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S A Cook

Publications and source records attributed to S A Cook.

At least 37 records · Page 2Linked to original sources
PubMed1996

Outcome of temporal lobe epilepsy surgery predicted by statistical parametric PET imaging.

UNLABELLED: PET is useful in the presurgical evaluation of temporal lobe epilepsy. The purpose of this retrospective study is to assess the clinical use of statistical parametric imaging in predicting surgical outcome. METHODS: Interictal 18FDG-PET scans in 17 patients with surgically-treated temporal lobe epilepsy (Group A-13 seizure-free, group B = 4 not seizure-free at 6 mo) were transformed into statistical parametric imaging, with each pixel representing a z-score value by using the mean and s.d. of count distribution in each individual patient, for both visual and quantitative analysis. RESULTS: Mean z-scores were significantly more negative in anterolateral (AL) and mesial (M) regions on the operated side than the nonoperated side in group A (AL: p < 0.00005, M: p = 0.0097), but not in group B (AL: p = 0.46, M: p = 0.08). Statistical parametric imaging correctly lateralized 16 out of 17 patients. Only the AL region, however, was significant in predicting surgical outcome (F = 29.03, p < 0.00005). Using a cut-off z-score value of -1.5, statistical parametric imaging correctly classified 92% of temporal lobes from group A and 88% of those from Group B. CONCLUSION: The preliminary results indicate that statistical parametric imaging provides both clinically useful information for lateralization in temporal lobe epilepsy and a reliable predictive indicator of clinical outcome following surgical treatment.

Adult↗
PubMed1995

Detergent solubilization of membrane-bound methane monooxygenase requires plastoquinol analogs as electron donors.

Quinols can provide reducing equivalents for the membrane-bound form of methane monooxygenase (pMMO), substituting for NADH in whole cells and membranes. Furthermore, quinols are effective reductants for the detergent-solubilized enzyme, whereas NADH is ineffective. The decyl analog of plastoquinol and duroquinol (2,3,5,6-tetramethylbenzoquinol) provide the greatest methane monooxygenase activity in whole cells and membrane suspensions, as well as detergent-solubilized samples. Lauryl maltoside is by far the best detergent for solubilization of catalytically active methane monooxygenase. Optimal pMMO activity in the detergent-solubilized fraction is obtained with a ratio of approximately 1.7 mg of detergent per milligram of membrane protein, independent of protein concentration. The detergent-solubilized pMMO retains its sensitivity to inhibition by cyanide, acetylene, and EDTA. It is also stimulated by exogenous copper, as in isolated membrane fractions. Reaction of the detergent-solubilized enzyme with [14C]acetylene results in labeling of a 26-kDa peptide, analogous to the behavior observed for isolated membrane suspensions. The selectivity of pMMO for duroquinol and decyl-plastoquinol, relative to other structurally similar quinols, suggests that the enzyme obtains reducing equivalents directly from a quinol (probably plastoquinol) in vivo.

Cell Membrane↗
PubMed1995

Neuromuscular degeneration (nmd): a mutation on mouse chromosome 19 that causes motor neuron degeneration.

Neuromuscular degeneration, nmd, is a spontaneous autosomal recessive mutation in the mouse producing progressive hindlimb impairment caused by spinal muscular atrophy. We used an intersubspecific intercross between B6.BKs-nmd2J/+ and Mus musculus castaneus (CAST/Ei) to map the nmd mutation to mouse Chromosome (Chr) 19 with the most likely gene order: nmd-(D19Sel2, Pygm)-Cntf-Pomc2-D19Mit16-Cyp2c-Got1. nmd maps near muscle deficient, mdf, and has a very similar clinical phenotype, but allele tests and histological differences suggest that nmd is a distinct mutation at a different locus. Although closely linked, nmd recombined with the candidate genes muscle glycogen phosphorylase, Pygm, and ciliary neurotrophic factor, Cntf.

Animals↗
PubMed1995

Evaluation of cAMP involvement in cannabinoid-induced antinociception.

