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Biomedical subjects

A D Nelson

Publications and source records attributed to A D Nelson.

At least 37 records · Page 2Linked to original sources

Tn4563 transposition in Streptomyces coelicolor and its application to isolation of new morphological mutants.

The Tn3-like transposon Tn4556 (and its derivatives Tn4560 and Tn4563) has been used for insertion mapping of genetic loci cloned on plasmids, but it has been difficult to obtain chromosomal insertions, largely because of the lack of a strong selection against transposon donor molecules. In this communication, we report two efficient selection techniques for transposition and their use in the isolation of chromosomal insertion mutations. A number of independent Streptomyces coelicolor morphological mutants (bld and whi) were obtained. Two of the bld mutations were mapped to locations on the chromosome by SCP1-mediated conjugation; at least one mutation, bld-5m1, appears to define a novel locus involved in control of S. coelicolor morphogenesis and antibiotic production.

Alleles↗

Continuous arterial positron monitor for quantitation in PET imaging.

Quantitative measures of physiologic function with PET require continuous monitoring of arterial positron isotope concentration. A device has been developed that automates this process. This device has advantages over manual sampling techniques with syringes since fewer personnel are required, measurements are less error prone, and more continuous measures of arterial positron concentration are available. A constant flow infusion/withdrawal pump withdraws blood from the radial artery through a catheter connected to 0.5 mm inner diameter teflon tubing. This tubing is wrapped around a 50 mm thick by 50 mm diameter NaI(T1) crystal that is interfaced to a photomultiplier tube (PMT) and encased in a cylindrical lead shield. This crystal detects 511 Kev photons that result from positron annihilation. The device sensitivity is greater than 240 (cts/sec)/(microCi/ml) corresponding to a peak activity of approximately 10,000 cts/sec for a 50 mCi bolus injection in an adult. The system dynamic response has been measured and the true arterial input function is recovered by deconvolution. The system has been used clinically for more than 400 human PET studies and has been a reliable continuous monitor of arterial positron concentration.

Arteries↗

Biodistribution and dosimetry of 3F8 neuroblastoma monoclonal antibody.

A method has been developed for quantitating radiolabeled antibody concentrations from images obtained with standard gamma cameras. The method is based on orthogonal projections and accounts both for the effective attenuation of gamma rays and the finite depth dependent resolution of a gamma camera. The method was verified in experimental phantoms and subsequently used in patient studies to quantitate radiolabeled antibody concentrations in neuroblastoma tumors. The in vivo measurements of tumor radioactivity levels were confirmed at biopsy in one patient.

Antibodies, Monoclonal↗

Pseudo-gating: elimination of periodic motion artifacts in magnetic resonance imaging without gating.

This note explains and illustrates a technique of reducing artifacts produced by periodic motion without using physiologic gating. The method is simple and can be applied on any standard MRI unit. For periodic motion, effective gating can be attained by setting the product of the number of acquisitions (at each phase-encoding step), N, times the repeat time, TR, equal to the period of the motion, T. This pseudo-gating can be used with any TR but, if changes in the period occur, is most robust with short TR values. The method is also applicable to multislice and volume imaging. For fast field echo methods, the above rule can be used if the period of the motion is smaller than the total scan time. Otherwise, the scan need only be repeated N times to avoid artifacts and improve signal-to-noise. The method has been implemented to remove both respiratory and/or cardiac motion artifacts.

Heart↗

Complete tumor ablation with iodine 131-radiolabeled disialoganglioside GD2-specific monoclonal antibody against human neuroblastoma xenografted in nude mice.

The antibody 3F8, an IgG3 murine monoclonal antibody (MoAb) against disialoganglioside GD2, could target iodine-131 (131I) to established subcutaneous human neuroblastoma (NB) xenografts in BALB/c nude mice. 131I-radiolabeled MoAb (0.125-1 mCi) was injected iv. Tumor radioactivity over time was calculated from scintigraphy, and radiation dose to individual tumors was calculated. Tumor shrinkage occurred only with 131I-labeled 3F8, but not with nonradioactive 3F8 or radiolabeled irrelevant antibody. While the tumor of the control mice enlarged by tenfold, the treated tumor showed over 95% shrinkage by 12 days. Both the rate of shrinkage and duration of tumor response were dose dependent. Calculated doses of more than 10,000 rad could be achieved. Only those tumors that received more than 4,200 rad were completely ablated without recurrence. Recurrent tumors were not antigen negative or radioresistant. These results confirmed the prediction based on imaging studies that human NB xenografts could be effectively eradicated with the use of 131I-labeled MoAb 3F8 with tolerable toxicities.

Animals↗

Diagnostic imaging of human neuroblastoma with radiolabeled antibody.

