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Biomedical subjects

C Boyer

Publications and source records attributed to C Boyer.

At least 19 recordsLinked to original sources

Giant-block twist grain boundary smectic phases.

Study of a diverse set of chiral smectic materials, each of which has twist grain boundary (TGB) phases over a broad temperature range and exhibits grid patterns in the Grandjean textures of the TGB helix, shows that these features arise from a common structure: "giant" smectic blocks of planar layers of thickness l(b) > 200 nm terminated by GBs that are sharp, mediating large angular jumps in layer orientation between blocks (60 degrees < Delta < 90 degrees ), and lubricating the thermal contraction of the smectic layers within the blocks. This phenomenology is well described by basic theoretical models applicable in the limit that the ratio of molecular tilt penetration length-to-layer coherence length is large, and featuring GBs in which smectic ordering is weak, approaching thin, melted (nematic-like) walls. In this limit the energy cost of change of the block size is small, leading to a wide variation of block dimension, depending on preparation conditions. The models also account for the temperature dependence of the TGB helix pitch.

Journal Article↗

Direct determination of niflumic acid in a pharmaceutical gel by ATR/FTIR spectroscopy and PLS calibration.

A simple, rapid and convenient analytical method without sample handling procedure is proposed for the determination of niflumic acid in a pharmaceutical gel with attenuated total reflectance/Fourier transform infrared spectroscopy (ATR/FTIR). A partial least square (PLS) calibration model for the prediction of niflumic acid contents was developed using 81 and 27 spectra of standard gels as training and validation sets, respectively. The used spectral range of niflumic acid for the establishment of this model was 2300-1100 cm(-1). All spectra were obtained in the transmittance mode, then normalized and first derivative transformed. The model yielded a regression coefficient R2 equal to 1 for the training set and a root mean square error of prediction (RMSEP) equal to 0.2 for the validation set. The percentage recoveries of the method for the analysis of Niflugel ranged from 96.60 to 101.02%.

Anti-Inflammatory Agents, Non-Steroidal↗

[Neonatal consequences of maternal smoking during pregnancy].

In utero tobacco consumption is a serious public health problem in France; it is very frequent and the long term consequences are not only numerous but also misinterpreted by our population. 25 to 29% of women arrive at the end of their pregnancy without stopping smoking and 50% of non smoking mothers live in an environment polluted by tobacco during pregnancy. The authors would like to stress the gravity of this situation. At the maternity hospital in Nîmes, 358 women who gave birth at term and after a normal pregnancy were enrolled in a survey and monitored with thiocyanate for their tobacco consumption. Birth weight, height, and cranial perimeter of the infants were noted at birth. Results confirmed earlier work on this subject: the three variables studied were consistently weakened by the mother's addiction to tobacco. The authors recall previous medical literature on the pathophysiology and other consequences on the brain: such as I.Q. behavior, sudden infant death syndrome, vascular alterations with possible long-term complications, as well as pulmonary alterations on which there has recently been much research. The question is raised as to why this problem is so neglected in our society and what could be done to change this state of affairs.

Child Development↗

The vesosome-- a multicompartment drug delivery vehicle.

Assembling structures to divide space controllably and spontaneously into subunits at the nanometer scale is a significant challenge, although one that biology has solved in two distinct ways: prokaryotes and eukaryotes. Prokaryotes have a single compartment delimited by one or more lipid-protein membranes. Eukaryotes have nested-membrane structures that provide internal compartments--such as the cell nucleus and cell organelles in which specialized functions are carried out. We have developed a simple method of creating nested bilayer compartments in vitro via the "interdigitated" bilayer phase formed by adding ethanol to a variety of saturated phospholipids. At temperatures below the gel-liquid crystalline transition, T(m), the interdigitated lipid-ethanol sheets are rigid and flat; when the temperature is raised above T(m), the sheets become flexible and close on themselves and the surrounding solution to form closed compartments. During this closure, the sheets can entrap other vesicles, biological macromolecules, or colloidal particles. The result is efficient and spontaneous encapsulation without disruption of even fragile materials to form biomimetic nano-environments for possible use in drug delivery, colloidal stabilization, or as microreactors. The vesosome structure can take full advantage of the 40 years of progress in liposome development including steric stabilization, pH loading of drugs, and intrinsic biocompatibility. However, the multiple compartments of the vesosome give better protection to the interior contents in serum, leading to extended release of model compounds in comparison to unilamellar liposomes.

