Search PubMed⌕ Search

Biomedical subjects

L Thibodeau

Publications and source records attributed to L Thibodeau.

At least 19 recordsLinked to original sources
PubMed1998

Clonal deletion of some V beta+ T cells in peripheral lymphocytes from C57BL/6 mice infected with MHV3.

Mouse hepatitis virus type 3 infection is generally accompanied by a severe immune dysfunction involving thymic or splenic T cell subpopulations. We postulate that the peripheral lymphoid cell depletions were caused by a selective deletion of some V beta subsets of mature T cells, as observed with superantigens. We have examined the expression of V beta 6, V beta 8 and V beta 14 in T cell subpopulations from the spleen and lymph nodes of pathogenic L2-MHV3-infected C57BL/6 mice. Cytofluorometric study showed decreases in splenic V beta 8+, V beta 6+, and V beta 14+ T cell subpopulations at 72 hrs post-infection. Single positive CD4+ T cells were diminushed but not the CD8+ cells. In contrast, the various V beta splenic cell populations were not modified in mice infected with a non- pathogenic YAC-MHV3 variant. However, the V beta 8/CD4 ratio increased in splenic cells but decreased in lymphocytes from lymph nodes. The V beta 14/CD4 ratio decreased only in splenic cells while V beta 6/CD4 ratios were not modified. These results suggest that alterations in V beta cell populations may play a role in the L2-MHV3-induced immunodeficiency.

Animals↗
PubMed1996

[Cloning, expression and characterization of HIV-1 gp60 partially or completely deleted in the V3 loop].

In order to better understand the role of the immunodominant V3 loop in the type-specific immune response and also to determine if this sequence has a role in AIDS pathogenesis, notably in the induction of apoptosis in CD4+ cells, we have introduced 2 modifications in the env gene from pNL4-3: a partial deletion in the V3 loop, keeping only the conserved tip of the loop GPGRAF consensus sequence (env delta V3-GPGRAF) and, secondly, a complete deletion of V3 sequence plus 43 nucleotides in C3 (env delta V3+). These constructions as well as the non-modified env gene, were cloned and expressed in a baculovirus system. Western blot analysis has shown that both modified env gene products reacted with a reference anti-HIV-1 serum to the same extent as the non-modified gp 160. However, in contrast to the non-modified env-protein and to env delta V3-GPGRAF, the env delta V3+ protein failed to bind to CD4 molecule, although V3 is not directly involved in receptor binding. These modified and non-modified recombinant proteins will be very useful to determine the potential of the partially or totally V3-deleted gp 160 to induce broadly reactive neutralizing antibodies and also to determine if V3 has a role in certain aspects of HIV-induced pathogenesis, notably apoptosis.

Base Sequence↗
PubMed1994

Analysis of long-term viral expression in CEM cells persistently infected with non syncytium-inducing HIV-1 strains.

CEM cells were infected with three HIV-1 non syncytium-inducing (NSI) strains obtained from AIDS patients or seropositive individuals. The surviving cells were followed for several months in the persistently infected cultures designated 65870/CEM, 65871/CEM and 3929/CEM, and analyzed for virus expression using light and electron microscopy, immunofluorescence, reverse transcriptase assay, polymerase chain reaction amplification (PCR), nucleic acid hybridization and flow cytometry. The virus isolates induced relatively few syncytia and other cytopathic effects in the corresponding cell lines and the number of cells positive for virus expression never rose above 44%. Distinct peaks of antigen-positive cells were obtained, coincident with high levels of reverse transcriptase activity. The cultures were strongly resistant to superinfection by laboratory strain Lai, with the exception of 65870/CEM which expressed HIV antigens in up to 15% of the cells for a few days. However, cell lysis was minimal in all cases. After long-term cultivation of the three cultures, no antigen-positive cells were detected and no trace of virus expression could be observed. The remaining cells consisted entirely of CD4-negative cells. PCR analyses indicated that cells harboring a provirus were progressively eliminated from the cultures, leaving only virus-free cells. In this system, cells carrying a latent provirus survive for a limited period of time before virus activation induces cell lysis. These results suggest that at least three types of cells exist in the CEM cell line: CD4-positive cells which are rapidly killed by the virus, a second type harboring a latent viral genome after the infection and which grow normally until activation of the resident genome by external or internal signal(s), and a third type which represents rare CD4-negative cells present in the initial CEM population and which are selected for by the NSI isolates. This is the first study documenting specific interactions between NSI strains of HIV-1 and distinct subpopulations of CEM cells grown as a single cell culture.

