The new environment for rural HMOs.
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Attitude of Health Personnel↗
Biomedical subjects
J McGee
Publications and source records attributed to J McGee.
Effects of viral infection on contraction of the diaphragm in mice.
Isometric contractile properties of isolated phrenic nerve-diaphragm muscle preparations were used to study the effects of picornavirus infections on diaphragm muscle function. Properties of muscles from virus-inoculated and control mice were similar during brief contractions. However, when subjected to a series of fatiguing contractions by indirect or direct stimulation, muscles of mice inoculated with a paralytic variant of encephalomyocarditis (EMC) virus showed a greater rate of fatigue and a reduced capacity to recover from fatigue than did muscles from uninoculated control mice or muscles from mice inoculated with a nonparalytic coxsackievirus B3 (CVB3). Mice paralyzed by EMC virus infection had high titers of virus in the brain and similar titers of virus in diaphragm muscle as found in diaphragm muscles of CVB3-inoculated mice. The results indicate that EMC virus infection of mice leads to increased fatigability of the diaphragm muscle and that there are both neural and muscular components of this enhanced fatigue.
Animals↗
The growth of HMOs in rural areas.
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Data Collection↗
Effect of soman on schedule-controlled behavior and brain acetylcholinesterase in rats.
Rats were trained to press a lever under a multiple fixed-ratio 25 fixed-interval 50-second (FR25 FI50-sec) schedule of food reinforcement. Soman, 70-90 micrograms/kg, s.c., suppressed response rates in both components, with a slightly greater effect in the FI schedule. The pattern of responding under the FI schedule, however, was maintained until lever-pressing was nearly completely suppressed. At the highest doses, soman occasionally caused tremors or mild tonic seizures with hindlimb abduction. The suppression of response rate was correlated with inhibition of acetylcholinesterase (AChE) in all brain regions examined: cortex, striatum, hippocampus, hypothalamus and brainstem. Cortical AChE was inhibited to the highest degree, while striatal AChE was most resistant to inhibition by soman.
Acetylcholinesterase↗
Enzymatic hydration of leukotriene A4. Purification and characterization of a novel epoxide hydrolase from human erythrocytes.
Human erythrocytes contained a soluble cytosolic epoxide hydrolase for stereospecific enzymatic hydration of leukotriene A4 into leukotriene B4. The enzyme was purified 1100-fold, to apparent electrophoretic homogeneity, by conventional DEAE-Sephacel fractionation followed by high performance anion exchange and chromatofocusing procedures. Its characteristics include a molecular weight of 54,000 +/- 1,000, an isoelectric point 4.9 +/- 0.2, a Km apparent from 7 to 36 microM for enzymatic hydration of leukotriene A4, and a pH optimum ranging from 7 to 8. The enzyme was partially inactivated by its initial exposure to leukotriene A4. There was slow but detectable enzymatic hydration (pmol/min/mg) of certain arachidonic acid epoxides including (+/-)-14,15-oxido-5,8-11-eicosatrienoic acid and (+/-)-11,12-oxido-5,8,14-eicosatrienoic acid, but not others, including 5,6-oxido-8,11,14-eicosatrienoic acid. Human erythrocyte epoxide hydrolase did not hydrate either styrene oxide or trans-stilbene oxide. In terms of its physical properties and substrate preference for leukotriene A4, the erythrocyte enzyme differs from previously described versions of epoxide hydrolase. Human erythrocytes represent a novel source for an extrahepatic, cytosolic epoxide hydrolase with a potential physiological role.
8,11,14-Eicosatrienoic Acid↗
Cell damage unmasks 15-lipoxygenase activity in human neutrophils.
Metabolism of arachidonic acid (10 microM) into 15(S)-hydroxyl-5,8,11-cis-13-trans-eicosatetraenoic acid (15-HETE) was proportional to lactate dehydrogenase release from human neutrophils incubated with supratherapeutic concentrations of non-steroidal anti-inflammatory agents. In contrast to others (Vanderhoek, J., and Bailey, J. (1984) J. Biol. Chem. 259, 6752-6756), we report that increased 15-HETE formation was not uniquely attributable to 5 mM ibuprofen, and it did not originate from enzymatic activation. For instance, ibuprofen (1-5 mM) did not affect the isolated 15-lipoxygenase enzyme in the 100,000 X g supernatant from neutrophil lysates, and dose-dependent increases in 15-HETE biosynthesis, proportional to lactate dehydrogenase release, were evident with benoxaprofen, naproxen, flurbiprofen, or etodolac. At similar supratherapeutic concentrations (1-5 mM), aspirin and phenylbutazone did not influence lactate dehydrogenase release or 15-HETE production. In further contrast, neutrophils did not tolerate 1-5 mM ibuprofen. Biochemical, morphological, flow cytometric, and fluorochromatic analyses each indicated cytological damage. A correlation between lactate dehydrogenase release and increased 15-HETE formation was a dose-dependent property also exhibited by arachidonic acid alone (10-100 microM). We conclude that cytological damage, facilitating access of arachidonic acid to 15-lipoxygenase in a cytosolic compartment, accounts for this phenomenon.
