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Biomedical subjects

S A Cook

Publications and source records attributed to S A Cook.

15 recordsLinked to original sources

Genetic mapping of the murine gene and 14 related sequences encoding chromosomal protein HMG-14.

The high-mobility-group chromosomal protein HMG-14 preferentially binds to nucleosomal core particles of mammalian chromatin and may modulate the chromatin configuration of transcriptionally active genes. The human gene for HMG-14 has been localized to the Down syndrome region of Chromosome (Chr) 21 and may be involved in the etiology of this syndrome. Here we show, by means of genetic linkage analysis of interspecific and intersubspecific backcross mice, that the murine functional gene, Hmg14, is located on the distal end of mouse Chr 16, a region known to have conserved synteny with human Chr 21. In addition to the functional gene for HMG-14, both human and mouse genomes contain many related sequences that are probably processed pseudogenes. Here we map the locations of 14 Hmg14-related sequences in two mouse genomes. The 14 mapped loci are widely dispersed on ten chromosomes (Chrs 3, 5, 7, 9, 11, 12, 16, 17, 19, and X) and can be detected efficiently with a single cDNA probe. Thus, the Hmg14 multigene family is well suited to serve as genetic markers for other linkage studies in mice.

Animals

Chromosomal localization of the murine gene and two related sequences encoding high-mobility-group I and Y proteins.

HMG-I and its isoform HMG-Y are members of the abundant high-mobility-group of nonhistone chromatin proteins; they bind to A + T-rich regions of chromosomal DNA and are expressed at high levels in rapidly dividing, undifferentiated mammalian cells. HMG-I and HMG-Y are alternatively spliced products of a single functional gene, designated Hmgi in the mouse. Here, we report the occurrence of at least three distinct Hmgi-related loci in the mouse. Only one of these loci was present in all of the 10 mouse strains examined; therefore, this locus most likely represents the transcriptionally active, functional gene, Hmgi. Genetic linkage analysis of interspecific and intersubspecific backcrosses showed that Hmgi is located in the t-complex region of mouse Chromosome 17. Two additional Hmgi-related sequences, Hmgi-rs1 and Hmgi-rs2, were found only in certain mouse strains and probably represent pseudogenes. Hmgi-rs1 is located on Chromosome 11; it was present in all of the standard laboratory inbred mouse strains examined but was absent in wild-derived inbred strains of Mus spretus, M. musculus castaneus, and M. m. molossinus. Hmgi-rs2 was found only in M. m. castaneus and is located on Chromosome 6. Hmgi genes have not been previously mapped in any species, but the location of the probable functional gene on murine Chromosome 17 suggests that the homologous gene in humans is located on Chromosome 6.

Animals

Myocardial perfusion imaging in the diagnosis of coronary artery disease.

The role of myocardial perfusion imaging has been extended from diagnosis to management and prognosis in patients with coronary artery disease. Great emphasis has been placed on improving the accuracy of the test to better define perfusion, viability, and the extent of damage of the myocardium. To achieve this goal, investigators have focused on several areas including imaging technique, in which the accuracy of single-photon emission CT has been compared with that of positron emission tomography; radiopharmaceuticals, in which 201Tl has been compared with 99mTc-sestamibi and 99mTc-teboroxime; stress modalities, in which dipyridamole and adenosine stress have been compared with exercise; myocardial viability, as determined by delayed and reinjection 201Tl imaging or by measurement of cellular integrity using 82Rb compared with 18fluorodeoxyglucose metabolic PET imaging; and assessment of myocardial salvage and prognosis by exercise or dipyridamole 201Tl imaging in acute myocardial infarction.

Adenosine

Influence of left ventricular mass on the diagnostic accuracy of myocardial perfusion imaging using positron emission tomography with dipyridamole stress.

This study assesses the influence of left ventricular hypertrophy (LVH) on the accuracy of myocardial perfusion imaging using pharmacologic coronary vasodilation. Seventy-five patients without previous infarction, and with known coronary anatomy, were studied by echocardiography and PET. LVH (defined by mass greater than 131 g/m2 in males or greater than 100 g/m2 in females) was identified in 25 patients; this group did not differ significantly from the remainder in terms of clinical or angiographic parameters. Twenty patients with hypertrophy had significant coronary artery stenoses, which were identified correctly by PET in 11 (55%), in contrast to 29 of 34 patients (85%, p = 0.03) with coronary disease but normal LV mass. Normal perfusion images were obtained in three of five patients (60%) with hypertrophy but no coronary disease; in contrast, 14 of 16 patients without either coronary disease or hypertrophy (88%, p = ns) had normal scans. The accuracy of PET was 14/25 (56%) in those with hypertrophy, and 43/50 (86%, p = 0.01) in patients with normal LV mass. In this group, the presence of hypertrophy was associated with reduction in the diagnostic accuracy of PET using dipyridamole stress. These findings may account for the phenomenon of "dipyridamole nonresponsiveness" in some patients.

Adult

Automated computer program for radionuclide cardiac output determination.

Radionuclides have provided a safe, reliable, and minimally invasive method for repeated determinations of cardiac output. A completely automated computer program for data analysis is described. Cardiac output values obtained by this technique correlated closely with values obtained by manual determination of the region of interest (r = 0.90 for right-ventricular and 0.98 for left-ventricular outputs, p less than 0.001 for both). Further, cardiac output determined by computer selection of either left-ventricular area of interest or of the "whole heart region" correlated significantly with that simultaneously determined by dye-dilution technique (indocyanine green; r = 0.86, p less than 0.001 for both). The automated approach allows greater objectivity in the selection of the regions of interest, faster turnaround of calculated results, and use of a smaller dose of radionuclide.

Adult

Computed tomography of the liver.

This work examines the scope and accuracy of CT in the detection of tumors, abscesses, cysts, and parenchymal disorders of the liver. While CT remains an emerging modality, it is shown to be equal to nuclear medicine in detecting mass lesions. It has also been possible to distinguish obstructive from nonobstructive jaundice. Presently, CT is not well suited to the study of cirrhosis. Technological advances in CT design and contrast agents offer promise of significantly improved resolution.

Biopsy

Preoperative localization of occult lesions of the breast.

An outpatient procedure that accurately localizes occult lesions of the breast has been used in 26 patients. A small biopsy is performed using local anesthesia, the excised specimen is xerographed and, if necessary, bread-loafed to identify the involved specimen. This has corroborated the xeromammographic diagnosis of cancer in six patients in whom the lesions were clinically not detectable.

Biopsy

Computed tomography of the thorax and abdomen; a preliminary report.

The utility of computed tomography (CT) in the study of the anatomy, physiology, and pathology of the human body has been the subject of considerable interest since the introduction of CT scanning. The advent of a new prototype scanning device has made it possible to examine a variety of abnormalities in the abdomen and thorax in a manner not previously possible. This development permits a remarkable insight into the study of human disease in vivo.

Aortography