LINE- and Alu-containing genomic instability hotspot at 16q24.1 associated with recurrent and nonrecurrent CNV deletions causative for ACDMPV.

Transposable elements modify human genome by inserting into new loci or by mediating homology-, microhomology-, or homeology-driven DNA recombination or repair, resulting in genomic structural variation. Alveolar capillary dysplasia with misalignment of pulmonary veins (ACDMPV) is a rare lethal neonatal developmental lung disorder caused by point mutations or copy-number variant (CNV) deletions of FOXF1 or its distant tissue-specific enhancer. Eighty-five percent of 45 ACDMPV-causative CNV deletions, of which junctions have been sequenced, had at least one of their two breakpoints located in a retrotransposon, with more than half of them being Alu elements.

Expansion Thoracoplasty for Thoracic Insufficiency Syndrome Associated with Jarcho-Levin Syndrome.

Introduction: Although surgical treatment of spondylothoracic dysplasia (STD) is controversial, we have found that an expansion thoracoplasty using a Vertical Expandable Prosthetic Titanium Rib (VEPTR; DePuy Synthes) results in favorable outcomes, including 100% survivability (at an average follow-up of 6.2 years), increased thoracic spinal length, and decreased requirements for ventilation support.

Step 1 Preoperative Preparation: Make anteroposterior and lateral radiographs of the spine.

Airways in smooth muscle α-actin null mice experience a compensatory mechanism that modulates their contractile response.

We hypothesized that ablation of smooth muscle α-actin (SM α-A), a contractile-cytoskeletal protein expressed in airway smooth muscle (ASM) cells, abolishes ASM shortening capacity and decreases lung stiffness. In both SM α-A knockout and wild-type (WT) mice, airway resistance (Raw) determined by the forced oscillation technique rose in response to intravenous methacholine (Mch). However, the slope of Raw (cmH(2)O·ml(-1)·s) vs.

The safety and effects of the beta-blocker, nadolol, in mild asthma: an open-label pilot study.

Beta-blockers are currently contraindicated in asthma because their acute administration may be associated with worsening bronchospasm. However, their effects and safety with their chronic administration are not well evaluated. The rationale for this pilot study was based on the paradigm shift that was observed with the use of beta-blockers in congestive heart failure, which once contraindicated because of their acute detrimental effects, have now been shown to reduce mortality with their chronic use.

Changes in beta 2-adrenoceptor and other signaling proteins produced by chronic administration of 'beta-blockers' in a murine asthma model.

Background: We have previously reported that chronic treatment with certain 'beta-blockers' reduces airway hyperresponsiveness (AHR) to methacholine in a murine model of asthma.

Methods: Airway resistance was measured using the forced oscillation technique in ovalbulmin-sensitized and ovalbulmin-challenged mice treated with several beta-adrenoceptor (beta-AR) ligands. We used the selective beta 2-AR ligand ICI 118,551 and the preferential beta 1-AR ligand metoprolol to investigate the receptor subtype mediating the beneficial effect.

Tidal breathing pattern differentially antagonizes bronchoconstriction in C57BL/6J vs. A/J mice.

There is abundant evidence that tidal breathing, and especially tidal breathing at elevated minute ventilation, antagonizes the development and persistence of airflow obstruction during bronchoconstrictor stimulation in normal animals and people. Here, we studied the antiobstructive effect of different tidal breathing patterns in C57Bl/6J and A/J mice during bronchoconstriction induced by continuous or bolus infusion of methacholine. Anesthetized, paralyzed mice were mechanically ventilated at 1,500 ml.

Desmin modulates lung elastic recoil and airway responsiveness.

Desmin is a structural protein that is expressed in smooth muscle cells of both airways and alveolar ducts. Therefore, desmin could be well situated to participate in passive and contractile force transmission in the lung. We hypothesized that desmin modulates lung compliance, lung recoil pressure, and airway contractile response.

Increased pulmonary artery pressures among adolescents with sickle cell disease.

