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Biomedical subjects

A R Barr

Publications and source records attributed to A R Barr.

At least 19 recordsLinked to original sources

QTL mapping of chromosomal regions conferring reproductive frost tolerance in barley ( Hordeum vulgare L.).

Spring radiation frost is a major abiotic stress in southern Australia, reducing yield potential and grain quality of barley by damaging sensitive reproductive organs in the latter stages of development. Field-based screening methods were developed, and genetic variation for reproductive frost tolerance was identified. Mapping populations that were segregating for reproductive frost tolerance were screened and significant QTL identified. QTL on chromosome 2HL were identified for frost-induced floret sterility in two different populations at the same genomic location. This QTL was not associated with previously reported developmental or stress-response loci. QTL on chromosome 5HL were identified for frost-induced floret sterility and frost-induced grain damage in all three of the populations studied. The locations of QTL were coincident with previously reported vegetative frost tolerance loci close to the vrn- H1 locus. This locus on chromosome 5HL has now been associated with response to cold stress at both vegetative and reproductive developmental stages in barley. This study will allow reproductive frost tolerance to be seriously pursued as a breeding objective by facilitating a change from difficult phenotypic selection to high-throughput genotypic selection.

Acclimatization↗

Variations in cartilage catabolism in different equine joints in response to interleukin-1 in vitro.

An explant system was used to investigate the hypothesis that cartilage from different equine joints might respond differently to challenge with interleukin-1alpha (IL-1alpha). Pairs of normal cartilage samples were taken from the metacarpophalangeal, proximal interphalangeal and distal interphalangeal joints of six horses. One of each pair was stimulated with 10 ng/ml human recombinant IL-1alpha for three days, and the supernatants and remaining cartilage explants were analysed for their total content of glycosaminoglycans. A significantly higher percentage of glycosaminoglycans was released from the cartilage of the proximal and distal interphalangeal joints than from the metacarpophalangeal joint.

Animals↗

Cross-sectional comparison of synovial fluid biochemical markers in equine osteoarthritis and the correlation of these markers with articular cartilage damage.

OBJECTIVE: To investigate the relationship between biochemical markers in the synovial fluid of osteoarthritic and contralateral equine joints and gross articular cartilage pathology. DESIGN: Twenty-two horses underwent bilateral arthroscopy of their carpal or metacarpophalangeal joints following recent onset lameness. The degree of cartilage damage in each joint was scored and synovial fluid, from both the clinically affected and the contralateral joint, was collected. Bone specific alkaline phosphatase (BAP), 5D4 epitope of keratan sulphate (KS), total glycosaminoglycans (GAG) and hyaluronan (HA) were measured. RESULTS: The mean age of the horses was 4.1 years and the maximum duration of lameness was three months. Joints examined were midcarpal, antebrachiocarpal and metacarpophalangeal. The median concentration (semi-interquartile range) of BAP was significantly higher in the clinically active joint than in the contralateral joint, 21.75 (6.22) vs. 12.35 (4.07) units, while the other biomarkers measured were significantly lower in the clinically active joint than in the contralateral joint, i.e. KS 8.79 (1.96) microg/ml vs. 16.39 (5.65) microg/ml, KS:GAG ratio 0.19 (0.04) vs. 0.31 (0.10) and HA 741.6 (222) microg/ml vs. 1061.75 (325) microg/ml. BAP was positively (R=0.57), and KS (R=-0.57) and KS:GAG ratio (R=-0.49) were negatively correlated to the degree of cartilage damage within the joint. CONCLUSION: The correlation between articular cartilage damage and synovial fluid BAP and KS imparts validity to their potential use as non-invasive diagnostic aids in equine osteoarthritis (OA). The positive correlation between BAP and cartilage damage suggests that there is a link between bone turnover and cartilage damage in OA.

Alkaline Phosphatase↗

Efficacy of oral calcium pentosan polysulphate for the treatment of osteoarthritis of the canine stifle joint secondary to cranial cruciate ligament deficiency.

