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Biomedical subjects

M Guy

Publications and source records attributed to M Guy.

At least 19 recordsLinked to original sources
PubMed2006

Serological survey of encephalomyocarditis virus infection in pigs in France.

Samples of serum from 76 gilts, 1440 sows, 1473 piglets and 3093 finishing pigs from 96 farrow-to-finish herds were tested for antibodies to encephalomyocarditis virus (EMCV) in microtitre serum neutralisation tests employing two strains of virus, one associated with myocarditis and the other with reproductive failure. The total seroprevalence of EMCV infection was 2.48 per cent. There was no significant difference between the seroprevalence of the reproductive failure strain (1.6 per cent) and the myocardial strain (1.85 per cent). The seroprevalence was higher in the gilts (6.57 per cent) and sows (5.13 per cent) than in the piglets (1 per cent) and finishing pigs (1.84 per cent), and the highest titres were observed in the sows (1:540) and finishing pigs (1:640). In the gilts, the difference in seroprevalence between the reproductive failure strain (3.95 per cent) and the myocardial strain (5.33 per cent) was wider than in the other groups.

Animals↗
PubMed2006

Characterization of a recombinant encephalomyocarditis virus expressing the enhanced green fluorescent protein.

A recombinant encephalomyocarditis virus (rEMCV2887A-egfp) expressing the enhanced green fluorescent protein (EGFP) was produced. The EGFP gene was inserted in frame within the leader protein coding sequence of a full-length cDNA clone of EMCV. RNA transcripts derived from the recombinant full-length cDNA were synthesized in vitro and transfected into BHK-21 cells. The recombinant transcript RNA remained infectious despite the insertion of EGFP as shown by cytopathic effects on BHK-21 cells and by propagation of the rescued virus. The replication kinetics in BHK-21 cells and the pathogenicity in mice of rEMCV2887A-egfp did not differ significantly from that of the parental virus. The recombinant virus was shown to produce fluorescence in infected cells after at least five passages in BHK-21 cells. However, a decrease of EGFP expression was observed following serial passages, and this was associated with the accumulation of deletion mutations within the EGFP gene. Nevertheless, using EGFP autofluorescence, infected cells were easily detected in the brain of mice infected with the first-passage recombinant virus. These data demonstrate that rEMCV2887A-egfp could be a useful tool to study virus dissemination and pathogenicity when used at low passages.

Animals↗
PubMed2003

[The safety and immunogenicity of an heptavalent pneumococcal polysaccharide conjugate vaccine (Prevenar) administered in association with a whole-cell pertussis-based pediatric combination vaccine (DTP-IPV/PRP-T) to French infants with a two-, three-, and four-month schedule].

UNLABELLED: Invasive pneumococcal disease is presently a leading cause of mortality due to bacterial infectious diseases in French children less than 2 years of age, and only the pneumococcal conjugate vaccines induce a protective immune response for those within this vulnerable age group. MATERIAL AND METHODS: The safety and immunogenicity of a heptavalent pneumococcal polysaccharide conjugate vaccine (PREVENAR was tested in French infants immunized with the 2, 3 and 4 month French schedule as part of an open, randomized, comparative clinical study, in association with a whole-cell pertussis-based pediatric combination vaccine. RESULTS: In the PREVENAR plus DTP-IPV/Hib association group, 90.6-100% of children achieved a post-dose three threshold IgG concentration of >0.15 microg/ml against each of the seven pneumococcal serotypes. Regarding immunogenicity, no interference with the antibody response to the various antigenic components of the DTP-IPV/Hib vaccine was observed. Local reactions were significantly less frequent at the PREVENAR injection site than at the DTP-IPV/Hib injection site; there was no increase in systemic adverse events in the vaccine association group compared to the DTP-IPV/Hib alone group, further exception of fever >38 degrees C which was more frequently reported in the PREVENAR + PENTACOQ group following the second dose of vaccines (56% vs. 35%); no serious adverse event could be considered to be related to the PREVENAR immunization in this study. CONCLUSION: The heptavalent pneumococcal conjugate vaccine is immunogenic when administered at 2, 3 and 4 months. PREVENAR can be administered simultaneously with the DTP-IPV/Hib combination vaccine.

