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Biomedical subjects

H J Esber

Publications and source records attributed to H J Esber.

At least 37 records · Page 2Linked to original sources

The concept of induction and elicitation as an immunotherapeutic approach.

The concept of "induction and elicitation," propounded by Stuart Mudd, circumvents the dangers of infecting the immunologically impaired individual without abrogating the effectiveness of the antigenic stimulus provided by an initial infection with living organisms. Mudd's concept utilizes the ubiquitous and naturally established delayed type hypersensitivity to Staphylococcus aureus as the primary induction step for the more effective use of bacterial fractions, such as staphylococcal phage lysate, a potent immunizing agent, commercially licensed and available, in the subsequent elicitation of a nonspecific, cell-mediated immune response. The results of an exploratory study in which induction and elicitation were applied as an immunotherapeutic modality, in combination with surgery, in a metastasizing animal tumor model (the F344 rat) are presented.

Animals↗

Influence of surgery, irradiation, chemotherapy, and immunotherapy on growth of a metastasizing rat mammary adenocarcinoma.

Based upon the hypothesis that a factor most pertinent to the absence of an effective immune response in cancer is the inadequacy of the antigenic stimulus provided by the neoplasm, either in terms of weak immunogenicity of the tumor antigen or of the necessary antigen mass available to the reticuloendothelial tissues at any one time for effective sensitization, the host immune response capabilities were stimulated within a time frame synchronous with a greater release of tumor antigens. In the treatment of a metastasizing, solid tumor model syngeneic with F344 rats, immunotherapy was most effectively applied in combinations with chemotherapy and/or localized radiotherapy, therapeutic modalities that induced a degree of oncolysis and tumor resorption. Surgery combined with chemotherapy permitted evaluation of therapeutic effects against metastases. The methanol-soluble fraction of Mycobacterium butyricum was used as the nonspecific immunologic adjuvant.

Adenocarcinoma↗

Predictive experimental animal tumor models: a concept.

As an introduction to the session on Animal Tumor Models, a concept of animal model systems in presented that differentiates between models of organ-related diseases such as prostate or bladder cancer and models of a certain class of neoplasms found within a specific organ disease. Thus defined, no one animal tumor can completely represent and be predictive for a disease entity, no more so than can a single clinical experience with prostate cancer, e.g., be representative of all clinical cases. Rather, a block of animal tumors originating from a specific organ that reflects a spectrum of carefully defined growth patterns and reactivities best mimics the overall responses obtained clinically. Because immunotherapy is most logically visualized and applied in an adjuvant mode, its effectiveness as a therapeutic modality is vulnerable to the vagaries of individual tumor response to a primary modality. Therefore, the selection of appropriate tumor models for developmental studies in immunotherapy is critical, and the need for well-defined and characterized test systems in terms of chemotherapy and radiation responsiveness is emphasized.

Animals↗

Circadian pattern of prolactin and growth hormone levels in female rats of two strains.

Plasma growth hormone and prolactin levels were determined by radioimmunoassay at intervals of 2 hr during the light phase of a controlled light-dark cycle in virgin female (COBS F/Crl BR) and [Sch:SPD(SD)BR] rats. Peak prolactin concentrations were observed in the afternoon during proestrus and estrus in both rat stocks. Growth hormone exhibited wide fluctuations in the Sch:SPD rat, attaining peak levels at 1300 hr, but no apparent periodicity was observed in the COBS rats.

Animals↗

Effect of androgens on maturation and metabolism of erythroid tissue.

Specific changes taking place in the erythroid tissue following depletion or replacement of androgens were studied in rats. The reduction of testosterone levels in blood of orchiectomized animals did occur in conjunction with a decline of erythrocyte glucose-6-phosphate (G6P) and lactate levels. No evidence of anemia was observed. The subcutaneous administration of testosterone propionate (16.0 mg/kg) to orchiectomized rats restored, within 12 hours, blood testosterone levels as well as erythrocyte G6P levels and lactate production. The in vitro incorporation of glucose-1-14C into rat erythrocytes incubated with testosterone was comparable to that of control cells. A radioautographic study of rat erythroid marrow pulsed with glucose-1-14C showed a lower labeling when testosterone propionate was administered. The authors conclude that testosterone does directly affect glucose metabolism of erythroid cells, via the pentose shunt pathway. The possible role of the androgen-dependent enhancement of erythroid glycolysis is discussed in relation to the function of testosterone receptocytes present in marrow cells and a 17beta-hydroxysteroid dehydrogenase present in erythrocytes.

Animals↗

Effects of cancer chemotherapeutic agents on endocrine organs and serum levels of estrogens, progesterone, prolactin, and luteinizing hormone.

The effects of the following cancer chemotherapeutic agents on serum hormonal levels, estrous cycles, and endocrine organs were studied in mature, normal Sprague-Dawley rats by radioimmunoassay, vaginal smear examination, and organ weight end point: estradiol mustard (NSC 112259), testosterone mustard (NSC 112260), phenoestrin (NSC 104469), methotrexate (NSC 740), 5-fluorouracil (NSC 19893), vinblastine (NSC 49842), vincristine (NSC 67574), nitrogen mustard (NSC 762), and 1,3-bis(2-chloroethyl)-1-nitrosourea (NSC 409962). Following 2 weeks of treatment, estradiol-17beta levels were markedly elevated by all compounds except testosterone mustard and nitrogen mustard, which caused a decrease. Estrone levels were elevated by methotrexate, 5-fluorouracil, vinblastine, vincristine, nitrogen mustard, and 1,3-bis(2-chloroethyl)-1-nitrosourea, but were lowered by estradiol mustard. Progesterone levels were elevated only by estradiol mustard and testosterone mustard and were not affected by other compounds. Prolactin surge during proestrus was suppressed by phenesterin and methotrexate. Luteinizing hormone levels were lowered by methotrexate and nitrogen mustard. Estrous cycles of rats treated with estradiol mustard were arrested at proestrus, and the uterine and pituitary weights of these rats markedly increased. Uterine weight loss was significant following treatment with testosterone mustard, 5-fluorouracil, and nitrogen mustard. Thyroid weight was reduced by all compounds except methotrexate and vinblastine. Significant increases in pituitary weights occurred following treatment with all compounds except 1,3-bis(2-chloroethyl)-1-nitrosourea. The effects on ovarian and adrenal weights were minimal although significant by some compounds. Thus, in addition to their direct antitumor effects, these agents also produced changes in endocrine system which may be synergistic or antagonistic to the chemotherapy of endocrine-responsive neoplasms.

Animals↗