The efficacy of calcium pentosan polysulphate (CaPPS) as a slow-acting drug for the treatment of osteoarthritis of the canine stifle joint, secondary to cranial cruciate ligament deficiency, was tested in a double-blind, placebo-controlled clinical trial over a period of one year. Dogs with the deficiency were treated surgically, matched for bodyweight, and randomly assigned to treatment or placebo groups. Active treatment began six weeks postoperatively and consisted of 10 mg/kg CaPPS orally, once weekly for four weeks, repeated every 12 weeks. The outcome was assessed in terms of function by the dogs' owners, by the radiographical grading of the osteoarthritis, and by the measurement of total sulphated glycosaminoglycans and the 5D4 epitope of keratan sulphate in the synovial fluids of affected joints. There were no differences either in functional outcome or in the radiographical progression of osteoarthritis between the two groups. Fifty-four weeks after surgery, the concentration of 5D4 in synovial fluid (expressed as change from baseline values) had decreased significantly in the treatment group compared with the placebo group (P=0.03).

Animals↗

Changes in concentrations of biochemical markers of osteoarthritis following surgical repair of ruptured cranial cruciate ligaments in dogs.

OBJECTIVE: To investigate longitudinal changes in concentrations of the 1/20/5D4 epitope (5D4) of keratan sulfate and total sulfated glycosaminoglycans (S-GAG) in synovial fluid and serum of dogs with cranial cruciate ligament (CCL) rupture that was repaired via intra-articular surgery. ANIMALS: 58 dogs with a ruptured CCL and osteoarthritis of the affected (index) joint. PROCEDURE: Prior to surgical repair of the ruptured CCL, 5D4 concentration was measured in serum and synovial fluid samples by use of an inhibition ELISA, and total S-GAG concentration was measured in synovial fluid samples by use of a direct dye-binding assay. Ruptured CCL were repaired surgically, using an intra-articular fascial graft. Dogs were reexamined 1.5, 7, and 13 months after surgery, and 5D4 and S-GAG concentrations in synovial fluid and serum were measured again. RESULTS: Serum 5D4 concentrations did not change significantly during the study. Concentrations of 5D4 in synovial fluid (expressed as a ratio of S-GAG concentration) did change significantly with time. In the index joint, the 5D4:S-GAG decreased from 0.19 at the beginning of the study to 0.09 1.5 months after surgery, but 7 months after surgery, the ratio increased again to 0.20. CONCLUSIONS AND CLINICAL RELEVANCE: Results support the hypothesis that serum concentration of 5D4 is not a useful marker of osteoarthritis in dogs. Surgical intervention transiently reduced the concentration of 5D4 in synovial fluid but had no effect on S-GAG concentration.

Animals↗

Clinical natural history of the postsurgical cruciate deficient canine stifle joint: year 1.

The aims of this prospective study were to investigate the associations and correlations between individual clinical features of osteoarthritis of the cruciate deficient stifle joint and to document the temporal changes in these features over a 13-month period following surgical treatment. Fifty-eight dogs with osteoarthritis of the stifle joint, secondary to cranial cruciate ligament deficiency, were examined before surgical treatment for cruciate deficiency and at one and a half, seven and 13 months after surgery. At each visit, clinical features were graded using four-point, discontinuous, ordinal grading (Likert) scales and intra-articular pathology was also scored in a similar fashion at arthrotomy. No attempt was made to construct an aggregate score because the relative importance of different disease features and the relationships between them were not understood at the time of writing. At entry, the relationships between background disease variables and clinical parameters were investigated as well as the relationships between clinical parameters and intra-articular pathology scores. Longitudinal analysis was performed to test for those features which showed significant change over the 13-month follow-up period. At entry, periarticular thickening and degree of crepitus were significantly correlated with disease duration. Several features showed significant change over the study period. Notably, the degree of quadriceps atrophy showed significant decrease from baseline scores at seven and 13 months while remaining different from normal, suggesting that a measure of quadriceps atrophy may be a useful measure of long-term outcome in this disease.

