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Biomedical subjects

F Michel

Publications and source records attributed to F Michel.

At least 199 records · Page 11Linked to original sources

Cytotoxic T lymphocytes in HIV-induced disease: implications for therapy and vaccination.

The immune response to HIV in infected humans leads to the production of HIV-specific cytotoxic T lymphocytes (CTL) which circulate in high frequencies. The presence of these CTL and their eventual protective activities have been studied by various laboratories, and correlations have been made with certain immunopathological manifestations of HIV infections. It seems probable that HIV-immune CTL participate in the induction of certain disorders by initiating inflammatory reactions in the lungs, central nervous system and lymph nodes. Various virus antigens recognized by HIV-immune CTL on the surface of the infected cell have been identified, and molecular definition of the epitopes recognized is well under way. Likewise, numerous HLA transplantation antigens that regulate HIV antigen recognition by CTL have been identified. These data are discussed with regard to the eventual development of a vaccine and of functional immunotherapies.

Acquired Immunodeficiency Syndrome↗

Immune recognition of AIDS virus antigens by human and murine cytotoxic T lymphocytes.

The CTL response to HIV was analyzed in humans and in mice. By using a novel and strictly autologous lymphocyte culture system, human CTL lines were established with PBL from seropositive asymptomatic donors and from patients suffering from AIDS or presenting AIDS-related complex. CTL from HLA-A2 donors recognize and kill murine P815 mastocytoma cells doubly transfected with the human HLA-A2 gene and the HIV env gene; they also kill HLA-compatible human macrophages infected with HIV. CTL specific for the HIV env Ag were also generated in BALB/c mice by immunization with syngeneic murine cells transfected with the HIV env gene. Human and murine HIV-immune CTL populations belong to the CD8 subset of T lymphocytes and are restricted by class I HLA or H-2 transplantation Ag, respectively, in the recognition of HIV env Ag. The two different experimental systems presented here can be used to study CD8 lymphocyte immunity against HIV. The murine model of CTL immunity offers the additional advantage of avoiding the manipulation of infectious virus isolates.

Animals↗

HIV-specific T lymphocyte immunity in mice immunized with a recombinant vaccinia virus.

Infection by the human immunodeficiency virus (HIV) induces T cell immunity in humans, chimpanzees and macaques. The protective value of this immune response is not clear. We have consequently developed a murine experimental system to study HIV-specific CD4 and CD8 T lymphocyte immunity in vitro and in vivo. BALB/c, DBA/2 and C3H/He mice were immunized with vaccinia virus (VV) recombinant VV-11.39 which expresses the gp160 glycoprotein of HIV-1. Primary and secondary cytotoxic T lymphocyte response to HIV were detected with histocompatible mouse target cells transfected with the HIV-1 env gene. Killer cells were positive for the Thy-1 and Ly-2 (CD8) T cell markers, and were restricted by class I H-2 histocompatibility antigens. Immunological memory specific for HIV-1 envelope antigens was clearly induced by vaccination with VV-11.39:spleen cells from mice vaccinated 4 weeks or more prior to assay generated CD4 and CD8 T lymphocyte responses following stimulation in vitro with HIV envelope antigens. The intensity of these responses increased with consecutive vaccinations, indicating that HIV-specific precursor T cell pools were progressively amplified. Finally, DBA/2 mice vaccinated with VV-11.39 developed protective immunity against a syngeneic tumor which expresses HIV-1 env antigens, leading to accelerated tumor rejection and increased survival.

Animals↗

DNA sequence and organization of the mitochondrial ND1 gene from Podospora anserina: analysis of alternate splice sites.

Earlier, we reported that the ND1 mitochondrial gene of Podospora anserina is mosaic, containing at least three class I introns. We have now completed the sequence of the ND1 gene and have determined that it contains four class I introns of 1,820, 2,631, 2,256 and 2,597 bp with the entire gene complex containing 10,505 bp, only 1,101 of which are exon sequences. Introns 1 and 3 appear to be related in that their open reading frames (ORFS) exhibit extensive amino acid sequence similarity and like the URFN sequence from Neurospora crassa have multiple sequence repetitions. Introns 2 and 4 are similar in that both appear to be mosaic introns. Where intron 2 has many short ORFS, intron 4 has two, 391 and 262 aa respectively. The first ORF has some patch work sequence similarity with one of the intron 2 ORFs but the second ORF is strikingly similar to the single intron ORF in the ND1 gene of N. crassa. Just upstream of the sequences necessary to form the central core of the P. anserina intron 4 secondary structure, there is a 17 bp sequence which is an exact replica of the exon sequence abutting the 5' flank of the 1,118 bp N. crassa ND1 intron. Secondary structure analysis suggests that the 2,597 bp intron 4 can fold as an entity but a similar structure can be constructed just from an 1,130 bp portion by utilizing the 17 bp element as an alternate splice site. Detailed structural analysis suggests that intron 4 (as well as the single ND1 intron from N. crassa) can utilize helical configurations which bring the downstream open reading frame into juxtaposition with the exon sequences.

