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Biomedical subjects

J U Gutterman

Publications and source records attributed to J U Gutterman.

At least 289 records · Page 16Linked to original sources

Bacillus Calmette-Guérin immunotherapy in combination with DTIC (NSC-45388) for the treatment of malignant melanoma.

Combination studies of immunotherapy and DTIC chemotherapy for patients with malignant melanoma are described. At our institute the combination of bacillus Calmette-Guérin (BCG) with DTIC, or DTIC plus methyl-CCNU, has resulted in augmentation of remissions in areas regional to BCG immunization, prolongation of chemotherapy-induced remissions, and significant prolongation of survival compared to the use of DTIC chemotherapy without immunotherapy. Data from other centers have shown that augmentation of remissions for melanoma patients occurred when BCG was combined with DTIC, vincristine, and allogeneic tumor cells. Finally, another study has shown that DTIC combined with BCG has prolonged the disease-free interval and survival in melanoma patients with regional lymph node metastases. The potential inhibition of DTIC metabolism by BCG or Corynebacterium parvum is discussed.

BCG Vaccine↗

Effect of haematological malignancies and their treatment on host defence factors.

Immunological factors are involved in all aspects of the lymphomas and leukaemias. The aetiology of these diseases is related at least in some cases to immunodeficiency, immunostimulation, autoimmunity and a dysregulation of the immune system. The majority of lymphomas and leukaemias are monoclonal proliferations of the B-lymphocyte series at different stages of maturation while some are derived from T lymphocytes and others have no recognisable B or T-cell markers. Each of the lymphoid malignancies has a characteristic and unique pattern of immunological deficiency, suggesting a unique aetiology. Hodgkin's disease and histiocytic lymphoma, the acute leukaemias and chronic myelogenous leukaemia have predominantly cell-mediated immune deficiencies, while lymphocytic lymphoma, chronic lymphocytic leukaemia, multiple myeloma, and the plasma cell dyscrasias have predominantly humoral immune deficiencies. There is a relationship between immunocompetence and prognosis and between immunocompetence and extent of disease in the lymphomas and leukaemias. Immunocompetent patients have a better prognosis and more limited disease than immunoincompetent patients. Therapy for these diseases profoundly suppresses host defence mechanisms, particularly those which are cell-mediated. Ability to resist or recover from this immunosuppression is also associated with an improved prognosis. Lymphoma and leukaemia also induce a tumour-specific immune response in the tumour-bearing host and this also correlates with prognosis. These factors form a rational basis for immunotherapy and indeed lymphomas and leukaemias respond to active nonspecific immunotherapy with BCG and active specific immunotherapy with tumor cells resulting in prolongation of remission duration and survival.

B-Lymphocytes↗

Fetal antigens in human leukemia.

Immunization of BALB/c male mice with human peripheral leukemic blasts effectively reduced the later formation of syngeneic fetal liver, but not bone marrow hematopoietic colonies in the spleen when these mice were lethally irradiated and challenged i.v. Fetal antigen was detected in 6 of 6 lymphocytic leukemic patients and in 4 or 8 myelocytic leukemia patients and was correlated with low cellular levels of sialic acid. A rabbit antiserum ot BALB/c 15-day fetal liver cells labeled only 0 to 2% of normal donor peripheral leukocytes in indirect immunofluorescence but reacted with 10 to 21% of leukemic peripheral blasts. Active disease bone marrow on the same patients gave 7 to 40% fluorescent cells. Two remission bone marrow smaples were negative and 1 had 44% fluorescent cells. Using this antiserum coupled to sepharose, affinity column separation of KCl extracts from mouse and human fetal liver and from chronic lymphocytic leukemia has produced 4 common protein bands (identifiable on polyacrylamide gel electrophoresis).

Animals↗

Epilesional scarification. Preliminary report of a new approach to local immunotherapy with BCG.

Because of the serious toxicity of intralesionally injected BCG, including high fever, local ulceration, chronic drainage, and disseminated BCG disease, 13 patients received local BCG immunotherapy by the new approach of epilesional scarification. Three patients had complete responses, four had partial responses, and six had no response. Toxic reactions were minimal compared to those reported for intralesionally given BCG.

Adult↗

Adjuvant immunotherapy and chemoimmunotherapy in colorectal cancer of the Dukes' C classification. Preliminary clinical results.

