991

Potentiation of delayed-type hypersensitivity response to syngeneic tumors in mice prevaccinated with cells modified by hydrostatic pressure and crosslinking.

Delayed-type hypersensitivity (DTH) to the chemically induced EL4 and virally induced ARadLV 136 leukemia cells was determined by the radioactive ear test. Prior to the DTH test, mice were prevaccinated with cells treated either with hydrostatic pressure or with the membrane-impermeant crosslinker adenosine dialdehyde or with a combination of these. For both tumor cells, DTH against unmodified cells was markedly potentiated by prevaccination with cells treated with hydrostatic pressure combined with adenosine dialdehyde. In vitro cytotoxicity data indicated that maximal lysis of target cells is induced by vaccination with adenosine-dialdehyde-treated cells, as well as by pressure in combination with adenosine dialdehyde treatment. In addition, increased [3H]thymidine uptake was observed in effector T cells induced by prevaccination with tumor cells modified by adenosine dialdehyde or pressure or both. This novel and innocuous potentiation of an antitumor immune response may have a practical utility in the treatment of human cancer.

Adenosine↗
PubMed1977

The real challenge: a self-health system with genuine commitment.

Major concepts and principles of health education have succeeded when they have been applied in the field with genuine commitment as illustrated by the programme at the Rural Health Training Centre in India and demonstrated by health education projects in Indonesia, Nepal, Sri Lanka and Thailand. But community health programmes have either failed or their progress been retarded by lack of true commitment to these concepts and principles. At the political, administrative and technical levels of administration, commitment can be developed and strengthened by involvement in health education programmes which apply and adapt health education concepts and principles. Commitment spreads vertically and horizontally, and health education faculty in the schools of public health should facilitate this process. Health education with commitment should operate as a self-reliant health care delivery system to meet the primary health needs of people. Its evolution and development into a self-health system which links and involves the individual, family, community, school, work place, institutions and the total environment in an integrated self-care process is a challenge to be faced. Though the individual and his family assume responsibility for their health, each component of the system has an important role in maintaining and promoting it. In addition there are facilitating systems like the drug industry, whose participation will be crucial for effective functioning of the self-health system. Development of self-health systems is the emerging challenge which the health education specialists of the future will have to meet and they have to be trained adequately in new areas of knowledge, relationships, experience and skills. The new role, in addition to traditional skills, requires a high degree of competence in pioneering, innovating, planning, coordinating and evaluating education for self-health care measures. Above all, health education specialists should be continuously engaged in action research activities which reinforce their commitment to the principles and concepts of health education and promote its spread to all the key levels of the administration.

Community Health Services↗