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P Gillis

Publications and source records attributed to P Gillis.

36 records · Page 2Linked to original sources

Lymphocyte subpopulations in healthy newborn infants: comparison of cord blood values with values five days after birth.

Significant differences (p < 0.0001) were demonstrated in lymphocyte subpopulations both in cord blood and in venous blood samples obtained at day 5 from the same healthy infants. Numbers of T lymphocytes increased, especially CD4+/CD45RA+ cells, whereas numbers of B lymphocytes and natural killer cells decreased without changes in CD8+ and other cytotoxic cells.

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The adenosine-uridine binding factor recognizes the AU-rich elements of cytokine, lymphokine, and oncogene mRNAs.

Selective mRNA degradation is an important control point in the transient expression of a variety of mRNAs coding for growth regulators. A variety of labile mRNAs coding for lymphokines, cytokines, and oncogenes contain within their 3'-untranslated region an AU-rich region shown to destabilize these messages. We recently identified a cytosolic protein, adenosine-uridine binding factor (AUBF), which complexes with four tandem AUUUA reiterations of a synthetic RNA transcript. We now show that AUBF forms RNase T1-resistant band-shifted complexes with a variety of in vitro transcribed mRNAs including granulocyte-macrophage colony-stimulating factor, interferon-gamma, interleukin-3, c-fos, and v-myc. Formation of complexes was specifically inhibited by AUUUA containing RNA, but not by irrelevant RNA. After brief ultraviolet light-induced cross-linking, AUBF.RNA complexes with the exception of c-fos comigrated on sodium dodecyl sulfate-polyacrylamide gel electrophoresis. Mutations within the AUUUA motifs demonstrate that both nucleotide sequence and secondary structure are important in AUBF.AUUUA RNA complex formation. Based upon these data, we suggest AUBF may interact with a variety of labile mRNAs with multiple AUUUA reiterations or single reiterations within an AU-rich 3'-untranslated region.

Adenosine↗

Transverse relaxivity of particulate MRI contrast media: from theories to experiments.

Computer simulations and experimental approach have been used to characterize the properties of particulate MRI contrast agents with special attention paid to the influence of particle size. Up to approximately 50 nm, an increase of the particle diameter leads to a strong enhancement of the transverse magnetization decay rate. For larger grains or aggregates, the decay rate measured without spin-echo formation reaches a plateau. When observed through a spin-echo sequence, the transverse magnetization decay rate becomes slower on increasing the particle size or on shortening the echo time. For these large particles, multiexponential decay rates are observed. Definition and measurement of relaxivity in such systems is discussed.

Computer Simulation↗

Fiber-to-field angle dependence of proton nuclear magnetic relaxation in collagen.

Longitudinal and transverse proton relaxation times were measured on pig tendon. For T1, dispersion curves and more accurate measurements at 20 MHz are presented. Values of T2 were obtained from CPMG pulse sequences, at 20 MHz. The dependence of relaxation times against the fiber-to-field angle was particularly investigated. Longitudinal relaxation rate was found to be almost orientation independent, and presented quadrupolar peaks between 1 and 4 MHz. On the contrary, transverse relaxation, that was well fitted by the sum of four exponentials, was highly orientation dependent. Deconvolution showed that the exponentials decaying most quickly are most orientation dependent. For those two fractions, a cross-relaxation model allowed explaining the fiber-to-field angle dependence, and the specially low rate corresponding to the magic angle of 55 degrees. Finally, each decaying mode was assigned to a fraction of protons localized in the macromolecular structure and characterized by particular dynamics.

Animals↗

Structure and dynamics of water in tendon from NMR relaxation measurements.

