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Biomedical subjects

M G Lewis

Publications and source records attributed to M G Lewis.

At least 109 records · Page 6Linked to original sources

Cellular localization of immunoglobulin within human maglignant melanomata.

The presence of antibody in patients with malignant melanoma is well established if one examines the serum. In this report we have attempted to identify antibody within solid tumours showing that they are rarely present in any appreciable quantity on the surface of tumour cells but can be seen frequently on a number of different types of host cell within the tumours. This is discussed in the light of the role of antibody in the circulation and the possibility of antibody behaving as a blocking factor in vivo.

Antibodies, Neoplasm↗

Immune complexes in human melanoma: a consequence of deranged immune regulation.

Circulating immune complexes were detected in 62 individuals with malignant melanoma by precipitation with isolated human C1q and polyclonal rheumatoid factors. In 56 patients the C1q deviation assay showed low to moderate levels of complexes, with increased amounts with advancing stage of disease. Both heavy (greater than 19S) and intermediate (7S to 19S) varieties were present, and complexes containing tumor antigen-antibody or antibody-anti-antibody were identified. Complexes were found in the kidneys of one patient with malignancy and the nephrotic syndrome and in two further patients with melanoma in whom there were no clinical manifestations of nephrosis. Serial determinations in 51 patients showed slow cyclic variations in the levels of complexes and fluctuations in response to therapy. The coexistence of anti-antibodies, immune complex disease, and anergy in melanoma patients may indicate a deranged immune regulation consequent to chronic antigenic stimulation by the tumor.

Adult↗

Tumor-associated antibodies in the serum of patients with uveal melanoma.

Antibodies reacting with autologous and allogeneic cytoplasmic antigens and with autologous surface membrane antigens of uveal melanoma cells were demonstrated in the serum of three patients with relatively small, histologically-proven malignant melanomas of the choroid. The significance of these findings and planned applications of these investigations with regard to diagnosis, prognosis, and therapy of patients with suspected or proven ocular melanomas are discussed.

Aged↗

Fetal antigens in nonneoplastic conditions.

During studies that showed the presence of fetal antigens on the surface of human malignant melanoma tumor cells, polyvalent antisera specific for human fetal tissues of varying ages were developed. These reagents demonstrated varying patterns of expression of fetal antigens at different ages in various tissues of the human fetus. The possibility that nonneoplastic adult cells showing either maturation arrest or excessive proliferation also might express fetal antigens led to studies of human bone marrow. Although normal bone marrow cells expressed low levels of fetal antigens, large amounts were seen on bone marrow cells of patients with anemias due to iron, B12, or folic acid deficiencies, as well as on those with leukemia. Moreover, normal adult tissues adapted to long-term culture also expressed fetal antigens. After 3 weeks in organ culture adult human skin showed morphological changes similar to those seen in fetal periderm and strongly expressed fetal antigens. In addition, lymphoblasts in long-term cultured human lymphoid cell lines established from normal donors also carried surface fetal antigens. These latter antigens were shared with neoplastic B-cells (chronic lymphocytic leukemia) but not with T-cells. Their expression varied with the cell cycle. The reexpression of fetal antigens on malignant cells is thought to signal a basic derangement in the control of differentiation which is considered to be peculiar to neoplasia. However, these studies indicate that normal adult cells also may reexpress fetal antigens under circumstances unrelated to neoplasia but associated with either maturation arrest or rapid and excessive proliferation.

Adult↗

Immunotherapy for cancer: an overview.

Immunotherapy of cancer is of interest to oncologists because it is specifically directed to cancer cells, sparing normal cells. While it is ineffective in most patients, especially those with widespread metastatic disease, it occasionally produces good results. Each of the available methods has inherent problems and, recently, attempts have been made to overcome some of these. There is a strong case for small-scale experimental trials in highly selected groups of patients who are intensively investigated for their immunologic status in relation to their tumour. Despite the lack of success in general, immunotherapy still appears to have a future as an adjunct to existing therapy in order to control as much as to cure residual tumour.

Adjuvants, Immunologic↗

Foetal-associated material: its expression in long-term cultured human skin.

Using immunofluorescence and electron microscopy, we have demonstrated the presence of "foetal substances" (antigens) in skin kept in tissue culture medium for periods of time ranging from 9 days-18 weeks. This is a specific reaction demonstrated with an anti-human foetal serum raised in New Zealand white rabbits. It is suggested that the expression of foetal substances by cells in the skin under these abnormal conditions might lead to the masking or modification of the normal histo-compatible antigens, enabling such skins to survive transplantation without rejection.

Adult↗

Long-term organ culture of human skin: an ultrastructural and immunochemical study.

Human skin grown in tissue culture medium for periods of up to 18 wk undergoes characteristic morphological changes. After an initial period of degeneration, new foci of epidermal cells arise at the dermo-epidermal junction and by rapid proliferation these cells spread out to form a complete second epidermal layer beneath the degenerating original strata. Stratification occurs in this new epidermis with incomplete keratinisation. The individual keratinocytes show ultrastructural similarities with fetal cells. There is a loss of complexity of the cytoplasm typified by a marked reduction in the numbers of keratin filaments and a decrease in the numbers of desmosomal contact areas. In addition, the formation of cilia and accumulation of glycogen in the cell cytoplasm are characteristic. The cytoplasm of the basal cells contains numerous polyribosomes and there is evidence of synthetic activity as illustrated by the proliferation of rough-surfaced endoplasmic reticulum and Golgi complex. Fluorescent and EM immunocytochemical staining with an anti-fetal antiserum demonstrates the development of fetal substances on the surface of cells during the regeneration stage occurring in the cultured skins. The significance of these observations concerning transplantability of cultured tissues is discussed.

Cell Division↗

The pathogenesis of reflux nephropathy (chronic atrophic pyelonephritis).

The relationship between vesico-ureteric reflux and coarse renal scarring (atrophic pyelonephritis) has been studied in swine. Scars were observed to develop where reflux took place into the kidney substance via the renal papillae (intrarenal reflux). They were confined to these regions and were similar in size, distribution and other features peculiar to those found in the human from early childhood onwards. Intrarenal reflux was found to be related to the pressure within the urinary tract as well as to vesico-ureteric reflux. Infection was not an essential factor in scar-formation, but it appeared to intensify the scarring process. The histological findings were a progressive focal interstitial fibrosis confined to the zones of intrarenal reflux, extending from the capsule to the papillary tip, and varying in severity with pressure, time and the extent of intrarenal reflux. Nephron and tubular damage accompanied all grades of fibrosis, with the possible exception of the earliest. In many respects the histological changes closely resemble those due to obstruction, except they are focal in distribution. Added features are the early peripheral lymphocytic aggregations and interstitial fibrosis which appear to suggest that some "irritant"--possibly urine--reaches the interstitium and drains away via the lymphatic system. Many of the phenomena observed were strikingly similar to those present in children with the more severe grades of vesico-ureteric reflux. In some cases a mixture of generalized obstructive nephropathy and focal scarring developed; in others focal scarring took place with normal papillae elsewhere. The results are readily reproducible. The basic questions as to whether it is bladder pressure, or infection, or a mixture of the two which is responsible for scar-formation are discussed.

Adult↗