Search

Archival formalin-fixed, paraffin-embedded (FFPE) tumor specimens were collected from advanced NSCLC patients enrolled in LETS phase III trial comparing first-line S-1/carboplatin with paclitaxel/carboplatin and subjected to multiplex genotyping for 214 somatic hotspot mutations in 26 genes (LungCarta Panel) and 20 major variants of ALK, RET, and ROS1 fusion genes (LungFusion Panel) with the Sequenom MassARRAY platform. MET amplification was evaluated by fluorescence in situ hybridization. A somatic mutation in at least one gene was identified in 48% of non-squamous cell carcinoma and 45% of squamous cell carcinoma specimens, with EGFR (17%), TP53 (11%), STK11 (9.8%), MET (7.6%), and KRAS (6.2%). Mutations in EGFR or KRAS were associated with a longer or shorter median overall survival, respectively. The LungFusion Panel identified ALK fusions in six cases (2.5%), ROS1 fusions in five cases (2.1%), and a RET fusion in one case (0.4%), with these three types of rearrangement being mutually exclusive. Nine (3.9%) of 229 patients were found to be positive for de novo MET amplification. This first multiplex genotyping of NSCLC associated with a phase III trial shows that MassARRAY-based genetic testing for somatic mutations and fusion genes performs well with nucleic acid derived from FFPE specimens of NSCLC tissue.

Mast cells (MCs) mature locally, thus possessing tissue-dependent phenotypes for their critical roles in both protective immunity against pathogens and the development of allergy or inflammation. We previously reported that MCs highly express P2X7, a receptor for extracellular ATP, in the colon but not in the skin. The ATP-P2X7 pathway induces MC activation and consequently exacerbates the inflammation. Here, we identified the mechanisms by which P2X7 expression on MCs is reduced by fibroblasts in the skin, but not in the other tissues. The retinoic-acid-degrading enzyme Cyp26b1 is highly expressed in skin fibroblasts, and its inhibition resulted in the upregulation of P2X7 on MCs. We also noted the increased expression of P2X7 on skin MCs and consequent P2X7- and MC-dependent dermatitis (so-called retinoid dermatitis) in the presence of excessive amounts of retinoic acid. These results demonstrate a unique skin-barrier homeostatic network operating through Cyp26b1-mediated inhibition of ATP-dependent MC activation by fibroblasts., (Copyright © 2014 Elsevier Inc. All rights reserved.)

Background: Secondary pulmonary alveolar proteinosis (sPAP) is a very rare lung disorder comprising approximately 10% of cases of acquired PAP. Hematological disorders are the most common underlying conditions of sPAP, of which 74% of cases demonstrate myelodysplastic syndrome (MDS). However, the impact of sPAP on the prognosis of underlying MDS remains unknown. The purpose of this study was to evaluate whether development of sPAP worsens the prognosis of MDS., Methods: Thirty-one cases of sPAP and underlying MDS were retrospectively classified into mild and severe cases consisting of very low-/low-risk groups and intermediate-/high-/very high-risk groups at the time of diagnosis of MDS, according to the prognostic scoring system based on the World Health Organization classification. Next, we compared the characteristics, disease duration, cumulative survival, and prognostic factors of the groups., Results: In contrast to previous reports on the prognosis of MDS, we found that the cumulative survival probability for mild MDS patients was similar to that in severe MDS patients. This is likely due to the poor prognosis of patients with mild MDS, whose 2-year survival rate was 46.2%. Notably, 75% and 62.5% of patients who died developed fatal infectious diseases and exacerbation of PAP, respectively, suggesting that the progression of PAP per se and/or PAP-associated infection contributed to poor prognosis. The use of corticosteroid therapy and a diffusing capacity of the lung for carbon monoxide of less than 44% were predictive of poor prognosis., Conclusion: Development of sPAP during the course of MDS may be an important adverse risk factor in prognosis of patients with mild MDS.

Bronchus-associated lymphoid tissue (BALT) lymphoma of the trachea, an important differential diagnosis for tracheal tumors, is a rare disease with characteristic bronchoscopic findings. In this study, we reviewed 2 cases of patients who were symptomatic at the time of diagnosis, with tumors in the trachea and left main bronchus, putting them at high risk for asphyxia. Chemotherapies including rituximab were administered, and complete remission was confirmed in both cases. Because tracheal tumors often have a pernicious course, it might be beneficial to initiate a chemotherapeutic treatment regimen instead of adopting the "wait-and-see" approach in patients with symptomatic tracheal BALT lymphoma., (© 2013 The Japanese Respiratory Society. Published by Elsevier B.V. All rights reserved.)

Carcinoma of unknown primary (CUP) is a common malignancy. In view of the poor prognosis of CUP, more effective therapy is needed. A 47-year-old man with CUP affecting the bone visited our institution. Treatment with heavy ion radiotherapy, cytotoxic chemotherapy, and resection of the bone tumor conferred neither control of the tumor nor the patient's symptoms such as tumor fever and bone pain. The bone biopsy at hemipelvectomy suggested undifferentiated adenocarcinoma with some features of clear cell carcinoma, although no lesions were detected in the kidneys. Based on the pathological diagnosis, treatment with sunitinib or everolimus was administered but resulted in progressive disease. However, axitinib showed favorable effects, controlling tumor progression and palliating his symptoms. To our knowledge, this is the first case of successful control of CUP with axitinib., (© 2015 S. Karger AG, Basel.)

