Biomedical subjects

R Turcotte

Publications and source records attributed to R Turcotte.

At least 37 records · Page 2Linked to original sources

PubMed1988

Androgens exert selective effects on protein kinase C induced LH and FSH release in rat anterior pituitary cells in culture.

This study compares the selective effect of androgens on luteinizing hormone (LH) and follicle-stimulating hormone (FSH) release induced either by LH-releasing hormone (LH-RH) or by protein kinase C activation in rat anterior pituitary cells in culture. In control cells, phorbol-12-myristate-13-acetate (PMA) stimulated the release of radioimmunoassayable LH and FSH in a dose-dependent manner at an ED50 value of 5.95 +/- 1.45 nM. The maximal release of gonadotropins induced during a 3-hour incubation with PMA was 40-60% of that induced by LH-RH. Preincubation of the cells for 2-4 days with 10 nM 5 alpha-dihydrotestosterone (DHT) decreased by approximately 60% the subsequent release of LH induced by 100 nM LH-RH or by 500 nM PMA during a subsequent 3-hour incubation. The inhibitory effect of DHT was completely suppressed by coincubation with the antiandrogen hydroxyflutamide. DHT exerted a similar inhibitory effect on LH release induced by another stimulator of protein kinase C activity, namely 1-oleoyl-2-acetylglycerol. The potent inhibitory action of DHT on LH-RH- or PMA-induced LH release was exerted at an ED50 value of approximately 10 pM. Contrary to the effect on LH, the FSH response to LH-RH or to PMA was increased by preincubation with 2 nM DHT, the stimulatory effect of the androgen being completely antagonized by hydroxyflutamide.(ABSTRACT TRUNCATED AT 250 WORDS)

Androgens↗

PubMed1987

Suppressor T cells for delayed-type hypersensitivity in susceptible mice infected with Mycobacterium lepraemurium.

Spleen cells from immunodepressed C3H mice, i.e., mice inoculated intravenously 4 months earlier with 1 X 10(7) Mycobacterium lepraemurium (Mlm) bacilli, were separated into different populations, and the T-cell-enriched population was treated further with gamma-irradiation or specific anti-Lyt antibodies plus complement. The cell populations obtained were then adoptively transferred to normal and Mlm-sensitized syngeneic mice in order to investigate whether or not suppressor cells regulate the delayed-type hypersensitivity (DTH) reaction to specific antigens. A radiosensitive cell population expressing the Lyt 1+, 2+ phenotype had the capacity to depress the induction (afferent phase) of DTH reaction. In contrast, a radioresistant cell population expressing the Lyt 1+, 2- phenotype possessed the capacity to depress the expression (efferent phase) of the cutaneous reaction. Thus, distinct populations of suppressor cells, each regulating a different phase of DTH, are induced in the spleen of Mlm-infected mice.

Animals↗

PubMed1987

A suppressor B lymphocyte inhibiting IL-2 consumption in spleen cell cultures from Mycobacterium bovis BCG-infected mice.

In concanavalin A (Con A)-activated spleen cell (SC) cultures from normal C57BL/6 mice, the production of IL-2 peaked at 18-20 hr after initiation of cultures and declined rapidly during the next 24 hr, the decline of IL-2 activity being due, at least in part, to its utilization by the Con A-induced IL-2 receptor cells. In Con A-activated SC from BCG-infected mice, significant levels of IL-2 activity persisted in the 48-hr and 72-hr culture supernatants, a situation which seemed to be related to the depressed capacity of infected splenocytes to acquire IL-2 receptors. In cell mixing experiments, SC from infected mice actively depressed the utilization of IL-2 by Con A-activated normal SC, thus indicating that suppressor cells can down-regulate IL-2 responsiveness. These suppressor cells may belong to the B-cell lineage since they possessed the Thy-1-, sIg+ and FcR+ phenotype.

Animals↗

PubMed1986

Mechanisms underlying the depressed production of interleukin-2 in spleen and lymph node cell cultures of mice infected with Mycobacterium bovis BCG.

