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Background and Objective: Weight and muscle loss are predictors of poor outcomes in chronic obstructive pulmonary disease. However, to our knowledge, no study has investigated the predictors of longitudinal weight loss or its composition from functional and morphological perspectives. Methods: This longitudinal observational study with a median follow‐up period of 5 years (range: 3.0–5.8 years) included patients with COPD and ever‐smokers at risk of COPD. Using chest computed tomography (CT) images, airway and emphysematous lesions were assessed as the square root of the wall area of a hypothetical airway with an internal perimeter of 10 mm (√Aaw at Pi10) and the percentage of low attenuation volume (LAV%). Muscle mass was estimated using cross‐sectional areas (CSAs) of the pectoralis and erector spinae muscles, and fat mass was estimated using the subcutaneous fat thickness at the level of the 8th rib measured using chest CT images. Statistical analyses were performed using the linear mixed‐effects models. Results: In total, 114 patients were enrolled. Their body mass index remained stable during the study period while body weight and muscle CSA decreased over time and the subcutaneous fat thickness increased. Reduced forced expiratory volume in 1 s and peak expiratory flow (PEF) at baseline predicted the future decline in muscle CSA. Conclusion: Severe airflow limitation predicted future muscle wasting in patients with COPD and ever‐smokers at risk of COPD. Airflow limitation with a PEF slightly below 90% of the predicted value may require intervention to prevent future muscle loss. [ABSTRACT FROM AUTHOR]

Extracorporeal membrane oxygenation (ECMO) is widely used for circulatory support in pediatric cardiac patients with low cardiac output and hypoxemia. We retrospectively evaluated the efficacy of ECMO support for respiratory and heart failure in infants and children. From April 2002 to February 2011, 14 patients aged 19 days to 20 years old (average 44 months), with body weight 2.6 kg to 71 kg (median 14.1 kg), underwent ECMO support for failing cardiac function, hypoxemia, and low cardiac output syndrome. In 12 patients, ECMO was introduced after operation for congenital heart disease (four with complete repair including Fontan circulation, and eight with palliative repair). In one patient, ECMO was introduced after partial pulmonary resection for congenital cystic adenomatoid malformation because of respiratory failure. ECMO was introduced in a patient with severe heart failure caused by fulminant myocarditis. Patients' demographics, duration of extracorporeal membrane oxygenation, additional support, and outcomes were analyzed. Ten patients (71%) were successfully weaned from ECMO, and eight patients (57%) were discharged from the hospital. The mean duration of ECMO support was 332 h (range 11-2030 h). Although management of the ECMO circuit, including anticoagulation (activated clotting time: 150-250), was conducted following the institutional practice guidelines, it was difficult to control the bleeding. Seven patients required renal replacement therapy during ECMO support using peritoneal dialysis or continuous hemodiafiltration. Five patients had additional operative procedures: systemic-pulmonary shunt in two, bidirectional Glenn takedown with right modified Blalock-Taussig shunt, total cavopulmonary connection takedown, and redo ECMO in one patient each. The patient who had the longest ECMO support for respiratory failure due to acute respiratory distress syndrome after lung surgery was successfully weaned from ECMO because high-frequency oscillation (HFO) improved respiratory function. ECMO for heart and respiratory failure in infants and children is effective and allows time for recovery of cardiac dysfunction and acute hypoxic insult. The long-term ECMO support for over 2000 h was very rare, but it was possible to wean this patient from ECMO using HFO. [ABSTRACT FROM AUTHOR]