Xilei san (XLS), a herbal preparation widely used in China for erosive and ulcerative diseases, has been shown to be effective in ulcerative colitis (UC). The present experiments were conducted to assess its efficacy and determine its mechanism of action in a rat model that resembles human UC. The model was induced by adding 4% dextran sulfate sodium (DSS) to the rats' drinking water for 7 days. XLS was administered daily by retention enema from day 2 to day 7; the rats were sacrificed on day 8. The colon tissues were obtained for further experiments. A histological damage score and the activity of tissue myeloperoxidase were used to evaluate the severity of the colitis. The colonic cytokine levels were detected in a suspension array, and epithelial proliferation was assessed using Ki-67 immunohistochemistry. Intrarectal administration of XLS attenuated the DSS-induced colitis, as evidenced by a reduction in both the histological damage score and myeloperoxidase activity. It also decreased the levels of proinflammatory cytokines, but increased the mucosal repair-related cytokines. In addition, the epithelial Ki-67 expression was upregulated by XLS. These results suggest that XLS attenuates DSS-induced colitis by degrading proinflammatory mediators and promoting mucosal repair. XLS could be a potential topical treatment for human UC.

The transient receptor potential ankyrin 1 (TRPA1) channel is well known as a sensor to environmental irritant compounds, cold, and endogenous proalgesic agents. TRPA1 is expressed on sensory neurons and is involved in pain modulation. Etodolac is a cyclooxygenase (COX)-2 inhibitor that belongs to the class of nonsteroidal anti-inflammatory drugs (NSAIDs). A recent study indicates that etodolac inhibits allyl isothiocyanate (AITC)-induced calcium influx in heterologous HEK293 cells and sensory neurons. To examine whether and how etodolac modulates the TRPA1 channels, we applied etodolac to TRPA1-transfected HEK293 cells or rat dorsal root ganglion (DRG) neurons and recorded the currents using the whole-cell patch clamp technique. We found that etodolac at higher doses could activate and then desensitize TRPA1 channels in heterologous expressing HEK293 cells as well as in DRG neurons. The etodolac-induced currents were significantly attenuated in cysteine residues mutated human TRPA1-transfected HEK293 cells. Interestingly, application of etodolac at drug plasma levels in clinical usage did not induce significant TRPA1 currents but reduced the subsequent AITC-induced currents to 25% in HEK293 cells expressing TRPA1. Moreover, no modulatory effect of etodolac on TRPA1 was detected in the cysteine mutant cells. These data indicate a novel mechanism of the anti-inflammatory and analgesic clinical effects of etodolac, which may be involved with its direct activation and the subsequent desensitization of TRPA1 through the covalent modification of cysteine residues., (Copyright © 2013 Wiley Periodicals, Inc.)

Objectives: Anthracyclines and taxanes are often used as first-line chemotherapy treatments in patients with breast cancer. There are, however, significant toxicity and side effects associated with these therapies. Previous studies have demonstrated that active hexose-correlated compound (AHCC) reduces such side effects. The present study explored the beneficial effects of AHCC on adverse events in patients receiving adjuvant chemotherapy for breast cancer., Subjects: Forty-one women who were treated with anthracyclines and taxanes at Nagumo Clinic in Tokyo from October 2004 to March 2011 were selected for this study., Outcome Measures: We compared the occurrence of adverse events in patients who received AHCC with those who did not receive AHCC. Using Fisher's exact tests, we also compared the worst-grade adverse events in each treatment cycle. Generalized estimating equations were employed to compare longitudinal changes, and the use of granulocyte colony-stimulating factor, in the two groups was analyzed using Student's t-test., Results: We found that, compared to the control group, the AHCC group had significantly fewer neutrophil-related events (odds ratio, 0.30; p=0.016), significantly lower use of granulocyte colony-stimulating factor, and a higher (although not significant) rate of adverse events associated with γ-glutamyl transpeptidase., Conclusions: AHCC has the potential to reduce the severity of neutropenia induced by breast cancer chemotherapy and the use of G-CSF during chemotherapy.

Huge tsunami waves associated with megathrust earthquakes have a severe impact on shallow marine ecosystems. We investigated the impact of a tsunami generated by the 2011 M9.0 Tohoku-Oki earthquake on the seafloor and large benthic animals in muddy and sandy ria coasts (Otsuchi and Funakoshi bays) in northeastern Japan. We conducted underwater field surveys using scuba equipment in water depths of <20 m before the tsunami (September 2010) and after the tsunami (September 2011 and September 2012). During the study period, episodic changes in topography and grain-size composition occurred on the seafloor of the study area. Megabenthos sampling revealed a distinct pattern of distribution succession for each benthic species. For example, the protobranch bivalve Yoldia notabilis (Bivalvia: Nuculanidae) and the heterodont bivalve Felaniella usta (Bivalvia: Ungulinidae) disappeared after the tsunami event, whereas the distribution of the venus clam Gomphina melanaegis (Bivalvia: Veneridae) remained unchanged. In addition, the patterns of succession for a single species, such as the giant button top shell Umbonium costatum (Gastropoda: Trochidae) and the heart urchin Echinocardium cordatum (Echinoidea: Loveniidae), varied between the two bays studied. Our data also show that reestablishment of some benthic animal populations began within 18 months of the tsunami disturbance.

