Structural and functional responses of enzymes to immobilization: new insights from EPR spectroscopy.
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Alcohol Dehydrogenase↗
Biomedical subjects
R R Miller
Publications and source records attributed to R R Miller.
Usual interstitial pneumonia: correlation of CT with clinical, functional, and radiologic findings.
Correlation between disease extent on computed tomographic (CT) scans and severity of clinical and functional impairment was obtained in 23 patients with usual interstitial pneumonia (UIP) by review of the clinical data, pulmonary function tests, chest radiographs, and CT scans. The CT scans and chest radiographs were each read twice by two independent observers. Disease extent was assessed on CT scans by a visual score (0%-100% involvement of the lung parenchyma) and on the radiograph by the International Labour Office classification. There was good intraobserver and interobserver agreement for both CT and radiograph scores (all r greater than or equal to .71). CT scans gave a better estimate of disease extent and showed more extensive honeycombing than did the radiograph. A significant correlation was found between the extent of disease as assessed with CT and the severity of dyspnea (r = .62, P less than .001), as well as between CT and impairment in gas exchange as assessed by the diffusing capacity (r = .64, P less than .001). There was poor correlation between disease severity as assessed with chest radiography and the clinical and functional variables (all r less than or equal to .39).
Adult↗
Disease activity in idiopathic pulmonary fibrosis: CT and pathologic correlation.
Computed tomography (CT) scans were compared with pathologic determinants of disease activity in 12 patients with idiopathic pulmonary fibrosis. The theory was that intraalveolar and interstitial cellularity would result in areas of opacification of air spaces on CT scans. All patients underwent open lung biopsy, and disease activity was assessed with a pathologic grading system. Seven patients had mild disease activity, five had moderate to marked disease activity. Opacification of air spaces was patchy in distribution, predominantly peripheral, and seen better on 1.5-mm rather than 10-mm collimation scans. Disease activity on CT scans was graded independently from 0 to 3 based on the presence and relative density of the areas of air space consolidation compared with the surrounding parenchyma. The pathologic score was significantly greater in the patients with high CT scores than in those with low CT scores (P = .001). Five patients with marked disease activity and five of seven patients with mild disease activity were correctly identified. CT may be useful in the assessment of disease activity in idiopathic pulmonary fibrosis.
Adult↗
Tension pneumopericardium: an unusual manifestation of invasive pulmonary aspergillosis.
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Adult↗
Metabolism and disposition of glycol ethers.
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Animals↗
Mechanisms underlying retarded emergence of conditioned responding following inhibitory training: evidence for the comparator hypothesis.
The comparator hypothesis posits that conditioned responding is determined by a comparison at the time of testing between the associative strengths of the conditioned stimulus (CS) and stimuli proximal to the CS at the time of conditioning. The hypothesis treats all associations as being excitatory and treats conditioned inhibition as the behavioral consequence of a CS that is less excitatory than its comparator stimuli. Conditioned lick suppression by rats was used to differentiate four possible sources of retarded responding to an inhibitory CS. These include habituation to the unconditioned stimulus (US), latent inhibition to the CS, blocking of the CS-US association by the conditioning context, and enhanced excitatory associations to the comparator stimuli. Prior research has demonstrated the first three phenomena. Therefore, we employed parameters expected to highlight the fourth one--the comparator process. In Experiment 1, our negative contingency training was shown to produce a conditioned inhibitor that passed inhibitory summation and retardation tests. In Experiment 2 we found transfer of retardation from an inhibitory CS to a novel stimulus when the location where retardation-test training occurred was excitatory, which is indicative of contextual blocking and/or comparator effects. In Experiment 3, extinction of the conditioning context was found to attenuate retardation regardless of whether extinction occurred before or after the CS-US pairings of the retardation test. This indicates that much of the present retardation was due to the comparator process rather than to contextual blocking. Experiment 4 demonstrated that habituation to the US did not contribute to retardation in the present case. Collectively, these studies suggest that retardation following inhibitory training can be explained without recourse to any of the traditional mechanisms of conditioned inhibition.
Animals↗
The comparator hypothesis of conditioned response generation: manifest conditioned excitation and inhibition as a function of relative excitatory strengths of CS and conditioning context at the time of testing.
