Muscle-derived neurotrophin-3 reduces injury-induced proprioceptive degeneration in neonatal mice.

During perinatal development, proprioceptive muscle afferents are quite sensitive to nerve injury. Here, we have used transgenic mice that overexpress neurotrophin-3 (NT-3) in skeletal muscle (myo/NT-3 mice) to explore whether NT-3 plays a neuroprotective role for perinatal muscle afferents following nerve injury. Measurements of NT-3 mRNA using RT-PCR revealed that levels of endogenous NT-3 mRNA in wild-type muscles remained constant during the first postnatal week following nerve crush or nerve section on postnatal day (PN) 1. In comparison, myo/NT-3 mice had significantly elevated levels of NT-3 mRNA that were maintained or increased following injury. To assess whether muscle-derived NT-3 could prevent injury-induced neuronal death, neuron survival in the DRG was analyzed in mice 5 days after sciatic nerve crush on PN3. Retrograde prelabeling of muscle afferents and parvalbumin immunocytochemistry both revealed that overexpression of NT-3 in muscle significantly reduced neuronal loss following injury. Similar neuroprotective effects of NT-3 were observed in wild-type mice injected with exogenous NT-3 in the gastrocnemius muscles. To test whether NT-3 could prevent muscle spindle degeneration, spindle number and morphology were assessed 3 weeks after sciatic nerve crush or section on PN1. No spindles were present in either wildtype or myo/NT-3 muscles after nerve section, demonstrating that NT-3 overexpression cannot maintain spindles following complete denervation. Moreover, NT-3 overexpression could not prevent moderate spindle loss in muscle and did not stimulate new spindle formation following nerve crush. Our results demonstrate that in addition to its early actions on sensory neuron generation and naturally occurring cell death, NT-3 has important neuroprotective effects on muscle afferents during postnatal development.

Concentration of collagen, aggrecan and cartilage oligomeric matrix protein (COMP) in synovial fluid from equine middle carpal joints.

The aim of the present investigation was to study the metabolic activity of the third carpal bone and the release of COMP, aggrecan and collagen type II molecules in the synovial fluid as a result of injury. Cartilage oligomeric matrix protein (COMP), aggrecan and collagen type II or fragments of these molecules released to the synovial fluid and serum (COMP) were quantified in samples from 73 left equine middle carpal joints from 2 breeds with different activity profiles (52 Standardbred trotters [STB] and 21 Swedish Warmblood riding horses [SWH]) and different articular cartilage lesions. Synovial and serum samples were analysed using inhibition ELISA for COMP and aggrecan. An ELISA that combines features of both the competitive and capture ELISAs was used for collagen type II. COMP and aggrecan concentrations decreased in synovial fluid from the joints with moderate lesions of STB compared with the normal joints; COMP from 16.6 to 12.0 microg/ml and aggrecan from 93.0 to 68.1 microg/ml. In serum, COMP concentrations were also lowered in the STB with moderate lesions compared with the normal joints, while in the SWH, the COMP concentration in synovial fluids from joints with moderate lesions was somewhat increased at 19.6 microg/ml compared with the normal joints (17.6 microg/ml). The ratio between aggrecan/COMP in the synovial fluid from joints with moderate lesions was higher in the STB (6.2) than in the SWH (3.4). The level of collagen type II in synovial fluid was higher in the SWH (8.8 microg/ml) than the STB (1.6 microg/ml), but there was no correlation between joint damage and collagen concentrations in synovial fluids (10.0 and 1.8 microg/ml in joints with moderate lesions from SWH and STB, respectively). A marked difference in COMP synthesised upon metabolic labelling between the normal and osteoarthritic cartilage was seen and the synthesis of COMP in the articular cartilage of the third carpal bone with moderate articular lesions (from an STB) was lower than in the joint with mild lesions. This difference between breeds may reflect different load characters, in release of macromolecules in osteoarthritic and normal joints. This a novel finding that should be considered in studies of equine traumatic arthritis.

Glial cell line-derived neurotrophic factor-responsive and neurotrophin-3-responsive neurons require the cytoskeletal linker protein dystonin for postnatal survival.