Amino Acid Sequence↗

Radioprotection by pretreatment with deuterated water: cytokinetic changes in the small intestine of the mouse.

All mice partially deuterated by ingestion of 29% heavy water for 12 days survived whole body gamma irradiation (8.5 Gy) from a 60Co source, whereas 42% of nondeuterated control animals died from bone marrow failure. The incorporation of 3HTdR into enterocytic DNA, as measured by autoradiography and liquid scintillation spectrometry, was used to assess the proliferative activity of small intestinal epithelium. The sequence and the magnitude of changes in tritium activity were in good agreement. Deuteration alone resulted in a reduced proliferative activity of small intestinal crypt epithelium, particularly in the basal cell positions and the first positions of the proliferation compartment. The number of positions occupied by the proliferative compartment and the crypt length were, however, barely affected by deuteration. The radiation-induced depression of DNA synthesis in the proliferative compartment was of similar magnitude in both groups. Crypt epithelium in deuterated mice, however, displayed signs of an accelerated and/or enhanced regeneration. The cytokinetic changes in deuterated animals are consistent with a protective effect for clonogenic intestinal epithelium at the time of irradiation.

Animals↗

A serious complication of vesical ether instillation: ether cystitis.

We report the fourth case of ether cystitis, which occurred after ether was used to dissolve a Foley catheter balloon. The severity of the lesions required an ileocystoplasty to preserve normal micturition. Ether dissolution of Foley catheter balloons should be replaced with mechanical disruption.

Administration, Intravesical↗

Structural conservation among three homologous introns of bacteriophage T4 and the group I introns of eukaryotes.

Three group I introns of bacteriophage T4 have been compared with respect to their sequence and structural properties. The introns include the td intervening sequence, as well as the two newly described introns in the nrdB and sunY genes of T4. The T4 introns are very closely related, containing phylogenetically conserved sequence elements that allow them to be folded into a core structure that is characteristic of eukaryotic group IA introns. Similarities extend outward to the exon sequences surrounding the three introns. All three introns contain open reading frames (ORFs). Although the intron ORFs are not homologous and occur at different positions, all three ORFs are looped-out of the structure models, with only the 3' ends of each of the ORFs extending into the secondary structure. This arrangement invites interesting speculations on the regulation of splicing by translation. The high degree of similarity between the T4 introns and the eukaryotic group I introns must reflect a common ancestry, resulting either from vertical acquisition of a primordial RNA element or from horizontal transfer.

Animals↗

Effect of long-term treatment with celiprolol on pulmonary function in a group of mild hypertensive asthmatics.

Previous studies have shown that single dose or short-term administration of celiprolol does not impair pulmonary function in patients with asthma. The long-term effects of celiprolol and chlorthalidone on respiratory function in mild hypertensive asthmatic patients were compared. Following a 1-month placebo washout period, five patients were randomized to 3 months of treatment with celiprolol, and four patients were treated with chlorthalidone. This double-blind study was followed by a 12-month open trial in 13 asthmatics. Forced expiratory volume at the first second of expiration (FEV1) remained unchanged throughout the 12-month treatment period. This finding is of interest since a spontaneous decrease in FEV1 of 20 ml/year has been observed in recent surveys of asthmatic patients. No changes in peak expiratory flow rate or maximum expiratory flow at 50% of vital capacity were observed during the study, but measurements of FEV1 before and 2 h after drug administration indicated that celiprolol had no direct bronchodilating effect. The responsiveness to inhaled salbutamol was unaltered during the 12-month trial period, demonstrating that celiprolol does not block the beta 2-adrenoceptors on bronchial smooth muscle. Our results indicate that celiprolol is a safe long-term treatment for hypertension in asthmatic patients. Nevertheless, a survey of a large number of patients may be useful in order to detect individuals at risk, since sensitivity to beta-blockade may vary between patients.

