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Biomedical subjects

J M Harrison

Publications and source records attributed to J M Harrison.

At least 19 recordsLinked to original sources
PubMed1992

Hypercholesterolemia and atherosclerosis in primary biliary cirrhosis: what is the risk?

Hypercholesterolemia is commonly associated with primary biliary cirrhosis. In the general population, elevated serum cholesterol is associated with an increased risk of atherosclerosis. The relative risk has been poorly defined in primary biliary cirrhosis patients with hyperlipidemia. In addition, the hyperlipidemic state seen with primary biliary cirrhosis has not been well studied. We prospectively observed 312 patients with primary biliary cirrhosis for a median of 7.4 yr. During this period, 128 patients died. The incidence of atherosclerotic death in patients with primary biliary cirrhosis was not statistically different when compared with an age-matched and sex-matched U.S. control population. A similar group of 50 consecutive PBC patients had detailed serum lipid profiles. Findings included progressive increases in total cholesterol and low-density lipoprotein cholesterol with an increasing histological stage or severity of disease. High-density lipoprotein cholesterol was elevated in all stages, with the highest levels in histological stage 2 and 3 disease. Triglycerides were normal or slightly elevated in all stages. Apoprotein A-I was elevated in all but histological stage 4 disease. Our study suggests the hyperlipidemia associated with primary biliary cirrhosis does not place these patients at risk for atherosclerotic death. In light of the limitations imposed by our relatively small sample size, however, additional patients should be studied. Furthermore, an examination of the pathophysiological mechanisms leading to hypercholesterolemia should be the topic of further study.

Adult↗
PubMed1992

Avoiding conflicts between the natural behavior of the animal and the demands of discrimination experiments.

Auditory discrimination experiments are traditionally designed without regard for ethological or ecological concerns, yet land dwelling mammals may have specialized behavior with respect to sound sources. Auditory discriminations occur under field conditions, and there is some fit or matching of the animal's behavior to the acoustic environment. Understanding this fit requires a knowledge of specializations. Understanding the specializations may also guide the design of discrimination experiments. This paper reviews a number of auditory discrimination experiments that were designed to reveal some of the specialized behaviors. These experiments showed the following: (i) The position of a sound source is the dominant sensory dimension, over riding the quality of the sound; (ii) the effect of reinforcing a response in the presence of a sound is to strengthen the response of approaching the source. This effect is ubiquitous in discrimination tasks; (iii) sounds that are novel at the start of discrimination training more rapidly gain control of responding than sound to which the animal has been pre-exposed; (iv) novel low-intensity sounds elicit approach and exploration of the source. These behaviors rapidly adapt. These four behavioral attributes are considered in terms of their impact upon behavior in the field, and of the requirements they impose on the design of experimental discriminations.

Animals↗
PubMed1992

Biological fate of sulphur mustard, 1,1'-thiobis(2-chloroethane): isolation and identification of urinary metabolites following intraperitoneal administration to rat.

1. The metabolism of sulphur mustard, 1,1'-thiobis(2-chloroethane), in vivo was investigated following i.p. administration to rat. 2. Approx. 60% of dose was excreted in the 24 h urine. Many metabolites were present; nine have been isolated by h.p.l.c. and characterized by mass spectrometry. Structural assignments were confirmed by comparison with authentic synthetic standards. 3. Some metabolites result from initial hydrolysis of the sulphur mustard, but the majority are formed by conjugation with glutathione. These are further metabolized to N-acetylcysteine conjugates, or to methylthio/methylysulphinyl derivatives by a pathway probably involving beta-lyase, accompanied by oxidation of the mustard sulphur atom to sulphoxide or sulphone. 4. Thiodiglycol sulphoxide, 1,1'-sulphonylbis[2-S(N-acetylcysteinyl)ethane] and 1,1'-sulphonylbis[2-methylsulphinyl)ethane] or 1-methylsulphinyl-2-[2-(methylthio ethylsulphonyl]ethane were the most prevalent metabolites resulting from the three major pathways. Metabolic pathways for the formation of the excretion products are proposed.

