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Biomedical subjects

M Girard

Publications and source records attributed to M Girard.

At least 217 records · Page 12Linked to original sources
PubMed1989

AIDS vaccines: concepts and first trials.

Two categories of obstacles impede the development of an AIDS vaccine. Virological obstacles are due to lentiviruses, to which HIV and SIV belong, having developed strategies to escape the immune responses of infected hosts and establish persistent infection. These strategies are based on two mechanisms: latency corresponding to restriction of viral gene expression that renders the virus antigenically invisible, and variability, the consequences of which are antigenic shift and permanent adaptation to selective pressures. Immunological obstacles are linked to a central unanswered question: is the global effect of the immune response against HIV beneficial or deleterious to the host and, if beneficial, is it able to resist the virally induced immunosuppression? These obstacles are difficult to overcome theoretically and empirical trials are necessary; live attenuated or recombinant vaccines, inactivated vaccines, subunit vaccines, anti-idiotypes, and synthetic and chimeric vaccines are currently being tested in animals or in humans. At present, promising results have been obtained with inactivated virus vaccines with the use of macaque monkeys infected by SIV as a model.

Acquired Immunodeficiency Syndrome↗
PubMed1989

Pheochromocytoma.

Explore the source record for details and available documents.

Adrenal Gland Neoplasms↗
PubMed1988

Chimpanzees and AIDS research.

Pressure is mounting to relax the regulations on importation of chimpanzees for research. Such a policy is unnecessary and would deepen the plight of an already endangered species.

Acquired Immunodeficiency Syndrome↗
PubMed1988

[Immunogenicity of a hepatitis B vaccine obtained by genetic recombination and containing products of S and pre-S2 genes].

Immunization against hepatitis B by means of a vaccine obtained by genetic recombination on chinese hamster ovary cells was attempted in 32 adult subjects. The HBs antigen was purified from the culture supernatant and contained S and pre S2 genes products. Three 20 micrograms doses were injected intramuscularly at intervals of one month. Anti-HBs seroconversion levels and the geometrical mean of antibodies were slightly higher than those observed with plasma vaccines or genetically engineered yeast-derived vaccine. Antibodies directed against HBs appeared more rapidly and at a higher titre. Anti-pre S2 antibodies were detected after the third injection in 84 per cent of the subjects vaccinated. This recombinant hepatitis B vaccine prepared from chinese hamster ovary cells will probably be as effective as the first generation vaccines obtained by purifying the HBs antigen obtained from the blood of asymptomatic carriers.

Adult↗
PubMed1988

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↗
PubMed1988

Engineering a poliovirus type 2 antigenic site on a type 1 capsid results in a chimaeric virus which is neurovirulent for mice.

Poliovirus type 2 (PV-2) Lansing strain produces a fatal paralytic disease in mice after intracerebral injection, whereas poliovirus type 1 (PV-1) Mahoney strain causes disease only in primates. Atomic models derived from the three-dimensional crystal structure of the PV-1 Mahoney strain have been used to locate three antigenic sites on the surface of the virion. We report here the construction of type 1-type 2 chimaeric polioviruses in which antigenic site 1 from the PV-1 Mahoney strain was substituted by that of the PV-2 Lansing strain by nucleotide cassette exchange in a cloned PV-1 cDNA molecule. These chimaeras proved to have mosaic capsids with composite type 1 and type 2 antigenicity, and induced a neutralizing response against both PV-1 and PV-2 when injected into rabbits. Moreover, a six-amino-acid change in PV-1 antigenic site 1 was shown to be responsible for a remarkable host-range mutation in so far as one of the two type 1-type 2 chimaera was highly neurovirulent for mice.

Animals↗
PubMed1988

Use of cRNA probes for the detection of enteroviruses by molecular hybridization.