Animals↗

Polarization-modulated smectic liquid crystal phases.

Any polar-ordered material with a spatially uniform polarization field is internally frustrated: The symmetry-required local preference for polarization is to be nonuniform, i.e., to be locally bouquet-like or "splayed." However, it is impossible to achieve splay of a preferred sign everywhere in space unless appropriate defects are introduced into the field. Typically, in materials like ferroelectric crystals or liquid crystals, such defects are not thermally stable, so that the local preference is globally frustrated and the polarization field remains uniform. Here, we report a class of fluid polar smectic liquid crystals in which local splay prevails in the form of periodic supermolecular-scale polarization modulation stripes coupled to layer undulation waves. The polar domains are locally chiral, and organized into patterns of alternating handedness and polarity. The fluid-layer undulations enable an extraordinary menagerie of filament and planar structures that identify such phases.

Journal Article↗

[Fetal thoracic MR imaging].

Ultrasonography is the method of choice for prenatal malformation screening, but it does not always provide sufficient informations to allow a correct diagnosis or an adequate abnormality evaluation. Fetal MRImaging (MRI) indications are increasing in order to complete sonographic findings. It has been initially used for evaluation of cerebral abnormalities, but it is more and more applied to other fetal areas. An adequate analysis of fetal chest and abdomen can be obtained with fast T2 and T1 weighted sequences. This allows an easy diagnosis of congenital diaphragmatic hernia and an evaluation of the consequences on pulmonary growth. Other pulmonary malformations can be also easily identified (cystic adenoid malformation, sequestration, bronchogenic cyst, tracheal or bronchial atresia). Therefore, fetal thoracic MRI contributes to a better understanding and evaluation of fetal thoracic malformations, which is particularly useful for their postnatal management.

Bronchi↗

Transplanted BM and BM side population cells contribute progeny to the lung and liver in irradiated mice.

BACKGROUND: BM cells have been shown to give rise to progeny of various cell lineages, including cells in lung and liver. This investigation evaluated whether purified BM mononuclear cells and side population (SP) cells that have hematopoietic stem-cell activity also had this property; whether a TBI preparative regimen was necessary for engraftment; and where BM-derived cells were engrafted. METHODS: Either 1-3 million BM mononuclear cells or 2000 BM SP cells from transgenic enhanced green fluorescent protein-expressing (EGFP) mice were transplanted i.v. to unirradiated or 7-9.5 Gy irradiated recipients. RESULTS: Flow cytometric analysis showed that lung cells (mean 45%, range 4-70%) and liver cells (mean 4%, range 0.4-8.3%) from irradiated, but not unirradiated recipients, were EGFP donor-derived. Similar results were obtained transplanting BM mononuclear cells or SP cells. Morphologically, donor-derived cells in the lung were primarily monocytes and macrophages. Additionally, lung fibroblasts and Type I, but not Type II, alveolar cells and rare cells in the bronchial epithelium were donor BM derived. In the liver, Kupffer cells, inflammatory cells and small clusters of hepatocytes, but not bile duct cells, were donor-derived. DISCUSSION: BM mononuclear and SP cells generated progeny in some compartments of the lung and liver, but only in TBI recipients. Stem cells in BM can contribute to repair of tissue injury in some compartments, but not to the same extent in the lung and liver.

Animals↗

[Magnetic resonance imaging applications in obstetrics].