Mice were infected intravenously with 1.0 mg of Mycobacterium bovis BCG. At various times thereafter, spleen and peripheral lymph node cells were stimulated with concanavalin A for 18 to 20 h, and their capacity to produce interleukin-2 (IL-2) was evaluated by means of a T-cell blast proliferation technique. A depression of IL-2 production that was complete in the spleen but partial in lymph node cell cultures occurred at 2 to 3 weeks and persisted till weeks 8 to 10 after infection. No direct evidence was found for an active suppressor mechanism depressing in vitro the production of IL-2. In spleen cell cultures the suppression of IL-2 production would result from a functional defect of the IL-2-producing T-cell subset, whereas in lymph node cell cultures the depression mainly results from a relative lack of IL-2-producing cells caused by an accumulation of immunoglobulin-positive and "null" cells. Spleen cells from BCG-infected mice maintained their capacity to acquire IL-2 receptors when activated by concanavalin A.

Animals↗

PubMed1986

Coordination of Ca2+ regulating and Ca2+ regulated processes in the study of muscle function.

The self-organization of biological systems is, in part, described by dynamical order and cooperativity of system elements. Consideration of this, therefore, should form the infrastructure of future Exercise/Sport Biochemistry Research in Canada since a solely elemental focus, in its' interpretation, may not be meaningful if the synergy among system elements is not appreciated. This approach is illustrated through a description of the central role of Ca2+ metabolism in coordinating subcellular events associated with muscle contraction. The decline in force generating capabilities associated with extreme muscle use (e.g. endurance type exercise) is, in our view, due to an uncoupling of excitation-contraction coupling leading a Ca2+ imbalance. The observed dissolution of the myofibril ultrastructure and altered SR function reflect a loss of normal order and synergy amongst Ca2+ regulated and Ca2+ regulating processes which will lead to an upcoupling of oxidative phosphorylation. These apparently catastrophic events may, paradoxically, establish a new order in which energy utilizing systems attempt to keep pace with the abbreviated energy production system.

Animals↗

PubMed1986

Control of the Bcg gene of early resistance in mice to infections with BCG substrains and atypical mycobacteria.

The effect of the Bcg gene on the early host response to intravenous infection with a variety of BCG substrains and some atypical mycobacteria was investigated. The numbers of live bacilli of BCG Pasteur and BCG Tice recovered from the spleens of Bcgs mice (C57BL/6, B10.A and BALB/c) at 3 weeks following infection exceeded the bacterial dose injected, whereas the number of CFU recovered from the spleens of Bcgr mice (A/J, DBA/2 and C3H/HeN) did not exceed the number of CFU injected, thus following the pattern observed in Bcgr mice and Bcgs infected with BCG Montreal. BCG Russia failed to multiply in both test groups; however, the number of CFU recovered in Bcgr mice was significantly lower than in Bcgs mice. On the other hand, the presence of live bacilli in the spleens of either Bcgr or Bcgs mice injected with BCG Japan was undetectable in most cases. Involvement of the Bcg gene in the early resistance to infection with BCG Pasteur, BCG Russia, Mycobacterium kansasii and M. intracellulare was documented by the significant differences in the kinetics of infections in mice of the C.D2 (BALB/c-Bcgr) and BALB/c (Bcgs) congenic lines. In BCG Russia, M. intracellulare and M. fortuitum infections, the phenotypic expression of the Bcg gene resulted in a more rapid elimination of the bacteria in the spleens of Bcgr when compared with Bcgs mice. On the other hand, the hepatic granuloma formation correlated with bacterial load except when C.D2 mice were infected with a small dose of BCG Pasteur or M. kansasii where extensive granulomatous hepatitis developed although no bacterial multiplication occurred in the spleen. It is suggested that granuloma formation could depend of the properties of the mycobacteria as well as the genetic background of the host without implicating the bacterial burden.

Animals↗

PubMed1985

Opposite effects of cyclophosphamide pretreatment on tuberculin hypersensitivity during the course of sensitization of mice with Mycobacterium bovis BCG.

The influence of cyclophosphamide (CY) pretreatment upon the development of tuberculin hypersensitivity has been studied during the course of infection of mice with BCG. An enhancement of the DTH response to BCG antigens occurred during the induction phase, whereas a depression of this response occurred at the peak and during the decay phase of sensitization. The development of the early DTH-promoting and of the late DTH-depressing effect of CY was favoured by the use of a supra-optimal dose of BCG. Both these effects were cell-dependent since they could be transferred adoptively to syngeneic recipient mice with sensitized lymphoid cells but not with specific immune sera. Pretreatment with CY favoured the emergence of cells capable of responding in vitro to BCG antigens in the draining lymph nodes of BCG-infected mice. No simple association however, exists between this in vitro lymphocyte transformation response and the DTH response.