Diphtheria-Tetanus-Pertussis Vaccine↗
PubMed2003

Transcriptional upregulation of the insulin-like growth factor binding protein IGFBP-3 by sodium butyrate increases IGF-independent apoptosis in human colonic adenoma-derived epithelial cells.

Sodium butyrate (NaBt) and the pro-apoptotic IGFBP-3 protein, expressed at the top of the normal colonic crypt, have both been implicated in the regulation of apoptosis in colonic epithelial cells. Recent studies in human breast and hepatic cell lines have shown that NaBt can transcriptionally upregulate IGFBP-3 expression. However, the role of butyrate in the regulation of IGFBP-3 expression in the colon is less clear, with reports of both up- and downregulation of the IGFBP-3 protein in colorectal cancer cell lines. In this study we have shown that the level of IGFBP-3 protein expression in colonic epithelial cells correlates with the p53 status of the cells; wildtype p53 cells secrete higher levels of IGFBP3 protein than mutant p53 cell lines. Data presented shows that, when treated with a dose of NaBt that induced significant apoptosis (4 mM for 48 h), there was an upregulation of IGFBP-3 protein in both wildtype and mutant p53 expressing cell lines. The NaBt-induced increase in secreted IGFBP-3 protein was associated with transcriptional upregulation of the IGFBP-3 gene. Using a transfected derivative of the S/RG/C2 adenoma-derived cell line, which stably expressed exogenous IGFBP-3 protein at levels equivalent to that secreted by the 4 mM NaBt-treated parental line (1-3 ng/10(6) cells), we have shown a >2-fold increase in the sensitivity of the cells to NaBt-induced apoptosis when compared with the vector control and parental cell lines. Furthermore, inhibition of the secreted IGFBP-3 protein, by addition of neutralizing antibodies, resulted in a significant decrease in NaBt-induced apoptosis. These data suggest that IGFBP-3 may act as a positive regulator of NaBt-induced apoptosis in colonic epithelial cells, and represents a potentially important mechanism whereby the sensitivity of colonic epithelial cells to NaBt-induced apoptosis can be increased.

Adenoma↗
PubMed2002

High activity Rhenium-186 HEDP with autologous peripheral blood stem cell rescue: a phase I study in progressive hormone refractory prostate cancer metastatic to bone.

We tested the feasibility and toxicity of high activities Rhenium-186 hydroxyethylidene diphosphonate, with peripheral blood stem cell rescue in patients with progressive hormone refractory prostate cancer metastatic to bone. Twenty-five patients received between 2500 and 5000 MBq of Rhenium-186 hydroxyethylidene diphosphonate followed 14 days later by the return of peripheral blood peripheral blood stem cells. Activity limiting toxicity was defined as grade III haematological toxicity, lasting at least 7 days, or grade IV haematological toxicity of any duration or any serious unexpected toxicity. Activity limiting toxicity occurred in two of six who received activities of 5000 MBq and maximum tolerated activity was defined at this activity level. Prostate specific antigen reductions of 50% or more lasting at least 4 weeks were seen in five of the 25 patients (20%) all of whom received more than 3500 MBq of Rhenium-186 hydroxyethylidene diphosphonate. The actuarial survival at 1 year is 54%. Administered activities of 5000 MBq of Rhenium-186 hydroxyethylidene diphosphonate are feasible using autologous peripheral blood peripheral blood stem cell rescue in patients with progressive hormone refractory prostate cancer metastatic to bone. The main toxicity is thrombocytopaenia, which is short lasting. A statistically significant activity/prostate specific antigen response was seen. We have now commenced a Phase II trial to further evaluate response rates.

