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Biomedical subjects

A L Alexander

Publications and source records attributed to A L Alexander.

11 recordsLinked to original sources
PubMed1997

Postmortem fetal MR imaging: comparison with findings at autopsy.

OBJECTIVE: The purpose of this study was to prospectively compare findings from postmortem fetal MR imaging with findings at autopsy. SUBJECTS AND METHODS: Twenty-six fetuses were imaged on a 1.5-T MR scanner using two-dimensional and high-resolution three-dimensional fast spin-echo techniques immediately before autopsy. The MR images were reviewed independently by three radiologists who evaluated then for major and minor malformations. These findings were then compared with those at autopsy. RESULTS: The 26 subjects had 47 major and 11 minor malformations. All three radiologists correctly identified 37 of the major malformations on the MR images (detection rate, 79%), and at least one of the three reviewers correctly identified 43 of the abnormalities (detection rate, 91%). Only one of the 11 minor anomalies was identified by any reviewer. Reviewers made six false-positive diagnoses. In two cases, both with major CNS malformations, MR imaging was superior to autopsy in defining in situ relationships. CONCLUSION: Although autopsy remains the study of choice for evaluating causes of fetal death, MR imaging is an excellent alternative when autopsy is refused. Additionally, MR imaging may be a valuable adjunct to autopsy for fetuses with CNS anomalies.

Abnormalities, Multiple↗
PubMed1996

Murine glomerulotropic monoclonal antibodies are highly oligoclonal and exhibit distinctive molecular features.

We recently produced a panel of seven glomerular-binding mAbs from a nephritic MRL-lpr mouse that bind to histones/nucleosomes (group I) or DNA (group II) adherent to glomerular basement membrane. To elucidate the molecular basis of their binding and ontogeny, we sequenced their variable (V) regions, analyzed the apparent somatic mutations, and predicted their three-dimensional structures. There were two clonally related sets (3 of 4 in group I, 3 of 3 in group II) both of the VHJ1558 family, and one mAb of the VH 7183 family. V region somatic mutations within clonally related sets had little effect on glomerular binding and did not appear to be selected for based on glomerular binding. The VH regions were most homologous with those from autoantibodies to histones, DNA, or IgG (i.e., rheumatoid factors), the Vkappa regions, with those from autoantibodies to small nuclear ribonucleoproteins (snRNP). The VH regions also exhibited an unusual VD junction (in the group I clonally related set) and an overall high content of charged amino acids (arginine, aspartic acid) in complementarity-determining regions (CDRs), particularly in CDR3. Molecular modeling studies suggested that the Fv regions of these mAbs converge to form a flat, open surface with a net positive charge. The CDR arginines in group I mAbs; appear to be located in Ag contact regions of the binding cleft. In sum, these data suggest that glomerulotropic mAbs are a highly restricted set of Abs with distinctive molecular features that may mediate their binding to glomeruli.

Amino Acid Sequence↗
PubMed1996

Modulation of renal disease in autoimmune NZB/NZW mice by immunization with bacterial DNA.

Preautoimmune New Zealand Black/White (NZB/NZW) mice immunized with Escherichia coli (EC) double standard (ds) DNA produce antibodies that bind mammalian dsDNA and display specificities similar to spontaneous lupus anti-DNA. Since calf thymus (CT) dsDNA fails to induce these antibodies, these results suggest a special potency of foreign DNA in inducing serological manifestations of lupus in a susceptible host. To assess the effects of DNA immunization on clinical manifestations in NZB/NZW mice, we measured renal disease and survival of mice immunized with either (a) EC dsDNA as complexes with methylated bovine serum albumin (mBSA) in adjuvant; (b) CT dsDNA with mBSA in adjuvant; (c)mBSA alone in adjuvant; or (d) unimmunized. After immunization with EC dsDNA, NZB/NZW mice developed significant levels of anti-dsDNA antibodies. Nevertheless, these mice had less proteinuria, nitrate/nitrite excretion, and glomerular pathology than mice immunized with either mBSA alone, CT dsDNA/mBSA complexes, or unimmunized mice. Survival of the EC dsDNA immunized mice was significantly increased compared with the other mice. Furthermore, immunization of mice after the onset of anti-DNA production and proteinuria stabilized nephritis and prolonged survival. The improvement in renal disease occurred despite the expression of autoantibodies that bound mammalian dsDNA as well as glomerular antigens. These results suggest that bacterial DNA has immunological properties that attenuate murine lupus despite the induction of pathogenic antibodies.

