Cloning, expression and characterization of monkey (Macaca fascicularis) CD137

CD137 plays an important role as a co-stimulatory molecule in activated T cells. Agonistic CD137 specific antibodies have been investigated as therapeutic agents to promote tumor-specific immune responses by direct activation of T cells. As part of the pre-clinical pharmacological evaluation of cynomolgus monkeys, monkey CD137 was cloned and characterized. The deduced amino acid sequence encoded a full-length gene of 254 amino acids 95% identical to human CD137. Sequence variants identified in monkey CD137 include four splice variants lacking the transmembrane domain. These variants were detectable in human including two previously unreported variants. Two missense single nucleotide polymorphisms were detected present in 42 and 50% of 36 monkeys tested. In both monkey and human, mRNA expression of full-length CD137 and splice variants were significantly increased in peripheral blood mononuclear cells (PBMCs) upon stimulation by anti-CD3 antibodies. Recombinant monkey CD137 protein was bound with high affinity by an agonistic anti-human CD137 antibody but not by an anti-mouse CD137 antibody. In summary, compared to human, monkey CD137 showed distinct extracellular domain amino acid sequence and sequence polymorphisms. Thus, antibodies directed against epitopes in this extracellular domain could have differences in pharmacologic activity between cynomolgus monkeys and human or across individual cynomolgus monkeys.     

Suspected paraspinal abscess and spinal epidural empyema in a dog

Epidural spinal cord compression was visualized myelographically in a dog presented for rapid development of paraparesis. A large, fluid-filled pocket in the epaxial musculature was found at surgery and appeared to communicate with the first lumbar vertebra. Unfortunately, cytopathological evaluation of the fluid was not performed. No etiological agents were isolated on aerobic culture. The dog responded well to decompressive surgery and medical therapy consisting of antibiotics, pain medication, and nursing care. In the veterinary literature, only two studies of spinal epidural empyema in the dog have been reported. Of these dogs, one had successful decompressive surgery performed. The other dogs in these two reports were euthanized. The dog presented in this report fully recovered. Spinal epidural empyema should be considered as a differential diagnosis in dogs presenting with a fever and a rapidly progressing myelopathy.     

Moment arms about the carpal and metacarpophalangeal joints for flexor and extensor muscles in equine forelimbs

OBJECTIVE: To determine whether muscle moment arms at the carpal and metacarpophalangeal joints can be modeled as fixed-radius pulleys for the range of motion associated with the stance phase of the gait in equine forelimbs. SAMPLE POPULATION: 4 cadaveric forelimbs from 2 healthy Thoroughbreds. PROCEDURE: Thin wire cables were sutured at the musculotendinous junction of 9 forelimb muscles. The cables passed through eyelets at each muscle's origin, wrapped around single-turn potentiometers, and were loaded. Tendon excursions, measured as the changes in lengths of the cables, were recorded during manual rotation of the carpal (180 degrees to 70 degrees) and metacarpophalangeal (220 degrees to 110 degrees) joints. Extension of the metacarpophalangeal joint (180 degrees and 220 degrees) was forced with an independent loading frame. Joint angle was monitored with a calibrated potentiometer. Moment arms were calculated from the slopes of the muscle length versus joint angle curves. RESULTS: At the metacarpophalangeal joint, digital flexor muscle moment arms changed in magnitude by < or = 38% during metacarpophalangeal joint extension. Extensor muscle moment arms at the carpal and metacarpophalangeal joints also varied (< or = 41% at the carpus) over the range of joint motion associated with the stance phase of the gait. CONCLUSIONS AND CLINICAL RELEVANCE: Our findings suggest that, apart from the carpal flexor muscles, muscle moment arms in equine forelimbs cannot be modeled as fixed-radius pulleys. Assuming that muscle moment arms at the carpal and metacarpophalangeal joints have constant magnitudes may lead to erroneous estimates of muscle forces in equine forelimbs.     

Assessment of Best-Management Practice Effects on Rangeland Stream Water Quality Using Multivariate Statistical Techniques

Quantifying the effects of watershed improvement efforts is critical to agencies responsible for protecting water resources of the semiarid western United States. A complex water quality data set collected from 1994 to 2004 of upper Muddy Creek Basin was subjected to cluster analysis, discriminant analysis, and canonical correlation analysis to improve understanding of basin fluvial processes and to investigate whether livestock grazing best-management practices (BMPs) improved the water quality of the watershed. Hierarchical agglomerative cluster analysis grouped nine sampling sites into two clusters based on similarity of biological indices, separating the clusters into aquatic communities more and less tolerant of degraded stream conditions. Discriminant analysis yielded strong spatial and temporal distinctions, providing important data reduction by rendering seven key parameters (total dissolved solids [TDS], temperature, elevation, slope, 10-dominant taxa, percent collector-gatherers, and percent Plecoptera) for the spatial variation and four parameters (TDS, dissolved oxygen, total taxa, and community tolerance quotient) for the temporal variation. Canonical correlation analysis identified strong negative relationships among Plecoptera taxa and total taxa with TDS and turbidity in addition to strong positive associations with elevation, slope, and channel substrate weighted embeddedness value. Despite the onset of severe drought midway through the study period, overall reductions of 13% for TDS and a 30% increase in macroinvertebrate total taxa occurred across years, strongly suggesting that improvements in water quality were correlated to BMPs that stabilized stream channels and improved the condition of riparian areas.     