In the present research water-deprived rats were used in a conditioned lick suppression paradigm to test and further develop Rescorla's (1968) contingency theory, which posits that excitatory associations are formed when a conditioned stimulus (CS) signals an increase in unconditioned stimulus (US) likelihood and that inhibitory associations develop when the CS signals a decrease in US likelihood. In Experiment 1 we found that responding to a CS varied inversely with the associative status of the context in which the CS was trained and that this response was unaltered when testing occurred in a distinctively dissimilar context with a different conditioning history, provided associative summation with the test context was minimized. These results suggest that manifest excitatory and inhibitory conditioned responding is modulated by the associative value of the training context rather than that of the test context. In Experiment 2 it was demonstrated that postconditioning decreases in the associative value of the CS training context reduced the effective inhibitory value of the CS even when testing occurred outside of the training context. Moreover, this contextual deflation effect was specific to the CS training context as opposed to any other excitatory context. Collectively, these studies support the comparator hypothesis, which states that conditioned responding is determined by a comparison of the associative strengths of the CS and its training context that occurs at the time of testing rather than at the time of conditioning. This implies that all associations are excitatory and that responding indicative of conditioned inhibition reflects a CS-US association that is below (or near) the associative strength of its comparator stimulus. It is suggested that response rules which go beyond a monotonic relation between associative value and response strength can partially relieve learning theories of their explanatory burdens, thereby allowing for simpler models of acquisition.
Animals↗
Associative effects of US preexposure: modulation of conditioned responding by an excitatory training context.
In two experiments we examined factors that contribute to retarded emergence of conditioned responding to a conditioned stimulus (CS) trained in a context in which unsignaled unconditioned stimuli (USs) had previously been administered. In both experiments water-deprived rats were used in a conditioned lick suppression task to measure the conditioned response elicitation potential of the CS and the training context. From Experiment 1 we determined that nonreinforced exposure to the excitatory context after US preexposure and prior to CS-US pairings in that context eliminated the conditioned response deficit observed on a subsequent test of the CS. The recovery from the US preexposure deficit was nearly as great in animals that received nonreinforced exposure to the excitatory training context after the CS-US pairings but prior to the ultimate test of the CS. From Experiment 2 we determined that the recovery induced by contextual deflation after CS training was specific to deflation of the context in which the CS was trained as opposed to another excitatory context. In total, these experiments suggest that context-US associations partially mask the expression of a learned CS-US association. These results are discussed in terms of recent models of conditioned response generation.
Animals↗
Predicting the response of obstructive endobronchial tumors to photodynamic therapy.
To investigate the usefulness of bronchoscopic examination, computerized tomography (CT), and radionuclide quantitative ventilation-perfusion lung scan to determine the response of patients with obstructive endobronchial tumors to photodynamic therapy (PDT), the findings in 24 patients treated with PDT were analyzed. PDT was found to be most effective when the tumor was bronchoscopically polypoid in appearance, with little or no submucosal invasion or peribronchial extension seen on CT scans. With increasing submucosal and/or peribronchial extension, the immediate response to treatment was poorer. Patients who had 50% or more of the airway obstruction due to mucosal tumor had no evidence of local tumor recurrence for a median interval of 22 weeks after treatment. In patients with predominant submucosal and/or peribronchial tumor, the duration of response was 7 weeks. Response to treatment did not correlate with the degree of airway obstruction. CT provided valuable information regarding the extent of the peribronchial involvement and airway distortion, which was often underestimated by bronchoscopy alone. Absent perfusion or reduction of regional perfusion out of proportion to ventilation on scintigraphy in the involved lung zone was found to be associated with extensive peribronchial involvement and a poor outcome. The authors conclude that the addition of CT and radionuclide quantitative ventilation-perfusion lung scan to bronchoscopic examination is useful in predicting the response of patients with obstructive endobronchial tumors to PDT.
Adult↗
Metabolism and disposition of propylene glycol monomethyl ether (PGME) beta isomer in male rats.
