Publications by authors named "Franck Michel"

21 Publications

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Response: Commentary: : 43 Cases Diagnosed in France by Real-Time PCR in Patients With Persistent Polymorphic Signs and Symptoms.

Front Med (Lausanne) 2020 23;7:586694. Epub 2020 Oct 23.

Hôpital Universitaire Raymond Poincaré (Assistance Publique - Hópitaux de Paris), Département d'Infectiologie, Université de Versailles - Saint Quentin, Paris-Saclay, Garches, France.

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http://dx.doi.org/10.3389/fmed.2020.586694DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC7645120PMC
October 2020

: 43 Cases Diagnosed in France by Real-Time PCR in Patients With Persistent Polymorphic Signs and Symptoms.

Front Med (Lausanne) 2020 28;7:55. Epub 2020 Feb 28.

Hôpital Universitaire Raymond Poincaré (Assistance Publique - Hôpitaux de Paris), Département d'Infectiologie, Université de Versailles - Saint Quentin, Paris-Saclay, Garches, France.

species are divided into three groups depending on the induced disease and the tick vector. is a relapsing fever but can induce symptoms related to Lyme disease. Discovered in 1995, it is found in ticks around the world. In France, this species of has been isolated in ticks and rodents, but was not yet observed in humans. The aim of the study was to look for in symptomatic patients. Real-time PCR was performed on 824 blood samples from patients presenting symptoms of persistent polymorphic syndrome possibly due to tick bite, a syndrome recognized by the French Authority for Health, which is close to the post-treatment Lyme disease syndrome. PCR was also performed on 24 healthy control persons. The primers were specifically designed for this particular species of . The sequence of interest of 94 bp is located on the gene. Sequencing of amplification products, randomly chosen, confirmed the amplification specificity. To better investigate cases, a clinical questionnaire was sent to the patients PCR-positive for and to their physician. This search revealed a positive PCR for in the blood from 43 patients out of 824 (5.22%). PCR was negative in all control persons. A clinical chart was obtained from 31 of the 43 patients. A history of erythema migrans was reported in five of these 31 patients (16%). All patients complained about fatigue, joint pain and neuro-cognitive disorders. Some patients complained about respiratory problems (chest tightness and/or lack of air in 41.9%). Episodes of relapsing fever were reported by 11 of the 31 patients (35.5%). Chilliness, hot flushes and/or sweats were reported by around half of the patients. may not cross-react with serology. This study is the first to detect in human blood in France. This series of human infection is the largest in patients with long term persistent syndrome. Our data suggest that this infection may be persistent, even on the long term.
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http://dx.doi.org/10.3389/fmed.2020.00055DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC7059645PMC
February 2020

The CI MuMuFe - A New MMN Paradigm for Measuring Music Discrimination in Electric Hearing.

Front Neurosci 2020 23;14. Epub 2020 Jan 23.

Center for Music in the Brain, Department of Clinical Medicine, Aarhus University and The Royal Academy of Music, Aarhus/Aalborg, Aarhus, Denmark.

Cochlear implants (CIs) allow good perception of speech while music listening is unsatisfactory, leading to reduced music enjoyment. Hence, a number of ongoing efforts aim to improve music perception with a CI. Regardless of the nature of these efforts, effect measurements must be valid and reliable. While auditory skills are typically examined by behavioral methods, recording of the mismatch negativity (MMN) response, using electroencephalography (EEG), has recently been applied successfully as a supplementary objective measure. Eleven adult CI users and 14 normally hearing (NH) controls took part in the present study. To measure their detailed discrimination of fundamental features of music we applied a new multifeature MMN-paradigm which presented four music deviants at four levels of magnitude, incorporating a novel "no-standard" approach to be tested with CI users for the first time. A supplementary test measured behavioral discrimination of the same deviants and levels. The MMN-paradigm elicited significant MMN responses to all levels of deviants in both groups. Furthermore, the CI-users' MMN amplitudes and latencies were not significantly different from those of NH controls. Both groups showed MMN strength that was in overall alignment with the deviation magnitude. In CI users, however, discrimination of pitch levels remained undifferentiated. On average, CI users' behavioral performance was significantly below that of the NH group, mainly due to poor pitch discrimination. Although no significant effects were found, CI users' behavioral results tended to be in accordance with deviation magnitude, most prominently manifested in discrimination of the rhythm deviant. In summary, the study indicates that CI users may be able to discriminate subtle changes in basic musical features both in terms of automatic neural responses and of attended behavioral detection. Despite high complexity, the new CI MuMuFe paradigm and the "no-standard" approach provided reliable results, suggesting that it may serve as a relevant tool in future CI research. For clinical use, future studies should investigate the possibility of applying the paradigm with the purpose of assessing discrimination skills not only at the group level but also at the individual level.
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http://dx.doi.org/10.3389/fnins.2020.00002DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC6990974PMC
January 2020

