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A 54 year old Japanese man was introduced to Saiseikai General hospital for an evaluation of an abnormal chest X-ray film. Abnormal soft tissue area was observed in the mediastinum surrounding anterior area of the trachea on chest CT. Because the mediastinal tumor showed slow enlargement after temporal decrease and surgical resection of the tumor was performed 3 years after the first visit. Pathologically, diffuse proliferation of oval-shaped plasmacytic or small lymphocytic cells with eccentrically-located nuclei with rough chromatin were observed in the tumor. Immunohistochemically, these cells were positive for CD20, weakly positive for IgM, negative for CD3, CD5, CD10, suggesting lymphoplasmacytic lymphoma (LPL). The patient was treated with rituximab after the surgical treatment, and showed no exacerbation for 3.5 years after surgery. LPL localized to the paratracheal mediastinum is rare, and a surgical approach is important for prompt and proper diagnosis.

We retrospectively evaluated the survival benefit of dispensing erlotinib after gefitinib administration in patients with nonsmall cell lung cancer. Ninety patients treated with erlotinib in our hospital were divided into two groups: G+ group patients who were treated with erlotinib with prior gefitinib administration, and G- group patients who were treated with erlotinib without prior gefitinib administration. Median survival time (MST) in all 90 patients was 275 days. MST of 22 patients in the G+ group was shorter than that of 68 patients in G- group, but this difference was not statistically significant (283 days vs 177 days, p=0. 329). MST in 19 patients of the G+group who were administered erlotinib for over 1 month was shorter than that of 49G-group patients who were administered erlotinib over 1 month. However, this difference was also not statistically significant(395 days vs 238 days, p=0. 575). Univariate analysis demonstrated that EGFR mutation unknown, time to progression (TTP) with gefitinib longer than 1 year, gefitnib administration longer than 1 year, and responder to gefitinib, suggest a better prognosis. Mutivariate analysis revealed that only TTP with gefitinib longer than 1 year was an independent prognostic factor for patients in the G+ group.

Thymic carcinoma is comparatively rare and no standard treatment has been established for advanced stage cases. We reviewed our therapeutic experience in 12 cases of thymic carcinoma. They consisted of 9 men and 3 women, ranging from 38 to 69 years of age, with a mean age of 56.5. According to Masaoka's classification, 5 cases were stage III and 7 were preoperative stage IVb. Nine cases were squamous cell carcinoma and 3 were adenocarcinoma. Four cases of preoperative clinical stage III underwent extended thymectomy, but none were completely resected and were classified as stage IV postoperatively. Chemotherapy combined with radiation therapy was given in 1 case, chemotherapy (monotherapy) was given in 4 cases, radiation therapy was given in 1 case, and 2 cases received best supportive care. The median survival time (MST) of patients who had undergone combined modality treatments including surgery was 1971 days, which was longer than the MST of 567 days of patients who were not able to undergo surgery. The prognosis outcome of advanced thymic carcinoma is poor, but combined modality therapies such as surgery, chemotherapy and radiation can be effective for some advanced thymic carcinoma cases.

Objectives: The aim of this study was to evaluate the usefulness of bronchofiberscopy (BFS) in the diagnosis of pulmonary non-tuberculous mycobacteriosis (PNTM)., Materials and Methods: Among 909 PNTM patients admitted to our hospital during the period from 1995 to 2006, BFS was performed for the diagnosis of PNTM in 107 patients (12%) who had either a negative sputum-smear for acid-fast bacilli (AFB) (n = 100) or from whom it had been impossible to collect sputum (n =7). For these 107 cases, we retrospectively compared and analyzed the findings from specimens obtained by BFS, such as smears, cultures, polymerase-chain reaction (PCR), and transbronchial lung biopsy (TBLB), with clinical, radiological, and sputum examination disease, was also seen in the positive ratios of other nontuberculous mycobacteriosis cases. Type and/or spread of MAC disease on chest radiographs did not relate to positive ratios of BFS obtained specimens. Based on overall BFS findings, including the examination of sputum immediately after BFS, 68 of 92 (74%) patients met the diagnostic criteria of MAC disease. Furthermore, through a combination of positive-TBLB findings and positive-PCR findings of BFS specimens, we were able to obtain an early and strong indication of MAC disease in 17 of 36 (47%) patients., Conclusion: Using BFS to obtain various kinds of specimens is a useful tool for the early and definite diagnosis of PNTM/pulmonary MAC disease.

