Kinetic analysis of dynamic 13C NMR spectra: metabolic flux, regulation, and compartmentation in hearts.

Control of oxidative metabolism was studied using 13C NMR spectroscopy to detect rate-limiting steps in 13C labeling of glutamate. 13C NMR spectra were acquired every 1 or 2 min from isolated rabbit hearts perfused with either 2.5 mM [2-13C]acetate or 2.

Brain mechanisms in human classical conditioning: a PET blood flow study.

Five healthy male subjects participated in a classical conditioning experiment, and positron emission tomography (PET) was used to compare regional cerebral blood flow before and after conditioning. The subjects participated in three different experimental phases. In the first (habituation) phase they listened to 24 repetitions of a tone with random intervals.

Cardiac V1 and V3 myosins differ in their hydrolytic and mechanical activities in vitro.

The two mammalian cardiac myosin heavy chain isoforms, alpha and beta, have 93% amino acid homology, but hearts expressing these myosins exhibit marked differences in their mechanical activities. To further understand the function of these cardiac myosins as molecular motors, we compared the ability of these myosins to hydrolyze ATP and to both translocate actin filaments and generate force in an in vitro motility assay. V1 myosin has twice the actin-activated ATPase activity and three times the actin filament sliding velocity when compared with V3 myosin.

Myocyte reorganization in hypertrophied and failing hearts.

In hypertrophied and failing hearts there are major changes in the overall contractile performance. We present a review of our previous work relating the alterations in myocardial force, work, power and relaxation, that lead to changes in overall ventricular performance, to changes in the actin-myosin cross-bridge cycle characteristics along with the degree of activation and inactivation (calcium cycling). Tissues from hypertrophied rabbit and failing human (volume overload, dilated cardiomyopathy) heart were used in these studies.

Functional neuroanatomy of antisaccade eye movements investigated with positron emission tomography.

Increasing interest in the role of the frontal lobe in relation to psychiatric and neurologic disorders has popularized tests of frontal function. One of these is the antisaccade task, in which both frontal lobe patients and schizophrenics are impaired despite normal performance on (pro)saccadic tasks. We used position emission tomography to examine the cerebral blood flow changes associated with the performance of antisaccades in normal individuals.

Effects of calcium sensitizers on intracellular calcium handling and myocardial energetics.

Calcium sensitizers may influence myocardial energetics by their action on calcium turnover and on crossbridge behavior. Using a myothermal method, the effects of the Ca2+ sensitizer EMD-53998 on calcium cycling, crossbridge behavior, and myocardial energy turnover were compared with the effects of an increase in extracellular calcium from 1.25 to 7.

Sarcoplasmic reticulum gene expression in pressure overload-induced cardiac hypertrophy in rabbit.

Pressure overload (PO)-induced cardiac hypertrophy in rabbits has been utilized extensively to study alterations in systolic and diastolic functions of the heart. In earlier studies we showed that the levels of mRNA encoding two important sarcoplasmic reticulum (SR) proteins, the cardiac/slow-twitch muscle Ca(2+)-ATPase (SERCA2a) and phospholamban, were decreased in PO rabbit hearts. In this study, we analyzed the expression of the Ca(2+)-release channel (ryanodine receptor), calsequestrin, SERCA2a, and phospholamban in PO-induced cardiac hypertrophy after 2, 4, 8, and 16 days of pulmonary artery banding.

A positron emission tomographic study of simple phobic symptom provocation.

Background: The goal of this study was to determine the mediating neuroanatomy of simple phobic symptoms.

Methods: Positron emission tomography and oxygen 15 were used to measure normalized regional cerebral blood flow in seven subjects with simple phobia during control and provoked states. Stereotactic transformation and statistical parametric mapping techniques were employed to determine the locations of significant activation.

Influence of isoproterenol on contractile protein function, excitation-contraction coupling, and energy turnover of isolated nonfailing human myocardium.