Blood cell disruption to significantly improve the Borrelia PCR detection sensitivity in borreliosis in humans.

Med Hypotheses 2018 Jul 15;116:1-3. Epub 2018 Apr 15.

Infectious Diseases Unit, University Hospital Raymond Poincaré, APHP, Versailles Saint Quentin University, Garches, France. Electronic address:

Lyme disease is the most frequently reported zoonotic tick-borne disease worldwide, and the number of infected humans is increasing. Lyme disease (or Lyme borreliosis) is an affection caused by the spirochete Borrelia burgdorferi, sensu lato. Lyme disease is also reported as a variety of misleading clinical symptomatologies. Infected patient's blood serology is the most currently test used for its diagnosis. However, serology has a low sensitivity, which ranges from 34% to 70%. Thus, there are numerous subsequent false-negative diagnoses despite an active clinical infection profile. Therefore, alternative and more sensitive techniques are required to detect the antigens or nucleic acids of Borrelia. Actually, the most appropriate methodological approach seems to be the polymerase chain reaction (PCR). However, PCR will detect the only "visible" part available of the targeted DNA presence in the blood of the infected patients. Consequently PCR alone will not be conclusive enough to reach the final diagnosis. Considering the ability of Borrelia to invade host cells, we hypothesize that a selective lysis of all blood cells should improve the diagnostic sensitivity of the detection of Borrelia by PCR in whole blood, and subsequently reduce the false-negative diagnostic rate, thus improving the patient's diagnosis and therapeutic management.
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http://dx.doi.org/10.1016/j.mehy.2018.04.012DOI Listing
July 2018

Comparison of threshold estimation in infants with hearing loss or normal hearing using auditory steady-state response evoked by narrow band CE-chirps and auditory brainstem response evoked by tone pips.

Int J Audiol 2017 02 7;56(2):99-105. Epub 2016 Oct 7.

a Department of Otorhinolaryngology, Audiology Clinic , Aarhus University Hospital , Aarhus , Denmark.

Objective: The objective of this study is to compare air-conduction thresholds obtained with ASSR evoked by narrow band (NB) CE-chirps and ABR evoked by tone pips (tpABR) in infants with various degrees of hearing loss.

Design: Thresholds were measured at 500, 1000, 2000 and 4000 Hz. Data on each participant were collected at the same day.

Study Sample: Sixty-seven infants aged 4 d to 22 months (median age = 96 days), resulting in 57, 52, 87 and 56 ears for 500, 1000, 2000 and 4000 Hz, respectively.

Results: Statistical analysis was performed for ears with hearing loss (HL) and showed a very strong correlation between tpABR and ASSR evoked by NB CE-chirps: 0.90 (n = 28), 0.90 (n = 28), 0.96 (n = 42) and 0.95 (n = 30) for 500, 1000, 2000 and 4000 Hz, respectively. At these frequencies, the mean difference between tpABR and ASSR was -3.6 dB (± 7.0), -5.2 dB (± 7.3), -3.9 dB (± 5.2) and -5.2 dB (± 4.7). Linear regression analysis indicated that the relationship was not influenced by the degree of hearing loss.

Conclusion: We propose that dB nHL to dB eHL correction values for ASSR evoked by NB CE-chirps should be 5 dB lower than values used for tpABR.
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http://dx.doi.org/10.1080/14992027.2016.1234719DOI Listing
February 2017

Progressively Recovering Auditory Brainstem Response in a Cochlear-implanted Child After Meningitis: A Case Report.

