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Biomedical subjects

M A Hill

Publications and source records attributed to M A Hill.

At least 19 recordsLinked to original sources

Relationship to growth performance of pneumonia and atrophic rhinitis lesions detected in pigs at slaughter among four seasons.

A commercial swine herd was selected for study, because pigs at slaughter repeatedly had lung lesions consistent with enzootic pneumonia and had snout lesions typical of atrophic rhinitis. Pigs born during various seasons of the year were allotted to 4 investigations and were evaluated from birth to slaughter. Individual lungs and snouts were identified and collected at the slaughter plant and later examined for gross lesions of bronchopneumonia and atrophic rhinitis, respectively. Each lesion was scored, and the following comparisons were made within investigations: prevalence and mean scores for lung lesions; prevalence and mean grades for snout lesions; correlations between lung lesion scores and growth indicators; correlations between snout lesion grades and growth indicators; and correlations between lung lesion scores and snout grade scores. Included in the growth indicators were average daily gain during the growing phase, average daily gain during the finishing phase, average daily gain during growing and finishing phases, and days to attain 104.5 kg of body weight. Prevalence of lung or snout lesions, mean values for lung lesion scores, mean values for snout lesion grades, and mean values for the various growth indicators were tested for statistical differences among the 4 investigations. Prevalence of lung lesions was highest (96%) for winter-slaughtered and lowest (81%) for autumn-slaughtered pigs. Mean scores for lung lesions were 7% (summer), 5% (autumn), 9% (winter), and 16% (spring). Prevalence of snout lesions was highest (85%) for spring-slaughtered pigs and lowest (42%) for autumn-slaughtered pigs.(ABSTRACT TRUNCATED AT 250 WORDS)

Abattoirs

Morphologic and biochemical changes in articular cartilages of immature beagle dogs dosed with difloxacin.

Quinolones are efficacious antibacterial compounds, but they have been associated with arthralgia in human patients; experimentally, they have caused lesions in articular cartilages of immature animals. The earliest morphologic and biochemical changes induced in articular-epiphyseal cartilage complexes by difloxacin, a fluoroquinolone, were investigated in 27 3-month-old Beagle dogs that were dosed orally with the drug at 300 mg/kg body weight per day. Paraffin-embedded sections of humeral and femoral heads that were stained with either hematoxylin and eosin or toluidine blue and fast green were evaluated histologically, and lesions were scored according to established criteria. Although morphologic changes were not observed in cartilages of the control dogs or of the treated dogs in the 24-hr group, the severity of lesions, as represented by mean scores for lesions, increased during the 36-48 hr after dosing. The initial morphologic change, observed in cartilages from the treated dogs of the 36- and the 48-hr groups, was necrosis of chondrocytes that was rapidly followed by disruption of extracellular matrix and formation of fissures. Although glycosaminoglycan was aggregated along the margins of fissures, its concentration was not reduced in cartilages of any group of treated dogs. Collagen, however, was depleted from the cartilages of the dogs that were euthanized 36 or 48 hr after the first dose of difloxacin. Because degenerative changes were observed ultrastructurally in chondrocytes by 24 hr in a previous study, it was concluded that collagen was lost from affected cartilages as an early sequel to the degeneration of chondrocytes.

Animals

Ultrastructural changes in articular cartilages of immature beagle dogs dosed with difloxacin, a fluoroquinolone.

The ultrastructural features of quinolone-induced arthropathy were studied in the humeral and femoral heads of nine skeletally immature Beagle dogs (3 months old) that were dosed orally with difloxacin at 300 mg/kg body weight and euthanatized 24, 36, or 48 hours later in groups of three. Three age-matched dogs were given a placebo and euthanatized after 48 hours. Mitochondria in chondrocytes had significantly greater cross-sectional areas (P less than 0.05) in electron micrographs from dogs euthanatized after 48 hours of treatment than did those in other groups. There was also a significantly greater percentage of chondrocytes with swollen mitochondria in treated dogs than in the controls (P less than 0.05). These changes preceded the necrosis observed in some chondrocytes in the dogs of the 48-hour group. Disruption of extracellular matrix was first observed in the pericellular matrix of necrotic chondrocytes, indicating that this change was secondary to the changes in chondrocytes. Fissures within cartilages apparently resulted from the loss of the normal association of proteoglycans with collagen fibrils.

