Genetic interactions controlling sex and color establish the potential for sexual conflict in Lake Malawi cichlid fishes.

Sex-determining systems may evolve rapidly and contribute to lineage diversification. In fact, recent work has suggested an integral role of sex chromosome evolution in models of speciation. We use quantitative trait loci analysis of restriction site-associated DNA -tag single nucleotide polymorphisms to identify multiple loci responsible for sex determination and reproductively adaptive color phenotypes in Lake Malawi cichlids. We detect a complex epistatic sex system consisting of a major female heterogametic ZW locus on chromosome 5, two separate male heterogametic XY loci on chromosome 7, and two additional interacting loci on chromosomes 3 and 20. Our data support the known chromosomal linkage between orange blotch color and ZW, as well as novel genetic associations between male blue nuptial color and two sex determining regions (an XY and ZW locus). These results provide further empirical evidence for a complex antagonistic sex-color system in this species flock and suggest a possible role for, and effect of, polygenic sex-determining systems in rapid evolutionary diversification.

A multi-institutional study evaluating the diagnostic utility of the spec cPL™ and SNAP® cPL™ in clinical acute pancreatitis in 84 dogs.

BACKGROUND: Pancreas-specific lipase is reported to aid in diagnosing acute pancreatitis (AP) in dogs but has not been rigorously evaluated clinically. HYPOTHESIS/OBJECTIVES: To describe variability of disease in dogs with suspected clinical AP, and to evaluate accuracy of 2 pancreatic-specific lipase immunoassays, Spec cPL (SPEC) and SNAP cPL (SNAP), in diagnosing clinical AP. We hypothesized that SPEC and SNAP provide better diagnostic accuracy than serum amylase or total lipase. ANIMALS: A total of 84 dogs; 27 without AP and 57 with clinical signs associated with AP. METHODS: Multicenter study. Dogs were prospectively enrolled based upon initial history and physical examination, then retrospectively classified into groups according to the likelihood of having clinical AP by a consensus of experts blinded to SPEC and SNAP results. Bayesian latent class analyses were used to estimate the diagnostic accuracy of SPEC and SNAP. RESULTS: The estimates for test sensitivities and specificities, respectively, ranged between 91.5-94.1% and 71.1-77.5% for SNAP, 86.5-93.6% and 66.3-77.0% for SPEC (cutoff value of 200 µg/L), 71.7-77.8% and 80.5-88.0% for SPEC (cutoff value of 400 µg/L), and were 52.4-56.0% and 76.7-80.6% for amylase, and 43.4-53.6% and 89.3-92.5% for lipase. CONCLUSIONS AND CLINICAL IMPORTANCE: SNAP and SPEC have higher sensitivity for diagnosing clinical AP than does measurement of serum amylase or lipase activity. A positive SPEC or SNAP has a good positive predictive value (PPV) in populations likely to have AP and a good negative predictive value (NPV) when there is low prevalence of disease.

Intravascular occlusion for the correction of extrahepatic portosystemic shunts in dogs.

BACKGROUND: Congential extrahepatic portosystemic shunts (EHPSS) are common in dogs. An effective minimally invasive technique for correction of EHPSS could result in reduced morbidity, reduced costs, and reduced hospitalization times. HYPOTHESIS: Use of an intravascular occlusion device can effectively and safely result in acute complete occlusion of EHPSS in dogs. ANIMALS: Seven dogs with naturally occurring EHPSS that presented to the Purdue University Veterinary Teaching Hospital. METHODS: Prospective, clinical trial. The 7 dogs were consecutively enrolled over a 2-year period. Results of serum biochemistry, total serum bile acids, fasting plasma ammonia, abdominal radiography, and ultrasonography suggested the diagnosis of portosystemic shunts in all dogs. Definitive diagnosis of EHPSS was achieved with cranial mesenteric arterial portography and acute occlusion was attempted by the deployment of the Amplatzer vascular plug (AVP). RESULTS: EHPSS were identified in all dogs consisting of 5 portocaval and 2 portoazygous variants; 1/7 dogs (14%) were intolerant to temporary complete occlusion of the EHPSS. Of the remaining 6 dogs, 5 (83%) had complete occlusion of the EHPSS by the AVP. There were no complications and resolution of abnormal clinical signs and laboratory values was achieved in 4/5 (80%) dogs with complete occlusion. CONCLUSIONS AND CLINICAL IMPORTANCE: Intravascular correction of EHPSS by the AVP is a viable option to surgical correction while larger studies will be required to determine the clinical applicability of this procedure in the broader portosystemic shunt population.

Comparative rates of lower jaw diversification in cichlid adaptive radiations.

The lower jaw (LJ) provides an ideal trophic phenotype to compare rates and patterns of macroevolution among cichlid radiations. Using a novel phylogeny of four genes (ND2, dlx2, mitfb, and s7), we examined the evolutionary relationships among two of the most phylogenetically disparate cichlid radiations: (i) the Central America Heroines; and (ii) the East African Lake Malawi flock. To quantify jaw morphology, we measured two LJ lever systems in approximately 40 species from each lineage. Using geologic calibrations, we generated a chronogram for both groups and examined the rates of jaw evolution in the two radiations. The most rapidly evolving components of the LJ differed between the two radiations. However, the Lake Malawi flock exhibited a much faster rate of evolution in several components of the LJ. This rapid rate of divergence is consistent with natural selection, promoting unparalleled trophic diversification in Lake Malawi cichlids.

