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Biomedical subjects

P Gillis

Publications and source records attributed to P Gillis.

At least 19 recordsLinked to original sources

Ultrasmall particulate iron oxides as contrast agents for magnetic resonance spectroscopy: a dose-effect study.

Long-distance effects of a superparamagnetic contrast agent (AMI227) were investigated by phosphorus-31 NMR spectroscopy at 7.05 Tesla. In an initial methodological approach, the effects observed on phantoms were compared to the results of theoretical calculations. In a second step, the particles were administered to excised and perfused rat livers (N = 5) and hearts (N = 5) through the perfusion medium for 12 minutes at various concentrations (0.9, 1.8, and 3.6 mM Fe). Organs were subsequently rinsed with the perfusion medium for 42 minutes. During particle perfusion, the spectral lines were shifted and exhibited a strong broadening, although the peak area remained constant, testifying to the inocuity of the material. For hearts only, these disturbances disappeared upon organ rinsing. These through-space susceptibility effects of the particles located in the vessels on phosphorus nuclei, which are strictly confined to the intracellular space, show that high-susceptibility intravascular agents could be useful to evaluate tissue perfusion by contrast-enhanced spectroscopy.

Analysis of Variance↗

Water relaxation by SPM particles: neglecting the magnetic anisotropy? A caveat.

Magnetometric and relaxometric data from SPM particles are revisited, leading to a double conclusion rather different from the original one: accounting for the anisotropy energy not only allows a considerable improvement of the fit of the data to theory, but it also invalidates the conclusion obtained from the high field data (without accounting for anisotropy) concerning an important reduction of the diffusion coefficient by the coating of the particles.

Anisotropy↗

On T2-shortening by weakly magnetized particles: the chemical exchange model.

Chemical exchange (CE) theory is compared with two theories of T2-shortening caused by microscopic magnetic centers: inner- and outer-sphere relaxation theory (long-echo limit) and mean gradient diffusion theory (short-echo limit). The CE equation is shown to be identical to these theories in the respective limits and appropriate parameter relationships are derived for spherical particles. The theories are then compared with computer simulations of spherical particles and with a recent general theory, with good agreement in the asymptotic regions. The CE model also reproduces the essential relaxation characteristics in the intermediate range. Finally, good agreement of a CE model with simulations for magnetized cylinders is also demonstrated. The discussion is limited to weakly magnetized particles such that the maximum phase shift during an echo interval is less than one radian, permitting the use of the Luz-Meiboom CE equation. Published 2001 Wiley-Liss, Inc.

Computer Simulation↗

Nuclear magnetic relaxation dispersion of ferritin and ferritin-like magnetic particle solutions: a pH-effect study.

The relaxation mechanism of water protons in the presence of ferritin is still being debated. In this work, the pH dependence of the relaxation induced by ferritin and Fercayl, a ferritin-like akaganeite particle, is studied through T1 and T2 nuclear magnetic relaxation dispersion (NMRD) profiles. To differing extents, the relaxation brought about by both systems is significantly affected by pH. A proton exchange time of 33 ns (at pH 6 and 37 degrees C) is deduced from the fittings of Fercayl T1 NMRD profiles. The linearity of the relationship between 1/T2 and the magnetic field B0 for ferritin and Fercayl solutions is not altered by changes in pH. The parameters of this linearity strongly depend on pH for the latter, while remaining unchanged for the former. These results are interpreted in terms of an exchange between protons belonging to hydroxyl groups at the surface of the particle and bulk water protons.

Animals↗

Protein malnutrition due to replacement of milk by rice drink.

UNLABELLED: We present the case of an 8-month-old boy with failure to thrive and hypoalbuminaemia due to protein malnutrition caused by the replacement of milk by a rice drink. All symptoms resolved with an appropriate feeding. CONCLUSION: Rice drinks are no alternatives to infant milk formulas and carry a serious risk for the development of protein malnutrition.

Diet, Vegetarian↗

Aneurysm of the ductus arteriosus in a neonate with 13q-deletion.

Aneurysm of the ductus arteriosus is a rare abnormality for which different ways of pathogenesis are described. We report the case of a fatal thrombosis of an aneurysm of the ductus arteriosus in an infant presenting feeding difficulties and a mild dysmorphic facies. Karyotype analysis revealed a de novo chromosomal deletion 46,XY, del (13)(q12.3,q22.3). To the best of our knowledge, this is the first case of an aneurysm of the ductus arteriosus associated with a chromosomal aberration.

Aneurysm↗

Relaxation induced by ferritin and ferritin-like magnetic particles: the role of proton exchange.

