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Biomedical subjects

S Brochu

Publications and source records attributed to S Brochu.

30 records · Page 2Linked to original sources
PubMed1993

Synthetic C5a receptor agonists. Pharmacology, metabolism and in vivo cardiovascular and hematologic effects.

Recent investigations have produced novel compounds that act on the receptor for anaphylatoxin C5a. These products are C-terminal analogues of C5a, some of which are modified extensively. We have measured the receptor affinities of such analogues in a binding assay on human neutrophils (PMNs). We have also characterized their pharmacological profiles in vitro on the isolated rabbit portal vein and pulmonary artery, on superoxide release by PMNs as well as in vivo in the anesthetized rabbit (acute hypotensive and neutropenic effects). The metabolic resistance of these analogues was also evaluated in the presence of different peptidases. One of these compounds, MePhe-Lys-Pro-D-Cha-Phe-D-Arg, behaved as an antagonist on the release of superoxide by neutrophils while exerting agonist activity in all other assays. Its partial agonist status was documented in a receptor down-regulation experiment on PMNs where its activity was compared with those of recombinant C5a and of protamine which behaves as a competitive antagonist on these cells. Degradation studies indicated that the discrepancy between the affinity of certain analogues in vitro and their potency in vivo was probably linked to their metabolic stability.

Amino Acid Sequence↗
PubMed1992

Tolerance to host minor histocompatibility antigens after allogenic bone marrow transplantation. Specific donor-host unresponsiveness is maintained by peripheral tolerizing cells.

The development of graft-host tolerance after allogeneic bone marrow (BM) transplantation is more demanding than the acquisition of self-tolerance because both donor-derived mature T cells and immature thymocytes encounter host Ag. The mechanism involved in tolerization of mature T cells, contained in unmanipulated BM, remains undefined. In previous experiments, we showed in vivo unresponsiveness to host minor histocompatibility Ag (MiHA) in immunocompetent chimeras obtained after MiHA-incompatible BM transplantation. In this study, we wanted to determine: first, what was the specificity of this graft-host unresponsiveness, and second, whether peripheral cells were involved in tolerization? LP recipients were irradiated (9, 5 Gy), injected with 10(7) undepleted BM cells from B10 donors and studied 100 to 150 days later. (B10-->LP) chimeras were immunized in vivo and restimulated in vitro with cells displaying one or multiple incompatible MiHA. In bulk culture experiments, chimeras demonstrated specific CTL unresponsiveness to host MiHA but responded normally to third party MiHA. In limiting dilution analysis conditions, chimeras showed a profound deficit, but not a complete absence of anti-host CTL precursor. Studies with congenic stimulators/targets showed that graft-host tolerance was induced against both immunodominant (e.g., H-3.2) and nonimmunodominant (e.g., H-8.2) MiHA although at the CTL precursor level, it was more complete against the former. Furthermore, chimera spleen cells inhibited the generation of CTL activity against host- and donor-type MiHA but not against third party Ag. This specific suppressor activity was not T cell dependent, and was mediated by radiosensitive cells that are not found in freshly explanted organs from normal mice. Taken together, our results suggest that peripheral tolerization can be a remarkably efficient process to maintain tolerance to MiHA after BM transplantation. Thus, peripheral tolerizing mechanisms may contribute not only to the induction of tolerance to Mls superantigens or to the product of transgenes (if expressed at high levels) but also to a wide array of MiHA.

Animals↗
PubMed1992

Profiles of alcoholics according to the SCL-90-R: a confirmative study.

The Symptom Checklist-90-Revised (SCL-90-R) has often been used in studies of alcoholic populations. Based on findings reported in the literature and data gathered on 712 alcoholics in treatment, this paper investigates the general trends in the responses of alcoholics to the SCL-90-R. On global measures as well as on each of the symptom scales, the scores of alcoholic groups reveal a symptomatology two to five times as severe as that observed in the general population. The Psychoticism dimension shows the most marked divergence with the general population. In almost each of the study groups, the Depression Scale registers the highest scores, followed by Obsessive-Compulsive, Interpersonal Sensitivity, and Anxiety.

Adult↗
PubMed1990

Studies of immunologic tolerance to host minor histocompatibility antigens following allogeneic bone marrow transplantation in mice.

We showed previously that transplantation of 10(7) unmanipulated C57BL/6 marrow cells to irradiated LP mice yields healthy (B6-LP) chimeras showing no signs of rejection or graft-versus-host disease (GVHD). The aim of this work was to gain more insight into the mechanism(s) responsible for tolerance to host minor histocompatibility antigens following allogeneic bone marrow transplantation (BMT). (B6-LP) chimeras showed very good immune reconstitution when studied in vitro for proliferative response to mitogens and alloantigens and generation of T cell cytotoxic activity. In co-culture experiments their spleen cells showed no natural suppressor activity. When used as cell donors, their capacity to initiate GVHD in four strains of mice presenting H-2 differences was normal when compared to C57BL/6 donors. However, they provoked no GVHD in the three strains of H-2 compatible mice studied. Re-irradiated (B6-LP) chimeras rapidly died of GVHD following injection of C57BL/6 marrow + spleen cells. (B6-LP.R111) chimera cells appeared tolerant to LP minor antigens presented in the context of H-2r or H-2b. No anamnestic anti-idiotypic suppressor response was noted when stable (B6-LP) chimeras were stimulated with naive C57BL/6 cells. These findings suggest that in BMT chimeras transplanted across minor histocompatibility barriers: (1) both host and donor-derived antigen-presenting cells can present host antigens to donor T cells whose numbers in the marrow inoculum will determine if GVHD or tolerance will ensue, (2) GVHD can be triggered by only a limited number of 'dominant' minor antigens, and (3) we found no evidence for the presence of natural suppressors, veto cells or anti-idiotypic suppressor T cells.

