Cardiovascular autonomic dysfunction in normotensive awake subjects with obstructive sleep apnoea syndrome

Cardiovascular autonomic function in normotensive awake patients with obstructive sleep apnoea syndrome was studied in 21 normotensive (mean age 48 ± 14 years), drug-free men with obstructive sleep apnoea syndrome. Cardiovascular reflex tests with continuous blood pressure monitoring and biochemical indices were performed the morning after a standard polygraphic sleep recording. A group of 20 agematched (mean age 49 ± 19 years) normal subjects was used as controls. The obstructive sleep apnoea syndrome patients showed higher heart rate and noradrenaline plasma levels (p < 0.05) at rest and a higher blood pressure response to head-up tilt (p < 0.01), suggesting sympathetic overactivity. Respiratory arrhythmia, baroreflex sensitivity index and Valsalva ratio were significantly lower in the obstructive sleep apnoea syndrome group (p < 0.01) whereas the decrease in heart rate induced by the cold face test was significantly higher (p < 0.05) showing a blunting of reflexes dependent on baroreceptor or pulmonary afferents with normal or increased cardiac vagal efferent activity. These abnormalities in autonomic regulation may predispose obstructive sleep apnoea syndrome patients to cardiovascular complications like hypertension and cardiac arrhythmias.     

Evaluation of allergenicity of genetically modified soybean protein extract in a murine model of oral allergen-specific sensitization

Background With the development of genetically modified crop plants there has been a growing interest in the approaches available to assess the potential allergenicity of novel gene products. For additional assessment of the potential allergenicity of expressed proteins, informative data can be generated using animal models. Soybean is one of the major source of protein in human and animal nutrition, and has also been well characterized as a major allergenic source. Advances in biotechnology have resulted in an increasing number of genetically engineered foods, and among these soybean is one of the most widespread. Objective To develop and characterize a murine model of IgE‐mediated soybean sensitization induced by intragastric immunization, in the presence of Cholera Toxin, with wild‐type soybean extract (wt‐SE) or with genetically modified soybean extract (gm‐SE). Methods Balb/c mice born in our animal facilities, from females fed on soy‐free food, were fed with the same soy‐free food and used in all the experiments. Mice were sensitized by gavages with soybean extracts, and allergen‐specific IgE and IgG responses were studied by direct ELISA and ELISA inhibition. Antigen‐specific cell proliferation and cytokine production were evaluated in spleen cell cultures. Results Sensitization with both soybean extracts induced high levels of antigen‐specific IgE and IgG1 and low levels of specific IgG2a. Both wt‐SE and gm‐SE were able to inhibit the binding of specific IgE from mice immunized with gm‐SE to the same antigen used for the ELISA coating. A comparable proliferative response was obtained with the homologous as well as with the heterologous extracts. Conclusion In sensitized mice, we observed a predominantly T‐helper type 2 (Th2)‐type immune response, with increased soybean‐specific IgE and IgG1 antibodies and a concomitant increase of IL‐4 and IL‐5 production. Results obtained by specific IgE ELISA inhibition and by antigen‐specific T cell proliferation demonstrated that wt‐SE and gm‐SE shared B and T epitopes. The present murine model of soybean sensitization established by the oral route should provide valuable information about risk assessment for food allergy from new proteins of genetically modified foods.     

Rapid isolation, characterization, and glycan analysis of Cup a 1, the major allergen of Arizona cypress (Cupressus arizonica) pollen

BACKGROUND: A rapid method for the purification of the major 43-kDa allergen of Cupressus arizonica pollen, Cup a 1, was developed. METHODS: The salient feature was a wash of the pollen in acidic buffer, followed by an extraction of the proteins and their purification by chromatography. Immunoblotting, ELISA, and lectin binding were tested on both the crude extract and the purified Cup a 1. Biochemical analyses were performed to assess the Cup a 1 isoelectric point, its partial amino-acid sequence, and its glycan composition. RESULTS: Immunochemical analysis of Cup a 1 confirmed that the allergenic reactivity is maintained after the purification process. Partial amino-acid sequencing indicated a high degree of homology between Cup a 1 and allergenic proteins from the Cupressaceae and Taxodiaceae families displaying a similar molecular mass. The purified protein shows one band with an isoelectric point of 5.2. Nineteen out of 33 sera (57%) from patients allergic to cypress demonstrated significant reactivity to purified Cup a 1. MALDI-TOF mass spectrometry indicated the presence of three N-linked oligosaccharide structures: GnGnXF(3) (i.e., a horseradish peroxidase-type oligosaccharide substituted with two nonreducing N-acetylglucosamine residues), GGnXF(3)/GnGXF(3) (i.e., GnGnXF with one nonreducing galactose residue), and (GF)GnXF(3)/Gn(GF)XF(3) (with a Lewisa epitope on one arm) in the molar ratio 67:8:23. CONCLUSION: The rapid purification process of Cup a 1 allowed some fine studies on its properties and structure, as well as the evaluation of its IgE reactivity in native conditions. The similarities of amino-acid sequences and some complex glycan stuctures could explain the high degree of cross-reactivity among the Cupressaceae and Taxodiaceae families.     