Previous animal experiments indicated that the effects of catecholamines on myocardial function and subcellular systems vary considerably depending on the species and type of myocardium investigated. In the present study, we used isometric force and heat measurements to investigate the influence of isoproterenol on energetics of excitation-contraction coupling and contractile proteins in isolated nonfailing human myocardium. Isoproterenol, in an average concentration of 0.

Identifying objects seen from different viewpoints. A PET investigation.

Positron emission tomography scans were acquired when subjects performed three tasks, each in a separate block of trials. They decided whether words named pictures of objects viewed from a canonical perspective, decided whether words named pictures of objects viewed from a non-canonical (unusual) perspective or saw random patterns of lines and pressed a pedal when they heard the word (this was a baseline condition). The dorsolateral prefrontal region was activated when subjects identified objects seen from non-canonical perspectives, as expected if the frontal lobes are involved in top-down perceptual processing.

The dose uptake ratio as an index of glucose metabolism: useful parameter or oversimplification?

Unlabelled: The dose uptake ratio (DUR) has been used as a quantitative index of glucose metabolism for tumor classification and monitoring response to treatment. In order to provide consistent results, DUR measurements should be made when the concentration of tracer has reached a plateau. The time of this plateau cannot be identified from a single static acquisition.

Tissue pharmacokinetics of fleroxacin in humans as determined by positron emission tomography.

The delivery of fleroxacin, a new broad-spectrum fluoroquinolone, to the major organs of the body was studied in 12 normal human volunteers (nine men and three women), utilizing positron emission tomography (PET). Following the infusion of 20 mCi of [(18)F]fleroxacin in conjuction with a standard therapeutic dose of 400 mg, images were acquired over 8 h. Beginning the next day, the subjects received unlabeled drug at a dose of 400 mg/day for 3 days, with a repeat PET study on the fifth day.

Positive inotropism and myocardial energetics: influence of beta receptor agonist stimulation, phosphodiesterase inhibition, and ouabain.

Objective: The aim was to study the effect of three positive inotropic interventions on myocardial force development and heat production in guinea pig papillary muscles in order to investigate the energetic consequences.

Methods: The positive inotropic agents used were epinine (beta adrenoceptor stimulation), E-1020 (phosphodiesterase inhibition), and ouabain (sodium-potassium ATPase inhibition). Heat measurements were accomplished using antimony-bismuth thermopiles, and initial heat was separated into tension dependent and tension independent heat using the butanedione-monoxime (BDM) and the shortening methods.

Synthesis of 2-[18F]fluoro-2-deoxy-L-glucose and positron emission tomography studies in monkeys.

2-[18F]Fluoro-2-deoxy-L-glucose was synthesized from its trifluoromethanesulfonyl precursor. The precursor was prepared by selective acetylation and triflation of L-mannose. L-Mannose was first treated with acetic anhydride in the presence of a catalytic amount of perchloric acid and then reacted with phosphorus tribromide followed by aqueous sodium acetate to produce pure 1,3,4,6-tetra-O-acetyl-a-L-mannopyranose in 32% yield.

Positron emission tomographic measurements of absolute regional myocardial blood flow permits identification of nonviable myocardium in patients with chronic myocardial infarction.

Objectives: This study tested the hypothesis that nonviable myocardium can be identified by quantitative measurements of regional myocardial blood flow obtained using positron emission tomography in conjunction with a mathematical model of nitrogen-13 (N-13) ammonia tracer kinetics.

Background: Under steady state basal conditions there is a minimal level of blood flow required to sustain myocardial viability. Therefore, the hypothesis predicts that regions with flow below a certain threshold are likely to be composed primarily of scar.

Myocardial extraction of 1-[11C] betamethylheptadecanoic acid.

Unlabelled: Betamethylheptadecanoic acid (BMHA) is a branched chain fatty acid analog that is transported into myocardial cells by the same long chain fatty acid carrier protein mechanism as natural fatty acids, but cannot be completely catabolized and accumulates in the tissue. Thus, 11C-labeled BMHA is a useful tracer for the noninvasive evaluation of myocardial fatty acid utilization by positron emission tomography (PET).

