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Biomedical subjects

J Doucet

Publications and source records attributed to J Doucet.

At least 19 recordsLinked to original sources
PubMed2003

Microbeam synchrotron imaging of hairs from ancient Egyptian mummies.

Developments in microfocus synchrotron techniques have led to new results regarding the long-term alteration of archaeological samples of biological origin. Here, ancient hair samples from two Egyptian mummies have been analyzed using a conjunction of structural and elemental synchrotron methods. In this favored context of conservation, structural analysis revealed a remarkable preservation of keratin supramolecular organization at any observed length scale. Bulk keratin structure has therefore not been modified significantly over 2000 years. However, infrared spectroscopy indicated a partial disorganization of keratins close to the hair surface through polypeptide bond breakage. Elemental mapping showed a strongly heterogeneous distribution which can be related to mummification and cosmetic treatments.

Archaeology↗
PubMed2003

Lead-revealed lipid organization in human hair.

Human hair lipids form a complex mixture of composition close to that of sebum. Part of these lipids appears in an organized state that has been studied by diffraction techniques in the literature. Nevertheless, information on the structure of these lipids remains very scarce due to their low contribution to global hair diffraction pattern. Here we show that appropriate lead treatment considerably enhances organized lipid features observed by microbeam synchrotron radiation diffraction experiments. We attribute these features to the formation of lead soaps of free fatty acids. Specific orientation of hair "lipid crystals" in planes parallel to the hair axis is clearly demonstrated. Inclusion of these lipids in the bulk of the hair shaft is shown by diffraction experiments following removal of the cuticular outermost layer of hair. Moreover, microfluorescence and diffraction experiments are consistent with part of the lipids being present as calcium soaps in native hair. We therefore consider lead fixation as a powerful tool to evaluate the lipid organization in human hair for medical, environmental and archaeological purposes, including lead poisoning.

Calcium↗
PubMed2003

Evidence for various calcium sites in human hair shaft revealed by sub-micrometer X-ray fluorescence.

New information about calcium status in human scalp hair shaft, deduced from X-ray micro-fluorescence imaging, including its distribution over the hair section, the existence of one or several binding-types and its variation between people, is presented. The existence of two different calcium types is inferred. The first one corresponds to atoms (or ions) easily removable by hydrochloric acid, located in the cortex (granules), in the cuticle zone and also in the core of the medulla, which can reasonably be identified as calcium soaps. The second type consists of non-easily removable calcium atoms (or ions) that are located in the medulla wall, probably also in the cuticle, and rather uniformly in the cortex; these calcium atoms may be involved in Ca(2+)-binding proteins, and their concentration is fairly constant from one subject to another. In addition to its nonuniform distribution across the hair section, the second striking feature of the first type calcium content is its high variability from one subject to another, by up to a factor 10. We expect this information to be useful for analyzing in more detail the relationship between hair calcium and environmental and medical factors.

Calcium↗
PubMed2002

[Inappropriate prescription of heparin at curative doses in the hospital. Can the information to prescribing physicians decrease misuse?].

OBJECTIVES: To control whether prescriptions of curative doses of heparin (non fractioned heparins, enoxaparin, tinzaparin) in the hospital complied with the official recommendations; to provide the physicians with information adapted to the recorded misuse and to evaluate the influence of this information. METHODS: A prospective study was conducted between May and October 1999 on the prescriptions of 20 residents from 6 services in 3 phases: phase P1 with initial evaluation (particularly on the indications for heparin, the molecule administered, initial dose and monitoring), phase P2 with analysis and diffusion of an adapted information and phase P3 with final evaluation. RESULTS: 111 inpatients were included in the phase P1 (66.7% aged over 75 years, 18.9% with creatinin clearance below 30 ml/mn) and 101 inpatients were included in the phase P3 (56.4% aged over 75 years, 10.8% with renal failure). During phase P1: among the prescriptions of low molecular weight heparin (LMWH) 54.3% did not comply with the official recommendations; initial doses were too high in 15.3% of patients; mean initial doses of LMWH were not adapted to age, weight or creatinin clearance. Only 58.5% of patients had their platelets monitored. On the other hand, 15.3% of patients exhibited heparin side effects. During phase P3, the main modifications in prescriptions were a reduction in inappropriate indications for LMWH, reduction in LMWH prescriptions in patients aged over 75 or with excessive body weight or with renal failure, and increased platelet monitoring, but without significant difference. On the other hand, mean initial doses of each heparin were not modified. Heparin complications decreased but not significantly. CONCLUSION: This study highlights a real context of heparin prescription at curative doses, often differing from clinical studies, particularly with regards to age, renal failure and comorbidity; prescriptions often unadapted to official recommendations on indications, dose and monitoring; a real but limited influence of appropriate information for the physicians, which partially depends on the accuracy of official recommendations, particularly in patients with increased hemorrhagic risk.