Animals↗
PubMed1992

Biological fate of sulphur mustard (1,1'-thio-bis(2-chloroethane)): urinary and faecal excretion of 35S by rat after injection or cutaneous application of 35S-labelled sulphur mustard.

1. A technique for the quantitative cutaneous application of sulphur mustard vapour is described. The maximum rate of uptake of the agent vapour by shaved rat skin in vivo was estimated as 7 micrograms/cm2 per min. 2. The major route of excretion was through the kidneys: greater than 70% of the radioactivity of all doses was excreted in 3 days after either i.v. or i.p. injections of 35S-labelled sulphur mustard, but less (50-70% depending on dose) was excreted in the same time following cutaneous application. 3. This urinary excretion of 35S had a half-life of 1.4 days, and the decreased proportion of the applied dose excreted following cutaneous application may be accounted for by retention of radioactivity in the skin. 4. The contribution of faecal excretion was greater following cutaneous application.

Administration, Cutaneous↗
PubMed1991

Eye injuries with metal missiles presenting to an emergency center: a three year study.

The authors retrospectively evaluated 33 eye injuries due to metal missiles in 31 patients presenting to our emergency center over the last 3 years. Injuries occurred most frequently when the patients were grinding metal or working on their cars. The type of metal involved in the injury often dictates the type of ophthalmic reaction that will occur. A discussion of intraocular metallic foreign bodies with an emphasis on electroretinograms and metal analysis is presented.

Adolescent↗
PubMed1990

Drug resistance trends in Mycobacterium tuberculosis: Blackburn 1985-89.

Drug resistance in Mycobacterium tuberculosis fell from 15.2% in 1980-1984 to 6.5% in 1985-89 in the Indian subcontinent (ISC) ethnic group and remained low in the white ethnic group. Resistance to isoniazid, which is of particular clinical significance, fell from 6.1% in 1980-84 to 2.7% in 1985-1989 in the ISC group. Factors which may affect this trend to reduction are discussed.

Antitubercular Agents↗
PubMed1990

Simultaneous auditory discrimination.

Stimuli in many visual stimulus control studies typically are presented simultaneously; in contrast the stimuli in auditory discrimination studies are presented successively. Many everyday auditory stimuli that control responding occur simultaneously. This suggests that simultaneous auditory discriminations should be readily acquired. The purpose of the present experiment was to train rats in a simultaneous auditory discrimination. The apparatus consisted of a cage with two response levers mounted on one wall and a speaker mounted adjacent to each lever. A feeder was mounted on the opposite wall. In a go-right/go-left procedure, two stimuli were presented on each trial, a wide-band noise burst through one speaker and a 2-kHz complex signal through the other. The stimuli alternated randomly from side to side across trials, and the stimulus correlated with reinforcement for presses varied across subjects. The rats acquired the discrimination in 400 to 700 trials, and no response position preference developed during acquisition. The ease with which the simultaneous discrimination was acquired suggests that procedures, such as matching to sample, that require simultaneous presentation of stimuli can be used with auditory stimuli in animals having poor vision.

Animals↗
PubMed1990

Comparison of two speech processing schemes using normal-hearing subjects.

Two speech processing schemes have been implemented on a real-time laboratory speech processor for speech perception studies on normal-hearing subjects. The first scheme presents the information of two spectral components, the first and second formant of the speech signal, and will be referred to as the ZC (zero-crossing) scheme. The second scheme presents the information of four spectral components, four spectral peaks of the speech signal determined from the output of a filter bank, and will be referred to as the FB (Filter-bank) scheme. Perceptual studies were conducted on 4 normal-hearing subjects. Two of the 4 subjects were first trained and tested using the ZC scheme while the other 2 used the FB scheme. The training and testing schedules were then repeated for the unused scheme. Vowel perception performance was similar across subjects and speech processing schemes. Percentage correct scores for consonant perception in noise were higher for the FB scheme than for the ZC scheme at signal-to-noise ratios ranging from 5 to 20 dB. Percentage correct scores for open set CNC words and speech tracking scores were also better for FB than for ZC.

