Search PubMed⌕ Search

Biomedical subjects

S Paris

Publications and source records attributed to S Paris.

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

Disconjugate vertical memory-guided saccades to disparate targets.

We studied the binocular coordination of normal memory-guided saccades and the possibility of inducing memory-based disconjugate learning. First, we report that normal vertical memory-guided saccades to non-disparate targets are yoked vertically in the two eyes as well as visually guided vertical saccades. To induce disconjugate vertical learning, at each trial we flashed a target that was disparate (i.e. 8% more elevated or more depressed for one eye); the memory delay was 1 s. Memory-guided vertical saccades developed a vertical disconjugacy that was appropriate for the disparity of the remembered target. After 15 min of repetition, this vertical disconjugacy persisted even when the target to be remembered was no longer disparate; this indicates disconjugate vertical learning based on short-term memory. However, this was observed only for a few individual cases and its amplitude was small. This contrasts with prior findings on horizontal saccades associated with horizontal disparities. We conclude that vertical memory-based disconjugate learning is possible but very limited. Together with other studies, this study suggests that the natural vertical conjugacy of vertical saccades relies little on rapid learning mechanisms. Rather it seems to be built-in, and this is consistent with earlier electrophysiological findings.

Convergence, Ocular↗
PubMed2000

MR imaging of septic sacroiliitis.

OBJECTIVE: To investigate the diagnostic value of magnetic resonance (MR) imaging in detecting septic sacroiliitis and to determine whether the MR characteristics allow this entity to be differentiated from sacroiliitis in spondylarthropathy (SpA). PATIENTS AND DESIGN: The imaging findings of 11 patients with septic sacroiliitis were retrospectively analyzed by two experienced radiologists. Radiographic surveys of the pelvis as well as computed tomography (CT) and MR images of the sacroiliac joints were available in all cases. Seven of the patients additionally underwent a follow-up MR examination. The MR imaging protocol comprised combinations of coronal and transverse T1-weighted spin-echo (SE) or fast SE sequences, T2-weighted gradient-echo (GE) sequences and short tau inversion recovery sequence (STIR) sequences as well as dynamic contrast-enhanced T1-weighted acquisitions. RESULTS: Three patients with a short disease history showed anterior and/or posterior subperiosteal infiltrations ("lava cleft phenomenon"), transcapsular infiltrations of juxtaarticular muscle layers, which obscured the fasciae, and periarticular bone marrow edema. The eight patients with more advanced stages of sacroiliitis additionally showed abscess formation, sequestration, and erosion. At follow-up MR examination (n=7) under systemic antibiotic treatment, the morphologic characteristics showed progression (n=1), regression (n=4), unchanged findings (n=1), or a mixed response (n=1). Clinical improvement precedes resolution of the MR findings. CONCLUSIONS: Anterior and/or posterior subperiosteal infiltrations and transcapsular infiltrations of juxtaarticular muscle layers were depicted in all patients. These MR imaging findings are characteristic of septic sacroiliitis and may be used to differentiate this entity from sacroiliitis in SpA.

Adolescent↗
PubMed2000

p95-APP1 links membrane transport to Rac-mediated reorganization of actin.

Motility requires protrusive activity at the cellular edge, where Rho family members regulate actin dynamics. Here we show that p95-APP1 (ArfGAP-putative, Pix-interacting, paxillin-interacting protein 1), a member of the GIT1/PKL family, is part of a complex that interacts with Rac. Wild-type and truncated p95-APP1 induce actin-rich protrusions mediated by Rac and ADP-ribosylation factor 6 (Arf6). Distinct p95-APP1-derived polypeptides have different distributions, indicating that p95-APP1 cycles between the cell surface and endosomes. Our results show that p95-APP1 functionally interacts with Rac and localizes to endosomal compartments, thus identifying p95-APP1 as a molecular link between actin organization, adhesion, and membrane transport during cell motility.

ADP-Ribosylation Factor 6↗
PubMed1999

Dual interaction of ADP ribosylation factor 1 with Sec7 domain and with lipid membranes during catalysis of guanine nucleotide exchange.