Subgenomic fragments of cDNA from poliovirus type 1 were inserted downstream from the SP6 or the T7 promoter in a Gemini riboprobe vector and their in vitro synthesized RNA transcripts were used as radiolabeled probes for the detection of enteroviral RNAs by molecular hybridization. The cRNA transcripts appeared to be more sensitive probes than the corresponding cDNAs. In vitro transcripts of the 5' noncoding region (5' nc riboprobe) were able to detect all of 14 reference enterovirus strains tested, as well as human rhinovirus 2, by dot blot hybridization with infected cell lysates. The same riboprobe also detected the enteroviral RNAs present in 16 of 18 samples of successive passages of stools in tissue culture and in some cases even in crude stool extracts. A riboprobe from the VP 1 region detected specifically poliovirus types 1, 2, and 3 in lysates of infected cells and in 50% of the infected stool specimens tested. These probes could be of particular interest for the epidemic survey of poliovirus infections.

Cell Line↗
PubMed1988

A poliovirus mutant defective for self-cleavage at the COOH-terminus of the 3C protease exhibits secondary processing defects.

By in vitro recombination between the wild-type full-length infectious cDNA of poliovirus and a clone generated by the construction of a cDNA bank from a chemically derived temperature-sensitive plurimutant, we obtained a mutant cDNA with a T to C change at nucleotide 5658. This mutation replaces the isoleucine at residue 74 of the viral protease 3C by a threonine. The mutant virus recovered after transfection exhibited a small-plaque phenotype, and was deficient for viral RNA synthesis. Both these defects were more marked at 39 than at 37 degrees. The mutation was introduced into a bacterial plasmid which expresses the 3C protease along with its flanking autocatalytic cleavage sites. Analysis of the cleavage products expressed in Escherichia coli provided direct evidence that the modification impaired cleavage at the COOH-terminus of 3C. Cleavage at this same site was partially defective in mutant virus-infected HeLa cells, reducing the production of mature 3C and the viral replicase, 3D. Cleavage of P1, the precursor to the capsid polypeptides, was apparently unaffected by this defect, whereas cleavage events within the P2 region of the genome occurred inefficiently. This is indicative of differential strategies for 3C-specific cleavage events in vivo.

DNA↗
PubMed1988

Nucleotide sequence of the M segment of Germiston virus: comparison of the M gene product of several bunyaviruses.

The complete nucleotide sequence of the M RNA segment of Germiston bunyavirus was determined from plasmids containing overlapping M cDNA inserts. The M segment is 4534 nucleotides long and contains a 50-base-long inverted terminal repeat which can form a stable hydrogen-bonded secondary structure with a delta G of -45.8 kcal/mol. The RNA molecule complementary to viral RNA contains a single large open reading frame that encodes a 1437 amino acid-long protein with hydrophobic amino and carboxy terminal regions, which could represent signal and anchor sequences, respectively. It is presumed that this gene product is the polyprotein precursor to glycoproteins G1 and G2 and to the nonstructural polypeptide NSM. The nucleotide and amino acid sequences of the M RNA of Bunyamwera virus (prototype of the serogroup) and snowshow hare and La Crosse viruses (California serogroup) (Lees et al., 1986; Eshita and Bishop, 1984; Grady et al., 1987) were compared to those of Germiston virus. An overall amino acid sequence homology of 44% was found between Germiston and snowshoe hare viruses and of 61% between Germiston and Bunyamwera viruses. Most of the cysteines, three out of seven of the potential glycosylation sites, as well as the N and C terminal hydrophobic domains, are conserved between the four viruses.

Amino Acid Sequence↗
PubMed1988

Construction and characterization of hybrid hepatitis B antigen particles carrying a poliovirus immunogen.