PURPOSE: To review the main indications and results of magnetic resonance imaging in the pregnant women. MATERIAL AND METHOD: We reviewed MRI practice during the pregnancy based on our own experience in a prenatal diagnostic center and data in the literature. Rapid improvement in MRI technology has allowed more extensive use, giving a good contrast-to-noise ratio and multiplanar imaging. RESULTS: Although ultrasound provides primary screening information, final diagnosis may require further investigations. MRI, to be performed in the second and third trimester, is the non-invasive second line tool of choice in this context. The most widespread indications are for brain disease: search for a cause of ventriculomegaly or biometric abnormality, confirmation of a malformative or acquired lesion. Progressively, indications were widened to head and neck, thorax, abdomen and pelvis areas. Moreover, systematic indications include previous fetal pathology or the pregnancy context. Other MRI indications have been suggested: placental malposition, pelvimetry and maternal genito-urinary tract. CONCLUSION: MRI is becoming the natural and necessary second line imaging technique, with increasing indications. It must be kept in mind however that all pathological conditions cannot be depicted by these morphological studies.

Congenital Abnormalities↗

A humanist's legacy in medical informatics: visions and accomplishments of Professor Jean-Raoul Scherrer.

OBJECTIVE: To report about the work of Prof. Jean-Raoul Scherrer, and show how his humanist vision, his medical skills and his scientific background have enabled and shaped the development of medical informatics over the last 30 years. RESULTS: Starting with the mainframe-based patient-centered hospital information system DIOGENE in the 70s, Prof. Scherrer developed, implemented and evolved innovative concepts of man-machine interfaces, distributed and federated environments, leading the way with information systems that obstinately focused on the support of care providers and patients. Through a rigorous design of terminologies and ontologies, the DIOGENE data would then serve as a basis for the development of clinical research, data mining, and lead to innovative natural language processing techniques. In parallel, Prof. Scherrer supported the development of medical image management, ranging from a distributed picture archiving and communication systems (PACS) to molecular imaging of protein electrophoreses. Recognizing the need for improving the quality and trustworthiness of medical information on the Web, Prof. Scherrer created the Health-On-the-Net (HON) foundation. CONCLUSIONS: These achievements, made possible thanks to his visionary mind, deep humanism, creativity, generosity and determination, have made of Prof. Scherrer a true pioneer and leader of the human-centered, patient-oriented application of information technology for improving healthcare.

History, 20th Century↗

[MRI in gynecology].

OBJECTIVES: To review the complementary role and contribution of magnetic resonance imaging (MRI) in gynecology diseases. RESULTS: Tissue characterization can be obtained with T2, T1 weighted images before and after contrast medium injection and T1 fat sat sequences. Localization of the lesion and relationships with adjacent structures are facilitated by multiplanar imaging. Endometrium and ovarian follicles display high signal intensity, visualizing the normal uterine and ovarian components. The relative high signal intensity of uterine tumors facilitates evaluation of extension. Uterine leiomyoma diagnosis is supported by its low signal intensity, allowing localization, size, and number assessment, and to distinguish adenomyoma. In doubtful malformation cases, MRI may be contributive. Ovarian mass characterization can be done with MRI, particularly for dermoid cyst and endometrioma. In this case, deep endometriosis can be associated and be extensive. Recent technical advances enable fast imaging, which can be useful for pelvic floor assessment with dynamic evaluation. CONCLUSION: MRI is becoming the complementary reference imaging tool for us. Its increasing indications are: gynecologic cancer, pelvis endometriosis, pelvis floor, indeterminate pelvis mass and fibroleiomyoma.

Endometriosis↗

T cell development and T cell responses in mice with mutations affecting tyrosines 292 or 315 of the ZAP-70 protein tyrosine kinase.