Sec7 domains catalyze the replacement of GDP by GTP on the G protein ADP-ribosylation factor 1 (myrARF1) by interacting with its switch I and II regions and by destabilizing, through a glutamic finger, the beta-phosphate of the bound GDP. The myristoylated N-terminal helix that allows myrARF1 to interact with membrane lipids in a GTP-dependent manner is located some distance from the Sec7 domain-binding region. However, these two regions are connected. Measuring the binding to liposomes of functional or abortive complexes between myrARF1 and the Sec7 domain of ARNO demonstrates that myrARF1, in complex with the Sec7 domain, adopts a high affinity state for membrane lipids, similar to that of the free GTP-bound form. This tight membrane attachment does not depend on the release of GDP induced by the Sec7 domain but is partially inhibited by the uncompetitive inhibitor brefeldin A. These results suggest that the conformational switch of the N-terminal helix of myrARF1 to the membrane-bound form is an early event in the nucleotide exchange pathway and is a prerequisite for a structural rearrangement at the myrARF1-GDP/Sec7 domain interface that allows the glutamic finger to expel GDP from myrARF1.

ADP-Ribosylation Factor 1↗
PubMed1999

Coordinated polar localization of auxin efflux carrier PIN1 by GNOM ARF GEF.

The plant hormone auxin is transported in a polar manner along the shoot-root axis, which requires efflux carriers such as PIN1. Asymmetric localization of PIN1 develops from a random distribution in Arabidopsis early embryogenesis. Coordinated polar localization of PIN1 is defective in gnom embryos. GNOM is a membrane-associated guanine-nucleotide exchange factor on ADP-ribosylation factor G protein (ARF GEF). Thus, GNOM-dependent vesicle trafficking may establish cell polarity, resulting in polar auxin transport.

ADP-Ribosylation Factors↗
PubMed1999

Histopathology of experimental invasive pulmonary aspergillosis in rats: pathological comparison of pulmonary lesions induced by specific virulent factor deficient mutants.

To investigate the pathology of invasive pulmonary aspergillosis (IPA) in detail, a new animal model of IPA was used to compare the histological features induced by three different strains of Aspergillus fumigatus; mutants devoided of exocellular protease and rodlet and their parental strain. To produce an experimental pulmonary lesion of IPA closely mimicking the human disease, suspension of agarose beads containing conidiae of A. fumigatus were used as an inocula to fix infallibly the causative agents in alveoli and rats were treated with a low-dose of immunosuppressive drugs to avoid an induction of agranulocytosis in rodents. There was no significant difference in the mortality of mice with an intravenous injection between these three strains. However, IPA model in the study was successful to demonstrate a significant difference in the histological feature of lungs of infected rats. Pulmonary lesions on the fifth day after infection induced by the rodletless mutant were limited and inflammatory responses were weak when compared to those induced by both no exocellular protease mutant as well as their parental strain. The evidence of rodlet layer in conidia of Aspergilli may play an important role in the physiopathology of the disease in eliminating the neutrophils and macrophages of hosts on the early stage of the infection.

Animals↗
PubMed1999

A model of spontaneous lung metastases visualised in fresh host tissue by green fluorescent protein expression.

The authors describe a model of spontaneous lung metastases in nude mice using green fluorescent protein (GFP) expression as a marker. The human lung cell line H460M was transfected with the humanised GFP-S65T cDNA and a stable fluorescent cell line termed H460M(GFP) was obtained. The latter kept in vitro biological features when compared to the parental H460M cell line, which suggests that GFP-expression does not influence H460M(GFP) cell line behaviour. In order to evaluate their metastatic potential and to determine the number of spontaneous metastases, H460M(GFP) cells were subcutaneously inoculated into nude mice. Animals were sacrificed at time intervals and tissues (lung, liver, spleen, node, and kidney) were analysed under fluorescence microscopy. These experiments demonstrated that 2 weeks after subcutaneous inoculation, 75% of animals exhibited fluorescent spontaneous lung micrometastases. From the third week, 100% of animals exhibited an increasing number of metastases (10-16) which were only localised in the lungs. At the end of the study, the number of lung metastases had dramatically increased (42-400 at 7 weeks). Although these metastases were mainly localised in lung, a few mice had an invasion of neighbouring lymph nodes. The H460M(GFP) cell line allowed to follow the seeding and development of spontaneous lung metastases and may be considered a simple and powerful tool to study each step of the metastasis to screen new anticancer drugs.

Animals↗
PubMed1999

Assembly and secretion of recombinant chains of human inter-alpha-trypsin inhibitor in COS-7 cells.