Authors:
Franck Michel

Otol Neurotol 2016 Jan;37(1):16-8

Objective: I describe the case of an 8-year-old boy who developed meningitis several years after implantation and how electrically evoked auditory brainstem response (EABR) is used in the assessment of his hearing performance after recovery.

Patient: An 8-year-old boy stopped using both his cochlear implants because of streptococcal meningitis accompanied with acute otitis media on the left ear. After recovery his hearing was quickly restored on the right ear, but he complained of not hearing well on the left ear.

Intervention: Diagnostic.

Main Outcome Measure: EABRs were measured on both ears 2 months after meningitis offset. Testing was repeated on the left ear 12 and 18 months after the first session. Responses were evoked by apical, mid-array, and basal electrodes.

Results: At initial testing EABRs were normal on the right ear. They were absent on the left ear for the apical electrode and present but with delayed wave latencies for the middle and basal electrodes. At the second and third sessions, EABRs were present for all electrodes and wave eV latencies were shorter. The stimulus level needed to evoke an EABR was considerably reduced on all electrodes from the first to the third session. There was good agreement between these findings and the subjective feedback from the patient.

Conclusion: EABR provided valuable information throughout the patient's hearing recovery. Its use should be considered in difficult patients, especially those who cannot give feedback.
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http://dx.doi.org/10.1097/MAO.0000000000000870DOI Listing
January 2016

Technical support for Life Sciences communities on a production grid infrastructure.

Stud Health Technol Inform 2012 ;175:81-90

CNRS/UNS, I3S laboratory, MODALIS team, Sophia Antipolis, France.

Production operation of large distributed computing infrastructures (DCI) still requires a lot of human intervention to reach acceptable quality of service. This may be achievable for scientific communities with solid IT support, but it remains a show-stopper for others. Some application execution environments are used to hide runtime technical issues from end users. But they mostly aim at fault-tolerance rather than incident resolution, and their operation still requires substantial manpower. A longer-term support activity is thus needed to ensure sustained quality of service for Virtual Organisations (VO). This paper describes how the biomed VO has addressed this challenge by setting up a technical support team. Its organisation, tooling, daily tasks, and procedures are described. Results are shown in terms of resource usage by end users, amount of reported incidents, and developed software tools. Based on our experience, we suggest ways to measure the impact of the technical support, perspectives to decrease its human cost and make it more community-specific.
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September 2012

Brain pericytes from stress-susceptible pigs increase blood-brain barrier permeability in vitro.

Fluids Barriers CNS 2012 Jun 29;9(1):11. Epub 2012 Jun 29.

Univ Lille Nord de France, F-59000, Lille, France.

Background: The function of pericytes remains questionable but with improved cultured technique and the use of genetically modified animals, it has become increasingly clear that pericytes are an integral part of blood-brain barrier (BBB) function, and the involvement of pericyte dysfunction in certain cerebrovascular diseases is now emerging. The porcine stress syndrome (PSS) is the only confirmed, homologous model of malignant hyperthermia (MH) in veterinary medicine. Affected animals can experience upon slaughter a range of symptoms, including skeletal muscle rigidity, metabolic acidosis, tachycardia and fever, similar to the human syndrome. Symptoms are due to an enhanced calcium release from intracellular stores. These conditions are associated with a point mutation in ryr1/hal gene, encoding the ryanodine receptor, a calcium channel. Important blood vessel wall muscle modifications have been described in PSS, but potential brain vessel changes have never been documented in this syndrome.

Methods: In the present work, histological and ultrastructural analyses of brain capillaries from wild type and ryr1 mutated pigs were conducted to investigate the potential impairment of pericytes, in this pathology. In addition, brain pericytes were isolated from the three porcine genotypes (wild-type NN pigs; Nn and nn pigs, bearing one or two (n) mutant ryr1/hal alleles, respectively), and tested in vitro for their influence on the permeability of BBB endothelial monolayers.

Results: Enlarged perivascular spaces were observed in ryr1-mutant samples, corresponding to a partial or total detachment of the astrocytic endfeet. These spaces were electron lucent and sometimes filled with lipid deposits and swollen astrocytic feet. At the ultrastructural level, brain pericytes did not seem to be affected because they showed regular morphology and characteristics, so we aimed to check their ability to maintain BBB properties in vitro. Our results indicated that pericytes from the three genotypes of pigs had differing influences on the BBB. Unlike pericytes from NN pigs, pericytes from Nn and nn pigs were not able to maintain low BBB permeability.