Animals↗
PubMed1996

Differences in V kappa gene utilization and VH CDR3 sequence among anti-DNA from C3H-lpr mice and lupus mice with nephritis.

To investigate the molecular properties of anti-DNA from lpr mice that express high levels of anti-DNA without immune-mediated nephritis, the sequences of VH and V kappa genes encoding 11 monoclonal anti-DNA antibodies derived from C3H-lpr/lpr (C3H-lpr) mice were studied. All of the C3H-lpr monoclonal anti-DNA bound single-stranded DNA while five also bound double-stranded DNA. Two of the hybridomas were clonally related as determined by Southern analysis and sequencing. Sequence analysis of C3H-lpr anti-DNA revealed the use of VH genes that encode anti-DNA from the MRL-lpr/lpr and (NZB X NZW) F1 mouse models of lupus, although differences occurred in the VH CDR3 amino acid content. In contrast, the V kappa genes from C3H-lpr mice lacked significant identity with previously reported V kappa genes for anti-DNA from lupus models. These results indicate that anti-DNA from C3H-lpr mice differ from anti-DNA from lupus mice with nephritis in patterns of V gene expression and suggest a molecular basis for the lack of pathogenicity of anti-DNA in these mice.

Amino Acid Sequence↗
PubMed1996

Microbubbles as novel pressure-sensitive MR contrast agents.

Magnetic resonance imaging contrast agents that are sensitive to pressure would be useful for evaluating cardiovascular function. One such potential contrast agent consists of gas-filled liposome microbubbles. The magnetic susceptibility of the microbubbles locally perturb the static magnetic field, which influences the transverse-relaxation properties of the surrounding medium. Changes in the pressure alter the bubble dimensions, which affects the magnetic field perturbations and, hence, the transverse-relaxation. The effect of these microbubbles on the T2 relaxation times of a water-based medium was measured for liposomes filled with different gases-nitrogen, argon, air, oxygen, xenon, neon, perfluoropentane, perfluorobutane, and sulfur hexafluoride. The air-filled, perfluoropentane-filled and the oxygen-filled liposomes demonstrated the largest effect on transverse-relaxation. The influence of pressure on both gradient-echo and spin-echo signal intensities for air-filled microbubbles was also evaluated. Pressure-induced changes in signal intensity were consistently observed for both the spin-echo and gradient-echo pulses sequences.

Contrast Media↗
PubMed1996

Magnetic resonance guidance of percutaneous ethanol injection in liver.

RATIONALE AND OBJECTIVES: Percutaneous ethanol injection (PEI) is used as a form of treatment for cancer, particularly malignant hepatic tumors. Little is known about the intratumoral distributions of ethanol following PEI. We assessed, using magnetic resonance (MR) imaging, the distribution of ethanol in liver and the concentration of ethanol needed to kill tumor cells in vivo. METHODS: MR imaging studies were performed using phantoms of alcohol, ex vivo bovine liver, and healthy human volunteers. A variety of pulse sequences were tested for their ability to maximize the signal intensity from alcohol while minimizing the signal from liver tissues as well as the regions of necrosis following ethanol injection. A cell culture model of in vitro cytotoxicity was developed to predict the target concentration of alcohol necessary for killing tumor cells. RESULTS: At 1.5 T, we found that an inversion-recovery spin-echo sequence using an inversion time of 250 msec and an echo time of 150 msec in combination with water saturation pulses effectively suppressed the tissue water signal from human liver while obtaining a clear signal from the ethanol. The cytotoxicity experiments suggested that a concentration of 20% or more ethanol is sufficient to completely kill all the tumor cells. CONCLUSION: A critical concentration of ethanol (e.g., 10%) is necessary for full tumoricidal effect. MR imaging should be able to determine the volume of distribution and the intratumoral concentrations of ethanol, thus potentially allowing researchers to achieve the requisite concentrations for maximal tumoricidal effects.

