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Biomedical subjects

C Desgranges

Publications and source records attributed to C Desgranges.

At least 109 records · Page 6Linked to original sources
PubMed1986

Geographical prevalence of two types of Epstein-Barr virus.

The Jijoye EBV strain is characterized by a substitution of 1.8 kb in the C-terminal part of the EBNA 2 gene compared to B95-8 or M-ABA virus. This made it possible to construct hybridization probes specific for M-ABA (type A) and Jijoye viruses (type B), which have been used to type the EBV genomes in 38 spontaneously established cell lines. Type A is more prevalent being found in 31 of 38 cases; type B virus was found in five cell lines (Jijoye, LY 67, QIMR-GOR, BL 16, and BL 29); and two cell lines, Daudi and EB-3, contained neither the M-ABA- nor the Jijoye-specific sequences. EBV type B appears to be less ubiquitous, since all type B isolates, including AG 876 virus, originated from Central Africa, La Réunion, and New Guinea. All the other cell lines, carrying EBV type A, were established from patients from Central Africa (4), North Africa (7), New Guinea (1), and Asia (6) and from white individuals (13). The restricted geographical localization of EBV type B in parts of the southern hemisphere and its similarity to herpesvirus papio (T. Dambaugh, K. Hennessy, L. Chamnankit, and E. Kieff (1984) Proc. Natl. Acad. Sci. USA 81, 7632-7636) could suggest that such viruses may have evolved by recombination of EBV with a related Old World monkey virus, alternatively, evolution of virus variants within the human species also being conceivable.

Cloning, Molecular↗
PubMed1986

Deoxyribosyl exchange reactions leading to the in vivo generation and regeneration of the antiviral agents (E)-5-(2-bromovinyl)-2'-deoxyuridine, 5-ethyl-2'-deoxyuridine and 5-(2-chloroethyl)-2'-deoxyuridine.

In the rat, the highly potent anti-herpes drug (E)-5-(2-bromovinyl)-2'-deoxyuridine (BVdUrd) is rapidly converted to its base (E)-5-(2-bromovinyl)uracil (BVUra) through the action of pyrimidine nucleoside phosphorylases. However, BVdUrd can be regenerated or even generated de novo from BVUra by a pentosyl transfer reaction upon the administration of 2'-deoxythymidine (dThd), 2'-deoxyuridine (dUrd) or 5-ethyl-2'-deoxyuridine (EtdUrd). The antiherpetic drugs EtdUrd and 5-(2-chloroethyl)-2'-deoxyuridine (ClEtdUrd) can also be regenerated or generated de novo from their respective bases 5-ethyluracil (EtUra) and 5-(2-chloroethyl)uracil (ClEtUra), by a pentosyl transfer mediated by the administration of dThd or dUrd as deoxyribosyl donor. The generation or regeneration of BVdUrd, EtdUrd and ClEtdUrd from their bases (BVUra, EtUra and ClEtUra, respectively) is readily achieved because the latter have long half-lifes. Thus, the active anti-herpes drugs can be (re)generated repeatedly after a single administration of these nucleosides or their bases, followed by repeated administrations of dUrd.

Animals↗
PubMed1986

Epstein-Barr virus-transformed lymphocytes from patients with bullous diseases produce autoantibodies to cytokeratins.

Human cell lines obtained after Epstein-Barr virus transformation of lymphocytes from seven patients with bullous diseases (Bullous pemphigoid, Pemphigus) and five controls were screened for the production of autoantibodies against skin antigens. In five out of seven patients, the culture supernatants tested by indirect immunofluorescence on frozen sections of normal human skin and rabbit lip showed the production of autoantibodies with different specificities: basal epidermal cells, whole epidermis, Merkel cells, fibroblasts endothelial cells, etc. All autoantibodies were of IgM class and reacted with intracellular structures. Some of them were further tested by immunoblotting against epidermal keratins and were found to react with the main human epidermal keratins (56 to 67 kDa). In contrast, even when patients had circulating autoantibodies, no supernatant showed any reactivity against the antigens usually involved in these diseases, i.e., the dermoepidermal junction or the intercellular spaces of epidermis. Supernatants from controls did not show any reactivity by immunofluorescence. The results demonstrated that human lymphoid cell lines obtained from patients with bullous diseases elicited the production of anti-intermediate filament autoantibodies known to occur spontaneously in normal patients. It is suggested that this phenomenon may be linked to the blistering conditions that provoke tissue destruction.

