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Biomedical subjects

A Ménard

Publications and source records attributed to A Ménard.

36 records · Page 2Linked to original sources

Morphological variability in Fasciola hepatica eggs in ruminants, rodents and lagomorphs.

The length and width of 1297 Fasciola hepatica eggs shed in cattle hosts, 337 in sheep and 199 in nutria, were measured from several parts of France. The data were compared with those obtained from other studies in Spain, France (where rats were also investigated), Germany and the Netherlands. One way analysis of variance and discriminant analysis were used to assess differences between host origins. The distribution of length and width of eggs were analysed using skewness and kurtosis Fisher coefficients. The eggs recovered from sheep, cattle, rodents and lagomorphs were different in size: the eggs found in rodents (length L x width W in microm: 8592) and lagomorphs (L x W in microm: 9100) were smaller than those found in sheep and cattle (L x W in microm: 10,000). These morphological differences in F. hepatica eggs were host-induced in rats (L x W in microM: 9709 in cattle to 8949 in rats) and rabbits (L x W in microm: 9709 in cattle to 8432 in rabbits). These differences in size of eggs might correspond to their being less able to develop into miracidia in less frequent hosts such as rodents and rabbits.

Analysis of Variance↗

Case report: DNA fragmentation in glial cells in a cerebral biopsy from a multiple sclerosis patient.

Multiple sclerosis is characterized by myelin destruction and oligodendrocyte loss. The neuropathological hallmark of the disease is the presence of demyelinated plaques in the central nervous system. We have recently found a gliotoxic factor in MS cerebrospinal fluid which induces programmed cell death in vitro, in glial cells. Here we show DNA fragmentation and glial cell death in biopsy samples, obtained from a patient who underwent surgery with suspicion of tumor, and whose disease record, including brain autopsy, demonstrated an active multiple sclerosis. We used the in situ TUNEL technique, a method which sensitively detects the DNA fragmentation accompanying programmed cell death in tissue sections, and compatible with classical fixation techniques. We found intense DNA fragmentation in nuclei of glial cells at-or very near-to the site of demyelination. A double labeling technique showed that glial fibrillary associated protein positive astrocytes may undergo programmed cell death in multiple sclerosis.

Astrocytes↗

Gliotoxicity, reverse transcriptase activity and retroviral RNA in monocyte/macrophage culture supernatants from patients with multiple sclerosis.

In investigating a possible link between a novel retroviral agent (provisionally called MSRV), recently characterised in multiple sclerosis (MS), and the neuropathology of MS, it was found that there was a significant correlation between gliotoxicity and reverse transcriptase activity in monocyte/macrophage culture supernatants (MMCS) unique to MS patients. MMCS from healthy controls and patients with other neurological diseases did not display either gliotoxicity or reverse transcriptase activity. The observed gliotoxic effect was an initial, intermediate filament network disorganization and subsequent cell death which was specific to astrocytes and oligodendrocytes. The reverse transcriptase activity and MSRV-specific RNA were observed during the first 2 weeks of culture in MMCS from patients with active MS. The further elucidation of the molecular form(s) of this gliotoxic factor and its original source may be crucial in elucidating important etiopathogenic mechanisms in MS.

Animals↗

A cytotoxic factor for glial cells: a new avenue of research for multiple sclerosis?

A novel retrovirus, provisionally called Multiple Sclerosis RetroVirus (MSRV), was recently described in multiple sclerosis (MS). We report here that monocyte/macrophage culture supernatants from MS patients containing reverse transcriptase activity secrete a cytotoxin which induces death of primary mouse cortical glial cells. This cytotoxin, which was also found in MS cerebrospinal fluid, specifically causes death of mouse immortalized astrocytes and oligodendrocytes in vitro and seems to be associated to MSRV-specific RNA. This toxic factor, called gliotoxin, is present only in active cases of MS and is a stable glycosylated protein of 17 kDa, in CSF as well as in monocyte/macrophage culture supernatants. Since this gliotoxin is highly toxic for glial cells, it may represent an initial pathogenic factor, leading to the neuropathological features of MS, like blood brain barrier disruption and demyelination.

Animals↗

The vacuolar ATPase proton pump is required for the cytotoxicity of Bacillus anthracis lethal toxin.

The nature of the cytopathic effect exerted by the lethal factor toxin (LF) of Bacillus anthracis on sensitive cells is unknown. The toxin requires the passage through acidic vesicles in order to exert its effect within the cytosol. Here, we show that bafilomycins and concanamycin A, selective inhibitors of the vacuolar ATPase proton pump, are the most powerful known inhibitors of LF macrophage toxicity. These inhibitors are fully active long after LF addition to macrophages, suggesting that LF enters the cytosol after having reached a late endosomal compartment.

Animals↗

Inhibition of activity of the protease from bovine leukemia virus.