Nuclear magnetic relaxation times were measured in collagen tissue when varying the orientation of the fiber with respect to the static field. T1 was found to be only slightly dependent on theta, the fiber-to-field angle, but T2 was very sensitive to the orientation, with a maximum value at the magic angle. The transverse decay curves were multiexponential. Their deconvolution displayed four components; the ones that decayed most slowly were almost independent of theta, but the two fastest ones showed a strong angular dependence that was interpreted with a cross-relaxation model. Quadrupolar dips were visible in the 1/T1 dispersion curves. These dips were independent of theta, so that the magnetization transfer could also be assumed to be independent of the fiber orientation. Finally, each component was assigned to a fraction of protons localized in the macromolecular structure and characterized by particular dynamics. The model of Woessner was applied to the water molecules tightly bound into the macromolecules, which resulted in a dynamical description of this water fraction. This description is compatible with the two-sites model of Ramachandran based on x-ray diffraction and with the extensive studies of Berendsen. However, the important indications obtained from the deconvolution lead to a less static representation of the tissue.

Animals↗

Adenosine-uridine binding factor requires metals for binding to granulocyte-macrophage colony-stimulating factor mRNA.

Post-transcriptional gene regulation plays an important role in the expression of granulocyte-macrophage colony-stimulating factor (GM-CSF). Cytokine secretion by activated lymphocytes or mast cells is preceded by dramatic stabilization of the normally labile GM-CSF mRNA. The 3'-untranslated region of GM-CSF and other labile mRNAs contain the destabilizing motif adenosine-uridine-uridine-uridine-adenosine (AUUUA). We recently identified a cytoplasmic protein denoted the adenosine-uridine binding factor (AUBF) which binds with high affinity and specificity to AUUUA elements in synthetic RNA transcripts. We now demonstrate that AUBF binds specifically to GM-CSF mRNA through the destabilizing AUUUA elements. The formation of AUBF-GM-CSF RNA complexes required calcium or magnesium which were sensitive to EDTA or EGTA. A variety of other divalent metals blocked magnesium-dependent AUBF activity. These observations suggest that AUBF may protect GM-CSF mRNA from rapid degradation and play a crucial role in the expression of cytokine genes.

Animals↗

Transverse relaxation (1/T2) of solvent protons induced by magnetized spheres and its relevance to contrast enhancement in MRI.

At typical imaging fields, the transverse relaxation rates 1/T2 of the protons of soft tissue are much greater than their longitudinal rates 1/T1. Because of this, clinical magnetic resonance images are generally collected using relatively short values of TR, an approach that both increases comfort for the patient and reduces medical costs. As a result, image contrast is dominated by the 1/T2 values of the tissue protons. Currently, small single-ion paramagnetic complexes--Gd-DTPA is the prime example--are being used to enhance contrast in clinical magnetic resonance imaging (MRI). However, such agents contribute comparably to 1/T1 and 1/T2 so that their utility is greatest when introduced into body fluids, for which 1/T1 and 1/T2 are also comparable; they are much less useful for enhancing contrast of soft tissue. For this, one must look elsewhere, to rather large aggregates of paramagnetic ions, which may either be paramagnetic or ferromagnetic. Iron in its many chemical and biochemical forms, both exogenous and endogenous, is important in this respect. Its presence in ferritin and hemosiderin--in excess in some diseases--is one example; deoxyhemoglobin in cells and methemoglobin in blood pools from trauma are others in which endogenous iron in several oxidation states is important. Magnetic particulates of various iron oxides are now being used as exogenous agents for enhancing 1/T2 preferentially at imaging fields. Predicting contrast enhancement under such circumstances can become rather complex, not because the theory is difficult, but because the underlying concepts are subtle.(ABSTRACT TRUNCATED AT 250 WORDS)

Animals↗

Transverse relaxation of solvent protons induced by magnetized spheres: application to ferritin, erythrocytes, and magnetite.