Proton T1 and T2 in solutions of ferritin and fercayl (a ferritin-like iron-dextran particle) solutions were measured, over a wide range of various parameters (Bo, temperature, interecho-time and pH). The window of the previously referred linear dependence of 1/T2 on the static field was increased, up to 500 MHz, and the independence of T2 on the echo time was confirmed. Correlation times were extracted from T1 nuclear magnetic relaxation dispersion profiles. In the pH range studied, no strong variation of the relaxivities of ferritin solutions was noticed. Fercayl, which, unlike ferritin, remains stable under large pH variations, is characterized by strongly pH-dependent relaxation rates. This feature is interpreted as due to the effect of proton exchange in the water relaxation process. Outer sphere theory, which ignores proton binding, is shown to be unable to describe the relaxation of ferritin and ferritin-like particles solutions, first because it predicts a quadratic rate dependence on Bo, but also because it severely underestimates the relaxation rate. Explaining relaxation induced by ferritin and ferritin-like particle solutions will likely require a model that accounts for proton binding.

Animals↗

Pigment epithelium-derived factor: a potent inhibitor of angiogenesis.

In the absence of disease, the vasculature of the mammalian eye is quiescent, in part because of the action of angiogenic inhibitors that prevent vessels from invading the cornea and vitreous. Here, an inhibitor responsible for the avascularity of these ocular compartments is identified as pigment epithelium-derived factor (PEDF), a protein previously shown to have neurotrophic activity. The amount of inhibitory PEDF produced by retinal cells was positively correlated with oxygen concentrations, suggesting that its loss plays a permissive role in ischemia-driven retinal neovascularization. These results suggest that PEDF may be of therapeutic use, especially in retinopathies where pathological neovascularization compromises vision and leads to blindness.

Animals↗

Corrected equations for susceptibility-induced T2-shortening.

Local field gradients created by paramagnetic entities shorten water proton relaxation times, particularly T2. This "novel" relaxation mechanism, now known as susceptibility-induced relaxation, was described twenty years ago by Gueron, and later extended by others to superparamagnetic particles which have a much larger magnetization. Unfortunately, because of subtle but significant errors, those results are valid only in the strict zero-field limit. These errors are corrected in the present article, and new versions of the relaxation equations are presented. The correction is shown to be significant, not only for transverse and longitudinal relaxation in aqueous superparamagnetic colloids, where the "Gueron" effect is known to be important, but even in some cases for transverse paramagnetic relaxation.

Colloids↗

Keratinocyte growth factor induces angiogenesis and protects endothelial barrier function.

Keratinocyte growth factor (KGF), also called fibroblast growth factor-7, is widely known as a paracrine growth and differentiation factor that is produced by mesenchymal cells and has been thought to act specifically on epithelial cells. Here it is shown to affect a new cell type, the microvascular endothelial cell. At subnanomolar concentrations KGF induced in vivo neovascularization in the rat cornea. In vitro it was not effective against endothelial cells cultured from large vessels, but did act directly on those cultured from small vessels, inducing chemotaxis with an ED50 of 0.02-0.05 ng/ml, stimulating proliferation and activating mitogen activated protein kinase (MAPK). KGF also helped to maintain the barrier function of monolayers of capillary but not aortic endothelial cells, protecting against hydrogen peroxide and vascular endothelial growth factor/vascular permeability factor (VEGF/VPF) induced increases in permeability with an ED50 of 0.2-0.5 ng/ml. These newfound abilities of KGF to induce angiogenesis and to stabilize endothelial barriers suggest that it functions in microvascular tissue as it does in epithelial tissues to protect them against mild insults and to speed their repair after major damage.

Animals↗

Omeprazole in infants with cimetidine-resistant peptic esophagitis.

Twelve neurologically normal infants (age 2.9+/-0.9 months) with peptic esophagitis (grade 2) who did not respond to cimetidine (in addition to positioning, cisapride, and Gaviscon) were treated with omeprazole, 0.5 mg/kg once a day, for 6 weeks. The effectiveness of omeprazole was evaluated in all infants by clinical assessment and endoscopy before and after treatment and by 24-hour gastric pH monitoring during treatment in seven infants. Omeprazole therapy led to a marked decrease in symptoms, endoscopic and histologic signs of esophagitis, and intragastric acidity.

Anti-Ulcer Agents↗

Magnetic resonance susceptibility contrast induced by capillaries: a numerical comparison of two models.