It has been proposed that cannabinoids act at a Gi protein-coupled receptor to produce antinociception. One action of Gi-proteins is to decrease intracellular cAMP via inhibition of adenylyl cyclase activity. Although cannabinoid inhibition of forskolin-stimulated adenylyl cyclase is used as a confirmation of functional cannabinoid receptors, it is unknown whether this second messenger system specifically mediates cannabinoid-induced antinociception. This in vivo study was conducted using enantiomeric cAMP analogs, Rp-cAMPS (an antagonist) and Sp-cAMPS (an agonist), and the cAMP agonist Cl-cAMP to test the hypothesis that cannabinoid-induced antinociception is due to decreased adenylyl cyclase activity. None of the cAMP analogs, forskolin, or 1,9-dideoxy-forskolin affected delta 9-THC or CP-55,940-induced antinociception produced by intrathecal (i.t.) or intracerebroventricular (i.c.v.) injections in mice. Experiments were also conducted to investigate whether i.c.v. administration of Sp-cAMPS would block i.c.v. cannabinoid-induced antinociception in rats. Sp-cAMPS failed to block CP-55,940-induced antinociception. However, Sp-cAMPS produced hyper-excitability and reactive behavior indicating that it did elicit a pharmacological effect. Although, adenylyl cyclase may mediate other cannabinoid-induced actions, these results do not support the hypothesis that it is involved in cannabinoid-induced antinociception. Alternatively, other effector systems such as calcium or potassium channels coupled to cannabinoid receptors may mediate cannabinoid-induced antinociception.

Analgesics↗
PubMed1995

Hibernating myocardium versus scar: severity of irreversible decreased myocardial perfusion in prediction of tissue viability.

PURPOSE: To determine whether quantitation of the relative severity of decreased perfusion in irreversible defects on myocardial perfusion images enables differentiation of viable hibernating myocardium from scar. MATERIALS AND METHODS: In 145 patients with previous myocardial infarction, 1,252 regions with irreversible defects proved by means of rubidium-82 rest-stress imaging were analyzed for relative severity (percentage decrease in perfusion). Myocardial tissue viability was determined by means of positron emission tomography with fluorine-18 fluorodeoxyglucose (FDG). RESULTS: The relative decreases in Rb-82 uptake in the 1,252 regions were categorized into nine levels of severity (30% to > or = 70%) in 381 regions of hibernating myocardium and 871 regions of scar. The values of relative decreased perfusion in the irreversible defects alone did not enable differentiation of hibernating myocardium and scar (P = .61). CONCLUSION: The results show no relationship between the relative severity of irreversible perfusion defects and the ability to distinguish between hibernating myocardium and scar.

Cell Survival↗
PubMed1994

Identification and genetic mapping of 151 dispersed members of 16 ribosomal protein multigene families in the mouse.

More than 150 individual members of 16 ribosomal protein multigene families were identified as DNA restriction fragments and genetically mapped. The ribosomal protein gene-related sequences are widely dispersed throughout the mouse genome. Map positions were determined by analysis of 144 progeny mice from both an interspecific (C57BL/6J x SPRET/Ei)F1 x SPRET/Ei and an intersubspecific (C57BL/6J x CAST/Ei)F1 x C57BL/6J backcross. In addition, 30 members of the multigene families encoding PGK1 ODC, and TPI, including five new loci for ODC and one new locus for TPI, were characterized and mapped. Interspecific backcross linkage data for 29 nonecotropic murine leukemia retroviruses endogenous to C57BL/6J mice are also reported. Transmission ratio distortions and recombination frequencies are compared between the two backcrosses.

Animals↗
PubMed1994

A frameshift mutation in the mouse alpha 1 glycine receptor gene (Glra1) results in progressive neurological symptoms and juvenile death.

