Identification of Rv2041c, a novel immunogenic antigen from Mycobacterium tuberculosis with serodiagnostic potential.

Novel immunogenic antigens are continually required for the improvement of diagnostic techniques for Mycobacterium tuberculosis infection. Some proteins with serodiagnostic value are not expressed under normal culture conditions, but may be induced under specific conditions such as gradual oxygen depletion and low pH, and from inside macrophages. Using a customized amplification library, we previously found that Rv2041c from M. tuberculosis H37Rv was highly expressed in vitro under conditions of low pH and hypoxia. In this study, recombinant (r)Rv2041c was produced in Escherichia coli to examine its role in immune responses. Increased Rv2041c expression in vitro during dormancy and during infection in human macrophages was confirmed by Western blotting and reverse transcription polymerase chain reaction, respectively. Interestingly, positive antibody responses to rRv2041c were detected only in those patients with active tuberculosis (TB) and in mice infected with M. tuberculosis H37Rv. Finally, Rv2041c was used successfully in the serodiagnosis of active M. tuberculosis infection in Korean patients in conjunction with other M. tuberculosis proteins, including Ag85 complex, 38 kDa, rESAT-6, rHSP-X and rCFP-10. Our Rv2041c-ELISA had comparable diagnostic sensitivity and equivalent specificity to the use of an M. tuberculosis H37Rv cellular extract. In addition, seven of 46 serum samples collected from TB patients (15.28%) showed positive antibody responses to Rv2041c, but not to the other proteins. These results suggest that Rv2041c can be used to increase assay sensitivity alongside well-known antigens for the serodiagnosis of M. tuberculosis infection.

Large cell neuroendocrine carcinoma of the lung: radiologic and pathologic findings.

PURPOSE: The purpose of this work was to determine the radiologic and pathologic findings of large cell neuroendocrine carcinoma (LCNEC). METHOD: We retrospectively evaluated chest radiographs, CT scans, and pathologic findings of five patients with pathologically confirmed LCNEC. They were confirmed by percutaneous needle biopsy (n = 2) and by surgery (n = 3). The average age of patients was 60 (51-70) years, and all five were smokers (mean 30 pack-years) and men. Radiologic findings were reviewed for the pattern of lesion, location, and associated findings by two radiologists under consensus. Pathologic findings were reviewed by two pathologists. RESULTS: In all five patients, tumors were represented as a peripherally located nodule or mass without associated secondary pneumonitis or distal atelectasis radiographically. On CT scan, masses were oval or round and well demarcated with lobulated margin in all cases, their sizes ranged from 2 to 5 cm, and they did not show internal calcification and necrosis. On contrast-enhanced CT, three cases showed moderate enhancement more than the chest wall muscle. Lymphadenopathy was observed in ipsilateral hilar and mediastinal areas in three cases. Distant metastasis to liver was noted in one case. One case of LCNEC was Stage IV, two were Stage IIIa, and two were Stage Ia at the time of diagnosis. CONCLUSION: Although the epidemiology of LCNEC is more similar to that of small cell carcinoma than atypical carcinoids, in its strong association with smoking, rapid progression, and poor prognosis, our five cases of LCNEC show peripherally located pulmonary nodule or mass with or without regional lymphadenopathy, which are findings similar to those of atypical carcinoids rather than small cell carcinoma.