We have investigated the fate of different neurotrophin-responsive subpopulations of dorsal root ganglion neurons in dystonia musculorum (dt) mice. These mice have a null mutation in the cytoskeletal linker protein, dystonin. Dystonin is expressed by all sensory neurons and cross links actin filaments, intermediate filaments, and microtubules. The dt mice undergo massive sensory neurodegeneration postnatally and die at around 4 weeks of age. We assessed the surviving and degenerating neuronal populations by comparing the dorsal root ganglion (DRG) neurons and central and peripheral projections in dt mice and wildtype mice. Large, neurofilament-H-positive neurons, many of which are muscle afferents and are neurotrophin-3 (NT-3)-responsive, were severely decreased in number in dt DRGs. The loss of muscle afferents was correlated with a degeneration of muscle spindles in skeletal muscle. Nerve growth factor (NGF)-responsive populations, which were visualized using calcitonin gene-related peptide and p75, appeared qualitatively normal in the lumbar spinal cord, DRG, and hindlimb skin. In contrast, glial cell line-derived neurotrophic factor (GDNF)-responsive populations, which were visualized using the isolectin B-4 and thiamine monophosphatase, were severely diminished in the lumbar spinal cord, DRG, and hindlimb skin. Analysis of NT-3, NGF, and GDNF mRNA levels using semiquantitative reverse transcriptase-polymerase chain reaction revealed normal trophin synthesis in the peripheral targets of dt mice, arguing against decreased trophic synthesis as a possible cause of neuronal degeneration. Thus, the absence of dystonin results in the selective survival of NGF-responsive neurons and the postnatal degeneration of many NT-3- and GDNF-responsive neurons. Our results reveal that the loss of this ubiquitously expressed cytoskeletal linker has diverse effects on sensory subpopulations. Moreover, we show that dystonin is critical for the maintenance of certain DRG neurons, and its function may be related to neurotrophic support.

Risk factors associated with hindlimb lameness and degenerative joint disease in the distal tarsus of Icelandic horses.

The aim of this study was to evaluate potential risk factors associated with hindlimb lameness and radiographic signs of degenerative joint disease (DJD) in the distal tarsus in Icelandic horses. The material consisted of riding horses (n = 420) age 6-12 years sired by 17 selected sires representing all major breeding lines, and of riding horses (n = 194) in the same age range sired by other sires. The examination protocol included the following: interview with owners/trainers, assessment of conformation, motion evaluation and radiographic examination. At the interview, data related to factors outside the horse (environmental variables) and data associated directly with the horse (intrinsic variables) were obtained. Data analysis was performed in 2 steps: screening using bivariate analysis, followed by testing with a multivariate logistic regression model. In the multivariate analysis, the factors of sire, age when broken to saddle and stud show participation were strongly associated with the prevalence of lameness. Height at the croup and ability to perform different gaits were also associated with the prevalence of lameness, but to a lesser degree. The risk factors of age, tarsal angle and birthplace were significantly associated with radiographic signs of DJD in the distal tarsus. Neither the variation in applied training intensity, the use of a professional or amateur trainer nor the temperament or front limb action of the individual horse was significantly associated with the prevalence of hindlimb lameness and/or radiographic signs of DJD in the distal tarsus in the Icelandic horse.

High-conversion-efficiency, diode-pumped continuous-wave Raman laser.

We demonstrate a diode-pumped cw Raman laser in H(2) with photon-conversion efficiency of (66+/-8)%. Pumped by an injection-locked diode laser at 792 nm, the Stokes laser produces a peak output power of ~16mW at 1180 nm. Accompanying the high Stokes power are deviations from the existing theory, which are believed to be caused by the thermal-lensing effect of the Raman gas.

Effects of a digital filter on detectability of a phantom lesion in a scintigram of the equine tarsus.

The aim of this study was to examine the effects of a digital filter on the detectability of a phantom lesion in a scintigram of the equine tarsus. Lateral images containing 50, 100, 150, 500, or 1000 kcounts were acquired. A created phantom lesion of 0 (normal), 10, 15, 20, or 30% increased intensity relative to local background was placed in the centrodistal tarsal joint area in the images of different count levels. Duplicate images were filtered with a Metz filter. The complete set of filtered and unfiltered images totaling 180 images was projected as slides to a group of 9 observers. The sensitivity in 50 and 100 kcount images was improved by applying the filter. Digital filtering increased the false positive fraction at all count levels but this effect was most pronounced in 500 and 1000 kcount images. Based on receiver operating characteristic analysis, filtering of a 50 kcount image improved image quality to that of a 150 kcount image.

Sclerosis of the third carpal bone. A prospective study of its significance in a group of young standardbred trotters.

