Total Internal Reflection Raman Spectra of Alamethicin Interacting with Supported Lipid Bilayers at a Silica/Water Interface.

We report total internal reflection (TIR)-Raman spectroscopy to study intermolecular interactions between membrane-binding peptides and lipid bilayer membranes. The method was applied to alamethicin (ALM), a model peptide for channel proteins, interacting with 1,2-dipalmitoyl-sn-glycero-3-phosphocholine (DPPC) bilayer membranes at a silica/water interface. After a dimethyl sulfoxide (DMSO) solution of ALM was added into the water subphase of the DPPC/DPPC bilayer, Raman signals in the CH stretching region increased in intensity reflecting the appearance of the Raman bands due to ALM and DMSO. To identify ALM-dependent spectral changes, we removed DPPC and DMSO contributions from the Raman spectra. We first subtracted the spectrum of the DPPC bilayer from those after the addition of the ALM solution. The contribution of DMSO was then removed by subtracting a DMSO spectrum from the resultant spectra. The DMSO spectrum was obtained in a similar way from a control experiment where DMSO alone was added into the subphase. With the use of this double difference approach, the ALM-dependent changes were successfully obtained. Experiments with DPPC bilayers with deuterated acyl chains revealed that most of the spectral change observed after the addition of ALM was due to the vibrational bands of ALM, not originated from ALM-induced conformational changes of the lipid bilayers.

Assessment of pathologically diagnosed patients with Castleman's disease associated with diffuse parenchymal lung involvement using the diagnostic criteria for IgG4-related disease.

BACKGROUND: IgG4-related disease (IgG4RD) is a recently recognized disease entity. Differentiating IgG4RD from plasma cell type Castleman's disease (PCD) is important but also difficult using only pathological findings. In addition, little is known about the association between these two diseases with diffuse parenchymal lung involvement. METHODS: We analyzed the serum IgG4 levels and the ratio of IgG4/IgG-positive plasmacytes in the lung and lymph node specimens of eight patients previously pathologically diagnosed of PCD with diffuse parenchymal lung involvement (DL-PCD). We also compared the clinical and laboratory findings observed in these patients. RESULTS: Six of the eight patients exhibited abundant IgG4-positive plasmacytes in the lung and lymph node tissues and elevated serum IgG4 levels, thereby fulfilling the diagnostic criteria of IgG4RD with DL (DL-IgG4RD) in addition to having obstructive phlebitis and massive lymphoplasmacytic infiltration with fibrosis. However, three of these six patients exhibited higher levels of serum interleukin-6 and were still diagnosed with DL-PCD. Accordingly, three of these eight patients were considered as IgG4RD with DL (DL-IgG4RD), and the other five patients were ultimately given a diagnosis of DL-PCD. These two diseases have different characteristics in terms of age, symptoms, serum levels of C-reactive protein, and IgA, complicating allergic disorders, response to corticosteroids, and prognosis. CONCLUSIONS: This is the first report to show a high prevalence of DL-IgG4RD in DL-PCD patients, although additional large investigations are necessary. Clinical and laboratory findings are important for distinguishing between these two diseases in other organs, as previously described.

[A case of lung cancer with hyperthyroidism].

We here report a case of metastasis from lung cancer to the thyroid. On presentation, this patient showed painful anterior cervical swelling and right supraclavicular lymph node swelling. Laboratory data showed primary hyperthyroidism. Although subacute thyroiditis was suspected, echo-guided needle aspiration biopsy and lymph node biopsy revealed poorly differentiated squamous cell carcinoma. As a result, primary lung cancer with thyroid metastasis was diagnosed based on mediastinal enlargement on chest X ray films and normal findings in organs other than the lung and thyroid. Chemotherapy for lung cancer induced a decrease in the size of tumor and the normalization of thyroid function. However, 2 months after the normalization, cervical swelling enlarged and a lung mass in right upper lobe and skin tumor appeared. Despite treatment with chemotherapy, she died. Postmortem revealed that the right upper lung carcinoma was the primary lesion and immunohistochemical staining for surfactant protein was positive in the thyroid, skin tumor and lymph node, which revealed these carcinomas had metastasized from lung cancer. To the best of our knowledge, thyrotoxicosis induced by thyroid metastasis of lung cancer is an uncommon case.

[A case of lung adenocarcinoma keeping complete remission by treatment with gefitinib].

A 74-year-old smoking man was admitted because of lung cancer with metastatic brain tumor. Examinations for lung cancer and brain tumor showed adenocarcinoma (clinical stage IV). Four courses of chemotherapy were not effective. Administration of gefitinib started from June 2003, but was halted after only two months because of skin rash. Lung tumor disappeared on chest computerized tomography in January 2004 and no recurrence has been detected as of March 2006. This is a rare male super-responder to gefitinib.

