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Biomedical subjects

S M Conolly

Publications and source records attributed to S M Conolly.

5 recordsLinked to original sources

Identification of ENV determinants in V3 that influence the molecular anatomy of CCR5 utilization.

The V3 loop of the ENV glycoprotein exerts a dominant influence on the interaction of gp120 with coreceptors. Primary env genes cloned from sequential isolates from two seroconverters revealed Pro-->Ala conversion in the conserved GPG motif of the V3 crown in seven of 17 R5 ENV. ENV containing the GPG motif in the V3 crown had fusogenic activity with chimeric receptors containing either the N terminus or loops of CCR5, whereas those with the GAG variant utilized only the former. Site-directed mutagenesis of multiple primary and prototypic R5 env genes demonstrated that the GPG motif was necessary for dual utilization of the N terminus and body of CCR5 in both gain and loss-of-function experiments. All ENV containing the GPG V3 crown showed CCR5 binding in the presence of soluble CD4, whereas it was not detected with the GAG variants. Molecular dynamic simulations of a V3 peptide predicts that the Pro-->Ala substitution results in a conformational change with loss of the crown structure. These studies demonstrate that sequences in the third hypervariable region determine the specificity of coreceptor utilization for fusion, and that a conserved motif in the crown directly influences the molecular anatomy of the interaction between gp120 and CCR5.

Amino Acid Motifs↗

Resistive homogeneous MRI magnet design by matrix subset selection.

A new technique for designing resistive homogeneous multicoil magnets for magnetic resonance imaging (MRI) is presented. A linearly independent subset of coils is chosen from a user-defined feasible set using an efficient numerical algorithm. The coil currents are calculated using a linear least squares algorithm to minimize the deviation of the actual magnetic field from the target field. The solutions are converted to practical coils by rounding the currents to integer ratios, selecting the wire gauge, and optimizing the coil cross-sections. To illustrate the technique, a new design of a short, homogeneous MRI magnet suitable for low-field human torso imaging is presented. Magnets that satisfy other constraints on access and field uniformity can also be designed. Compared with conventional techniques that employ harmonic expansions, this technique is flexible, simple to implement, and numerically efficient.

Algorithms↗

MR imaging of articular cartilage using driven equilibrium.

The high incidence of osteoarthritis and the recent advent of several new surgical and non-surgical treatment approaches have motivated the development of quantitative techniques to assess cartilage loss. Although magnetic resonance (MR) imaging is the most accurate non-invasive diagnostic modality for evaluating articular cartilage, improvements in spatial resolution, signal-to-noise ratio (SNR), and contrast-to-noise ratio (CNR) would be valuable. Cartilage presents an imaging challenge due to its short T(2) relaxation time and its low water content compared with surrounding materials. Current methods sacrifice cartilage signal brightness for contrast between cartilage and surrounding tissue such as bone, bone marrow, and joint fluid. A new technique for imaging articular cartilage uses driven equilibrium Fourier transform (DEFT), a method of enhancing signal strength without waiting for full T(1) recovery. Compared with other methods, DEFT imaging provides a good combination of bright cartilage and high contrast between cartilage and surrounding tissue. Both theoretical predictions and images show that DEFT is a valuable method for imaging articular cartilage when compared with spoiled gradient-recalled acquisition in the steady state (SPGR) or fast spin echo (FSE). The cartilage SNR for DEFT is as high as that of either FSE or SPGR, while the cartilage-synovial fluid CNR of DEFT is as much as four times greater than that of FSE or SPGR. Implemented as a three-dimensional sequence, DEFT can achieve coverage comparable to that of other sequences in a similar scan time. Magn Reson Med 42:695-703, 1999.

Cartilage, Articular↗

Pulsed saturation transfer contrast.

In vivo 1H conventional NMR image contrast generation usually relies on the macroscopic T1 and T2 relaxation parameters of the tissues of interest. Recently cross-relaxation related image contrast has been reported by Wolff and Balaban in animal models. Due primarily to the broad lineshape of the intended saturation spin pool and the use of off-resonance irradiation, high specific absorption rate and an auxiliary RF amplifier have been necessary to produce these images. The relatively long spin-lattice relaxation property of this spin pool, however, suggests the use of pulse methods to achieve saturation. In this paper, we show that short-T2 spin pools can be selectively saturated with short intense RF pulses. Cross-relaxation time constants can be measured using the technique of saturation recovery. In vivo magnetization-transfer-weighted images can be produced using pulses on commercial whole-body imagers without additional hardware.

Adipose Tissue↗

MR angiography by selective inversion recovery.

A modified inversion-recovery sequence is introduced which performs subtraction angiography by varying time-of-flight effects of blood flowing into an imaged slab. The selective 180 degrees excitation inverts different regions between measurements to isolate arterial and/or venous blood. On normal human subjects, high-resolution carotid artery angiograms have been obtained.

Carotid Arteries↗