Bone Neoplasms↗
PubMed2001

Synthetic mannosides act as acceptors for mycobacterial alpha1-6 mannosyltransferase.

A series of synthetic mannosides was screened in a cell-free system for their ability to act as acceptor substrates for mycobacterial mannosyltransferases. Evaluation of these compounds demonstrated the incorporation of [14C]Man from GDP-[14C]Man into a radiolabeled organic-soluble fraction and analysis by thin layer chromatography and autoradiography revealed the formation of two radiolabeled products. Each synthetic acceptor was capable of accepting one or two mannose residues, resulting in a major and a minor mannosylated product. Both products from each acceptor were isolated and their mass was confirmed by fast-atom bombardment-mass spectrometry (FABMS). Characterization of each mannosylated product by exo-glycosidase digestion. acetolysis and linkage analysis by gas chromatography mass spectrometry of partially per-O-methylated alditols, revealed only alpha1-6-linked products. In addition. the antibiotic amphomycin selectively inhibited the formation of mannosylated products suggesting polyprenolmonophosphate-mannose (C15 50-P-Man) was the immediate mannose donor in all mannosylation reactions observed. The ability of synthetic disaccharides to act as acceptor substrates in this system, is most likely due to the action of a mycobacterial polyprenol-P-Man:mannan alpha1-6 mannosyltransferase involved in the biosynthesis of linear alpha1-6-linked lipomannan.

Carbohydrate Sequence↗
PubMed2001

Transcriptional down-regulation of the retinoblastoma protein is associated with differentiation and apoptosis in human colorectal epithelial cells.

The aim of this study was to investigate the regulation of Rb protein expression in relation to increased differentiation and induction of apoptosis in colonic epithelial cells. In vivo, Rb protein expression was found to be down-regulated towards the top of the normal colonic crypt, coincident with the region of differentiation and apoptosis, but highly expressed in colonic carcinoma tissue. Using in vitro models to study the regulation of Rb expression in pre-malignant colonic epithelial cells, we have been able to show for the first time that Rb protein expression is transcriptionally down-regulated in differentiated pre-malignant cells (in post-confluent cultures) but not in malignant colorectal epithelial cells. Furthermore, suppression of rb protein function by the HPV-E7 viral oncoprotein increased both spontaneous and DNA damage-induced apoptosis. These results suggest that Rb is able to act as a survival factor in colonic epithelial cells by suppressing apoptosis, and that over-expression of pRb in colorectal tumour cells can cause a loss of sensitivity to apoptotic signalling, resulting in aberrant cell survival and resistance to therapy.

Antibodies, Monoclonal↗
PubMed2001

Paracellular transport of avidin saturated or not with biotinylated cobalamin through Caco-2 cell epithelium monolayer.

BACKGROUND: The cationic charge of molecules may promote their uptake across epithelia, which are rich in brush border anionic sites. The transport of unsaturated avidin and avidin saturated with a biotinylated compound was investigated across Caco-2 adenocarcinoma cell with fetal enterocyte phenotype. METHODS: The unsaturated avidin and avidin saturated with either biotin or a biotinyl-cobalamin conjugate (biotinyl-Cbl) were iodinated to follow their transport through the cell monolayer. Their apparent permeability coefficient (Papp) and transepithelial pathway were determined and compared to those for control radiolabeled markers [3H]-mannitol, [125I]-beta-lactoglobulin and [57Co]-cobalamin/intrinsic factor (Cbl/IF). RESULTS: The Papp of [125I]-avidin estimated at 2.8 x 10(-7) +/- 0.08 cm/s was close to that for mannitol that uses paracellular pathway. The binding of biotin or biotin conjugate to avidin enhanced its tetrameric conformation. The Papp for [125I]-avidin/biotin and [125I]- avidin/biotinyl-Cbl were respectively increased by 2-fold, compared to that for [125I]-avidin and 4-fold, compared to that for [125I]-beta-lactoglobulin and [54Co]-Cbl/IF. The protein was not accumulated in the cell and was found in intact form in the basolateral side, after its transport across the monolayer. Chloroquine (0.66 micromol/ml) did not significantly decrease the Papp for [125I]-avidin/biotinyl-Cbl. Conversely it decreased by 80% the Papp for Cbl/IF, that uses transepithelial pathway. CONCLUSIONS: Avidin (either saturated or not with biotin and biotinyl-Cbl) was able to cross the monolayer of Caco-2 cell line through a paracellular pathway. This study pointed out the interest for using this protein as a shuttle for increasing the transport rate of biotinylated compounds through fetal epithelial barriers.