To assess the significance of radiographic signs of sclerosis of the third carpal bone (C3) in young Standardbred trotters in relation to performance, lameness and bone turnover both carpi in 14 Standardbred trotters were radiographically and scintigraphically examined 6 times, from the beginning of speed training until the beginning of racing, between the mean ages of 20 and 42 months. At the end of the study 8 horses had raced in official qualifying races and 14 limbs in 11 horses had been diagnosed with carpal lameness. All horses but 2 developed sclerosis and all but one had increased bone turnover in the C3 area by scintigraphy. C3 sclerosis increased continuously over time and with increased performance. Carpal lameness was significantly associated with progression of sclerosis but in most cases sclerosis developed without concomitant signs of carpal lameness. No association between carpal lameness and increased scintigraphic uptake was found, but horses that had qualified for racing had significantly higher C3 to carpus ratio of radiopharmaceutical uptake. We conclude that there is a continuous increase in C3 radiographic sclerosis with time in young Standardbred trotters in professional training, but radiographic sclerosis appears to be of limited value as an indicator of clinical carpal disease or level of performance in Standardbred trotters.

Radiographic and clinical survey of degenerative joint disease in the distal tarsal joints in Icelandic horses.

The prevalence of degenerative joint disease (DJD) in the distal tarsal joints and the relation between radiographic and clinical signs compatible with the disease were estimated in a population of Icelandic horses used for riding. The material consisted of 614 horses age 6-12 years (mean age = 7.9 years). Radiographs with 3 projections of each tarsus were made and a clinical examination, including palpation of the medial aspect of the distal tarsus and motion evaluation of the hindlimbs before and after a flexion test of the tarsus, was performed. Radiographic signs of DJD in the distal tarsal joints were found in 30.3% of the horses and the prevalence was strongly correlated with age. Hindlimb lameness before and after flexion test and palpation abnormalities were significantly associated with the radiographic findings. The lameness was usually mild and, in most cases, detectable only after the flexion test. The prevalence of lameness was not significantly correlated with age. Lameness could not be predicted by details of the radiographic findings.

Scintigraphic characterization of distal radial physeal closure in young Standardbred racehorses.

A longitudinal scintigraphic and radiographic study of distal radial physeal activity in 14 Standardbred trotters was conducted to quantify and visually evaluate physeal uptake around the time of physeal closure. Initial intense 99mTc-HDP uptake was seen, followed by a rapid decrease of activity starting at a mean age of 20 months. Mean physeal to distal diaphyseal ROI and line profile ratios compared to ratios of mature horses decreased from 2.8 to 1.4 at the time of radiographic closure at 24-32 months. Ratios then gradually decreased until values of mature horses were reached at the end of the study (mean age 42 months). Visually discernible distal radial physeal activity was present with declining frequency throughout the study. This study indicates that, in the normal Standardbred trotter, there is mild distal radial physeal uptake present after radiographic evidence of physeal closure. This uptake is not likely to confound evaluation of pathologic conditions of the physeal or carpal regions.

Widely tunable continuous-wave Raman laser in diatomic hydrogen pumped by an external-cavity diode laser.

What is to the authors' knowledge the first experimental demonstration of a nonresonant cw Raman laser pumped by a tunable external-cavity diode laser (ECDL) is presented. The ECDL is phase-frequency locked to a high-finesse Raman laser cavity containing diatomic hydrogen (H(2)) by the Pound-Drever-Hall locking technique. The Stokes lasing threshold occurs at a pump power of 400 +/- 30 muW, and a maximum photon conversion efficiency of 12.0 +/- 1.3% is achieved at 1.6 mW of pump power. A 40-nm tuning range of the cw Stokes emission, 1174-1214 nm, is obtained by tuning of the wavelength of the ECDL pump source.

Laser diode facet modal reflectivity measurements.

A simple and accurate method for measuring the front facet modal reflectivity of a Fabry-Perot laser diode is presented. In this method, optical feedback from an external mirror of known reflectivity, R(ext), is used to alter the laser diode threshold current. The effect of the external mirror and front facet reflectivities on the threshold current then allows for a measurement of the front facet modal reflectivity of the laser diode and is theoretically and experimentally studied. This method was used to measure a facet reflectivity of R(2) = 0.0151(+0.0018/-0.0032) [R(2) = 0.00592(+0.00085/-0.00123)] for a commercially antireflection-coated facet of a laser diode with a center wavelength of 795 nm (935 nm). The results of the reflectivity measurements based on the threshold current as a function of the external mirror reflectivity are compared with the results of the reflectivity measurements based on modulation depth of the optical spectrum [IEEE J. Quantum Electron. QE-19, 493 (1983)].