The neurologic mutant mouse, oscillator, is characterized by a fine motor tremor and muscle spasms that begin at 2 weeks of age and progressively worsen, resulting in death by 3 weeks of age. We report the localization of the oscillator mutation to the central region of mouse Chr 11, and demonstrate its allelism with spasmodic, a recessive viable neurological mutation which displays excessive startle. Oscillator is caused by a microdeletion in the gene coding for the alpha 1 subunit of the adult glycine receptor (Glra1). Glra1 assembles into a pentameric complex with the beta subunit of the glycine receptor (3 alpha (1)2 beta 5) to form a glycine-gated chloride channel. This receptor is the major adult glycine receptor, and the site of action of the poison strychnine. The oscillator deletion causes a frameshift resulting in loss of the highly conserved third cytoplasmic loop and fourth transmembrane domain of the protein. Membranes isolated from oscillator homozygote spinal cords display a 90% reduction in glycine-displaceable strychnine binding. This lack of ligand binding function confirms that oscillator is a complete loss of function allele. The oscillator mutation provides evidence that although at least four different alpha subunits exist for the glycine receptor, none of the other subunits can compensate for the loss of alpha 1 function. Mutations which impair GLRA1 function in humans have been shown to cause dominant familial startle disease. The identification of the oscillator mutation suggests that severe loss of function alleles in humans would result in prenatal or neonatal lethality.

Amino Acid Sequence↗
PubMed1994

Prognosis of patients with left ventricular dysfunction, with and without viable myocardium after myocardial infarction. Relative efficacy of medical therapy and revascularization.

BACKGROUND: The uptake of F-18 deoxyglucose into dysfunction segments after myocardial infarction identifies metabolically active (FDG+) or inactive (FDG-) myocardium. Although patients with FDG+ segments have been found to be at risk for adverse events, the prognostic significance of viable myocardium in relation to other influences on postinfarction prognosis, including revascularization, remain ill defined. The purpose of this study was to investigate the relative prognostic significance of FDG+ tissue and to establish whether myocardial revascularization in patients with viable tissue attenuates the risk of adverse outcome. METHODS AND RESULTS: One hundred thirty-seven patients with left ventricular dysfunction and resting perfusion defects after myocardial infarction underwent positron emission tomography with both dipyridamole stress Rb-82 perfusion imaging and FDG imaging. After the exclusion of 4 patients proceeding to transplantation, 2 with uninterpretable scans and 2 lost to follow-up, 129 patients were followed clinically for 17 +/- 9 months. Four groups were defined: patients with FDG+ dysfunctional myocardium who were revascularized (n = 49) or treated medically (n = 21) and those with FDG- segments who were revascularized (n = 19) or treated medically (n = 40). The groups of patients with FDG+ or FDG- findings, with and without revascularization, did not differ with respect to known determinants of postinfarction prognosis: age, left ventricular ejection fraction, or the prevalence of multivessel disease. Nonfatal ischemic events occurred in 48% of medically treated FDG+ patients compared with 8% of revascularized patients with FDG+ tissue (P < .001) and 5% of patients with FDG- myocardium (P < .001). Thirteen patients died from cardiac causes; 11 (85%) had a left ventricular ejection fraction of < 30%, and these patients were evenly distributed between FDG+ and FDG- groups. Using Cox's proportional hazards model, only the presence of FDG+ myocardium (odds ratio, 12.9; P < .001) and the absence of revascularization (odds ratio, 5.8; P = .002) independently predicted ischemic events, while only age (P = .02) and ejection fraction (P < .001) but not the presence of viable myocardium were predictive of death. CONCLUSIONS: Residual viable myocardium after myocardial infarction may act as an unstable substrate for further events unless it is revascularized. Despite this association, age and left ventricular dysfunction remained the strongest predictors of cardiac death after myocardial infarction in these patients with a spectrum of left ventricular dysfunction.

Aged↗
PubMed1994

Current status of the clinical applications of cardiac positron emission tomography.

At the present time, positron emission tomography (PET) has evolved into an accurate clinical diagnostic imaging procedure for coronary artery disease that provides unique information, presently unavailable from other imaging modalities, for the management of patients with previous myocardial infarction. The superior accuracy of PET for the diagnosis of coronary artery disease has had a positive influence on the management decision process to perform revascularization. In addition to the superior accuracy of PET compared with single photon emission computed tomography, PET has the advantage of being able to identify viable hibernating myocardium.

