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Biomedical subjects

M R Murphy

Publications and source records attributed to M R Murphy.

At least 37 records · Page 2Linked to original sources

Current state and implications of research on biological effects of millimeter waves: a review of the literature.

In recent years, research into biological and medical effects of millimeter waves (MMW) has expanded greatly. This paper analyzes general trends in the area and briefly reviews the most significant publications, proceeding from cell-free systems, dosimetry, and spectroscopy issues through cultured cells and isolated organs to animals and humans. The studies reviewed demonstrate effects of low-intensity MMW (10 mW/cm2 and less) on cell growth and proliferation, activity of enzymes, state of cell genetic apparatus, function of excitable membranes, peripheral receptors, and other biological systems. In animals and humans, local MMW exposure stimulated tissue repair and regeneration, alleviated stress reactions, and facilitated recovery in a wide range of diseases (MMW therapy). Many reported MMW effects could not be readily explained by temperature changes during irradiation. The paper outlines some problems and uncertainties in the MMW research area, identifies tasks for future studies, and discusses possible implications for development of exposure safety criteria and guidelines.

Animals↗

Chlamydia pneumoniae as a new source of infectious outbreaks in nursing homes.

OBJECTIVE: To determine the extent and severity of illness and mode of transmission of Chlamydia pneumoniae infection in 3 nursing home outbreaks. DESIGN AND SETTING: Retrospective cohort study in 3 nursing homes in Ontario from September to November 1994. SUBJECTS: A total of 549 residents and 65 staff members. MAIN OUTCOME MEASURES: Morbidity and mortality were determined by a review of disease surveillance forms, residents' charts, and a self-administered questionnaire to staff. Single and paired serum samples for C pneumoniae serological testing and nasopharyngeal swabs for C pneumoniae culture were collected, and direct fluorescent antibody assays were performed to confirm C pneumoniae infection. RESULTS: The attack rates for confirmed and suspected cases combined were 68%, 46%, and 44% among residents in nursing homes A, B, and C, respectively, and 34% among nursing home C staff. A total of 16 cases of pneumonia confirmed by chest x-ray and 6 deaths were identified. The spectrum of illness among nursing home C residents included a new cough in 58 (100%), fever in 37 (64%), sore throat in 14 (24%), and hoarseness in 8 (14%). Staff members at nursing home C were more likely to report hoarseness (P<.001) and sore throat (P<.001). Residents who smoked had onset of illness earlier than nonsmokers (P=.007), which perhaps is related to airborne transmission in a designated smoking room. CONCLUSIONS: Chlamydia pneumoniae caused serious morbidity and mortality among residents and morbidity among staff; C pneumoniae is an important cause of respiratory disease outbreaks in nursing homes, and diagnostic tests must be readily available for early recognition of C pneumoniae infections.

Aged↗

Blockade of hippocampal long-term potentiation following soman pretreatment in the rat.

One of the most potent toxins known is the cholinesterase inhibitor, soman, which produces severe convulsions and cell loss in the central nervous system. In these experiments the effect of multiple low doses of soman on the acquisition and maintenance of long-term potentiation (LTP) was determined in rats. LTP is a form of synaptic plasticity that has been studied as a cellular substrate for learning and memory mechanisms. Under urethane anesthesia, electrodes were positioned in the dentate gyrus for recording evoked potentials before and after tetanic stimulation of the perforant path. LTP levels were greatly reduced in rats recovering from convulsion-inducing soman treatment. Rats exposed to similar amounts of soman, but not displaying convulsions, also displayed reduced levels of LTP. The responses recorded from these animals were highly variable, ranging from control levels of potentiation to no LTP. The variability could be attributed to some animals having convulsions that were not detected before surgery or to other interanimal differences in the degree of soman-induced toxicity. The long range goal of the experiments presented here is to develop a better rodent model for studying soman-induced functional changes in the CNS that can be detected prior to the gross morphological changes.

Analysis of Variance↗

Dietary variety via sweetening and voluntary feed intake of lactating dairy cows.

