Clinical Features, Imaging Characteristics, and Long-term Outcome of Dogs with Cranial Meningocele or Meningoencephalocele.

BACKGROUND: The term meningoencephalocele (MEC) describes a herniation of cerebral tissue and meninges through a defect in the cranium, whereas a meningocele (MC) is a herniation of the meninges alone. HYPOTHESIS/OBJECTIVES: To describe the clinical features, magnetic resonance imaging (MRI) characteristics, and outcomes of dogs with cranial MC and MEC. ANIMALS: Twenty-two client-owned dogs diagnosed with cranial MC or MEC. METHODS: Multicentric retrospective descriptive study. Clinical records of 13 institutions were reviewed. Signalment, clinical history, neurologic findings and MRI characteristics as well as treatment and outcome were recorded and evaluated. RESULTS: Most affected dogs were presented at a young age (median, 6.5 months; range, 1 month - 8 years). The most common presenting complaints were seizures and behavioral abnormalities. Intranasal MEC was more common than parietal MC. Magnetic resonance imaging identified meningeal enhancement of the protruded tissue in 77% of the cases. Porencephaly was seen in all cases with parietal MC. Cerebrospinal fluid (CSF) analysis identified mild abnormalities in 4 of 11 cases. Surgery was not performed in any affected dog. Seventeen patients were treated medically, and seizures were adequately controlled with anti-epileptic drugs in 10 dogs. Dogs with intranasal MEC and mild neurologic signs had a fair prognosis with medical treatment. CONCLUSION AND CLINICAL IMPORTANCE: Although uncommon, MC and MEC should be considered as a differential diagnosis in young dogs presenting with seizures or alterations in behavior. Medical treatment is a valid option with a fair prognosis when the neurologic signs are mild.

Cervical intervertebral foraminal disc extrusion in dogs: clinical presentation, MRI characteristics and outcome after medical management.

The aim of the present study was to retrospectively evaluate the clinical signs, MRI characteristics, interobserver agreement and outcome after medical treatment in dogs affected by cervical intervertebral foraminal disc extrusion (CIFDE). The medical records of three referral institutions were searched for dogs diagnosed with CIFDE between 2010 and 2012. Thirteen dogs were identified with CIFDE; affected dogs often had a normal neurological examination, with cervical hyperaesthesia and lameness as the most common clinical signs. On MRI, sagittal images showed no evidence of compression of the spinal cord; CIFDE could be identified only on transverse sections in all cases. An excellent interobserver agreement was found in the localisation of the affected intervertebral disc space, and a substantial agreement was found on the detection of CIFDE versus foraminal stenosis caused by overgrowing articular processes. All but two dogs recovered completely, and they were considered free of clinical signs without analgesia within a median of 7.5 weeks (range: 2-20) after medical management was started. The remaining two dogs were surgically treated followed by complete recovery. In view of our findings, the importance of a thorough MRI investigation in dogs presenting with cervical hyperaesthesia as the sole clinical sign should be highlighted.

Magnetic resonance imaging of suspected idiopathic bilateral C2 hypertrophic ganglioneuritis in dogs.

OBJECTIVES: To report the magnetic resonance imaging and clinical features of suspected idiopathic bilaterally symmetric hypertrophic ganglioneuritis affecting the C2 nerve roots. METHODS: Retrospective analysis of case records of dogs with imaging findings suggestive of idiopathic bilateral C2 neuritis. Data analysed included signalment, history, clinical signs, clinical pathology results and magnetic resonance imaging findings. Nerve root enlargement and spinal cord changes were classified as clinically significant or incidental, and further graded as mild, moderate or severe based on the degree of spinal cord distortion/compression. Imaging features were also correlated with severity of neurological deficits. RESULTS: Twelve dogs, including nine Staffordshire bull terriers showed magnetic resonance imaging features suggestive of idiopathic hypertrophic neuritis of C2 nerve roots. Findings were considered incidental (4/12) or clinically significant (8/12) based on prior neurological examination. Changes were best visualised on transverse images at the level of the C1-2 intervertebral foramina. The degree of associated spinal cord compression subjectively correlated with the severity of the neurological deficits. All cases with clinically significant lesions that were treated with corticosteroids responded favourably. CLINICAL SIGNIFICANCE: Bilaterally symmetric C2 neuritis likely represents idiopathic hypertrophic ganglioneuritis. Staffordshire bull terriers appear over represented. Immunosuppressive doses of corticosteroids should be considered for clinically significant lesions.