Cochlear Implants↗
PubMed1988

Muscle composition and its relation to sprint running in the lizard Dipsosaurus dorsalis.

Iguanid lizards exhibit considerable intraspecific variation in several aspects of their muscle composition. To determine the relationship of this variation to the variation in locomotor performance, running speeds of 20 male desert iguanas (Dipsosaurus dorsalis) of similar mass were measured from video recordings of animals as they sprinted down a 4.9-m runway maintained at 40 degrees C, the preferred body temperature of Dipsosaurus. Mean sprint speed ranged from 2.2 to 4.2 m/s. Selected muscles from these animals were then analyzed histochemically for fiber type size and composition, and the activities of citrate synthase, pyruvate kinase, and creatine kinase were measured. Muscle fiber cross-sectional areas were highly correlated within individuals, in three leg muscles and across all three fiber types, so that individuals could be characterized as possessing large or small fibers relative to the sample mean. Activities of all three enzymes also covaried within individuals so that individual lizards could be characterized as possessing high or low leg muscle catabolic capacity. There existed a significant and inverse relationship between fiber cross-sectional areas and muscle enzyme activities so that individuals with small muscle fibers tended to have higher catabolic capacities. Approximately 25-30% of the variation in mean sprint running speed could be predicted by variation in muscle fiber areas alone. The use of muscle fiber areas and snout vent length as independent variables in a multiple-regression equation explained approximately 50% of the sprint-running variation.(ABSTRACT TRUNCATED AT 250 WORDS)

Animals↗
PubMed1988

Control of responding by sounds of different quality: an evolutionary analysis.

Two experiments investigated the acquisition of discriminations between two acoustic stimuli of different quality (noise bursts vs. a 2-kHz pulsed signal) when features of the everyday environment were incorporated into the experiments. In Experiment 1, rats were trained, using food, to press a lever. Throughout all sessions, 5-s trials of noise bursts (the random stimulus) were presented, after variable intertrial intervals, through a remote speaker mounted outside the experimental enclosure. The noise burst occurred randomly with respect to reinforcement of lever pressing and had no programmed relationship to the animal's behavior. When lever pressing was established, the 2-kHz signal was presented through a speaker adjacent to the response lever according to a different set of variable intertrial intervals. A response in the presence of the 2-kHz signal terminated the trial and was reinforced. The 2-kHz signal acquired control of responding within the first few trials, whereas the random stimulus exerted no control of responding. In Experiment 2, rats were trained to press the lever in the presence of the 2-kHz signal presented through the adjacent speaker on a variable intertrial interval. After 14 sessions, 5-s trials of noise bursts (random stimulus) were presented through the remote speaker on the second variable intertrial interval. The random stimulus initially elicited exploratory behavior, which then rapidly declined. Subsequently, the random stimulus exerted no or weak control of responding. The introduction of the random stimulus had no effect on responding in the presence of the adjacent stimulus. In Experiments 3 and 4 the random stimulus was presented through the adjacent speaker, and the stimulus correlated with reinforcement was presented through the remote speaker. In both experiments, there was persistent control of responding by the random stimulus and slow development of control by the stimulus correlated with reinforcement. In Experiment 5, both stimuli were presented through the adjacent speaker. There was persistent control of responding by the random stimulus.

Animals↗
PubMed1987

Roles of individual honeybee workers and drones in colonial thermogenesis.

The individual roles of honeybee workers and drones in heat regulation were investigated using single combs of bees and brood (about 1,000 individuals) placed in boxes at 15 degrees C. After 1 h and before cluster formation, I measured the elevation of bee thoracic surface temperature (Tths) above local ambient temperature (Ta). Bees were then left overnight at 15 degrees C. During the preclustering period, the density of bees over the brood slowly increased. In the clusters left overnight, bees in the innermost layer were significantly younger than bees in the outermost layer. One-day-old bees and drones were always located in the innermost cluster layer. 89% of all workers measured had Tths - Ta greater than or equal to 2 degrees C, indicating that most workers contribute to colonial thermogenesis. Average Tths - Ta was 4.1 degrees C. Drones measured had the same average Tths - Ta as unmarked workers. Tths - Ta did not differ among bees 2 days of age and older. Location on or off the brood did not affect Tths - Ta. Cooling constants of dead bees placed near the comb in the box averaged 1.036 min-1 and were independent of location on the comb. Calculated average thoracic conductance was 0.829 cal g-1 degree C-1 min-1. Average calculated heat production per worker was 0.095 cal min-1, less than 15% of the maximal oxygen consumption of 4-day-old bees. Calculations indicate that the larger drones contribute more heat per bee than do the workers.(ABSTRACT TRUNCATED AT 250 WORDS)