Deletion of the mental retardation gene Gdi1 impairs associative memory and alters social behavior in mice

Non-specific mental retardation (NSMR) is a common human disorder characterized by mental handicap as the only clinical symptom. Among the recently identified MR genes is GDI1, which encodes alpha Gdi, one of the proteins controlling the activity of the small GTPases of the Rab family in vesicle fusion and intracellular trafficking. We report the cognitive and behavioral characterization of mice carrying a deletion of Gdi1. The Gdi1-deficient mice are fertile and anatomically normal. They appear normal also in many tasks to assess spatial and episodic memory and emotional behavior. Gdi1-deficient mice are impaired in tasks requiring formation of short-term temporal associations, suggesting a defect in short-term memory. In addition, they show lowered aggression and altered social behavior. In mice, as in humans, lack of Gdi1 spares most central nervous system functions and preferentially impairs only a few forebrain functions required to form temporal associations. The general similarity to human mental retardation is striking, and suggests that the Gdi1 mutants may provide insights into the human defect and into the molecular mechanisms important for development of cognitive functions.     

Phenotypic and phoniatric findings in mosaic cri du chat syndrome

We report on mosaic 46,XY/46,XY,del(5)(p15) cri du chat syndrome. The clinical findings are compared with those compiled from a literature survey. A phoniatric evaluation was performed and compared with that of a cri du chat patient without mosaicism previously observed by the authors.     

COVID-19 in pediatric kidney transplantation: The Improving Renal Outcomes Collaborative

There are limited data on the impact of COVID-19 in children with a kidney transplant (KT). We conducted a prospective cohort study through the Improving Renal Outcomes Collaborative (IROC) to collect clinical outcome data about COVID-19 in pediatric KT patients. Twenty-two IROC centers that care for 2732 patients submitted testing and outcomes data for 281 patients tested for SARS-CoV-2 by PCR. Testing indications included symptoms and/or potential exposures to COVID-19 (N = 134, 47.7%) and/or testing per hospital policy (N = 154, 54.8%). Overall, 24 (8.5%) patients tested positive, of which 15 (63%) were symptomatic. Of the COVID-19-positive patients, 16 were managed as outpatients, six received non-ICU inpatient care and two were admitted to the ICU. There were no episodes of respiratory failure, allograft loss, or death associated with COVID-19. To estimate incidence, subanalysis was performed for 13 centers that care for 1686 patients that submitted all negative and positive COVID-19 results. Of the 229 tested patients at these 13 centers, 10 (5 asymptomatic) patients tested positive, yielding an overall incidence of 0.6% and an incidence among tested patients of 4.4%. Pediatric KT patients in the United States had a low estimated incidence of COVID-19 disease and excellent short-term outcomes.     

Feasibility and reliability of flow-cytometry (fcm) DNA analysis of fresh and fixed urine samples

The qualitative results of FCM DNA analysis on fresh and fixed urine specimens (28 and 97, respectively) from 68 normal subjects and 10 patients with a past history of bladder cancer were compared. FCM DNA evaluability was not significantly different in fresh and fixed samples (63% vs 73%, respectively) whereas mean CV was significantly higher (7.3% vs 5.7%, respectively; p=0.04). A double FCM analysis on fresh and fixed urine was also performed in 16 cases. In this subgroup, the percentage of evaluable histograms from fixed urine specimens was slightly higher than that from fresh specimens. Aneuploid cases were found only in the fixed urine samples but the CVs from fresh and fixed cell suspensions did not differ. The absence of inflammatory cells with cytological analysis of the same samples was associated with low percentages of FCM evaluability and higher CVs. The use of fixed samples improves the quality of FCM DNA analysis permitting its use for screening programs.