Radiographic and ultrasonographic changes of the patellar ligament following tibial tuberosity advancement in 25 dogs.

INTRODUCTION: Patellar ligament thickening is a recognized response following osteotomy of the proximal tibia as a treatment for cranial cruciate disease. In humans this is seen as a response to increased loading, but the reason for this thickening in dogs is unclear. A prospective study was undertaken to assess the degree and frequency of patellar ligament desmopathy in 25 consecutive cases undergoing tibial tuberosity advancement (TTA). OBJECTIVES: To determine the incidence of patellar ligament thickening following TTA. METHODS: Consecutive cases undergoing TTA had ultrasonographic and radiographic measurements performed of the patellar ligament, at multiple positions on the ligament. This was performed at the time of surgery, and at six weeks and six months (ultrasound only) following surgery. The radiographic measurements were performed by two reviewers who were blinded to the timeframe of each image. RESULTS: There was great variation in both the incidence and degree of thickening of the ligament. Fifty percent of the cases showed no changes in the thickness of the patellar ligament. A clinical pain response was not associated with patellar ligament thickening. No statistically significant variables which predicted the development of patellar ligament thickening were identified . CLINICAL SIGNIFICANCE: The presence of signs of patellar ligament thickening is of questionable clinical significance and is probably an incidental finding.

Frontal sinus depth at four landmarks in breeds of dog typically affected by sinonasal aspergillosis.

The objective of this study was to assess whether the frontal sinuses in dogs with aspergillosis and of breeds typically affected by this condition were deeper at a more caudal location. CT scans of the head performed at the Small Animal Teaching Hospital, University of Liverpool, between April 2007 and March 2009 for dogs diagnosed with aspergillosis (group 1) and unaffected dogs of similar breeds (group 2) were selected for study. Sinus depth was measured at four standardised locations from reconstructed images of these CT scans. Data were compared for differences in sinus depth between groups and between landmarks. No significant difference was found between measurements within individual dogs or for each of the various landmarks between groups. Difference in depth of the sinuses between landmarks was significant (P<0.001). Sinus depth was significantly greater at the more caudal landmarks and was shallowest at the previously recommended landmark for sinus entry. In 54 per cent of dogs, the frontal sinus depth measured less than or equal to 2 cm at one or more of the landmarks. Sinus entry at the deepest point will reduce the risk of accidentally damaging underlying structures. This may be approximately 1 cm caudal, in breeds of dog that typically develop aspergillosis, to a previously suggested landmark.

Observer variation in the evaluation and classification of severe central tarsal bone fractures in racing Greyhounds.

OBJECTIVES: To determine observer agreement on radiographic evaluation of central tarsal bone (CTB) fractures and compare this with evaluation of the same fractures using computed tomography (CT). METHODS: Radiographs and CT scans were obtained of the right tarsi from limbs of Greyhounds euthanatized after sustaining severe CTB fracture during racing. Four observers described and classified each fracture. Inter- and intra-observer agreements were calculated. RESULTS: Inter-observer agreement was higher for assessment of fractures using CT. Several fractures assessed by radiography were misclassified as a less severe type. Intra-observer agreement for assessment and classification of CTB fractures via radiography versus CT was variable. Overall agreement among all four observers was higher for CT than radiography. Additionally, when identifying fractures of the adjacent tarsal bones, observer agreement was higher for CT than radiography. CLINICAL SIGNIFICANCE: Computed tomography improved observer ability to correctly evaluate CTB fracture and detect the degree of displacement and extent of any comminution. Identification of fractures of adjacent tarsal bones was also improved when tarsi were assessed using CT. These data suggest that treatment decisions based solely on radiographic assessment of CTB fractures may not produce the expected outcome.