Animals↗

Can owners assess outcome following treatment of canine cruciate ligament deficiency?

Forty-seven owners of 48 dogs surgically treated for cranial cruciate ligament deficiency were asked to assess the outcome of treatment at one year postsurgery. A standard visual analogue scale assessment tool was used in all cases and owners were asked to score a variety of generic and disease-specific features. The reliability and responsiveness of the assessment tool were estimated and found to be acceptable; generic features, such as 'level of disability', showed the greatest reliability and responsiveness. The results of assessments by owners were compared to assessments by a veterinary surgeon but few significant correlations were found. Assessments by owners appear to be a useful outcome measure in this disease but are unlikely to be directly comparable to assessments by a veterinary surgeon.

Animals↗

Relations between biochemical markers of osteoarthritis and other disease parameters in a population of dogs with naturally acquired osteoarthritis of the genual joint.

OBJECTIVE: To investigate the hypothesis that concentrations of the keratan sulfate epitope, 1/20/5D4 (5D4) and total sulfated glycosaminoglycans (S-GAG) in synovial fluids, and of 5D4 in serum of dogs with naturally acquired osteoarthritis of the genual joint (stifle), secondary to cranial cruciate ligament deficiency, are associated with other disease parameters of osteoarthritis. ANIMALS: 58 dogs with stifle osteoarthritis secondary to naturally acquired cranial cruciate ligament (CCL) deficiency. PROCEDURE: All dogs were examined clinically, radiographically and, in some instances, scintigraphically. Serum and synovial fluid from both stifles were assayed for 5D4 concentration, using an inhibition ELISA, and for S-GAG, using a direct dye-binding assay. RESULTS: Serum 5D4 concentration was not significantly associated with other disease features. Total S-GAG values were high, and 5D4 values were low, in synovial fluid from clinically active, compared with contralateral joints. The S-GAG concentration in synovial fluid from clinically active joints was negatively correlated with radiographic severity score (rs = -0.389, P = 0.004, Spearman's rank correlation). Other associations between marker concentrations and disease parameters could not be detected. CONCLUSIONS: Serum 5D4 concentration is not a useful marker of stifle osteoarthritis in dogs; however, synovial fluid S-GAG and 5D4 values may hold more promise as disease measures.

Animals↗

Discospondylitis in an adult horse.

Discospondylitis, of presumed bacterial origin, was diagnosed in an adult thoroughbred racehorse. The clinical signs were vague and associated with abnormal mobility of the neck and forelimbs. Clinical pathology showed only a non-specific inflammatory response. A scintigraphic examination revealed the site of the lesion and the diagnosis was confirmed by the identification of radiographic changes affecting two thoracic vertebrae. A prolonged course of antimicrobial agents produced a complete recovery and the horse returned to full athletic use.

Animals↗

Variation of an epitope of keratan sulphate and total glycosaminoglycans in normal equine joints.

An epitope of keratan sulphate (KS) and total glycosaminoglycans (GAG) were measured in synovial fluid samples from joints of 53 horses immediately following humane destruction. Internal examination of the joints post mortem ensured that there was no gross evidence of osteoarthritis or other joint disease. Joints sampled were distal interphalangeal (DIP), proximal interphalangeal (PIP), metacarpophalangeal (MCP), metatarsophalangeal (MTP), tarsometatarsal (TMT), tarsocrural (TC), femoropatellar (FP) and antebrachiocarpal (ABC) joints. The age of each horse was assessed by examination of the teeth. Samples were analysed for the KS epitope using a monoclonal antibody 5D4 and an inhibition ELISA and for total GAG level by a direct dye binding technique. There was no significant correlation between KS or GAG concentration and age. However, there were significant differences in the concentrations of KS and GAG in different joints. The median level (+semi interquartile range) of KS:GAG ratio in the MCP was significantly lower than the PIP (0.25 [0.05] vs. 0.35 [0.08]; P < 0.007) and also the DIP joints (0.25 [0.05] vs. 0.47 [0.09] P < 0.001). This study provides information which is both valuable in the investigation of normal joint metabolism and essential in the interpretation of synovial fluid KS and GAG values in their potential role as aids in the evaluation of joint disease.