Simple method for measuring frequency chirps with a Fabry-Perot interferometer.

A simple method for measuring the frequency-chirped response of lasers is presented. This method relates the deviation from the Lorentzian line shape of the transmission of a Fabry-Perot interferometer to the frequency chirp of the laser and allows a direct measurement of the frequency chirp. Two chirps produced by an external-cavity laser diode with an intracavity electro-optic crystal were measured. The first measurement was of a linear chirp of 800 MHz occurring in a time of 12.3 micros, and the second measurement was of eight repeated 800-MHz linear chirps each occurring in 337 micros. Agreement between the measured and the expected frequency-chirped response of the laser is shown.

Hind limb skeletal lesions in 12-month-old bulls of beef breeds.

In the present study, right hind limb bones from 46 12-month-old bulls with no clinical signs were examined to identify and describe lesions that could predispose the stifle and tarsal joints to osteoarthritis. The bulls came from a performance testing station and were slaughtered due to a low index at the end of the testing period 1996-97. Differences in frequency of lesions among breeds as well as the relationship between lesions and growth rate were evaluated. Forty-five (97.8%) of the 46 bulls had lesions in the joints and/or growth plates. Prevalence of lesions was 100% in the Charolais (22/22), the Hereford (8/8), and the Limousin (4/4) breeds, and 85.7% (6/7) in the Simmental breed. The stifle was affected in 37, the tarsus in 33, and the growth plates in 34, of the 46 bulls. Lesions found in the stifle joint were: osteochondrosis of the articular-epiphysical cartilage complex (AECC) (25), subchondral bone cyst of the distal femur (1), fragmentation of the medial intercondylar eminence of the tibia (20), cleft in the distal part of the patellar groove (28), and an avulsion fracture of the lateral condyle together with a partial tear of the cranial cruciate ligament (1). Lesions found in the tarsal joint were: osteochondrosis of the AECC (23), ulcerative lesions of the articular cartilage of the talus (25), and fracture of the medial malleolus (4). Twenty-eight bulls had lesions of osteochondrosis at the AECC and 37 at the growth plates. When osteochondrosis at the AECC and thickening of the growth plates were combined, 44 of the 46 bulls had at least one lesion at the AECC and/or the growth plate. Prevalence of bulls with at least one lesion was similar between breeds, but the number of lesions per bull was significantly higher in Charolais followed by Simmental, Hereford, and Limousin. Number of lesions per bull was significantly correlated with daily weight gain, carcase weight, and the width of the proximal tibial epiphysis. Lesions were statistically independent, indicating that local biomechanical factors within the joints are important in the pathogenesis. In conclusion, we suggest that the high incidence of hind limb osteoarthritis reported in the Swedish beef bull population can be explained by the high prevalence of skeletal lesions found in the present material. The lesions appeared to be related to high growth rate and to the breed.

Retrospective study of subchondral sclerosis and lucency in the third carpal bone of Standardbred trotters.

The aim was to investigate radiographic findings of subchondral sclerosis and subchondral lucency in the dorsoproximal-dorsodistal (DPr-DDi) projection of the third carpal bone (C3) in relation to clinical appearance and to prognosis for racing. In a retrospective study, case records of 89 Standardbred trotters diagnosed with traumatic carpitis confirmed with intra-articular anaesthesia were examined. Records included data on degree of lameness at presentation and after flexion tests and a radiographic examination of the carpus, including a DPr-DDi projection of the C3. Subchondral lucency was found significantly to influence the degree of lameness at presentation and the time to start but did not significantly affect the chance of racing within 30 months post examination. In the present material no significant relationship between degree of sclerosis and lameness or prognosis for racing within 30 months was found, but the low number of C3 with severe sclerosis limited conclusions about that group.

Evaluation of different projections for radiographic detection of tarsal degenerative joint disease in Icelandic horses.

Radiographs from 196 tarsi in 98 Icelandic horses were evaluated to compare the accuracy of four different projections in detecting radiographic signs of degenerative joint disease in the distal tarsus. The extent and localization of tarsal degenerative joint disease found in one projection when reading all four projections of the same tarsus together was compared with the combined findings from all four projections. The results of reading individual radiographic projections without knowledge of the other three projections was also evaluated. Degenerative joint disease was detected most frequently in the plantarolateral-dorsomedial oblique (P1L-DMO) projection. The location with the highest relative frequency of radiographic findings was the dorsolateral aspect of the centrodistal and tarsometatarsal joints respectively. Radiographic signs of active bone remodelling was detected in 30 (33%) and periarticular osteophytes in 51 (56%) of 91 tarsi with degenerative joint disease.