Adult↗
PubMed2002

A new deformation model of hard alpha-keratin fibers at the nanometer scale: implications for hard alpha-keratin intermediate filament mechanical properties.

The mechanical behavior of human hair fibers is determined by the interactions between keratin proteins structured into microfibrils (hard alpha-keratin intermediate filaments), a protein sulfur-rich matrix (intermediate filaments associated proteins), and water molecules. The structure of the microfibril-matrix assembly has already been fully characterized using electron microscopy and small-angle x-ray scattering on unstressed fibers. However, these results give only a static image of this assembly. To observe and characterize the deformation of the microfibrils and of the matrix, we have carried out time-resolved small-angle x-ray microdiffraction experiments on human hair fibers stretched at 45% relative humidity and in water. Three structural parameters were monitored and quantified: the 6.7-nm meridian arc, which is related to an axial separation between groups of molecules along the microfibrils, the microfibril's radius, and the packing distance between microfibrils. Using a surface lattice model of the microfibril, we have described its deformation as a combination of a sliding process and a molecular stretching process. The radial contraction of the matrix is also emphasized, reinforcing the hydrophilic gel nature hypothesis.

Hair↗
PubMed2002

[Respiratory tract infections in the elderly living in institutions: prevention].

Pneumonia amongst elderly people living in institutions is common and is a frequent cause of mortality and hospital admission. It is important to distinguish between prevention of viral pneumonia, which primarily consists of influenza vaccination programmes, and prevention of bacterial pneumonia. Prevention of influenza infection in institutions requires the vaccination of as many as possible of both residents and caregivers. In the event of a declared epidemic then amantadine can be used to reduce the severity of, and complication rate of, influenza infection. The indications for giving this therapy need to be balanced against potential side-effects, especially neurological ones. For the prevention of bacterial pneumonia risk factors such as immobility or impaired swallowing should be first identified and dealt with as necessary. Anti-pneumoncoccal vaccination may be considered, but on current evidence, the value of systematic vaccination of residents has not yet been established.

Aged↗
PubMed2001

Coactosin-like protein, a human F-actin-binding protein: critical role of lysine-75.

Coactosin-like protein (CLP) was recently identified in a yeast two-hybrid screen using 5-lipoxygenase as bait. In the present study, we report the functional characterization of CLP as a human filamentous actin (F-actin)-binding protein. CLP mRNA shows a wide tissue distribution and is predominantly expressed in placenta, lung, kidney and peripheral-blood leucocytes. Endogenous CLP is localized in the cytosol of myeloid cells. Using a two-hybrid approach, actin was identified as a CLP-interacting protein. Binding experiments indicated that CLP associates with F-actin, but does not form a stable complex with globular actin. In transfected mammalian cells, CLP co-localized with actin stress fibres. CLP bound to actin filaments with a stoichiometry of 1:2 (CLP: actin subunits), but could be cross-linked to only one subunit of actin. Site-directed mutagenesis revealed the involvement of Lys(75) of CLP in actin binding, a residue highly conserved in related proteins and supposed to be exposed on the surface of the CLP protein. Our results identify CLP as a new human protein that binds F-actin in vitro and in vivo, and indicate that Lys(75) is essential for this interaction.

Actins↗
PubMed2001

Investigation of human hair cuticle structure by microdiffraction: direct observation of cell membrane complex swelling.