Acetates↗
Inhibition of acetylcholinesterase in the gut inhibits schedule-controlled behavior in the rat.
Rats were trained to press a lever under a multiple Fixed-Ratio 25 Fixed-Interval 50-second schedule of food reinforcement. Subcutaneous injection of soman, 80 micrograms/kg, suppressed responding under both schedules and inhibited acetylcholinesterase (AChE) in the brain. AChE activity in the gastrointestinal tract was not significantly inhibited. In contrast, i.p. injection of either soman (10-40 micrograms/kg), neostigmine (75 micrograms/kg) or DFP (350 micrograms/kg) caused marked suppression of behavior and AChE activity of the gut, without affecting brain AChE. These doses caused marked increases in peristaltic activity and likely caused gastrointestinal spasm. Injection of DFP, 500 micrograms/kg, s.c., inhibited AChE in both the brain and gut. The results indicate that inhibition of AChE in the gastrointestinal tract by certain anticholinesterase agents may be involved in the behavioral effects attributed to these drugs.
Animals↗
Effect of repeated intraperitoneal injections of soman on schedule-controlled behavior in the rat.
Intraperitoneal (IP) administration of the acetylcholinesterase inhibitor, soman (10-40 micrograms/kg), suppressed in a dose-related manner response rates in rats maintained under a multiple fixed-interval 50-s fixed-ratio 25 schedule of food delivery. Chronic administration of soman at weekly intervals resulted in tolerance to the response. When soman administration was separated by 2-5 weeks in individual rats, the suppressive effects of the agent again became apparent. Analysis of acetylcholinesterase activity revealed that enzyme inhibition was limited to gastrointestinal areas near the site of injection. There was no significant effect on brain acetylcholinesterase even following IP injection of doses which completely suppressed responding. The IP route may be useful for studying tolerance and other chronic effects of soman without producing generalized toxicity.
Acetylcholinesterase↗
Metabolism of leukotriene A4 by human erythrocytes. A novel cellular source of leukotriene B4.
Human erythrocytes transformed leukotriene A4 into leukotriene B4. Metabolism was proportional to the erythrocyte concentration, even at subphysiological levels (0.08-4 X 10(9) erythrocytes/ml). Comparative metabolic studies excluded the possibility that leukotriene B4 originated from trace amounts of polymorphonuclear leukocytes or platelets present in the purified erythrocyte suspensions. For example, suspensions of isolated platelets (100-500 X 10(6) cells/ml) failed to convert leukotriene A4 into leukotriene B4; and conversion by suspensions of isolated polymorphonuclear neutrophils was insufficient to account for the amounts of leukotriene B4 formed by erythrocytes. Leukotriene B4 formation was maximal within 2 min and substrate concentration dependent. Enzymatic activity originated from a 56 degrees C labile nondialyzable (Mr greater than 30,000) soluble component in the 100,000 X g supernatant obtained from lysed erythrocytes. In contrast to the contemporary view, our results indicate that human erythrocytes are not metabolically inert in terms of eicosanoid biosynthesis. The role of human erythrocytes during inflammatory or pulmonary disorders deserves re-examination in this context.
Arachidonic Acids↗
The hypertensive response to soman and its relation to brain acetylcholinesterase inhibition.
Intravenous injection of soman in the rat produced a rapid and dose related increase in blood pressure. The dose response curve was very steep, threshold responses occurring after intravenous injection of 10 micrograms/kg, and maximum increases of about 50 mmHg occurring after 40 micrograms/kg. Heart rate also generally increased. An increase in blood pressure also followed injection of soman subcutaneously, intramuscularly, intraperitoneally and into the cerebral ventricles, although the onset was slower and higher doses were required. The magnitude of the pressor response was correlated with the degree of AChE activity in the cortex, hypothalamus and brain stem, but not in the striatum. The pressor response was aborted or prevented by atropine, but not by methylatropine. It also was prevented by phenoxybenzamine. Atropine increased survival following an LD50 dose of soman; phenoxybenzamine prevented the pressor response but did not alter the survival rate.
Acetylcholinesterase↗
ABR measurements in the cat using a forward-masking paradigm.
Probe-elicited wave V amplitudes of the auditory brainstem response (ABR) were measured using a forward-masking paradigm. Subjects were anesthetized cats. For individual experiments, probe frequency and intensity were fixed and masker frequencies and intensities were varied. For each masker frequency, the extent to which the probe-elicited wave V amplitude was reduced by the preceding masker was plotted as a function of masker intensity. The rising segments of the masking functions were fitted with straight lines, using a least-squares procedure, to obtain estimates of their slopes. Masking grew most rapidly for masker frequencies below probe frequency, becoming progressively less steep as masker frequency increased. ABR tuning curves were constructed by using the linear fits to define the masker intensity that caused a 50% reduction in probe-elicited wave V amplitude. The shapes of these tuning curves were comparable to whole-nerve action potential (AP) tuning curves obtained under similar stimulus conditions. These results indicate that ABR amplitude measurements in a forward-masking paradigm can be used to estimate the growth of response to masking stimuli and frequency selectivity in a manner similar to AP amplitude measurements.