Animals↗

PubMed1985

Cellular immune response to Mycobacterium bovis (BCG) in genetically-susceptible and resistant congenic mouse strains.

Congenic Bcgr (C.D2, resistant) and Bcgs (BALB/c, susceptible) mice were infected intravenously with Mycobacterium bovis (BCG, strain Montreal) in order to establish the relationship between different indicators of the cell-mediated immune response and the bacterial load attained in the host. There was a correlation between the bacterial burden and the splenomegaly response, granuloma formation in the liver and cross-protection against an heterologous pathogen (Listeria monocytogenes) in Bcgr and Bcgs mice. No relationship was found between bacterial load or granuloma formation and the development of specific acquired protection against an homologous organism (BCG or M. tuberculosis, H37Rv) as assessed by the level of resistance attained in BCG-primed mice challenged with virulent H37Rv or by the adoptive immunity conferred by BCG-primed spleen cells transferred to naïve irradiated recipients challenged with BCG.

Animals↗

PubMed1984

Increasing the effectiveness of clinical supervision.

Effective use of preceptors in the clinical training and supervision of residents involves four essential steps: careful screening of the preceptor's practice to ensure it reflects the goals of the residency program and teaching the preceptor about the goals; setting a realistic contract for learning between resident and preceptor; teaching the preceptor to use constructive feedback techniques in the day-to-day supervision of residents; and developing the preceptor's skills in the reliable and valid evaluation of the resident's performance. Clinical preceptors must be trained to become effective teachers and evaluators in residency programs.

Canada↗

PubMed1984

Myofibril ATPase activity of cardiac and skeletal muscle of exhaustively exercised rats.

The activation characteristics of Mg-ATP and Ca2+ on cardiac and skeletal muscle myofibril ATPase activity were studied in rats following a run to exhaustion. In addition, the effect of varying ionic strength was determined on skeletal muscle from exhausted animals. The exhausted group (E) ran at a speed of 25 m min-1 with an 8% incline. Myofibril ATPase activities for control (C) and E were determined with 1, 3 and 5 mM Mg-ATP and 1 and 10 microM Ca2+ at pH 7.0 and 30 degrees C. For control skeletal muscle, at 1 and 10 microM Ca2+, there was an increase in ATPase activity from 1 to 5 mM Mg-ATP (P less than 0.05). For E animals the myofibril ATPase activities at 10 microM Ca2+ and all Mg-ATP concentrations were similar to C (P greater than 0.05). At 1.0 microM Ca2+ and all Mg-ATP concentrations were similar to C (P greater than 0.05). At 1.0 microM Ca2+ the activities at 3 and 5 mM Mg-ATP were greater for the E animals (P less than 0.05). Increasing KCl concentrations resulted in greater inhibition for E animals. With cardiac muscle, the myofibril ATPase activities at 1.0 microM free Ca2+ were lower for E at all Mg-ATP levels (P less than 0.05). In contrast, at 10 microM Ca2+, the E group exhibited an elevated myofibril ATPase activity. The results indicate that Mg-ATP and Ca2+ activation of cardiac and skeletal muscle myofibril ATPase is altered with exhaustive exercise.

Adenosine Triphosphatases↗

PubMed1984

Enhancement of resistance in Mycobacterium lepraemurium infected C3H mice by treatment with sonicated M. lepraemurium or splenectomy.

C3H mice were first infected in a hind footpad with 10(7) freshly harvested Mycobacterium lepraemurium bacilli. Four weeks later, when a granulomatous reaction was detected at the inoculation site, the animals were treated with two doses of a whole sonicated preparation of M. lepraemurium administered 2 weeks apart in the contralateral footpad. Such treatment was found to prolong the survival time of infected mice by 55-60 days. To study the involvement of the spleen in the immunomodulation of resistance to M. lepraemurium infection, splenectomy was performed in mice prior to infection via two different routes. Splenectomy significantly prolonged the mean survival time of mice infected in the footpad but did not affect survival of those infected intraperitoneally. Treatment of splenectomized footpad infected mice with sonicated bacilli abrogated almost completely the beneficial effect of splenectomy.

Animals↗

PubMed1983

Cutaneous unresponsiveness to Mycobacterium bovis BCG in intravenously infected mice.