Endomysial antibody production is not related to histological damage after in vitro gluten challenge.

OBJECTIVE: To determine whether in vitro induction of endomysial antibodies is an in vitro marker of coeliac toxicity. DESIGN: To determine whether in vitro endomysial antibodies induced by gliadin incubation correlate with histological damage induced by in vitro gliadin challenge. METHODS: Small-bowel organ cultures from seven patients with treated coeliac disease were incubated in an organ culture system with gliadin; histological damage was morphometrically evaluated and endomysial antibodies were measured in the organ culture supernatant by indirect immunofluorescence. RESULTS: Although incubation with gliadin caused histological damage, there was no detectable production of endomysial antibody. CONCLUSIONS: In vitro, endomysial antibody induction cannot be used as a marker of coeliac toxicity. Endomysial antibodies are not necessary for generating the histological lesion of coeliac disease.

A non-toxic analogue of a coeliac-activating gliadin peptide: a basis for immunomodulation?

BACKGROUND: A-gliadin residues 31-49 (peptide A) binds to HLA-DQ2 and is toxic to coeliac small bowel. Analogues of this peptide, which bind to DQ2 molecules but are non-toxic, may be a potential route to inducing tolerance to gliadin in patients with coeliac disease. METHODS: Toxicity was investigated with small bowel organ culture in six patients with untreated coeliac disease, four with treated coeliac disease and six controls. Analogue peptides comprised alanine substituted variants of peptide A at L31 (peptide D), P36 (E), P38 (F), P39 (G) and P42 (H). RESULTS: Peptides D and E were toxic in biopsies from some patients. Peptides F, G and H were not toxic. CONCLUSIONS: Peptide F, which binds to DQ2 more strongly than peptide A, is not toxic in patients with coeliac disease in-vitro; this could be an initial step towards investigation of the induction of tolerance to gliadin in patients affected by coeliac disease.

Hypoadrenocorticism as the primary manifestation of lymphoma in two cats.

Hypoadrenocorticism secondary to bilateral lymphomatous invasion of adrenocortical tissue was diagnosed in 2 adult castrated domestic shorthair cats. In both cats, findings during initial physical examination (ie, lethargy, anorexia, weight loss, and severe weakness) were consistent with severe hypoadrenocorticism. Hyperkalemia, hyponatremia, and azotemia were also detected, which were consistent with hypoadrenocorticism. Hypoadrenocorticism was documented on the basis of finding low baseline and ACTH-stimulated serum cortisol concentrations. The cats initially responded well to treatment, but both owners chose to have the cat euthanatized. Multicentric lymphoma with infiltration and destruction of the adrenal glands was confirmed during necropsy.

Review article: coeliac disease and its management.

Coeliac disease (CD) is a disorder of the small intestine, characterized by villous atrophy, due to an intolerance to dietary gluten in genetically susceptible individuals, which responds to gluten withdrawal. The underlying immunological mechanisms causing the disorder are still being worked out. In recent years a wide range of clinical presentations has become increasingly apparent, as has a lengthening list of associated conditions. Severe malabsorption with steatorrhoea and profound weight loss is seen infrequently, perhaps as a result of earlier diagnosis and the recognition of 'silent' and 'latent' disease. The prevalence of CD as judged by population screening with, in particular, anti-endomysial antibodies, appears to be much higher than that found with clinically apparent cases. There are a variety of well recognized complications, the commonest probably being osteopenia and osteoporosis. The marked increased risk of lymphoma can be avoided by a strict gluten-free diet. Follow-up of patients needs to be lifelong with prompt investigation of new symptoms and blood test abnormalities.

Celiac disease.

There continues to be much research interest in celiac disease, with well over 200 papers published in the year under review, covering a multitude of areas from population screening to the molecular immunology of disease pathogenesis. The high prevalence of "silent" disease again has been demonstrated, and there is continued emphasis on the increasingly wide recognized range of associated conditions and extraintestinal manifestations. The case for the safety of oats is further strengthened by a study involving patients with dermatitis hepetiformis. One of the most significant scientific advances has been the discovery of a potential role for tissue transglutaminase, recently found to be the autoantigen of antiendomysial antibodies, in disease pathogenesis, by enhancing gliadin peptide class II binding and consequent T-cell activation. However, the very central role of T cells has been thrown into doubt with an elegant study that assessed the effect of blocking costimulation in T-cell activation.

Binding of gluten-derived peptides to the HLA-DQ2 (alpha1*0501, beta1*0201) molecule, assessed in a cellular assay.

The nature of the immunopathogenic relationship underlying the very strong association of coeliac disease (CD) to the HLA-DQ (A1*0501, B1*0201) genotype is not known, but probably relates to binding of gluten-derived epitopes to the HLA-DQ (alpha1*0501, beta1*0201) heterodimer (DQ2). These epitopes have not yet been defined. In this study we have tested the binding of various gluten-derived peptides to DQ2 in a cellular assay using Epstein-Barr virus (EBV)-transformed B lymphocytes and murine fibroblast transfectants. One of these peptides (peptide A), which has previously been shown to exacerbate the CD lesion in vitro and in vivo, was found to bind to DQ2, albeit only moderately, lending further credence to its possible role in the pathogenesis of CD. The nature of peptide A's binding to DQ2 was explored with truncated and conservative point substituted analogues and compared with the published DQ2 binding motif, the results of which explain the observed level of binding.