In a previous study, the authors showed that iodine-131 labeled monoclonal antibody (Mab 3F8) could be used to image human neuroblastoma xenografts in mice with excellent tumor-to-tissue ratios. In this study they report their experience with six patients scanned with radiolabeled 3F8. There was strong accumulation of the labeled antibody in viable tumor, but no significant uptake was noted in normal brain, liver, spleen, or adrenal glands. Tumor-to-nontumor activity ratios varied but were approximately 10:1-20:1. This ratio yields good contrast for visualization. Time-activity curves show that radioactivity levels in normal tissue have a half-time of about 40 hours, whereas tumor tissues show a half-time of about 60 hours. Significant gastric secretion of free iodine demonstrated that the Mab was being deiodinated. Calculated radiation doses indicate that tumors receive at least ten times the dose to other tissues. The results indicate that Mab 3F8 has clinical potential for both imaging and therapy of human neuroblastomas.

Adolescent↗

Magnetic resonance imaging of the prostate.

The prostate was examined by magnetic resonance imaging (MRI) in 33 subjects, including five normal volunteers, 18 with prostatic carcinomas, seven with benign nodular hyperplasias, two cases of acute prostatitis, and one case of chronic prostatitis. Of 18 prostatic carcinomas, 16 produced an inhomogeneous signal intensity, with areas of diminished signal on T1-weighted scans and usually increased signal on T2-weighted images relative to the rest of the prostate. However, a similar appearance was also seen in five cases of benign nodular hyperplasia. It is doubtful at present whether MRI is able to reliably differentiate benign from malignant prostatic disease. Extraprostatic tumor extension and pelvic adenopathy was well shown, and MRI is very promising as a method for the preoperative staging of known prostatic carcinomas.

Carcinoma↗

Abdominal neuroblastoma: magnetic resonance imaging and tissue characterization.

Magnetic resonance imaging was performed in eight children with abdominal neuroblastomas. Five patients had serial examinations after diagnosis, and 15 computed tomography (CT) scans were available for comparison. MR imaging was as precise as CT in detecting the presence or absence of liver involvement and more efficient in determining the relationship of tumor to vascular structures. However, it did not differentiate tumor from normal kidney as accurately as CT. Inversion recovery (IR) images yielded the greatest soft-tissue contrast resolution between liver and tumor. T1 values of tumor were much higher than those of normal liver but overlapped those of normal kidneys. T2 values of tumor were significantly higher than those of the liver and were slightly, but not significantly, lower than those of the kidneys. Either T1- or T2- weighted pulse sequences should, therefore, provide adequate liver-tumor differentiation, but more heavily T2- weighted images appear necessary to distinguish between tumor and kidney. T1 values of tumors usually decreased with rapid tumor regression, while T2 values changed independently. The ability to quantitate tissue parameters helps in selecting appropriate imaging sequences and may be of use in following the progress of tumors.

Abdominal Neoplasms↗

MR imaging in patients with metallic implants.

A total of 305 magnetic resonance (MR) examinations were performed in 236 patients with metallic implants. Most examinations were performed at 0.3 T. The metallic implants included central nervous system shunting devices, tantalum mesh, surgical wire, skin staples, surgical clips, metallic orthopedic devices, and a few miscellaneous metallic objects. Patients with cardiac pacemakers, electrical implants, prosthetic cardiac valves, and aneurysm clips were excluded from MR examinations. The images were reviewed for evidence of metallic artifact. The conspicuity of artifact was related to the composition, mass, orientation, and position of the metallic object in the body. In most instances, the metallic artifact did not interfere with the interpretation of the image. The patients' records were also reviewed for adverse effects noted by each patient during the MR examination. Only two patients reported discomfort that could possibly have been related to their metallic implants, but in both cases it seemed unlikely that the symptoms were actually related to the imaging process. There were no apparent short-term adverse effects demonstrated in these patients.

Cerebrospinal Fluid Shunts↗

Altered acoustic reflectance on two-dimensional echocardiography as an early predictor of myocardial infarct size.

P6 area of increased acoustic reflectance was readily observed by 2-dimensional echocardiography (2-D echo) in the acutely ischemic canine myocardium. Fifteen mongrel dogs subjected to closed-chest coronary artery occlusion were used to test the hypothesis that these areas of altered acoustic reflectance were predictors of subsequent myocardial infarction (MI). Each dog was studied by 2-D echo in short-axis views of the left ventricle at 4 levels before and after coronary artery occlusion. The dogs were killed after 48 hours and heart sections were stained with triphenyltetrazolium chloride to identify the areas of necrosis. Four sections were then selected, approximating the same location within the left ventricle as the short-axis views taken for 2-D echocardiographic analysis. The in vivo 2-D echocardiographic examination revealed alteration of acoustic reflectance immediately after coronary occlusion, which detected the presence of MI with a sensitivity of 92% and a specificity of 90%. The extent of altered acoustic reflectance seen by echo correlated closely (r = 0.81) with the extent of MI detected by triphenyltetrazolium staining of the excised heart. Altered acoustic reflectance seen by 2-D echo immediately after coronary artery occlusion reflects acute ischemic changes and may be an early predictor of MI size.