Introduction: Smoking status is one of the prognostic factors in advanced non-small-cell lung cancer (NSCLC). Currently, adenocarcinoma (Ad) histology is considered a predictive factor in advanced NSCLC. We investigated the correlation between histology or smoking status and survival of NSCLC patients receiving chemotherapy., Methods: We retrospectively reviewed clinical data from stage IIIB or IV NSCLC patients who started first-line chemotherapy at affiliated institutions of West Japan Oncology Group from 2004 to 2005. We also collected information on pack-years of cigarette smoking and years since cessation. Overall survival was compared using log-rank test, and Cox regression analysis was used to identify independent prognostic factors., Results: In total, 2542 consecutive patients were enrolled at 40 institutions. Of those, 71 were excluded because of unknown smoking history. The median overall survival of nonsmoking Ad patients (593 days) was longer than that of smoking Ad, nonsmoking non-Ad, and smoking non-Ad patients (384, 374, and 319 days, respectively; p < 0.001). In Cox regression with sex, age, stage, performance, and treatment as covariates, we found significant interaction (p = 0.039) between histology (Ad/non-Ad) and smoking status (smoker/nonsmoker); smoking conferred a hazard ratio of 1.34 (95% confidence interval, 1.15-1.55) in Ad, but only 0.99 (0.75-1.31) in non-Ad. Higher pack-years and shorter period since cessation were significantly associated with poorer survival in Ad (p < 0.001), but not in non-Ad (p ≥ 0.434)., Conclusion: Ad histology is associated with better prognosis, and only smoking status had a prognostic impact in Ad.

Background: Resveratrol (3,5,4' - trihydroxy-trans-stilbene), a widely distributed natural stilbenoid, was proposed to account for the unique effects of red wine on life span and health. It has been reported to possess various biological and pharmacological activities, such as anti-oxidant, anti-inflammatory, and anti-carcinogenic effects. Here, using whole-cell patch-clamp techniques and behavioral analyses, we investigated whether resveratrol and other stilbenoids can modulate TRP channels in sensory neurons in vitro, and have analgesic effects in vivo., Results: We found that resveratrol dose-dependently suppressed the allyl isothiocyanate (AITC)-induced currents (I AITC) in HEK293 cells that express TRPA1, as well as in rat dorsal root ganglion (DRG) neurons. Instead, pinosylvin methyl ether (PME), another derivate of stilbene which has a similar structure to resveratrol, dose-dependently blocked the capsaicin-induced currents (I CAP) in HEK293 cells that express TRPV1 as well as in DRG neurons. Interestingly, resveratrol had no inhibitory effect on the I CAP, and PME had no effect on the I AITC. Otherwise, trans-stilbene showed no any effect on I AITC or I CAP. The concentration response curve of AITC showed that resveratrol inhibited the action of TRPA1 not by changing the EC50, but by suppressing the AITC-induced maximum response. By contrast, the inhibition of TRPV1 by PME did not change the capsaicin-induced maximum response but did cause a right shift of the EC50. Moreover, pre-administration of resveratrol suppressed intraplantar injections of AITC-evoked nocifensive behaviors, as well as that PME suppressed capsaicin-evoked one., Conclusions: These data suggest that resveratrol and other stilbenoids may have an inhibitory effect on TRP channels. In addition, these stilbenoids modulate TRP channel activity in different ways.

Background: Several studies have reported that specimens from mediastinal lesions located adjacent to the esophagus can be sampled using an ultrasound bronchoscope instead of an ultrasound endoscope., Objectives: The aim of this study was to evaluate the diagnostic utility of transesophageal bronchoscopic ultrasound-guided fine needle aspiration using an ultrasound bronchoscope in patients with stage I/II sarcoidosis., Methods: Thirty-three patients suspected of having stage I/II sarcoidosis were included in this prospective study. Needle aspiration through the esophagus using an ultrasound bronchoscope was performed for hilar and/or mediastinal lymph nodes. The final diagnosis of sarcoidosis was based on clinicoradiological compatibility and pathological findings., Results: A total of 62 lymph nodes with a mean shortest diameter of 13.6 mm were examined. Of the 33 patients enrolled, 29 were given a final diagnosis of sarcoidosis. Four of the residual patients had other diseases (1 lung cancer, 1 tuberculosis, 2 non-specific lymphadenitis). Transesophageal bronchoscopic ultrasound-guided fine needle aspiration showed noncaseating epithelioid cell granulomas in 25 of 29 patients (86%; 95% confidence interval 73-100) with the final diagnosis of sarcoidosis. No complications were observed., Conclusions: Transesophageal bronchoscopic ultrasound-guided fine needle aspiration is feasible, safe and accurate for the diagnosis of stage I/II sarcoidosis., (Copyright © 2012 S. Karger AG, Basel.)

Background: Although rapid on-site cytologic evaluation (ROSE) is widely used during endobronchial ultrasound-guided transbronchial needle aspiration (EBUS-TBNA), its role remains unclear., Objectives: The purpose of the present study was to evaluate the efficacy of ROSE during EBUS-TBNA in the diagnosis of lung cancer., Methods: One hundred and twenty patients highly suspected of having lung cancer who had hilar/mediastinal lymphadenopathy or a tumor adjacent to the central airway were enrolled in this study and randomized to undergo EBUS-TBNA with or without ROSE., Results: Twelve patients with visible endobronchial lesions were excluded in the analysis. Thus, a total of 108 patients (55 in the ROSE group, 53 in the non-ROSE group) were analyzed. Additional procedures including EBUS-TBNA for lesions other than the main target lesion and/or transbronchial biopsy in the same setting were performed in 11% of patients in the ROSE group and 57% in the non-ROSE group (p < 0.001). Mean puncture number was significantly lower in the ROSE group (2.2 vs. 3.1 punctures, p < 0.001), and mean bronchoscopy time was similar between both groups (22.3 vs. 22.1 min, p = 0.95). The sensitivity and accuracy for diagnosing lung cancer were 88 and 89% in the ROSE group, and 86 and 89% in the non-ROSE group, respectively. No complications were associated with the procedures., Conclusions: ROSE during EBUS-TBNA is associated with a significantly lower need for additional bronchoscopic procedures and puncture number., (Copyright © 2013 S. Karger AG, Basel.)

