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H J Rapp

Publications and source records attributed to H J Rapp.

At least 37 records · Page 2Linked to original sources

Immunoprophylaxis of an ocular solid malignant tumor in cattle.

Individual Hereford cows bearing benign precursor lesions of ocular squamous cell carcinoma were treated by intralesional injection of mycobacterial cell walls in an oil-in-water emulsion in an attempt to interrupt neoplastic progression. Thirty-one months after treatment, statistical analysis of data indicated that intralesional BCG cell wall vaccine can interrupt this process and provides effective immunoprophylactic prevention of malignant disease.

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Immunotherapy of guinea pigs with a transplanted hepatoma: comparison of intralesionally injected emulsions containing heat-killed Nocardia rubra, Mycobacterium bovis (BCG) and Mycobacterium phlei.

Heat-killed cells of Mycobacterium bovis (BCG), Mycobacterium phlei and Nocardia rubra were each tested in emulsified form for their ability to cause regression of established dermal transplants and lymph node metastases of a syngeneic hepatocarcinoma in guinea pigs. On a weight basis, BCG was superior to N. rubra in causing tumor regression. Under the conditions tested N. rubra was inferior to M. phlei in its antitumor activity. M. phlei and BCG were approximately the same in their therapeutic potency. In BCG-sensitized guinea pigs, N. rubra provoked a weaker delayed cutaneous hypersensitivity (DCH) reaction than did BCG. In N. rubra-sensitized guinea pigs, BCG provoked a weaker DCH reaction than did N. rubra. Purified protein derivative of M. tuberculosis was more active in eliciting DCH in BCG-sensitized guinea pigs than in animals sensitized with N. rubra.

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Effect of bacille Calmette-Guerin immunotherapy on feline sarcoma virus-induced neoplasms in the cat.

Kittens infected experimentally with feline sarcoma virus (FeSV) were inoculated with emulsions of bacille Calmette-Guerin (BCG) cell wall preparations to determine the effect of BCG immunotherapy on FeSV-induced sarcoma-genesis. The BCG preparations or emulsificant control preparations were administered (i) subcutaneously at the same time and site as was the FeSV inoculation, (ii) at the same site but 1 week after FeSV inoculation, or (iii) with a mixture of viable autochthonous neoplastic cells approximately 35 days after FeSV inoculation. There was no difference in the percentage of kittens that developed neoplasms, the prepatent period for neoplastic development, the percentage of kittens with neoplastic regression, or the survival rate among groups given BCG, emulsificant control, or FeSV alone. Significantly (P less than 0.05) greater dissemination of neoplasms was seen in groups given BCG or emulsificant control preparations, compared with dissemination in groups given FeSV alone.

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Mechanisms of immunologic eradication of a syngeneic guinea pig tumor. I. Quantitative analysis of adoptive immunity.

Adoptive immunity against a syngeneic hepatoma (line-10) of Sewall-Wright inbred strain 2 guinea pigs was analyzed by a two-dimensional titration of iv transferred immune lymphoid cells versus intradermal tumor challenges. Tumor resistance increased exponentially as a function of the number of immune lymphoid cells transferred. Within the tumor challenge doses analyzed, suppression of tumor growth mediated by the transferred immune lymphoid cells appeared to be independent of the primary immune response in the recipient. Quantitatively, rejection of a given number of tumor cells reflected the number of transferred immune cells and was independent of the presence of the same tumor at other skin sites. There was no evidence indicating that transferred immune cells were attracted specifically to the tumor inoculation site. The number of tumor cells that could be rejected at a skin site by adoptive immunity was greater than the estimated number of immune lymphoid cells present at the challenge site.

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Immunotherapy by intralesional injection of BCG cell walls or live BCG in bovine ocular squamous cell carcinoma: a preliminary report.

