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Biomedical subjects

J J O'Neil

Publications and source records attributed to J J O'Neil.

6 recordsLinked to original sources

Multiple TCR V beta usage by infiltrates of young NOD mouse islets of Langerhans. A polymerase chain reaction analysis.

Because a restricted repertoire of T-cell receptor (TCR) V beta gene expression has been reported in other autoimmune diseases, the possibility of similarly restricted V beta gene expression by T-cell infiltrates of NOD mouse islets was examined. With isolated islets from 4- to 12-wk-old NOD mice, a prospective polymerase chain reaction analysis with 18 V beta-specific oligonucleotide primers was performed on the noncloned and unexpanded islet-infiltrating T cells. The methodology used permitted the detection of a minimum of 50 T cells. In contrast to the restricted TCR V beta gene usage reported for other autoimmune diseases, infiltrates of even the youngest mice were characterized by expression of multiple V beta gene segments.

Animals

Effects of 4 percent and 6 percent carboxyhemoglobin on arrhythmia production in patients with coronary artery disease.

In this study, we assessed the effects of exposure to 4 percent and 6 percent carboxyhemoglobin on ventricular arrhythmias in 41 subjects (nonsmokers) with documented coronary artery disease. We used a randomized, double-blind, crossover design. On day 1, a training session with no exposure, the baseline carboxyhemoglobin level was measured, and a supine bicycle exercise test was done. On days 2 through 4, subjects were exposed to room air, 100 parts per million (ppm)2 carbon monoxide (target, 4 percent blood carboxyhemoglobin), or 200 ppm carbon monoxide (target, 6 percent blood carboxyhemoglobin), and they then did a supine bicycle exercise test. Radionuclide ventriculography was performed at rest and during exercise. Ambulatory electrocardiogram recordings were made during the four consecutive days to determine the frequency of premature ventricular contractions at various intervals. The frequency of single premature ventricular contractions per hour during exercise was significantly greater on the 6 percent carboxyhemoglobin day than on the room air day (167.72 +/- 37.99 for 6 percent carboxyhemoglobin compared with 127.32 +/- 28.22 for room air, p = 0.03). The frequency of multiple premature ventricular contractions per hour was also significantly greater during exercise on the 6 percent carboxyhemoglobin day compared with the room air day (9.59 +/- 3.70 for the 6 percent carboxyhemoglobin day compared with 3.18 +/- 1.67 for the room air day, p = 0.02). Patients who developed increased arrhythmias during exercise on the 6 percent carboxyhemoglobin day were significantly older than those who had no increased arrhythmia, and, in addition, exercised longer and had a higher peak workload during exercise. No effect of carbon monoxide exposure was seen on the 4 percent carboxyhemoglobin day.

Aged

Production of arrhythmias by elevated carboxyhemoglobin in patients with coronary artery disease.

OBJECTIVE: To assess the effects of exposure to 4% and 6% carboxyhemoglobin on ventricular arrhythmias in patients with coronary artery disease. DESIGN: Randomized, double-blind, crossover design. SETTING: Exercise laboratory with an environmentally controlled exposure. PATIENTS: Forty-one nonsmokers with documented coronary artery disease. INTERVENTION: On day 1, a training session with no exposure, the baseline carboxyhemoglobin level was measured, and a supine bicycle exercise test was done. On days 2 to 4, patients were exposed to room air, 100 ppm carbon monoxide (target, 4% carboxyhemoglobin) or 200 ppm carbon monoxide (target, 6% carboxyhemoglobin), and they then did supine bicycle exercise with radionuclide ventriculography. Ambulatory electrocardiogram recordings were made during the 4 consecutive days to determine the frequency of ventricular premature depolarization (VPD) at various intervals. MEASUREMENTS AND MAIN RESULTS: The frequency of single VPD/h was significantly greater on the 6% carboxyhemoglobin day than on the room air day during the exercise period (167.72 +/- 37.99 for 6% carboxyhemoglobin compared with 127.32 +/- 28.22 for room air, P = 0.03). During exercise, the frequency of multiple VPD/h was greater on the 6% carboxyhemoglobin day compared with room air (9.59 +/- 3.70 on the 6% carboxyhemoglobin compared with 3.18 +/- 1.67 on room air, P = 0.02). Patients who developed increased single VPD during exercise on the 6% carboxyhemoglobin day were significantly older than those who had no increased arrhythmia, whereas patients who developed complex arrhythmias were also older and, in addition, exercised longer and had a higher peak workload during exercise. CONCLUSION: The number and complexity of ventricular arrhythmias increases significantly during exercise after carbon monoxide exposure producing 6% carboxyhemoglobin compared with room air but not after exposure producing 4% carboxyhemoglobin.

