Thyroid hormone coordinates respiratory control maturation and adenine nucleotide translocator expression in heart in vivo.

BACKGROUND: The signal transduction mechanism linking mitochondrial ATP synthesis with cytosolic ATP utilization in heart changes during postnatal development in vivo. This maturational process occurs in parallel with accumulation of mitochondrial adenine nucleotide translocator (ANT), which provides a possible site for respiratory control. We postulated that thyroid hormone regulates these maturational processes. METHODS AND RESULTS: We used (31)P MR spectroscopy to determine the relationship between myocardial high-energy phosphates, phosphocreatine, and ADP and oxygen consumption (MVO(2)) during epinephrine stimulation in 32- to 40-day-old lambs thyroidectomized after birth (THY) and age-matched controls. Steady-state protein and mRNA levels for ANT isoforms and beta-F(1)-ATPase were assessed from left ventricular tissues by Western and Northern blotting. With greater doses of epinephrine, THY attained lower peak MVO(2) than controls (P:<0.05). Controls maintained high-energy phosphate levels, unlike THY, which demonstrated significantly decreased phosphocreatine/ATP and increased cytosolic ADP despite lower peak MVO(2). No significant differences in beta-F(1)-ATPase protein or mRNA occurred between groups. However, ANT isoform mRNA levels were 2-fold greater and protein levels 4-fold greater in control hearts. CONCLUSIONS: These data imply that the maturational shift away from ADP-mediated respiratory control is regulated by thyroid hormone in vivo. Specific thyroid-modulated increases in ANT mRNA and protein imply that this regulation occurs in part at a pretranslational level.

The genetics of the Dras3-Roughened-ecdysoneless chromosomal region (62B3-4 to 62D3-4) in Drosophila melanogaster: analysis of recessive lethal mutations.

The genetic organization of interval 62B3-4 to 62D3-4 on the Drosophila third chromosome was investigated. The region (designated DRE) includes four known loci: Roughened (R; 3-1.4), defined by a dominant mutation disrupting eye morphology; the nonvital locus Aprt, structural gene for adenine phosphoribosyltransferase; Dras3, a homolog of the vertebrate ras oncogene; and 1(3)ecdysoneless (1(3)ecd), a gene that has been implicated in the regulation of larval molting hormone (ecdysteroid) synthesis. Overlapping chromosomal deletions of the region were generated by gamma-ray-induced reversion of the R mutation. Recessive lethal mutations were isolated based upon failure to complement the recessive lethality of Df(3L)RR2, a deletion of the DRE region that removes 16-18 polytene chromosome bands. A total of 117 mutations were isolated following ethyl methanesulfonate and gamma-ray mutagenesis. These and two additional define 13 lethal complementation groups. Mutations at two loci were recovered at disproportionately high rates. One of these loci is preferentially sensitive to radiation-induced mutational alterations. Additionally, an unusually low recovery rate for cytologically detectable rearrangement breakpoints within the gamma-ray-sensitive locus suggests that an interval of the DRE region closely linked to the R locus may be dominantly sensitive to position effects. Lethal phase analysis of mutant hemizygotes indicates that a high proportion of DRE-region loci (11 of 13) are necessary for larval development. Mutations in five loci cause predominantly first-instar larval lethality, while mutations in four other loci cause predominantly second-instar lethality. Mutations in two loci cause late-larval lethality associated with abnormal imaginal disc development. A temperature-sensitive allele of one newly identified complementation group blocks ecdysteroid-induced pupariation. This developmental block is overcome by dietary 20-hydroxyecdysone, suggesting that a second locus in the region in addition to l(3)ecd may play a role in the regulation of late larval ecdysteroid levels.

Bone scintigraphy in the diagnosis of sacroiliac injury in twelve horses.

Nuclear bone scintigraphy was used to diagnose sacroiliac injury in 12 horses presented for nonspecific rear limb lameness. The most common history was decreased performance and/or a mild chronic rear limb lameness which could not be localised by routine lameness examination. The scintigraphic patterns of the 12 affected horses were compared to 5 normal horses and 10 horses with lameness not related to the pelvic region. Subjective and quantitative evaluation of the bone scans clearly separated the 12 affected horses from the 5 normal horses and the 10 horses with lameness from causes other than the sacroiliac joint disease. The 12 affected horses had a scintigraphic pattern of moderate to marked increased uptake of the radiopharmaceutical within the sacroiliac joint region on the side of lameness. In contrast, the 5 normal horses and 10 horses scanned for other causes of lameness, had a symmetric, or only slightly asymmetric pattern of radioisotope uptake. Although nonspecific for the type of injury, nuclear bone scintigraphy is considered sensitive for the detection of sacroiliac injuries in horses.

Evaluation of canine red blood cells stored in a saline, adenine, and glucose solution for 35 days.