In view of the close similarity between bovine leukemia virus (BLV) and human T-cell leukemia virus type I (HTLV-I) we investigated the possibility of developing specific inhibitors of the proteases of these retroviruses using the purified enzyme from BLV. We tested the ability of this protease to specifically cleave various short oligopeptide substrates containing cleavage sites of BLV and HTLV-I proteases, as well as a recombinant BLV Gag precursor. The best substrate, a synthetic decapeptide bearing the natural cleavage site between the matrix and the capsid proteins of BLV Gag precursor polyprotein, was used to develop an inhibition assay. We determined the relative inhibitory effect of synthetic Gag precursor-like peptides in which the cleavable site was replaced by a non-hydrolyzable moiety. The encouraging inhibitory effect of these compounds indicates that potent non-peptidic inhibitors for retroviral proteases are not unattainable.

Amino Acid Sequence↗

Modelling, synthesis and biological activity of a BLV proteinase, made of (only) 116 amino acids.

Bovine leukaemia virus (BLV) is the aetiological agent of Leukosis enzootica bovis [Viral Oncology (1980), G. Klein (Ed.) Raven Press, New York, pp. 231-238], a widely spread disease in cattle. BLV is reported as the animal model of human T-cell leukaemia virus (HLTV) which is the causative agent of adult T-cell leukaemia and tropical spastic paraparesis. Like the viruses themselves, the two retroviral proteinases (PR) are very closely related [Virology 142 (1985) 357-377]. BLV and HTLV-I PR are reported as putative proteins made of 126 [J. Virol. 57 (1986) 826-832] and 125 [FEBS Lett. 293 (1991) 106-110] amino acids, respectively (long sequences), belonging to the aspartyl proteinase family [Nature 329 (1987) 351-354], with the aid of molecular modelling, we show that BLV and HTLV-I proteinases made of only 116 and 115 amino acids, respectively (short sequences), display three-dimensional structures similar to that observed for other retroviral aspartyl proteinases. The models are based on three-dimensional structures of Rous sarcoma virus (RSV PR) and the human immunodeficiency virus (HIV-1 PR). We used solid phase peptide synthesis to produce the putative proteolytic enzyme of BLV (116 amino acids). In this study, we show that the folded synthetic protease accurately hydrolyzes a decapeptide corresponding to the sequence of the Matrice-Capside (MA/CA) cleavage site of the gag polyprotein. In addition, the proteolytic activity is inhibited by a statine ((4S,3S)-4-amino-3-hydroxyl-6-methylheptanoic acid) containing an analogous sequence.

Amino Acid Sequence↗

[Endometriosis: indications, operative techniques, results].

Laparoscopic treatment of endometriosis is essential, elegant, efficacious. It is a more complex laparoscopic surgical procedure because of the adnexial lesions, now performed thank's to recent improved instrumentation. At the time of diagnosis, a complete evaluation of lesions appropriately staged according to the American Fertility Society classification scheme is necessary before destruction of endometriotic implants, adhesiolysis and ovarian cystectomy. CO2 videolaseroscopy with laser adhesiolysis and vaporization has been developed with precise destructions of disease tissue and minimal tissue reaction. Laser surgery with complex operative laparoscopy has many advantages: minimal damage of the adjacent normal tissue, minimal ovarian destruction, minimal bleeding and minimal postoperative adhesion formation.

Endometriosis↗

Tissue effects of methotrexate injected into the uterine horn of pregnant female rats.

Methotrexate has been proposed as a treatment for unruptured extra-uterine pregnancy, but its effects on the tubal wall remain unknown. In order to analyse these effects, an experimental study was carried out on two groups of pregnant female rats, one receiving methotrexate (n = 8) and the other sodium chloride (n = 6). In both groups, a single intra-embryonic injection was performed in the uterine horn. The genital tract was prepared for histological examination. In all rats which received a single dose of methotrexate (5 mg per 100 g body weight) six days after mating and were killed nine days later, the labyrinthine part and the junctional zone of the placenta were necrotic at the site of the injection, with no embryonic development. The other parts of the genital tract were not visibly altered. In rats receiving sodium chloride and killed under the same conditions, necrosis of the placenta was observed at the site of injection in three animals. In the other three rats, a focal necrosis of the placenta was found, which was probably of mechanical origin. From this study, we conclude that methotrexate is efficient in killing normally implanted embryos and is, at least under light microscopy, non-toxic to the adjacent portions of the genital tract.

Animals↗

Treatment of unruptured tubal pregnancy by local injection of methotrexate under transvaginal sonographic control.

