Leukocyte aggregation test: evaluation of reactivities and clinical allograft rejection.
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Evaluation Studies as Topic↗
Biomedical subjects
B H Tom
Publications and source records attributed to B H Tom.
Active specific immunotherapy potential for the treatment of large bowel cancer.
Active specific immunotherapy, harnessing the strength and specificity of the host immune response to destroy neoplastic cells, may offer an ideal surgical adjuvant treatment modality for human colon cancer. Unfortunately, achievement of this goal has been obscured by 1) the effect of excess residual disease to interfere with the host's destructive response, 2) the weak nature of tumor resistance, 3) the potential adverse effect of concomitant treatments such as chemotherapy, and 4) the present limitation of poorly defined immunogens to induce, as well as insensitive assay systems to detect, host sensitizaion. Recent immunologic and chemical research revealing distinctive surface membrane structures on colon cancer cells suggests that a controlled trial of irradiated, autochtonous cell vaccines (without mycobacterial adjuvants) may provide a new therapeutic tool for Dukes B2 and C stages of human colon cancer.
Antigens, Neoplasm↗
Human colon adenocarcinoma cells. II. Tumorigenic and organoid expression in vivo and in vitro.
A human colon epithelial tumor cell line (LS174T) recultured in vitro following passage through hamsters displayed differences in its cell doubling time and synthesis of carcinoembryonic antigen when compared with the cells grown solely in vitro. These animal-passaged cells more closely resembled the parent tumor cell line (LS180) derived from the primary tumor than LS174T, the trypsinized variant of LS180. Analysis of lactate dehydrogenase isoenzymes indicated that the tumor cells recovered from the hamsters were free of xenogeneic host tissue. Furthermore, LS174T grafted to athymic (nude) mice grew as a mucinous adenocarcinoma microscopically resembling the original tumor. The altered growth potential of LS174T was also demonstrated on confluent feeder monolayers of normal cells and by uninhibited multiplication in vitro. These results suggest that, at least in this one case, short-term passage of long-term cultured cells into xenogeneic hosts may effect a phenotypic reversion such that the cells regain properties observed in the primary tumor and the initial in vitro explant.
Adenocarcinoma↗
Human colonic adenocarcinoma cells. I. Establishment and description of a new line.
A series of human colonic epithelial cell lines have been cultured from a single patient: LS-180 the original adenocarcinoma, LS-174T a trypsinized variant, and normal colonic tissue. The malignant cells, 20 to 40, mum in diameter and oval to polygonal, exhibited characteristics of normal colonic mucosal cells, namely, abundant microvilli prominent in secretory cells, and the presence of intracytoplasmic mucin vacuoles. The cultured adenocarcinoma cells, but not normal, demonstrated neoplastic properties by producing high levels of carcinoembryonic antigen (CEA) and by the ability to be propagated in hamster cheek pouches and in immunodeprived mice. The CEA production by the newly established line LS-180 released 900 times more CEA per cell into the culture medium and bore 30 times more cell-associated material than the established line, HT-29. These cell lines may permit detection of distinctive chemical, physiological, pharmacologic, and immunologic characteristics of neoplastic colonic cells.
Adenocarcinoma↗
Cell surface alterations on colon adenocarcinoma cells.
By the use of five independent techniques, cell surface alterations distinctive of malignant as compared to normal colon cells were detected on in vivo surgical specimens and on cultured cell lines established in our laboratory. The findings, which were distinctive of the malignant as compared to the normal cell included: (a) polymorphism of surface microvilli on scan electron microscopy; (b) decreased susceptibility to infection with vaccinia and reovirus, but not to herpes, adeno- or echovirus: (c) production of large quantities of carcinoembryonic antigen; (d) presence of specific membrane proteins on sodium dodecyl sulfate-polyacrylamide gel analysis of plasma membranes purified from cell homogenates by ultracentrifugation in polyethylene glycol-dextran partitions; and (e) reaction with specific, cytotoxic, rabbit heteroantisera. Solubilized extracts of the malignant cells formed precipitin lines with the heteroantisera, suggesting that the distinctive antigens could be released from the cell surface. These results suggest that human colon carcinomas bear tumor-distinctive proteins and offer the prospect of specific immunodiagnostic reagents and immunotherapeutic tools.
Adenocarcinoma↗
The leukocyte aggregation test: immunodiagnostic applications and immunotherapeutic implications for clinical renal transplantation.
The leukocyte aggregation test (LAT) detects the in vitro adhesion of sensitized, but not nonimmune, recipient leukocytes onto donor kidney cell monolayers. The test specifically detects cell-mediated homograft immunity up to 15 days prior to the appearance of clinical signs or alteration of chemical indexes. The presence of a positive reaction always signified incipient homograft rejection, which was usually controlled by intravenously administered, high-dose methylprednisolone sodium succinate (Solu-Medrol) therapy. There was no instance in which methyl-prednisolone treatment effectively reversed rejection in the presence of a negative leukocyte aggregation test. One common form of homograft rejection may be characterized by positive LAT results, a cellular infiltrate on the renal biopsy specimen, and sensitivity to methylprednisolone therapy.
Animals↗
Purification of tumor-specific antigens. An overview of the relevance to human colon carcinoma.
Methods which dissociate intramolecular noncovalent bonds have been used to prepare soluble derivatives of cell-surface antigens. Applications of these techniques to human colon carcinoma are underway. Continuous tissue-culture strains derived from primary lesions were developed and shown to be composed of malignant epithelial elements. Parallel data on the preparation and activity of soluble materials in a murine model methylcholanthrene system reveal that although cultured cells are a satisfactory source for antigen extraction, they are poor targets of the immune response. The development of methods to quantitate the biologic activity of colon-specific, soluble materials may provide indicator systems to define the antigenic determinants, to permit purification, and to serve as assays of the efficacy of immunotherapy.
Adenocarcinoma↗
Complement-dependent anaphylactic reactions.
The concept of elicitation of reactions of anaphylactic type by non-tissue-fixing antibody, through activation of complement and release of anaphylatoxins by antigen-antibody complexes in vivo, is not clearly defined by published evidence. Experimental data are presented to demonstrate that guinea pig immunoglobulin G2 (noncytotropic) complexed with antigen in vitro elicits dermal reactions in guinea pigs, and that pretreatment of animals with complement-inactivating cobra venom factor diminishes such reactions. The various pathways through which immediate hypersensitive reactions may occur are discussed.
Anaphylaxis↗
Characteristics of the leucocyte-aggregation assay for cell-mediated immunity.
The leucocyte aggregation assay detects cell-mediated immunity by the specific adherence of sensitized lymphocytes onto target cell monolayers. Leucocyte aggregates appear to develop by instruction of non-immune cells by sensitized T lymphocytes. B cells may function in a secondary capacity to amplify aggregate formation. The reactions are sensitive to low temperatures and to metabolic inhibitors of protein and RNA synthesis and function. Serum factors alternatively enhanced or blocked the phenomenon, depending upon the immune status of the patient. This assay may prove useful for the dissection of allograft rejection and tumor resistance due to its brevity, reflection of T-cell immunity, and sensitivity to host humoral factors.
B-Lymphocytes↗