Monte-Carlo computer simulations have proven to be very powerful tools for the analysis of the magnetization decay induced by susceptibility gradients, as well for contrast agent characterization, as for the BOLD effect allowing fMRI. A recent vasculature model containing capillaries and venules uses homogeneous magnetized cylinders as models for the vessels. This modeling is questioned by comparing results obtained from simulation results based on two different models, one using homogeneous cylinders and another taking into account the existence of red blood cells, treated as homogeneous magnetized spheres. The results show the nonequivalence of both models, with the modeling by cylinders systematically overestimating the transverse relaxation rates, and the difference increasing with the adopted value of the diffusion coefficient. The discrepancy is attributed to the dominating role, regarding relaxation, of the local magnetic field in the immediate vicinity of the capillaries, which results in the suggestion of elaborating a "mixed modeling": the analytical expressions corresponding to the homogeneous cylinder model could be used except when the spin packets are wandering in the immediate vicinity of the capillaries, where accounting for the existence of individual red blood cells (whose motion may be neglected) seems unavoidable.

Blood Flow Velocity↗

Peripheral blood T and B lymphocyte subpopulations in infants with acute respiratory syncytial virus brochiolitis.

Most data concerning immunopathogenetic mechanisms involved in respiratory syncytial virus (RSV) infection are derived from animal studies. In infants with RSV bronchiolitis the target organ i.e. the airway is hard to explore. We looked for specific alterations in peripheral blood lymphocyte subpopulations in infants hospitalized for RSV bronchiolitis. Flow cytometric analysis with a large panel of monoclonals was performed on peripheral blood lymphocytes in thirty-two infants (mean age: 4.9 months) admitted for RSV bronchiolitis. Data collected on admission were compared with age-matched control values and also with results obtained at the end of the first week of hospitalization. Differences between age-groups (older or younger than 4 months) and between clinical subgroups (clinical severity score more or less than 6) were looked for. In the group of infants as a whole, regardless of age and clinical score the number of CD4+ cells on admission was significantly elevated compared to normal values for age (p<.0001) including a high fraction of the naive suppressor-inducer subpopulation (CD4+/CD45RA+) and a low fraction of the reciprocal memory helper-inducer subpopulation (CD4+/CD29+). Within the CD8+ cell population the number of T cells with cytotoxic activity (CD8+/S6F1+) was significantly elevated (p<.0001) as were other types of cytotoxic cells. A significant decrease (p<.0001) in the proportion of the precursor/suppressor-effector subpopulation (CD8+/S6F1-) was seen. Absolute numbers and percentages of CD19+ B cells were significantly elevated (p<.0001) with a significant increase in the CD5+ subfraction (p<.0001) as well as in the CD10+ subfraction (p<.0001). In the older age group immunophenotypic cytotoxicity was more pronounced with increased clinical score. During recovery the CD45RA+:CD29+ ratio tended to normalize within the CD4+ T cells. Within the B lymphocyte subsets significant increase in the CD19+/CD5+ fraction (p<.05) was seen. We conclude that there are significant changes in the number of peripheral blood lymphocyte subsets in infants with RSV bronchiolitis as compared to age-related controls. We hope that present data could be useful in further exploration of RSV immunology in humans. A possible link between RSV bronchiolitis and the subsequent development of atopy is mentioned.

B-Lymphocytes↗

Facial asymmetry, cardio-vascular anomalies and adducted thumbs as unusual symptoms in Dubowitz syndrome?

The authors report a young girl with Dubowitz syndrome associated with Tetralogy of Fallot, facial asymmetry and fixed adducted thumbs. At least 80 cases of Dubowitz syndrome have been reported in the literature. Among these patients only 11 have a cardiovascular malformation. Facial asymmetry and adducted thumbs have been noticed in one previously reported patient. They suggest that these findings may be regarded as uncommon manifestations of the syndrome.

Abnormalities, Multiple↗

Proton transverse nuclear magnetic relaxation in oxidized blood: a numerical approach.

When red blood cells are deoxygenated, hemoglobin, which is then transformed into deoxyhemoglobin or methemoglobin, becomes paramagnetic. The transverse nuclear magnetic relaxation rate of water protons is considerably enhanced by this chemical transformation. A general agreement exists about the origin of the phenomenon--local field inhomogeneities induced by paramagnetic centers randomly distributed within the cell--but the localization of the region that dominates the relaxation is unclear. We addressed this problem with a computer simulation devoted to the determination of transverse magnetic relaxation of water protons in the presence of superparamagnetic MRI contrast agent candidates. The simulation confirms an earlier experimental result that shares equitably the responsibility for the observed relaxation between intracellular and extracellular water.

Blood↗