Age Factors

Metabolism in rat lung tissue slices: technical factors.

We compared several sets of conditions used to estimate metabolism in rat lung slices. 14CO2 production from [14C]glucose, oxygen consumption, lactate production, and glucose consumption were used as measures of metabolic activity. The calculated results differed when we used 1) different techniques for estimating tissue weight, 2) tissue slices of 0.3-, 0.5-, 0.7-, and 1.0-mm thickness, 3) 95% air or 95% oxygen with 5% CO2 4) a delay after slice preparation and 4 degrees C and room temperature or periods of anoxia before incubation, 5) shaking rates of 60, 90, 120, or 150/min, 6) phosphate or bicarbonate buffers. Conditions of maximal activity were found using 95% O2 with 1.0-mm tissue slices, shaking at 120/min in phosphate buffer without periods of hypoxia or undue delays before incubation. Tissue weight should be obtained without exposure to aqueous solutions or dehydration by contact with cotton gauze or filter paper.

Animals

Isolated perfused lung--substrate utilization.

Lung metabolism has been extremely difficult to determine in vivo primarily because the lung is overwhelmed by a great blood flow that generally makes the Fick principle inadequate. Largely for reasons such as this, investigators have had to rely on in vitro preparations. The isolated perfused lung has the apparent advantage of being similar to the lung in vivo when compared with other preparations. For instance, there is evidence that the capillary bed of the lung may alter substrates and influence their subsequent metabolism. Substrates have contact with the capillary endothelium in isolated perfused lungs but not to tissue slices, homogenates, or isolated cells. Our studies indicate that precursors of saturated phosphatidylcholine may include lipids, which are hydrolyzed in the capillary of the isolated perfused lung and thus become substrates such as free fatty acids, etc. However, tissue slices do not use the esterified lipids to the same extent, presumably because in this preparation the enzymes in the capillary endothelium do not have contact with the esterified lipids. Substrate utilization of the isolated perfused lung may be considerably altered by inflation of the lung or by pulmonary edema. Although glucose utilization and palmitate oxidation by the isolated perfused lung and by tissue slices of the rat lung are very similar, if the isolated perfused lung develops pulmonary edema, glucose utilization increases by nearly 100%. This phenomenon is apparently not due solely to fluid in the airspaces because in control studies with fluid added into the airways the glucose utilization did not increase to the degree observed with edematous lungs. Lung distention is associated with increased glucose consumption but marked distention is also associated with pulmonary edema. The effect of lung distension may be a direct effect or it may be secondary to the pulmonary edema.

Animals

Respiratory response of humans exposed to low levels of ozone for 6.6 hours.

Recent evidence suggests that prolonged exposures of exercising men to 0.08 ppm ozone (O3) result in significant decrements in lung function, induction of respiratory symptoms, and increases in nonspecific airway reactivity. The purpose of this study was to confirm or refute these findings by exposing 38 healthy young men to 0.08 ppm O3 for 6.6 h. During exposure, subjects performed exercise for a total of 5 h, which required a minute ventilation of 40 l/min. Significant O3-induced decrements were observed for forced vital capacity (FVC, -0.25 l), forced expiratory volume in 1 s (FEV1.0, -0.35 l), and mean expiratory flow rate between 25% and 75% of FVC (FEF25-75, -0.57 l/s), and significant increases were observed in airway reactivity (35%), specific airway resistance (0.77 cm H2O/s), and respiratory symptoms. These results essentially confirm previous findings. A large range in individual responses was noted (e.g., percentage change in FEV1.0; 4% increase to 38% decrease). Responses also appeared to be nonlinear in time under these experimental conditions.

Adolescent