Search PubMed⌕ Search

Biomedical subjects

L Picard

Publications and source records attributed to L Picard.

At least 37 records · Page 2Linked to original sources
PubMed2000

[Exploration of visual memory by functional MRI].

PURPOSE: The aim of our study was to evidence the location of the cortical area triggered by visual memory tasks by he mean of functional magnetic resonance imaging examination (fMRI). METHODS: Twelve healthy volunteers underwent fMRI examination on a 1.5 Tesla magnet with echoplanar imaging sequence during figurative and non-figurative memory tasks. An area was considered to be activated if at least 10 contiguous voxels activation was noted. Activated areas were defined for both tasks and the brain mapping was realized according to Talairach atlas. RESULTS: For all examinations a bilateral activity was evidenced (area 17 and 18). In addition, a frontal activation was also noted in 83% of the cases for both tasks. However, frontal activation was bilateral in 9/10 cases for the figurative task and 6/10 cases for the non-figurative task. CONCLUSION: FMRI was able to evidence activation of cerebral areas during visual memory tasks in all our study cases. Frontal activation was not discriminative of figurative or non figurative memory. This might be probably explain by inappropriate non-figurative tests. FMRI should allow a better knowledge of memory mechanisms as well as an enhancement of functional cerebral mapping before surgery.

Adult↗
PubMed2000

Palliative care on Manitoulin Island. Views of family caregivers in remote communities.

OBJECTIVE: To describe family caregivers' experiences with palliative care services in rural communities. DESIGN: Qualitative study. SETTING: Manitoulin Island, Ont. PARTICIPANTS: Thirteen family caregivers of 12 deceased patients who had received palliative care services. METHOD: Twenty-five family caregivers were recruited by mail and local newspaper. Eight were excluded because they lived off the Island or were too recently bereaved; one declined an interview; and three were excluded by researchers. Initial contact was by telephone; those retained (13 people) were interviewed at home. Interviews were conducted by the same researcher using a semistructured interview guide. All interviews were audiotaped and transcribed, and content was analyzed. MAIN FINDINGS: Three interwoven themes were identified: access to services, quality of services, and support and caring. Hospital and community-based services were accessed with ease at the local level; difficulties were noted when accessing services in tertiary care centres. Participants were generally grateful for and pleased with services received. Two areas of concern raised by participants were communication and pain and symptom control. Participants suggested to the Ministry of Health ways to improve rural palliative care services. More public funding for in-home palliative care services was identified as a priority. CONCLUSION: Participants thought good services and supportive care at the local level made up for difficulties in accessing and using palliative services in tertiary care centres. Community spirit and culture were seen as making situations more bearable.

Aged↗
PubMed2000

[Radioanatomy of the cerebral cortex. Practical guide of identification].

Cerebral sulci identification process is based on several formal rules: it consists a series of steps allowing the identification of the major sulci. The process may be variable for each of us and we propose to read the images in certain order starting with the frontal lobe and its superior frontal gyrus than precentral and central gyri followed by the lateral fissure. Then the insular, lateral parietal and medial hemispheric regions. Finally the major sulci within the temporal and occipital lobes are described in the frontal plane. This presentation indicates the principal rules of cerebral lobes'identification, the basis of variability perception and the localization of small lesions allowing an accurate correlation with clinical findings and a suitable therapeutic procedure.

Cerebral Cortex↗
PubMed1999

Regulation of cerebellar Ins(1,4,5)P3 receptor by interaction between Ins(1,4,5)P3 and Ca2+.