Male Fischer 344 rats were given a single po dose of approximately 1 or 8.7 mmol/kg of radiolabelled propylene glycol monomethyl ether (PGME) beta isomer (2-methoxy-1-propanol). After dosing, expired air, excreta, and tissues were analyzed for 14C activity and metabolites in urine were isolated and identified. Approximately 70 to 80% of the 14C was excreted in urine while about 10 to 20% was eliminated as 14CO2 within 48 hr after dosing. The major urinary metabolite was 2-methoxypropionic acid, which accounted for approximately 93 and 79% of the radioactivity in urine from high- and low-dose animals, respectively. A glucuronide conjugate of the PGME beta isomer was also identified in urine; this metabolite accounted for approximately 3 to 4% of the radioactivity in the urine at both dosages. These results indicate that the PGME beta isomer is metabolized via different routes to different types of metabolites in comparison to the PGME alpha isomer. While the two isomers are biotransformed differently, there is a substantial toxicological data base which clearly shows that the commercial grade PGME mixture (2 to 5% beta isomer) has a low degree of biological activity.
Animals↗
Incapacitation and treatment of rats exposed to a lethal dose of sulfuryl fluoride.
Rats exposed to 4000 ppm sulfuryl fluoride (VIKANE gas fumigant, SO2F2) were incapacitated within 45 min and died within several hours after exposure. Exposure to higher concentrations resulted in a shorter time to incapacitation and death occurred within minutes. Treatment with calcium gluconate before exposure to 4000 ppm SO2F2 for 45 min resulted in 80% survival. However, calcium gluconate did not alleviate SO2F2-induced convulsions. Administration of phenobarbital before or after exposure to 4000 ppm SO2F2 for 45 min effectively reduced the frequency and severity of convulsions and resulted in survival of all animals. Exposure of rats to 10,000 ppm SO2F2 for 15 min followed by treatment with phenobarbital reduced the frequency of convulsions and delayed death, but did not prevent death. Diazepam was less effective than phenobarbital while diphenylhydantoin had no beneficial effect and, in fact, made the convulsions more severe and longer in duration. The results of this study indicate that phenobarbital was effective in ameliorating the acute toxic effects of an overexposure to SO2F2 in rats.
Animals↗
CT in the qualitative assessment of emphysema.
To assess the ability of CT to demonstrate the different types of emphysema, the CT appearance was compared with the corresponding barium-impregnated pathologic specimens cut in the transverse plane, in four patients with emphysema. The CT appearance was also compared with the chest radiographs of two patients with irregular emphysema associated with progressive massive fibrosis. The parenchymal destruction visualized on CT in the patients with mild and moderate centriacinar emphysema was distinctly different from that seen in the patient with panacinar emphysema in appearance and distribution. Paraseptal and irregular emphysema were also well demonstrated using CT. Window widths between 800 and 1,500 were found to demonstrate the parenchymal changes most accurately. We conclude that CT can help to identify the presence of emphysema and to distinguish radiologic characteristics of the different types of emphysema.
Humans↗
Fibrosing alveolitis: CT-pathologic correlation.
Computed tomography (CT) was performed within 10 days of open lung biopsy in nine patients with fibrosing alveolitis. One-centimeter collimation contiguous scans through the chest were obtained in all patients. Additional 1.5-mm collimation scans were obtained in the area in which lung biopsy was later performed in six patients. In seven patients, CT demonstrated patchy involvement of the lung parenchyma, areas with a reticular pattern being intermingled with areas of normal lung. The reticular pattern was associated with cystic spaces 2-4 mm in diameter and was more severe in the lung periphery. Histologically, the reticular pattern corresponded to areas of irregular fibrosis. One patient had diffuse honeycombing (2-20-mm cysts), and one had honeycombing only in the lung periphery. In all patients, CT clearly defined the architectural changes seen on open lung biopsy. These changes were much better seen on the 1.5-mm than on the 10-mm collimation scans. CT may be helpful in determining the pattern and distribution of lung involvement in patients with fibrosing alveolitis and in guiding the surgeon to the most appropriate area(s) for biopsy.
Adult↗
Intestinal blood flow and O2 uptake during hypoxemia in the newborn piglet.
Previous work has indicated that the neonatal intestinal circulation responds to hypoxemia with vasoconstriction and subsequent intestinal ischemia. This work was carried out in newborn lambs, a ruminant species, and may not be representative of all newborns. Therefore, we measured intestinal blood flow, vascular resistance, tissue O2 uptake, and cardiac output during normoxemia and varying degrees of hypoxemia in newborn piglets, a nonruminant species. Hypoxemia was induced by adding N2 gas to the inspired gas mixture, and measurements were obtained over a wide range of arterial O2 contents (2.2-15.6 ml O2 X dl-1). Intestinal blood flow increased in response to moderate hypoxemia and decreased in response to severe hypoxemia. The changes in intestinal blood flow were primarily due to change in intestinal vascular resistance, not cardiac output. Intestinal O2 was independent of arterial O2 content until the latter decreased below approximately 6.5 ml O2 X dl-1. These data indicate that the response of the neonatal intestinal circulation to hypoxemia is species specific and that the nonruminant neonatal intestine is capable of vasodilation in response to moderate hypoxemia.