The inter-alpha-trypsin inhibitor (ITI) family is a group of structurally related plasma serine protease inhibitors. The ITI family members consist of combinations of mature heavy chains named HC1, HC2, HC3 linked to bikunin (a Kunitz-type protease inhibitor) by a covalent interchain protein-glycosaminoglycan-protein cross-link. The biosynthesis of the ITI family members takes place in the liver. In this report we examine the biosynthesis of these proteins using transient transfected COS-7 cells expressing one or more combinations of human ITI chains. The processing and secretion of alpha1-microglobulin and bikunin does not require the ITI heavy chains. A small proportion of the H3 chain seems to be processed into the HC3 form in the absence of the other ITI chains. In contrast, the processing of H2 into HC2 needs the presence of the L chain. The COS-7 cells are able to link the HC2 and HC3 heavy chains with bikunin by means of a chondroitin sulfate bridge, and thus to generate 260-kDa ITI-like proteins as well as pre-alpha-trypsin inhibitor (PalphaI). However, the maturation of the Hl chain into HC1 and the assembly of HC1 inside multichain proteins may take place according to a mechanism which differs from that of the H2 and H3 chains. These results indicate that the assembly of the constituent chains of the ITI-like proteins and PalphaI is not dependent on the liver machinery.

Alpha-Globulins↗
PubMed1999

The role of the rodlet structure on the physicochemical properties of Aspergillus conidia.

Physico-chemical properties of Aspergillus conidia rely on their outer cell-wall rodlet layer. In A. fumigatus and A. nidulans, the rodlet structure is due to an hydrophobin encoded by homologous rodA genes. To evaluate the role of the rodlet structure on the physico-chemical properties of conidia, we compared hydrophobicity, Lewis acid-base (i.e. electron donor/acceptor) characteristics and electrostatic charge of hydrophobin-less (rodletless) mutant and wild-type conidia of A. fumigatus and A. nidulans. The results obtained by aqueous-solvent partitioning assays, microsphere adhesion assays and microelectrophoresis showed that the disruption of the rodA gene modifies surface properties of A. fumigatus and A. nidulans conidia, and confirmed that the rodlet layer plays a key role in their physico-chemical behaviour. The absence of this layer on A. fumigatus spores led to the appearance of weakly basic and acidic characteristics, and had a slight effect on the hydrophobicity of conidia. Whereas in A. nidulans, it induced a basic character, a marked decrease in hydrophobicity and in the polarization capacity (electronegativity) of conidia. These physico-chemical differences between A. fumigatus and A. nidulans rodletless conidia may be attributed to differences in the composition of the conidial outer cell-wall of the two species.

Aspergillus fumigatus↗
PubMed1999

Unrecognized pattern of von Willebrand factor abnormalities in hemolytic uremic syndrome and thrombotic thrombocytopenic purpura.

Heterogeneous abnormalities in multimeric structure and fragmentation of endothelial-derived von Willebrand factor (vWF) have been reported in hemolytic uremic syndrome (HUS) and thrombotic thrombocytopenic purpura (TTP). This study was conducted to establish whether different patterns of vWF abnormalities were associated with different clinical syndromes. Plasmatic levels of vWF antigen (vWF:Ag), vWF release from endothelial cells (EC) exposed to patient sera, and vWF multimeric pattern were studied during episodes and again in remission in three groups of patients with severe forms of HUS and TTP paradigmatic of the most common clinical patterns of disease presentation: (1) plasma-responsive; (2) plasma-resistant; and (3) frequently relapsing. Plasma vWF:Ag and serum-induced vWF release from EC were increased in the acute phase of either plasma-responsive and plasma-resistant HUS and TTP, but normalized at remission only in plasma-responsive cases. Both indices were persistently normal in the relapsing forms. Enhanced vWF fragmentation as defined by disappearance of high molecular weight and increase in low molecular weight forms was a consistent finding of the acute phases, and always normalized in remission in all three groups. Unusually large vWF multimers were found exclusively in plasma of relapsing forms of HUS and TTP both during and between relapses. Enhanced levels of vWF:Ag and serum capability to induce vWF release in vitro are markers of disease activity and may reflect systemic endothelial injury and consequent activation. Their presence discriminates acute single-episode cases from relapsing forms and, when failing to normalize with plasma therapy, predicts plasma resistance. Enhanced low molecular weight multimers that closely paralleled disease activity suggest a permissive role of fragmented vWF in the formation of microvascular thrombi. Finally, finding of unusually large multimers exclusively in relapsing forms of HUS and TTP even between relapses, when no other clinical signs of disease activity could be detected, suggests that they cannot be the only factor in microvascular thrombosis.

Adolescent↗
PubMed1999

[Interventional radiology--an option in minimally invasive therapy].

