Striking identity between HIV-1 envelope glycoprotein gp120 and its CD4 receptor.
Explore the source record for details and available documents.
Biomedical subjects
Publications and source records attributed to J Bernard.
Explore the source record for details and available documents.
Previous results have indicated that phospholipase A2 (PLA2) treatment of telencephalic membranes produced opposite effects on [3H]amino-3-hydroxy-5-methylisoxazole-4-propionic acid (AMPA) binding in neonatal and adult rats. In the present study, we compared the effects of PLA2 treatment of telencephalic membranes on the binding characteristics of agonists and antagonists of the AMPA receptors in the developing rat brain. Whereas PLA2 treatment of telencephalic membranes from postnatal day (PND) 5 and 10 animals produced an important decrease in [3H]AMPA binding, the same treatment performed on PND 20, 25 and adult membranes resulted in a marked increase in [3H]AMPA binding; the shift from decreased to increased [3H]AMPA binding occurred at about PND 15. In contrast to [3H]AMPA binding, [3H]6-cyano-7-nitroquinoxaline-2,3-dione (CNQX) binding was substantially reduced following PLA2 treatment at PND 5, 10 and 20, and effect due to a decrease in the maximal number of [3H]CNQX binding sites. In adult membranes, the effect of PLA2 treatment on [3H]CNQX binding was markedly reduced when compared to neonatal membranes. Pretreatment of synaptic membranes with PCMBS (a sulfhydryl reagent) increased [3H]AMPA binding in both young (PND 10) and adult telencephalic membranes, without significantly changing [3H]CNQX binding. The various effects of PLA2 treatment on agonist and antagonist binding did not appear to be due to major differences in the pharmacological properties of the AMPA receptors at different ages. The present results indicate that the characteristics of the binding sites for agonists and antagonists of the AMPA receptors are differentially modulated by the lipid environment during the postnatal period.(ABSTRACT TRUNCATED AT 250 WORDS)
Explore the source record for details and available documents.
A bacteriophage for Escherichia coli 0103 was isolated during a study on E. coli diarrhoea in intensive breeding units of rabbits. The phage had an isometric head and a short tail and resembled coliphage N4 (Podoviridae). It had a very narrow host range and seemed to be specific for serogroup 0103, suggesting that it might be used for preliminary identification of E. coli strains of this serogroup instead of the usual slide agglutination. In view of its possible use as a therapeutic phage, we investigated its dissemination in rabbit organs after oral administration. The phage persisted in the spleen for at least 12 days. However, in vivo studies showed that this phage and a mixture of more virulent phages for E. coli 0103 were ineffective in preventing disease in rabbits inoculated with an enteropathogenic strain of E. coli 0103.
HIV-1 antigens generate in man both a humoral and cellular immune reaction. However, in ARC/AIDS patients, the cellular response is inhibited by HIV-1 which induces an antiproliferative (suppressive) effect on activated T cells. To overcome this inhibition and up-regulate the cellular response, we designed a new vaccine strategy directed both against HIV-1 and immunosuppression and we used an immunizing preparation composed of HIV-1 antigens combined with immunoregulatory peptides prepared in a biologically inactivated but immunogenic form. In mice, this preparation induced anti-HIV-1 antibodies and a cell-mediated cytotoxicity directed against H2 restricted cells carrying HIV-1 antigens.
We have designed two software systems allowing the study of proteins through a comparison to those stored in data banks. The first one, "Automat", locates in a systematic manner all identities shared by a given protein and the proteins in a data bank. The second, "Critic" enables the selection of specific segments in a given molecule by comparing them with those gathered in a data bank. These sites were termed "critical" since they mostly correspond to functional sites (active sites) of the well-known proteins which were studied with the aid of this program (somatostatin, insulin, IL2, etc). Automat allowed us to reveal homologies between HIV-1 and the CD4, which have remained unsolved until now. These similitudes proved to be critical sites (according to Critic). The putative involvement of these sites in the physiopathological processes as induced by HIV-1 are worth considering since the results of our experiments are consistent with this assumption.