We have characterized in detail the Ca(2+)-dependent inhibition of [(3)H]Ins(1,4,5)P(3) ([(3)H]InsP(3)) binding to sheep cerebellar microsomes, over a short duration (3 s), with the use of a perfusion protocol. This procedure prevented artifacts previously identified in studies of this Ca(2+) effect. In a cytosol-like medium at pH 7.1 and 20 degrees C, a maximal inhibition of approx. 50% was measured. Both inhibition and its reversal were complete within 3 s. Ca(2+) decreased the affinity of the receptor for InsP(3) by approx. 50% (K(d) 146+/-24 nM at pCa 9 and 321+/-56 nM at pCa 5.3), without changing the total number of binding sites. Conversely, increasing the [(3)H]InsP(3) concentration from 30 to 400 nM tripled the IC(50) for Ca(2+) and decreased the maximal inhibition by 63%. This is similar to a partial competitive inhibition between InsP(3) binding and inhibitory Ca(2+) binding and is consistent with InsP(3) and Ca(2+) converting InsP(3) receptor into two different states with different affinities for these ligands. Mn(2+) and Sr(2+) also inhibited [(3)H]InsP(3) binding but were respectively only 1/10 and 1/200 as effective as Ca(2+). No inhibition was observed with Ba(2+). This selectivity is the same as that previously reported for the inhibitory Ca(2+) site of InsP(3)-induced Ca(2+) flux, suggesting that the same site is used by Ca(2+) to convert cerebellar InsP(3) receptor to a low-affinity state and to inhibit its channel activity. Our results also suggest a mechanism by which InsP(3) counteracts this Ca(2+)-dependent inhibition.

Amino Acid Sequence↗
PubMed1999

The time interval between FSH administration and ovarian aspiration influences the development of cattle oocytes.

Depriving the ovary of exogenous FSH for 1, 2 or 3 d following a bolus injection of FSH was shown to influence the quality of the recovered oocytes. Thus, we compared the developmental competence of oocytes from heifers which had been stimulated for 3 d with FSH (Folltropin-V) and, after an interval of 36, 48 or 60 h, underwent blind transvaginal aspiration. The ovaries of heifers with a palpable or functional corpus luteum were aspirated to remove all large follicles 2 d prior to being injected with either 6 doses of saline (S), 6 doses (20 mg/mL) of FSH (F), or in 6 decreasing doses of FSH (3, 3, 2, 2, 1, 1 mL; Fd). Follicles were counted and classified (medium: 5 to 10 mm, large: >10 mm) with ultrasonography before each aspiration. The oocytes recovered were classified, matured, fertilized, and developed in vitro. On a per animal basis, 1.5, 5.2 and 4.7 large and 1.5, 10.7 and 10.7 medium follicles were counted for S, F and Fd, respectively. A mean of 3.3, 9.1 and 7.7 oocytes was recovered for treatments S, F and Fd, respectively and 58, 94 and 82% were enclosed in a nonexpanded cumulus or a corona layer. Oocyte development rates were based on counts of embryos with 32 or more nuclei at Day 6.5. When oocytes were recovered 36 h after the last injection, an average of 1, 2.7 and 2 embryos per animal was obtained with S, F and Fd, respectively; at 48 h, 0.75, 4.25 and 1 embryo; and at 60 h, 0, 2.5 and 2.7 embryos. Variance analysis was performed, and the protected LSD test indicated that treatment F at 48 h resulted in a significantly higher embryo rate than Fd at 48 h (P<0.05) or S (all times; P<0.05). The reduced effect of the Fd regimen could be due to the decreasing FSH support during follicular growth or to the lower total amount of FSH given. In conclusion, these results indicate an advantage of using moderate (3 d) follicle stimulation followed by a period of FSH starvation to obtain optimal embryo production.

Animals↗
PubMed1999

Total chemical synthesis and high-resolution crystal structure of the potent anti-HIV protein AOP-RANTES.