Changes in intracellular Ca concentration ([Ca2+]i) play dominant roles in the regulation of ion channel activity. Thus, analyses of Ca-related ion channels, whose activation is responsible for and/or dependent on the changes in [Ca2+]i, are important to understand the physiological and pharmacological characteristics of smooth muscle cells (SMCs) and endothelial cells (ECs). We have clarified that, in SMCs, Ca mobilization by membrane depolarization and bioactive substances affects the activity of Ca-activated K (IK-Ca) and Cl channel currents. On the other hand, by measuring IK-Ca as an indicator of Ca mobilization, we found that palmitoylcarnitine (PC), a lipid released under ischemic conditions, mobilizes Ca in ECs via stimulation of endothelial differential gene (Edg) receptors. Moreover, sphingosine-1-phosphate, which is a lipid mediator and has a similar structure to PC, elevated [Ca2+]i in ECs via the activation of cation channels through Edg1 receptors. A myo-endothelial interaction is another regulatory factor of Ca mobilization in ECs as well as in SMCs. Nifedipine and levcromakalim, which have no effects on ion channels in ECs themselves, changed the membrane potential of ECs via a myo-endothelial pathway. These integral analyses provide better understanding of the functional roles of Ca-related ion channels and their involvement in Ca mobilization in SMCs and ECs.

Effects of sphingosine-1-phosphate (S1P), a putative lipid mediator, was examined in vascular smooth muscle and endothelial cells by means of measuring intracellular Ca2+ concentration ([Ca2+]i), whole-cell membrane currents and tension. Application of S1P in a concentration range from 30 to 1000 nM to human umbilical vein endothelial cells (HUVECs) induced a slowly developing increase in [Ca2+]i. and concomitant non-selelctive cationic inward currents. Pretreatment of HUVECs with pertussis toxin (PTX) almost abolished the S1P-induced elevation of [Ca2+]i, suggesting that PTX sensitive edg1 receptors are involved in the S1P-induced response in HUVECs. Moreover, treatment of HUVECs with S1P for 24 hrs caused cell-proliferation to 150% of the control. On the other hand, application of S1P had no effect on [Ca2+]i in rabbit, rat and mouse aortic myocytes. When S1P applied to rabbit aorta with endothelium, the muscle ring had small relaxation which disappeared in endothelium-denuded aorta. In contrast, rat cerebral arterial myocytes had increase in [Ca2+]i in the presence of S1P. These results suggest that responses of vascular tissues to S1P vary from cell to cell. To clarify physiological and pharmacological significance of S1P in cardiovascular system, comprehensive analyses are required.

The major functional roles of K channels in smooth muscle cells are as follows: (i) Keeping resting membrane potential (RMP). (ii) Induction of hyperpolarization (HP) in response to bioactive substances. (iii) Facilitation of action potential repolarization (APR). (iv) Induction of action potential after-hyperpolarization (AH). (v) Facilitation of slow wave repolarization. (vi) Inhibition of depolarization and/or action potential. Major background K channels responsible for RMP have not been identified yet, whereas it is been postulated that several K channels including Ca-dependent K channels and ATP-dependent K channels may co-contribute in part to RMP. Further activation of these channels by bioactive substances results in hyperpolarization and muscle relaxation. APR and AH in several types of smooth muscles are due to activation of mainly large conductance Ca-dependent K channels (BK) and additionally delayed rectifier K channels. Moreover, another type of delayed rectifier K channels and early inactivating K channels may also contribute to some of the functional roles shown above. Although activation of Ca-dependent Cl channels in response to agonists depolarizes the cell membrane in several types of smooth muscle cells, a single channel current has not been identified. Ca-dependent K and Cl currents can be regulated by intracellular Ca store sites, which may be exhausted after a large release induced by inositol 1,4,5-trisphosphate or caffeine. The Ca-pump activity in the store sites may also regulate indirectly but strongly the activity of the channels and consequently membrane excitability.