In the first AIDS vaccine trial, immunizing preparations were based on HIV-1 Env protein (gp160). Immunogenic properties of gp160 which trigger both a humoral and cellular immune response have since justified its use in various vaccine programs, both past and present. Many reports however have underlined deleterious effects on the immune system--anti-HIV-1 enhanced antibodies, anti-CD4 autoantibodies, and inhibition of T cell activation by HIV-1--particularly associated with the Env protein. The present study shows that gp160 presented in a biologically inactivated but immunogenic form, as used in our trial, could avoid these complications. Bio-hazards associated with gp160 which indeed could be removed by appropriate treatment of the native protein, should be taken into consideration in AIDS vaccine programs.
Viral haemorrhagic septicaemia is the most important viral disease of trout in Europe. The causative agent, viral haemorrhagic septicaemia virus (VHSV), a member of the lyssavirus genus of the rhabdoviridae family, was formerly believed to be confined to portions of the European continent; however in 1988, VHSV was isolated from adult chinook (Oncorhynchus tshawytscha) and coho (O. kisutch) salmon returning to two hatcheries in the northwestern part of the State of Washington, U.S.A. Initial fears were that the virus had been imported into North America, perhaps by aquaculture activities. The nucleotide and deduced amino acid sequences of the nucleocapsid (N) gene of one of the North American (Makah) isolates of VHSV were determined and compared with published sequences of a European reference strain of VHSV (07-71) and the Round Butte strain of infectious haematopoietic necrosis virus (IHNV), another salmonid fish rhabdovirus that is enzootic in western North America. The N gene of the Makah isolate of VHSV shared a similarity of 88.433% at the nucleotide level and 94.802% at the amino acid level with the N gene of the European strain of VHSV, and 62.121% amino acid similarity with the N protein of IHNV. Like the European reference isolate, the North American isolate of VHSV showed three domains in the N protein, the central one being the most conserved and the likely site of interaction with genomic RNA. This was also the region of highest similarity with the amino acid sequence of IHNV. The sequence data suggested that the Makah and 07-71 isolates were of independent origin.
Potassium-induced depolarization of synaptoneurosomes prepared from rat telencephalon was found to increase [3H]amino-3-hydroxy-5-methylisoxazole-4-propionate ([3H]AMPA) binding to the AMPA receptor. The effect required the presence of calcium because it was blocked by the calcium chelator EGTA but was not blocked by an antagonist of the N-methyl-D-aspartate receptor, aminophosphonopentanoate. The depolarization-induced increase in [3H]AMPA binding was markedly reduced by a blocker of voltage-dependent calcium channels, verapamil. Saturation kinetic experiments revealed that the increase in [3H]AMPA binding produced by potassium depolarization was due to an increase in the affinity of the AMPA receptor. These results provide additional support for a critical role of calcium in the regulation of the AMPA receptors. The synaptoneurosome preparation might represent an interesting tool to determine the role of different calcium-dependent enzymes involved in the regulation of the AMPA receptor.
A three-phase marketing program was implemented to increase referrals for examination with computed tomographic (CT) or magnetic resonance (MR) imaging and improve services in an academic radiology department. In the research phase, a data base of 135 referring physicians was developed, and a questionnaire was mailed to 130 physicians. The market research identified three key issues: waiting time to get an appointment, scheduling procedures, and communication of findings. In the implementation phase, additional equipment was installed and a program of expanded appointments, service improvements, and public relations was introduced. In the evaluation phase, 1 year after the completion of phase 2, the effect of the marketing program was measured. The average number of physicians who made referrals per month increased from 609 to 653 (an increase of 7.2% over baseline); the average number of CT and MR examinations performed each month increased by 57.3% and 45.2%, respectively. Referrers' ratings of 10 imaging services improved significantly (P = .02). It is concluded that a well-designed marketing program can boost the productivity of a teaching hospital department.