BACKGROUND: RANTES is a CC-type chemokine protein that acts as a chemoattractant for several kinds of leukocytes, playing an important pro-inflammatory role. Entry of human immunodeficiency virus-1 (HIV-1) into cells depends on the chemokine receptor CCR5. RANTES binds CCR5 and inhibits HIV-1 entry into peripheral blood cells. Interaction with chemokine receptors involves a distinct set of residues at the amino terminus of RANTES. This finding was utilized in the development of a chemically modified aminooxypentane derivative of RANTES, AOP-RANTES, that was originally produced from the recombinant protein using semisynthetic methods. RESULTS: AOP-RANTES has been produced by a novel total chemical synthesis that provides efficient, direct access to large amounts of this anti-HIV protein analog. The crystal structure of chemically synthesized AOP-RANTES has been solved and refined at 1.6 A resolution. The protein is a dimer, with the amino-terminal pentane oxime moiety clearly defined. CONCLUSIONS: Total chemical synthesis of AOP-RANTES provides a convenient method of producing the multi-milligram quantities of this protein needed to investigate the molecular basis of receptor binding and antiviral activity. This work provides the first truly high-resolution structure of a RANTES protein, although the structure of RANTES was known from previous nuclear magnetic resonance (NMR) determinations.

Amino Acid Sequence↗
PubMed1999

Highly potent RANTES analogues either prevent CCR5-using human immunodeficiency virus type 1 infection in vivo or rapidly select for CXCR4-using variants.

The natural ligands for the CCR5 chemokine receptor, macrophage inflammatory protein 1alpha (MIP-1alpha), MIP-1beta, and RANTES (regulated on T-cell activation, normal T-cell expressed and secreted), are known to inhibit human immunodeficiency virus (HIV) entry, and N-terminally modified RANTES analogues are more potent than native RANTES in blocking infection. However, potent CCR5 blocking agents may select for HIV-1 variants that use alternative coreceptors at less than fully inhibitory concentrations. In this study, two N-terminal chemical modifications of RANTES produced by total synthesis, aminooxypentane (AOP)-RANTES[2-68] and N-nonanoyl (NNY)-RANTES[2-68], were tested for their ability to prevent HIV-1 infection and to select for coreceptor switch variants in the human peripheral blood lymphocyte-SCID mouse model. Mice were infected with a CCR5-using HIV-1 isolate that requires only one or two amino acid substitutions to use CXCR4 as a coreceptor. Even though it achieved lower circulating concentrations than AOP-RANTES (75 to 96 pM as opposed to 460 pM under our experimental conditions), NNY-RANTES was more effective in preventing HIV-1 infection. However, in a subset of treated mice, these levels of NNY-RANTES rapidly selected viruses with mutations in the V3 loop of envelope that altered coreceptor usage. These results reinforce the case for using agents that block all significant HIV-1 coreceptors for effective therapy.

Amino Acid Sequence↗
PubMed1999

Multivariate analysis of predictors of cerebral vasospasm occurrence after aneurysmal subarachnoid hemorrhage.

BACKGROUND AND PURPOSE: The role of type of treatment on cerebral vasospasm occurrence after aneurysmal subarachnoid hemorrhage (SAH) has not been studied. Through multivariate analysis we determined the independent prognostic factors of the occurrence of symptomatic vasospasm following aneurysmal SAH in a study cohort of 244 patients undergoing either surgical or endovascular treatment. The prognostic factors of sequelae after aneurysmal SAH were studied as well. METHODS: Symptomatic vasospasm was defined as the association of deterioration in a patient's neurological condition between 3 and 14 days after SAH with no other explanation and an increase in mean transcranial Doppler velocities of >120 cm/s. The prognostic factors were registered on admission and during the intensive care stay. RESULTS: Symptomatic vasospasm occurred in 22.2% surgical patients compared with 17.2% endovascular treatment patients (P=0.37). Multivariate analysis revealed that the probability of occurrence of symptomatic vasospasm decreased with age >50 years (relative risk [RR], 0.47 [0.25 to 0.88]) and severe World Federation of Neurological Surgeons (WFNS) grade measured on admission (RR, 0.43 [0.20 to 0.90]) and increased with hyperglycemia occurring during the intensive care stay (RR, 1.94 [1.04 to 3.63]). No difference in risk of symptomatic vasospasm could be identified between surgical and endovascular treatment. Symptomatic vasospasm (OR, 4.73 [CI, 1. 77 to 12.6]) as well as WFNS grade of >2 (OR, 8.95 [3.46 to 23.2]), treatment complications (OR, 8.39 [3.16 to 22.3]), and secondary brain insults were associated with an increased risk of 6-month sequelae. CONCLUSIONS: Age <50 years, good neurological grade, and hyperglycemia were all associated with an increased risk of cerebral vasospasm whereas treatment was not. This provides a basis for future clinical prospective randomized trials comparing both treatments.