Animals↗
PubMed1995

The application of magnetization transfer to MR angiography with reduced total power.

Magnetization transfer (MT) techniques have been shown to significantly reduce background soft-tissue signal in time-of-flight magnetic resonance angiography. To achieve sufficient suppression, radio frequency (RF) pulses with tip angles on the order of 1000 degrees are typically used, resulting in significant RF power deposition in the patient. Although these power deposition levels do not exceed the FDA guidelines, they are significantly higher than those used in typical imaging techniques. The use of these same magnetization transfer pulses in applications at field strengths higher than 1.5 T will require MT power levels which exceed FDA safety standards. This report demonstrates that the total power deposition required to achieve background tissue suppression can be significantly reduced by the application of the saturation pulses only during the phase-encoding steps corresponding to the central portion of "k space." This technique allows equivalent soft tissue suppression with approximately 10% of the energy deposition of conventional magnetization transfer techniques.

Artifacts↗
PubMed1994

A new nonionic macrocyclic gadolinium(III) chelate as a potential magnetic-resonance-imaging contrast agent.

A new GdIII complex of a 17-membered macrocycle with three pendant carboxymethyl groups has been synthesized; the ligand has been obtained in a single step from diethylenetriaminepentaacetic dianhydride (pentetic dianhydride) and 1,4-butanediamine (putrescine). An X-ray crystal analysis has shown that the complex is a nonionic metal chelate with a coordinated water molecule. The near-zero electrical conductivity, 1 omega-1 cm2 mol-1, of a 1 mM solution indicated that the metal chelate is essentially undissociated. The NMR T1 relaxivity is 2.5 s-1 mM-1 at a resonance field of 64 MHz, and 3.4 s-1 mM-1 at 250 MHz. This new GdIII complex is a potentially important magnetic resonance imaging contrast agent.

Chelating Agents↗
PubMed1994

Sensitivity of muscle proton spin-spin relaxation time as an index of muscle activation.

The purpose of this study was to determine the minimum number of contractions that are needed to detect an increase in the muscle proton spin-spin relaxation time (T2) at a given exercise intensity. Five healthy human subjects performed five sets of an exercise that included concentric and eccentric contractions of the elbow-flexor muscles with loads that were 25 or 80% of maximum. With the 80% load, the five sets involved 1, 2, 5, 10, or 20 repetitions of the exercise; with the 25% load the five sets were 2, 5, 10, 20, or 40 repetitions. The upper arm of each subject was imaged before and immediately after each set of the exercise. Spin-echo images (repetition time/echo time = 2,000 ms/30, 60, 90, and 120 ms) were collected using an extremity coil, and T2 values were calculated. The signal intensity was measured from the elbow-flexor and -extensor muscles and from the bone marrow of the humerus. With the 80% load, T2 increased in the short head of the biceps brachii after two repetitions of the elbow exercise and after five repetitions in the brachialis and the long head of the biceps brachii. With the 25% load, T2 became longer after five repetitions of the exercise for the short head of the biceps brachii and after 10 repetitions for the brachialis and the long head of the biceps brachii. T2 varied linearly with the number of contraction repetitions for each of the elbow-flexor muscles at either load (r2 > or = 0.97, P < 0.001).(ABSTRACT TRUNCATED AT 250 WORDS)

Adult↗
PubMed1993

Use of a projection reconstruction method to decrease motion sensitivity in diffusion-weighted MRI.

Diffusion-weighted MRI is a clinically useful technique, but its utility is compromised by high sensitivity to patient motion. Use of radial-scan data acquisition and projection reconstruction, rather than the conventional Fourier imaging method, can substantially reduce the sensitivity to global translational motion of the object. The basis of this concept and a demonstration of the technique in an animal imaging experiment are presented.

Animals↗