Fifty-eight patients with Dukes' C classification of carcinoma of the large bowel were placed on adjuvant immuno- or chemoimmunotherapy with Bacillus calmette guerin (BCG) or combination of 5-fluorouracil (5-FU) plus BCG following primary and definitive surgery, and were followed for up to 21 months. Of twenty-six patients receiving BCG alone by scarification, five have relapsed with 75% of freedom from disease estimated at 15.1 months compared with 10.1 months in a group of carefully selected historical controls who had surgery alone (p = 0.12). The survival of all patients receiving BCG alone has not reached the 75 percentile yet, and the difference from controls is currently estimated at the 18% level. The combination of 5-FU plus BCG (studied in 32 patients) may be superior to BCG alone at this time, in that it appears to more effectively protect against tumor recurrence (75 percentile not yet reached compared to control, (p = 0.08). The survival of patients on 5-FU plus BCG also appears to be improved (p = 0.09). No patients have expired compared to a 75 percentile survival of 16.6 months in the control. Serial determination of plasma CEA was crucial in the clinical follow-up of these patients. Frequent CEA detetminations have led to early detection of clinical relapse. In the elevation of CEA suggests tumor recurrence with a high degree of probability in patients with past history of cancer of the large bowel.

BCG Vaccine↗

Active specific immunization in malignant melanoma.

The effects of active specific immunization with nonirradiated autologous and irradiated cultured allogeneic melanoma tumor cells (TC) on cell-associated immunity was studied in 11 patients with widespread malignant melanoma receiving chemoimmunotherapy. Immunization with 1 X 10(6)-8 X 10(7) TC was done in the draining area of a BCG scarification on day 7 of the study. The in vitro lymphocyte blastogenic response (BR) to autologous TC was studied in terms of the stimulation index on day 1, 7, 14, and 21. The stimulation index (SI) was the counts per min (cpm) in the TC stimulated culture minus the cpm among the TC alone divided by the cpm in the unstimulated controls. A positive BR was considered as a SI equal to or greater than 3. Six out of 11 patients had a significant increase in BR lasting 7-14 days after immunization. The pre- to post-immunization changes in the SI of the 6 patients were 2.5 to 7.5; 0.7 to 3.2; 0 to 5.2; 0 to 16; 0.1 to 6.6; and 6.5 to 30.0. Nine out of 11 patients showed a delayed local inflammatory reaction at the immunization site. Five out of 11 patients mounted a cutaneous delayed hypersensitivity reaction to autologous tumor cells at a separate test site following immunization. There were no side effects. Active specific immunization in the drainage of a BCG reaction appears to be safe. Since a positive BR to autologous TC correlates with a good prognosis in patients with solid tumors, studies of the immunotherapeutic efficacy of this approach may be warranted.

Adolescent↗

Permanent slide preparations of T lymphocyte-sheep red blood cell rosettes.

Rosette formation between sheep erythrocytes (SRBC) and human thymus-derived lymphocytes (T cells) is used to monitor T cells in various human diseases. Rosettes are usually counted in a hemacytometer immediately after preparation. This paper reports a technique for permanently fixing and staining rosettes for serial and comparative studies, a procedure which has probably been less well standardized, less reproducibly performed, and less widely used than many investigators appreciate. The technique describedhas the advantages of providing distinct morphological identification of the rosette-forming cell and it produces a permanent mount for further reference.

Animals↗

A rapid method for establishing short-term primary cultures of human tumor cells from fresh tumor biopsies.

A rapid method for the establishment of short-term primary cultures of human tumor cells obtained from fresh surgical biopsies is described. The method consists of the separation of the viable fraction of tumor cells by differential flotation on ficoll-hypaque density solution and its subsequent seeding into culture flasks. Tumor cell growth is established within 2-3 days. The incidence of overgrowth with fibroblasts is apparently reduced and usually delayed for 4-5 weeks, but cannot be prevented by this method.

Biopsy↗

Subpopulations of thymus dependent and thymus independent lymphocytes in human gut associated lymphoid tissues.

Human gut associated lymphoid tissues were studied in terms of the presence of subpopulations of thymus dependent and thymus independent lymphocytes. Both thymus dependent and thymus independent lymphocytes were present in substantial numbers, as judged from their ability to form spontaneous and complement mediated rosettes with sheep red blood cells and the presence of surface bound immunoglobulins. The relationship between this finding and the question of what is the lymphoid organ which may be the human equivalent of the avian bursa is discussed.

Animals↗