Adult↗
PubMed1999

[Endovascular treatment of vasospasm].

Cerebral vasospasm remains a leading cause of heightened morbidity and mortality rates following aneurysmal subarachnoid hemorrhage despite the apparent benefit of recent medical therapeutics. Successful resolution of medically refractory angiographically demonstrated vasospasm with concomitant reversal of delayed neurological deficit has been observed after balloon angioplasty. Subsequent reports confirmed these encouraging results but also emphasized the limitations of the technique and the risks of complications. Intraarterial papaverine infusion has been performed for the treatment of diffuse cerebral vasospasm with controversial results and has also been combined with angioplasty either to facilitate balloon navigation or to treat arteries inaccessible to balloon catheterization. All these different endovascular approaches explain the confusion existing about the indications, timing and efficacy of the endovascular treatments. This article reviews several clinical and experimental studies dealing with these questions.

Angioplasty, Balloon↗
PubMed1999

[Diffusion imaging in asymptomatic focal vasospasm. Apropos of a case].

We report a case of an asymptomatic vasospasm with a focal, reversible apparent diffusion coefficient (ADC) decrease after a middle cerebral artery aneurysm rupture. This isolated decrease of ADC has not yet been reported in this pathological situation. It could be interesting to predict the risk of ischemic delayed complications of vasospasm.

Adult↗
PubMed1998

Multiple mechanisms of regulation of the inositol 1,4,5-trisphosphate receptor by calcium.

Ca2+ mobilisation by inositol 1,4,5-trisphosphate (InsP3) is a complex phenomenon which involves positive and negative feedback regulation by cytosolic Ca2+. It has been shown that Ca2+ increased the affinity of [3H]-InsP3 binding to liver membranes and inhibited [3H]-InsP3 binding to cerebellar membranes. We investigated the effects of Ca2+ on the [3H]-InsP3 binding to receptor solubilised and rapidly purified by immunoprecipitation. The InsP3 binding to the purified liver receptor was insensitive to the addition of Ca2+, indicating that Ca2+ did not interact directly with the receptor. The loss of the Ca2+ effect on liver receptor affinity was reproduced by alkaline treatment of liver membranes, which is known to extract the peripheral membrane proteins. This suggests that Ca2+ regulates the liver InsP3 receptor by interacting with a membrane-associated protein. Ca2+ inhibited the binding of [3H]-InsP3 to purified cerebellar receptors as was found with the membrane fraction. The treatment of the purified cerebellar receptor with media of high ionic strength or at alkaline pH did not abolish the effect of Ca2+ on the receptor. This indicates that the inhibitory effect of Ca2+ on [3H]-InsP3 binding to cerebellar membranes occurs either via direct interaction with the receptor or via an integral protein strongly associated with the receptor. In conclusion, the mechanisms of regulation of InsP3-induced Ca2+ release by Ca2+ involve different molecular support in cerebellum and in liver. This may reflect different regulation dependent on the receptor type.

Amino Acid Sequence↗
PubMed1998

The second extracellular loop of CXCR4 is involved in CD4-independent entry of human immunodeficiency virus type 2.

Human immunodeficiency virus type 2 (HIV-2) strains that infect cells in the absence of cellular CD4 emerge spontaneously in vitro after culture in CD4+ T-cell lines. The HIV-2ROD/B strain can use the CXCR4 chemokine receptor for efficient entry into CD4+ cells. Here we have shown that the rat homologue of CXCR4, in the absence of CD4, failed to mediate CD4-independent entry by ROD/B. Furthermore, using rat-human chimeric CXCR4 receptors we have demonstrated that the second extracellular loop (E2) of human CXCR4 is critical for HIV-2 infection of CD4+ cells. E2 is also important for HIV-1 infection of CD4+ cells. Our results therefore indicate that the role of E2 in HIV entry is conserved for HIV-1 and HIV-2 and for infection in the presence or absence of CD4.