Administration, Oral

Association between growth indicators and volume of lesions in lungs from pigs at slaughter.

Conflicting findings exist among studies on the effect of pneumonia on growth in pigs. We determined the extent of pneumonia in market-weight pigs by use of an objective, volumetric method and linear regression analyses of mean daily gain and days-to-slaughter weight on the percentage of pneumonic lung. In a range of extent of pneumonia between 1.33 and 70.44%, a 10% increase in the volume of pneumonic lung was associated with a decrease in mean daily gain by 41.1 g and a 16.7-day increase in number of days to a slaughter weight of 104.5 kg.

Animals

Epizootic of pseudorabies among ten swine herds.

An epizootic of pseudorabies in 10 swine herds located near Greensburg in Decatur County, Indiana was investigated. Records of Decatur County swine herds previously quarantined because of pseudorabies were obtained. For the 1988 epizootic, clinical findings were considered, location of each of the 10 swine herds in relation to the other herds was determined, and potential fomites were considered. Meteorologic data prior to, during, and after the epizootic were obtained, correlated, and analyzed. A source-receptor model, based on wind direction and speed data, was used to determine whether weather conditions in the Greensburg area enhanced the potential for aerosol spread of pseudorabies virus between herds. On the basis of lack of other modes of spread of pseudorabies and on meteorologic and source-receptor data, aerosol transmission of pseudorabies virus between the 10 herds was probable.

Air Microbiology

Biosynthesis of bacterial glycogen. Mutagenesis of a catalytic site residue of ADP-glucose pyrophosphorylase from Escherichia coli.

Site-directed mutagenesis was used to explore the role of Lys-195 in ADP-glucose pyrophosphorylase from Escherichia coli. This residue, which is conserved in every bacterial and plant source sequenced to date, was originally identified as a potential catalytic site residue by covalent modification studies. Mutation of Lys-195 to glutamine produces an enzyme whose Km for glucose 1-phosphate is 600-fold greater than that measured for the wild-type enzyme. The effect on glucose 1-phosphate is very specific since kinetic constants measured for ATP, Mg2+, and the allosteric activator, fructose 1,6-bisphosphate, are unchanged relative to those measured for the wild-type enzyme. Furthermore, the catalytic rate constant, Kcat, for the glutamine mutant is similar to that of the wild-type enzyme. Taken together, the results suggest a role for Lys-195 in binding of glucose 1-phosphate and exclude its role as a participant in the rate-determining step(s) in the catalytic reaction mechanism. To further study the effect of charge, shape, size, and hydrophobicity of the amino acid residue at position 195, a series of mutants were prepared including arginine, histidine, isoleucine, and glutamic acid. In every case, the kinetic constants measured for ATP, Mg2+, and fructose 1,6-bisphosphate were similar to wild-type constants, reinforcing the notion that this residue is responsible for a highly localized effect at the glucose 1-phosphate-binding site and also suggesting that the protein can accommodate a wide range of substitutions at this position without losing its global folding properties. Thermal stability measurements corroborate this finding. The mutations did, however, produce a range of glucose 1-phosphate Km values from 100- to 10,000-fold greater than wild-type, which indicate that both size and charge properties of lysine are essential for proper binding of glucose 1-phosphate at the catalytic site. AMP binding was also affected by the nature of the mutation at position 195. A model for glucose 1-phosphate, ATP, and AMP binding is presented.

Base Sequence

Cartilage canals and lesions typical of osteochondrosis in growth cartilages from the distal part of the humerus of newborn pigs.

Vessels in cartilage canals supplying the articular-epiphyseal cartilage complex and growth plate of the distal part of the humerus of pigs between on day and 15 weeks old were examined in perfused and cleared specimens, and histochemical preparations. An extensive capillary network surrounded the arterioles and venules and probably maintained the circulation of blood as the ends of the cartilage canals underwent involution. Pits and grooves were in predilection sites for osteochondrosis and osteoarthrosis and were typical of early lesions of these conditions. Some ghosts that were observed mesoscopically were chondrified cartilage canals or remnants of cartilage canals in histological sections, and were considered to be the result of a normal process. However, abnormal involution may predispose to chrondrolysis, and the presence of involuting transverse cartilage canals at predilection sites implicated damaged canals in the aetiopathogenesis of osteochondrosis and osteroarthrosis in some pigs. Cleared specimens provided the most useful demonstration of the form and distribution of cartilage canals, ghosts, and pits or grooves. The association of cartilage canals with areas of chondrolysis, and the distribution of ghosts in the predilection sites for lesions, warrant further investigation of blood vessels within cartilage canals.