The prevalence of pulmonary hypertension (PHT) among adolescents with sickle cell disease (SCD) is unknown. A tricuspid regurgitant (TR) jet peak velocity of 2.5 m/s or more is a screening test for PHT.

Effects of acute and chronic administration of beta-adrenoceptor ligands on airway function in a murine model of asthma.

The clinical effects of treatment with beta-adrenoceptor (beta-AR) agonists and antagonists in heart failure vary with duration of therapy, as do the effects of beta-AR agonists in asthma. Therefore, we hypothesized that chronic effects of "beta-blockers" in asthma may differ from those observed acutely. We tested this hypothesis in an antigen (ovalbumin)-driven murine model of asthma.

Differential requirement for CD18 in T-helper effector homing.

To understand the integrin requirements of T-helper (T(H)) effector subsets, we investigated the contribution of CD18 (beta(2) integrin) to T(H)1 and T(H)2 function in vitro and in relevant disease models. CD18-deficient (Itgb2(-/-)) T cells showed largely normal in vitro function. Compared with wild-type mice, Itgb2(-/-) mice were better able to resolve Leishmania major infection and generated a superior T(H)1 immune response, as assessed from draining lymph nodes.

Frequency dependence of respiratory system mechanics during induced constriction in a murine model of asthma.

Airway dysfunction in asthma is characterized by hyperresponsiveness, heterogeneously narrowed airways, and closure of airways. To test the hypothesis that airway constriction in ovalbumin (OVA)-sensitized OVA-intranasally challenged (OVA/OVA) mice produces mechanical responses that are similar to those reported in asthmatic subjects, respiratory system resistance (Rrs) and elastance (Edyn,rs) spectra were obtained in OVA/OVA and control mice during intravenous methacholine (MCh) infusions. In control mice, MCh at 1,700 microg x kg(-1) x min(-1) produced 1) a 495 and 928% increase of Rrs at 0.

The role of Mac-1 (CD11b/CD18) in antigen-induced airway eosinophilia in mice.

Mac-1 (CD11b/CD18) is an important adhesion molecule involved in the migration of leukocytes, cell signaling, and subsequent secretory responses. Its precise role in eosinophil recruitment and activation in vivo is not entirely clear. We wished to directly examine the role of Mac-1 in eosinophil migration in a murine model of allergic pulmonary inflammation.

Respiratory mechanics and lung development in the rat from early age to adulthood.

The purpose of the present study was to establish how the dependence of respiratory mechanics on lung inflation changes during development. We studied seven groups of rats from 10 days to 3 mo of age at five levels of positive end-expiratory pressure (PEEP) from 0 to 7 hPa (1 hPa = 0.1 kPa approximately 1 cmH(2)O).

Effects of smooth muscle activation on axial mechanical properties of excised canine bronchi.

This study tested the hypothesis that airway smooth muscle (ASM) activation produces an airway active axial force (AAAF). Bronchi (n = 10) immersed in a tissue bath containing 95% O2-5% CO2-equilibrated Krebs solution were subjected to passive axial lengthening and shortening at 0-20 cmH2O of transmural pressure. ASM was relaxed with isoproterenol and activated with methacholine.

Recurrent milk aspiration produces changes in airway mechanics, lung eosinophilia, and goblet cell hyperplasia in a murine model.

Recurrent aspiration of milk into the respiratory tract has been implicated in the pathogenesis of a variety of inflammatory lung disorders including asthma. However, the lack of animal models of aspiration-induced lung injury has limited our knowledge of the pathophysiological characteristics of this disorder. This study was designed to evaluate the effects of recurrent milk aspiration on airway mechanics and lung cells in a murine model.

Therapeutic efficacy of an anti-IL-5 monoclonal antibody delivered into the respiratory tract in a murine model of asthma.

Background: IL-5 is central to the pathogenesis of airway eosinophilic inflammation and hyperresponsiveness associated with both atopic and nonatopic asthma. The therapeutic potential of IL-5 antagonists in asthma is supported by the inhibition of airway eosinophilia and hyperresponsiveness in animal models receiving neutralizing anti-IL-5 mAbs intravenously or intraperitoneally.