Animals↗
PubMed1998

The second extracellular loop of CXCR4 determines its function as a receptor for feline immunodeficiency virus.

The feline homolog of the alpha-chemokine receptor CXCR4 has recently been shown to support cell-cell fusion mediated by CXCR4-dependent strains of human immunodeficiency virus (HIV) and strains of feline immunodeficiency virus (FIV) that have been selected for growth in the Crandell feline kidney (CrFK) cell line. In this report we demonstrate that expression of CXCR4 alone is sufficient to render cells from diverse species permissive for fusion with FIV-infected cells, suggesting that CXCR4 is the sole receptor for CrFK-tropic strains of FIV, analogous to CD4-independent strains of HIV-2. To identify the regions of CXCR4 involved in fusion mediated by FIV, we screened panels of chimeric CXCR4 molecules for the ability to support fusion with FIV-infected cells. Human CXCR4 supported fusion more efficiently than feline CXCR4 and feline/human CXCR4 chimeras, suggesting that the second and third extracellular loops of human CXCR4 contain a critical determinant for receptor function. Rat/human CXCR4 chimeras suggested that the second extracellular loop contained the principal determinant for receptor function; however, chimeras constructed between human CXCR2 and CXCR4 revealed that the first and third loops of CXCR4 contribute to the FIV Env binding site, as replacement of these domains with the corresponding domains of CXCR2 rendered the molecule nonfunctional in fusion assays. Mutation of the DRY motif and the C-terminal cytoplasmic tail of CXCR4 did not affect the ability of the molecule to support fusion, suggesting that neither signalling via G proteins nor receptor internalization was required for fusion mediated by FIV; similarly, truncation of the N terminus of CXCR4 did not affect the function of the molecule as a receptor for FIV. CXCR4-transfected feline cells were rendered permissive for infection with both the CrFK-tropic PET isolate of FIV and the CXCR4-dependent RF strain of HIV-1, and susceptibility to infection correlated well with ability to support fusion. The data suggest that the second extracellular loop of CXCR4 is the major determinant of CXCR4 usage by FIV.

3T3 Cells↗
PubMed1998

3D angiography. Clinical interest. First applications in interventional neuroradiology.

3D angiography is a true technical revolution that allows improvement in the quality and safety of diagnostic and endovascular treatment procedures. 3D angiography images are obtained by reconstruction of a rotational angiography acquisition done on a C-arm (GE Medical Systems) spinning at 40 degrees per second. The carotid or vertebral selective injection of a total of 15 ml of non-ionic contrast media at 3 ml/sec over 5 seconds allows the selection of the "arterial phase". Four hundred sixty 3D angiographic studies were performed from December 1996 to September 1998 on 260 patients and have been analyzed in MIP (Maximum Intensity Projection) and SSD (Shaded Surface Display) views. The exploration of intracranial aneurysms is simplified and only requires, for each vascular axis, a biplane PA and Lateral run followed by a single rotational angiography run. The 3D angiography image is available on the workstation's screen (Advantage Workstation 3.1, GE Medical Systems) in less than 10 minutes after the acquisition of the rotational run. It therefore allows one to analyze, during the intervention, the aneurysm's angioarchitecture, in particular the neck, and select the best therapeutic technique. When endovascular treatment is the best indication, 3D angiography allows one to define the optimal angle of view and accurately select the microcoils dimensions. 3D angiography replaces the multiple oblique views that used to be required to analyze the complex aneurysms and therefore allows a reduction of the total contrast medium quantity, the patient X-ray dose and the length of the intervention time which is a safety factor. Also, in particular for complex cases, it brings additional elements complementing the results of standard 2D DSA and rotational angiograms. In the cervical vascular pathology, 3D angiography allows for a better assessment of the stenosis level and of dissection lesions. Our current research activities focus on the matching without stereotactic frame between 3D X-ray angiography and volumetric MR acquisition, which should allow us to improve the treatment of intracerebral arterio-venous malformations (AVMs).