Animals↗
PubMed1986

Establishment of human cell lines producing anti-D monoclonal antibodies: identification of Rhesus D antigen.

Two cell lines producing monoclonal antibodies have been established from peripheral blood of a negative Rhesus blood donor which has been immunized with positive Rhesus red blood cells. Two monoclonal antibodies Co II 8.8 and Co II 7.12 have been selected. Both are IgG1 antibodies, but recognize different epitopes on the Rhesus D antigen, apparently associated with different subunits of the D antigen. Thus the Co II 8.8, like the positive serum, immunoprecipitates an antigen of a relative molecular weight of 33 kDa, while the Co II 7.12 recognizes an antigen of Mr 42 kDa.

Antibodies, Monoclonal↗
PubMed1986

Synthesis and antiviral activity of (E)-5-(2-bromovinyl)uracil and (E)-5-(2-bromovinyl)uridine.

(E)-5-(2-Bromovinyl)uracil (BVU) and (E)-5-(2-bromovinyl)uridine (BVRU) were synthesized starting from 5-formyluracil via (E)-5-(2-carboxyvinyl)uracil or starting from 5-iodouridine via (E)-5-(2-carbomethoxyvinyl)uridine and (E)-5-(2-carboxyvinyl)uridine, respectively. Depending on the choice of the cell system, BVU and BVRU exhibited a marked activity against herpes simplex virus type 1 (HSV-1) in vitro. Although BVU and BVRU were less potent than the reference compound (E)-5-(2-bromovinyl)-2'-deoxyuridine (BVDU), their antiviral activity spectrum was remarkably similar to that of BVDU. The latter findings suggest that BVU and BVRU are metabolically converted to BVDU or a phosphorylated product thereof. In vivo, BVU protected mice against a lethal disseminated HSV-1 infection.

Animals↗
PubMed1986

T lymphocyte cloning from rejected human kidney allografts. Growth frequency and functional/phenotypic analysis.

Mechanically harvested lymphocytes invading an irreversibly rejected human kidney allograft were seeded at limiting dilution to calculate the frequency of growing precursors. Optimal growth frequency (1/13) was obtained when Epstein-Barr virus (EBV)-transformed donor B lymphocytes were used as stimulators (D-BLCL) in the presence of interleukin 2 (IL-2). The 55 clones analyzed were all T11+ and T3+, and all expressed DR antigens (45% were T8+ and 55% T4+). Only one clone had a double-labeled (T4+ T8+) surface. All cells proliferated significantly against D-BLCL, although T4+ clones had a significantly shorter average doubling time than T8+ clones. Nearly all T8+ clones were specifically cytotoxic for D-BLCL, while both T4 and T8 did not react against K562, autologous EBV-BLCL, and third-party EBV-BLCL. Detectable IL-2 was found in the culture supernatants of only a minority of clones (all T4+).

Antibodies, Monoclonal↗
PubMed1986

Effect of (E)-5-(2-bromovinyl)uracil on the catabolism and antitumor activity of 5-fluorouracil in rats and leukemic mice.

In contrast to thymine and 5-fluorouracil (FUra) which were cleared from the bloodstream within 2-4 h after their i.p. administration (200 mumol/kg) to rat, (E)-5-(2-bromovinyl)uracil (BVUra) maintained a concentration of 50-70 microM for at least 6 h and was still present in the plasma 24 h after its administration. In vitro experiments with rat liver extracts indicated that BVUra was not a substrate but an inhibitor for the reductive step in pyrimidine degradation catalyzed by dihydrothymine dehydrogenase. Kinetic and dialysis experiments suggested that BVUra was an irreversible inhibitor of this enzyme. The binding of BVUra to the enzyme depended on the presence of reduced nicotinamide adenine dinucleotide phosphate in the reaction mixture. Dihydrothymine dehydrogenase activity was also inhibited in the dialysed 105,000 X g supernatant fraction of livers from rats that had previously been treated with BVUra. Such inhibitory effects also occurred in vivo; previous administration of BVUra increased the plasma half-lives of thymine and FUra by 10- and 5-fold and their area under the curve by 9- and 8-fold, respectively. The effect of BVUra on the antitumor activity of FUra was evaluated in DBA/2 mice inoculated with 10(6) P388 leukemia cells. The mean survival times for the control and FUra-treated mice (5 mg/kg at 1, 3, 5, and 7 days after tumor cell inoculation) were 9.7 and 12.4 days, respectively. When BVUra (200 mumol/kg) was administered 1 h before each injection of FUra, the mean survival time was extended to 17.1 days. BVUra alone did not affect the mean survival time. When the dose of FUra was increased to 20 mg/kg, the mean survival time was 15.3 days; upon a preceding injection of BVUra the mean survival time decreased to 9.2 days. The latter effect probably resulted from an increased toxicity of FUra. Similar results were obtained if FUra was replaced by 5-fluoro-2'-deoxyuridine and BVUra by (E)-5-(2-bromovinyl)-2'-deoxyuridine. The enhancement of both the antitumor and toxic effects of FUra by BVUra were most probably due to an inhibition of FUra degradation, since, like in rats, BVUra increased the plasma half-life of FUra in DBA/2 mice. Hence BVUra appears to be an interesting compound, increasing the potency of FUra by decreasing its degradation.