Proinflammatory agents trypsin and mast cell tryptase cleave and activate protease-activated receptor-2 (PAR-2), which is expressed on sensory nerves and causes neurogenic inflammation. P2X3 is a subtype of the ionotropic receptors for adenosine 5'-triphosphate (ATP), and is mainly localized on nociceptors. Here, we show that a functional interaction of the PAR-2 and P2X3 in primary sensory neurons could contribute to inflammatory pain. PAR-2 activation increased the P2X3 currents evoked by α, β, methylene ATP in dorsal root ganglia (DRG) neurons. Application of inhibitors of either protein kinase C (PKC) or protein kinase A (PKA) suppressed this potentiation. Consistent with this, a PKC or PKA activator mimicked the PAR-2-mediated potentiation of P2X3 currents. In the in vitro phosphorylation experiments, application of a PAR-2 agonist failed to establish phosphorylation of the P2X3 either on the serine or the threonine site. In contrast, application of a PAR-2 agonist induced trafficking of the P2X3 from the cytoplasm to the plasma membrane. These findings indicate that PAR-2 agonists may potentiate the P2X3, and the mechanism of this potentiation is likely to be a result of translocation, but not phosphorylation. The functional interaction between P2X3 and PAR-2 was also confirmed by detection of the α, β, methylene-ATP-evoked extracellular signal-regulated kinases (ERK) activation, a marker of neuronal signal transduction in DRG neurons, and pain behavior. These results demonstrate a functional interaction of the protease signal with the ATP signal, and a novel mechanism through which protease released in response to tissue inflammation might trigger the sensation to pain through P2X3 activation., (© 2012 The Authors. European Journal of Neuroscience © 2012 Federation of European Neuroscience Societies and Blackwell Publishing Ltd.)

Objective: Endobronchial ultrasound-guided transbronchial needle aspiration (EBUS-TBNA) has been reported to be an accurate and safe method to confirm a pathologic diagnosis of sarcoidosis. However, only a few retrospective or small prospective studies have been published on EBUS-TBNA versus transbronchial lung biopsy (TBLB), which has been the standard method for making a pathologic diagnosis of sarcoidosis so far. The aim of this study was to compare the diagnostic yield of EBUS-TBNA and TBLB through a flexible bronchoscope in patients with stage I and II sarcoidosis., Methods: A total of 62 patients with suspected stage I and II sarcoidosis were included in this prospective study. EBUS-TBNA was performed (2 lymph nodes, 2 needle passes for each lymph node), followed by TBLB (5 biopsy specimens from multiple lung segments) in the same setting. The final diagnosis of sarcoidosis was based on clinicoradiologic compatibility and pathologic findings., Results: Of the 62 patients enrolled, 54 were given a final diagnosis of sarcoidosis. The diagnostic yield of EBUS-TBNA and TBLB for sarcoidois by showing noncaseating epithelioid cell granuloma was 94% (stage I, 97%; stage II, 88%) and 37% (stage I, 31%; stage II, 50%), respectively. The difference was statistically significant (P < .001). One case of pneumothorax and 3 cases of moderate bleeding (7%) resulted from TBLB, and 1 case of severe cough (2%) from EBUS-TBNA., Conclusions: The diagnostic yield of EBUS-TBNA for stage I and II sarcoidosis is higher than for TBLB., (Copyright © 2012 The American Association for Thoracic Surgery. All rights reserved.)

Introduction: In endobronchial ultrasound-guided transbronchial biopsy (EBUS-TBB), techniques using a thin bronchoscope or a guide sheath have been proposed for accurate biopsy instrument reinsertion into the bronchial route indicated by a radial ultrasonic probe. The purpose of this study was to compare the diagnostic yields of these techniques for peripheral pulmonary lesions., Methods: Patients with suspected peripheral pulmonary lesions were included in this prospective, randomized, noninferiority study and assigned to undergo EBUS-TBB under fluoroscopic guidance using a prototype 3.4-mm thin bronchoscope or a 4.0-mm bronchoscope with a guide sheath., Results: A total of 205 patients were enrolled and randomized, of whom 203 patients (101 thin bronchoscopic method; 102 guide sheath method) were included in the analysis. Diagnostic histologic specimens were obtained in 65% (41% for benign and 75% for malignant lesions) of the thin bronchoscopy group and 62% (25% for benign and 71% for malignant lesions) of the guide sheath group. Diagnostic performance of the thin bronchoscopic method was confirmed to be noninferior to the guide sheath method (difference in diagnostic yields, 3.6%; 90% confidence interval, -7.5 to 14.7%). Mean procedure time was significantly shorter in the thin bronchoscopy group than the guide sheath group (27 versus 33 minutes; p = 0.002). Complications including pneumothorax, moderate bleeding, and pneumonia occurred in 5% and 2% in the respective groups (p = 0.28)., Conclusions: EBUS-TBB using the thin bronchoscope was noninferior to the guide sheath method for the diagnosis of peripheral pulmonary lesions and was associated with shorter procedural time.

Background: : Histologic specimens obtained by endobronchial ultrasound-guided transbronchial needle aspiration (EBUS-TBNA) often provide valuable information for diagnosis or management decisions; however, little has been reported about the sampling yield. Besides the conventional 22-gauge needle, a 21-gauge needle is now available for this procedure. The purpose of this study was to elucidate and compare the respective histologic specimen retrieval yields of EBUS-TBNA using 21-gauge and 22-gauge needles., Methods: : Sixty patients with hilar/mediastinal lymphadenopathy or a tumor adjacent to the central airway were enrolled and randomized to undergo EBUS-TBNA using a 21-gauge or a 22-gauge needle. Each histologic specimen obtained by EBUS-TBNA on the initial 2 punctures of each patient (total 120 punctures) was blindly categorized by a pathologist as follows: I, diagnostic; II, nondiagnostic but adequate (eg, lymphoid tissue); III, nondiagnostic and inadequate (eg, clot); and IV, no specimens., Results: : The specimens obtained by the 21-gauge needle were interpreted as I in 35, II in 8, III in 15, and IV in 2. The specimens obtained by the 22-gauge needle were judged to be I in 34, II in 13, III in 7, and IV in 6. The sampling yield of adequate histologic specimens (I and II) obtained by the 21-gauge and 22-gauge needles was 72% and 78% (P=0.40), respectively. No complications were associated with the procedures., Conclusions: : Histologic specimens can be obtained with a high sampling yield using either of the needles. Our study found no difference in the sampling yield between the 2 needles.