Aortic Dissection↗
PubMed1998

[MRI aspects of spinal cord abscesses. Report of 5 cases and review of the literature].

The spinal canal is an uncommon site for abscess formation resulting from bloodstream disseminated infection. Prognosis is often unfavorable. Rapid treatment is essential for satisfactory neurological recovery. Abscesses within the spinal canal are thus diagnostic and therapeutic emergencies. The neuro-infectious and inflammatory manifestations and laboratory findings vary considerably and are insufficient for diagnosis. MRI plays a decisive role. The most commonly reported signs are the presence of an intramedullary collection giving a low-intensity signal on T1-weighted images and a high-intensity signal on T2-weighted images with peripheral contrast uptake and generally extended adjacent medullary edema. We report here five cases of spinal canal abscesses diagnoses with MRI at different stages of development (pre-suppurative myelitis in two cases, constituted abscess in three cases). For each case we reviewed the clinical course and describe the details of the imaging findings. In our series, the collected abscesses presented as round lesions within the canal with contrast uptake. It is noteworthy that the periependymal gray matter adjacent to the lesion also took up the contrast agent in all patients with a collected abscess. This sign has not been described previously and appears to be a going argument orienting the diagnosis towards an infectious rather than tumoral formation.

Abscess↗
PubMed1997

Role of the amino-terminal extracellular domain of CXCR-4 in human immunodeficiency virus type 1 entry.

We have studied the role of the N-terminal extracellular domain of the human immunodeficiency virus type 1 (HIV-1) coreceptor, CXCR-4, in the entry and fusion of syncytium-inducing strains of HIV-1. Progressive deletions were introduced in the N-terminal extracellular domain of CXCR-4 and the effect on infection by different isolates was tested. Infection of cells expressing the different CXCR-4 deletion mutants by HIV-1 LAI and 89.6 was reduced only about twofold. In contrast, the HIV-1 GUN-1 and RF isolates were substantially more impaired in their ability to mediate cell-free infection and cell-cell fusion. Since LAI and RF are T-cell line-tropic viruses while 89.6 and GUN-1 are dual tropic, no clear correlation between tropism and requirements for CXCR-4 N-terminal sequences emerged. We also introduced point mutations at the two N-linked glycosylation sites. The isolates tested (LAI, RF, GUN-1, and 89.6) were not affected by the removal of predicted N-linked glycosylation sites in CXCR-4. We conclude that distinct virus strains interact differently with the CXCR-4 coreceptor and that the N-terminal extracellular domain is not the sole functional domain important for HIV-1 entry.

Amino Acid Sequence↗
PubMed1997

Potent inhibition of HIV-1 infectivity in macrophages and lymphocytes by a novel CCR5 antagonist.

The chemokine receptors CXCR4 and CCR5 have recently been shown to act as coreceptors, in concert with CD4, for human immunodeficiency virus-type 1 (HIV-1) infection. RANTES and other chemokines that interact with CCR5 and block infection of peripheral blood mononuclear cell cultures inhibit infection of primary macrophages inefficiently at best. If used to treat HIV-1-infected individuals, these chemokines could fail to influence HIV replication in nonlymphocyte compartments while promoting unwanted inflammatory side effects. A derivative of RANTES that was created by chemical modification of the amino terminus, aminooxypentane (AOP)-RANTES, did not induce chemotaxis and was a subnanomolar antagonist of CCR5 function in monocytes. It potently inhibited infection of diverse cell types (including macrophages and lymphocytes) by nonsyncytium-inducing, macrophage-tropic HIV-1 strains. Thus, activation of cells by chemokines is not a prerequisite for the inhibition of viral uptake and replication. Chemokine receptor antagonists like AOP-RANTES that achieve full receptor occupancy at nanomolar concentrations are strong candidates for the therapy of HIV-1-infected individuals.

Animals↗