Since 1/T2 of protons of tissue water is generally much greater than 1/T1 at typical imaging fields, small single-ion contrast agents--such as Gd(DTPA), which make comparable incremental contributions and therefore smaller fractional contributions to 1/T2 compared to 1/T1--are not as desirable for contrast-enhancement as agents that could enhance 1/T2 preferentially. In principle, such specialized agents will only be effective at higher fields because the field dependence (dispersion) of 1/T1 is such that it approaches zero at high fields whereas 1/T2 approaches a constant value. The residual 1/T2 is called the "secular" contribution and arises from fluctuations in time--as sensed by the protons of diffusing solvent or tissue water molecules--of the component of the magnetic field parallel to the static applied field. For solutions or suspensions of sufficiently large paramagnetic or ferromagnetic particles (greater than or equal to 250 A diameter), the paramagnetic contributions to the relaxation rates satisfy 1/T2 much greater than 1/T1 at typical imaging fields. We examine the theory of secular relaxation in some detail, particularly as it applies to systems relevant to magnetic resonance imaging, and then analyze the data for solutions, suspensions, or tissue containing ferritin, erythrocytes, agar-bound magnetite particles, and liver with low-density composite polymer-coated magnetite. In most cases we can explain the relaxation data, often quantitatively, in terms of the theory of relaxation of protons (water molecules) diffusing in the outer sphere environments of magnetized particles. The dipolar field produced by these particles has a strong spatial dependence, and its apparent fluctuations in time as seen by the diffusing protons produce spin transitions that contribute to both 1/T1 and /T2 comparably at low fields; for the larger particles, because of dispersion, the secular term dominates at fields of interest. On the basis of the agreement of theory with data for solutions of small paramagnetic complexes, large magnetite particles, and liver containing low-density polymer-coated magnetite agglomerates, it is argued that the theory is sufficiently reliable so that, e.g., for ferritin--for which 1/T2 is unexpectedly large--the source of its large relaxivity must reside in nonideal chemistry of the ferritin core. For blood, it appears that diffusion through intracellular gradients determines 1/T2.

Animals↗

Lesions in the cat prepositus complex: effects on the optokinetic system.

The effects of bilateral lesions within and around the prepositus hypoglossi (p.h.) nuclei on the optokinetic system were studied. The pure optokinetic nystagmus (o.k.n.) was evoked by a step of velocity (60 deg/s, 30 s duration) of the surrounding. The visual-vestibular interaction was investigated by measuring the gain and phase of the vestibulo-ocular reflex (v.o.r.) as a function of frequency before and after lesion under three different conditions of testing: basic v.o.r. tested in the dark, v.o.r. tested in the light and v.o.r. suppressed by vision. The tested amplitude was +/- 20 deg. A posterior vermectomy was performed for controls in two cats. A bilateral electrolytic p.h. lesion including the rostral pole of this nucleus was added to the posterior vermectomy in three cats. A lesion similar but sparing the rostral pole of the nucleus was carried out in three other cats. In one cat a bilateral electrolytic lesion of the medial vestibular nuclei (m.v.n.) was combined with a posterior vermectomy. In two cats the medulla was cut on the mid line after a posterior vermectomy. The posterior vermectomy affected neither the optokinetic response nor the visual-vestibular interactions. In cats where p.h. lesion included its rostral pole and in the cat with m.v.n. lesion, all the tested optokinetic effects (step o.k.n., and visual-vestibular interactions) were abolished. In the three cats where p.h. lesion spared its rostral pole, the optokinetic effects were quite normal in one cat, mildly reduced in the second one, and seriously affected but not completely abolished in the third one. The surgical cut of the medulla on the mid line did not dramatically disturb the various optokinetic effects. The most marked deficit was the loss of the optokinetic after-nystagmus (o.k.a.n.). From the comparison of these results with the neuroanatomical data and with the Robinson's model concerning the optokinetic processing, it was suggested that: (a) the rostral p.h. could be the location of the o.k.n. integrator or could be an essential link on the o.k.n. pathway, (b) the posterior four-fifths of the p.h. could not be an essential relay on the o.k.n. pathway, (c) the loss of o.k.a.n. after mid-line lesion could be due to the interruption of the positive feed-back loop formed by the reciprocal inhibitory connexions between the two m.v.n.

Animals↗

The optokinetic reflex in the cat: modeling and computer simulation.

After a brief comparative review of the dynamic characteristics of the optokinetic reflex ( OKR ) in different species and after a brief description of the main anatomical structures involved in this reflex, a mathematical model of the OKR in the cat is presented. The experimental results obtained by Godaux and Vanderkelen (1984) in the normal and in the totally cerebellectomized cat were used to validate the model and to obtain an estimation of its parameters.

Animals↗