Lymphoid tissue inducer cells: bridges between the ancient innate and the modern adaptive immune systems.

Phylogeny indicates that adaptive immunity evolved first in diffusely distributed lymphoid tissues found in the lamina propria (LP) of the gut. B follicular structures appeared later, probably initially in isolated lymphoid follicles in the LP and then in organized lymphoid tissues such as lymph nodes and Peyer's patches. The development of these new lymphoid structures was enabled by gene duplication and evolution of new tumor necrosis family members. Here, we argue that lymphoid tissue inducer cells (LTis) had a pivotal role, not only in the development of organized lymphoid structures, but also in the subsequent genesis of the CD4-dependent class-switched memory antibody responses. In this review, we concentrate on the latter function: the sustenance by LTis of CD4 T-cell responses for protective immunity.

Lymphoid tissue inducer cells: architects of CD4 immune responses in mice and men.

In this review, we summarize the current understanding of the multiple functions of the mouse lymphoid tissue inducer (LTi) cells in: (i) the development of organized lymphoid tissue, (ii) the generation and maintenance of CD4-dependent immunity in adult lymphoid tissues; and (iii) the regulation of central tolerance in thymus. By contrast with mouse LTi cells, which have been well described, the human equivalent is only just beginning to be characterized. Human LTi-like cells expressing interleukin (IL)-22 have been identified recently and found to differentiate into natural killer (NK) cells. The relationship of LTi cells to NK cells is discussed in the light of several studies reporting a close relationship in the mouse between LTi cells and transcription factor retinoid-related orphan receptor gammat-dependent IL-22 producing NK cells in the gut. We also outline our data suggesting that these cells are present in adult human lymphoid tissues.

Congenital hyposomatotropism in a domestic shorthair cat presenting with congenital corneal oedema.

A six-month-old, female, domestic shorthair cat was presented with a history of failure to grow and bilateral corneal opacity caused by corneal oedema. Congenital hyposomatotropism and possible secondary hypothyroidism were diagnosed on the basis of fasting serum levels of insulin-like growth factor-1 and thyroxine levels, respectively. These endocrinopathies are rare in the cat and have not been reported to cause ocular signs. The cat died during investigation of these diseases, and histopathological examination of the eyes showed significantly reduced corneal endothelial cell density and number of corneal epithelial cell layers when compared with age-matched healthy control corneas. These changes were implicated in the development of the corneal oedema.

Dendritic cell subsets and costimulation for effector T-cell responses.

The past year has seen major advances in the understanding of dendritic cell biology and of the costimulatory molecules that dendritic cells use to prime effector T cells and memory T cells. Recent work has revealed the specialization between different dendritic cell subsets and how this relates to their different functions in optimizing T-cell help for antibody responses and inflammatory T-cell responses.

Epidemiology and clinical impact of Pseudomonas aeruginosa infection in cystic fibrosis using AP-PCR fingerprinting.

Arbitrarily primed PCR (AP-PCR) was utilized to genetically fingerprint 252 Pseudomonas aeruginosa strains isolated from the sputa of 50 cystic fibrosis (CF) patients attending the Cork CF clinic over a period of 3 years. Ten distinct P. aeruginosa strains were identified and the distribution, temporal trends and clinical impact of colonization with these individual P. aeruginosa clones was studied. A number of random isolates from each AP-PCR group were analysed using pulsed field gel electrophoresis (PFGE) in order to confirm the discriminatory power of the AP-PCR technique. The majority of patients were colonized with a single strain over the time period of the study, but it was also possible to harbour two or more strains transiently or simultaneously. Four main strains were relatively evenly distributed throughout the CF population, and it was noted that patients from the same family or attending the same school tended to harbour the same P. aeruginosa clone. Disease severity was significantly associated with the age of the patient (P < 0.001), clearly indicating an increase in severity with increase in age. The general clinical status of the CF patients was not significantly associated with the P. aeruginosa variant isolated from their sputa. Lung status was defined by FEV1 measurement and chest X-ray score (CXR). The non parametric Kruskal-Wallis significance test of FEV1, CXR and age by colonizing P. aeruginosa clone indicated that FEV1 (P = 0.017), but not CXR (P = 0.19) or age (P = 0.842), differed significantly across the clones of P. aeruginosa isolated. Patients harbouring P. aeruginosa strains B, F or G clearly had lower FEV1 scores while those harbouring clones A, C, D or H generally had higher FEV1 scores. Thus, the sub-species variant of P. aeruginosa colonizing CF patients may be associated with the severity of progressive lung disease.

