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Biomedical subjects

R E Kast

Publications and source records attributed to R E Kast.

30 records · Page 2Linked to original sources

Cancer diagnostic test of Field and Caspary: Part I. Spontaneous aggregation of lymphocytes in saline suspension is blocked by albumin and histone in normals but not in various disease states: the lymphocyte aggregation blocking test.

A blood test is described which is often positive in diverse disease states. In this test washed patient lymphocytes are incubated with histone or albumin. Early aggregation indicates that the patient might have inflammatory, malignant, or other disease, while absence of aggregation is the pattern found in normals. The test is called the lymphocyte aggregation blocking (LAB) test. Positive results when testing cancer patients were 86%, normals 14%, and non-malignant hospitalized patients were 50%. Lymphocyte aggregation was not an active process mediated by added protein. All washed lymphocyte suspensions will aggregate in the test conditions, whether, from normals, cancer or non-cancer patients if no protein is added. Normals' lymphocyte suspensions are prevented from aggregating by the added histone or albumin.

Antigens, Neoplasm↗

Cancer diagnostic test of Field and Caspary: Part II. A review and interpretation of the collected data.

Tables are presented showing data collected to date on the clinical trials of the macrophage electrophoretic mobility test for cancer of Field and Caspary. Seven variations on the original technique are summarized. The original antigen used in these tests was the basic protein of CNS myelin. Four additional proteins have been shown to function in these tests in place of the basic protein. There appears not to be a strong immunological crossreaction between these proteins. This paper discusses a possible solution to the problem of why non-crossreactive proteins appear to crossreact when testing cancer patients with the macrophage electrophoretic mobility related tests. All lymphocytes in saline suspension without added protein will aggregate. This is prevented in normals by the addition of some proteins to the culture, but is not so prevented in cancer and other diseases. Aggregation results in lymphokine release that makes the macrophage electrophoretic mobility test and variants positive. Aggregation occurs in the first incubation step of these tests and this non-immunological aggregation is the underlying phenomenon detected rather than specific antigen recognition as has been heretofore presumed.

Antigens, Neoplasm↗

Predominance of autoimmune and rheumatic diseases in females.

This paper offers an explanation for the higher female incidence found in many of the autoimmune and rheumatic diseases. A list of these diseases (Table 1) shows that half of them occur in three females for each male affected. Females are genetic and hence antigenic mosaics, half their somatic cells expressing antigens derived from the paternal X, half from the maternal X (female heterochromatinization). The Burnet-Jerne theory of somatic generation of antibody diversity and forbidden clone elimination states that lymphocytes under maturation in the thymus are killed or suppressed if they recognize and hence react to a histocompatibility antigen. If this were to hold for other self antigens as well, as recent models of clonal generation and selection mechanisms predict, then lymphocytes happening to pass the crucial stage in the thymus meeting only cells expressing one of the parental X's could be released still able to react to self i.e. those somatic cells expressing the other parental X with which the lymphocyte had not been in contact. Thus, self-tolerance would be more easily broken in females than in males.

Autoimmune Diseases↗

Lymphocytes and cells in malignant transformation: similarities and possible relationship between the two cell types.

This paper points out some similarities between the behaviour and characteristics of lymphocytes and their transformation to lymphoblasts on one hand and malignant cells on the other. The areas of similarity are (1) anomalous communicating junction formation; (2) recruitment of neighbouring cells; (3) random antigen expression; (4) Fc synthesis; (5) stimulation by immune attack; (6) relation to a plasminogen activator, and (7) inhibition of stimulation by trypsin inhibitors. It is argued that, considering the anomalous membrane characteristics shown by lymphocytes and malignant cells and the list of similarities, carcinogenesis could represent a normal cell line infected with lymphocytic information. Two incidental ideas are presented based on the main idea. These concern lymphocytes but are related to malignant cells and their characteristics too. They are (1) a mechanism whereby generation of randomness in the variable region of Ig molecules could take place, and (2) a mechanism whereby the lymphocyte, in order to kill its target, could use the normal cell's propensity to form communicating intercellular junctions.

Animals↗

A solution to the graft-versus-host problem in bone marrow transplantation to humans.

Many clinical situations arise where it would be desirable to transplant bone marrow to a marrow function deficient patient. However, bone marrow is immunologically competent by virtue of its content of lymphocyte precursors. Marrow transplantation in these patients is followed by the graft's immunological rejection of the patient - a fatal disease. A system for specific abrogation of this graft-versus-host disease after xenogeneic bone marrow transplantation to humans is presented. In this system, prospective patient cells are removed by skin biopsy for example, and injected into a fetal chimpanzee. The fetal chimpanzee becomes tolerant to this patient's antigens and will not attack or reject them when its bone marrow is removed after birth and injected into the specific patient from whom the tolerogenic cells were obtained. A simple and straightforward experimental test of this system's clinical applicability is also presented.

Animals↗

Ribavirin in cancer immunotherapies: controlling nitric oxide helps generate cytotoxic lymphocyte.

Either ribavirin, RBV, or cyclophosphamide, CY, can shift an immune response from Th2 towards a Th1 cytokine profile. CY is used in this role in various current cancer immunotherapy attempts but with mixed success. More potent and reliable immunoadjuvants and Th 1 response biasing methods are needed. RBV is used today mainly to augment interferon-alpha treatment of hepatitis C. RBV shifts an immune response from Th2 towards Th1 more effectively than CY and may be a safe and useful adjuvant for current cancer immunotherapeutic efforts. RBV is thought to act by inhibition of tetrahydrobiopterin synthesis. Tetrahydrobiopterin is an essential co-factor for all known isoforms of nitric oxide synthase. Lowered nitric oxide favors Th1 development as high levels favor Th2 weighting.

Animals↗