Aging↗

Parameters of forelimb ground reaction force in 48 normal ponies.

Recordings of forelimb ground reaction forces were made from 48 normal ponies moving at the trot, to evaluate the relationships between bodyweight, vertical ground reaction forces, the timing of individual events within the stance phase and the total contact time. There were highly significant correlations between the mean vertical ground reaction forces and bodyweight. The mean vertical ground reaction forces, corrected for bodyweight, were inversely correlated with the total contact time suggesting that higher trotting speeds may be associated with greater vertical ground reaction forces. The ponies' bodyweights were positively correlated with the contact time, implying a reduced stride frequency with increasing size. The ground reaction force events in the mid and late stance phases occurred at consistent fractions of the total stance time. The ground reaction forces and time parameters were highly symmetrical.

Animals↗

Susceptibility of various mosquitoes of California to subperiodic Brugia malayi.

Laboratory experiments were conducted to determine the susceptibility of six species of mosquitoes, representing three genera, to subperiodic Brugia malayi. The black-eye, Liverpool strain of Aedes aegypti was the susceptible control. Mosquitoes were fed on microfilaremic jirds (Meriones unguiculatus). All mosquitoes, except wild caught Culex erythrothorax, were laboratory-reared and allowed to feed when 8 to 10 days old. Anopheles freeborni, Anopheles hermsi, and Culiseta inornata proved refractory. Both Anopheles species allowed invasion of flight muscle and development to the late first stage, after which larval growth ceased and melanization occurred. Culiseta inornata prevented any larval development. Culex tarsalis and Cx. erythrothorax proved highly susceptible to B. malayi infection. In all, 95.6% and 88.7% of the Cx. tarsalis harbored third-stage larvae after infective feedings of 15.7 and 81.8 mf/microliters of blood, respectively, while only 11.5% were found susceptible when microfilaremia was low (1.1 mf/microliters). Culex erythrothorax demonstrated a susceptibility rate of 82.3% with 17.0 mf/microliters. Both Culex species appear to be excellent experimental hosts for subperiodic B. malayi. This is the first conclusive evidence that mosquitoes of the genus Culex can naturally support the complete development of a stain of subperiodic B. malayi.

Animals↗

Tendonitis of the deep digital flexor tendon in the distal metacarpal/metatarsal region associated with tenosynovitis of the digital sheath in the horse.

Twenty-four horses with ultrasonographic evidence of tendonitis of the deep digital flexor tendon in the metacarpal/metatarsal region were seen over a 7 year period. Most horses had mild to moderate lameness and distension of the digital flexor tendon sheath in the affected limb. Intrasynovial analgesia of the digital flexor tendon sheath consistently improved the degree of lameness. Ultrasonography most commonly revealed small, distinct, often circular, focal hypoechoic areas within the deep digital flexor tendon which usually extended less than 1 cm proximodistally. The degree of lameness and swelling generally improved with box rest and controlled exercise, however, exacerbation of the clinical signs and ultrasonographic lesions was common when affected horses were returned to work or allowed free exercise at pasture. Of 24 cases, only 7 horses made a full recovery and returned to their intended athletic activity.

Animals↗

Carpal conformation in relation to carpal chip fracture.

An objective radiological method of assessing the degree to which horses are conformationally 'back at the knee' (hyper-extended) is described. The effects on the measurements of variations in the direction of the incident X-ray beam and variations in weight bearing by the horse were assessed. A change from a lateromedial projection towards a plamaro-lateral-dorsomedial oblique projection consistently tended to reduce the observed degree of hyperextension of the carpus. Raising the contralateral limb to increase the load on the carpus had little effect on the measurements. The carpi of 21 thoroughbred racehorses with carpal chip fractures were not significantly more hyperextended than those of 10 thoroughbred racehorses with normal carpi. Back at the knee conformation was unlikely to have played a major role in the aetiopathogenesis of the carpal injuries.