Objective: The purpose of this study was to test the hypothesis that mAbs against IL-5 delivered by way of the respiratory tract are as effective as those delivered intraperitoneally in diminishing the pulmonary eosinophilic inflammation and airway hyperresponsiveness in a murine model of ovalbumin-induced asthma.

Frequency dependence of pulmonary and chest wall mechanics in young and adult cats.

The frequency (f) dependence of pulmonary and chest wall mechanics was assessed in nine kittens and four cats. Kittens and cats were anesthetized, paralyzed, and mechanically ventilated at various f between 0.13 and 1.

Effects of positive end-expiratory pressure on lung tissue mechanics in rabbits.

The effects of positive end-expiratory pressure (PEEP) on lung tissue resistance (Rti) and dynamic elastance (Edyn,L) were examined separately during histamine-induced lung constriction and after saline lung lavage in anesthetized paralyzed New Zealand White rabbits. During mechanical ventilation in the open-chest state, Rti and Edyn,L were estimated by fitting the appropriate signals to the equation of motion of the single-compartment linear model of the lung. Data were analyzed in relation to the structural damping hypothesis, which assumes that energy dissipation (Rti) and energy storage (Edyn,L) within the lung tissues are coupled at a fundamental level; the coupling parameter, termed hysteresivity (eta), = Rti.

Effect of body posture on concentration-response curves to inhaled methacholine.

Lung volume has been shown to be a major determinant of the bronchoconstrictor response to inhaled methacholine (MCh). Because a change in body posture from sitting to supine is associated with a reduction in lung volume, we hypothesized that airway responsiveness to inhaled MCh should be affected by body posture. Responsiveness to MCh was assessed in both sitting and supine postures on separate days in 10 subjects aged 24 to 42 yr.

Effects of volume history and vagotomy on pulmonary and chest wall mechanics in cats.

Using the technique of rapid airway occlusion during constant-flow inflation, we studied the effects of inflation volume, different baseline tidal volumes (10, 20, and 30 ml/kg), and vagotomy on the resistive and elastic properties of the lungs and chest wall in six anesthetized tracheotomized paralyzed mechanically ventilated cats. Before vagotomy, airway resistance decreased significantly with increasing inflation volume at all baseline tidal volumes. At any given inflation volume, airway resistance decreased with increasing baseline tidal volume.

Low-frequency respiratory system resistance in the normal dog during mechanical ventilation.

The low-frequency resistances of the respiratory system, lung, and chest wall were investigated in four anesthetized paralyzed dogs mechanically ventilated at various frequencies between 0.08 and 0.83 Hz.

Airway pressures during crying: an index of respiratory muscle strength in infants with neuromuscular disease.

The purpose of this study was to assess the strength of the respiratory muscles in 12 infants with neuromuscular disease (age range: 0.17-2.08 years) by measuring the maximal inspiratory and expiratory airway pressures (Pimax and PEmax) during crying efforts.

High-frequency characteristics of respiratory mechanics determined by flow interruption.

When flow at the airway opening is suddenly interrupted, the pressure measured just behind the point of interruption generally exhibits certain characteristic features, including some rapid and highly damped oscillations immediately after the interruption. It has previously been assumed that these oscillations reflect ringing of central airways gas. In the present study we investigated this hypothesis by performing flow interruptions during relaxed expiration in normal, tracheostomized, anesthetized, paralyzed dogs while the lungs were filled with four different gas mixtures having widely varying physical properties.

Effect of serotonin on expiratory pulmonary resistance in cats.

In five anesthetized paralyzed cats, mechanically ventilated with tidal volumes of 36-48 ml, the isovolume pressure-flow (IVPF) relationships of the lung were studied under control conditions and during serotonin-induced bronchoconstriction. At the end of a tidal inspiration, airway opening pressure was set between +3 and -15 cmH2O for single tidal expirations. After control measurements, animals were treated with progressively increasing doses of intravenous serotonin (10, 20, 50, and 100 micrograms.