A 64-year-old man accidentally fell into a wood chip tank and nearly suffocated in 1970. He frequently suffered from pneumonia after reaching the age of 40. In 2009, he suffered from pneumonia again, and a chest computed tomography revealed a foreign body in the left main stem bronchus. Flexible bronchoscopy showed a wood chip lodged firmly in his bronchus. Removal using a flexible bronchoscope was attempted twice but failed. Rigid bronchoscopy was then performed under general anesthesia, and the chip was successfully extracted by cutting it in two using rigid scissors.

The silicone stent has been widely used to re-establish airway patency for patients with airway stenosis. The ideal shape of the stent should be well adapted to the tracheobronchial anatomic structures, and its optimal length should cover the entire inner wall of the stenotic airway. Although the silicone Y-stent was developed as a dedicated prosthesis for main carinal stenosis, we often encounter patients with tracheobronchial stenosis that cannot be treated by a single silicone Y-stent. The present study reports 2 cases of malignant disease who underwent double Y-stent placement on the involved carina between the right upper lobe bronchus and the bronchus intermedius as well as on the involved main carina as a unit. The procedure provided successful palliation., (Copyright 2009 S. Karger AG, Basel.)

Paclitaxel (PTX) is one of the most important breast cancer treatment drugs. However, severe hypersensitivity reactions such as decreases in blood pressure and impaired breathing occur with high frequency. For the prevention of such hypersensitivity reactions, administration of a premedication composed of three components, diphenhydramine, ranitidine (or famotidine), and dexamethasone, has been advised in package insert information of medicine. Administration of diphenhydramine is difficult in breast cancer patients complicated with closed-angle glaucoma, because diphenhydramine has a weak anticholinergic adverse effect which can induce mydriasis and glaucoma attack. We studied the prevention of severe hypersensitivity reactions and of glaucoma attack in 2 breast cancer patients complicated with closed angle glaucoma at our hospital from April 2007 to March 2008. We switched from diphenhydramine to fexofenadine as the medicine to prevent hypersensitivity reactions. Hypersensitivity reactions were not observed throughout all courses in both patients, and no glaucoma attack was observed.

Background: Acquired pulmonary alveolar proteinosis (PAP) has been reclassified into autoimmune or secondary PAP according to the occurrence of serum granulocyte macrophage colony-stimulating factor autoantibody. Most patients undergo high-resolution CT (HRCT) scanning in order for physicians to make a differential diagnosis of diffuse lung diseases, but no information is available to distinguish the HRCT scan features of secondary PAP from those of autoimmune PAP. The objective of this study was to characterize the HRCT scan features of autoimmune and secondary PAP., Methods: HRCT scans of 42 patients (21 patients each in the autoimmune PAP and secondary PAP groups) were centrally collected and evaluated in a blinded manner., Results: Ground-glass opacities (GGO) were a major finding in both the autoimmune PAP and secondary PAP groups. In the secondary PAP group, GGOs typically showed a diffuse pattern (62%), whereas GGOs showed a patchy geographic pattern in the autoimmune PAP group (71%; p < 0.005). The so-called "crazy-paving" appearance and subpleural sparing were frequently seen in the autoimmune PAP group (both 71%), whereas they were less frequently seen in the secondary PAP group (14% and 33%, respectively). The involved area of GGO was even in craniocaudal distribution for the secondary PAP group, whereas it was predominant in the lower lung field compared with the upper lung field in the autoimmune PAP group (p < 0.05)., Conclusions: Typical HRCT scan findings for autoimmune PAP patients were GGO with a patchy geographic pattern, subpleural sparing, crazy-paving appearance, and predominance in the lower lung field. These findings were rather infrequent for secondary PAP patients.

Background: The aim of this study was to evaluate the diagnostic utility of endobronchial ultrasound (EBUS)-guided transbronchial biopsy (TBB) using a novel 3.4-mm thin bronchoscope and a 1.4-mm ultrasonic probe for peripheral pulmonary lesions., Methods: A total of 86 patients with suspected peripheral lesions were included in this prospective study. EBUS-TBBs were performed using a prototype 3.4-mm thin bronchoscope and a 1.4-mm radial ultrasonic probe under fluoroscopic guidance., Results: Twelve patients with endobronchial lesions within the segmental bronchi and three patients who did not return to follow-up were excluded from this analysis. Thus, a total of 71 patients with peripheral pulmonary lesions (mean size, 31.2 +/- 12.7 mm) were included in the final analysis. The mean bronchus level reached with the thin bronchoscope was 4.6 generations. Diagnostic histologic specimens were obtained in 49 of 71 patients (69%:80% for malignant lesions and 52% for benign lesions). A definitive diagnosis of malignancy for lesions > or =20 mm and lesions < 20 mm was made in 82% (31 of 38) and 67% (four of six), respectively. There were no significant complications., Conclusion: The EBUS-TBB using a 3.4-mm thin bronchoscope and a 1.4-mm radial probe is feasible, accurate, and safe for the diagnosis of peripheral pulmonary lesions.

