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C Auger

Publications and source records attributed to C Auger.

At least 19 recordsLinked to original sources
PubMed2000

Quantal currents at single-site central synapses.

The mode of operation of synaptic transmission has been primarily worked out at the vertebrate neuromuscular junction, thus providing a framework for the interpretation of studies at central synapses. However, differences have been found between the two systems, and a coherent model is still lacking for central synapses. Research in this area revolves around several questions. (1) Is the variability of quantal amplitudes determined pre- or postsynaptically? (2) What is the occupancy of postsynaptic receptors following the release of a synaptic vesicle? And (3) does multivesicular release occur at single release sites following one presynaptic action potential? To answer these questions, it is essential to investigate synaptic processes at the level of single release sites. This is technically difficult because of the complex morphology and small dimensions of central synapses. Nevertheless significant advances have been made in the past few years.

Action Potentials↗
PubMed2000

Fast removal of synaptic glutamate by postsynaptic transporters.

Glutamate transporters are believed to remove glutamate from the synaptic cleft only slowly because they cycle slowly. However, we show that when glutamate binds to postsynaptic transporters at the cerebellar climbing fiber synapse, it evokes a conformation change and inward current that reflect glutamate removal from the synaptic cleft within a few milliseconds, a time scale much faster than the overall cycle time. Contrary to present models, glutamate removal does not require binding of an extracellular proton, and the time course of transporter anion conductance activation differs from that of glutamate removal. The charge movement associated with glutamate removal is consistent with the majority of synaptically released glutamate being removed from the synaptic cleft by postsynaptic transporters.

ATP-Binding Cassette Transporters↗
PubMed2000

Canine large granular lymphocyte leukemia and its derived cell line produce infectious retroviral particles.

We describe a case of large granular lymphocyte (LGL) leukemia in a dog that we followed over a period of 2 years. Analysis of a hematological profile revealed lymphocytosis (19,500 lymphocytes per microliter; reference values, 1,000-4,800 lymphocytes per microliter), with a majority of LGL on the blood smear. LGL is defined as a lymphoid subset comprising 10% of peripheral blood mononuclear cells and corresponding to either CD3- CD8- NK cells or CD3+ CD8+ T cells. The cells are characterized by abundant basophilic cytoplasm containing distinct granules of variable size and number. The characteristic phenotype of our leukemic LGL is of a cytotoxic T cell, CD3+ and CD8+. A new cell line, DLC 02, was established from the peripheral lymphocytes of the leukemic dog. Particles with type C retroviral morphology were found in ultrathin sections of DLC 02 cell pellets. These particles were found to have a sucrose gradient density of 1.17 g/liter and a reverse transcriptase activity with an Mn2+ preference, suggesting that they correspond to a mammalian type C oncovirus.

Animals↗
PubMed2000

[Post-traumatic stress disorder. After the flood in Saguenay].

OBJECTIVE: To measure the prevalence of posttraumatic stress disorder and emotional distress among victims of the Saguenay flood compared with those who were not affected by the flood. DESIGN: Cross-sectional study using a telephone survey of victims and a control group. SETTING: Chicoutimi, Que. PARTICIPANTS: Sixty-two adults in a flooded area and a control group of 79 volunteers chosen randomly from an adjacent area. MAIN OUTCOME MEASURES: Diagnostic criteria for posttraumatic stress disorder measured using the Post-traumatic Stress Disorder Reaction Index and high scores on the Self-Reporting Questionnaire on emotional distress. RESULTS: Socially and demographically, study group and control group were comparable. Prevalence of posttraumatic stress disorder in the study group was close to 20% (odds ratio [OR] 6.08; 95% confidence interval [CI] 1.63 to 22.64). Prevalence of emotional distress in the study group was 29% (OR 2.42; 95% CI 1.04 to 5.61). CONCLUSION: The Saguenay flood caused psychological distress that was measurable 4 months later. Health care professionals should be aware of the psychological effects of natural disasters.

Adolescent↗
PubMed1999

Characterization of a canine long-term T cell line (DLC 01) established from a dog with Sézary syndrome and producing retroviral particles.

The canine DLC 01 cell line derives from a lymph node of a dog with Sézary syndrome. The DLC 01 cell phenotype is CD4-, CD8+, CD45+, DQ+, similar to that of original cells after treatment with dimethylsulfoxide or phorbol myristate. Canine cutaneous T cell lymphoma are usually CD4-, CD8+ in contrast to their human counterparts which are CD4+, CD8-. Therefore, the DLC 01 cell line appears to be a unique model to study the mechanism of all surface molecule expression in vitro. Viral particles with retrovirus type-C morphology were found in ultrathin sections of DLC 01 cell pellets. Retroviral particles are spontaneously produced after the 50th cell passage or after induction with 0.5% dimethylsulfoxide. This is the first description of a dog lymphoid cell line spontaneously growing and producing a retrovirus. It was found to share several features in common with feline and murine leukemia viruses.