Animals↗
PubMed1989

The mechanism of graft-host-tolerance in murine radiation chimeras transplanted across minor histocompatibility barriers.

A better understanding of the mechanism(s) involved in graft-host-tolerance following allogeneic bone marrow transplantation is needed to develop new strategies to prevent graft-versus-host disease (GVHD). Based on previous studies, mainly in MHC-mismatched donor-recipient pairs, three hypotheses have been proposed: clonal deletion, active suppression and lack of adequate antigen-presenting cells. Our goal was to identify the mechanism(s) by which tolerance is achieved and maintained in radiation chimeras transplanted across minor histocompatibility barriers. Healthy (B6----LP) chimeras were obtained following injection of 10(7) C57BL/6 marrow cells to irradiated (9.5 Gy) LP hosts and used experimentally 100 days after chimerization. The tolerance state of (B6----LP) chimeras could not be abrogated after i.v. transfer of 5 x 10(7) donor-type spleen cells alone or with repeated i.p. injection of host-type antigen-presenting cells. No GVHD was observed when 10(7) marrow cells plus 5 x 10(7) spleen cells from (B6----LP) chimeras were injected to irradiated LP recipients. Chimera spleen cells suppressed GVHD when adoptively transferred to LP recipients of a C57BL/6 graft. These results suggest that in this model the presence of suppressor cells is both necessary and sufficient to maintain graft-host-tolerance.

Animals↗
PubMed1989

Evaluation of Fc-dependent monocyte-macrophage function in bone marrow transplant recipients.

Allogeneic bone marrow recipients exhibit a complex and multifactorial immunodeficiency affecting numerous effector functions for various periods of time. In order to evaluate their Fc-mediated monocyte-macrophage (MM) function we studied the clearance of IgG-coated Rh-positive erythrocytes (EA) in healthy control subjects and recipients of unmanipulated marrow. We measured the survival of radiolabeled EA prior to myeloablation and on days 0, +14, +38, +124, +368, and greater than or equal to +730 following bone marrow transplant (BMT). Simultaneously we evaluated the interaction of adherent peripheral blood monocytes (PBMs) with EA (in vitro phagocytosis and attachment). Fc-mediated function appeared normal prior to BMT despite the fact that most patients had received chemotherapy previously. We found no deficit in the Fc-dependent MM activity (in vivo and in vitro) at any time after transplantation. On the contrary we demonstrated an enhanced Fc-dependent clearance during the first month after BMT (p less than 0.001; Mann-Whitney test). These results suggest that we can expect efficient MM function to eliminate IgG-coated cells and particles in BMT recipients.

Bone Marrow Transplantation↗
PubMed1987

Alcohol treatment outcome evaluation methodology: state of the art 1980-1984.

The methodology of alcohol treatment outcome studies published during two sequential intervals from 1976 through mid-1984 is critically reviewed. Although considerable methodological improvements have occurred over time, major methodological deficiencies continue to characterize much of the literature, with inadequate reporting of subjects' pretreatment characteristics (e.g., severity of dependence) being the most striking problem. Pervasive differences across studies regarding the types of data gathered and the ways in which findings are reported seriously impede attempts to compare studies and weaken the types of conclusions that can be drawn about treatment efficacy in general. It is suggested that journal editors establish standards of reporting for follow-up studies.

Alcoholism↗
PubMedDate not supplied

Abstinence versus nonabstinence: the objectives of alcoholism rehabilitation programs in Quebec.

Since the end of the nineteenth century, various attitudes toward alcoholism--from moralistic and legalistic to those rooted in medicine and psychology--have been adopted. Some of these have persisted and continue to influence the treatment programs available to alcoholics. One of the most popular explanatory models today is the traditional model, which prescribes abstinence as a treatment objective. However, more and more studies are showing that controlled drinking can be a viable alternative for many alcoholics. The aim of the present study is to determine the type of treatment goal preferred by alcoholism rehabilitation centers in the province of Quebec. As of March 31, 1987, the general directors of 78 of the 81 rehabilitation centers operating in Quebec were contacted and interviewed. The data most relevant to the present study came from the response to the following question: "Is a treatment goal other than complete abstinence acceptable for every client who registers in your program to resolve a problem of alcoholism?" The results indicate that most centers will not allow their clients to work toward any goal other than abstinence.

Alcohol Drinking↗