Surgical treatment for endocardial radiofrequency ablation-resistant sustained monomorphic ventricular tachycardia with mural thrombus including dense calcification in the left ventricle

Catheter ablation provides effective results for sustained monomorphic ventricular tachycardia (VT), but the presence of mural thrombus including dense calcification occasionally causes unfavorable outcomes. The case of a 67-year-old man in whom sustained monomorphic VT, which was resistant to endocardial radiofrequency ablation, in the presence of mural thrombus including dense calcification after coronary artery bypass grafting was successfully treated by left ventricular reconstruction with cryoablation is reported.     

High-affinity autoantibodies specifically eliminate granulocyte-macrophage colony-stimulating factor activity in the lungs of patients with idiopathic pulmonary alveolar proteinosis

Deficiency of granulocyte-macrophage colony-stimulating factor (GM-CSF) in mice results in pulmonary alveolar proteinosis (PAP) from impaired surfactant catabolism by alveolar macrophages (AMs). Recently, we have shown that neutralizing anti-GM-CSF autoantibodies develop specifically in patients with idiopathic pulmonary alveolar proteinosis (iPAP). Analogous to murine PAP models, it is plausible that the autoantibodies reduce GM-CSF activity, resulting in AM dysfunction and surfactant accumulation. To examine this hypothesis, we estimated the neutralizing activity of the autoantibodies in the lungs of patients and characterized their biologic properties. GM-CSF bioactivity was completely abrogated in the bronchoalveolar lavage fluid (BALF) of patients with iPAP but not in healthy subjects. Autoantibodies were present in the alveoli in high concentrations and colocalized with GM-CSF. They recognized human GM-CSF with high avidity (K(AV) = 20.0 +/- 7.5 pM) and high specificity, reacting with its superstructure and neutralizing GM-CSF activity to a level 4000 to 58 000 times the levels of GM-CSF normally present in the lung. Although target epitopes varied among patients, GM-CSF amino acids 78 to 94 were consistently recognized. Thus, autoantibodies bind GM-CSF with high specificity and high affinity, exist abundantly in the lung, and effectively block GM-CSF binding to its receptor, inhibiting AM differentiation and function. Our data strengthen the evidence associating anti-GM-CSF autoantibodies with the pathogenesis of this disease.     

Correlation of somatic hypermutation specificity and A-T base pair substitution errors by DNA polymerase eta during copying of a mouse immunoglobulin kappa light chain transgene

To test the hypothesis that inaccurate DNA synthesis by mammalian DNA polymerase eta (pol eta) contributes to somatic hypermutation (SHM) of Ig genes, we measured the error specificity of mouse pol eta during synthesis of each strand of a mouse Ig kappa light chain transgene. We then compared the results to the base substitution specificity of SHM of this same gene in the mouse. The in vitro and in vivo base substitution spectra shared a number of common features. A highly significant correlation was observed for overall substitutions at A-T pairs but not for substitutions at G-C pairs. Sixteen mutational hotspots at A-T pairs observed in vivo were also found in spectra generated by mouse pol eta in vitro. The correlation was strongest for errors made by pol eta during synthesis of the non-transcribed strand, but it was also observed for synthesis of the transcribed strand. These facts, and the distribution of substitutions generated in vivo, support the hypothesis that pol eta contributes to SHM of Ig genes at A-T pairs via short patches of low fidelity DNA synthesis of both strands, but with a preference for the non-transcribed strand.     

A novel sialyl Lewis(x) analogue attenuates ischemia reperfusion injury in rabbit lung

BACKGROUND: We investigated the effects of OJ-R9545, a novel Sialyl Lewis x analogue, on lung ischemia-reperfusion (IR) injury using an in vivo rabbit model. METHODS: The left hilum of the lung was clamped for 110 minutes; the lung was then reperfused for 90 minutes. Either OJ-R9545 (10 mg/kg) or vehicle solution was administered from 10 minutes before reperfusion to 60 minutes after reperfusion in the OJ-R (+) and OJ-R (-) group (n = 6 in each group), respectively. The sham group (n = 3) underwent an identical procedure without ischemia. RESULTS: Arterial oxygen tensions in the OJ-R (+) group were superior to those in the OJ-R (-) group from 30 to 90 minutes after reperfusion (p < 0.05 and p < 0.01). Lung wet/dry weight ratio and myeloperoxidase activity after reperfusion in the OJ-R (+) group were both significantly lower than the corresponding figures in the OJ-R (-) group (p < 0.05). The intrapulmonary leukocytes were significantly reduced in the OJ-R (+) group compared with those in the OJ-R (-) group (p < 0.01). CONCLUSIONS: OJ-R9545 attenuates lung IR injury by preventing leukocyte infiltration into the lung.     

Small peripheral lung carcinomas with five-year post-surgical follow-up: assessment by semi-automated volumetric measurement of tumour size, CT value and growth rate on TSCT

Objectives  

To retrospectively assess the utility of semi-automated measurements by stratification of CT values of tumour size, CT value and doubling time (DT) using thin-section computed tomography (CT) images. The post-surgical outcomes of favourable and problematic tumours (more advanced p stage than IA, post-surgical recurrence or mortality from lung cancer) were compared using the measured values. The computed DTs were compared with manually measured values.     

Thymic papillo-tubular adenocarcinoma containing a cyst: report of a case

We report a case of thymic papillo-tubular adenocarcinoma in a 55-year-old man, who had no symptoms. Sternotomy revealed a tumor in the anterior mediastinum, tightly adhered to the pericardium. It was resected completely. Interestingly, the tumor contained a unilocular cyst filled with mucinous fluid, suggesting that it originated from a pre-existing thymic cyst. Pathological examination of the tumor revealed a primary thymic papillo-tubular adenocarcinoma resembling a tumor of gut origin. Thymic adenocarcinomas, particularly of the tubular subtype, are extremely rare.