Animals↗

Gated magnetic resonance imaging of congenital cardiac malformations.

Magnetic resonance (MR) images of a variety of cardiac malformations in 19 patients aged 1 week to 33 years were obtained using pulse plethysmographic- or ECG-gated spin echo pulse sequences. Coronal, axial, and sagittal images displaying intracardiac structures with excellent spatial and contrast resolution were acquired during systole or diastole. It is concluded that MR will be a valuable noninvasive method of diagnosing congenital heart disease.

Adolescent↗

Osteomyelitis in children: detection by magnetic resonance. Work in progress.

Magnetic resonance (MR) imaging was performed in five children, ages 9 to 12, with acute, subacute, chronic, and recurrent osteomyelitis. Saturation recovery (SR), T2-weighted spin echo, and inversion recovery (IR) pulse sequences were employed. A reduction in the normally bright image of bone marrow corresponded with abnormalities seen on radiographs, CT scans, and radionuclide scans. SR images produced the best signal-to-noise ratios. Contrast between normal and abnormal marrow was most pronounced on IR sequences, which suggested an increase in water content of inflamed marrow. Abnormalities were sometimes seen on MR images before they could be detected on radiographs. Some MR abnormalities were present when CT and radionuclide studies were normal or equivocal.

Bone Marrow↗

The effect of motion on two-dimensional Fourier transformation magnetic resonance images.

The effect of motion on two-dimensional Fourier transformation magnetic resonance (MR) images was investigated using phantoms, animals, and normal volunteers. All images were obtained with a 0.30-Tesla superconducting magnet using spin echo pulse sequences. Respiratory motion was simulated while imaging the phantoms. In addition to image blurring, motion produced ghost images, or image harmonics. These ghost images were copies of the static image that was produced at periodic intervals. Canine images, which were obtained during respiration and after the administration of curare, showed significant improvement after respiratory motion was eliminated. Images of normal volunteers were improved with respiratory and cardiac gating, but data acquisition time was significantly increased. These results indicate that MR image quality could be improved with a system that acquires all necessary data within a single breathhold .

Animals↗

Gated magnetic resonance imaging of the normal and diseased heart.

Gated cardiac magnetic resonance (MR) images were obtained in two normal volunteers and 21 adults with a variety of cardiovascular abnormalities. The images were correlated with data from clinical examinations, electrocardiograms, and cardiac catheterization. Gated cardiac images were superior to nongated images. Combined cardiac and respiratory gated images were superior to images obtained with cardiac gating only, but acquisition time was longer. Portions of the coronary arteries were visualized in seven of 23 examinations (30%), and subacute and old myocardial infarcts were seen in five of nine patients (55%) as areas of thinned myocardium. No signal changes were observed in the patients with subacute infarctions or the patient with myocarditis. Coronary atherosclerotic lesions were not visualized in any of the patients. Normal cardiac anatomy (chambers, valves, and papillary muscles) was well visualized. Examples of aortic stenosis and atherosclerosis of the abdominal aorta are shown.

Aortic Valve Stenosis↗

Magnetic resonance imaging: evaluation of palliative systemic-pulmonary artery shunts.

Eleven patients with a total of 17 palliative systemic-pulmonary artery shunts underwent evaluation by electrocardiogram-gated magnetic resonance imaging (GMRI). GMRI successfully imaged 11 of 17 shunts (65%), including five of nine Blalock-Taussig shunts, four of six Glenn shunts, and both aortopulmonary shunts. All shunts except for the Waterston were imaged on coronal sections during end-systole. The single Waterston shunt was seen on sagittal and transverse scans. Shunt localization and identification were facilitated by obtaining multiple, contiguous sections through the body. Glenn shunts could be imaged entirely in one section, although multiple sections were required to locate the correct plane. Blalock-Taussig shunts generally required multiple sections to image different segments of the shunt. Both aortopulmonary shunts were seen as direct side-to-side connections of the aorta and pulmonary artery. GMRI permitted assessment of the size, course, patency, and distribution of systemic-pulmonary artery shunts as well as the size and morphology of the proximal pulmonary arteries. We conclude that GMRI is a useful, noninvasive method for imaging the anatomy of systemic-pulmonary artery shunts.

Adolescent↗

Magnetic resonance imaging of the heart.

Magnetic resonance (MR) has noninvasively imaged the proximal coronary arteries, areas of infarction, and a variety of congenital heart lesions. Further technical improvement may extend cardiac MR from the realm of research to clinical utility.

Adult↗