Cows of the Dutch Frisian and Maas-Rijn-IJssel breed with histologically confirmed ocular squamous cell carcinoma showed complete regression of the primary tumor in 70 or 60% of the cases after intralesional injection of a BCG cell wall or live BCG vaccine, respectively. Recurrence of the tumor was observed in 57% of the animals treated with BCG cell walls and in 25% of the animals treated with live BCG vaccine. Spontaneous regression was seen in 20% of the untreated cows. In a second control group, radical surgery, the most successful treatment for primary stage I tumors in humans, resulted in a 90% cure. Influence of immunotherapy on metastases could not yet be fully evaluated. White blood cell counts were not changed after therapy. It was not possible to link a favorable response to BCG therapy with the intensity of the delayed type hypersensitivity (DTH) reaction to purified protein derivative of mycobacteriae (PPD) or the formation of antibodies to BCG as determined by a micro-enzyme-linked immunosorbent assay. However, in animals that showed tumor regression, the DTH reaction to PPD had a tendency to persist for a longer period of time. It was concluded that 1) block resection was the best method of treatment for this tumor, 2) a single intralesional injection of a BCG cell wall vaccine was as effective as live BCG vaccine in the induction of complete regression of the primary tumor, 3) in this preliminary study BCG cell wall vaccine was less effective than live BCG vaccine in the prevention of recurrence, and 4) this naturally occurring tumor model is well suited for the study of the influence of BCG immunotherapy in a primary stage I tumor.

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Eradication by active specific immunotherapy of established tumor transplants and microscopic lymph node metastases.

Guinea pigs, each with an established syngeneic dermal line 10 tumor and microscopic lymph node metastases, were immunized by injection of a mixture of irradiated line 10 tumor cells and an oil-in-water emulsion containing heat-killed cells of Mycobacterium bovis strain Bacillus Calmette-Guérin. Squalane or squalene-in-water emulsions, prepared by ultrasonication and containing mg doses of mycobacterial cells, were effective adjuvants. Immunization eradicated established dermal tumors (about 10 mm in diameter) and prevented growth of microscopic lymph node metastases. Untreated animals, animals treated by intradermal administration of Bacillus Calmette-Guérin cells attached to oil droplets alone or with irradiated tumor cells alone, all died with progressive tumor growth.

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Treatment by limited surgery and specific immunization of guinea pigs with stage II experimental cancer.

The malignant disease produced in guinea pigs by intradermal inoculation of line-10 was allowed to progress to stage II, at which time the dermal tumor and the first draining lymph node were grossly evident. At that stage, the external appearance of the next draining lymph node was normal, but it contained tumor cells. Limited surgery consisting of excision of the dermal tumor and first draining lymph node was not curative; palpable metastases developed in the second and other draining lymph nodes, and at autopsy, some animals were found to have gross, visible lung metastases. Immunization of guinea pigs with a mixture of irradiated syngeneic tumor cells plus mycobacterial cell walls in an oil-in-water emulsion eradicated tumor cells remaining in lymph nodes after limited surgery for stage II experimental cancer and prevented progression of the disease to stage III. Tumor intravenously implanted in the lungs of animals after limited surgery for stage II disease was also eliminated by immunization.

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Regression by active specific immunotherapy of established dermal tumor transplants and lymph node metastases in guinea pigs.

Guinea pigs, each with an established, syngeneic dermal tumor (line-10) and microscopic lymph node metastasis, were treated by intradermal inoculation of living line-10 tumor cells admixed with emulsified heat-killed Mycobacterium bovis BCG cells. This treatment caused complete regression of established dermal tumors (about 10 mm in diameter) and prevented the growth of microscopic lymph node metastases in 25 of 39 treated animals (64%). All control animals treated by intradermal inoculation with heat-killed M. bovis BCG cells attached to oil droplets died with progressive dermal and lymphatic tumor growth.

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Immunotherapy of experimental cancer with a mixture of synthetic muramyl dipeptide and trehalose dimycolate.

The antitumor activity of a mixture of synthetic N-acetylmuramyl-L-alanyl-D-isoglutamine (MDP) and trehalose-6,6'-dimycolate (TDM) (MDP+TDM) in emulsified form was studied in guinea pigs, each with a syngeneic dermal tumor and microscopically detectable metastases in regional lymph nodes. A single intralesional administration of an ultrasonically prepared emulsion containing MDP+TDM in squalane or in mineral oil caused tumor regression and elimination of lymph node metastases. Similar emulsions of MDP+TDM made with squalene or hexadecane were immunotherapeutically inactive.

Acetylmuramyl-Alanyl-Isoglutamine↗

Aryl hydrocarbon (benzo[a]pyrene) hydroxylase in guinea pig lymphoid tissue.

Aryl hydrocarbon hydroxylase (AHH) activity was detected in a variety of guinea pig lymphoid tissues and was increased by intradermal or ip administration of 3-methylcholanthrene AHH levels were generally greater in spleen than in lymph node, bone marrow, or thymus. Similar AHH activities were observed in lymphoid tissues from Sewall-Wright inbred strain 2 and strain 13 guinea pigs. Greater AHH activities were associated with peritoneal and alveolar macrophages than with lymph nodes lymphocytes in the absence of mitogens.