Percutan transluminal angioplasty (incl. implantation of stents) in the region of pelvic arteries and renal arteries, ct-guided facet joint injections/epidural injections and ct-guided block of lumbar sympathetic chain are some examples for the possibilities of interventional radiology as minimal invasive therapy. Indications, technique, clinical correlation, results and complications are described and discussed.

Angioplasty, Balloon, Coronary↗
PubMed1998

Overexpression of a neural-specific rho family GTPase, cRac1B, selectively induces enhanced neuritogenesis and neurite branching in primary neurons.

Rho family GTPases have been implicated in cytoskeletal reorganization during neuritogenesis. We have recently identified a new gene of this family, cRac1B, specifically expressed in the chicken developing nervous system. This GTPase was overexpressed in primary neurons to study the role of cRac1B in the development of the neuronal phenotype. Overexpression of cRac1B induced an increment in the number of neurites per neuron, and dramatically increased neurite branching, whereas overexpression of the highly related and ubiquitous cRac1A GTPase did not evidently affect neuronal morphology. Furthermore, expression of an inactive form of cRac1B strikingly inhibited neurite formation. The specificity of cRac1B action observed in neurons was not observed in fibroblasts, where both GTPases produced similar effects on cell morphology and actin organization, indicating the existence of a cell type-dependent specificity of cRac1B function. Molecular dissection of cRac1B function by analysis of the effects of chimeric cRac1A/cRac1B proteins showed that the COOH-terminal portion of cRac1B is essential to induce increased neuritogenesis and neurite branching. Considering the distinctive regulation of cRac1B expression during neural development, our data strongly support an important role of cRac1B during neuritogenesis, and they uncover new mechanisms underlying the functional specificity of distinct Rho family GTPases.

Actins↗
PubMed1998

A glutamic finger in the guanine nucleotide exchange factor ARNO displaces Mg2+ and the beta-phosphate to destabilize GDP on ARF1.

The Sec7 domain of the guanine nucleotide exchange factor ARNO (ARNO-Sec7) is responsible for the exchange activity on the small GTP-binding protein ARF1. ARNO-Sec7 forms a stable complex with the nucleotide-free form of [Delta17]ARF1, a soluble truncated form of ARF1. The crystal structure of ARNO-Sec7 has been solved recently, and a site-directed mutagenesis approach identified a hydrophobic groove and an adjacent hydrophilic loop as the ARF1-binding site. We show that Glu156 in the hydrophilic loop of ARNO-Sec7 is involved in the destabilization of Mg2+ and GDP from ARF1. The conservative mutation E156D and the charge reversal mutation E156K reduce the exchange activity of ARNO-Sec7 by several orders of magnitude. Moreover, [E156K]ARNO-Sec7 forms a complex with the Mg2+-free form of [Delta17]ARF1-GDP without inducing the release of GDP. Other mutations in ARNO-Sec7 and in [Delta17]ARF1 suggest that prominent hydrophobic residues of the switch I region of ARF1 insert into the groove of the Sec7 domain, and that Lys73 of the switch II region of ARF1 forms an ion pair with Asp183 of ARNO-Sec7.

ADP-Ribosylation Factor 1↗
PubMed1998

A new member of the Rho family, Rnd1, promotes disassembly of actin filament structures and loss of cell adhesion.

Members of the Rho GTPase family regulate the organization of the actin cytoskeleton in response to extracellular growth factors. We have identified three proteins that form a distinct branch of the Rho family: Rnd1, expressed mostly in brain and liver; Rnd2, highly expressed in testis; and Rnd3/RhoE, showing a ubiquitous low expression. At the subcellular level, Rnd1 is concentrated at adherens junctions both in confluent fibroblasts and in epithelial cells. Rnd1 has a low affinity for GDP and spontaneously exchanges nucleotide rapidly in a physiological buffer. Furthermore, Rnd1 lacks intrinsic GTPase activity suggesting that in vivo, it might be constitutively in a GTP-bound form. Expression of Rnd1 or Rnd3/RhoE in fibroblasts inhibits the formation of actin stress fibers, membrane ruffles, and integrin-based focal adhesions and induces loss of cell-substrate adhesion leading to cell rounding (hence Rnd for "round"). We suggest that these proteins control rearrangements of the actin cytoskeleton and changes in cell adhesion.

3T3 Cells↗
PubMed1998

Static magnetic resonance imaging of the pelvic floor muscle morphology in women with stress urinary incontinence and pelvic prolapse.