Acquired Immunodeficiency Syndrome↗
PubMed1994

Long-term lumboureteral shunt removed secondary to iatrogenic meningitis.

With the advent of ventriculoperitoneal cerebrospinal fluid shunts for communicating hydrocephalus, rarely does the physician see patients with alternate types of shunting devices. The once popularized lumboureteral shunt is unique for its potential complications of dehydration, electrolyte imbalances, infection, and the sacrifice of a functioning kidney. This article presents the case of a woman with a longstanding lumboureteral shunt that was removed after the onset of iatrogenic meningitis secondary to an ascending urinary tract infection.

Adult↗
PubMed1991

[Oral and parenteral immunization with HIV immunosome induce the secretion of IgA specific of HIV-1 in the salivary and the production of circulatory IgA in mice and rabbits].

Given the sexual transmission of HIV, the establishment of a genital mucosal immunity through secretory IgA may be necessary to achieve protection. We have investigated if repeated stimulations of oral mucosa with HIV-Immunosomes would lead to the production of secretory IgA in saliva and also, if such an oral immunization could prime the immune system to an early systemic immune response following a parenteral immunisation with a low dose of the antigen. HIV-1 gp 160-specific secretory IgA were detected in the saliva of all rabbits orally immunized with HIV-Immunosomes. As early as one week after the parenteral immunization, high titers of serum IgA, IgM and IgG were detected both in mice and rabbits that had been orally stimulated with the antigen. These antibodies could neutralize HIV infectivity in vitro. Animals that were immunized only parenterally showed a very weak humoral immune response.

Administration, Oral↗
PubMed1991

Insert earphones for speech recognition testing.

Performance-intensity functions for PB word lists were run on 19 normal-hearing subjects and 15 subjects with sensorineural hearing losses. Comparisons were made between standard supra-aural earphones (TDH-49P) and insert phones (ER-3A). Results showed that, at least for the higher sensation levels where word recognition tests are usually performed, the phones may be used interchangeably. Using insert earphones for word recognition tests can have several beneficial effects with respect to cross hearing and masking.

Adult↗
PubMed1990

Use of electrophysiologic tests to measure disease progression in ALS therapeutic trials.

A battery of electrophysiologic tests was developed to assess the relative degree of lower and upper motor neuron (spasticity) deficit in a group of ALS patients enrolled in a therapeutic trial. Test results were correlated with strength in the tibialis anterior muscle as determined by measurement of maximum voluntary isometric contraction (MVIC), using strain gauge tensiometers, and were also correlated with a clinical spasticity rating scale. Patients were tested every 6 to 8 weeks over more than 1 year. Compound muscle action potential amplitude (CMAPa) from tibialis anterior correlated best with MVIC and also showed a strong linear correlation with time, as did MVIC. Other tests correlated poorly with MVIC on the average, although individual patients did show high correlations. In those patients where correlation between CMAPa and MVIC was low, MVIC did not show a high linear correlation with time and was also highly variable. This study suggests that the addition of CMAPa should be considered in ALS therapeutic trials if MVIC is not available. In addition, CMAPa can be useful in study samples where MVIC deterioration is not linear over time or is highly variable.

Action Potentials↗
PubMed1990

5-azacytidine and 5-azadeoxycytidine inhibit human immunodeficiency virus type 1 replication in vitro.