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Efficacy of intratumorally administered mycobacterial cell walls in the treatment of cattle with ocular carcinoma.

Individual Hereford cows with naturally occurring ocular squamous cell carcinoma were treated by intralesional injections of mycobacterial cell walls in an oil-in-water emulsion. Six of 23 treated animals were alive (5 free of tumor and 1 with arrested disease) at a minimum of 2.5 years after treatment, as compared to 1 of 18 controls. A necropsy, lymph node metastases were found in most animals with progressive disease. The disease progressed to an advanced stage (which required death of the animals) at a faster rate for control animals than for treated animals.

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BCG and cancer.

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Adoptive immunity to the guinea pig line 10 hepatoma and the nature of in vitro lymphoid-tumor cell interactions.

Adoptive transfer of spleen cells from specifically immunized donors to nonimmunized recipients was used to study tumor immunity in vivo to the syngeneic line 10 guinea pig hepatoma. Hepatoma cells cultured as monolayers on fibronectin-coated surfaces served as targets for immune splenocytes in a 3H release cytotoxicity assay in vitro. An antigenically distinct syngeneic guinea pig hepatoma (line 1) was used to study the specificity of adoptive systemic immunity and of the cytotoxicity in vitro. The protection afforded by adoptive immunization against challenge with hepatoma cells was tumor line specific, while in most cases cytotoxicity in vitro was not. The in vitro cytotoxic effect was abolished after absorption of the immune spleen cells with monolayers of either line 10 or line 1. In contrast, the in vivo tumor-specific rejection activity of line 10 immune spleen cells was depleted after absorption with line 10 but not with line 1 or other control monolayers. These studies revealed that the immune cells mediating cytotoxicity in vitro were functionally distinct from those conveying adoptive protection in vivo. Immune cells possessed receptors for tumor-specific rejection antigens on hepatoma cells, and their interaction did not lead to destruction of the neoplastic cells in vitro.

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Influence of type of oil and surfactant concentration on the efficacy of emulsified Mycobacterium bovis BCG cell walls to induce tumor regression in guinea pigs.

The influence of mineral ol, squalane, squalene, hexadecane, or peanut oil and of the concentration of Tween 80 on the immunotherapeutic capability of emulsified Mycobacterium bovis Bacillus Calmette-Guérin (BCG) cell walls was studied in guinea pigs, each with an established dermal transplant of a syngeneic hepatocarcinoma and tumor cells in the draining lymph node. Immunotherapy consisted of an intratumoral injection of emulsified cell walls. Conditions were established under which therapeutically effective emulsions could be made with mineral oil, squalane, squalene, or hexadecane. Emulsions made with peanut oil failed to cause tumor regression. Emulsions of squalene or hexadecane were effective substitutes for mineral oil as carriers of cell walls in the absence of added Tween or at a Tween concentration one-hundredth of that used to stabilize the mineral oil-containing emulsions. Cell wall emulsions made with squalane were therapeutically effective over the same range of Tween concentrations used to prepare emulsions containing mineral oil. Cell wall emulsions made without added Tween demonstrated effective antitumor activity even after autoclaving. Emulsions made with Tween separated after autoclaving. Emulsions of whole killed BCG were immunotherapeutically as active as those made with cell walls.

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Immunotherapy of experimental cancer by intralesional injection of emulsified nonliving mycobacteria: comparison of Mycobacterium bovis (BCG), Mycobacterium phlei, and Mycobacterium smegmatis.

Mycobacterium bovis (BCG), Mycobacterium phlei, and Mycobacterium smegmatis were each tested in emulsified form for their potency to cause regression of transplants of a syngeneic murine fibrosarcoma and of a syngeneic guinea pig hepatoma. On a weight basis, M. phlei and M. smegmatis were as effective as BCG in causing tumor regression. M. phlei and M. smegmatis were comparable to BCG in provoking delayed cutaneous hypersensitivity reactions in guinea pigs sensitized to M. phlei or M. smegmatis. In BCG-sensitized guinea pigs, M. phlei and M. smegmatis provoked weaker delayed cutaneous hypersensitivity reactions than did BCG. Purified protein derivative of M. tuberculosis was more active in eliciting delayed cutaneous hypersensitivity in BCG-sensitized guinea pigs than in animals sensitized with M. phlei or M. smegmatis.

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