A gene network model accounting for development and evolution of mammalian teeth

Generation of morphological diversity remains a challenge for evolutionary biologists because it is unclear how an ultimately finite number of genes involved in initial pattern formation integrates with morphogenesis. Ideally, models used to search for the simplest developmental principles on how genes produce form should account for both developmental process and evolutionary change. Here we present a model reproducing the morphology of mammalian teeth by integrating experimental data on gene interactions and growth into a morphodynamic mechanism in which developing morphology has a causal role in patterning. The model predicts the course of tooth-shape development in different mammalian species and also reproduces key transitions in evolution. Furthermore, we reproduce the known expression patterns of several genes involved in tooth development and their dynamics over developmental time. Large morphological effects frequently can be achieved by small changes, according to this model, and similar morphologies can be produced by different changes. This finding may be consistent with why predicting the morphological outcomes of molecular experiments is challenging. Nevertheless, models incorporating morphology and gene activity show promise for linking genotypes to phenotypes.     

Celiac disease in patients with severe liver disease: gluten-free diet may reverse hepatic failure

BACKGROUND & AIMS: Mild liver abnormalities are common in patients with celiac disease and usually resolve with a gluten-free diet. We investigated the occurrence of celiac disease in patients with severe liver failure. METHODS: Four patients with untreated celiac disease and severe liver disease are described. Further, the occurrence of celiac disease was studied in 185 adults with previous liver transplantation using serum immunoglobulin A endomysial and tissue transglutaminase antibodies in screening. RESULTS: Of the 4 patients with severe liver disease and celiac disease, 1 had congenital liver fibrosis, 1 had massive hepatic steatosis, and 2 had progressive hepatitis without apparent origin. Three were even remitted for consideration of liver transplantation. Hepatic dysfunction reversed in all cases when a gluten-free diet was adopted. In the transplantation group, 8 patients (4.3%) had celiac disease. Six cases were detected before the operation: 3 had primary biliary cirrhosis, 1 had autoimmune hepatitis, 1 had primary sclerosing cholangitis, and 1 had congenital liver fibrosis. Only 1 patient had maintained a long-term strict gluten-free diet. Screening found 2 cases of celiac disease, 1 with autoimmune hepatitis and 1 with secondary sclerosing cholangitis. CONCLUSIONS: The possible presence of celiac disease should be investigated in patients with severe liver disease. Dietary treatment may prevent progression to hepatic failure, even in cases in which liver transplantation is considered.     

Bipolar radiofrequency thermal ablation of the soft palate in habitual snorers without significant desaturations assessed by magnetic resonance imaging

Sleep-disordered breathing, including habitual snoring, is a major health problem. Treatment of primary habitual snoring should be individualized using both conservative and active treatment methods. Active surgical interventions are, however, associated with significant morbidity. Therefore, procedures causing far less morbidity should be preferred. Our aim was to assess the efficacy and acceptability of bipolar radiofrequency thermal ablation of the soft palate in habitual snorers without significant desaturations associated with excessive daytime sleepiness. We treated 20 nonobese habitual snorers (median age, 43 years, range 35-63). All the patients had the major site of obstruction at the level of the soft palate, and they were treated on an outpatient basis in two treatment sessions separated by 1 week. The pretreatment and post-treatment symptoms and findings as well as the overall efficacy of the procedure were evaluated by questionnaires, visual analogue scales, and magnetic resonance imaging. All the questionnaires showed a statistically significant change, indicating decreased snoring and daytime sleepiness. The magnetic resonance studies showed that the procedure induced notable T1-signal alterations in the treated tissue, and when compared with the pretreatment images, certain dimensions of the soft palate were significantly changed. Bipolar radiofrequency thermal ablation of the soft palate seems to be well tolerated and effective regarding primary habitual snorers without significant desaturations associated with excessive daytime sleepiness.     

Carotid artery intima-media thickness in Finnish families with familial combined hyperlipidemia

BACKGROUND: Familial combined hyperlipidemia (FCHL) is the most common hereditary lipid disorder that predisposes the patients to premature coronary heart disease. Members of FCHL families are categorised as affected or unaffected according to serum lipid levels. This study is aimed to evaluate whether there is a difference in carotid artery wall thickness between asymptomatic FCHL family members who are affected and those who are unaffected according to the currently used lipid criteria. METHODS AND RESULTS: Carotid artery ultrasonography with intima-media thickness (IMT) measurements was performed for 148 members of 39 Finnish FCHL families. Study subjects who had no history of coronary heart disease or stroke were divided into two groups according to their serum total cholesterol and/or triglyceride levels. The average carotid IMT of the affected subjects (0.75+/-0.15 mm) was not significantly different from that of their unaffected relatives (0.73+/-0.13 mm), P=0.90. In multivariate analysis, age, gender, and pulse pressure, but no lipid variables, contributed significantly to the variation of carotid IMT. CONCLUSIONS: The IMT findings in FCHL family members indicate that the current lipid criteria alone are of limited value in predicting long-term risk of cardiovascular disease in asymptomatic members of FCHL families.     

IgE Reactivity of the Dog Lipocalin Allergen Can f 4 and the Development of a Sandwich ELISA for Its Quantification

Purpose

Divergent results on the IgE reactivity of dog-allergic subjects to Can f 4 have been reported. The aim of this study was to evaluate the significance of Can f 4 in dog allergy and to develop an immunochemical method for measuring Can f 4 content in environmental samples.

Methods

We purified the natural dog allergen Can f 4 from a dog dander extract by monoclonal antibody-based affinity chromatography and generated its variant in a recombinant form. Sixty-three dog-allergic patients and 12 nonallergic control subjects were recruited in the study. The IgE-binding capacity of natural Can f 4 and its recombinant variant was assessed by ELISA, immunoblotting, and skin prick tests (SPT).

Results

Eighty-one percent of the dog-allergic patients showed a positive result to the immunoaffinity-purified natural Can f 4 in IgE ELISA, but only 46% in IgE immunoblotting. Respective results with the recombinant Can f 4 variant were 54% and 49%. SPT results reflected those obtained in ELISA and immunoblotting. The overall IgE reactivity of the immunoaffinity-purified natural Can f 4 was found to depend strongly on the integrity of the allergen''s conformation. A sandwich ELISA based on monoclonal antibodies was found to be functional for measuring Can f 4 in environmental samples.

Conclusions

Can f 4 is a major allergen of dog together with Can f 1 and Can f 5. In combination with other dog allergens, it improves the reliability of allergy tests in dog allergy.