Presumptive pseudohypoaldosteronism secondary to chronic urinary tract obstruction from sloughed urinary bladder mucosa and urinary tract infection in a cat

Objective – To describe a case of presumptive secondary pseudohypoaldosteronism (PHA) in a cat with urinary tract infection and chronic urethral obstruction. The obstruction was believed to have resulted from sloughed urinary bladder mucosa secondary to pressure necrosis. Case Summary – A 5‐year‐old, 4 kg, castrated male Siamese cat presented for vomiting and stranguria. Medical history included a perineal urethrostomy for urethral obstruction. Physical examination revealed a large, painful, nonexpressible urinary bladder. Point‐of‐care testing demonstrated electrolyte derangements consistent with a postrenal azotemia and metabolic acidosis. Results of urine culture was positive for bacterial growth. Diagnostic imaging revealed presence of retroperitoneal fluid, marked urinary bladder wall thickening, bilateral hydroureter, mild bilateral pyelectasia, and small nephroliths. The patient was treated for a urinary tract obstruction and infection. In the 3 weeks following initial discharge, the patient was evaluated on multiple occasions for lethargy, intermittent vomiting, inappropriate urination, and progressive polyuria and polydipsia. Although the urinary bladder was easily expressed during repeat examinations, it was persistently distended and subjectively thickened upon palpation. Repeat ultrasound of the urinary tract showed evidence of sloughed tissue in the bladder lumen, likely secondary to chronic urethral obstruction and pressure necrosis. A cystotomy was performed to remove the necrotic tissue, and a revised perineal urethrostomy was done due to a partial urethral stricture. Bladder biopsies were obtained at this time. Postoperatively, the cat was reported by the owners to be urinating normally but continued to be polyuric and polydipsic in the week following discharge. One week after surgery, the cat presented in hypovolemic shock with laboratory findings consistent with a presumptive diagnosis of secondary PHA. New or Unique Information Provided – PHA has not been reported previously in a cat. This case report suggests that aldosterone resistance should be considered in cats with consistent laboratory findings and a history of documented obstructive uropathy and urinary tract infection.     

Disseminated candidiasis secondary to fungal and bacterial peritonitis in a young dog

Objective – To describe a severe case of bacterial sepsis and disseminated candidiasis in a previously healthy dog.
Case Summary – Fungal sepsis was identified in a 2-year-old dog following intestinal dehiscence 4 days after abdominal surgery. Septic peritonitis was identified at admission and evidence of dehiscence at the previous enterotomy site was found during an exploratory laparotomy. Both gram-positive cocci and Candida albicans were cultured from the abdominal cavity. Candida sp. was also subsequently cultured from a central venous catheter. Euthanasia was performed due to failure to respond to therapy. Fungal organisms, morphologically consistent with Candida spp., were found in the lungs and kidney on postmortem histopathologic examination indicating disseminated candidiasis.
New or Unique Information Provided – Candida peritonitis is a well-recognized entity in humans and contributes to morbidity and mortality in critically ill patients. Abdominal surgery, intestinal perforation, presence of central venous catheters, and administration of broad-spectrum antibiotics are all considered to be suspected risk factors. This report describes the first known case of systemic candidiasis occurring secondary to Candida peritonitis and bacterial sepsis in a critically ill dog.     

Association between cribbing and entrapment of the small intestine in the epiploic foramen in horses: 68 cases (1991-2002)

OBJECTIVE: To determine whether there was an association between a history of cribbing and epiploic foramen entrapment (EFE) of the small intestine in horses. DESIGN: Retrospective study. ANIMALS: 68 horses examined at the University of Illinois or the University of Liverpool veterinary teaching hospitals. PROCEDURE: For horses examined at the University of Illinois that underwent surgery because of strangulating small intestine lesions, information about cribbing was obtained through telephone calls with owners. For horses examined at the University of Liverpool that underwent surgery for colic for any reason, information about cribbing was obtained through a preoperative questionnaire. RESULTS: 13 of 19 (68%) horses with EFE examined at the University of Illinois had a history of cribbing, compared with only 2 of 34 (6%) horses with other strangulating small intestine lesions (odds ratio, 34.7; 95% confidence interval, 6.2 to 194.6). Similarly, 24 of 49 (49%) horses with EFE examined at the University of Liverpool had a history of cribbing, compared with 72 of 687 (10.5%) horses with colic caused by other lesions (odds ratio, 8.2; 95% confidence interval, 4.5 to 15.1). CONCLUSIONS AND CLINICAL RELEVANCE: Results suggest that there may be an association between cribbing and EFE in horses, with horses with a history of cribbing more likely to have EFE than horses without such a history.