Low-field magnetic resonance imaging characteristics of multifocal vertebral lesions in dogs.

BACKGROUND: There is a lack of information regarding magnetic resonance imaging (MRI) features of polyostotic vertebral lesions in dogs. The aim of this retrospective study was to identify and differenciate low-field MRI features of aggressive versus benign multifocal vertebral diseases in dogs. METHODS: MRI examinations from 49 dogs with polyostotic vertebral lesions were reviewed. Images were evaluated for vertebral intensity changes, expansile lesions, new bone formation, cortical bone interruption, paravertebral musculature changes, lymphadenomegaly, spinal cord compression and spinal cord signal changes. RESULTS: Twenty-nine dogs with non-aggressive bone lesions and 20 dogs with aggressive vertebral lesions were included. Non-aggressive lesions had variable T2-weighted fast spin-echo (T2W) signal intensity and the majority displayed low signal intensity on short tau inversion recovery (STIR). Aggressive lesions predominantly had high T2W and STIR signal intensity, with variable signal intensity on T1-weighted spin-echo and contrast enhancement. Aggressive lesions were associated with spinal pain (p < 0.01), new bone formation (p = 0.02), spinal cord compression (p < 0.01) and lymphadenomegaly (p < 0.01). Cortical interruption (p < 0.01) and paravertebral musculature changes (p < 0.01) were the strongest indicative imaging features for aggressive lesions. CONCLUSION: Spinal pain, spinal cord compression, new bone formation, lymphadenomegaly and especially cortical interruption and paravertebral musculature signal intensity changes were the best discriminators for differentiating malignant from benign vertebral lesions.

Convergence-Retraction Nystagmus in a Dog With Presumptive Ischemic Encephalopathy Following Acute Cervicothoracic Myelopathy.

A 6.5-year-old male neutered Trailhound was admitted for hyperacute, nonprogressive, left-sided hemiparesis. Physical and neurologic examination revealed nonpainful, left-sided poorly ambulatory hemiparesis, decreased left-sided postural reactions and thoracic limbs hyporeflexia. Neuroanatomic localisation was consistent with a left-sided C6-T2 myelopathy. Haematology and biochemistry revealed nonspecific abnormalities. Magnetic resonance imaging of the neck revealed a focal intramedullary lesion at the level of C6-C7 vertebrae compatible with acute hydrated noncompressive nucleus pulposus extrusion or ischemic myelopathy. During the second day of hospitalization, the dog developed convergence-retraction nystagmus, up-gaze palsy and eyelid retraction (Collier's sign) compatible with dorsal midbrain syndrome. Magnetic resonance imaging of the brain revealed a focal lesion compatible with dorsal midbrain ischemic infarct. Further clinicopathologic testing, thoracic and abdominal imaging were unremarkable. Ischemic encephalopathy of unknown etiology was additionally diagnosed. Physiotherapy was performed therapeutically. At 1-year follow-up the dog was normal. This is an unusual report of a dog with myelopathy followed by ischemic encephalopathy with manifestation of convergence-retraction nystagmus in the absence of vestibular signs. This saccadic intrusion is a characteristic clinical manifestation of a dorsal midbrain syndrome localization. The importance of a complete differential diagnoses list formation in a dog with ischemic encephalopathy which leads to a thorough diagnostic investigation plan is highlighted. Moreover, this report contributes to the enrichment of the clinical reasoning veterinary literature on convergence-retraction nystagmus. To the authors' knowledge, this is the second case report (fourth dog) to describe convergence-retraction nystagmus in dogs as a manifestation of dorsal midbrain syndrome.

Chlamydia-induced curvature of the host-cell plasma membrane is required for infection.

During invasion of host cells, Chlamydia pneumoniae secretes the effector protein CPn0678, which facilitates internalization of the pathogen by remodeling the target cell's plasma membrane and recruiting sorting nexin 9 (SNX9), a central multifunctional endocytic scaffold protein. We show here that the strongly amphipathic N-terminal helix of CPn0678 mediates binding to phospholipids in both the plasma membrane and synthetic membranes, and is sufficient to induce extensive membrane tubulations. CPn0678 interacts via its conserved C-terminal polyproline sequence with the Src homology 3 domain of SNX9. Thus, SNX9 is found at bacterial entry sites, where C. pneumoniae is internalized via EGFR-mediated endocytosis. Moreover, depletion of human SNX9 significantly reduces internalization, whereas ectopic overexpression of CPn0678-GFP results in a dominant-negative effect on endocytotic processes in general, leading to the uptake of fewer chlamydial elementary bodies and diminished turnover of EGFR. Thus, CPn0678 is an early effector involved in regulating the endocytosis of C. pneumoniae in an EGFR- and SNX9-dependent manner.

The chlamydial OTU domain-containing protein ChlaOTU is an early type III secretion effector targeting ubiquitin and NDP52.

Chlamydia are obligate intracellular pathogens. Upon contact with the host, they use type III secretion to deliver proteins into the cell, thereby triggering actin-dependent entry and establishing the infection. We observed that Chlamydia caviae elicited a local and transient accumulation of ubiquitinated proteins at the entry sites, which disappeared within 20 min. We investigated the mechanism for the rapid clearance of ubiquitin. We showed that the OTU-like domain containing protein CCA00261, predicted to have deubiquitinase activity, was detected in infectious particles and was a type III secretion effector. This protein is present in several Chlamydia strains, including the human pathogen Chlamydia pneumoniae, and we further designate it as ChlaOTU. We demonstrated that ChlaOTU bound ubiquitin and NDP52, and we mapped these interactions to distinct domains. NDP52 was recruited to Chlamydia entry sites and was dispensable for infection and for bacterial growth. ChlaOTU functioned as a deubiquitinase in vitro. Heterologousexpression of ChlaOTU reduced ubiquitin accumulation at the entry sites, while a catalytic mutant of the deubiquitinase activity had the opposite effect. Altogether, we have identified a novel secreted protein of chlamydiae. ChlaOTU targets both ubiquitin and NDP52 and likely participates in the clearance of ubiquitin at the invasion sites.