Seventeen unruptured tubal gestations were managed on an outpatient basis using local methotrexate (MTX) injection. A single 50-mg dose of MTX was injected into the gestational sac under transvaginal sonographic control. Follow-up included serial assays of the beta-subunit of human chorionic gonadotropin (beta-hCG), clinical and sonographic evaluation. Resolution was obtained in 13 out of 17 patients. The regression curve between days after treatment versus beta-hCG (y = 82.2 - 10.8x + 0.37x2) demonstrated a significant negative correlation (R2 = 0.77; R = 0.88; P less than or equal to 0.02). The mean beta-hCG level on day 15 was 3.2% +/- 3.1% of the initial value. Laparoscopy was performed in 4 patients. Pathological findings suggested that resolution was underway in these four cases despite a slow decline in beta-hCG. No systemic side effects were observed in any of the 17 patients. Long-term follow-up is needed to evaluate tubal patency and reproductive outcome. Our experience suggests that local injection of MTX may be an effective alternative for the treatment of unruptured ectopic pregnancy.

Chorionic Gonadotropin↗

Imported cutaneous gnathostomiasis: report of five cases.

Gnathostomiasis has rarely been described outside endemic countries. We report on a series of 5 patients (4 females, 1 male, mean age 42.2 years) who returned to France from South-East Asia and presented with cutaneous gnathostomiasis. The cutaneous lesions appeared within a mean period of 62 d (range 10-150 d) after return. They consisted of creeping eruptions in 3 patients (in addition one also had papules, one had nodules and hepatitis, and one had hepatitis; all 3 had profound asthenia) and recurring migratory swellings in 2 patients. The mean eosinophil count was 1546/mm3 (range 398-3245/mm3). Diagnosis was based on positive serological tests in 3 patients and seroconversion in 2 patients, and was confirmed by identification of Gnathostoma hispidum in a biopsy specimen from one of the seropositive patients. Albandazole (1-4 courses) was given as treatment. Recurrences may occur up to 24 months after apparent cure without reinfection. Gnathostomiasis should be considered when patients return from tropical countries and present with migratory swellings or creeping eruption that does not respond to the usual treatment for cutaneous larva migrans. Serological tests may be negative initially and thus need to be repeated to check for seroconversion. Treatment may require multiple courses of albendazole and a prolonged period of follow-up is necessary before cure can be confirmed.

Adult↗

Myocastor coypus as a reservoir host of Fasciola hepatica in France.

To clarify the role of the nutria Myocastor coypus in the epidemiology of domestic fasciolosis in Loire-Atlantique (department of western France), 438 nutrias were trapped in 9 humid areas of the department and 304 nutrias were trapped in 3 farms where Fasciola hepatica was present; all animals were necropsied. Liver flukes were found in 160 nutrias: 38 nutrias randomly taken in the department (8.7%) and 122 trapped in fasciolosis areas (40.1%). The average parasitic burden was 5.7 flukes per nutria. Sixty-five percent of the liver flukes measured more than 18 mm (size of sexual maturity). The coproscopic examinations carried out on 144 infected nutrias showed that 90% of the infected nutrias shed fluke eggs. The hatching rate was 39.6%. Two groups of 100 Lymnaea truncatula snails, originating from 2 different populations, were exposed to F. hepatica miracidiae hatched from eggs collected from infected nutrias. The prevalence of the infection was 74% and 58.6% in the 2 groups of snails. The average redial burden was 6.2 rediae per snail. The total number of metacercariae was 72.4 metacercariae per snail producing cercariae. Two groups of 5 sheep were orally infected by 150 metacercariae of nutria or sheep origin, respectively. The installation rates of F. hepatica in sheep were respectively 31.6% and 29.6% for the two groups. Specific antibody kinetics of sheep were similar whether the metacercariae were of nutria or sheep origin. M. coypus allows the complete development of F. hepatica and releases parasitic elements that are infective for domestic ruminants. Because of its eco-ethologic characteristics, the nutria could be a potential wild reservoir of F. hepatica in France.

Animals↗

Language development in a child with left hemispherectomy.

A longitudinal study of a left hemispherectomized boy (AB) was conducted to document linguistic evolution and maturation and determine the extent to which right hemisphere processes allow development of language. Resection of the left hemisphere occurred at age 5 years 6 months, following intractable epilepsy. Tests of language comprehension (pointing, understanding of prepositions, understanding of narratives) and production (naming, repetition, lexical diversity, grammatical production) were administered at ages 6:2, 6:4, 6:6, and 6 years 9 months. Observations showed little progress, if any, in most aspects of linguistic performance. In contrast to studies with left-hemispherectomized children, AB showed only a modest expansion of the semantic lexicon and the phonological repertoire more than a year after the surgical intervention. These observations indirectly suggest (1) poor functional involvement of the right hemisphere in the development of adequate linguistic abilities, (2) the necessary integrity of the LH for adequate development of language, or (3) that variations in individual brain maturation rates may account for AB's linguistic progress.

Brain↗