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Biomedical subjects

P Grondin

Publications and source records attributed to P Grondin.

At least 19 recordsLinked to original sources
PubMed2004

Thixotropic organogels based on a simple N-hydroxyalkyl amide: rheological and aging properties.

The thixotropic properties ofthermoreversible organogels composed ofN-3-hydroxypropyl dodecanamide and various apolar fluids have been investigated by X-ray scattering, light microscopy, and rheo-optics experiments. This revealed that gel formation occurs via a precipitation process. Depending upon the cooling rate, large interconnected aggregates are formed and induce an elastic behavior. When submitted to a shear flow, these aggregates disentangled and became aligned in the direction of the velocity. Nevertheless, shear does not alter the structure of the individual aggregate and connections between the aggregates are quickly rebuilt due to gravity and thermal fluctuations when the applied flow is stopped. The alignment under flow and the reformation of the connections after the cessation of the shear induces the thixotropic behavior.

Journal Article↗
PubMed1999

The carboxyl-terminal region of biliary glycoprotein controls its tyrosine phosphorylation and association with protein-tyrosine phosphatases SHP-1 and SHP-2 in epithelial cells.

Biliary glycoprotein (Bgp, C-CAM, or CD66a) is an immunoglobulin-like cell adhesion molecule and functions as a tumor suppressor protein. We have previously shown that the Bgp1 isoform responsible for inhibition of colonic, liver, prostate, and breast tumor cell growth contains within its cytoplasmic domain two tyrosine residues positioned in immunoreceptor tyrosine-based inhibition motif (ITIM) consensus sequences. Moreover, we determined that these residues, upon phosphorylation, associate with the protein-tyrosine phosphatase SHP-1. In this report, we have further evaluated the structural bases of the association of Bgp1 with Tyr phosphatases. First, we demonstrate that Bgp1 also associates with the SHP-2 Tyr phosphatase, but not with an unrelated Tyr phosphatase, PTP-PEST. Association of Bgp1 and SHP-2 involves the Tyr residues within the Bgp1 ITIM sequences, Val at position +3 relative to the second Tyr (Tyr-515), and the SHP-2 N-terminal SH2 domain. In addition, our results indicate that residues +4, +5, and +6 relative to Tyr-515 in the Bgp1 cytoplasmic domain play a significant role in these interactions, as their deletion reduced Bgp1 Tyr phosphorylation and association with SHP-1 and SHP-2 by as much as 80%. Together, these results indicate that both SHP-1 and SHP-2 interact with the Bgp1 cytoplasmic domain via ITIM-like sequences. Furthermore, they reveal that the C-terminal amino acids of Bgp1 are critical for these interactions.

Amino Acid Sequence↗
PubMed1998

Effect of a cGMP-specific phosphodiesterase inhibitor on retinal function.

Multiple forms of phosphodiesterase have been reported in many tissues. Phosphodiesterase 6, a cGMP-specific phosphodiesterase, is described as a photoreceptor cell-specific phosphodiesterase. Phosphodiesterase 6 is known to play a crucial role in visual function. A novel phosphodiesterase inhibitor, GF248 (5["(propoxy),7'(4-morpholino)-phenacyl],[1-methyl-3 propyl]pyrazolo[4,3d]pyrimidin-7-one), has been described to be a very potent cGMP-specific phosphodiesterase inhibitor. In the present study, we compared the potency of GF248 and other known cGMP-specific phosphodiesterase inhibitors on phosphodiesterase 5 and phosphodiesterase 6. GF248 displayed an IC50 of 2 and 5 nM for phosphodiesterase 5 and phosphodiesterase 6, respectively. Thereafter, we assessed the effect of GF248 on retinal function, using an ex vivo model of isolated retina electroretinogram recording. Exposure of retina to GF248 resulted in a dose-dependent decrease in electroretinogram amplitude (PIII and b-waves), with no marked modification of PIII and b-wave implicit time. Among other phosphodiesterase inhibitors, DMPPO (1,3-dimethyl-6-(2-propoxy-5-methanesulfonylamidophenyl)pyrazol ol[3,4d]-pyrimidin-4-(5H)-one) and dipyridamole, cGMP-specific phosphodiesterase inhibitors, and IBMQ (1-isobutyl-3-methylimidazol[1,5a]quinoxalin-4-(5H)one), a nonselective phosphodiesterase inhibitor, altered retinal function but less potently than GF248, consistent with their in vitro phosphodiesterase 6 inhibition. Phosphodiesterase 3- and phosphodiesterase 4-selective inhibitors, cilostamide and rolipram, respectively, did not affect retinal function at 10 micromol l(-1). Our conclusion from these data is that GF248, a potent phosphodiesterase 6 inhibitor, could interfere with visual transduction by cGMP accumulation.