The cuticle of mammalian hair fibres protects the core of the fibre against physical and chemical stress. The structure and some of the properties of the cuticle have been extensively studied by electron microscopy. However, there is still a need for a less invasive structural probe. For this purpose, microdiffraction experiments have been carried out on human hair samples showing a characteristic small-angle X-ray scattering pattern for the cuticle. This pattern has been assigned to the cell membrane complex (CMC) between each cuticle scale. Using a simple model of the electron density within the CMC, values have been derived for the average thickness of the beta- and delta-layers which are close to those obtained by electron microscopy. In order to illustrate the potentialities of microdiffraction in studying the properties of the cuticle, the effect of water sorption has been monitored. Using the intensity modelling described above, a 10% swelling of the delta-layer's thickness has been observed. This study shows that structural modifications of the CMC by physical or chemical stress can be followed directly on the cuticle of human hair fibres by microdiffraction analysis.

Cell Membrane↗
PubMed2001

Unraveling double stranded alpha-helical coiled coils: an x-ray diffraction study on hard alpha-keratin fibers.

Transformations of proteins secondary and tertiary structures are generally studied in globular proteins in solution. In fibrous proteins, such as hard alpha-keratin, that contain long and well-defined double stranded alpha-helical coiled coil domains, such study can be directly done on the native fibrous tissue. In order to assess the structural behavior of the coiled coil domains under an axial mechanical stress, wide angle x-ray scattering and small angle x-ray scattering experiments have been carried out on stretched horse hair fibers at relative humidity around 30%. Our observations of the three major axial spacings as a function of the applied macroscopic strain have shown two rates. Up to 4% macroscopic strain the coiled coils were slightly distorted but retained their overall conformation. Above 4% the proportion of coiled coil domains progressively decreased. The main and new result of our study is the observation of the transition from alpha-helical coiled coils to disordered chains instead of the alpha-helical coiled coil to beta-sheet transition that occurs in wet fibers.

Animals↗
PubMed2001

5-Lipoxygenase interacts with coactosin-like protein.

We have recently identified coactosin-like protein (CLP) in a yeast two-hybrid screen using 5-lipoxygenase (5LO) as a bait. In this report, we demonstrate a direct interaction between 5LO and CLP. 5LO associated with CLP, which was expressed as a glutathione S-transferase fusion protein, in a dose-dependent manner. Coimmunoprecipitation experiments using epitope-tagged 5LO and CLP proteins transiently expressed in human embryonic kidney 293 cells revealed the presence of CLP in 5LO immunoprecipitates. In reciprocal experiments, 5LO was detected in CLP immunoprecipitates. Non-denaturing polyacrylamide gel electrophoresis and cross-linking experiments showed that 5LO binds CLP in a 1:1 molar stoichiometry in a Ca(2+)-independent manner. Site-directed mutagenesis suggested an important role for lysine 131 of CLP in mediating 5LO binding. In view of the ability of CLP to bind 5LO and filamentous actin (F-actin), we determined whether CLP could physically link 5LO to actin filaments. However, no F-actin-CLP.5LO ternary complex was observed. In contrast, 5LO appeared to compete with F-actin for the binding of CLP. Moreover, 5LO was found to interfere with actin polymerization. Our results indicate that the 5LO-CLP and CLP-F-actin interactions are mutually exclusive and suggest a modulatory role for 5LO in actin dynamics.

Actins↗
PubMed2001

Cardiac malignant lymphoma successfully treated with chemotherapy.

We report the case of an 83-year-old woman with diffuse large B-cell lymphoma located in the right cardiac ventricle revealed by acute congestive heart failure. Complete and long-lasting disappearance of the cardiac tumor was observed with monochemotherapy (cyclophosphamide).

Journal Article↗
PubMed2001

Does age play a role in mylohyoideus muscle function?