In a study, the magnetic resonance imaging (MRI) findings of 69 women were analyzed to define the typical MRI appearance of the pelvic floor musculature in healthy subjects (n = 20) and women with urinary incontinence (UI) and/or genitourinary prolapse (GP) (n = 49). The following parameters were determined: thickness and signal intensity of the levator muscles on each side, distance between the urethra and symphysis, diameter of the proximal urethra, and thickness and configuration of the anterior vaginal wall. These parameters were correlated with the patients' age and parity, urodynamic parameters, and the clinical assessment of the pelvic floor. In contrast to healthy subjects, the frequent findings in women with UI and/or GP are higher signal intensity of the levator muscles (p < 0.05) and loss of the hammock-like configuration of the vagina (p < 0.01). On static MRI, the morphometry of the levator musculature identified no findings typical of either UI or GP. Analysis of MRI combined with patients' parity suggests that the severity of damage to the pelvic floor at delivery is determined by the traumatic event as such and not by the number of deliveries. Urethral diameter, distance of the symphysis to the urethra, and vaginal wall thickness cannot distinguish between controls and women with UI and/or GP. Urodynamic and functional clinical parameters do not correlate with the changes in the pelvic floor musculature demonstrated by static MRI. Although morphological changes in UI and/or GP can be demonstrated by MRI, they can be assigned a pathogenic role only if clinical symptoms are present.

Adolescent↗
PubMed1998

[Lymphoma of the cerebellopontile angle as etiology of retrochochlear damage. Case report and review of the literature].

The clinical features of progression sensorineural hearing loss and vertigo in combination with the radiologic finding of a contrast-enhancing mass within the inner auditory canal are suggestive of an acoustic neuroma. We report our findings in a 57-year-old woman with known mixed connective tissue disease who was presumed to have a neuroma. A large malignant lymphoma of the cerebellopontine angle presented clinically with a primary acoustic none palsy and no other central neurological deficits. Both the primary radiological examinations and the exclusively peripheral nerve palsy failed to indicate manifestations of a lymphoma. The development of a progressive facial palsy within 8 weeks of presentation and an atypical occipital headache were uncommon findings for an acoustic neuroma. Such changes in symptoms despite the occurrence of cardinal symptoms require further diagnostic measures. Manifestations of a malignant lymphoma in the cerebellopontine angle are extremely rare. To our knowledge a case of an intracerebral lymphoma in a patient with Sjögren's syndrome has never been reported before.

Cerebellar Neoplasms↗
PubMed1998

Use of contrast-enhanced MR imaging to detect sacroiliitis in children.

PURPOSE: To verify the diagnostic value of contrast-enhanced MR imaging compared with conventional radiography in the diagnosis of sacroiliitis in children. DESIGN AND PATIENTS: Radiography and MR imaging of the sacroiliac joints were performed in 185 children subdivided into the following groups according to the modified European Spondyloarthropathy (SpA) Study Group (ESSG) criteria: group 1, undifferentiated spondyloarthropathy (uSpA) (n=53, 94.5% HLA-B27+); group 2, differentiated SpA (n=45, 93.3% HLA-B27+); group 3, patients with no signs of SpA other than oligoarthritis (n=39, 92.3% HLA-B27+); group 4, HLA-B27+ controls with various other non-SpA diagnoses (n=22); and group 5, HLA-B27-controls with various other non-SpA diagnoses (n=26). Radiographs were evaluated on the basis of the modified New York criteria independently by three experienced radiologists masked to the clinical data. In a second step, the same radiologists independently evaluated the MR images without knowledge of the clinical data and radiographic findings using the recently published criteria developed by our group. These criteria allow differentiation of acute and chronic inflammatory changes. RESULTS: Radiography demonstrated sacroiliitis in 18 patients: 4 of 53 in group 1 (7.5%), 14 of 45 in group 2 (31%), but none in groups 3, 4 and 5. In contrast, MR imaging demonstrated acute and/or chronic sacroiliitis in 44 patients: 18 of 53 in group 1 (34%), 21 of 45 in group 2 (46.7%) and 5 of 39 in group 3 (12.8%), but none in groups 4 and 5. The percentage of sacroiliitis detected by MR imaging was significantly higher than that detected by radiography (P<0.001). CONCLUSION: Contrast-enhanced MR imaging is a useful method for detecting sacroiliitis in children. Advantages of contrast-enhanced MR imaging compared with conventional radiography are a higher sensitivity due to the ability to document early and acute changes and the absence of radiation exposure.

Adolescent↗