Avidin↗
PubMed2000

Transcytosis and coenzymatic conversion of [(57)Co]cobalamin bound to either endogenous transcobalamin II or exogenous intrinsic factor in caco-2 cells.

We have examined the intracellular route, coenzyme conversion and transcytosis rate of [(57) Co]-labeled cobalamin (Cbl) in function of its presentation to the apical side of Caco-2 cells, either free or bound to intrinsic factor (IF). The free-presented Cbl was progressively bound to endogenous transcobalamin II (TCII) which may stem, in part, from a basolateral to apical passage. Its transcytosis was TCII-mediated as it was abolished when antibodies to TCII were added to the apical medium. The apparent permeability coefficient (P(app)) was estimated at 20.8+/-3.6, 103.5+/-17.7, 0.9+/-0.3 x 10(-5) cm/h for TCII-Cbl, IF-Cbl and haptocorrin-Cbl, respectively. Chloroquine inhibited the transcytosis rate of both TCII and IF-bound Cbl in a dose-dependent manner. Approximately 80% of apical Cbl, bound to either exogenous IF or endogenous TCII, was transported to the basolateral side as intact cyano[(57)Co]Cbl whereas the remainder was converted into Ado-Cbl and CH(3)-Cbl within the cells, as shown by HPLC analyses of a 1,000-g pellet and a 12,000-g supernatant. Coenzymatic conversion was virtually abolished by chloroquine. In conclusion, we suggest that apically presented free Cbl is internalized via TCII-dependent transport. The apically internalized CN-Cbl, bound to either IF or TCII, is processed via an acidic vesicle and part of it is converted to coenzymes, whereas bulk of CN-Cbl is transcytosed intact.

Biological Transport↗
PubMed1999

OESCLIM: pre-clinical and clinical profile.

INTRODUCTION: The majority of women will suffer some form of vasomotor symptoms at the menopause. Hormone replacement therapy (HRT) has been shown to reduce the incidence of these symptoms although compliance with HRT is still poor. OESCLIM is a transdermal estrogen-replacement therapy for the treatment of estrogen deficiency. METHODS: In this paper, the main pre-clinical and clinical data relating to OESCLIM are reviewed. RESULTS: OESCLIM has a stable pharmacokinetic profile over the treatment period of 3-4 days and has been shown to have advanced pharmacokinetics when compared to other leading transdermal systems. It has been shown to reduce vasomotor symptoms by 94% in post-menopausal women, with near maximal reduction in symptoms after 4 weeks of treatment. In highly symptomatic women, low dose (25 microg/day) OESCLIM therapy resulted in a statistically significant reduction in symptoms compared to placebo from week 3. OESCLIM also has good local skin tolerability, and is significantly better tolerated than Estraderm TTS 50. It is also well accepted among patients. In long-term studies, 79.8% of patients wished to continue OESCLIM therapy at the end of a 3-year study. CONCLUSION: OESCLIM is an innovative first-line transdermal estrogen-replacement therapy with good efficacy and tolerability. The ability to initiate treatment at a low dose (25 microg/day) may have advantages for the patient starting therapy by reducing symptoms of hyperestrogenism whilst allowing for dose titration upwards if necessary.