An additive solution for the storage of red blood cells was evaluated for use in dogs. Blood collected from 6 dogs was processed into packed red blood cells and stored for 35 days in the additive solution Nutricel (Miles, Inc, Pharmaceutical Division, West Haven, CT). Packed red blood cells stored in citrate-phosphate-dextrose-adenine (CPDA-1; Fenwal Laboratories, Baxter Health Care Corp, Deerfield, IL) also were evaluated for comparison. Red blood cell 2,3-diphosphoglycerate (2,3-DPG) concentration, adenosine triphosphate (ATP) concentration, percentage hemolysis, and pH were determined. The red blood cell post-transfusion viability (PTV) after 35 days of storage was assessed with both single-labeled chromium 51 (51Cr) and double-labeled technetium 99m/chromium 51 (99mTc/51Cr) techniques. Mean ATP concentration and percentage hemolysis of the cells stored in Nutricel were 1.1 mumol/g hemoglobin (Hb) and 0.28% respectively and did not differ significantly (P < .05) from the values of 1.0 mumol/g Hb and 0.33% from the CPDA.1-stored red blood cells. The mean pH of red blood cells stored in Nutricel was 6.19, which was significantly lower than the pH of 6.47 for cells stored in CPDA-1. The mean 2,3-DPG concentration of red blood cells stored in Nutricel was significantly higher at 10.1 mumol/g Hb than the 2,3-DPG concentration of 3.4 mumol/g Hb for cells stored in CPDA-1. The mean PTV of canine red blood cells stored in Nutricel for 35 days was 85% with 51Cr and 90% with 99mTc/51Cr. This was significantly higher than the mean PTVs of 38% and 36% for the CPDA-1 stored cells as assessed with 51Cr and 99mTc/51Cr techniques, respectively. It was concluded that 35-day-old canine red blood cells stored in Nutricel are of acceptable quality for transfusion purposes.

In vitro comparison of equine granulocytes labeled with 99mTc-hexamethylpropyleneamine oxime or 111In-oxine.

Isolated equine granulocytes (WBC), radiolabeled with 99mTc-hexamethylpropyleneamine oxime (99mTc-HMPAO) or 111In-oxine, were evaluated in vitro for their labeling characteristics, viability, and phagocytic function over a 6-hour postlabeling period. Mean +/- SD labeling efficiency for 111In-oxine-WBC was 62.2 +/- 15.3%, which was significantly (P less than 0.001) higher than that for 99mTc-HMPAO-WBC (32.0 +/- 17.0%). In vitro elution of radiolabel from cells was significantly (P less than 0.02) greater for 99mTc-HMPAO-WBC at 0.5, 2, and 4 hours, but was not significantly different from elution of radiolabel for 111In-oxine-WBC at 6 hours. Viability, assessed by trypan blue dye exclusion, for 99mTc-HMPAO-WBC, 111In-oxine-WBC, and nonlabeled control WBC ranged from 97 to 100%, and was not significantly different among groups. Cell function was assessed by use of a phagocytosis assay and was reported as phagocytic index. The phagocytic index ranged from 0.86 to 0.96 for 99mTc-HMPAO-WBC, and from 0.76 to 0.97 for 111In-oxine-WBC. The phagocytic index was not significantly different at 0.5, 2, or 4 hours, but was significantly (P = 0.038) greater at 6 hours for 99mTc-HMPAO-WBC. Because of the superior imaging characteristics of 99mTc-HMPAO-WBC and equal or better labeling characteristics than those for 111In-oxine at 6 hours, 99mTc-HMPAO-WBC appear to be a good alternative to 111In-oxine-WBC.

Use of an in vitro biotinylation technique for determination of posttransfusion viability of stored canine packed red blood cells.

OBJECTIVE: To determine posttransfusion viability (PTV) of canine RBC stored for 35 days in an additive solution, using in vitro biotinylation and technetium-99m and chromium-51 (99mTc/51Cr) labeling techniques. SAMPLE POPULATION: 6 random source, adult dogs. PROCEDURE: RBC from dogs were labeled with N-hydroxysuccinimide biotin (NHS-biotin) or 99mTc/51Cr in a crossover design. One unit (450 ml) of whole blood was collected from each dog, processed into packed RBC, and stored for 35 days in an additive solution. The process was repeated at a later date, so that each dog had 2 units stored under similar conditions. Stored autologous RBC were then labeled with either NHS-biotin or 51Cr and reinfused. When 51Cr was used, labeled cells were infused simultaneously with freshly drawn cells labeled with 99mTc. Posttransfusion viability of labeled cells was determined by dividing counts per minute (99mTc/51Cr) or percentage of cells (NHS-biotin) labeled at 24 hours by counts per minute or percentage of cells labeled after infusion. RESULTS: Mean PTV of packed RBC stored for 35 days in an additive system was 80% when determined by biotinylation, 83% as determined by 99mTc/ 51Cr, and 81% as determined by 51Cr alone. CONCLUSIONS: In vitro biotinylation provides an acceptable, nonradioisotopic means of determining PTV of stored canine packed RBC. CLINICAL RELEVANCE: NHS-biotin can be used to determine maximal storage time of canine RBC prepared for transfusion purposes.

Synovial sarcoma in a cat.