Adult↗

[Mechanism of renal allograft rejection].

Renal allograft rejection, in an immunocompetent subject, résults from a cellular and humoral interaction. Lymphokines, which are immunity mediators (particularly interleukin 1 and 2, and gamma interferon) modulate these different cellular populations, among which T lymphocytes play a major role. The current knowledge of rejection mechanisms allows us to evaluate the principal targets of immunosuppressive drugs used to treat allograft rejection.

Animals↗

[Spontaneous epiphyseal separation in children with spina bifida. Apropos of a series of 12 cases].

Unknown complication but nevertheless frequent, the spontaneous slipped epiphyseal injury in child with spina bifida states the problem for its diagnosis and its treatment. The authors give their experience about 12 cases in 10 children, insisting on the problem of the pseudo-infected and the pseudo-tumoral cases with an early diagnosis. A review of the literature is made about this subject. The treatment is generally orthopaedic excepted at the hip where it is surgical. A physiopathogenic study is made; explaining the mechanism, the frequency of this pathology and its complications.

Bone Neoplasms↗

Multiple exon-binding sites in class II self-splicing introns.

Partial deletion of the exon 5' to S. cerevisiae intron a5, a self-splicing mitochondrial class II intron, reveals the existence of several sites of intron-exon interaction. We have identified two of the corresponding exon-binding sites in intron a5 by comparative sequence analysis and RNAase H digestion of the intron complexed to a DNA version of its 5' exon. Introduction of mutations in either the intronic sites or the complementary exonic sequences affects splicing in vitro, whereas double mutants in which intron-exon pairings have been restored show normal activity. Some of the mutants accumulate a product that was shown to be the intron-3' exon lariat, a postulated splicing intermediate. The possible role of one of the intronic sites in aligning exons for the ligation step is discussed.

Base Sequence↗

Effects of RU 41740 aerosol treatment on mouse bronchoalveolar cells, and protection afforded against influenza virus infection.

RU 41740, an immunomodulating compound extracted from Klebsiella pneumoniae, was previously shown to enhance mice resistance to bacterial and viral lung infections. To explore lung defense mechanisms, we studied the influence of RU 41740 aerosol treatment on the bronchoalveolar cell populations. Five successive daily RU 41740 aerosol treatments induced a large accumulation of leukocytes in the lungs 4h after the last treatment. Polymorphonuclear leukocytes predominated. The numbers of lymphocytes and monocytes rose significantly. A single RU 41740 aerosol treatment significantly raised the number of polymorphonuclears only. A luminol-dependent chemiluminescence assay was used to test the effect of RU 41740 on the opsonized zymosan induced response of alveolar macrophages. In vitro, addition of RU 41740 enhanced this chemiluminescence. After a single RU 41740 aerosol treatment of mice, the chemiluminescence of purified alveolar macrophages from these mice increased significantly. The protective effect of five daily RU 41740 aerosol treatments against influenza virus infection was believed to be due to the great intensity of the cellular response and the polymorphonuclear influx. The alveolar macrophage activation observed might also explain the enhanced resistance of mice to influenza virus infection.

Adjuvants, Immunologic↗

Enhancement of bronchoalveolar cell recovery and stimulation of alveolar macrophage chemiluminescence and resistance to influenza virus after treatment with RU 41821 aerosol.

Aerosol treatment with RU 41821, a glycoprotein extract from Klebsiella pneumoniae, was tested in mice for its effect on the kinetics of the induction of bronchoalveolar cells (i.e., alveolar macrophages, monocytes, lymphocytes, and polymorphonuclear leukocytes). RU 41821 led to an increase in the total number of bronchoalveolar cells. The largest increase was observed for polymorphonuclear leukocytes, and more moderate increases occurred in the numbers of alveolar macrophages, monocytes, and lymphocytes. The alveolar macrophages recruited in response to RU 41821 were activated, as indicated by luminol-dependent chemiluminescence in response to stimulation by opsonized zymosan. The effects of five RU 41821 aerosol treatments and those of a single treatment were further examined in vivo by aerosol infection of mice inoculated with a mouse-pathogenic influenza virus. The maximum protective effect was obtained after five once-a-day treatments and was correlated with the largest increase in the total number of bronchoalveolar cells.

Aerosols↗