After stimulation of the T cell receptor (TCR), the tyrosine residues 292 and 315 in interdomain B of the protein tyrosine kinase ZAP-70 become phosphorylated and plausibly function as docking sites for Cbl and Vav1, respectively. The two latter proteins have been suggested to serve as substrates for ZAP-70 and to fine-tune its function. To address the role of these residues in T cell development and in the function of primary T cells, we have generated mice that express ZAP-70 molecules with Tyr to Phe substitution at position 292 (Y292F) or 315 (Y315F). When analyzed in a sensitized TCR transgenic background, the ZAP-70 Y315F mutation reduced the rate of positive selection and delayed the occurrence of negative selection. Furthermore, this mutation unexpectedly affected the constitutive levels of the CD3-zeta p21 phosphoisoform. Conversely, the ZAP-70 Y292F mutation upregulated proximal events in TCR signaling and allowed more T cells to produce interleukin 2 and interferon gamma in response to a given dose of antigen. The observation that ZAP-70 Y292F T cells have a slower rate of ligand-induced TCR downmodulation suggests that Y292 is likely involved in regulating the duration activated TCR reside at the cell surface. Furthermore, we showed that Y292 and Y315 are dispensable for the TCR-induced tyrosine phosphorylation of Cbl and Vav1, respectively. Therefore, other molecules present in the TCR signaling cassette act as additional adaptors for Cbl and Vav1. The present in vivo analyses extend previous data based on transformed T cell lines and suggest that residue Y292 plays a role in attenuation of TCR signaling, whereas residue Y315 enhances ZAP-70 function.

Animals↗

Contribution of the plasmalemma to Ca2+ homeostasis in hair cells.

Calcium influx through transduction channels and efflux via plasmalemmal Ca(2+)-ATPases (PMCAs) are known to contribute to calcium homeostasis and modulate sensory transduction in vertebrate hair cells. To examine the relative contributions of apical and basolateral pathways, we analyzed the calcium dynamics in solitary ciliated and deciliated guinea pig type I and type II vestibular hair cells. Whole-cell patch-clamp recordings demonstrated that these cells had resting potentials near -70 mV and could be depolarized by 10-20 mV by superfusion with high potassium. Fura-2 measurements indicated that ciliated type II cells and deciliated cells of either type had low basal [Ca(2+)](i), near approximately 90 nm, and superfusion with high potassium led to transient calcium increases that were diminished in the presence of Ca(2+) channel blockers. In contrast, measurements of type I ciliated cells, hair cells with large calyceal afferents, were associated with a higher basal [Ca(2+)](i) of approximately 170 nm. High-potassium superfusion of these cells induced a paradoxical decrease in [Ca(2+)](i) that was augmented in the presence of Ca(2+) channel blockers. Optical localization of dihydropyridine binding to the kinocilium suggests that they contain L-type calcium channels, and as a result apical calcium influx includes a contribution from voltage-dependent ion channels in addition to entry via transduction channels localized to the stereocilia. Eosin block of PMCA significantly altered both [Ca(2+)](i) baseline and transient responses only in ciliated cells suggesting that, in agreement with immunohistochemical studies, PMCA is primarily localized to the bundles.

Animals↗

Enzyme-catalyzed therapeutic agent (ECTA) design: activation of the antitumor ECTA compound NB1011 by thymidylate synthase.

The in vivo administration of enzyme-inhibiting drugs for cancer and infectious disease often results in overexpression of the targeted enzyme. We have developed an enzyme-catalyzed therapeutic agent (ECTA) approach in which an enzyme overexpressed within the resistant cells is recruited as an intracellular catalyst for converting a relatively non-toxic substrate to a toxic product. We have investigated the potential of the ECTA approach to circumvent the thymidylate synthase (TS) overexpression-based resistance of tumor cells to conventional fluoropyrimidine [i.e. 5-fluorouracil (5-FU)] cancer chemotherapy. (E)-5-(2-Bromovinyl)-2'-deoxy-5'-uridyl phenyl L-methoxyalaninylphosphoramidate (NB1011) is a pronucleotide analogue of (E)-5-(2-bromovinyl)-2'-deoxyuridine (BVdU), an antiviral agent known to be a substrate for TS when in the 5'-monophosphorylated form. NB1011 was synthesized and found to be at least 10-fold more cytotoxic to 5-FU-resistant, TS-overexpressing colorectal tumor cells than to normal cells. This finding demonstrates that the ECTA approach to the design of novel chemotherapeutics results in compounds that are selectively cytotoxic to tumor cell lines that overexpress the target enzyme, TS, and therefore may be useful in the treatment of fluoropyrimidine-resistant cancer.