Action Potentials↗
Suppression of auditory nerve responses. II. Suppression threshold and growth, iso-suppression contours.
Two-tone "synchrony suppression" was studied in responses of single auditory nerve fibers recorded from anesthetized cats. Suppression thresholds for suppressor tones set to a fiber's characteristic frequency (CF) were approximately equal to discharge rate thresholds for CF tones. Suppression thresholds above and below CF were usually lower than the corresponding discharge rate thresholds. However, at all frequencies studied (including CF), suppression thresholds were higher than the corresponding thresholds for discharge synchronization. Across fibers, rates of suppression growth for suppressors at CF were greatest in low-CF fibers and least in high-CF fibers, and there was a systematic decrease in suppression growth rate at CF as CF increased. Within fibers, rates of suppression growth above CF were typically less than at CF, and slopes were monotonically decreasing functions of frequency. Within-fiber rates of suppression growth below CF were variable, but they usually were greater than rates of growth at CF. Iso-suppression contours (frequencies and intensities producing criterion amounts of suppression) indicated that tones near CF are the most potent suppressors at near-threshold intensities, and that the frequency producing the most suppression usually shifts downward as the amount of suppression increases. These data support the notion that synchrony suppression arises primarily as a passive consequence of hair cell activation.
Acoustic Stimulation↗
Auditory brainstem responses during systemic infusion of lidocaine.
Auditory brainstem-evoked responses (ABR) to clicks were recorded in unanesthetized restrained cats before, during, and after systemic intravenous infusion of lidocaine hydrochloride. The drug was infused continuously at varying rates. Lidocaine's major effect on ABR was to lengthen latent periods to all wave-form peaks in proportion with the infusion rate. The effect on latent periods was cumulative throughout the auditory brainstem, ie, all interpeak time intervals increased. Increases in ABR latencies were not due to reductions in effective stimulus intensity because lidocaine did not reduce ABR component amplitudes or increase thresholds. The effects of the drug were reversible. The data are consistent with the notion that lidocaine, directly or indirectly, works throughout the auditory brainstem to increase axonal and synaptic conduction times.
Animals↗
Gender typing and androgyny in later life. New directions for theory and research.
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Aged↗
Deference and dominance in old age: an exploration in social theory.
Nonverbal expressions of power and control in the daily lives of old people are examined from a life span perspective that combines social exchange theory, Goffman's classic work on deference and demeanor, and Henley's power theory of nonverbal communication and paralinguistics. Because of societal devaluation of the aged and the typical later life declines in power resources, old people are likely to experience a loss of status and social control during everyday nonverbal rituals of dominance nd deference. Supporting evidence is drawn from studies of the social impact of the physical setting and interactions between institutional old people and staff members. Discussion emphasizes the generally subtle nature of nonverbal expressions of dominance and deference, the impact of normal sensory declines in typical later life role transitions, and the potential for ageist interpretations of nonverbal cues.
Aged↗
Survey of New England hospital libraries.
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Libraries, Hospital↗
The mystery of the frozen M-K medium.
Donor corneal material stored or transported in M-K medium can freeze easily if placed in an insulated environment, such as a styrofoam container, with ice that is colder than 0 degrees C. To assure proper maintenance of the recommended temperature of M-K medium of + 4 degrees C, the ice used should be allowed to stand at room temperature until it has a glistening, wet look to its surfaces. M-K medium already cooled to + 4 degrees C can be safely stored and maintained at + 4 degrees C in a well-insulated styrofoam container for approximately 24 hours if this type of glistening-wet, melting ice is used.
Corneal Transplantation↗
Cellular electrophysiological marker of irreversible ischemic myocardial injury.
Glass microelectrode studies on posterior papillary muscle (PPM) slice preparations from 20 pentobarbital-anesthetized dogs (15 subjected to prior circumflex coronary artery ligation, 5 to sham ligation) have resulted in the definition of an electrophysiological marker of irreversible ischemic injury, namely, findings of areas composed of cells unable to generate a significant resting potential (less than -25) mV), designated "electrically inactive areas." Electrically inactive areas were essentially confined to PPM from dogs with circumflex coronary ligation; the incidence and distribution of the areas was related to duration of ischemia. Correlative phase- and light-microscopic studies demonstrated close correspondence between such areas and morphological evidence of irreversible ischemic injury. Analysis of frequency and distribution of electrically inactive areas permits quantitative assessment of the extent and spatial distribution of irreversible injury. This method has been used to quantitate injury in PPM from dogs that had been subjected to ligation for varying time periods. The potential utility of this method for evaluation of interventions designed to protect against ischemic injury and to assess electrical properties of surviving cells is considered.
Animals↗