Evidence that induction of tolerance in vivo involves active signaling via a B7 ligand-dependent mechanism: CTLA4-Ig protects V beta 8+ T cells from tolerance induction by the superantigen staphylococcal enterotoxin B.

Co-stimulation through CD28 is thought to be necessary for the activation of unprimed CD4+ T cells, which are otherwise rendered tolerant. However, we previously found that CD4+ T cell priming was normal or augmented in mice which overexpressed a soluble form of CTLA4 where co-stimulation through CD28 was abrogated. To investigate this CD4+ T cell response, we exploited the capacity of the superantigen staphylococcal enterotoxin B to stimulate T lymphocytes bearing V beta 8+, which represent approximately 30% of all CD4+ T cells. In litter-mate controls of CTLA4-Ig transgenic mice, immunization with staphylococcal enterotoxin B leads to expansion, followed by deletion of V beta 8+ T cells, and the remaining cells are tolerant when stimulated in vitro. Comparable expansion and deletion of V beta 8 T cells occurs in CTLA4-Ig transgenic mice. However, in contrast to normal mice, the remaining V beta 8+ T cells from CTLA4-Ig transgenic mice are not anergic and remain responsive to superantigen in vitro.

CD40 ligand-independent B cell activation revealed by CD40 ligand-deficient T cell clones: evidence for distinct activation requirements for antibody formation and B cell proliferation.

We report the capacity of CD40 ligand (CD40L)-negative T cell clones to activate human B cells. CD40L-negative T cells induce a level of B cell proliferation 10-20% of that seen with normal T cells. The signal provided by the negative clones is synergistic with that derived from a CD40L transfectant, and restores B cell proliferation to normal levels, showing that CD40L-negative T cell clones are not inherently inhibitory for B cells. Although their capacity to induce proliferation was much reduced, CD40L-negative T cell clones were still strong inducers of B cell differentiation to plasma cells. This differentiation to plasma cells was inhibited by a CD40L transfectant. The data are discussed with regard to the normal in vivo mechanism for maintaining B cell memory and memory antibody responses to T-dependent antigens.

B cell function in mice transgenic for mCTLA4-H gamma 1: lack of germinal centers correlated with poor affinity maturation and class switching despite normal priming of CD4+ T cells.

This report outlines the B cell phenotype of transgenic mice that overexpresses the mouse CTLA-4-human gamma 1 (mCTLA4-H gamma 1) protein. Despite the fact that these mice prime CD4+ T cells (Ronchese, F., B. Housemann, S. Hubele, and P. Lane. 1994. J. Exp. Med. 179:809), antibody responses to T-dependent antigens are severely impaired. In contrast, T-independent responses are normal which suggests mCTLA4-H gamma 1 does not act directly on B cells, but acts indirectly by impairing T cell help. The impaired antibody defect is associated with impaired class switching, with low total immunoglobulin (Ig)G and antigen-specific IgG responses, and an absence of germinal center formation in spleen and lymph nodes but not gut-associated tissues. The defective germinal center formation is associated with a reduction in the degree of somatic mutation in hybridomas made from transgenic mice in comparison with those made from normal mice. It seems likely that mCTLA4-H gamma 1 exerts its effect by blocking an interaction between T and B cells that induce T cell help for B cells.

Nucleotide sequence analysis and potential environmental distribution of a ferric pseudobactin receptor gene of Pseudomonas sp. strain M114.