Because swallowing disorders are frequent in the elderly, we assessed the relationship between age and mylohyoideus muscle contraction, which is an important component of the initial step in swallowing. In a prospective study, 120 subjects without any personal history of diseases associated with swallowing disorders underwent electromyographic recording (EMG) of mylohyoideus muscle activity. Four groups of equal size (n = 30) were defined according to age (< or = 50, 51-70, 71-85, >85 years). The frequency and duration of mylohyoideus muscle asynchronisms were compared among the four groups. The comparison of mylohyoideus muscle EMG among groups did not show a significant difference in the mean number of asynchronisms, in duration per subject or in the frequency of long-lasting asynchronisms. Asynchronisms were a very frequent event, observed in 98% of subjects, and were mostly short, lasting less than 0.1 s in 90% of subjects. In healthy elderly patients, there was no linear relationship between the mean duration of asynchronisms and ageing. The occurrence of one or more long-lasting asynchronisms or of at least six asynchronisms during a sequence of 10 successive swallows should be considered to be abnormal.

Aged↗
PubMed2001

Effects of combination of low doses of angiotensin-converting enzyme inhibitor and diuretics on renal function in spontaneously hypertensive rats: comparison between acute and chronic treatment.

The goal of this study was to assess the effect of acute or chronic treatment with S5590, a combination of the angiotensin-converting enzyme inhibitor perindopril (0.76 mg/kg/day) and the diuretic indapamide (0.24 mg/kg/day) on renal function in spontaneously hypertensive rats with moderate renal injury. Renal function was evaluated in conscious rats by clearance methods using labelled inulin and PAH, after catheterisation of the carotid artery, jugular vein and bladder. Both acute and chronic treatment normalised renal vascular resistance, although the effect on blood pressure was more marked after chronic than after acute treatment. Although acute treatment with S5590 increased glomerular filtration rate and renal blood flow, chronic treatment did not affect these parameters. Diuresis and natriuresis were only slightly modified and the results suggest a marked renal vasodilatation. In conclusion, the maintenance of renal function after chronic treatment, in a setting of normalisation of arterial pressure, suggest that such a combined treatment may exert marked renal functional protective effects in hypertension.

Animals↗
PubMed2000

Aberrant expression of active leukotriene C(4) synthase in CD16(+) neutrophils from patients with chronic myeloid leukemia.

Elevated leukotriene (LT)C(4) synthase activity was observed in peripheral blood granulocyte suspensions from patients with chronic myeloid leukemia (CML). Magnetic cell sorting (MACS) with CD16 monoclonal antibodies (mAbs), which were used to fractionate granulocytes from CML patients and healthy individuals, yielded highly purified suspensions of CD16(+) neutrophils. The purity of these cell fractions was verified by extensive morphologic examination. Reverse transcriptase-polymerase chain reaction (RT-PCR) analyses, demonstrating the absence of interleukin-4 messenger RNA (IL-4 mRNA), further confirmed the negligible contamination of eosinophils in these fractions. Notably, purified CML CD16(+) neutrophils from all tested patients transformed exogenous LTA(4) to LTC(4). These cells also produced LTC(4 )after activation with ionophore A23187 or the chemotactic peptide fMet-LeuPhe (N-formylmethionyl-leucyl-phenylalanine). Subcellular fractionation revealed that the enzyme activity was exclusively distributed to the microsomal fraction. Expression of LTC(4) synthase mRNA in CML CD16(+) neutrophils was confirmed by RT-PCR. Furthermore, Western blot analyses consistently demonstrated expression of LTC(4) synthase at the protein level in CML CD16(+) neutrophils, whereas expression of microsomal glutathione S-transferase 2 occurred occasionally. Expectedly, LTC(4) synthase activity or expression of the protein could not be demonstrated in CD16(+) neutrophil suspensions from any of the healthy individuals. Instead, these cells, as well as CML CD16(+) neutrophils, transformed LTA(4) to LTB(4). The results indicate that aberrant expression of LTC(4) synthase is a regular feature of morphologically mature CML CD16(+) neutrophils. This abnormality, possibly associated with malignant transformation, can lead to increased LTC(4) synthesis in vivo. Such overproduction may be of pathophysiological relevance because LTC(4 )has been demonstrated to stimulate proliferation of human bone marrow-derived myeloid progenitor cells. (Blood. 2000;95:1456-1464)

Antigens, CD↗