The effects of choice of diets on feed intake were studied using 12 lactating Holstein cows. A switchback design was used that had three periods and two sequential blocks. Diets were 1) a control total mixed ration (TMR), which consisted of alfalfa haylage, corn silage, and a concentrate mixture based on ground corn and soybean meal (25:25:50 on a dry matter basis) and 2) a sweetened TMR in which a brown sugar food product constituted 1.5% of the dietary dry matter. Treatments consisted of the control TMR fed on both sides of divided feed bunks, the sweetened TMR fed on both sides of divided feed bunks, or both TMR fed on alternating (daily) sides of divided feed bunks in tie stalls. Periods were 2 wk in duration, and cows averaged 67 and 53 d of lactation at the start of blocks 1 and 2, respectively. The dry matter intake, body weight, milk yield, and percentages of milk fat, protein, and solids not fat were similar when either TMR was fed alone. A choice of control TMR or sweetened TMR did not affect any of these variables. The dry matter intake, body weight, milk yield, and milk protein percentage were affected by block; however, these effects were probably caused by differences between the blocks in environment and stage of lactation. The results of this experiment might have been affected by the composition of the control TMR, its similarity to the sweetened TMR, availability of both diets simultaneously when a choice was offered, and use of a TMR instead of separate feeds or simpler mixtures.

Animal Feed↗

Substitution of neutral detergent fiber from forage with neutral detergent fiber from by-products in the diets of lactating cows.

Four lactating dairy cows that were ruminally and duodenally cannulated were used in an experiment with a 4 x 4 Latin square design to determine the effects of the substitution of neutral detergent fiber (NDF) from forage with NDF from wheat middlings, corn gluten feed, or a blend of distillers dried grains and hominy. Dietary crude protein and NDF averaged 18 and 31%, respectively, for the diet with 71.2% of the NDF from forage (control diet) and for diets with 55% of the NDF from forage (by-product diets). The substitution of NDF from these by-products for forage NDF did not affect dry matter intake (20.1 kg/d) or digestibility of organic matter. Total tract digestibility of acid detergent fiber was lower for cows fed the diet containing a blend of distillers dried grains and hominy than for cows fed the diet containing corn gluten feed. Microbial crude protein synthesis, milk production (23.9 kg/d), and milk fat percentage were similar for all cows, regardless of diet. Cows fed the diets containing wheat middlings or a blend of distillers dried grains and hominy had reduced ruminal pH compared with that of cows fed the diet containing corn gluten feed or the control diet. Diets containing 55% of total NDF from forage with 31% of total NDF from corn gluten feed, wheat middlings, or a blend of distillers dried grains and hominy can supply sufficient effective fiber to maintain normal ruminal function.

Ammonia↗

A comparison of general self-efficacy with self-esteem.

General self-efficacy (GSE) is defined as the global confidence a person has to successfully perform tasks. GSE is theorized to be linked to task-specific self-efficacy (TSSE). The GSE concept is controversial because some researchers claim that it is the same as self-esteem. In this study, 165 undergraduates were administered five GSE scales, a self-esteem scale, a locus of control scale, a TSSE scale, a sample-performance test, and a performance test. Results of multiple-regression analyses indicated that the GSE scales are measuring self-esteem and are poor predictors of performance.

Adolescent↗

Sucrose supplementation and feed intake of dairy cows in early lactation.

Based on results from previous 14-d sequential elimination trials, which indicated that cows in early lactation preferred a sucrose-sweetened diet, a 12-wk lactation trial was conducted to evaluate further the effects of sucrose supplementation. Twenty-four cows (16 multiparous Jerseys and 8 primiparous Holsteins) were assigned at parturition to a control or sucrose-sweetened (1.5% of dietary DM) TMR in a randomized complete block design. The diet included 10% corn silage, 30% alfalfa haylage, and 60% concentrate based on corn and soybean meal on a DM basis and was fed to ensure 10% orts. An additional 2.3 kg of alfalfa hay were fed for the first 5 d postpartum. Covariant-adjusted (BW on the day of parturition) mean DMI, milk yields, 3.5% FCM yields, and percentages of milk fat, milk protein, and SNF were unaffected by treatment and averaged 19.0 and 19.1 kg/d, 28.4 and 29.3 kg/d, 28.4 and 28.4 kg/d, and 3.40 and 3.30%, 3.51 and 3.28%, and 8.4 and 8.3%, respectively, for cows on control and sucrose-supplemented diets. In the absence of a choice of diets, sucrose at 1.5% of dietary DM did not enhance mean DMI over the first 12 wk postpartum; however, a transient increase in consumption of the sucrose-supplemented diet may have occurred over the a 2-wk period after parturition. Variation in feed consumption during early lactation suggests that additional data are needed to examine this potential effect.