Metal ions were determined by ESI-MS in the negative ion mode as monovalent negative ions of their aminopolycarboxylic acid (APC) complexes, e.g., [Al(cydta)](-), [Pb(Hcydta)](-), where excess amounts of the APC agents were added to sample solutions. Among several APCs studied, we chose trans-1,2-diaminocyclohexane-N,N,N',N'-tetraacetic acid (CyDTA) as the best chelating agent because of higher stabilities and higher sensitivities of the complexes. The ionization efficiency of these metal complexes was strongly affected by the presence of matrix salts, e.g., NaCl, KNO(3), and etc. Thus, a size exclusion column (Sephadex G-10) was used for the online separation of the metal-APC complexes from other matrix salts. This method was successfully applied to the quantitative analyses for total amounts of Al, Ni, Cu, Zn, and Pb in the biological certified reference materials, olive leaves (BCR-062) and plankton (BCR-414). The detection limits of the present methods for these elements were several to several ten nanomolar levels. Moreover, this approach was extended to determine ultratraces of fluoride based on the formation of the ternary complex of aluminum, fluoride and nitrilotriacetic acid (NTA), i.e., [AlF(nta)](-). Its detection limit was 10 nM and was 2 orders of magnitude better than that of a fluoride ion selective electrode method. This method was applied to determine fluoride in tap water, river water, and green tea samples.

Airway stenting using a silicone stent has become widespread for the palliation of airway stenosis. We often encounter patients with tumors involving the carina between the bronchus to the right upper lobe and bronchus intermedius. However, there has not been ideal stenting for such cases, especially to maintain the patency of the right upper lobe bronchus. We report three cases of malignant disease inserted with a Y-stent so that the bronchial limbs of the stent saddle the involved carina between the bronchus to the right upper lobe and bronchus intermedius. The respiratory symptoms improved immediately after the procedure.

As a combination of medical information and Telecommunication technologies, telemedicine plays a more and more important role in supporting doctors to diagnose and taking care of people's daily health. It is also an appropriate means to solve the conflict between aging of population and inadequacy of doctors, which are the actual condition and inevitable developing trend of the society not only in developed countries. In this paper, some new functions are developed for a ICU/CCU Remote Monitoring System using a 3G mobile phone. Furthermore, some evaluations of the system have been implied on several different mobile phones. The system is anticipated to be adopted by hospitals for its accuracy and real-time performance to supporting telediagnosis for patients in ICU/CCU.

Telemedicine systems have become an important supporting for the medical staffs. As the development of the mobile phones, it is possible to apply the mobile phones to be a part of telemedicine systems. We developed an innovative Remote Patient Monitoring System using a Java-enabled 3G mobile phone. By using this system, doctors can monitor the vital biosignals of patients in ICU/CCU, such as ECG, RESP, SpO2, EtCO2 and so on by using the real-time waveform and data monitoring and list trend data monitoring functions of installed Java jiglet application on the mobile phone. Futhermore, doctors can check the patients' information by using the patient information checking function. The 3G mobile phone used has the ability to implement the application as the same time as being used to mak a voice call. Therefore, the doctor can get more and more information both from the browsing the screen of the mobile phone and the communicating with the medical staffs who are beside the patients and the monitors. The system can be conducted to evaluate the diagnostic accuracy, efficiency, and safety of telediagnosis.

We report two cases of mature mediastinal teratoma complaining of sudden chest pain. Both cases had cystic lesions, multilocular and unilocular, and pleural effusion. One case had fat density by CT and MRI and calcification was not recognized in either case. Surgical resection of the tumor revealed pancreatic tissue in both cases, suggesting that pancreatic enzymes might have led to the rupture of the tumor. The diagnosis of teratoma and its rupture should be considered in the cases of cystic lesion in mediastinal with sudden onset of chest pain.

A remote patient monitoring system is described. This system is to monitor information of multiple patients in ICU/CCU via 3G mobile phones. Conventionally, various patient information, such as vital signs, is collected and stored on patient information systems. In proposed system, the patient information is recollected by remote information server, and transported to mobile phones. The server is worked as a gateway between hospital intranet and public networks. Provided information from the server consists of graphs and text data. Doctors can browse patient's information on their mobile phones via the server. A custom Java application software is used to browse these data. In this study, the information server and Java application are developed, and communication between the server and mobile phone in model environment is confirmed. To apply this system to practical products of patient information systems is future work.

Because MDCT use narrow cone beam x-ray, to quantitatively evaluate cone beam artifact and helical artifact is very important with different x-ray beam width (detector configuration) . The both effect (helical artifact and cone beam artifact) was confirmed on the MDCT helical scan. It does not have cone beam artifact in the Isocenter or using center detector row for conventional scan, but helical artifact basically does not depend position of x-y plane. From quantitative evaluation of cone beam artifact, helical scan has fewer cone beam artifact than conventional scan on the 200 mm position of x-y plane: the cone beam artifact index is 11.76 (8 x 2.5mm conventional scan with most edge detector row) , 6.86 (8 x 2.5mm helical pitch 0.625) and 4.9 (8 x 2.5mm helical pitch 1.675). From phantom experiment, it was concluded that cone beam angle more contribute cone beam artifact than increasing slice numbers. And it was concluded that helical scan has fewer cone beam artifact than conventional scan, because helical scan use multi detector row information and special recon algorithm with cone beam correction on the GE LightSpeed MDCT scanner.