Administration, Cutaneous↗
PubMed1999

Morphological and morphometric studies of the splenic antitumor immune response, elicited by liposome-covered soluble p53 kDa antigen, in chemically-induced rat colon cancer.

We evaluated the splenic morphometric changes in rats treated with carcinogen to study development of anti-cancer immune response. When liposome-covered soluble 53 kDa antigen (s53) was injected into these rats, significant tumor-suppression was seen and the percentage of tumor-free animals rose from 15.4% in non-vaccinated rats to 53.8%. In the spleens of carcinogen treated rats that did not develop tumors, activity of B lymphocytes increased significantly. This was manifested by the expansion of the germinal centers to 50.9% of the follicular area reflecting depletion of B cells, and the decrease of the mantle layer to 48.9% of the follicles. A similar picture was seen with T lymphocytes: the area of the marginal zone decreased to 55.2% of the T zone of the white pulp, and that of the periarterial lymph sheaths (PALS) to 33.6%. In tumor-bearing rats features of the immune decompensation were seen: the germinal centers increased to 96.5% of the follicular area, and the mantle layer and PALS decreased significantly. Vaccination prevented these effects, especially in tumor-bearing rats: the PALS occupies 30.4% of the white pulp and the marginal zone 56.1%, and the mantle layer occupied 58.1% of the follicular zone. Similar changes were found in vaccinated rats without tumors reflecting the compensatory character of the immune reaction in vaccinated rats. In conclusion, we found that treatment with carcinogen followed by vaccination with the s53-liposomes complex stimulated the activity of the splenic B, and to a lesser degree the T systems.

Animals↗
PubMed1999

Transplacental effects of IgG generated against soluble 53 kDa protein on the splenic lymph system of rat progeny exposed to carcinogen: rate of apoptosis, proliferation of lymphocytes and expression of Fas and Fas ligand proteins.

BACKGROUND: We have previously shown that vaccination with IgG generated against the soluble 53 kDa (s53) protein modified the splenic response to carcinogens. Here we studied whether such immunization could affect the splenic lymphatic system of the offspring. METHODS: Offspring of normal female rats or of rats immunized with anti-s53 IgG were exposed to a carcinogen (dimethyl-benz(a)antracene). After 4 months, their spleens were resected and evaluated immunohistochemically for lymphocyte proliferation, apoptosis and apoptosis-related proteins (Fas and Fas ligand), in tumor-free and tumor-bearing animals. RESULTS: Spleens of progeny of unvaccinated rats had a significant decrease in the areas of follicles, germinal centers and the mantle layer after exposure to carcinogens, while maternal vaccination resulted in a significant expansion of the progeny's splenic follicles and germinal centers, the zones of B cell proliferation. The area of periarterial lymph sheaths (PALS) expanded in these offspring, reflecting activation of the T-zone. Maternal vaccination also resulted in a significant rise of Fas ligand-positive lymphocytes in the follicles and PALS of their tumor-free offspring. Tumorigenesis stimulated the Fas activity of B and T cells in the spleens, and this was much enhanced by maternal vaccination. CONCLUSIONS: Maternal vaccination before pregnancy results in altered morphological and functional attributes of the splenic immune system of the offspring. This increased immunoreactivity could reduce the risk of tumors in progeny of vaccinated mothers.

9,10-Dimethyl-1,2-benzanthracene↗
PubMed1998

Isoelectrofocusing phenotype and relative concentration of transcobalamin II isoproteins related to the codon 259 Arg/Pro polymorphism.

