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Biomedical subjects

R Turcotte

Publications and source records attributed to R Turcotte.

At least 55 records · Page 3Linked to original sources

Pathogenesis of hypercalcemia in lymphosarcoma cell leukemia. Role of an osteoclast activating factor-like substance and a mechanism of action for glucocorticoid therapy.

The pathogenesis of hypercalcemia and mode of action of glucocorticoid therapy was examined in a patient with lymphosarcoma cell leukemia. Circulating neoplastic cells were cultured in vitro and secreted a bone-resorbing factor. The bone-resorbing factor was partially purified with the use of a bioassay for bone resorption, and was found to be chromatographically and pharmacologically similar to osteoclast activiating factor (OAF), which is produced by normal mitogen-activated peripheral blood lymphocytes. Other factors which stimulate bone resorption, such as parathyroid hormone, prostaglandins and the vitamin D metabolites, were excluded by criteria which included dose-response curves, radioimmunoassays, extraction in organic solvents and failure of glucocorticoids to inhibit bone-resorbing activity. The patient's hypercalcemia responded rapidly to prednisone therapy. The effects of the bone-resorbing factor secreted by the neoplastic cells on bone cultures to which cortisol was added were examined. Cortisol inhibited bone resorption directly at low doses (10(-8) M), which suggests that prednisone may have lowered the serum calcium in this patient by direct inhibition of bone resorption.

Aged↗

Opposite effects of BCG on spleen and lymph node cells: lymphocyte proliferation and immunoglobulin synthesis.

C57BL/6 mice were immunized intravenously (i.v.), intraperitoneally (i.p.), or subcutaneously with one dose of Bacillus Calmette-Guérin (BCG). At various time intervals after injection, the lymphocyte response, as measured by thymidine incorporation into DNA, and the number of immunoglobulin-secreting cells were determined in vitro before and after mitogenic stimulation with phytohemagglutinin, concanavalin A, or lipopolysaccharide. In unstimulated cultures, the spontaneous thymidine incorporation and immunoglobulin synthesis of spleen cells were increased to some extent in mice infected i.p. or i.v. with BCG, as compared with noninfected mice. In contrast, after mitogenic stimulation, a marked depression of the proliferative response of spleen cells to both T- and B-cell mitogens and a marked inhibition of LPS-induced immunoglobulin secretion were observed in mice infected i.v. and to a lesser extent in those infected i.p. The depression of lymphoblastogenesis in spleens was fully established 15 days after infection and persisted for a long period of time. When unfractionated or plastic-adherent spleen cells from BCG-infected mice were cultured with normal spleen cells, a strong depression of their reactivity to phytohemagglutinin, concanavalin A, and lipopolysaccharide was observed. After the removal of cells adherent to plastic, the response was partially restored in the nonadherent population from mice infected i.p., but not in that from mice infected i.v. After mitogenic stimulation, lymph node cells of mice inoculated subcutaneously showed a response to mitogen higher than that of normal cells. These results thus demonstrate that, depending on the route of administration, BCG exerts very different effects.

Animals↗

Regression of Ehrlich ascites carcinoma in BCG-sensitized mice.

Intraperitoneal inoculation of CF1 mice with Bacillus Calmette-Guérin (BCG) protected many of them against the ascites form of Ehrlich carcinoma; and, for those that developed cancer, complete regression occurred in up to 50% of the cases at an advanced state of the neoplastic disease. In contrast, when a booster dose of BCG was administered in admixture with tumor cells, the incidence of the tumor was lower and tumor regressions were very rarely observed in mice that developed cancer. Trypan blue, an inhibitor of lysosomal enzymes of macrophages, was found to markedly suppress the natural (innate) antitumor resistance of control mice as well as the acquired resistance and tumor regressions of BCG-sensitized mice. Moreover, a comparison of the cytotoxic activity of the adherent (macrophages) and nonadherent (predominantly lymphocytes) cells isolated from the peritoneal cavity of BCG-sensitized mice, as measured by the inhibition of DNA synthesis, revealed that the effector cells were amongst the macrophages. In contrast, spleen macrophages were devoid of cytotoxicity. The spleen lymphocytes from both BCG-sensitized and control mice possessed about the same significant cytotoxic activity. These results indicate that the activated peritoneal macrophages, induced by a local injection of BCG, could play an important role in the antitumor immunity against Ehrlich carcinoma.

Animals↗

Enhancement activity of anti-mycobacterial sera in experimental Mycobacterium bovis (BCG) infection in mice.