Animals↗

[The lessons of medical cooperation (1995-1998): the formation of young teams trained in emergency services at two Romanian pediatric hospitals].

UNLABELLED: A cooperation programme, aimed at improving the running of pediatric hospitals in Bucharest (Romania) was conducted by a team of Assistance Publique-Hôpitaux de Paris from 1995 to 1998. MATERIAL AND METHODS: The introduction mentions the context of the health care system in order to help to follow the role of emergency services. The method to improve the child health services was based on an initial evaluation of emergency structures and procedures. A questionnaire was filled in after a four-year programme to test the impact of the counselling concerning the organization of the casualties and emergency division, the medical and nursing training and the use of equipment. RESULTS: The results show: a centralization of the emergencies and the implementation of an intensive care unit in one out of the two hospitals. The discussion points out the criteria of efficacy for cooperation programmes and gives examples of medical cooperation in eastern countries. CONCLUSION: The conclusion insists on the multidisciplinary approach of medical programmes, with training of young teams.

Child↗

A novel approach to thymidylate synthase as a target for cancer chemotherapy.

Tumor cell resistance to fluoropyrimidines and other inhibitors of thymidylate synthase (TS) is a serious problem often associated with increased intracellular TS. Clinically, another problem that arises from the use of TS inhibitors is toxicity, which develops, in part, because normal cells may be adversely affected by doses of inhibitor that do not impact tumor cells. To circumvent this problem, we have devised a new strategy called enzyme-catalyzed therapeutic activation (ECTA), which takes advantage of overexpressed TS to enzymatically generate cytotoxic moieties preferentially in tumor cells. We show herein that tumor cells expressing elevated levels of TS are preferentially sensitive to NB1011, a phosphoramidate derivative of (E)-5-(2-bromovinyl)-2'-deoxyuridine. We find support for the proposed mechanism of NB1011 in the following results: 1) positive relationship between TS protein level and sensitivity to NB1011 in engineered HT1080 tumor cells, designed to express defined levels of TS protein; 2) NB1011 activity is enhanced on tumor cells which express endogenous elevated TS; 3) cytotoxicity of NB1011 is blocked by raltitrexed (Tomudex); 4) NB1011 selection of TS-overexpressing MCF7TDX tumor cells results in recovery of cell populations and clones with diminished TS levels (and restored sensitivity to raltitrexed). A preliminary comparison of TS mRNA levels in multiple normal tissues versus colon tumor samples suggests that selective tumor cytotoxicity of NB1011 may be possible in the clinical setting. Because NB1011 cytotoxicity is dependent upon activation by TS, its proposed mechanism of action is distinct from current TS-targeted drugs, which require inhibition of TS to be effective.

Antineoplastic Agents↗

[Preoperative management of hip osteochondritis: comparison of MRI and arthrography with abduction views].

PURPOSE: Comparison between conventional arthrography and MRI in the preoperative work up of Legg-Calvé-Perthes disease. MATERIAL: ans methods. We studied 17 children (18 hips) who had arthrography and MRI (open-magnet configuration) the same day. Coronal and sagittal T1 weighted were realised with the hip in neutral position. Additional coronal T1 weighted with abduction of the hip were obtained. Two readers analysed individually MRI and arthrographic findings: shape of femoral head, index of Heyman (antero-external covering), came effect, recentering of femoral head and quality of examimation. RESULTS: No statistical difference between MRI and arthrography could be noted-exception made for the index of Heyman. CONCLUSION: MRI can replace arthrography in Legg-Calvé-Perthes disease.

Adolescent↗