3',5'-Cyclic-GMP Phosphodiesterases↗
PubMed1996

Appearance of low signal intensity lines in MRI of silicone breast implants.

Magnetic resonance (MR) images of five explanted mammary prostheses were obtained with a 1.5 T GE Signa system using a conventional spin-echo pulse sequence, in order to investigate the low-intensity curvilinear lines which may be observed in MR images of silicone gel-filled breast implants under pressure from fibrous capsules. MR images showed ellipsoid prostheses, often containing multiple low-intensity curvilinear lines which in some cases presented an appearance very similar to that of the linguine sign. Upon opening the fibrous capsules, however, all of the prostheses were found to be completely intact demonstrating that the appearance of multiple low signal intensity curvilinear lines in MR images of silicone gel-filled prostheses is not necessarily a sign of prosthesis rupture. The MR image features which are specific to the linguine sign must be more precisely defined.

Breast Implants↗
PubMed1995

Characterization of a novel potent and specific inhibitor of type V phosphodiesterase.

Guanosine cyclic 3':5'-monophosphate (cGMP) plays a crucial role in regulating vascular smooth muscle contractile state. In rat aortic smooth muscle cells (RSMC) three isozymes of phosphodiesterase (PDE) may be involved in the degradation of cGMP, namely PDE I, PDE III, and PDE V. To study the effective contribution of PDE V to the control of intracellular cGMP levels, a specific and potent PDE V inhibitor 1,3-dimethyl-6-(2-propoxy-5-methanesulfonylamidophenyl)pyrazolo[3, 4d]- pyrimidin-4-(5H)-one (DMPPO) was synthesized. DMPPO is a competitive inhibitor with respect to cGMP (Ki = 3 nM) and displayed high selectivity for PDE V as compared to other PDE isozymes. DMPPO strongly potentiated the cGMP response of atrial natriuretic peptide- or sodium nitroprusside-treated RSMC (EC50 = 0.5 microM). In addition, similar intracellular cGMP levels were obtained in the presence of a saturating concentration of DMPPO or 3-isobutyl-1-methylxanthine, a nonspecific PDE inhibitor, suggesting that cGMP is almost exclusively hydrolyzed by PDE V in RSMC. Stimulation of RSMC with atrial natriuretic factor resulted in accumulation of cGMP in the extracellular media. This egression was shown to be proportional to the intracellular level of cGMP and a first-order rate constant of 0.04 min-1 was determined for the egression process. DMPPO did not interfere with the efflux and allowed us to show that intracellular cGMP levels are mainly controlled by PDE V, rather than by egression in RSMC. DMPPO is, therefore, a useful tool for determining the role of PDE V in the control of cGMP levels in living cells and tissues.

Allopurinol↗
PubMed1995

Adrenoleukodystrophy: magnetic resonance follow-up after Lorenzo's oil therapy.

PURPOSE: To determine the therapeutic value of Lorenzo's oil (a mixture of glyceryl trioleate and glyceryl trierucate oils) in treating the childhood form of adrenoleukodystrophy (ALD), as indicated by magnetic resonance imaging (MRI) follow-up. PATIENTS AND METHODS: Between January 1992 and March 1994 eight males with biochemically proven ALD, ranging in age from 1 to 28 years, were referred for cerebral MRI and initiation of Lorenzo's oil dietary therapy; treatment continued for a period of 6 to 24 months. Five of the patients underwent follow-up cerebral MRI, and the images were reviewed without knowledge of medical status or chronology of imaging relative to therapy; the other three patients were excluded from the study because follow-up examinations were lacking. Signal abnormalities were evaluated according to a modified Loes scale, which yielded a minimum rating of 0 (for normal findings) and a maximum rating of 35 (for the most severe abnormalities). Because an untreated control group was not available for comparison, the Wilcoxon signed-rank test was used to analyse the results. RESULTS: There was no statistically significant improvement in the ratings of abnormalities after treatment (p = 0.31, alpha = 0.10). However, the correlation between MRI findings and clinical symptoms was good. CONCLUSIONS: The Wilcoxon signed-rank test is a useful statistical tool for evaluating the results of studies in which the sample population is small and there is no control group. The authors suggest that although Lorenzo's oil may not be curative, it may have a role in preventing the progress of ALD in asymptomatic patients. A multicentre control trial of Lorenzo's oil treatment, with emphasis on asymptomatic patients, is now underway.