Animal Feed↗

Lack of behavioral effects in non-human primates after exposure to ultrawideband electromagnetic radiation in the microwave frequency range.

The effect of acute exposure to ultrawideband (UWB) electromagnetic radiation on the Primate Equilibrium Platform (PEP) task, where the monkey's task is to manipulate a joystick control to compensate for the random perturbations in the pitch plane that are generated by a computer at unpredictable intervals, was examined. The duration of the UWB exposure was 2 min at a pulse repetition rate of 60 Hz (total of 7200 pulses). The bandwidth of the pulse was 100 MHz to 1.5 GHz (peak power between 250-500 MHz) with a peak E-field strength of 250 kV/m. Each monkey was exposed twice. The interval between exposures was 6 days. The exposure to UWB electromagnetic radiation had no effect on PEP performance when tested immediately after exposure.

Animals↗

Acute behavioral toxicity of pyridostigmine or soman in primates.

Effects of a peripherally active carbamate (pyridostigmine bromide) and a centrally active organophosphate (OP) nerve agent (soman) on performance by rhesus monkeys of a compensatory tracking (primate equilibrium platform, or PEP) task were measured using a balanced Latin-square design to determine the ED50 for pyridostigmine (0.66 mg/kg) and the up-and-down (titration) method to determine the ED50 for soman (2.50 micrograms/kg). We concluded that the PEP performance model is a sensitive and reliable indicator of anticholinesterase (anti-ChE) behavioral toxicity. We also found that soman, an irreversible inhibitor of acetylcholinesterase (AChE), is more than 100 times more behaviorally disruptive than the reversible peripheral inhibitor pyridostigmine, as indicated by the difference in ED50 doses expressed in molar terms. Soman's behavioral toxicity is severe at levels of serum cholinesterase inhibition (70-80%) at which pyridostigmine does not significantly affect performance. As a prophylactic treatment for OP agent poisoning, pyridostigmine has a substantial safety factor, since behavioral toxicity becomes significant only at approximately four times the proposed therapeutic dose.

Animals↗

Primate performance decrements following acute soman exposure: failure of chemical countermeasures.

Three experiments are reported: 1) a feasibility study on using laboratory primates repeatedly in behavioral toxicity studies of organophosphate (OP) agents or of chemical countermeasures against OPs; 2) a study of the efficacy of pyridostigmine pretreatment and 2-PAM therapy; and 3) a study to determine the effects of these treatments on soman-induced cholinesterase (ChE) inhibition and its recovery. In rhesus monkeys, three repeated acute low-dose (2.1 to 2.8 micrograms/kg) soman exposures, separated by intervals > 5 weeks, did not change baseline compensatory tracking performance or the soman ED50. Atropine therapy (97 micrograms/kg) alone had no effect on soman ED50. Addition of pyridostigmine pretreatment (150 micrograms/kg) and 2-PAM therapy (17 mg/kg) to atropine therapy increased the soman ED50 for a performance decrement from 2.27 micrograms/kg to 2.58 micrograms/kg, an insignificant protective effect. At the soman ED50 for behavioral decrements, pyridostigmine pretreatment increased the inhibition of serum ChE observed immediately after soman exposure, but reduced the extent of permanent inhibition. The 2-PAM therapy reduced serum ChE inhibition from about 80% to less than 70%. These effects on the time course of ChE inhibition following soman exposure appear to combine additively. These chemical countermeasures do not prevent soman-induced performance decrements, even though they are effective in protecting lives after much higher doses. The soman doses used produce only small, transient performance decrements; animals so exposed can, thus, be used repeatedly in such studies.

