The p21-activated kinases (Pak) are major targets of the small GTPases Cdc42 and Rac. We, and others, recently identified a family of proteins termed Cool/Pix, which interact with Pak3. In cells, p50Cool-1 suppresses Pak activation by upstream activators; p85Cool-1 has a permissive effect on Pak activation, and we now show that the closely related Cool-2 stimulates Pak kinase activity. To understand the differential regulation of Pak by Cool proteins, we screened for Cool-interacting proteins by affinity purification and microsequencing. This has led to the identification of two closely related proteins called Cat (Cool-associated, tyrosine phosphorylated), which contain a zinc finger followed by three ankyrin repeats. Cat-1 is identical to the recently identified binding partner for the -adrenergic receptor kinase (ARK or GRK-2), which was shown to have Arf-GAP activity. Cat-1 and Cat-2 both bind to the COOHterminal region of p85Cool-1 and p85 Cool-2 but do not bind to p50Cool-1 . Cat-1 is tyrosine-phosphorylated in growing NIH 3T3 fibroblasts, and its tyrosine phosphorylation is increased following cell spreading on fibronectin, decreased in cells arrested in mitosis, and increased in the ensuing G 1 phase. Cat proteins are tyrosine-phosphorylated when co-expressed in cells with the focal adhesion kinase Fak and Src. These findings suggest that in addition to playing a role in Cool/Pak interactions, Cat proteins may serve as points of convergence between G protein-coupled receptors, integrins, Arf GTPases, cell cycle regulators, and Cdc42/Rac/Pak signaling pathways.
A 7-week-old, female Siberian husky was presented to Murdoch University Veterinary Hospital with an acute onset of respiratory distress and regurgitation. Thoracic imaging identified an intraluminal esophageal mass with concurrent aspiration pneumonia. Esophagoscopy identified the mass as stomach, and a diagnosis of gastroesophageal intussusception was made. The intussusception was reduced endoscopically, and fixation of the stomach to the abdominal wall was performed using a tube gastropexy. Gastroesophageal intussusception is an uncommon disease in small animals and traditionally has been managed surgically. This case report describes an alternative method of treatment associated with a good outcome in this puppy.
The sonographic appearance of gastrointestinal lymphoma in dogs is non-specific. Gastrointestinal lymphoma in dogs should be maintained as a differential diagnosis despite a sonographically normal appearing bowel.
A 12‐year‐old male neutered Miniature Poodle with confirmed pituitary‐dependent hyperadrenocorticism was treated with trilostane. After three doses, it developed clinical and laboratory changes suggestive of isolated hypocortisolism (‘atypical hypoadrenocorticism’), which persisted and progressed for more than 3 months despite immediate withdrawal of the trilostane. The clinical signs of hyperadrenocorticism resolved without further trilostane. After 3 months, prednisolone treatment was started and the clinical signs of hypocortisolism resolved. Prednisolone therapy was required for more than 1 year. Ultrasonography initially demonstrated large hypoechoic adrenal cortices, typical of dogs with hyperadrenocorticism, which then became small and heteroechoic, consistent with the development of adrenal necrosis. Persistent isolated hypocortisolism has not been reported previously as a complication of trilostane therapy. The case is also remarkable for the very short duration of trilostane therapy that elicited this complication. Clinicians should be aware that trilostane therapy may result in adrenal necrosis, even in the very earliest stages of therapy, but prompt action can prevent a life‐threatening situation.
A 4-year-old Siberian Husky dog was treated with brown snake antivenom by his regular veterinarian after a witnessed episode of brown snake envenomation. The dog was discharged 5 hours post presentation despite an ongoing coagulopathy. The dog was presented to the emergency centre 2 hours later because the owner believed the dog to be in pain. Initial examination revealed an ambulatory but neurologically normal patient with thoracolumbar pain and laboratory evidence of a coagulopathy. Despite correction of the coagulopathy, the signs progressed to bilateral hind limb paresis after approximately 3 hours of hospitalisation, and continued to deteriorate over the next 56 hours to loss of deep pain perception in the right hind limb. Computed tomography imaging identified the presence of an extradural haematoma which was subsequently removed via a hemilaminectomy. Surgical decompression was successful in treating the spinal compression and the dog recovered with minimal complications. To our knowledge this is the first report of extradural haematoma secondary to coagulopathy induced by brown snake envenomation.Keywords brown snake; envenomation; coagulopathy; dog; elapid; extradural haematoma; Pseudonaja Abbreviations ACT, activated clotting time; CT, computed tomography; CTM, computed tomography with myelography; FFP, fresh frozen plasma; L2, second lumbar vertebra; L3, third lumbar vertebra; MRI, magnetic resonance imaging Envenomation is common in the warmer months and is typically associated with lower motor neuron paresis or paralysis and evidence of a coagulopathy without significant muscle damage.To our knowledge a confirmed case of compressive spinal disease in the dog has not been reported as a complication of brown snake envenomation. This case report describes the presentation, diagnosis and treatment of a dog that developed hind limb paralysis secondary to extradural haematoma formation following brown snake envenomation.A 4-year-old, male neutered Siberian Husky dog was presented to his local veterinarian after his owner observed him being bitten by a snake. The history detailed collapse followed by apparent recovery, approximately 10 minutes post envenomation (Figure 1), however ongoing hind limb weakness prompted presentation to the local veterinary practice. On presentation, examination revealed hindlimb paresis, ataxia and a marked coagulopathy with an activated clotting time (ACT) of greater than 300 s (normal < 120 s). Brown snake envenomation was confirmed on a urine sample using a snake venom detection kit test (CSL Ltd, Australia) and subsequent visual identification of the snake. Gross pigmenturia was also noted in the voided urine sample. Treatment was commenced with 500 U of brown snake antivenom (CSL Ltd, Australia) after premedication with 3 mg dexamethasone sodium phosphate (Troy Laboratories, Australia). Two and 4 h after antivenom administration, ACT was still greater than 300 s however the ataxia and hind limb weakness had resolved. No further antivenom was administered. Despite the ongo...
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