Methods: As a prelude to PET studies, the metabolism of BMHA was studied by classical techniques.

Smooth, cardiac and skeletal muscle myosin force and motion generation assessed by cross-bridge mechanical interactions in vitro.

Differences in the mechanical properties of mammalian smooth, skeletal, and cardiac muscle have led to the proposal that the myosin isozymes expressed by these tissues may differ in their molecular mechanics. To test this hypothesis, mixtures of fast skeletal, V1 cardiac, V3 cardiac and smooth muscle (phosphorylated and unphosphorylated) myosin were studied in an in vitro motility assay in which fluorescently-labelled actin filaments are observed moving over a myosin coated surface. Pure populations of each myosin produced actin filament velocities proportional to their actin-activated ATPase rates.

Regional cerebral blood flow measured during symptom provocation in obsessive-compulsive disorder using oxygen 15-labeled carbon dioxide and positron emission tomography.

Background: The study was designed to determine the mediating neuroanatomy of obsessive-compulsive disorder (OCD).

Methods: The short half-life tracer oxygen 15-labeled carbon dioxide was used to allow for repeated positron emission tomographic determinations of regional cerebral blood flow on each of eight patients with OCD during a resting and a provoked (symptomatic) state.

Results: Individually tailored provocative stimuli were successful in provoking OCD symptoms, in comparison with paired innocuous stimuli, as measured by self-report on OCD analogue scales (P = .

Myocardial force-frequency defect in mitral regurgitation heart failure is reversed by forskolin.

Background: Postoperative ejection phase parameters and patient survival rates for mitral valve replacement surgery are considerably lower than for similar aortic valve surgery. While chordal transection probably is the major contributor to the lowered values, there is also evidence for decreased preoperative myocardial contractile reserve in mitral regurgitation patients. This study characterizes abnormalities in the force-frequency relation that may underlie impaired function of myocardium isolated from mitral regurgitation patients with New York Heart Association class II-III heart failure.

Using locations to store shape: an indirect effect of a lesion.

This study had three general points. First, it examined possible visual consequences of frontal lesions. A patient with focal damage to the subcortical regions of the left frontal lobe, and a small amount of damage near Broca's area, was predicted to have impaired brain function in posterior regions that are anatomically connected to the damaged site.

Pharmacokinetics of [18F]fleroxacin in healthy human subjects studied by using positron emission tomography.

Positron emission tomography (PET) with [18F]fleroxacin was used to study the pharmacokinetics of fleroxacin, a new broad-spectrum fluoroquinolone, in 12 healthy volunteers (9 men and 3 women). The subjects were infused with a standard therapeutic dose of fleroxacin (400 mg) supplemented with approximately 20 mCi of [18F]fleroxacin. Serial PET images were made and blood samples were collected for 8 h, starting at the initiation of the infusion.

Fluorodeoxyglucose PET of abdominal and pelvic neoplasms: potential role in oncologic imaging.

Fluorine-18-fluoro-2-deoxyglucose (FDG) positron emission tomography (PET) was used to image 38 patients with known or suspected malignant processes involving the abdomen or pelvis (including primary [n = 2] and secondary [n = 19] liver tumors, recurrent colon carcinoma [n = 1], lymphoma [n = 15], and cavernous hemangioma [n = 1]). PET results were compared with those from concurrent computed tomographic (CT) studies. Conspicuity of metastatic liver lesions on PET images often exceeded that of lesions on CT scans.

Visual Mental Imagery Activates Topographically Organized Visual Cortex: PET Investigations.

Abstract Cerebral blood flow was measured using positron emission tomography (PET) in three experiments while subjects performed mental imagery or analogous perceptual tasks. In Experiment 1, the subjects either visualized letters in grids and decided whether an X mark would have fallen on each letter if it were actually in the grid, or they saw letters in grids and decided whether an X mark fell on each letter. A region identified as part of area 17 by the Talairach and Tournoux (1988) atlas, in addition to other areas involved in vision, was activated more in the mental imagery task than in the perception task.