Long-term treatment with theophylline reduces neutrophils, interleukin-8 and tumor necrosis factor-alpha in the sputum of patients with chronic obstructive pulmonary disease.

BACKGROUND: The non-selective phosphodiesterase inhibitor theophylline has bronchodilator/anti-inflammatory properties and is widely used in the treatment of airways diseases. We determined the effect of long-term theophylline treatment on airway inflammation in patients with chronic obstructive pulmonary disease (COPD). POPULATIONS AND METHODS: Seventeen stable COPD patients were enrolled in the 12-month study. Theophylline was administered at 400mg/day. We studied changes in symptoms, spirometry, sputum volume, and sputum inflammatory cytokines levels. We also examined the effects of theophylline on the release of inflammatory cytokines in vitro by measuring interleukin (IL)-8 and tumor necrosis factor (TNF)-alpha levels from lipopolysaccharide (LPS)-stimulated neutrophils and THP-1 cells. RESULTS: Forced vital capacity was increased and sputum IL-8 levels decreased after 4 weeks of theophylline treatment. After 6 months of theophylline treatment, forced expiratory volume in 1s was increased, and neutrophils counts and TNF-alpha levels in sputum were reduced. Levels of IL-8 and TNF-alpha released by LPS-stimulated THP-1 cells were reduced by treatment with theophylline at 10microg/ml. In contrast, IL-8 levels released by LPS-stimulated neutrophils were reduced by treatment with theophylline at 100microg/ml. CONCLUSION: Our clinical study of small population showed that long-term treatment with theophylline seems to reduce airway inflammation in stable COPD patients.

[A case of Westermani Paragonimiasis with atypical change of CT findings].

A 47-year-old man presented with bloody sputum and a cavitary mass shadow was formed in his right middle lobe. Transbronchial lung biopsy revealed the presence of parasite eggs and eosinophil infiltration. Based on the positive reaction against Westermani Paragonimus by multiple dot ELISA, Westermani Paragonimiasis was diagnosed. The cavitary mass shadow disappeared after the treatment with Pragiquantel. This is a rare case of Westermani Paragonimiasis showing interesting changes of chest CT findings during its clinical course.

High concentrations of alpha-defensins in plasma and bronchoalveolar lavage fluid of patients with acute respiratory distress syndrome.

alpha-Defensins, antimicrobial peptides localized in neutrophils, participate in tissue damage through their cytotoxic effects in neutrophil-mediated pulmonary diseases. Neutrophils play an important role in the pathogenesis of acute respiratory distress syndrome (ARDS). We measured alpha-defensins levels in plasma and bronchoalveolar lavage fluid (BALF) of ARDS patients to assess the kinetics of alpha-defensins in ARDS. Plasma alpha-defensins levels were higher in ARDS patients than in control subjects, and BALF levels were also higher in ARDS patients than in control subjects. In ARDS, BALF alpha-defensins levels correlated with those of interleukin (IL)-8, and plasma alpha-defensins levels also correlated with Lung Injury Score. Peripheral neutrophil alpha-defensins contents were higher in ARDS than the control. IL-8 dose-dependently stimulated alpha-defensins release from cultured neutrophils and these levels were higher in ARDS than the control. Reverse-phase high performance liquid chromatography showed high plasma levels of pro-defensins, precursors of alpha-defensins from the bone marrow in ARDS, although alpha-defensins in peripheral and BALF neutrophils were mature type. In conclusion, high plasma alpha-defensins in ARDS patients result from the release of pro-defensins from bone marrow, rather than mature alpha-defensins from neutrophils that accumulate in the alveolar space. The alpha-defensins contents of peripheral neutrophils in ARDS are higher and easier to release than control.

Acute eosinophilic pneumonia with fine nodular shadows.

A 19-year-old woman presented with acute onset of cough and dyspnea. She started smoking two weeks before the appearance of symptoms. On admission, arterial blood gas analysis on room air breathing revealed PaO2 55 Torr. Chest roentgenogram and high resolution computed tomograms showed localized fine nodular shadows at the right lower lung field. Bronchoalveolar lavage fluid revealed a high eosinophil count. Eosinophil infiltration was also observed in transbronchial lung biopsy specimens. The final diagnosis was acute eosinophilic pneumonia (AEP). Although few reports have demonstrated diffuse fine nodular shadows in AEP, localized fine nodular shadows on chest roentgenogram and CT may sometimes be the sign of AEP especially in the early phase of the clinical course.