A 9-year-old male castrated cat was examined because of right forelimb lameness of 2 months' duration. The right cubital area was large, and the range of motion of the cubital joint was limited. Radiography revealed a mild periosteal reaction of the humerus, radius, and ulna. There was cortical remodeling of the distal portion of the humerus and punctate osteolysis within the proximal portion of the ulna. Arthrocentesis was performed and neoplastic cells were found, which led to a tentative diagnosis of osteogenic sarcoma or synovial cell sarcoma. Histologic diagnosis of synovial cell sarcoma was made after amputation of the limb.

Injury to the origin of the gastrocnemius muscle as a possible cause of lameness in four horses.

Four horses were evaluated because of hind limb lameness. Two had a distinct gait abnormality at the walk characterized by lateral rotation of the point of the calcaneus and medial rotation of the toe during the stance phase. Nuclear scintigraphy revealed a focal area of intense radioisotope uptake in the caudodistal aspect of the femur in all 4 horses, and 3 of the horses had a corresponding proliferative reaction on the caudodistal cortex of the femur on radiographs. In all 4 horses, a diagnosis of injury to the origin of the gastrocnemius muscle was made. Three of the horses returned to athletic endeavors after an extended period of rest and a gradual return to exercise. The fourth improved after 5 months of rest but became lame again when returned to exercise and was euthanatized.

Endoscopy of the auditory tube diverticula in four horses with otitis media/interna.

Endoscopic examination of the auditory tube diverticula was a diagnostic aid in the evaluation of 4 horses with otitis media/interna and associated osseous changes of the stylohyoid and petrous temporal. One of the horses was examined because of persistent head shaking; the other 3 were examined because of an acute onset of facial and vestibulocochlear nerve dysfunction. Proliferative lesions involving the petrous temporal bone and proximal portion of the stylohyoid bone were identified endoscopically in all 4 horses. Endoscopy is a noninvasive procedure that provides an alternative to skull radiography and tympanocentesis in the diagnosis of otitis media/interna in horses. In addition, risks associated with general anesthesia are avoided.

Lag screw stabilization of a cervical vertebral fracture by use of computed tomography in a horse.

A traumatic fracture of C2 was diagnosed radiographically in a 1-year-old German Warm-blood stallion. Fracture configuration was difficult to see on survey radiographs. Computed tomography yielded a more accurate assessment of the fracture and facilitated fracture repair with cortical lag screws. Precise screw placement, to avoid spinal cord damage, was obtained by use of computed tomography. Follow-up radiography revealed normal bone healing, and the horse was in dressage schooling 24 months after surgery.

Diagnostic imaging of lameness in small animals.

The demand for advanced diagnostic imaging procedures such as nuclear scintigraphy, ultrasonography, computed tomography, and magnetic resonance imaging has increased dramatically over the past 10 years. Veterinarians, seeking to improve their diagnostic capabilities and clients willing to pursue "best medicine" have driven this demand, resulting in installation of advanced imaging facilities at most academic and private referral practices. Knowledge of potential benefits of various modalities will allow the veterinarian to optimize his or her use of diagnostic imaging in his or her own practice or in a referral practice.

Brain imaging.

Advances in medical technology have revolutionized diagnostic brain imaging. Traditional radiography and invasive contrast studies for intracranial imaging have been superseded by several newer imaging modalities which provide high resolution, cross-sectional images. Ultrasonography, computed tomography, magnetic resonance, and nuclear scintigraphy are now used for anatomical and functional imaging of the brain. These noninvasive modalities are available at most veterinary teaching institutions and are offered through many larger referral practices. The diagnostic usefulness and clinical limitations for each of these modalities are described.

Thyroid adenocarcinoma in a bald eagle (Haliaeetus leukocephalus).

Thyroid adenocarcinoma was diagnosed in an adult bald eagle (Haliaeetus leukocephalus) with clinical signs of weakness manifested by inability to fly. Physical examination at the time of admission revealed dried blood in the pharynx and glottis and the presence of pharyngeal trichomonads. Radiographs revealed a large soft tissue mass in the area of the left coracoid and clavicular bones. One month following successful treatment for trichomoniasis, the bird suffered an acute episode of tracheal hemorrhage and died. Necropsy revealed a large mass within the interclavicular air sac. The histologic features were consistent with thyroid adenocarcinoma. This is the first report of thyroid neoplasia in a member of the order Falconiformes.

Lumbosacral foraminal ratios and areas using MRI in medium-sized dogs.

OBJECTIVE: To examine conventional magnetic resonance imaging planes of the lumbosacral foramina to obtain objective measurements of foraminal size in medium-sized (20-28 kg) normal dogs. METHOD: Ten canine cadavers were evaluated using magnetic resonance imaging in neutral, flexed and extended position. Foraminal ratios, areas and lumbosacral angles were calculated and their relationship to body weight was evaluated. RESULTS: Foraminal ratios were found to be independent of body weight in medium sized dogs (p >0.42). Foraminal areas were dependent on body weight (p <0.05). Flexion and extension were shown to significantly change both the foraminal ratio and area. CLINICAL SIGNIFICANCE: Lumbosacral foraminal stenosis is common in working dogs. Foraminal ratios were evaluated in medium-sized dogs and were found to be independent of body weight, which may provide objective evaluation of surgical decompression techniques if calculated pre- and post-surgery. Foraminal areas were not independent of body weight.