Fluoroacetate dehalogenase from Moraxella sp. B (FAc-DEX) catalyzes cleavage of the carbon-fluorine bond of fluoroacetate, whose dissociation energy is among the highest found in natural products. Asp105 functions as the catalytic nucleophile that attacks the alpha-carbon atom of the substrate to displace the fluorine atom. In spite of the essential role of Asp105, we found that site-directed mutagenesis to replace Asp105 by Asn does not result in total inactivation of the enzyme. The activity of the mutant enzyme increased in a time- and temperature-dependent manner. We analyzed the enzyme by ion-spray mass spectrometry and found that the reactivation was caused by the hydrolytic deamidation of Asn105 to generate the wild-type enzyme. Unlike Asn10 of the l-2-haloacid dehalogenase (L-DEX YL) D10N mutant, Asn105 of the fluoroacetate dehalogenase D105N mutant did not function as a nucleophile to catalyze the dehalogenation.

l-2-Haloacid dehalogenase from Pseudomonas sp. YL catalyzes the hydrolytic dehalogenation, in which Asp(10) acts as a nucleophile to attack the alpha-carbon of l-2-haloalkanoates to form an ester intermediate, which is subsequently hydrolyzed to produce d-2-hydroxyalkanoates. Surprisingly, replacement of the catalytic residue, Asp(10), by Asn did not result in total inactivation of the enzyme (Kurihara, T., Liu, J.-Q., Nardi-Dei, V., Koshikawa, H., Esaki, N., and Soda, K. (1995) J. Biochem. 117, 1317-1322). In this study, we monitored the D10N mutant enzyme reaction by ion-spray mass spectrometry, and found that the enzyme shows a unique structural change when it was incubated with the substrate, l-2-chloropropionate. LC/MS and tandem MS/MS analyses revealed that Asn(10) attacks the substrate to form an imidate, and a proton and d-lactic acid are eliminated to produce a nitrile (beta-cyanoalanine residue), followed by hydrolysis to reproduce Asn(10). This is the first report of the function of Asn to catalyze nucleophilic substitution through its conversion to beta-cyanoalanine residue as an intermediate structure. Also, these results demonstrate that mass spectrometry is remarkably useful in monitoring enzyme reactions.

The adiabatic elastic constants ( C(ij)) of cristobalite have been evaluated successfully over the temperature range of 300-1800 K using the molecular-dynamics method with a fluctuation formula. Cristobalite shows a negative Poisson ratio over this temperature range. However, the mechanisms differ between the alpha and beta phases. In the cubic beta phase, C44 exhibits a value extremely close to C11 rather than C12, in contrast to the Cauchy relation. This predicts a remarkable property that the longitudinal and transverse velocities coincide for the acoustic waves propagating along the [100] direction.

This study was undertaken to evaluate the potential of HMG-CoA reductase inhibitors, pravastatin sodium (hereafter abbreviated to pravastatin) and simvastatin, for induction of myopathy and influence on the ubiquinone content of skeletal and cardiac muscles and other tissues in the rabbit. Both drugs were administered orally to New Zealand White rabbits (n = 5) at the dose of 50 mg/kg per day for 14 days. Serum cholesterol levels in the pravastatin- and simvastatin-treated groups were reduced significantly by 47% an 58% on day 14 (P < 0.05), respectively, as compared with the control group, but the difference between the two treatment groups was not significant. In animals of the simvastatin-treated group, abnormal elevations of creatine kinase (CK) and lactate dehydrogenase (LDH) levels were observed, in association with severe lesions in skeletal muscles, but not cardiac muscle. The ubiquinone content in skeletal muscle in this treatment group was not affected, even in the muscles that had severe lesions, whereas that in liver and cardiac muscle was significantly reduced compared with the control group. The results suggest that there is no direct correlation between myopathy and the decrease of ubiquinone content in skeletal muscles. In contrast, the animals in the pravastatin-treated group did not show any changes in CK and LDH levels, ubiquinone content in liver and muscles, or in histopathological features of muscle fibers. The difference between the adverse effects seen with the two drugs could be attributed to physicochemical properties: simvastatin permeates the plasma membrane because of its hydrophobic nature, whereas pravastatin does not, because it is hydrophilic.

A case of Nelson's syndrome with an adrenocorticotropic hormone-secreting pituitary chromophobe microadenoma is presented to demonstrate the potential capability of rapid sequential (dynamic) computerized tomography (CT) scanning for the diagnosis of a pituitary microadenoma that was isodense with the adjacent pituitary gland on conventional enhanced CT scanning. The dynamic CT scans showed transient high density in this microadenoma contrasting with the pituitary gland in the early-enhancement phase, and thereafter the contrast density was indistinguishable from that of the pituitary gland in the delayed-enhancement phase. For the detection of pituitary microadenoma, dynamic CT combined with subsequent delayed CT scanning can provide diagnostic and localizing information.

Nine cases with hyponatremia were precisely examined during the past 2 years. Seven of them showed normal plasma volume, serum aldosterone and pituitary function, although ADH was detected. Therefore, those seven cases were diagnosed without dilutional hyponatremia due to SIADH (a syndrome of inappropriate secretion of antidiuretic hormone). The mechanism of hyponatremia of such a type has not been yet explained definitely, but it may be referring to excess natriuresis. Only each one case of hyponatremia due to hypopituitarism and dilutional hyponatremia due to SIADH was verified in this series. SIADH showing high plasma volume value was thought to be rare. Differential diagnosis between SIADH and hyponatremia due to excess natriuresis is essential and simple. Non-invasive plasma volume measurement using RISA is significantly useful for it. For the hyponatremia due to excess natriuresis, water restriction is not necessary, but digestive supply of NaCl is needed.