We carried out in 1989 a non randomized comparative study in French army units which had been in Central Africa (Central African Republic and Gabon) for 4 months, in order to compare in 758 men on return from malaria areas the usual strategy of chemoprophylaxis with chloroquine and a radical cure by halofantrine (Halfan). Chloroquine was taken by 278 men (100 mg daily for 6 weeks after their return to France); the other 480 men were given two doses of 1,500 mg halofantrine on the third and on the tenth day after their return to France. In Africa both of the units were on chloroquine prophylaxis (100 mg daily for 4 months). The Plasmodium falciparum attack rates were, during a period of 5 months after the return to France, 0.2% in the halofantrine group (1/480) and 4.7% (13/228) in the chloroquine group (P < 10(-4)). The radical cure by halofantrine was more effective than chloroquine prophylaxis in preventing falciparum malaria on return from malaria areas.
Explore the source record for details and available documents.
The first trial of an anti-HIV immunization, using a recombinant vaccinia virus expressing gp160 (rV) for priming and paraformaldehyde-fixed rV-infected PBLs and soluble gp 160 for boosting, clearly showed an in vitro HIV-protective immune reaction. This result led us to carry out an additional 2 year Phase I clinical trial in 25 HIV-seronegative volunteers, using HIV gp 160 antigens for immunization in four different protocols. The 2 year trial showed (a) the safety of the preparations, (b) a transient humoral immunity following each boost, and (c) a long-lasting memory T-cell response. Memory cytotoxic T-lymphocytes (CTLs) induced by gp 160 antigen with or without vaccinia vector lysed HLA class I restricted target cells expressing HIV-1 env antigens. These results are consistent with CTLs being an effective component of an AIDS vaccine to control cell-to-cell viral replication, dissemination in the organism, and subsequent evolution toward AIDS.
Immunization of AIDS/ARC patients with autologous cells expressing HIV antigens, although providing clinical and biological benefits, fails to restore cellular immunity. The latter result is due partly to the antiproliferative effect of HIV-1 on activated T-cells (immune suppression), which leads to blockade of specific immune reactions. To overcome immune suppression, a new vaccine strategy was designed consisting of an immunization against HIV-1 combined with components of the T-cell-suppressive (antiproliferative) network. This new vaccine treatment proved to be innocuous in mice, monkeys, and two non-HIV-infected humans. A Phase I clinical trial was performed in six patients previously under cellular immunotherapy and still presenting a cellular immune defect. Preliminary results confirmed, after a 1-year follow-up of the patients, the safety of the new vaccine, which also partially restored the cellular immune response, including anti-HIV HLA-restricted cell-mediated cytotoxicity, delayed hypersensitivity to recall antigens, and proliferation of T-cells specifically activated by recall antigens.
Explore the source record for details and available documents.
Two hundred and sixty one men aged between 17 and 21 were questioned concerning their sports activities and underwent "whole body" osteodensitometry. Values found in terms of bone density rose harmoniously and proportionally from the ages of 17 to 21. Studied in terms of sports activities claimed, figures were higher in athletes and this essentially concerning the lower limbs and pelvis. These data contrast a "growth" effect with a "physical activity" effect, the first being of a systemic nature involving total bone mass and the second of a locoregional nature concerning only those bone segments involved in a particular activity. Our study failed to reveal any arguments in favour of spinal bone steal to the advantage of the lower limbs in athletes. The authors feel that "whole body" osteodensitometry by simultaneous and prospective study of bone segments involved or not involved in exercise should enable a distinction to be drawn between the systemic and locoregional effects of physical activity and thus, in the context of primary prevention, to define the optimal calcium intake and physical activity leading to acquisition of maximum bone capital and to maintain it to the best possible extent.
The authors report a new case of osteoid osteoma of the lunate. The absence of any specific clinical or radiographic features emphasises the importance of computed tomography, which not only confirms the diagnosis, but, more importantly, defines the topography and also guides the surgical approach and even the surgical technique.