Diagnostic imaging of foreign body reactions in dogs with diffuse back pain.

Six hunting dogs were investigated after showing signs of diffuse back pain. In three of the dogs, prodromal signs included coughing. Swelling in the dorsal lumbar region was noted in four of the dogs, but in two there was no visible or palpable swelling. Initial radiographs of the lumbar region were normal in two of the dogs and showed mild to moderate ventral periosteal reactions in the L1 to L4 region in the remaining four. On ultrasonography and magnetic resonance imaging, changes were seen in the sublumbar muscles (e.g., abnormal echogenicity and increased signal intensity) in five dogs examined. Exploratory surgery revealed plant material foreign bodies in the sublumbar muscles in the L1 to L4 region in five of the six dogs. The concurrent infections were caused predominantly by anaerobic bacteria common to the mucous membranes of the oropharyngeal and respiratory tracts. All dogs recovered, with restored hunting ability. The mean follow-up period was five years (range 1.3 to 7.8 years). It is proposed that the plant parts were inhaled, and then migrated along either diaphragmatic crus to lodge in the sublumbar muscles.

Programmable frequency reference for subkilohertz laser stabilization by use of persistent spectral hole burning.

We report what is believed to be the first demonstration of laser frequency stabilization directly to persistent spectral holes in a solid-state material. The frequency reference material was deuterated CaF(2): Tm(3+) prepared with 25-MHz-wide persistent spectral holes on the H(6)(3)?H(4)(3) transition at 798 nm. The beat frequency between two lasers that were independently locked to persistent spectral holes in separate crystal samples showed typical root Allan variances of 780+/-120Hz for 20-50-ms integration times.

Diode-pumped nonresonant continuous-wave Raman laser in H2 with resonant optical feedback stabilization.

We demonstrate a nonresonant cw Raman laser pumped by an optically locked diode laser at 790 nm that produces cw Stokes (1178-nm) and coherent anti-Stokes (595-nm) emission. Considering the modest pump powers, relative low cost, and predicted spectral purity, we expect that frequency downconversion of tunable diode lasers through stimulated Raman scattering will provide an attractive source for remote sensing, spectroscopic, and atomic physics applications. The Stokes laser threshold is 240+/-19muW pump power, and emission is observed over a roughly 10-nm range by adjustment of the optical locking feedback phase. Photon-conversion efficiency rises throughout the pump-power region, with a peak value of 15+/-2% .

The accuracy of the dorsoproximal-dorsodistal projection in assessing third carpal bone sclerosis in standardbred trotters.

Thirty-five carpal joints from 20 standardbred trotters, age 1 to 7 years, all euthanized for nonorthopedic reasons, were examined to investigate the correlation between assessments of subchondral bone sclerosis in the third carpal bone from radiographs in the dorsoproximal-dorsodistal (DPr-DDi) projection and histomorphometric bone volume density measurements. The agreement between assessments of sclerosis from antemortem versus postmortem radiographs was also evaluated. Bones graded as sclerotic in the DPr-DDi projection had significantly higher bone volume density values for all areas of measurement than nonsclerotic bones. For sclerotic bones, grading of sclerosis was significantly associated with volume density measurements in the central cancellous bone only. There was a good agreement (Kw = 0.71) between assessments of radiographic bone sclerosis from antemortem versus postmortem radiographs.

Prevalence and risk factors of bone spavin in Icelandic horses in Sweden: a radiographic field study.

The present field study was performed to estimate the prevalence of radiographic signs of bone spavin (RSBS) and to evaluate some possible risk factors for RSBS in the Icelandic horse in Sweden. The survey included horses from 11 farms involving 379 horses, comprising 238 geldings, 125 mares and 16 stallions. Age ranged from 0 to 19 years with a mean age of 8.1 years. Horses were radiographed with a dorsolateral-plantaromedial-oblique projection of both tarsi. Information about age, gender, origin, working intensity, number of gaits and age when saddle broken were obtained by interviewing the owners. Features of each horse's conformation were obtained by measurement or inspection. Radiographic signs of bone spavin were found in 23% (n = 88) of the horses. Horses younger than 5 years did not show any RSBS and the prevalence increased from zero to 33% between 4 and 8 years of age. Using a multivariate logistic regression model increasing age and sickle hock conformation were found to be significantly associated with increased risk of RSBS. Age when saddle broken in combination with height at the withers also influenced the multivariate logistic regression model significantly.