Quantitative and qualitative changes in V-J alpha rearrangements during mouse thymocytes differentiation: implication for a limited T cell receptor alpha chain repertoire

Knowledge of the complete nucleotide sequence of the mouse TCRAD locus allows an accurate determination V-J rearrangement status. Using multiplex genomic PCR assays and real time PCR analysis, we report a comprehensive and systematic analysis of the V-J recombination of TCR alpha chain in normal mouse thymocytes during development. These respective qualitative and quantitative approaches give rise to four major points describing the control of gene rearrangements. (a) The V-J recombination pattern is not random during ontogeny and generates a limited TCR alpha repertoire; (b) V-J rearrangement control is intrinsic to the thymus; (c) each V gene rearranges to a set of contiguous J segments with a gaussian-like frequency; (d) there are more rearrangements involving V genes at the 3' side than 5' end of V region. Taken together, this reflects a preferential association of V and J gene segments according to their respective positions in the locus, indicating that accessibility of both V and J regions is coordinately regulated, but in different ways. These results provide a new insight into TCR alpha repertoire size and suggest a scenario for V usage during differentiation.     

Preliminary performance evaluation of blood gas analyzers.

BACKGROUND: We evaluated the imprecision and bias of three instruments for the determination of blood gases, pH and ionized calcium (Ca(2+)) in human arterial blood samples, in comparison with the performance of an established methodology. METHODS: The ABL 735, Omni S and Rapidpoint 405 blood gas analyzers were evaluated and compared to the ABL 620 analyzer. Imprecision was determined according to the NCCLS EP10-A2 evaluation protocol. The NCCLS EP9-A2 evaluation protocol was used to determine bias relative to the ABL 620 system. Experimental data were compared against preset quality specifications. RESULTS: The three new instruments showed excellent imprecision for the measurement of pH, but only the ABL 620 met the preset imprecision goals for all analytes tested. All new instruments showed good correlation with the comparative instrument. The slope of the regression equation was significantly different from 1.0 in six out of the 12 comparisons, indicating systematic differences between the instruments. Nevertheless, the predicted bias values relative to the comparative instrument did not exceed the preset quality specifications for two out of the three new instruments. CONCLUSIONS: Preliminary evaluation using the NCCLS evaluation protocols EP10-A2 and EP9-A2, may provide valuable information on performance characteristics of blood gas analyzers.     

Gain-of-function mutant of angiotensin II receptor, type 1A, causes hypertension and cardiovascular fibrosis in mice

The role of the renin-angiotensin system has been investigated by overexpression or inactivation of its different genes in animals. However, there is no data concerning the effect of the constitutive activation of any component of the system. A knockin mouse model has been constructed with a gain-of-function mutant of the Ang II receptor, type 1A (AT(1A)), associating a constitutively activating mutation (N111S) with a C-terminal deletion, which impairs receptor internalization and desensitization. In vivo consequences of this mutant receptor expression in homozygous mice recapitulate its in vitro characteristics: the pressor response is more sensitive to Ang II and longer lasting. These mice present with a moderate (~20 mmHg) and stable increase in BP. They also develop early and progressive renal fibrosis and cardiac fibrosis and diastolic dysfunction. However, there was no overt cardiac hypertrophy. The hormonal parameters (low-renin and inappropriately normal aldosterone productions) mimic those of low-renin human hypertension. This new model reveals that a constitutive activation of AT(1A) leads to cardiac and renal fibrosis in spite of a modest effect on BP and will be useful for investigating the role of Ang II in target organs in a model similar to some forms of human hypertension.     

Revascularization of the superficial femoral artery with paclitaxel-coated balloon for claudication

Background: Percutaneous angioplasty of the superficial femoral artery (SFA) with paclitaxel-coated balloon, intended to reduce restenosis, has been proven safe and effective in recent randomized controlled trials.

Objective: To assess outcome results of angioplasty of the SFA with paclitaxel-coated balloon in claudicants in real-world practice of a single center.

Material &; Methods: A continuous prospective cohort study of 53 claudicants (62 lower limbs) from January 2015 to December 2016. Study end points include primary patency, freedom from clinically driven target-lesion revascularization and symptom relief.

Results: It concerns 17 women (32%) and 36 men (68%) with a mean age of 67.8 years, suffering life-style-limiting claudication. Only short to intermediate-length stenoses or occlusions (30.6%), with a mean length of 59.6?mm were selected for percutaneous angioplasty with a paclitaxel-coated balloon. Technical success was 100%. At 16 months, primary patency attained 92.0% (3 early occlusions, 2 restenoses). There were two re-interventions at 6 and 9 months, resulting in a clinically driven target lesion revascularization rate of 3.2%. At the end of the follow-up of 16 months, all but two patients (96.2%) remained symptom-free. Two patients died during follow-up (no procedure-related deaths).

Conclusion: Paclitaxel-coated balloon angioplasty of the SFA gives in routine clinical practice excellent midterm results, with a restenosis rate of 6.5% at 1 year. This procedure has authors’ preference as first-choice technique for correction of short- and intermediate-length symptomatic stenoses of the SFA.     

Longitudinal Association Between Peer Victimization and Sleep Problems in Preschoolers: The Moderating Role of Parenting

This study examined the moderating role of parental behaviors in the longitudinal link between peer victimization and sleep problems during preschool. The sample consisted of 1,181 children (594 girls) attending day care between the ages of 3 and 6 years. Participants were part of the Quebec Longitudinal Study of Child Development, a longitudinal study of child development led by the Institut de la Statistique du Quebec. Controlling for potential confounders, latent growth curve analyses revealed that the association between peer victimization and sleep problems varied depending on parents’ behaviors. Coercive parenting exacerbated the link between peer victimization and parasomnias. In contrast, positive parenting mitigated the link between peer victimization and insomnia. The findings suggest that persistent sleep problems at a young age may be an indicator of chronic peer victimization but that parents’ behaviors can play a key role in victimized children’s sleep problems.     

Mitochondrial function following downhill and/or uphill exercise training in rats

Introduction: The goal of this study was to compare the effects of downhill (DH), uphill (UH), and UH‐DH exercise training, at the same metabolic rate, on exercise capacity and skeletal muscle mitochondrial function. Methods: Thirty‐two Wistar rats were separated into a control and 3 trained groups. The trained groups exercised for 4 weeks, 5 times per week at the same metabolic rate, either in UH, DH, or combined UH‐DH. Twenty‐four hours after the last training session, the soleus, gastrocnemius, and vastus intermedius muscles were removed for assessment of mitochondrial respiration. Results: Exercise training, at the same metabolic rate, improved maximal running speed without specificity for exercise modalities. Maximal fiber respiration was enhanced in soleus and vastus intermedius in the UH group only. Conclusions: Exercise training, performed at the same metabolic rate, improved exercise capacity, but only UH‐trained rats enhanced mitochondrial function in both soleus and vastus intermedius skeletal muscle. Muscle Nerve 54 : 925–935, 2016