Mice injected with 1 mg (about 1 X 10(7) CFU) of Mycobacterium bovis BCG in the footpad showed high levels of delayed-type hypersensitivity (DTH) to BCG antigens and a continuous increase in circulating specific anti-immunoglobulin G (IgG) antibodies throughout a 6-week observation period. In contrast, mice injected intravenously with a 1-mg dose failed to mount a DTH and showed a depression in antibody production at week 5 postinfection. A dose-response study revealed that an optimum dose of BCG, when injected intravenously, can induce a small but significant DTH response. The delayed cutaneous unresponsiveness in intravenously infected mice lasted at least 6 weeks and was not antigenically specific, in that it depressed the DTH response to Corynebacterium parvum. No simple relationship existed between levels of DTH and the amount of circulating anti-IgG antibodies. Splenectomy and treatment with a high dose of cyclophosphamide before infection, although greatly reducing the humoral response, did not reverse the BCG-induced unresponsiveness nor enhance levels of DTH in mice infected in the footpad. It is concluded that the intravenous infection of mice with BCG exerts a nonspecific inhibitory effect on delayed-type immune reactions by the induction of some type of suppressor mechanisms that are resistant to cyclophosphamide.

Animals↗

PubMed1983

Impairment of virulence of in vitro subcultures of Mycobacterium lepraemurium.

Mycobacterium lepraemurium was cultivated in vitro on Ogawa egg-yolk medium. The pathogenicity of the third and eighth subcultures for C3H and C57BL mice was compared with that of in vivo grown murine bacilli by evaluating the mean survival time of infected mice. The results strongly suggest that a significant drop of virulence occurs during the in vitro cultivation of M. lepraemurium.

Animals↗

PubMed1982

Mechanisms of action of Mycobacterium bovis BCG-induced suppressor cells in mitogen-induced blastogenesis.

Spleen cells from Mycobacterium bovis BCG-infected C57B1/6 mice when cultured in vitro for 72 h elicited soluble suppressor mediators capable of nonspecifically suppressing the mitogen-induced blastogenesis of normal splenocytes. Maximal production of suppressor mediators occurred during the first 24 h in culture, and their production ceased after 72 h. Attempts to isolate the mediators from fresh nonincubated splenocytes failed. After incubation, a strong residual suppressive activity was constantly detected in cell preparations used for production of suppressor factors. Supernatants prepared from cultures of spleen cells of mice infected 14 days earlier possessed higher suppressive activity than did those obtained 28 days after infection. In contrast, the residual cellular suppressive activity increased during the course of the infection. Although the activity of soluble factors was not inhibited, the residual activity of incubated cells was highly depressed by the presence of mouse erythrocytes in the cultures. Thus, the incubated cells appear to act through a direct cell-to-cell contact with the mitogen-responding cells. Finally, the results of depletion experiments suggest that the two populations of BCG-induced suppressor cells, namely, T lymphocytes and macrophage-like cells, are able to elicit suppressor mediators and to retain thereafter suppressive activity.

Animals↗

PubMed1982

Lack of a sustained protection against murine leprosy in C3H mice vaccinated with extracts of Mycobacterium lepraemurium in admixture with Mycobacterium bovis (BCG).

Inbred C3H mice were vaccinated intradermally with a single dose of live BCG, whole extracts of mechanically disrupted Mycobacterium lepraemurium (MLM), or a mixture of both these agents. Four weeks later, they were infected in one hind foot pad with freshly harvested MLM. Vaccination with BCG-containing preparations significantly reduced the multiplication of MLM in the infected foot pad and the bacillary dissemination to the draining popliteal lymph node and the spleen, while vaccination with MLM extracts solely limited the growth of MLM in the foot pad. MLM antigens in admixture with BCG did not offer a better protection than BCG alone. The protective effect was observed near the 15th week after the infection. At 30 weeks post-infection, no significant difference in bacillary counts was noted between the vaccinated and unvaccinated mice. In addition, the mean survival time of vaccinated mice did not significantly differ from that of control mice. Thus, in the C3H mouse, vaccination was able to limit temporarily the growth and dissemination of MLM, but these effects were unable to stop the fatal progression of murine leprosy.

Animals↗

PubMed1981

Differences in response among inbred mouse strains to infection with small doses of Mycobacterium bovis BCG.