The passive transfer of rabbit anti-mycobacterial immunoglobulins was directed against either living or soluble extracts of Mycobacterium tuberculosis strain H37Rv, which promotes the multiplication of the BCG strain of M. tuberculosis in the spleen of mice infected with low doses of this latter strain. This enhancing effect was reduced significantly when antisera were absorbed with living BCG. Moreover, such treatment led to the removal of all hemagglutinating antibodies when antisera were tested against either BCG or H37Rv soluble extracts. Therefore, it is most probable that the enhancing effect is related to the presence of mycobacterial antibodies.

Animals↗

Partial characterization of a factor extracted from sensitized lymphocytes that inhibits the growth of Mycobacterium tuberculosis within macrophages in vitro.

Spleen lymphocytes of BCG-immunized mice contain a soluble factor that inhibits in vitro the growth of the H37Rv strain of Mycobacterium tuberculosis within normal peritoneal macrophages. The water-soluble extracts of sensitized lymphocytes, disrupted by freezing and thawing, although less active than the corresponding viable cells retained a significant growth-inhibiting activity. Dialysis against distilled water, lyophilization, exposure to ribonuclease and deoxyribonuclease, and storage at -20 degrees C of the water-soluble extracts did not affect their antimycobacterial activity, whereas extracts heated at 100 degrees C were completely devoid of such an activity. All the inhibiting activity was recovered in the void volume of the column after chromatography on Sephadex G-200. Water-soluble constitutents of sensitized lymphocytes did not affect BCG grown in vitro, and on repeated treatments of tuberculous mice they led to a negligible protection against pulmonary tuberculosis. Preliminary observations seem to indicate that other soluble factors in lymphocytes of BCG-sensitized mice have the capacity to potentiate in vitro the phagocytic activity of normal macrophages.

Animals↗

Isolation and characterization of phenotypes of mycobacteria.

Several strains of mycobacteria grown as surface pellicle on liquid Sauton's medium under semianaerobic conditions dissociated into three phenotypes: phenotypes 1, 2, and 3. Only phenotype 1 could be obtained in a pure state. None of these phenotypes was found to be stable: they convert from one into another and all revert to the parental strain when replaced in their usual aerobic cultural conditions. Comparative studies of phenotypes 1 and 3 have shown that significant differences exist in their physiological behaviour and antigenic composition.

Epitopes↗

The effect of acetylsalicylic acid on TSH and PRL secretion after TRH stimulation in the human.

In order to study the effect of prostaglandins on TSH release in the human, Acetylsalicylic Acid was given to 9 normal subjects at doses necessary to obtain a salicylate level of 20 mg/dl. TRH, 400 mug was injected prior to and after the medication. Thyroid hormone parameters were measured at time 0, and TSH and PRL at time 10, 20, 30, 45 minutes after the injection. The free fraction of thyroid hormones remained constant during treatment but a significant decrease of TSH concentration (30%) was noted after TRH injection on Acetylsalicylic Acid treatment whereas no changes were noted for PRL. As noted in the animal, this study indicates that in the human, prostaglandins potentiate the effect of TRH on TSH liberation by the pituitary where it has no effect on PRL.

Adult↗

The participation of common and species-"specific" antigens of Mycobacteria in the tuberculin skin reaction.

Protoplasmic extracts isolated from four different species of mycobacteria contained common and species-specific antigens. Both the common and the specific antigens were involved in the elicitation of the tuberculin reaction in sensitized guinea pigs. The elimination of the common antigens from the extracts by means of cross absorption with heterologous mycobacterial antibodies led to preparations which, at the doses used in this study, elicited a cutaneous reaction in animals sensitized with the corresponding strains only. Moreover, the tuberculin activity of the common antigens was about the same in animals sensitized either with homologous or heterologous strains.

Animals↗

Purification and characterization of tuberculin-active components from BCG.

The tuberculin activity of protoplasmic extracts isolated from living BCG was purified successively by gel filtration on Sephadex G-100 and G-75, and by electrophoresis on 7.5% and on gradient (6-18%) polyacrylamide gels. The tuberculin-active fractions, as determined in BCG-sensitized guinea pigs, were used as the starting material for each of the following fractionation steps. The physicochemical properties and the antigenic activity of the biologically active fractions have shown that a single component, or only a few ones with similar properties, possessed high tuberculin activity. These active components were proteins having relatively high molecular weights (about 72,000) and could behave as antigens.

Animals↗

Asparaginase activity of BCG and its phenotypes in relation to culture phases.

The asparaginase activity of the Montreal strain of BCG and of 2 of its phenotypes varies with the age of the culture; it starts to increase at the midlog phase of growth, reaches a maximum value near the end of this phase and decreases during the stationary or autolytic phase. However, the variations in this enzyme activity are greater in 2 the phenotypes than in the parental BCG.

Asparaginase↗