Animals↗
PubMed1985

Magnesium enhances human pancreatic elastase digestion of 125I-labeled elastin.

The effect of some divalent cations, especially Mg++, on elastinolysis by porcine or human pancreatic elastase has been determined using 125Iodine-labeled elastin as substrate. Elastin degradation was significantly increased in the presence of 10(-3) M Mg++. If elastin was pre-incubated with 0.5 (w/v) Triton, there was a further increase in elastinolysis to 2.6 times the original rate.

Animals↗
PubMed1985

[Human monoclonal antibodies against surface antigens of Langerhans cells from lymphocytes of diabetics transformed by Epstein-Barr virus].

Human monoclonal antibody against islet cell surface antigens was generated from a pre-diabetic patient's peripheral blood lymphocytes transformed with Epstein-Barr virus. Reactivity of these transformed lymphocytes was evaluated using indirect immunofluorescence on rat islet cell suspensions and frozen sections of human pancreas. Several lymphoblastoid cell lines that react with islet cell surface were obtained. Preliminary immunoblots with enriched rat islet cell membrane antigens suggest a reactivity toward a 64 kdalton antigen.

Animals↗
PubMed1985

[Production of human monoclonal antibodies against various antigens of erythrocyte stages of Plasmodium falciparum].

Peripheral blood lymphocytes from 20 individuals living in a malaria endemic area (Burkina Faso) were transformed with Epstein-Barr virus. No antigen specific selection, nor stimulation of B-cells were performed prior to transformation. 20 cell lines were established, 14 secreted polyclonal antibodies directed against erythrocytic stages of Plasmodium falciparum. 4 lines were cloned and the supernatant analysed and characterised against Plasmodium falciparum antigens.

Animals↗
PubMed1984

Regeneration of the antiviral drug (E)-5-(2-bromovinyl)-2'-deoxyuridine in vivo.

The highly potent and selective antiherpes drug BVdUrd [(E)-5-(2-bromovinyl)-2'-deoxyuridine] is cleared within 2-3 hours from the bloodstream upon intraperitoneal administration to rats. It is degraded to BVUra [(E)-5-(2-bromovinyl)uracil] and this inactive metabolite is cleared very slowly from the bloodstream so that 24 hours after the administration of BVdUrd, BVUra is still detectable in the plasma. This contrasts with several other 5-substituted uracils, i.e. 5-fluorouracil, 5-iodouracil, 5-trifluorothymine and thymine itself, which are, like their 2'-deoxyuridine counterparts FdUrd, IdUrd, F3dThd and dThd, cleared from the plasma within 2-3 hours. The injection of dThd or any of the other 5-substituted 2'-deoxyuridines at 3 hours after the injection of BVdUrd, that is at a time when BVdUrd has disappeared completely from the circulation, results in the re-apparition of BVdUrd in the plasma. Apparently, BVdUrd is regenerated from BVUra following the reaction catalyzed by pyrimidine nucleoside phosphorylases : BVUra + dThd----BVdUrd + Thy. BVdUrd can even be generated de novo if dThd (or FdUrd, IdUrd or F3dThd) are administered 3 hours after a preceding injection of BVUra. These findings represent a unique example of the (re)generation of an active drug from its inactive metabolite in vivo.

Animals↗
PubMed1984

Infectious mononucleosis-like response in common marmosets infected with Epstein-Barr virus.