Conclusions: Electron microscopy observations demonstrated brain capillary modifications in PSS condition, but no change in pericyte morphology. Results from in vitro experiments suggest that brain pericytes from ryr1 mutated pigs, even if they are not affected by this condition at the ultrastructural level, are not able to maintain BBB integrity in comparison with pericytes from wild-type animals.
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http://dx.doi.org/10.1186/2045-8118-9-11DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC3386891PMC
June 2012

NeuroLOG: sharing neuroimaging data using an ontology-based federated approach.

AMIA Annu Symp Proc 2011 22;2011:472-80. Epub 2011 Oct 22.

INSERM / INRIA / CNRS / Univ. Rennes 1, IRISA Unit VISAGES U746, Rennes, France.

This paper describes the design of the NeuroLOG middleware data management layer, which provides a platform to share heterogeneous and distributed neuroimaging data using a federated approach. The semantics of shared information is captured through a multi-layer application ontology and a derived Federated Schema used to align the heterogeneous database schemata from different legacy repositories. The system also provides a facility to translate the relational data into a semantic representation that can be queried using a semantic search engine thus enabling the exploitation of knowledge embedded in the ontology. This work shows the relevance of the distributed approach for neurosciences data management. Although more complex than a centralized approach, it is also more realistic when considering the federation of large data sets, and open strong perspectives to implement multi-centric neurosciences studies.
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http://www.ncbi.nlm.nih.gov/pmc/articles/PMC3243145PMC
February 2013

Grid-wide neuroimaging data federation in the context of the NeuroLOG project.

Stud Health Technol Inform 2010 ;159:112-23

INSERM / INRIA / CNRS / Univ. Rennes 1, IRISA Unit-Project VISAGES, Paris, UK.

Grid technologies are appealing to deal with the challenges raised by computational neurosciences and support multi-centric brain studies. However, core grids middleware hardly cope with the complex neuroimaging data representation and multi-layer data federation needs. Moreover, legacy neuroscience environments need to be preserved and cannot be simply superseded by grid services. This paper describes the NeuroLOG platform design and implementation, shedding light on its Data Management Layer. It addresses the integration of brain image files, associated relational metadata and neuroscience semantic data in a heterogeneous distributed environment, integrating legacy data managers through a mediation layer.
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http://www.ncbi.nlm.nih.gov/pmc/articles/PMC2938713PMC
October 2010

Difficulties improving ovarian functional recovery by microvascular transplantation and whole ovary vitrification.

Fertil Steril 2009 Jun 28;91(6):2697-706. Epub 2008 Apr 28.

Unité INSERM 846, Institut Cellule Souche et Cerveau, Bron, France.

Objective: To evaluate recovery of endocrine function and fertility after transplantation and vitrification of whole ovaries.

Design: Animal study.

Setting: Lyon Veterinary School, France.

Animal(s): Ewes.

Intervention(s): In group 1 (n = 5), the left ovary was removed with its vascular pedicle and was transplanted onto the contralateral pedicle. In group 2 (n = 5), the left ovary with its pedicle was cryopreserved after a vitrification procedure. After thawing, transplantation was performed by microvascular anastomosis to the contralateral ovarian pedicle.

Main Outcome Measure(s): Median ischemia time, progesterone levels, histologic examination.

Result(s): Successful microsurgical transplantation was performed in both groups. The median ischemia time was statistically significantly longer in group 2 (287 minutes, range: 226 to 349] versus 129 minutes [range: 125 to 130]) in group 1. In group 1, four sheep recovered spontaneous ovarian endocrine function about 2.5 (range: 2.00 to 3.75) months after transplantation. Two ewes gave healthy live births at 12 and 25 months, respectively, after transplantation. In group 2, one ewe recovered ovarian endocrine function 6 months after transplantation. However, histologic evaluation showed a follicular survival rate of 6% in group 1, and total follicle loss in group 2.