Animals↗
Alterations in cerebral blood flow and oxygen consumption during prolonged hypocarbia.
The effect of prolonged (2 h) hypocarbia on cerebral blood flow, oxygen delivery, extraction, and consumption was studied in eight, 1- to 4-day-old piglets. Hyperventilation to PaCO2 less than 20 mm Hg acutely (30 min) decreased cerebral blood flow and oxygen consumption. Cerebral oxygen consumption was subsequently restored via increases in cerebral blood flow and thus, cerebral oxygen delivery. Cerebral oxygen extraction rose from a normocarbic baseline of 50 to 75% with acute hypocarbia and was maintained at this level. The percent decrease in blood flow to the cerebrum was greater than that to other brain regions during hypocarbia.
Animals↗
The effect of naloxone on the hemodynamics of the newborn piglet with septic shock.
Naloxone has been shown to reverse the hemodynamic sequelae of experimental septic shock in adult animal models. Its effectiveness in the newborn has not been studied. To further investigate the efficacy of naloxone, we instrumented 18 piglets for continuous measurement of mean arterial pressure, mean pulmonary arterial pressure, central venous pressure, heart rate, left ventricular pressure, contractility, cardiac output, and O2. Oxygen consumption, systemic vascular resistance, and pulmonary vascular resistance were calculated. Following a stabilization period, group B beta-hemolytic Streptococci were infused over 30 min. Following the infusion, naloxone (1 mg/kg) was given followed by a continuous infusion of 1 mg/kg/h in nine treatment animals. Nine control animals were given an equal volume of saline. Both groups developed significant increases in mean pulmonary arterial pressure followed by a return to baseline. Oxygen consumption, cardiac output, contractility and mean arterial pressure decreased in both groups. Treatment with naloxone was associated with a cessation in the fall in the mean arterial pressure and the contractility. The difference in mean arterial pressure and contractility between groups was significant. The naloxone group had significantly improved 5-h survival. We speculate that naloxone may reverse some of the hemodynamic sequelae and improve survival in newborns with septic shock.
Animals↗
Retrieval variability: sources and consequences.
A memory model that differentiates between active traces (ongoing electrochemical neural transmission) and passive traces (chemical/structural modification of neurons) is briefly outlined. Evidence suggests that new information is initially encoded as a passive representation within a fraction of a second, leaving little opportunity for retroactive interference with storage processes. Instead, it appears that retroactive interference results from disruption of post-acquisition processing which is necessary for subsequent retrieval. Using this hybrid cognitive-physiological framework, we examine possible sources of associative performance deficits. A distinction is made between similarity interference (arising from the content similarity of the target and interfering traces) and processing interference (arising from the competition between the two traces for use of a limited capacity processor). Both types of interference can act proactively or retroactively, and the similarity-processing and proactive-retroactive dimensions are viewed as orthogonal to the question of whether information is permanently lost or merely subject to a reversible retrieval failure. When reminder techniques (pretest cuing) are used, numerous instances of memory failure commonly identified as "acquisition failures" are found to be reversible without the occurrence of relevant new learning. This literature review constitutes the greater part of the paper. It is concluded that many memory failures are due at least in part to retrieval failure. Consideration of potential retrieval processes in light of the studies that are reviewed argues for the expansion of the initial active-passive trace distinction to three types of traces. In addition to active traces, these include two distinct types of passive traces, i.e., a small content-addressable reference catalog with innately defined dimensions that is used to locate more detailed passive traces, and a large capacity store of detailed passive traces that is location-addressable. The latter type of passive trace presumably is laid down almost instantaneously as events occur, i.e., in real time, whereas the reference catalog type of passive trace, which is used to address the detailed traces, is established somewhat after the sequence of events is complete. Hence, the reference catalog trace is more vulnerable and results in retrieval failure when it is disrupted.(ABSTRACT TRUNCATED AT 400 WORDS)
Amnesia↗