Animals↗

Quantitative analysis of cyanogen bromide-cleaved peptides for the assessment of type I: type II collagen ratios in equine articular repair tissue.

Cyanogen bromide was used to solubilise and specifically fragment purified equine Type I and II collagen and equine articular surface repair tissue. The resultant peptides were separated by sodium dodecyl sulphate-polyacrylamide gel electrophoresis and quantified by densitometric scanning. Measurement of the relative amounts of the peptides alpha 2(I) CB3, 5 and alpha 1(II)CB10 provided an accurate method of establishing the ratio of Type I to Type II collagen in mixtures of purified equine collagens. The method was sensitive to 6% Type II collagen when the band areas were corrected for peptide molecular weight and the number of chains in the parent tropocollagen molecule which contain that particular peptide. Use of this technique showed that repair tissue in full thickness osteochondral defects in the dorso-distal margins of the intermediate carpal bones of ponies did not contain detectable amounts of Type II collagen 11 weeks after defect induction.

Animals↗

Effect of central or marginal location and post-operative exercise on the healing of osteochondral defects in the equine carpus.

The effects of osteochondral defect location and post-operative walking exercise on structural repair and recovery of joint function were examined in the midcarpal joints of ponies. Functional recovery was monitored by measuring ground reaction forces using a force plate. Structural repair was evaluated histologically and by measuring the total collagen and uronic acid content and relative proportions of Type I and II collagen in the repair tissue. Central defects tended to cause a more marked functional disturbance but were repaired with fibrocartilage rather than fibrous tissue in 3 out of 6 ponies while marginal defects were repaired almost exclusively with fibrous tissue. There was no significant difference between defect locations with regard to the biochemical measures evaluated. Exercise produced no beneficial effect on structural repair of the defects. Secondary 'kissing' lesions in the third carpal bones opposite the defects appeared grossly more severe in the exercised ponies which also showed a trend to more marked functional disturbance.

Animals↗

Influence of intra-articular sodium hyaluronate and polysulphated glycosaminoglycans on the biochemical composition of equine articular surface repair tissue.

The influence of repeated intra-articular injections of sodium hyaluronate and polysulphated glycosaminoglycan on the repair of full-thickness osteochondral defects was examined in the midcarpal joints of ponies. The study showed no significant difference between treated and control groups with regard to total collagen content, uronic acid content or the relative proportions of Type I and Type II collagen in the repair tissue, indicating that the drugs did not affect the biochemical composition of the repair tissue 11 weeks after defect induction.

Animals↗

Typhus and typhuslike rickettsiae associated with opossums and their fleas in Los Angeles County, California.

The recent discovery of cat fleas (Ctenocephalides felis) infected with a typhuslike rickettsia (designated the ELB agent) raises the question of whether similar rickettsial infections exist in wild cat flea populations. We verified the presence of the ELB agent and Rickettsia typhi in urban and suburban areas of Los Angeles, Calif. Opossums trapped in close proximity to the residences of human murine typhus cases in Los Angeles county and other areas within the city of Los Angeles were tested for the presence of typhus group rickettsiae by the polymerase chain reaction (PCR). The presence of rickettsiae in the spleen tissues of three opossums (n = 9) and in 66 opossum fleas (n = 205) was determined by PCR and was verified by dot blot and Southern transfer hybridization. Further analysis of the amplified PCR products generated by a series of primer pairs derived from either the 17-kDa antigen gene or the citrate synthase gene revealed that both R. typhi and the ELB agent were present in the tested samples. Dual infection was not noted in the samples; however, the fleas were infected with either R. typhi or the ELB agent. The presence of the ELB agent in the cat flea population may have implications for public health. Whether this agent is responsible for the mild cases of human murine typhus in urban and suburban areas of Los Angeles or in other endemic foci remains to be determined.

Animals↗