Animals↗
PubMed1993

Parametric phase display for biventricular function from gated cardiac blood pool single-photon emission tomography.

Complete assessment of biventricular function from planar ECG-gated cardiac blood pool studies has been limited because of the overlap of adjacent activity-containing structures. Theoretically, single-photon emission tomography (SPET) can be used to comprehensively evaluate both ventricles by isolating them from surrounding anatomy. However, an enormous amount of parametric data is generated from gated SPET studies, and much of it is diagnostically irrelevant for ventricular wall motion analysis. To compress this information to a more easily interpretable format, a two-dimensional parametric display has been developed. Fourier analysis of short-axis tomograms from a gated cardiac blood pool SPET study generates three-dimensional, first-harmonic phase data. Circumferential profile data from the parametric tomograms of the right and left ventricle are mapped onto a two-dimensional polar display. This method is demonstrated in a normal patient and in three patients with abnormal ventricular contraction patterns and appears to have potential application for the analysis and characterization of biventricular wall motion.

Aged↗
PubMed1993

Identification and genetic mapping of the murine gene and 20 related sequences encoding chromosomal protein HMG-17.

HMG-17 is an abundant, nonhistone chromosomal protein that binds preferentially to nucleosomal core particles of mammalian chromatin. The human gene for HMG-17 has been localized to Chromosome (Chr) 1p, but the murine gene has not been previously mapped. Here we identify the murine functional gene, Hmg17, from among more than 25 related sequences (probably processed pseudogenes) and show that it is located on mouse Chr 4, in a region known to have conserved linkage relationships with human Chr 1p. We also report the map locations of 20 additional Hmg17-related sequences on mouse Chrs 1, 2, 3, 5, 7, 8, 9, 13, 15, 16, 17, 18, and X. The multiple, dispersed members of the Hmg17 multigene family can be detected efficiently with a single cDNA probe and provide useful markers for genetic mapping studies in mice.

Animals↗
PubMed1993

Pulmonary embolism: increased ventilation in areas of decreased perfusion.

An abnormal finding that is considered characteristic of large or extensive pulmonary embolism has been observed on ventilation-perfusion (V-P) lung scans. This observation is a regional area of increased ventilation radioactivity in the embolized region of the lung that is more than the normal ventilation radioactivity in the adjacent or contralateral normally perfused lung. It has been designated the "enhanced V-P mismatch sign." This sign was noted in 15 cases among approximately 700 routine V-P lung scans interpreted by a nuclear radiologist. Of these, large or extensive emboli were confirmed in only 10 cases, nine by means of angiography and one by means of autopsy studies. The remaining five cases demonstrated clinical correlation only and are not included in this report. Of the 10 confirmed cases with enhanced V-P mismatch sign, increased ventilation radioactivity involved unilateral lung distribution in five and zonal or lobar distribution in five. The Westermark sign was seen in only seven of the 10 cases. It is hoped that this observation will prove useful in the diagnosis of large or extensive pulmonary emboli.

Adult↗
PubMed1993

Clinical outcome of cardiac patients with negative thallium-201 SPECT and positive rubidium-82 PET myocardial perfusion imaging.

In a previous comparison of 202 consecutive patients who underwent myocardial perfusion imaging with both 201Tl SPECT and 82Rb PET, 27 patients were identified as having true-positive 82Rb images, but false-negative 201Tl images. The purpose of this report is to determine the effect of correct image interpretation of coronary artery disease on the final management of those patients and compare it to the previous management scheme wherein a negative image was usually accepted as the end point unless clinical symptoms dictated otherwise. A follow-up study of the clinical course and outcome of these studies showed that 63% (17/27) of the patients with a true-positive 82Rb PET image were recommended for revascularization procedures. It is doubtful that this majority of patients would have received either surgical or interventional management based on the false-negative 201Tl SPECT procedure alone.

Angioplasty, Balloon, Coronary↗
PubMed1992

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↗
PubMed1992

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↗
PubMed1992

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↗