We investigated transcobalamin II (TC) isoelectrofocusing (IEF) phenotype and codon 259 polymorphism, in Caco-2 and HT-29 cells and in blood drawn from 39 healthy Caucasians. Caco-2 cells expressed a single TC variant (259-Arg), while HT-29 cells expressed TC with either Arg or Pro at codon 259 and exhibited two isoproteins in IEF with urea, but only one in IEF without urea. Among the Caucasians, 7 subjects expressed the TC 259-Arg variant, 10 the 259-Pro variant, and 22 were heterozygous. The TC 259-Pro isoprotein issued from HT-29 cells and heterozygous caucasian sera, was, respectively, 2. 4-fold and 1.6-fold higher than the TC 259-Arg isoprotein. Apo-TC and vitamin B12 serum concentrations in 259-Pro homozygotes were, respectively, 1.7 and 1.4-fold higher than those in 259-Arg homozygotes (p<0.005 and p=0.05). In conclusion, the 259-Arg/Pro polymorphism yields two TC variants only titratable in denaturing conditions and affects the blood level of both Apo-TC and vitamin B12.

Adult↗
PubMed1998

Evaluation of coupling of cobalamin to antisense oligonucleotides by thin-layer and reversed-phase liquid chromatography.

We have evaluated by chromatography two strategies of oligonucleotide binding to vitamin B12 (cobalamin). The first one was based on a covalent linkage of aminooligonucleotide to carboxycobalamin in presence of 1-ethyl-3-(3-dimethylaminopropyl)-carbodiimide hydrochloride (EDC). Carboxycobalamin and EDC-cobalamin were eluted with a retention time of 16.5 and 21.6 min, respectively, in RP-HPLC, while aminooligonucleotide and oligonucleotide-cobalamin were coeluted at 19.4 and 19.8 min. In the second strategy, avidin was coupled to both biotinylated oligonucleotide and vitamin B12. Aminocobalamin and biotinylated cobalamin had respective retention times of 13 and 15.7 min in RP-HPLC and respective Rf values of 0.3 and 0.8 in thin-layer chromatography. Incubation of avidin with biotinylated cobalamin produced, in Superose 12 gel permeation, a peak with a retention time of 28 min, which corresponded to avidin-biotinylated cobalamin as it disappeared with an excess of either biotin or biotinylated oligonucleotide. In conclusion, we have prepared and purified by RP-HPLC and gel permeation chromatography an oligonucleotide-avidin-cobalamin complex which will be used as a vector complex of antisense oligonucleotides.

Avidin↗
PubMed1998

Runaway pacemaker in an implantable cardioverter defibrillator.

INTRODUCTION: Runaway pacemaker is a potentially catastrophic complication of any permanent pacing system. METHODS AND RESULTS: A 70-year-old man was found to have erratic behavior of his implantable cardioverter defibrillator (ICD) during a routine outpatient interrogation. His device was turned off, and he was hospitalized in preparation for a pulse generator replacement. During his hospitalization, his ICD unexpectedly began pacing rapidly. Despite prompt resuscitation attempts, the patient died. Postmortem examination of the device demonstrated a crystal oscillator failure. CONCLUSION: A previously unrecognized component malfunction is a potentially lethal complication of ICDs.

Aged↗
PubMed1998

[Analysis of natural family planning failures. In 7007 cycles of use].

MATERIALS AND METHODS: The analysis concerned 626 users using NFP in order to avoid a conception during a total of 6740 cycles. Participation in the study did not interfere with their plan of conception, and they were invited to behave, as far as possible, as though they ignored the study. Of these 626 couples, 530 were french, 61 belgian and 35 swiss. On the whole, 39.3% used birth control to limit births and 60.7% to space them. RESULTS: The observed pregnancy rates are 1.13, 6.47 and 17.58 for one year in actuarial method respectively for method, method + user and total pregnancy rate. The pregnancy rate was higher for women before 35 years (RR: 3.8; 95 p100 confidence interval: 1.4-10.3), during the six months after delivery (RR: 2.5; 1.0-4.6) and, of course, for couples with inprotected sexual intercourse in fertile phase (RR: 4.8; 2.1-11.2). DISCUSSION: NFP can be placed among methods of great theorical effectiveness. But pregnancies as a result of intercourses during the fertile phase despite its identification are frequent: couples have to be informed.

Actuarial Analysis↗