Animals↗
PubMed1987

Auditory discrimination: the Konorski quality-location effect.

Konorski showed that when a go/no-go procedure was used, sound quality discriminations were rapidly acquired and sound location discriminations were slowly acquired. These findings have been interpreted as a general constraint on the acquisition of auditory discriminations (quality-location effect). However, experiments carried out within an evolutionary framework (Harrison, 1984) have shown that the rate of acquisition of sound location discriminations varies widely as a function of the inclusion or exclusion of naturalistic features. These data suggest that Konorski's findings were a function of the special conditions of the experiments. The first purpose of the present experiments was to assess whether rats showed the effects noted by Konorski when studied under similar conditions. The second purpose was to study the effect of manipulating two natural features (novelty and stimulus-response adjacency) to assess whether the acquisition rates of quality and location discriminations could be greatly modified or made approximately equal, or both. When a go/no-go procedure was used and the other conditions were similar to those of Konorski, rats acquired a quality discrimination but did not acquire a location discrimination. However, when the S+ or S- were presented through a closely adjacent speaker, the sound location discrimination was acquired as rapidly as the quality discrimination. Finally, preexposing the animal to either S+ or S- retarded the rate of or prevented the acquisition of the quality discrimination. The experiments showed that the quality-location effect was determined primarily by the conditions used in Konorski's experiments, and that the effect is not a general constraint on learning.

Animals↗
PubMed1987

The fate of 2-chlorobenzylidene malononitrile (CS) in rats.

1. The fate of 3H-ring labelled, 14C-cyanide labelled and (14C = C) side chain labelled 2-chlorobenzylidene malononitrile (CS), 2-chlorobenzyl alcohol and 2-chlorobenzyl malononitrile (dihydro CS) in rats and isolated rat liver cells has been examined. 2. CS was administered both i.v. and i.g. to rats at doses from 0.08 to 159 mumol/kg and in most cases the greatest proportion of the dose was eliminated in the urine (44-100%). The principal urinary metabolites were 2-chlorohippuric acid, 1-O-(2-chlorobenzyl) glucuronic acid, 2-chlorobenzyl cysteine and 2-chlorobenzoic acid. Lesser amounts of 2-chlorophenyl acetyl glycine, 2-chlorobenzyl alcohol and 2-chlorophenyl 2-cyano propionate were identified. 3. The major urinary metabolite from 2-chlorobenzyl alcohol was 2-chlorohippuric acid (43%), 2-chlorobenzyl cysteine, 2-chlorobenzoic acid and 2-chlorobenzyl glucuronic acid were identified. 4. The products of dihydro-CS metabolism were 2-chlorophenyl acetyl glycine, 2-chlorophenyl 2-cyanopropionate and 2-chlorophenyl proprionamide. 5. Urinary thiocyanate levels increased with the dose of CS up to 159 mumol/kg. At 212 mumol/kg there was a large increase in the amount of thiocyanate produced (molar conversion: 21.5-29.9%). Similarly malononitrile, the hydrolysis product of CS, gave a dose related increase in urinary thiocyanate levels. However at a higher dose (212 mumol/kg) the molar conversion was greater than 60%. 6. The metabolism of CS by isolated rat liver cells confirmed the results in vivo but demonstrated a marked limitation of this preparation to form conjugates. 7. It is concluded that CS in vivo is hydrolysed mainly to 2-chlorobenzaldehyde which is then either oxidized to 2-chlorobenzoic acid for subsequent glycine conjugation, or reduced to 2-chlorobenzyl alcohol for ultimate excretion as 2-chlorobenzyl acetyl cysteine or 1-O-(2-chlorobenzyl) glucuronic acid. Malononitrile is converted to thiocyanate via the formation of cyanide.

