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Biomedical subjects

M Guy

Publications and source records attributed to M Guy.

At least 19 recordsLinked to original sources
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↗
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↗
PubMed1996

Adrenal cortical adenoma with extensive fat cell metaplasia.

This report describes a large adrenal cortical tumor with a significant component of mature adipose tissue in a 40 year old woman. No bone marrow elements were identified in multiple sections. This lesion, representing most likely an adrenal cortical adenoma with extensive fat cell metaplasia, has not been previously reported and must be differentiated from adrenal myelolipoma.

Adrenal Cortex Neoplasms↗
PubMed1996

[Epidemiology of certain endemic parasitic diseases in the town of Guadalupe (Republic of Sao Tome and Principe) I. Schistosomiasis intercalatum and intestinal worms].

Schistosomiasis intercalatum in known to exist in Saõ Tomé since 1988, (Corachan et al.). It is transmitted by Bulinus forskalii, (Brown et al., 1989). Stool, blood and urine specimens have been collected from 380 inhabitants of all age groups living in the small town of Guadalupe close to the Agua Traź river and Agua Polino. The prevalence of schistosomiasis by detection of S. intercalatum eggs in a 10 mg stool thick smear (Kato technique) is 25.5%. An excreted Schistosoma polysaccharide antigen, detected by means of a monoclonal antibody (Ripert et al., 1992), is found in 49.1% of the urine samples. Patients voiding S. intercalatum eggs in stools have been treated with praziquantel (40 mg/kg body weight), as recommended by WHO Expert Committee on Schistosomiasis, but it might be wise to also treat persons excreting antigen in urine. The prevalence of intestinal helminthiasis, ascariasis (73.7%), trichuriasis (73.7%) and necatoriasis have been measured.

Adolescent↗
PubMed1995

Limitations and late complications of third-generation automatic cardioverter-defibrillators.

BACKGROUND: This study examines the limitations and complex management problems associated with the use of tiered-therapy, implantable cardioverter-defibrillators (ICDs). METHODS AND RESULTS: The study group comprises the first 154 patients undergoing implantation of tiered-therapy ICDs at our institution. Pulse generators from three different manufacturers were used. In 39 patients, a complete nonthoracotomy lead system was used. The perioperative mortality was 1.3%. Of these 154 patients, 37% experienced late postoperative problems. Twenty-one patients required system revision within 36.5 months (mean, 8.57 +/- 11.3) of surgery. Reasons for revision were spurious shocks due to electrode fractures (3) or electrode adapter malfunction (2), inadequate signal from endocardial rate-sensing electrodes (3), superior vena cava or right ventricular coil migration (5), failure to correct tachyarrhythmias due to a postimplant rise in defibrillation threshold (5), or pulse generator failure (3). One of these patients required system removal for infection after revision of an endocardial lead. A further 32 patients received inappropriate shocks for atrial fibrillation with a rapid ventricular response or sinus tachycardia. Two of these patients also received shocks for ventricular tachycardia initiated by antitachycardia pacing triggered by atrial fibrillation. Ventricular pacing for bradycardia was associated with inappropriate shocks due to excessive autogain in 2 patients. CONCLUSIONS: Despite the major diagnostic and therapeutic advantages of tiered-therapy ICDs, a significant proportion of patients continue to experience hardware-related complications or receive inappropriate shocks.

Algorithms↗
PubMed1994

[Retrograde ejaculation as a side-effect of clozapine].

3 chronic paranoid schizophrenic men, aged 29, 30 and 37 years, respectively, developed retrograde ejaculation, a rare side-effect of clozapine. It disappeared after the dose was lowered in 1 of the patients and after stopping the drug in the other 2. On rechallenging with the drug, retrograde ejaculation recurred.

Adult↗
PubMed1994

Assessment of retinol-binding protein excretion in normal children.

Retinol-binding protein (RBP) is a low molecular weight protein freely filtered at the glomerulus. The fractional tubular reabsorption of RBP is 99.97% and increased excretion is therefore a sensitive marker of tubular dysfunction. We obtained early-morning urine specimens from 151 well children, from newborn to 16 years of age. RBP was measured using an enzyme-linked immunosorbent assay, albumin by a radioimmunoassay and creatinine by a modified Jaffé reaction. Protein excretion was assessed by calculating the protein:creatinine ratio for early-morning urine samples. We found a fall in both RBP and albumin excretion with increasing age, particularly in the 1st year of life, with a much wider variation in values from the infants studied. The mean excretion of RBP for children aged 0-6 months [51.4 (0.6-4,719) micrograms/mmol] was significantly higher (P < 0.001) than the mean for children aged 6 months to 16-years [15.0 (3.8-60) micrograms/mmol]. It has been shown that measurement of tubular proteinuria using the RBP: creatinine ratio is useful in the assessment of children with renal disease and we propose a value two standard deviations above the geometric mean for the age of the patient as an upper limit of normal.

Adolescent↗