Conclusion(s): Autograft of whole sheep ovaries with microvascular anastomosis seems technically feasible but resulted in a very poor follicle survival rate (6%), in spite of endocrine function recovery and birth of two lambs. Attempts at cryopreservation with vitrification resulted in no follicle survival at all.
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http://dx.doi.org/10.1016/j.fertnstert.2008.03.012DOI Listing
June 2009

Proteome analysis of the sarcoplasmic fraction of pig semimembranosus muscle: implications on meat color development.

J Agric Food Chem 2006 Apr;54(7):2732-7

Qualité des Produits Animaux, INRA, 63122 St. Genès-Champanelle, France.

Two-dimensional electrophoresis was used to investigate sarcoplasmic protein expression in pig Semimembranosus muscles sampled 20 min after slaughter. Two groups (light and dark) of 12 animals were selected from 1000 pigs, based on meat L values measured 36 h postmortem. Twenty-two proteins or fragments (p < 0.05) were differentially expressed. Muscles leading to darker meat had a more oxidative metabolism, indicated by more abundant mitochondrial enzymes of the respiratory chain, hemoglobin, and chaperone or regulator proteins (HSP27, alphaB-crystallin, and glucose-regulated protein 58 kDa). Conversely, enzymes of glycolysis were overexpressed in the lighter group. Such samples were also characterized by higher levels of glutathione S-transferase omega, which can activate the RyR calcium channels, and higher levels of cyclophilin D. This protein pattern is likely to have severe implications on postmortem metabolism, namely, acceleration of ATP depletion and pH fall and subsequent enhanced protein denaturation, well-known to induce discoloration.
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http://dx.doi.org/10.1021/jf052569vDOI Listing
April 2006

Normal gestations and live births after orthotopic autograft of vitrified-warmed hemi-ovaries into ewes.

Hum Reprod 2005 Oct 24;20(10):2745-8. Epub 2005 Jun 24.

Département de Médecine de la Reproduction, Hôpital Edouard Herriot, Lyon, France.

Background: The aim of this study was to evaluate the long-term outcome of autotransplantation of vitrified warmed hemi-ovaries into ewes.

Methods: Six hemi-ovaries from six ewes aged 6 to 12 months were vitrified. After dissection of the medulla, the hemi-ovarian cortex was stored at -196 degrees C in liquid nitrogen. Four to six weeks after the first laparotomy, the left ovary was removed and the vitrified-warmed hemi-ovary was sutured.

Results: Plasma progesterone concentration increased in a regular manner in all ewes. Three pregnancies occurred, from which four lambs were born. The first delivery of a normal lamb occurred in February 2003. The second delivery of two normal lambs occurred in March 2003 (a 2.5 kg male and a 2.8 kg female). The last lamb had a normal delivery but had a malformation of the left leg and the oesophagus. This lamb died two months after delivery from pneumariae. Histological examination of the grafted vitrified ovaries showed few primordial and antral follicles.

Conclusions: These three pregnancies in a ewe model may indicate that ovarian vitrification gives results as good as those from a slow cooling protocol in autograft. It is impossible to establish a link between the vitrification procedure and the malformation of the last lamb, and further studies are needed to evaluate the feasibility of ovarian vitrification.
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http://dx.doi.org/10.1093/humrep/dei155DOI Listing
October 2005

Characterisation of PSE zones in semimembranosus pig muscle.

Meat Sci 2005 May;70(1):167-72

Station de Recherches sur la Viande, INRA, 63122 St Genès-Champanelle, France.

Pig semimembranosus muscles, sampled from normal hams or from PSE-zones of defective hams, were analysed by histochemistry and electrophoretic techniques. PSE zones were characterised by a disorganisation of fibre alignment and a significant increase of inter fibre spacing (26.2% vs. 16.9%, p<0.05). Protein solubility was significantly lower in defective muscle (55.4 vs. 91.5mg/g, p<0.001). SDS-PAGE evidenced in such samples a lower abundance of the 97, 40 and 26kDa bands in the sarcoplasmic fraction and a higher abundance of the 97, 58, 34, 31, 15 and 11kDa bands in the myofibrillar fraction. Intensity of the MHC band (200kDa) was lower in PSE zone samples. By 2-D electrophoresis, it was shown that troponin T, MLC 1 and alpha-crystallin were less proteolysed in defective muscles, while creatine kinase fragments were more represented. One form of HSP 27 was absent from PSE zone samples. Overall, meat from PSE-zones and fast pH fall-PSE meat show numerous histological and biochemical similarities, particularly in their protein characteristics.
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http://dx.doi.org/10.1016/j.meatsci.2004.12.008DOI Listing
May 2005

Alkali ocular burns in Martinique (French West Indies) Evaluation of the use of an amphoteric solution as the rinsing product.