Animals↗

Behavioral toxicity of anticholinesterases in primates: effects of daily repeated soman exposure.

The effects of repeated daily exposure to soman, an organophosphate nerve agent, on the performance of a well-learned, compensatory tracking task were tested in rhesus monkeys. The ED50 daily exposure required to produce a performance decrement on or before the fifth daily exposure (0.97 microgram/kg) was about 40% of the acute dose required to produce a similar performance decrement. After repeated, low-dose exposures, performance decrements appeared when serum cholinesterase (ChE) activity was inhibited 85-90%. Acute exposures that produced similar performance effects were associated with lower levels of ChE inhibition (65-70%), suggesting that repeated daily exposure may lead to the development of a tolerance (physiological or behavioral) to low levels of ChE activity.

Animals↗

Kinetics of niacin supplements in lactating dairy cows.

The kinetics of niacin supplements in lactating dairy cows and the stability of supplements during in vitro fermentation were examined. Four multiparous Holstein cows (200 DIM) with ruminal and duodenal cannulas were fed a TMR either unsupplemented or supplemented with 12 g/d of nicotinic acid, 12 g/d of nicotinamide, or 6 g/d combination of each niacin source in a 4 x 4 Latin square design. Ruminal and duodenal concentrations of nicotinic acid increased with niacin supplementation, but DMI, yields of milk and FCM, most measures of milk composition, ruminal VFA, and plasma NEFA and BHBA concentrations were unaffected by niacin supplementation at this stage of lactation. Apparent digestibilities of most nutrients were greater when both sources of niacin were supplemented than when either source was supplemented separately. Duodenal nicotinic acid concentrations were higher for cows supplemented with nicotinamide than for cows receiving nicotinic acid, but the opposite was true for nicotinic acid concentrations in plasma. The results of both experiments indicated that nicotinamide was converted rapidly to nicotinic acid by microorganisms in the reticulorumen. Supplementation with either nicotinic acid or nicotinamide effectively can increase the amount of nicotinic acid available to the cow; however, some source effects remain to be explained.

Animal Feed↗

Dietary preferences in early lactation cows as affected by primary tastes and some common feed flavors.

A sequential elimination trial was conducted to test the effects of primary tastes on the preference ranking of TMR diets by six multiparous Holstein cows from 8 to 21 DIM. Four additives and a control were examined; the most preferred (highest total intake) was eliminated after segments of 5, 4, 3, and then 2 d. Diets tasting sweet (sucrose, 1.5% of dietary DM), sour (HCl, 1.25%), bitter (urea, 1%), and salty (NaCl, 4%) were tested. Four of the cows most preferred the sweet diet, and DMI of that diet averaged 12.8% more than for the control, which was next preferred. The probability of a diet being chosen first when all diets were presented together was sucrose, .59; control, .36; urea, .04; NaCl, .01; and HCl, .003. Another experiment used the same procedure; however, the additives tested were anise, monosodium glutamate, dehydrated alfalfa meal flavor, and molasses flavor (1.48 g of flavor/kg of DM). Control and monosodium glutamate ranked first equally. The probability of choosing each flavor first in this set was .5 for the control and monosodium glutamate diets and < .01 for molasses, alfalfa, and anise. Rankings were not significantly affected by variation among cows in either experiment. Of the additives tested, only sucrose seemed to have the potential to increase intake.

Animal Feed↗

DNA-protein interactions at the S.cerevisiae alpha 2 operator in vivo.