Animals

Calcium measurement in isolated arterioles during myogenic and agonist stimulation.

Vascular smooth muscle calcium was measured during agonist treatment or pressure-induced stimulation of the myogenic response in isolated first-order skeletal muscle arterioles. Arterioles (40-180 microns) with spontaneous tone were isolated from rat cremaster muscle and cannulated. Arterioles were loaded with the calcium-sensitive dye fura-2 and excited at 340 and 380 nm. Images of vessel fluorescence were formed with a fluorescence microscope and digitized using an image processor coupled to a low light level camera. The fluorescent images allowed individual vascular smooth muscle cells to be seen within the arteriolar wall. Fluorescent intensity of the vessel wall, expressed as the ratio of fluorescence at 340 nm/380 nm, was used to estimate changes in vessel wall calcium. Topical application of norepinephrine (10 microM) to the arterioles caused a rapid and sustained constriction of the arterioles (64% of basal diam). The calcium response was biphasic consisting of a transient spike to 271% of basal followed by a decrease to a new steady state at 143% of basal. In comparison, steady-state indolactam (1 microM) produced a similar degree of constriction without an increase in calcium. Adenosine significantly dilated (35%) the arterioles and produced a decrease (24%) in vessel wall calcium. To investigate the myogenic response, intravascular pressure was step increased from 90 to 130 cmH2O. Increasing intravascular pressure caused an initial increase in vessel diameter of approximately 5% followed by active constriction that returned diameter to basal diameter. In association with this diameter change, estimated vessel wall calcium increased rapidly 8 +/- 2% and then continued to increase more slowly and remained elevated at 10-15% above basal levels. This study demonstrates the successful application of calcium-imaging technology in isolated arterioles for study of the role of calcium in arteriolar function. Results indicate that the calcium-contraction relationship differs for different agonists and are further consistent with a role for pressure-induced increases in vascular smooth muscle calcium during the myogenic response.

Adenosine

Effect of vasodilation and vasoconstriction on microvascular pressures in skeletal muscle.

The effect of topically applied papaverine (PAP) and norepinephrine (NE), on the microvascular pressure distribution was studied in the cremaster muscle of anesthetized rats. The cremaster muscle was exteriorized into a tissue bath containing Krebs bicarbonate buffer, and microvessel diameters and pressures were measured using a video caliper and the resistance servo-null method, respectively. Pressures were measured in the 1st through 4th branch order arterioles (1A to 4A) and 1st through 4th branch order venules (1V to 4V). Resistances were calculated across each segment from pressure gradients and 1A blood flow which was estimated from red cell velocities. PAP (10 microM) produced approximately a 15% decrease in arteriolar pressures with a concomitant increase in venular pressures of between 15 and 50%. In contrast, NE (0.1 microM) significantly increased arteriolar pressure by approximately 30% and decreased venular pressure by about 25%. Changes in systemic pressure during treatment with PAP and NE were small or insignificant and could not account for the observed changes in microvascular pressure. Significant dilation was observed in 3A, 4A, and 3V vessels after papaverine. In comparison, NE caused significant constriction in all vessel orders except 4V. PAP decreased resistance across all segments between 1A and 4V by 22-42% and increased venular resistance by almost 400%. NE increased resistance in all microvascular segments with the largest changes occurring in 2A to 3A (+276%) and 4A to 4V (+277%) segments. These data demonstrate that PAP and NE induce significant and opposite changes in arteriolar and venular pressures. Such network alterations in microvascular pressure should be considered when evaluating microvascular reactivity and exchange in the presence of vasoactive agents.

Animals

Use of histochemical techniques in the characterisation of osteochondroses affecting pigs.