Adolescent↗
PubMed1994

Radiographic features of cauda equina syndrome complicating ankylosing spondylitis.

Cauda equina syndrome is an uncommon complication of ankylosing spondylitis. The characteristics of this disease, as shown by plain radiography, computed tomography and magnetic resonance imaging (MRI) in a 56-year-old man, are described. The MRI features are pathognomonic, allowing accurate noninvasive diagnosis of the disorder.

Cauda Equina↗
PubMed1994

Magnetic resonance imaging in moyamoya disease.

The authors describe the characteristic magnetic resonance imaging (MRI) findings of moyamoya disease in a 51-year-old woman; the disease was confirmed by angiography. MRI demonstrated well the occlusions and collateral vessels that typically occur secondary to this rare disease. Although hemorrhagic complications often result in a poor prognosis for patients with moyamoya disease, the patient described here recovered.

Angiography↗
PubMed1991

Involvement of platelet glycoprotein IIb-IIIa (alpha IIb-beta 3 integrin) in thrombin-induced synthesis of phosphatidylinositol 3',4'-bisphosphate.

32P-Labeled human platelets were incubated with thrombin (1 unit/ml) for 5 min at 37 degrees C under conditions allowing maximal synthesis of [32P]phosphatidylinositol 3',4'-bisphosphate (PtdIns(3,4)P2). Incorporation of 32P into the latter phosphoinositide was dose-dependently reduced (to a maximal level averaging 60%) by the tetrapeptide RGDS, an inhibitor of fibrinogen binding to activated glycoprotein IIb-IIIa (alpha IIb-beta 3 integrin). Identical results were obtained with the fibrinogen gamma-chain dodecapeptide HHLGGAKQAGDV, whereas the tripeptide RGD and the tetrapeptide RGES displayed reduced or undetectable effects on 32P labeling of PtdIns(3,4)P2, respectively, in good correlation with their ability to inhibit platelet aggregation and fibrinogen binding to activated alpha IIb-beta 3 integrin. In addition, pathological platelets from three patients suffering thrombasthenia, which lack alpha IIb-beta 3 integrin and fail to aggregate in response to thrombin, displayed hardly detectable increases in the 32P labeling of PtdIns(3,4)P2. In contrast, thrombin-stimulated synthesis of PtdIns(3,4)P2 was unaltered in other deficient platelets lacking the glycoprotein Ib-IX complex (Bernard-Soulier syndrome). Although additional pathways seem to be involved in the regulation of phosphatidylinositol-3-kinase, these data indicate a strong relationship between platelet aggregation involving fibrinogen binding to activated alpha IIb-beta 3 integrin and the synthesis of the novel phosphoinositides phosphorylated at position D-3 of the inositol ring.

Amino Acid Sequence↗
PubMed1991

Interaction of pp60c-src, phospholipase C, inositol-lipid, and diacyglycerol kinases with the cytoskeletons of thrombin-stimulated platelets.

Phosphatidylinositol (PtdIns)-4- and -3-kinases, PtdIns(4)P-5-kinase, diacylglycerol (DAG) kinase, and PtdIns-phospholipase C were all detected in cytoskeletons of resting human platelets. The total cytoskeletal enzyme activities were greatly increased upon thrombin stimulation of the intact cells. Those reached a maximum after a 60-s stimulation for PtdIns(4)P-5-kinase and phospholipase C, while the other kinases appeared to be slightly delayed. Specific activities were stimulated from about 4-fold (PtdIns-3-kinase) to about 6-fold (PtdIns-4-kinase). Thrombin treatment also promoted a co-extraction of pp60c-src with the cytoskeletons and its disappearance from the Triton X-100 soluble fraction. These results suggest that stimulation of platelets by thrombin causes the association of enzymes responsible for lipid phosphorylation and hydrolysis with the cytoskeletons. This could occur at cytoskeleton anchoring points to the membranes.