The nucleotide sequence of the Pseudomonas sp. strain M114 pbuA gene, encoding the outer membrane receptor for ferric pseudobactin M114, has been determined. The region sequenced spans 2788 bases of plasmid pCUP3, within which the receptor gene had previously been localised. A single open reading frame, potentially encoding 826 amino acids and including a leader peptide of 44 amino acids, is evident and is followed by an inverted repeat segment, which may act as a transcriptional terminator. A 20 bp region of DNA, having significant homology with the E. coli Fur-binding consensus sequence, is located upstream of the open reading frame. PbuA displays characteristics in common with other outer membrane proteins and displays strong homology with the TonB boxes of both E. coli and Pseudomonas receptors. More extensive homologies were found with the PupA receptor of P. putida WCS358 and the FhuE and BtuB receptors of E. coli. It is suggested that areas exhibiting the least homology between these receptors may represent ferric siderophore-specific recognition sites of the PbuA protein. The deduced amino acid sequence of pbuA was compared with that of pupX, encoding the outer membrane receptor for ferric pseudobactin B10, of Pseudomonas sp. strain B 10. A direct alignment of the two proteins gave an identity score of 92.5%. The distribution of PbuA-like receptors among Pseudomonas isolates was investigated by DNA-DNA hybridisation analysis. The results suggest that a PbuA-like receptor may be widely distributed among Pseudomonas rhizosphere isolates.

Expression and functional properties of mouse B7/BB1 using a fusion protein between mouse CTLA4 and human gamma 1.

We report the construction and expression of a fusion protein made from the extracellular portion of the mouse CTLA-4 gene and the constant region of human IgG1. This fusion protein behaves like an antibody to mouse B7/BB1, binding to activated B cells and purified dendritic cells. In addition, we found it to bind to activated T cells. The fusion protein interfered with the ability of antigen-pulsed antigen-presenting cells to induce proliferation of T-cell clones, although the degree of inhibition varied. These findings are discussed in the light of the physiological activation of T cells in secondary lymphoid organs.

Soluble CD40 ligand can replace the normal T cell-derived CD40 ligand signal to B cells in T cell-dependent activation.

We have constructed a soluble chimeric fusion protein between the mouse CD8 alpha chain and the mouse CD40 T cell ligand. This protein binds to both human and mouse B cells. By itself it induced a modest degree of B cell proliferation, but together with anti-immunoglobulin (anti-Ig) antibody it greatly stimulated B cell proliferation, as determined by both [3H]thymidine uptake and increase in cell numbers. These data are evidence that the CD40 ligand on T cells provides a signal that drives B cell proliferation. This signal is synergistic with that delivered by anti-Ig antibody.

Relationships between the degree of cross-linking of surface immunoglobulin and the associated inositol 1,4,5-trisphosphate and Ca2+ signals in human B cells.

Cross-linking of surface immunoglobulin (Ig) receptors on human B cells leads to the activation of a tyrosine kinase. The activated tyrosine kinase subsequently phosphorylates a number of substrates, including phospholipase C-gamma. This enzyme breaks down phosphoinositol bisphosphate to form two intracellular messengers, diacylglycerol and inositol 1,4,5-trisphosphate, leading to the activation of protein kinase C and the release of intracellular Ca2+ respectively. We have used h.p.l.c. and flow cytometry to measure accurately the inositol phosphate turnover and Ca2+ release in anti-Ig-stimulated human B cells. In particular, we have examined the effect of dose of the cross-linking antibody on the two responses. The identity of putative messenger inositol phosphates has been verified by structural analysis, and the amounts of both inositol phosphates and Ca2+ present have been quantified. In the Ramos Burkitt lymphoma, which is very sensitive to stimulus through its Ig receptors, both inositol phosphate production and Ca2+ release were found to be related to the dose of anti-Ig antibody applied. This suggests that phospholipase C-mediated signal transduction in human B cells converts the degree of cross-linking of the immunoglobulin receptor quantitatively into intracellular signals.