Chemotherapeutic agents which affect the integration, stability, or inducibility of the human immunodeficiency virus (HIV) provirus would have considerable value in treating acquired immunodeficiency syndrome. Two nucleoside analogs of cytosine, 5-azacytidine and 5-azadeoxycytidine, which seem to have such value because of their capabilities to affect both the stability and the methylation patterns of the nucleic acids into which they are incorporated, were tested for their ability to inhibit the replication of HIV type 1 (HIV-1) in human CEM T cells in vitro. 5-Azadeoxycytidine (1 microM) completely inhibited HIV replication in CEM cells, by the criteria of reduced viral antigen expression and decreased supernatant reverse transcriptase activity, with little toxicity for the treated cells. 5-azacytidine (1 microM) also inhibited HIV replication, but less effectively. When added 2 or more h after CEM cells were infected with HIV-1, both 5-azacytosine derivatives were less effective than they were when added at the time of infection. Even 2 h of exposure to 5-azadeoxycytidine was sufficient for inhibition of HIV replication. Although long exposure to either analog at concentrations of 1 microM would result in pronounced cellular cytotoxicity, the the fact that short exposures to the same dose of drug inhibit HIV replication but are not toxic for the cells implies that cellular toxicity itself is not an important mechanism of the antiviral action of the analogs.

Antineoplastic Agents↗
PubMed1989

Production and characterization of neutralizing monoclonal antibodies against poliovirus type 1, 2, and 3.

Neutralizing monoclonal antibodies were produced against a reference vaccine or a reference wild strain of poliovirus type 1, 2, and 3. After 26 fusions, 55 monoclonal antibodies were obtained with serotype 1 as the immunizing antigen, 180 with serotype 2, and 115 with serotype 3. The neutralizing activity of these monoclonal antibodies was tested first with the two reference strains and then if reactive, against a panel of 10 well-characterized strains of each serotype, 5 vaccinelike (VL) and 5 nonvaccinelike (NVL). All monoclonal antibodies were type specific without reactivity with any of the heterologous strains. There was a wide range of reactivity within the strains of each serotype. Several monoclonal antibodies to serotype 1 reacted with all type 1 strains, while several neutralized strongly all VL strains and weakly one or more of the NVL strains. Most of the 180 monoclonal antibodies to serotype 2 neutralized to various degrees all strains of this serotype and about half reacted very strongly with all homologous strains whether VL or NVL. None could differentiate all VL and NVL homologous strains. Of the 115 monoclonal antibodies to serotype 3, several monoclonal antibodies neutralize to various levels all homologous strains and some can differentiate VL and NVL strains.

Animals↗
PubMed1989

[Role of liposomes in the presentation of HIV envelope glycoprotein and the immune response in mice].

The role of antigen presentation in the induction of humoral as well as cell-mediated immune responses has been investigated by anchoring HIV-1 envelope glycoprotein (gp 160/120) into the phospholipidic bilayer of preformed liposomes to produce HIV-Immunosomes. HIV-Immunosomes induced high titres of HIV-specific antibodies when tested by ELISA, IFA and neutralization, whereas equal amounts of purified glycoprotein alone produced lower antibody response. Similarly, HIV-Immunosomes induced antigen-specific Interleukin-2 production and blastogenic response upon restimulation with the same antigen, in animals vaccinated with HIV-Immunosomes, whereas no secondary response was observed in animals vaccinated with equal amounts of purified gp 160/120. Taken together, these results underline the importance of antigen presentation in the establishment of an adequate immune status and show the potential of HIV-Immunosomes as vaccine against AIDS.

Animals↗
PubMed1988

Enhancement of antigen-specific interleukin 2 production by adding liposomes to rabies antigens for priming.

Antigen-specific IL-2 production was assessed, using splenocytes from rabies immune mice incubated for 24 h with rabies virus antigen. The antigenic material used for in vivo priming was either purified glycoprotein from rabies virus, or the inactivated virus. The time between priming, harvesting and restimulation of the splenocytes was 7 days. It was found that when antigenically inert liposomes were injected, together with antigenic material, to the prospective splenocyte donor mice, IL-2 production was enhanced. This augmentation was observed particularly when priming was performed with the inactivated rabies virus.

Animals↗
PubMed1988

Interleukin-2 production in vitro: a new approach to the study of rabies vaccine immunogenicity as appraised by testing different glycoprotein presentations.