Burns 2005 Mar;31(2):205-11

Service d'Ophtalmologie, Centre Hospitalier Universitaire de Fort de France, Hôpital Pierre Zobda Quitman, BP 632, 97261 Fort de France Cedex, Martinique -- France (French West Indies).

Precis: During the 4 years of this study, we noted 66 cases of alkali ocular burns, or approximately 16 cases per year, nearly half (45.5%) of which are due to an assault. For grade 1 and 2 burns the time elapsed to reepithelialization appears to be shorter when rinsed with Diphoterine* versus physiological solution.

Purpose: Comparison of the effectiveness of two rinsing solutions for emergency use: a physiological solution and an amphoteric solution (Diphoterine*, Laboratories Prevor, Valmondois, France). Description of the clinical and progressive characteristics of alkali burns treated at the University Hospital Center of Fort de France in Martinique (French West Indies).

Design: Prospective consecutive observational case series and nonrandomized comparative study.

Participants: Sixty-six patients were included. The total number of burned eyes is 104. Forty-eight eyes (46%) were rinsed with physiological solution and 56 eyes (54%) with Diphoterine*.

Methods: All patients benefited from an ocular rinse with 500ml of physiological solution or Diphoterine*, followed by a complete ophthalmologic exam. The ocular injuries were classified according to the Roper-Hall modification of the Hughes classification system. The same standardized therapeutic protocol was applied and adapted to the seriousness of the burn.

Main Outcome Measures: Demographic data, time to corneal reepithelialization, final best corrected visual acuity and complications were analysed.

Results: Twenty-eight (42.4%) patients have a unilateral burn and 38 (57.6%) patients have bilateral burns. In decreasing order of frequency, the circumstances surrounding the injury are: assaults in 45.5% of cases (n=30), work-related accidents in 32% of cases (n=31), and domestic accidents in 23% of cases (n=15). For grade 1 and 2 burns the time elapsed to reepithelialization appears to be shorter when rinsed with Diphoterine* versus physiological solution (respectively): 1.9+/-1 days versus 11.1+/-1.4 days (p=10(-7)) and 5.6+/-4.9 days versus 10+/-9.2 days (p=0.02). For grade 3 and 4 burns, there are complications in 11 cases (11.6%): 8 corneal opacities and 3 perforations.

Conclusions: This study is the first conducted in humans that takes into account the type of ocular rinse product used in the progressive follow-up study of injuries. The time elapsed to reepithelialization is shorter with Diphoterine* for grade 1 and 2 burns. There are not enough cases of grade 3 and 4 burns to make a conclusion. Diphoterine* seems very effective in terms of its mechanism of action and the experimental and clinical results.
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http://dx.doi.org/10.1016/j.burns.2004.09.001DOI Listing
March 2005

Identification of five chromosomal regions involved in predisposition to melanoma by genome-wide scan in the MeLiM swine model.

Int J Cancer 2004 May;110(1):39-50

Laboratoire de Radiobiologie et d'Etude du Génome, Commissariat à l'Energie Atomique, Institut National de la Recherche Agronomique, 78352 Jouy-en-Josas Cedex, France.