Growth cartilages with dyschondroplastic foci (osteochondrosis) or areas of chondrolysis were selected from the ribs and bones of the appendicular skeleton of 132 commercial pigs euthanased between one and 169 days old or at a liveweight of 100 kg. Histochemical staining techniques that identified proteoglycans, collagen and deposits of calcium enhanced the visualisation of the lesions, were valuable for recognising the distribution of lesions, and helped to elucidate the development of the lesions. On the basis of the histochemical and morphological differences, it was considered that the lesions associated with growth plates and the lesions associated with articular-epiphyseal cartilage complexes should be considered as different entities. Lesions were identified in the articular-epiphyseal cartilage complexes of pigs at 15 days old, earlier than has been reported previously. Toluidine blue and safranin O were more useful than alcian blue and, in terms of staining intensity, toluidine blue gave more consistent results than safranin O.

Age Factors

Relationship of growth performance to pneumonia and atrophic rhinitis detected in pigs at slaughter.

Three commercial swine herds were selected for study, because pigs at slaughter consistently had lung lesions typical of bronchopneumonia and snout lesions consistent with atrophic rhinitis. Pigs were reared in the conventional system for each herd except that they were identified at birth and weighted at various intervals. At slaughter, individual pig lungs and snout were examined for lesions of pneumonia and atrophic rhinitis, respectively. Lesions were scored and correlated with growth indicators for each pig. Included in the growth indicators were: average daily gain (growing phase), average daily gain (finishing phase), average daily gain (total), and days to reach 104.5-kg body weight. Additionally, for each pig, scores for lung lesions were correlated to grades for snout lesions. Three correlation coefficients for measurements of pigs within herd B were significant and included days to 104.5-kg body weight and grades for snout lesions, -0.15 (P less than 0.02); average daily gain (finishing) and grades for snout lesions, 0.17 (P less than 0.01); and average daily gain (total) and grades for snout lesions, 0.16 (P less than 0.01). Contrary to findings in other investigations, pigs that attained market weight at the youngest age did not have the lowest score for lung lesions, the lowest grade for snout lesions, or the least extensive or severe lesions. Combining data from all 3 herds, the mean scores for lung lesions and mean grades for snout lesions decreased significantly (P less than 0.05) as the age of pigs at slaughter increased. All other statistical correlations were not significant.(ABSTRACT TRUNCATED AT 250 WORDS)

Animals

Altered cremaster muscle hemodynamics due to disruption of the deferential feed vessels.

Surgical preparation of the cremaster muscle for microvascular studies typically requires disruption of collateral vessels within the muscle and between the cremaster and the structures of the epididymis/ductus deferens. To study the effect of interrupting these vascular connections on cremaster hemodynamics, two modified preparations were examined in addition to the conventional open cremaster muscle preparation. One of these preparations enabled the measurement of feed vessel (1A) pressure and diameter with all cremaster vascular connections intact. The second preparation involved interruption of intramuscle collaterals to open the cremaster sac but with intact collateral pathways between the cremaster and deferential vessels. Intravascular pressures in the main cremasteric arteriole (1A) were similar in all three preparations with pressure in the 1A, expressed as a percentage of femoral artery pressure, varying between 53% in the intact preparation and 48% in the standard open preparation. These data support the existence of substantial upstream vascular resistance regardless of the extent of surgery. Selective occlusion of the branches of the deferential vessels significantly increased red cell velocity in the cremasteric 1A and major draining venule (1V) so that calculated blood flow increased by approximately 40% (P less than 0.01) in the 1A and 95% (P less than 0.01) in the 1V. Also, intravascular pressure fell significantly (P less than 0.01) in the 1A and increased in the 1V. Despite these compensatory changes total blood flow to the muscle was reduced by approximately 40% in the standard open preparation, compared to the preparation with the deferential feed pathway intact. Further studies where the 1A flow was transiently occluded indicated that the deferential pathway was capable of providing significant collateral blood flow to the muscle. Collectively these studies demonstrate that the surgical modifications of the cremaster vascular supply required for in vivo microscopy significantly alter normal hemodynamics within the vascular bed. The surgery does not, however, entirely explain the large pressure drop that exists upstream of the cremasteric 1A.

Analysis of Variance

Personality alterations in multi-infarct dementia.

Multi-infarct dementia (MID) produces changes in intellectual function and in overt behavior, but alterations in demeanor have received little systematic investigation. In this study, an assessment of personality change occurring after the onset of the dementia was performed using an inventory completed by the subjects' spouses. Personality alterations in MID were compared to those occurring in a group of healthy elderly individuals. Twelve of the 18 inventory items changed more in the MID patients than in normal control subjects. Personality changes are a consistent part of the clinical syndrome of MID and occur early in the course of the disease.

Aged