Retinal photoreceptor phosphodiesterase (PDE6), a key enzyme for phototransduction, consists of a catalytic subunit complex (Pαβ) and two inhibitory subunits (Pγs). Pαβ has two noncatalytic cGMP-binding sites. Here, using bovine PDE preparations, we show the role of these cGMP-binding sites in PDE regulation. Pαβγγ and its transducin-activated form, Pαβγ, contain two and one cGMP, respectively. Only Pαβγ shows [H]cGMP binding with a K∼ 50 n and Pγ inhibits the [H]cGMP binding. Binding of cGMP to Pαβγ is suppressed during its formation, implying that cGMP binding is not involved in Pαβγγ activation. Once bound to Pαβγ, [H]cGMP is not dissociated even in the presence of a 1000-fold excess of unlabeled cGMP, binding of cGMP changes the apparent Stokes' radius of Pαβγ, and the amount of [H]cGMP-bound Pαβγ trapped by a filter is spontaneously increased during its incubation. These results suggest that Pαβγ slowly changes its conformation after cGMP binding, i.e. after formation of Pαβγ containing two cGMPs. Binding of Pγ greatly shortens the time to detect the increase in the filter-trapped level of [H]cGMP-bound Pαβγ, but alters neither the level nor its Stokes' radius. These results suggest that Pγ accelerates the conformational change, but does not add another change. These observations are consistent with the view that Pαβγ changes its conformation during its deactivation and that the binding of cGMP and Pγ is crucial for this change. These observations also imply that Pαβγγ changes its conformation during its activation and that release of Pγ and cGMP is essential for this change. Pαβγ slowly changes its conformation after cGMP binding, i.e., after formation of Pαβγ containing two cGMPs. Binding of Pγ accelerates the conformational change caused by cGMP, but does not add another change. Pαβγ changes its conformation during its inactivation and that the binding of cGMP and Pγ is crucial for this change. [ABSTRACT FROM AUTHOR]

Background: Right upper lobectomy with right cervical and bilateral mediastinal lymph node dissection via a median approach was performed for non-small cell lung cancer. Methods: From 1995 to 2003, 48 patients aged ≤ 70 years underwent resection of cancer in the right upper lobe, including 26 with N0, four with N1 and 18 with N2 disease. Results: Metastases to the right cervical, highest mediastinal, pretracheal and bilateral tracheobronchial lymph nodes were frequent. There were no operative or hospital deaths. Preoperative accuracy of N-factor diagnosis was only 35.4%. The overall 5-year survival rate was 58.8%. The rate for C-N2 disease ( n = 18) was 42.6%, and the rate for p-N2 disease ( n = 7) and p-N3 disease ( n = 13) was 57.1% and 0%, respectively, using the Kaplan−Meier method. Conclusions: Patients without N3 disease have a good prognosis, and extended and systematic radical lymphadenectomy via median sternotomy improves the staging, and possibly the prognosis of pure N2 disease. [ABSTRACT FROM AUTHOR]

Two guanylate-cyclase-activating proteins (GCAP) encoded by a tail-to-tail gene array have been characterized in the mammalian retina. Using frog retina as a model, we obtained evidence for the presence of a photoreceptor Ca2+-binding protein closely related to GCAP. This protein (206 amino acids) does not stimulate guanylate cyclase (GC) in low [Ca2+], but inhibits GC in high [Ca2+], and is therefore termed guanylate-cyclase-inhibitory protein (GCIP). Sequence analysis indicates that GCIP and GCAP1 and GCAP2 have diverged substantially, but conserved domains present in all vertebrate GCAP are present in GCIP. Moreover, partial characterization of the GCIP gene showed that the positions of two introns in the GCIP gene are identical to positions of corresponding introns of the mammalian GCAP gene array. As to the major differences between GCIP and GCAP, the fourth EF hand Ca2+-binding motif of GCIP is disabled for Ca2+ binding, and GCIP does not stimulate GC. Monoclonal and polyclonal antibodies raised against recombinant GCIP identified high levels of GCIP in the inner segments, somata and synaptic terminals of frog cone photoreceptors. The results suggest that GCIP is a Ca2+-binding protein of the GCAP/recoverin subfamily. Its localization in frog cones closely resembles that of GC in mammalian cones. GCIP inhibits GC at high free [Ca2+], competing with GCAP1 and GCAP2 for GC regulatory sites. [ABSTRACT FROM AUTHOR]