Two homodimeric proteins, alpha 2 and MCM1, are required to repress transcription of a-cell type specific genes in haploid yeast alpha-cells. In vitro studies by others of the interactions of these proteins with operator DNA have suggested that MCM1 binds to the middle and alpha 2 to the ends of the 31 bp operator. We have previously shown that alpha 2 organizes chromatin structure adjacent to the operator; in the presence of alpha 2 repressor, a precisely positioned nucleosome abuts the operator in both minichromosomes and the genome. We present in vivo footprinting evidence consistent with occupancy of the operator by MCM1 in both a- and alpha-cells and by alpha 2 repressor in alpha-cells. Interestingly, our in vivo results differ from previous in vitro work in detail. In contrast to the broad block of reagent accessibility to DNA by the factors seen in vitro, we find a pattern of strand-specific protection or augmented reactivity in vivo. The in vivo results are consistent with genetic data concerning transcriptional regulation of a-cell specific genes and corroborate the crystallographic data of others.

Base Sequence↗

Cholinesterases as scavengers for organophosphorus compounds: protection of primate performance against soman toxicity.

The present treatment for poisoning by organophosphates consists of multiple drugs such as carbamates, antimuscarinics, and reactivators in pre- and post-exposure modalities. Recently an anticonvulsant, diazapam, has been included as a post-exposure drug to reduce convulsions and increase survival. Most regimens are effective in preventing lethality from organophosphate exposure but do not prevent toxic effects and incapacitation observed in animals and likely to occur in humans. Use of enzymes such as cholinesterases as pretreatment drugs for sequestration of highly toxic organophosphate anticholinesterases and alleviation of side effects and performance decrements was successful in animals, including non-human primates. Pretreatment of rhesus monkeys with fetal bovine serum acetylcholinesterase protected them against lethal effects of soman (up to 5 LD50) and prevented signs of OP toxicity. Monkeys pretreated with fetal bovine serum acetylcholinesterase were devoid of behavioral incapacitation after soman exposure, as measured by serial probe recognition or primate equilibrium platform performance tasks. Use of acetylcholinesterase as a single pretreatment drug provided greater protection against both lethal and behavioral effects of potent organophosphates than current multicomponent drug treatments that prevent neither signs of toxicity nor behavioral deficits. Although use of cholinesterases as single pretreatment drugs provided complete protection, its use for humans may be limited, since large quantities will be required, due to the approximately 1:1 stoichiometry between organophosphate and enzyme. Bisquaternary oximes, particularly HI-6, have been shown to reactivate organophosphate-inhibited acetylcholinesterase at a rapid rate. We explored the possibility that enzyme could be continually reactivated in animals pretreated with fetal bovine serum acetylcholinesterase, followed by an appropriate dose of reactivator, and challenged with repeated doses of sarin. In in vitro experiments, stoichiometry greater than 1:400 for enzyme:sarin was achieved; in vivo stoichiometry in mice was 1:65. Pretreatment of mice with fetal bovine serum acetylcholinesterase and HI-6 amplified the effectiveness of exogenous enzyme as a scavenger for organophosphate.

Acetylcholinesterase↗

Efficacy of physostigmine as a pretreatment for organophosphate poisoning.

Continuous administration of the carbamate physostigmine, producing approximately 40% serum cholinesterase (ChE) inhibition, provides significant protection against the lethal effects of the organophosphorous nerve agent pinacolyl methylphosphonofluoridate (soman). Rats pretreated with physostigmine were also protected against the development of cholinergic symptoms and loss of body weight. Soman and physostigmine both inhibit ChE, yet animals pretreated with physostigmine exhibited less ChE inhibition in serum and brain than did animals exposed to soman alone. In addition, there did not appear to be any additive effect of presenting both anticholinesterases simultaneously. To further examine the effectiveness of physostigmine, we compared the results of this study with previously collected pyridostigmine data from our laboratory. This comparison indicates that physostigmine is more effective than pyridostigmine in protecting against the detrimental effects of soman.

Animals↗

Behavioral toxicity of anticholinesterases in primates: chronic physostigmine and soman interactions.

Dose rates for continuous infusion of physostigmine salicylate required to inhibit 30 and 60% of normal serum cholinesterase activity in rhesus monkeys were determined. The effects of continuous physostigmine infusion at these dose rates on the behavioral toxicity of daily repeated low-dose soman were determined not to be deleterious; in fact, they were slightly (and variably) protective.

Animals↗