Callithrix jacchus marmosets infected with Epstein-Barr virus (EBV) with or without concurrent treatment with cyclosporin A (CySA) remained healthy. Five marmosets given virus alone developed lymphocytosis and heterophile antibody. Antibody to EBV capsid antigens (VCA) appeared and remained at titers of 1:40-1:80 from 15 weeks onward. Two animals produced antibody to the R component of early antigens (EA) from six weeks onward. Five CySA-treated EBV-infected marmosets showed no increase in total lymphocyte counts; only two developed heterophile antibody. Four developed persistent antibody to the EA-R component. All developed antibody to VCA, and mean titers were higher than in animals given EBV alone. Antibody to VCA also appeared in animals given EBV into Waldeyer's ring. Because these responses to EBV resemble those of humans, C. jacchus may provide a useful model for exploring the potential of cofactors in inducing EBV-associated malignancy.

Animals↗
PubMed1984

Purification of human alpha 1 antiprotease-pancreatic elastase complex. Interaction with homologous elastin.

A human alpha 1-antiprotease (alpha 1.AP)-human pancreatic elastase ( HPE11 ) complex was isolated from plasma, or prepared from commercial alpha 1.AP. The complex was identified and isolated by affinity chromatography, using Concanavalin A or IgG anti-elastase as ligands, in association with Sephacryl gel filtration. The alpha 1.AP- HPE11 complex was shown to bind with aorta and with purified aortic elastin. In both cases, the complex exhibited elastinolytic activity.

Aorta↗
PubMed1983

Phosphorolysis of (E)-5-(2-bromovinyl)-2'-deoxyuridine (BVDU) and other 5-substituted-2'-deoxyuridines by purified human thymidine phosphorylase and intact blood platelets.

Various 5-substituted-2'-deoxyuridines (dUrd), including 5-ethyl,5-propyl-, 5-trifluoromethyl-, 5-hydroxymethyl-, 5-formyl-, 5-vinyl-, (E)-5-(2-chlorovinyl)-, (E)-5-(2-bromovinyl)-, 5-fluoro-, 5-chloro-, 5-bromo-, 5-iodo-, 5-cyano-, 5-thiocyano-, 5-nitro- and 5-amino-dUrd, were shown to be effective substrates for the thymidine (dThd) phosphorylase isolated from human blood platelets. Some of dUrd analogs, i.e. the highly potent and selective antiherpes agent (E)-5-(2-bromovinyl)-dUrd, were degraded more rapidly than the natural substrates, dUrd and dThd. All dUrd analogs were also readily catabolised by intact human blood platelets. The potent inhibitors of thymidine phosphorylase, 6-amino-thymine and 6-amino-5-bromo-uracil, strongly inhibited the phosphorolysis of (E)-5-(2-bromovinyl)-dUrd by both purified enzyme and intact platelets.

Blood Platelets↗
PubMed1983

Presence of EBV-DNA sequences in nasopharyngeal cells of individuals without IgA-VCA antibodies.

Exfoliated nasopharyngeal (NP) cells from 62 normal Cantonese Chinese having IgA/VCA antibodies for more than a year and from 39 similar persons without IgA/VCA antibodies, were tested for the presence of EBV/DNA sequences by spot followed by blot hybridization tests, using the cloned internal repeat of B95-8 viral DNA as probe. Thirteen out of 62 specimens from IgA/VCA-positive (21%) and six out of 39 specimens (15.4%) from IgA/VCA-negative individuals were found to contain EBV/DNA sequences. Forty-six cases (20 IgA/VCA-positive and 26 IgA/VCA-negative) were followed a year later for EBV/DNA sequences and EBV serology. Half of the individuals having EBV/DNA sequences in their exfoliated NP cells in 1981 did not have detectable EBV sequences a year later, and to out of 15 negative individuals became EBV/DNA-positive. There was no obvious correlation between EBV/DNA detectability and EBV serology. (We conclude that the best marker for NPC risk remains the increasing IgA/VCA and/or EA antibody titers.

Antigens, Viral↗
PubMed1983

Herpes simplex virus glycoprotein D: human monoclonal antibody produced by bone marrow cell line.

Normal bone marrow cells from a donor positive for herpes simplex virus were transformed with Epstein-Barr virus. The resulting lymphoblastoid cell line has secreted immunoglobulin G1 of the kappa type continuously for 2 years. This immunoglobulin, detected both on the cell surface and in the cytoplasm, reacts with cells infected with herpes simplex virus. It defines an antigen that comigrates with the 55-kilodalton glycoprotein D of herpes simplex virus type 1 and neutralizes the infectivity of herpes simplex viruses 1 and 2.

Aged↗