1-Phosphatidylinositol 4-Kinase↗
PubMed1990

The novel inositol lipid phosphatidylinositol 3,4-bisphosphate is produced by human blood platelets upon thrombin stimulation.

Radioactive PtdIns(3)P was detected in human platelets incubated with [32P]Pi, but remained unaffected by thrombin treatment. In contrast, [32P]PtdIns(3,4)P2 was absent from resting platelets, but was produced by thrombin-activated platelets in a dose- and time-dependent manner. [32P]PtdInsP3 was never found under these conditions. These changes are similar to those elicited in other cells by platelet-derived growth factor or the oncogene product pp60c-src.

Blood Platelets↗
PubMed1990

Purification and characterization of a novel phospholipid transfer protein from filamentous fungi.

1. We have isolated from mycelia of Mucor mucedo, a filamentous fungus, a phospholipid transfer protein. 2. The purification steps were gel filtration, hydroxyapatite chromatography, blue affinity column and fast protein liquid chromatography on anion exchanger. 3. A purified protein was obtained with a molecular mass of 24 kDa and a pI of 5.05 and its N-terminal sequence was established. 4. This protein transfers phosphatidylinositol, as well as phosphatidylcholine and phosphatidylethanolamine.

Amino Acid Sequence↗
PubMed1987

Aseptic necrosis of the cricoid: a complication of tracheal intubation.

Necrosis of the cricoid is a rare complication of tracheal intubation. Almost all cases previously reported were purulent. A 25-year-old man presented with a respiratory distress, two months after 2 days of tracheal intubation. The posterior larynx was the site of a major inflammation with fixity of the arytenoids. After an emergency control of the airway in the acute phase, a posterior cricoid split with widening by a laryngeal stent was performed for treatment of sequelae. Evolutional data from clinical examinations, direct fiberoptic laryngoscopy, CT scan, respiratory function tests, and pathology are described. Successive phases of latency, then acute manifestations, then sequelae can be distinguished. The work-up did not reveal any sign in favor of a septic necrosis. A physiopathologic hypothesis is suggested, explaining the necrosis as an ischemic one, due to destruction of the internal perichondrium vascular network of the cricoid.

Acute Disease↗
PubMed1986

Cancer of the kidney invading the vena cava and heart. Results after 11 years of treatment.

Between October, 1973, and October, 1983, 18 patients with cancer of the kidney or adrenal gland that had invaded the vena cava, and in 11 cases had reached the heart, were operated on by seven surgical teams. The surgical excision in all patients was performed with extracorporeal circulation, circulatory arrest and deep hypothermia. No deaths occurred. If there are no detectable metastases before operation, the 5 year survival rate is 75% as compared to 6 months with medical treatment. This clinical situation is not uncommon, as 3% to 10% of cancers of the kidney invade the inferior vena cava and 40% of them reach the heart. The possibility of curing the cancers with minimal operative risk should prompt a systematic search for venous invasion with any cancer of the kidney.

Adolescent↗
PubMed1979

Natural history of saccular aneurysms of the left ventricle.

We have studied the natural history of left ventricular aneurysms (LVA) in 40 patients not treated surgically who were followed for a mean period of 5 years, 8 months. These patients have been divided into two groups according to the presence (Group B) or absence (Group A) of significant symptomatology. The causes of death are dominated by arrhythmias and congestive heart failure (CHF). The survival rate at 10 years is 66.7% for the entire group. In asymptomatic patients the 10 year survival rate is 90%, but it is only 46.3% in those who were symptomatic at the time of the initial diagnosis. In general, the clinical course of survivors is stable in Group A but has deteriorated steadily in Group B. Nonfatal complications include arrhythmias (observed in 34% of all patients), thromboembolic phenomena (29%), CHF (29%), and recurrent myocardial infarction (22.5%). Factors influencing prognosis are the extent of the aneurysm, the association of asynergic segments, the ejection fraction of the residual ventricle, the left ventricular end-diastolic pressure (LVEDP), and the presence of ventricular extrasystoles at the time of diagnosis. The mere presence of aneurysm is not, in itself, an indication for operation. Incapacitating angina and refractory CHF are the most valuable indications for surgical resection. The question is raised as to the value of operation in patients with little or no symptoms, in those with isolated life-threatening arrhythmias, and in those in whom a mural thrombus is the only distressing feature.

Adult↗