[A case of rapidly progressing lung spindle cell carcinoma presenting as Pancoast syndrome].

We report a case of rapidly progressing spindle cell carcinoma presenting as Pancoast syndrome. The patient was a 59-year-old woman with a chief complaint of right forearm paresthesia. A chest computed tomography revealed a huge tumor in S1 and S2 in the right lung, invading the upper mediastinum and the first rib. A CT-guided lung biopsy was performed. H-E stain of the tissue revealed spindle-shaped tumor cells proliferating diffusely in a streaming pattern without definitive squamous or glandular differentiation. Immunohistochemical stains with CAM 5.2 and vimentin were positive for tumor cells. Based on a pathological diagnosis of spindle cell carcinoma (cT4N3M1, stage IV) she was treated with chemoradiotherapy. Despite treatment, the patient died 6 months after presenting.

[Pasteurella multocida pneumonia with molecular evidence of zoonotic transmission].

We report the case of a patient with pneumonia caused by Pasteurella multocida (P. multocida). An 83-year-old woman admitted for bronchiectasis, productive cough, and a high fever was found in chest radiography on admission to have a new infiltrative shadow in the left lower lung field. Chest computed tomography indicated bilateral bronchiectasis and an infiltrative lingular shadow. P. multocida was isolated from sputum samples. Biapenem and minocycline therapy ameliorated symptoms. Pulsed-field gel electrophoresis (PFGE) showed that the clinical isolate recovered was identical to the P. multocida isolate recovered from the pharyngeal swab specimen culture obtained from the patient's dog. Several years later, P. multocida subsp. gallicida isolates were recovered from human sputum and a canine pharyngeal swab specimen. PFGE confirmed these isolates to be identical and PFGE band patterns were identical to those of previous P. multocida isolates. These findings suggest that P. multocida was transmitted from the patient's dog to the patient and underscore the need to inform susceptible hosts at risk of contracting zoonotic agents about basic hygiene rules for keeping pets. PFGE data strengthened the evidence of zoonotic transmission of P. multocida through casual contact in a patient with a respiratory infection caused by this organism. PFGE should prove useful in both epidemiological tracing and preventing pasteurellosis and clarifying its pathology. Case reports of respiratory infections including pneumonia caused by P. multocida are increasing in humans, and P. multocida respiratory infections appear to occur mostly in patients with chronic respiratory disease. A history of pet exposure, even without bites or scratches, should alert the physician to P. multocida as a potential respiratory pathogen.

[Micafungin therapy for a case of chronic necrotizing pulmonary aspergillosis].

The patient was a 42-year-old man who visited a physician with fever, and was diagnosed with pulmonary abscess. Antibiotic therapy was ineffective, and he was referred to our hospital. Chest CT scanning revealed a lesion with cavity formation with an infiltrative shadow in the right upper lobe, and another infiltrative shadow in the left upper lobe. Chronic necrotizing pulmonary aspergillosis (CNPA) was diagnosed on the basis of positive culture of bronchial lavage specimens and positive serological test results for Aspergillus, in addition to the clinical and radiographic features. Intravenous administration of micafungin (MCFG) was initiated with combination therapy of percutaneous cavity drainage, inhaled amphotericin B and oral itraconazole. Clinical symptoms and findings gradually improved, and he was discharged after 40 days of MCFG therapy. MCFG was safe and effective therapy in this case, and may be considered a new therapeutic option for CNPA.

[Moderately differentiated adenocarcinoma of the lung presenting as multiple pulmonary metastases with thin-walled cavities].

A 63-year-old woman was admitted because of diabetes mellitus and abnormal chest radiographic findings. Computed tomographic scan showed a large mass in the S1 region of the right lung and many pulmonary nodules with thin-walled cavities in both lung fields. A transbronchial biopsy specimen revealed moderately differentiated adenocarcinoma of bronchial gland origin. The patient could not receive systemic chemotherapy because of her poor physical status, and died of respiratory failure due to advanced pulmonary metastases. Histopathological examination of an autopsy specimen confirmed the diagnosis of primary bronchial adenocarcinoma with multiple cavitary metastases. The cavity wall consisted of moderately differentiated adenocarcinoma cells, and central necrosis with neutrophil infiltration and fibrin precipitation were recognized. These findings suggest that the mechanism of cavity formation in this case may depend on the ischemic tumor necrosis or colliquative tumor necrosis associated with neutrophil infiltration into the central portion of metastatic lesion.

GADD34 induces p53 phosphorylation and p21/WAF1 transcription.

Recently, others and we have shown that one of the functions of GADD34 is a recovery from a shutoff of protein synthesis induced by endoplasmic reticulum stress. GADD34 has been shown to induce growth arrest and apoptosis. Main protein of apoptosis is p53, especially phosphorylation of p53. And one of the main proteins of growth arrest is p21/WAF1. Here we analyzed the effects of GADD34 on p53 phosphorylation and p21/WAF1 transcription. Transfected Myc-tagged p53 was dose-dependently phosphorylated at Ser15 by increasing the amount of GADD34. Transfection of GADD34 also induced the endogenous phosphorylation of p53 and enhanced p21 protein expression. Transfection of GADD34 induced p21/WAF1 promoter activity. This activity was dependent on p53, because GADD34 transfection to p53-deficient cells produced only a slight increase of p21/WAF1 promoter activity. The p21/WAF1 promoter activity was greatly enhanced by the transfection of p53. Both GADD34 and p53 transfection induced much higher p21/WAF1 promoter activity. The promoter activity of p21/WAF1 was very low in GADD34 deficient MEF. The transfection of GADD34 increased the p21/WAF1 promoter activity in GADD34 deficient MEF.

The function of GADD34 is a recovery from a shutoff of protein synthesis induced by ER stress: elucidation by GADD34-deficient mice.

GADD34 is a protein that is induced by stresses such as DNA damage. The function of mammalian GADD34 has been proposed by in vitro transfection, but its function in vivo has not yet been elucidated. Here we generated and analyzed GADD34 knockout mice. Despite their embryonic stage- and tissue-specific expressions, GADD34 knockout mice showed no abnormalities at fetal development and in early adult life. However, in GADD34-/- mouse embryonic fibroblasts (MEFs), recovery from a shutoff of protein synthesis was delayed when MEFs were exposed to endoplasmic reticulum (ER) stress. The phosphorylation of eukaryotic translation initiation factor 2 alpha (eIF2alpha) at Ser51 induced by thapsigargin or DTT was prolonged in GADD34-/- MEF, although following treatment with tunicamycin, the eIF2alpha phosphorylation level did not change in either GADD34+/+ or GADD34-/- cells. ER stress stimuli induced expressions of Bip (binding Ig protein) and CHOP (C/EBP homologous protein) in MEF of wild-type mice. These expressions were strongly reduced in GADD34-/- MEF, which suggests that GADD34 up-regulates Bip and CHOP. These results indicate that GADD34 works as a sensor of ER stress stimuli and recovers cells from shutoff of protein synthesis.