Intravenous infection of six inbred mouse strains with small doses of dispersed cells of Mycobacterium bovis BCG (15.5 x 10(3) or 15.5 x 10(4) colony-forming units) separated them into resistant (C3H/HeCr, A/J, and DBA/2) and sensitive (B10.A, C57BL/6, and BALB/c) strains as assessed by the magnitude of bacterial multiplication in the spleens at 28 days. The two groups were more sharply separated after infection with the lower dose of BCG (15.5 x 10(3) colony-forming units), which allowed for true multiplication of the bacteria in the spleens of permissive hosts, expressed as the ratio of the number of BCG recovered from the spleens to the number of BCG injected. This coefficient of increase was less than 1 in resistant strains, whereas it was higher than 2.5 in sensitive strains. Significant splenomegaly developed only in mice of the sensitive strains infected with BCG when compared with uninfected controls. There was no correlation between the magnitude of the delayed-type hypersensitivity (DTH) to BCG and susceptibility to infection: DTH was absent in both the sensitive and the resistant strains when the smaller dose of BCG was used for infection. Moreover, significant DTH was detected in animals of the most sensitive (BALB/c) as well as of the most resistant (C3H/HeCr) strain when the higher dose of BCG (15.5 x 10(4)) was used for immunization. These results document significant genetic differences in the ability of inbred mice to inhibit bacterial multiplication after infection with small dispersed doses of BCG. Resistance to BCG multiplication, in this model, does not appear to be related to the establishment of DTH.

Animals↗

PubMed1981

Evidence for two distinct populations of suppressor cells in the spleens of Mycobacterium bovis BCG-Sensitized mice.

Spleen cells from female C57BL/6 mice infected intravenously with 1 mg (about 10(7) viable units) of bacillus Calmette-Guérin (BCG) were shown to suppress the blastogenic responses induced by the T-cell mitogens phytohemagglutinin and concanavalin A and by the B-cell mitogen lipopolysaccharide in spleen cells from normal syngeneic mice. By using various separation procedures or cellular treatments, evidence was found for two distinct populations of splenic suppressor cells. One population belonged to the monocyte-macrophage lineage on the basis of their adherence to plastic surfaces, their removal after treatment with carbonyl iron, and their resistance to gamma irradiation. The other population of suppressor cells belonged to the T lymphocytes due to their sensitivity to an anti-Thy 1 antiserum and complement and to gamma irradiation. After separation on nylon wool columns, inhibitory activity was found in both the nonadherent and the adherent spleen cell populations. Both populations of suppressor cells were present in the spleens 14 days after BCG inoculation and persisted for at least 40 days after infection.

Animals↗

PubMed1980

Influence of route of Mycobacterium lepraemurium injection on susceptibility to mouse leprosy and on lymphoblastic transformation.

Groups of female C57BL/6 and C3H/St mice were inoculated intraperitoneally (i.p.) with 10(9), 10(7), and 10(5) bacilli and into the right hind footpad with 10(7) and 10(5) bacilli of Mycobacterium lepraemurium. The incidence of death from leprosy and the mean survival time of leprous mice were recorded. In addition, the blastogenic responses to the T-cell mitogens phytohemagglutinin and concanavalin A and to the B-cell mitogens lipopolysaccharide and dextran sulfate were evaluated at various times during the course of infection in the spleen and peripheral lymph nodes of mice infected with 10(7) bacilli. When M. lepraemurium was administered i.p., the two strains of mice succumbed to the disease at about the same time, except for the C57BL/6 mice infected with 10(9) bacilli, which died earlier than the C3H/St mice. Moreover, in both strains of mice, a progressive depression of blastogenesis, first to the T-cell mitogens and then to the B-cell mitogens in the spleen, and to the T-cell mitogens in the peripheral lymph nodes, occurred during the course of the infection, whereas the response to the B-cell mitogens in the nodes increased slowly during the advanced stage of the disease. When 10(7) and 10(5) bacilli were injected into the footpad, the C3H/St mice succumbed to the disease at 298 and 344 days, respectively, and the modifications of blastogenesis were similar to those observed in i.p.-infected C3H/St mice. In contrast, the C57BL/6 mice appeared resistant to footpad inoculation of M. lepraemurium, since they lived until the end of the observation period (466 days postinfection) and the depression of blastogenesis was not detectable until 1 year after the infection. Thus, it is concluded that for the C57BL/6 mice (but not for the C3H/St mice), the route of administration of M. lepraemurium can markedly influence the susceptibility or resistance to leprosy.

Animals↗