Animals↗
PubMed1998

New helper cells and matched early region 1-deleted adenovirus vectors prevent generation of replication-competent adenoviruses.

The presence of replication-competent adenoviruses (RCAs) in batches of replication-defective adenovirus (Ad) vectors is a major problem for the application of these vectors in gene therapy. RCAs are generated by recombination between sequences in the Ad vector and homologous Ad sequences in the helper cells, resulting in the acquisition by the vector of early region 1. To prevent the formation of RCAs, we have developed helper cell lines, which we named PER, and matched Ad vectors that do not have sequence overlap. PER cells contain the Ad serotype 5 (Ad5) E1A- and E1B-encoding sequences (Ad5 nucleotides 459-3510) under the control of the human phosphoglycerate kinase (PGK) promoter. We demonstrate that PER cells synthesize high levels of the Ad5 E1A and E1B proteins. The yields from PER cells of E1-deleted Ads are similar to those obtained from earlier helper cells, such as 911 and 293 cells. Propagation of matched Ad vectors, which lack Ad5 nucleotides 459-3510, in one of the PER clones, PER.C6, does not result in the generation of RCAs, in contrast to propagation in 293 cells. We conclude that the combination of PER.C6 cells and nonoverlapping E1-deleted adenoviral vectors eliminates the problem of RCA generation by homologous recombination, and allows cost-effective production of safe, clinical-grade batches of recombinant Ad vectors.

Adenovirus E1A Proteins↗
PubMed1998

Multivesicular release at single functional synaptic sites in cerebellar stellate and basket cells.

The purpose of the present work was to test the hypothesis that no more than one vesicle of transmitter can be liberated by an action potential at a single release site. Spontaneous and evoked IPSCs were recorded from interneurons in the molecular layer of cerebellar slices. Evoked IPSCs were obtained using either extracellular stimulation or paired recordings of presynaptic and postsynaptic neurons. Connections were identified as single-site synapses when evoked current amplitudes could be grouped into one peak that was well separated from the background noise. Peak amplitudes ranged from 30 to 298 pA. Reducing the release probability by lowering the external Ca2+ concentration or adding Cd2+ failed to reveal smaller quantal components. Some spontaneous IPSCs (1.4-2.4%) and IPSCs evoked at single-site synapses (2-6%) were followed within <5 msec by a secondary IPSC that could not be accounted for by random occurrence of background IPSCs. Nonlinear summation of closely timed events indicated that they involved activation of a common set of receptors and therefore that several vesicles could be released at the same release site by one action potential. An average receptor occupancy of 0.70 was calculated after single release events. At some single-site connections, two closely spaced amplitude peaks were resolved, presumably reflecting single and double vesicular release. Consistent with multivesicular release, kinetics of onset, decay, and latency were correlated to IPSC amplitude. We conclude that the one-site, one-vesicle hypothesis does not hold at interneuron-interneuron synapses.

Animals↗
PubMed1998

Necrotizing fasciitis of the retroperitoneum: an unusual presentation of group A Streptococcus infection.

A 14-year-old girl presented with symptoms resembling acute appendicitis. Five days after appendectomy and continued fever and severe abdominal pain, blood cultures were found positive for Streptococcus pyogenes. Two days later a diagnosis of group A streptococcal peritonitis with necrotizing retroperitoneal fasciitis was confirmed by retroperitoneal cultures obtained at laparotomy. Although multiple organ systems showed impaired functioning, including hepatic, renal and respiratory changes, she did not meet the criteria for streptococcal toxic shock syndrome. She was treated with a combination of high-dose parenteral penicillin and clindamycin, followed by prolonged treatment with clindamycin orally. Recovery was complicated by persistent hydronephrosis, which was slow to resolve.

Adolescent↗
PubMed1997

Heterogeneity of functional synaptic parameters among single release sites.

Following alpha-latrotoxin application to cerebellar slices, bursts of miniature IPSCs (mIPSCs) were observed in interneurons of the molecular layer. Within bursts, mIPSCs had homogeneous amplitudes with a narrow Gaussian distribution. Analysis of successive event amplitudes revealed an interaction between consecutive IPSCs, indicating that bursts originate at single release sites. A mean receptor occupancy of 76% was calculated. IPSCs within a burst were analyzed using nonstationary noise analysis. The results indicate that individual release sites differ in the number, unitary conductance, and peak opening probability of their postsynaptic channels. In addition, the IPSC decay kinetics were very different among release sites. Finally, a significant correlation was found between several pairs of single site synaptic parameters.