In human familial melanoma, 3 risk susceptibility genes are already known, CDKN2A, CDK4 and MC1R. However, various observations suggest that other melanoma susceptibility genes have not yet been identified. To search for new susceptibility loci, we used the MeLiM swine as an animal model of hereditary melanoma to perform a genome scan for linkage to melanoma. Founders of the affected MeLiM stock were crossed with each other and with healthy Duroc pigs, generating MeLiM, F1 and backcross families. As we had previously excluded the MeLiM CDKN2A gene, we paid special attention to CDK4 and MC1R, as well as to other candidates such as BRAF and the SLA complex, mapping them on the swine radiation hybrid map and/or isolating close microsatellite markers to introduce them into the genome scan. The results revealed, first, that swine melanoma was inherited as an autosomal dominant trait with incomplete penetrance, preferably in black animals. Second, 4 chromosomal regions potentially involved in melanoma susceptibility were identified on Sus Scrofa chromosomes (SSC) 1, 2, 7 and 8, respectively, in intervals 44-103, 1.9-18, 59-73 and 47-62 cM. A fifth region close to MC1R was revealed on SSC 6 by analyzing an individual marker located at position 7.5 cM. Lastly, CDK4 and BRAF were unlikely to be melanoma susceptibility genes in the MeLiM swine model. The 3 regions on SSC 1, 6 and 7, respectively, have counterparts on human chromosomes (HSA) 9p, 16q and 6p, harboring melanoma candidate loci. The 2 others, on SSC 2 and 8, have counterparts on HSA 11 and 4, which might therefore be of interest for human studies.
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http://dx.doi.org/10.1002/ijc.20053DOI Listing
May 2004

The cryopreservation of ovarian tissue: uses and indications in veterinary medicine.

Theriogenology 2003 Oct;60(6):999-1010

Laboratoire de Zootechnie, Ecole Vétérinaire de Lyon, Marcy l'Etoile 69280, France.

Animal experiments have shown that cryopreservation of the ovarian cortex, containing primordial follicles, could be used to preserve gametes thereby restoring fertility in humans and animals. During the last 100 years, many hundreds of species have been lost, and a third of the breeding animals are threatened with extinction. To preserve genetic diversity, notably for the conservation of endangered species, it is essential to conserve female and male gametes. Today, biotechnologies such as artificial insemination and embryo transfer are used in breeding programs and are well developed. However, even using these advanced techniques, there are problems due to the limited number of individuals used as the source of gametes, so that the risk of inbreeding is high, even in large populations. To preserve genetic diversity, it is necessary to create gene banks of male and female gametes and embryos, using a very large number of individual donors. Cryopreservation of ovarian tissue could present a means for enlarging the gene pool. Cryopreserved ovarian tissue could be used in auto- or xenografts, or for in vitro maturation (IVM) of primordial follicles. In this review, we describe the processes for cryopreservation of ovarian tissue and the various possibilities for using it.
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http://dx.doi.org/10.1016/s0093-691x(03)00121-3DOI Listing
October 2003

Long-term follow-up of cryopreserved hemi-ovary autografts in ewes: pregnancies, births, and histologic assessment.

Fertil Steril 2003 Jul;80(1):172-7

Département de Médecine de la Reproduction, Hôpital Edouard Herriot, Ecole Nationale Vétérinaire de Lyon, Lyon, France.

Objective: To evaluate a 2-year follow-up of cryopreserved hemi-ovary autografts in ewes.

Design: Animal study. SERTTING: University fertility center, Hospices Civils de Lyon; Ecole Nationale Vétérinaire de Lyon, INSERM U 418 Hocaron;pital Debrousse, Lyon; and Hôpital Edouard Herriot, Lyon, France.

Patient(s): Grivette ewes.

Intervention(s): Recently we reported four pregnancies and six live births after transplantation of frozen-thawed hemi-ovary in six different ewes. The four remaining ewes were monitored for 2 years. After the last birth, the autografted ovary was removed in each ewe during a final laparotomy. The entire grafted ovary was sliced to estimate the remaining primordial follicle population 2 years after grafting.

Main Outcome Measure(s): Uterine ultrasound scanning was performed to diagnose pregnancy. Histological assessment of the grafted ovary was performed after delivery.

Result(s): The four remaining ewes began new gestations. For two of them, this was a second gestation obtained more than 2 years after the autograft. These two ewes delivered male lambs, which died immediately after delivery because of distocia. The lambs were both oversized for gestational age; autopsy found no malformation. A twin pregnancy of a healthy male and a healthy female occurred in May 2002, and a singleton male was born in February 2002. All grafted ovaries showed drastic reduction in follicle population.