When injected as an immunosome presentation (molecules anchored to preformed liposome), rabies glycoprotein (GP) is capable of protecting animals against rabies either before or after viral infection. The presentation of the GP molecules in the correct form seems to be essential for the induction of antirabies protection. This condition must be taken in account in the making-up of a rabies subunit vaccine. In order to study the relationship between the immune responses induced by the rabies GP and its protective activity, different presentations of the GP were prepared. Purified glycoprotein molecules were associated under different physical forms: liposome-anchored, self-aggregated (rosettes) and associated with the viral lipids (virosomes). These presentations appeared different on electron microscopy. They also exhibited differences in the expression of an immunodominant epitope and in their protective activity. The non-specific immune response, as appraised by interferon production and natural cytotoxicity, was induced at a high level only by the purified viral particles. Specific immune responses (namely virus neutralizing antibody and interleukin-2 production) was induced at high levels only by the viral particle and by the liposome-anchored glycoprotein. A parallelism has previously been established between protection by glycoprotein preparations and interleukin-2 production in primed mice splenocytes. This suggests that the measure of interleukin-2 production in vitro could be used to evaluate the capability of a rabies antigen to induce a T-cell response and to confer protection.

Animals↗
PubMed1988

Interleukin 2 increases protection against experimental rabies.

Vaccination with either whole inactivated rabies virus or immunosome (rabies glycoprotein anchored on liposomes) induces a high level of interleukin 2 (IL 2) production after in vitro specific stimulation of splenocytes from primed mice (9). On the contrary, infection with a live rabies virus does not specifically induce the production of IL 2: splenocytes from ill mice previously infected with wild rabies virus cannot be specifically stimulated by rabies antigens, whereas they can be non-specifically stimulated by a mitogen (Concanavalin A (Con A]. When injected in mice, exogenous IL 2 (purified rat IL 2 or human recombinant IL 2) exhibits an adjuvant effect on rabies virus vaccine or subunit vaccine tested in a pre-exposure potency test (NIH test). When injected in hamsters, according to a post-exposure potency test (infection with a wild rabies virus followed by vaccination), IL 2 has no adjuvant effect on the rabies vaccine. Nevertheless, when injected alone, IL 2 protects thirty to fifty percent of the infected animals treated (1 hour, 3 and 7 days post-infection) with 10 international units of human recombinant IL 2.

Animals↗
PubMed1988

Biomechanics of healing of posterior cervical spinal injuries in a canine model.

The authors performed an in vivo experiment in a canine model to study the natural history of spinal stability as a function of healing time post-injury. Three injuries, in addition to sham, were investigated: 1) transection of supra- and interspinous ligaments at C4-C5; 2) laminectomy at C4; and 3) bilateral facetectomy at C4-C5. Standardized functional flexion/extension stereo-radiographs of the cervical spine were obtained before injury and at 1, 3, 6, 9, 12, and 24 weeks postinjury. The authors found decreased ranges of motion (ROM) at the C4-C5 level for all injuries, including the sham. The decreases, in general, seemed to be in direct proportion to the severity of the injury. When the ROM were normalized to that of the sham at each time point, the relative ROM at C4-C5 increased for Injury 1, remained the same for Injury 2, and decreased for Injury 3. The relative ROM remained the same or increased at C3-C4, and increased at C5-6 for all injuries. It should be emphasized that care should be taken in extrapolating any data from this animal study to the human cervical spine.

Animals↗
PubMed1988

The natural history of motoneuron loss in amyotrophic lateral sclerosis.

Using a quantitative, reliable, sensitive and valid measurement technique, we analyzed the rate and pattern of motor deterioration in 50 strictly defined ALS patients for up to 67 months. We observed that the rate of motoneuron loss was linear and symmetric. Bulbar function deteriorated more slowly than respiratory, arm, and leg function. The loss of leg strength was slower than in the arm. No correlation was observed between age at onset and rate of deterioration, or with different regions of onset. Arm strength changed more slowly in women, but other functions showed no male-female differences. These data should prove useful in the design of clinical trials and in generating testable hypotheses of the etiology of this disease.

Adolescent↗