Animals↗
PubMed1987

The pattern ERG in man following surgical resection of the optic nerve.

Pattern electroretinogram (PERG) results recorded in different laboratories from patients with unilateral traumatic transections of the optic nerve have led investigators to opposite conclusions about the sources of this response. There was no absolute demonstration of complete transection in any of these studies. In the present study, PERGs and flash ERGs were recorded from a patient who, 30 months earlier, had undergone surgical resection of the right optic nerve to remove a glioma. The histological section of the biopsied nerve confirmed complete optic nerve transection. Ophthalmoscopically and angiographically, the right eye was normal except for marked optic atrophy. PERGs were produced by 10 Hz reversal of high contrast checks with check widths from 13 deg 30 min to 12 min arc. Field size was 27 deg X 21 deg and space-averaged screen luminance was 110 cd/m2. Smaller checks (3 deg 23 min to 12 min) produced responses in both eyes, but the responses in the right eye were much smaller than those in the left eye. Large checks and diffuse flashes produced approximately equal responses in the two eyes. The implicit times of the PERGs produced by stimulation of the right eye with smaller checks were shorter than those of the left eye. The authors conclude that, in humans, there is a contribution to the high contrast pattern reversal ERG from cells which are not dependent upon the integrity of the ganglion cell layer. These cells and cells dependent upon ganglion cells may both contribute to the high contrast PERG in the normal human eye.

Adult↗
PubMed1987

Contrast sensitivity: characteristics of a large, young, adult population.

Contrast sensitivity functions and complete eye examinations were obtained from 103 normal, healthy young adults (ages 21 to 40 years). Descriptive statistics were compiled for the group in order to provide normative information. Subsets of the population were evaluated with respect to the relations among the attributes of accommodation, visual acuity, refraction, spectacle wear, and contrast sensitivity. The influence of age in this restricted population was seen only at 16 cpd. In those subjects with better than 6/6 (20/20) Snellen acuity, there were statistically significant relations with the parameters of the contrast sensitivity function as compared to those observers with 6/6 (20/20) or poorer acuity. High spatial frequency resolution was significantly better for those observers with better than 6/6 (20/20) acuity in either eye. In addition, this study provides a broad base of normative data for variability from a large population confined to a specific age range and with refractive errors that ranged from minimal to more than average.

Adult↗
PubMed1986

Retinal toxicity of intravitreal cefoperazone.

Cefoperazone is a broad spectrum, third-generation cephalosporin with potential usefulness in treating endophthalmitis because of its in vitro activity against Gram-negative organisms. Retinal toxicity was evaluated via serial indirect ophthalmoscopy, electrophysiologic testing and histopathologic examination of 43 Dutch-belted rabbit eyes injected intravitreally with 2, 4, 8, 16 or 32 mg of cefoperazone in a volume of 0.1 cc each. They were compared with seven eyes injected with sterile saline. Results show electroretinographic and histological evidence of retinal toxicity at concentrations of 16 mg or greater, while a single intravitreal dose of 8 mg or less of cefoperazone produced no evidence of retinal toxicity.

Animals↗
PubMed1986

Drug resistance in Mycobacterium tuberculosis: a survey over 25 years in Blackburn.

Over the past 25 years the incidence of tuberculosis in Blackburn has changed from one that was below the national average to one which is consistently in the 10 highest local authority areas in England and Wales. A survey of primary and acquired drug resistance over the same period included 974 ethnic white patients and 538 of Indian subcontinent ethnic origin. Primary drug resistance in the white population has fallen consistently from 1965 onwards and is now zero. Only one case of acquired resistance has occurred in the last five years. Primary resistance in the immigrant community has been 11-15% from 1965 onwards, and five cases of acquired resistance have occurred since 1970. The pattern of drug resistance over this period supports the view that there is no evidence of cross infection between the native white and immigrant ethnic groups.

Antitubercular Agents↗