Conclusion(s): Frozen-thawed ovary autograft allowed recovery of fertility a very long time after the procedure despite a drastic reduction in the total number of follicles.
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http://dx.doi.org/10.1016/s0015-0282(03)00554-5DOI Listing
July 2003

Morphological alterations and DNA fragmentation in oocytes from primordial and primary follicles after freezing-thawing of ovarian cortex in sheep.

Fertil Steril 2002 Mar;77(3):595-600

Laboratoire de Zootechnie, Ecole Nationale Vétérinaire de Lyon, Marcy l'Etoile, France.

Objective: To evaluate DNA fragmentation in the oocyte of primordial and primary follicles and morphology of these follicles after freezing and thawing of ovarian cortex in sheep using two freezing protocols.

Design: Fragmentation of DNA was evaluated by the terminal deoxynucleotidyl transferase-mediated dUTP-biotin nick end-labeling (TUNEL) technique.

Setting: Fertility clinic in a large university hospital.

Animals: Five- to 6-month-old lambs.

Intervention(s): Two-millimeter-thick slices of hemi-ovary cortex were prepared.

Main Outcome Measure(s): Histological structure and DNA fragmentation.

Result(s): In the frozen fragments, the percentage of morphologically normal follicles was significantly lower for both protocols compared with the case of the control group of fresh fragments. There was no significant difference between the two types of freezing protocols (60.4% +/- 13.2% vs. 68.4% +/- 13.7%). However, the distribution of abnormalities (nucleus, cytoplasm, and nucleus and cytoplasm) was dissimilar. The results of the TUNEL technique for the three groups showed no significant difference, but the percentage of the TUNEL-positive follicles was slightly lower for the frozen fragments for both protocols with respect to the control group.

Conclusion(s): The freezing and thawing process of the ovarian cortex does not induce fragmentation of the DNA on the oocyte of primary and primordial follicles.
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http://dx.doi.org/10.1016/s0015-0282(01)03205-8DOI Listing
March 2002

Normal pregnancies and live births after autograft of frozen-thawed hemi-ovaries into ewes.

Fertil Steril 2002 Feb;77(2):403-8

Ecole National Vétérinaire de Lyon, Marcy l'Etoile, 69437 Lyon, France.

Objective: To evaluate long-term outcome of autotransplantation of cryopreserved hemi-ovaries into ewes.

Design: Animal study.

Setting: University fertility center, Hospices Civils de Lyon; and Ecole Nationale Vétérinaire de Lyon.

Patient(s): Grivette ewes.

Intervention(s): Six hemi-ovaries from 6 ewes aged 6 to 12 months were frozen with a slow cooling protocol using 2 M of dimethyl sulfoxide as cryoprotectant. After dissection of the medulla, the hemi-ovarian cortex was stored at -196 degrees C in liquid nitrogen. Freezing procedure was performed with a programmable freezer. Semiautomatic seeding was performed before crystallization. Four to 6 weeks after the first laparotomy, the left ovary was removed and the frozen-thawed hemi-ovary was sutured.

Main Outcome Measure(s): Mean plasma concentrations of FSH, LH, and progesterone after autotransplantation of frozen-thawed hemi-ovary. Ultrasonography was done to confirm pregnancy. Blood samples were collected weekly to measure FSH, LH, and progesterone. After the first birth, the autografted ovary was removed for histologic examination.

Result(s): Plasma progesterone concentration increased in a regular manner in all ewes except one 4 weeks after the graft. Concentrations of FSH and LH did not reach the menopausal level. Four pregnancies occurred, from which 6 lambs were born. The first delivery of a normal lamb occurred after 135 days of gestation; the lamb died immediately after birth. The second delivery of two normal lambs occurred after 130 days of gestation. A caesarean section was performed on the third pregnant ewe the 110th days of gestation because the ewe had a vaginal prolapsus. The two normal lambs and the ewe died after surgery. The fourth birth of a normal lamb occurred after 132 days of gestation. Histologic examination of the grafted frozen-thawed ovary showed a regressing corpus luteum and few primordial and antral follicles.

Conclusion(s): These four pregnancies in a ewe model may indicate that women who undergo preservation of their ovaries before chemotherapy or radiotherapy can have successful pregnancy.
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http://dx.doi.org/10.1016/s0015-0282(01)02960-0DOI Listing
February 2002
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