The hepatitis B surface antigen (HBsAg) has the unique property of assembling with cellular lipids into spherical or elongated particles of 22 nm diameter which are secreted by mammalian cells expressing HBsAg. We have studied the structural requirements for particle formation and secretion by creating in-phase insertions into different regions of the S gene of the hepatitis B virus, coding for HBsAg. Modified genes were integrated into an appropriate vector and expressed in mouse L cells. Various single and double inserts in the two major hydrophilic domains of HBsAg were compatible with particle synthesis and secretion. The level of secretion was influenced by the length of the insert, its primary structure, and the site of insertion into the HBsAg molecule. One of the inserted sequences was a synthetic DNA fragment encoding a continuous type 1 poliovirus neutralization epitope (the C3 epitope). Mammalian cells expressing the modified hepatitis B virus S gene secreted hybrid particles carrying the poliovirus antigen. The hybrid polio-HBsAg particles reacted with a monoclonal antibody specific for the C3 epitope and induced poliovirus neutralizing antibodies at low, but significant, titers in mice and at high titers in rabbits. However, the immune response to HBsAg was weaker to hybrid particles than to unmodified HBsAg particles. By cotransfection with two different plasmids carrying either modified or unmodified genes, we obtained phenotypically mixed particles containing both polio-HBsAg and HBsAg molecules. Inoculated into rabbits, the mixed particles induced high antibody titers against both poliovirus and HBsAg.

Amino Acid Sequence↗
PubMed1988

Improved antigenicity of the HIV env protein by cleavage site removal.

The HIV env glycoprotein mediates virus infection and cell fusion through an interaction with the CD4 molecule present at the surface of T4+ lymphocytes. Although env presents a major antigenic target, vaccinia recombinants expressing env elicit low titres of anti-env antibody (Kieny et al., Bio/Technology, 4, 790-795, 1986). To delimit the functional domains of env and to improve the immunogenicity of the vaccinia recombinants we constructed variants expressing env proteins in which the site permitting cleavage of the gp160 precursor to yield gp120 and gp41 was removed, the gp120 and gp41 moieties separated or in which the signal sequence and hydrophobic domains were replaced by equivalents from rabies virus G. Analysis of variants revealed that the gp120 moiety is alone capable of interacting with CD4 and of provoking aggregation of T4+ lymphocytes, whereas cell-associated gp41 liberated by gp160 cleavage was essential for cell fusion. The identity of the signal and transmembrane zones however appeared unimportant. Although removal of the consensus sequence permitting cleavage of gp160 prevented syncytium formation but not aggregation of T4+ lymphocytes, significant cleavage continued to take place. Removal of a second potential cleavage site blocked gp160 cleavage. The live viruses were examined for immunogenicity: recombinant 1139 which lacks both putative cleavage sites was found to elicit a 10-fold higher antibody response in experimental animals than the parental recombinant.

Amino Acid Sequence↗
PubMed1988

Technical expertise as an ethical form: towards an ethics of distance.

The present article proceeds from the observation that the therapeutic relationship is basically unequal. This inequality essentially concerns the respective situation of the patient and his or her doctor vis-à-vis medical knowledge. A strict professionalism guarantees that this inequality remains factual and without essential value. Yet, if both partners unreflectively allow affectivity excessively to intrude into their relationship, their behaviour may then be inspired by subconscious, rather than rational, motives. In that case, the unverifiable allegations of philanthropy or paternalism may be used to rationalise a kind of 'medical sadism' which attempts to justify the will to humiliate the patient by means of the constraints inherent in medical care. The concept of ethical form is introduced as a non-verbal criterion of ethical reliability. It is mainly a way of training the will through the application of rationally justified rules of behaviour. In this context, it is suggested that an effort to remain constantly within the limits of professionalism represents a method of training for the achievement of some degree of ethical credibility in the therapeutic relationship. In the long term, such abstinence could constitute a sort of catharsis, and thereby help to reveal the non-rational motives in medical behaviour. Contrary to the belief prevailing in modern society, the established limits of medical knowledge are not so broad. The application of these limits would probably be the best method of preventing emotions from interfering undesirably in the therapeutic relationship.

Dehumanization↗