Animals↗
PubMed1996

Detection on immunoblot of new proteins from the microsomal fraction recognized by anti-liver-kidney microsome antibodies type 1.

Previous studies have demonstrated that sera from patients with autoimmune hepatitis type 1 contain antibodies which react with proteins other than the endoplasmic reticulum integral membrane protein of apparent Mr 50,000, now known to be a cytochrome P450 of the IID subfamily. Sera from 141 patients found by immunofluorescence to be positive for anti-liver-kidney microsome antibodies type 1, and sera from 50 blood donors used as controls, were analyzed by immunoblotting experiments on rat liver microsomes, microsomal subfractions, and also microsomes subjected to various treatments, as described in the text. These fractions were characterized morphologically by electronic microscopy and biochemically by different enzymatic activities. Five bands were found to be stained more often by the patients' sera than by the controls' and with a statistically significant difference in frequency. These antigenic proteins were located at apparent Mr 62,000, 58,000, 50,000, 40,000, and 35,000. The 50,000 protein was of course more often stained than the others. Antibodies against these antigens belonged essentially to the IgG1 subclass. For some of them, subcellular localization and membrane topography are discussed. Interestingly, the 58,000 protein is not an integral membrane protein.

Adult↗
PubMed1994

Induction of apoptosis in mouse thymocytes by cyclosporin A: in vivo study.

We investigated the in vivo effect of cyclosporin A (CsA) on mouse thymus and thymocytes. Administration of CsA (10 mg/kg of body weight) was found to induce a marked reduction in the size, weight and consistency of the thymus. These modifications were associated with thymic reticulo-epithelial cells (TREC) and thymocyte damage. Some of the damaged thymocytes displayed characteristic of cells undergoing apoptosis. Ultrastructural study of thymocytes and thymic tissue, as well as DNA electrophoresis of thymocytes, showed chromatin condensation, cellular shrinkage, and nuclear fragmentation in oligonucleosomal fragments. DNA labeling with propidium iodide (PI) of thymocytes from CsA treated mice cultured for 24 hrs showed an increased number of apoptotic nuclei. Furthermore, flow cytometric analysis using monoclonal antibodies (mAbs) specific for thymocyte subsets confirmed that CsA induces a large decrease in the relative number of mature single positive (SP) CD4+CD8- and CD8+CD4- thymocytes expressing high densities of CD3 and T cell receptor ab (TCR alpha beta) surface molecules, but also a decrease in the absolute number of the other thymocyte subsets. These results suggest that CsA causes macroscopic and ultrastructural modifications of the thymus, associated with an active process of cell death in mouse thymocytes in vivo. In line with these results we formulate a hypothesis concerning the stage of T-cell development at which CsA induces apoptosis.

Animals↗
PubMed1994

Induction of apoptosis in mouse thymocytes by cyclosporin A: an in vitro study.

The effect of cyclosporin A (CsA) on mouse thymocytes was investigated in vitro. Ultrastructural examination and DNA electrophoresis of 24hr-CsA-treated thymocytes showed chromatin condensation, cellular shrinkage and nuclear fragmentation in oligonucleosomal fragments. DNA labeling of CsA-treated-thymocytes with propidium iodide (PI) showed an increase in the number of apoptotic nuclei compared to untreated thymocytes. Furthermore, flow cytometric analysis using monoclonal antibodies (mAbs) specific to particular thymocyte subsets showed that CsA induces a decrease in the relative number of immature double positive (DP) CD4+CD8+ thymocytes in direct proportion to the concentration of CsA. No significant changes were observed in mature single positive (SP) CD4+CD8- and CD8+CD4- cells. Moreover, the cell viability of CsA-treated thymocytes was decreased. These results suggest that CsA induces the programmed cell death of thymocytes in vitro. Taken together with our previous study on the in vivo effect of CsA on mouse thymus and thymocytes, the present study confirms that, in addition to its effect on the thymic epithelium, CsA acts directly on thymocytes by inducing their programmed cell death. We postulate that immature DP thymocytes are the most likely targets of CsA.

Animals↗
PubMed1992

Effects of cyclosporin A on mouse thymus: immunochemical and ultrastructural studies.

The in vivo effect of cyclosporin A (CsA) on the murine thymus was investigated by studying the ultrastructural cellular alterations, which are described for the first time, and the immunohistochemical modifications of thymocytes and thymic reticulo-epithelial cells (TREC). A marked reduction of the thymus size became apparent after 6 days of CsA treatment (10 mg/kg/day). Light microscopy studies using polyclonal antibodies (Ab) or monoclonal Ab specific to lymphoid sub-populations (anti-CD4, anti-CD5, anti-CD8), and specific to epithelial cells (anti-keratin: AKs, K8), to cortical TREC (TR4) and to subcapsular/medullary TREC (TR5, 3H9) showed that the number of CD4- 8+ or CD4+ 8- medullary thymocytes dramatically decreased and that the cortical TREC are affected, after 10 days of CsA treatment. These observations were confirmed by electron microscopy studies demonstrated that the medullary lymphoid population disappeared almost entirely. TREC, principally cortical type, presented signs of cellular lysis. A few cortical thymocytes showed some damage. At day 8 the medullary thymic tissue was disorganized, but no change was noted in the subcapsular area right up to the final day (day 10) of CsA treatment. These results suggest that CsA has a harmful effect on cortical TREC, which affects the development of immature thymocytes.