The present study was designed to induce plateau waves by electrical stimulation of the brain stem and examine the changes in EEG during the plateau waves. Experiments were carried out on 10 adult mongrel dogs which were slightly anesthetized, immobilized and artificially respired. Electroencephalogram (EEG), intracranial pressure (ICP), systemic blood pressure (SBP) and cerebral perfusion pressure were simultaneously recorded on the electromagnetic tape after transorbital puncture of the intracavernous internal carotid artery. EEGs were recorded from cortical electrodes, and were analyzed by a frequency analysis. At the stage of increased ICP, the mesencephalic reticular formation was stimulated. Stimulation parameters, i.e., intensity, duration and frequency, were 0.1 mA, 1 msec and 40 - 50 Hz, respectively. The total duration of each period was 5 seconds. Spontaneous plateau waves occurred in 2 dogs associated with subarachnoid hemorrhage, subdural hematoma and intraventricular hemorrhage. Plateau waves were induced by electrical stimulation in the mesencephalic reticular formation in one of two dogs with spontaneous plateau waves. Twenty-one repetitions of electrical stimulation induced ten plateau waves. Two plateau waves were induced during slow EEG associated with desynchronization of EEG. Eight plateau waves were induced during fast EEG activity with no changes in EEG before and after the stimulation. In addition, plateau waves occurred immediately after short duration (5 seconds) of electrical stimulation. It seems that CBV increases during plateau waves are due to rapidly occurring neurogenic vasodilatation of cerebral vessels, later augmented by increases in cerebral metabolism. In conclusion, plateau waves are produced in a rigid condition within the cranial cavity by stimulation of the brainstem reticular formation which influences cortical activation and cerebral vasodilatation.

The intrathecal administration of amikacin (AMK) (50--100 mg/day) was effective for 3 cases of postoperative refractory meningitis caused by gentamicin (GM) resistant organisms. The infecting pathogen of case 1 was K. pneumoniae and that of case 2 was S. epidermidis, while no pathogen was cultured in case 3. The causative pathogens in the former were eradicated only with AMK. No therapeutic response was gained with GM, but with AMK in the latter. High tone hearing impairment was observed in case 1 and transient vomiting was observed in case 3. However, these side effects were trivial for the severity of disease. It is suggested in these 3 cases that the high dose intrathecal administration of AMK may be extremely useful in the treatment of postoperative refractory meningitis which has shown no response to GM.

Discussed is an 8-year-old girl with a history of convulsive seizures. A sharply demarcated tumor, measuring 3 X 4 cm, was located in the right frontal lobe. The mass grey and cystic in the center, and microscopic specimen demonstrated bizarre, irregular, giant cell with a long vesicular nuclei and spindle-shaped cell. A perivascular pseudo-rosette formation also was seen, and silver impregnation revealed reticulin network and extracellular collagen fibers. The pathological entity of an intracranial giant celled glioblastoma remains controversial. This entity is considered a giant celled glioblastoma by some and a monstrocellular sarcoma by others. In this that the authors experienced, a CT scan showed a ring that formed a high density area and low density in the center at the right frontal lobe. Also reviewed and discussed are the historical aspects of a giant celled glioblastoma and radiologic problems that have been encountered.

A 76-year-old female developed depression and loss of appetite. On admission, in June of 1987, she was disoriented. Computed tomography (CT) revealed enhanced masses without perifocal edema in the cerebellar vermis and left occipital lobe. The cerebellar tumor was subtotally removed through a suboccipital craniectomy. Histological examination disclosed malignant lymphoma of the diffuse, large cell type. The patient underwent postoperative irradiation, and no other tumors were detected by whole-body CT or gallium scans. Her 51-year-old son had been admitted to another hospital in April of 1987, with complaints of depression and change in mental status. Neurological examination revealed right hemiparesis, and CT demonstrated an enhanced left frontal paraventricular mass and severe perifocal edema. The histological diagnosis was malignant lymphoma, and the patient received postoperative irradiation and chemotherapy. A few cases of familial extracranial malignant lymphoma have been described. However, to the authors' knowledge, this is the first reported occurrence of familial primary intracranial malignant lymphoma.

Neurogenic mechanisms of pressure waves were investigated by means of electrical stimulation of the upper pons and the lower midbrain of 32 dogs in which subarachnoid hemorrhage had experimentally been made. The dogs were slightly anesthetized, immobilized and artificially respired. After subarachnoid infusion of red blood cells, continuous recordings of systemic blood pressure (SBP), intracranial pressure (ICP) and cerebral perfusion pressure (CPP) were made simultaneously. At the stage of increased ICP, pressure waves were induced by electrical stimulation of the upper pons and the lower midbrain from 6 to 12 mm rostral to external auditory meatus. Stimulation parameters, i.e., intensity, duration and frequency, were kept constant at 0.1 mA, 1 msec and 40-50 Hz, respectively, throughout experiments. The induced pressure waves were classified into three types: fast, slow and plateau waves. Fast waves had a duration of 10-30 sec, being associated with a marked increase in SBP. They were induced by stimulation of 41 points in various portions of the pontine and mesencephalic tegmentum. Slow waves had a duration of 30 sec to 3 min, being associated with no change or a decrease in SBP. They were induced by stimulation of 12 points in the rostral pontine reticular formation and the mesencephalic reticular formation. Plateau waves had a duration of 3 min or more, being associated with no change or a decrease in SBP. They were induced by stimulation of 2 points in the mesencephalic reticular formation 2 mm lateral to the red nucleus, where slow waves had been induced at the early stage.(ABSTRACT TRUNCATED AT 250 WORDS)

A patient having glioblastoma accompanied with calcification in the cervical spinal cord is presented. A calcifying lesion, detected on preoperative x-ray computed tomograms, was histologically confirmed as calcified areas in the tumor tissue. We discuss the difficulty in differentiating glioblastomas containing calcified masses from benign tumors with areas of calcification and present our hypothesis regarding the cause of calcification in the tumor tissue.