Animals↗
PubMed1990

Human epithelial thymic tumours: heterogeneity in immunostaining of epithelial cell markers and thymic hormones.

Different hormones (thymulin, thymosin alpha 1, vasopressin), antigenic markers of cortical and subcapsular/medullary thymic areas and tumour associated antigens were studied on paraffin or frozen section and cultures of human epithelial thymic tumours ('thymomas'). Thymulin, thymosin alpha 1 and for the first time vasopressin are found in most tumours. The epithelial cells of five 'thymomas' had markers of both cortical (TE3) and subcapsular/medullary thymic regions (A2B5 and/or TE4 and/or anti-p19). Leu-7, a marker of subcapsular epithelial cells was positive only in two tumours. The histological classification into cortical and medullary tumours does not correspond to our immunofluorescence results. The presence of these markers does not support the theory of different embryologic origin of the cortical and subcapsular/medullary epithelial cells. Transferrin receptors were detected on only some epithelial cells of thymic 'carcinomas'. Adenocarcinoma related antigen and carcino embryonic antigen only stained a few epithelial cells of all the tumours. There is no expected correlation between the presence of epidermal growth factor receptors on cell membranes and the number of proliferative cells stained by the anti-Ki67 antibodies. Immunostainings were heterogeneous according to the epithelial thymic tumours, independent of histological classification and not yet useful for prognosis.

Adult↗
PubMed1989

Study of a monoclonal antibody specific to epithelial cells of mammalian thymuses.

Hybridomas between spleen cells from BALB/c mice and Sp2/O-Ag14 mycloma cell line are performed by PEG fusion. An in vitro booster is realized with human thymic reticulo-epithelial cell cultures as antigen. A monoclonal antibody (3H9) directed against the thymic epithelium and stratified epithelia of mammals has been obtained and characterized.

Animals↗
PubMed1989

Quantitative analysis of cultured thymic reticulo-epithelial cells labelled by different antibodies: a flow cytometric study.

Quantitative measurements of cultured human and murine thymic, and human thymoma reticuloepithelial cells (REC), immunolabeled by different antibodies (Ab) (TE3, TE4, anti-HTLV p19(p19), lu5, K11 and Aks) and by thymic hormones (thymulin and thymosin alpha 1 (Ta1)) within these cells, were performed using a flow cytometric technique. The anti-keratin polyclonal Ab labeled nearly the whole human or murine population. The p19 monoclonal Ab (MoAb), specific for the subcortical/medullary thymic regions, labelled 37-77% of the human REC. The TE3 MoAb, specific for the cortical region, labelled 54-83% of the REC. These percentages suggest that the cultured thymic REC (TREC) had markers of both regions together and therefore that these markers are not absolutely specific to determine their subcortical/medullary or cortical thymic origin. For the three populations there were more cells containing Ta1 than thymulin. The overlap of the percentage of labelled cells suggests that the same cell could synthesize the two hormones and that these hormones could be localized within the TE3 positive cells.

Animals↗
PubMed1988

Immunolocalization of thymosin alpha 1, thymopoietin and thymulin in mouse thymic epithelial cells at different stages of culture: a light and electron microscopic study.

The secretory evolution of the thymic hormones (thymulin, thymosin alpha 1 and thymopoietin) in cultured thymic reticuloepithelial cells (TREC) was studied by immunocytochemical techniques using monoclonal anti-thymulin or anti-thymosin alpha 1 and polyclonal anti-thymopoietin antibodies (Ab). The culture of TREC was performed with a medium where L-valine was replaced by D-valine, thus ensuring rapid and selective development of these cells. The number of thymulin, thymosin alpha 1 or thymopoietin-containing cells increased progressively from Day 6 to Day 12 of the culture. The localization of the three thymic hormones within the TREC also varied according to the age of the culture. By light microscopy the staining of the three hormones was localized in some cytoplasmic granules at the beginning of the culture and at Day 90, while at Day 12 it was throughout the cytoplasm. In electron microscopy these localizations corresponded respectively to vacuoles of different sizes and to cytosol. All these results show that the synthesis and excretion of thymulin, thymosin alpha 1 and thymopoietin evolve during the development of TREC in culture.

Animals↗