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Radiologic diagnosis of chronic hypersensitivity pneumonitis (CHP) presenting a usual interstitial pneumonia (UIP) pattern is challenging. The aim of this study was to identify the high-resolution CT (HRCT) findings which are useful to discriminate CHP–UIP from idiopathic pulmonary fibrosis (IPF). This study included 49 patients with well-established bird-related CHP–UIP, histologically confirmed, and 49 patients with IPF. Two groups of observers independently assessed HRCT, evaluated the extent of each abnormal HRCT finding. When their radiological diagnosis was CHP–UIP, they noted the HRCT findings inconsistent with IPF. Correct CT diagnoses were made in 79% of CHP–UIP and 53% of IPF. Although no apparent difference was seen in the extent of each HRCT finding, upper or mid-lung predominance, extensive ground-glass abnormality, and profuse micronodules were more frequently pointed out as inconsistent findings in CHP–UIP than IPF (p = 0.007, 0.010, 0.001, respectively). On regression analysis, profuse micronodules [OR 13.34 (2.85–62.37); p = 0.001] and upper or mid-lung predominance of findings [OR 2.86 (1.16–7.01); p = 0.022] remained as variables in the equation. In this cohort, some IPF cases were misdiagnosed as CHP–UIP. Profuse micronodules and upper or mid-lung predominance are important clues for the differentiation of CHP–UIP from IPF.

Background Idiopathic pulmonary fibrosis (IPF) is a chronic, progressive fibrotic lung disease that leads to respiratory failure and death. Although there is a greater understanding of the etiology of this disease, accurately predicting the disease course in individual patients is still not possible. This study aimed to evaluate serum cytokines/chemokines as potential biomarkers that can predict outcomes in IPF patients. Methods A multi-institutional prospective two-stage discovery and validation design using two independent cohorts was adopted. For the discovery analysis, serum samples from 100 IPF patients and 32 healthy controls were examined using an unbiased, multiplex immunoassay of 48 cytokines/chemokines. The serum cytokine/chemokine values were compared between IPF patients and controls; the association between multiplex measurements and survival time was evaluated in IPF patients. In the validation analysis, the cytokines/chemokines identified in the discovery analysis were examined in serum samples from another 81 IPF patients to verify the ability of these cytokines/chemokines to predict survival. Immunohistochemical assessment of IPF-derived lung samples was also performed to determine where this novel biomarker is expressed. Results In the discovery cohort, 18 cytokines/chemokines were significantly elevated in sera from IPF patients compared with those from controls. Interleukin-1 receptor alpha (IL-1Rα), interleukin-8 (IL-8), macrophage inflammatory protein 1 alpha (MIP-1α), and cutaneous T-cell-attracting chemokine (CTACK) were associated with survival: IL-1Rα, hazard ratio (HR) = 1.04 per 10 units, 95% confidence interval (95% CI) 1.01–1.07; IL-8, HR = 1.04, 95% CI 1.01–1.08; MIP-1α, HR = 1.19, 95% CI 1.00–1.36; and CTACK, HR = 1.12 per 100 units, 95% CI 1.02–1.21. A replication analysis was performed only for CTACK because others were previously reported to be potential biomarkers of interstitial lung diseases. In the validation cohort, CTACK was associated with survival: HR = 1.14 per 100 units, 95% CI 1.01–1.28. Immunohistochemistry revealed the expression of CTACK and CC chemokine receptor 10 (a ligand of CTACK) in airway and type II alveolar epithelial cells of IPF patients but not in those of controls. Conclusions CTACK is a novel prognostic biomarker of IPF. Trial registration None (because of no healthcare intervention)

Oxidative stress plays a pivotal role in the pathogenesis of asthma. Aquaporin-3 (AQP3) is a small transmembrane water/glycerol channel that may facilitate the membrane uptake of hydrogen peroxide (H2O2). Here we report that AQP3 potentiates ovalbumin (OVA)-induced murine asthma by mediating both chemokine production from alveolar macrophages and T cell trafficking. AQP3 deficient (AQP3−/−) mice exhibited significantly reduced airway inflammation compared to wild-type mice. Adoptive transfer experiments showed reduced airway eosinophilic inflammation in mice receiving OVA-sensitized splenocytes from AQP3−/− mice compared with wild-type mice after OVA challenge, consistently with fewer CD4+ T cells from AQP3−/− mice migrating to the lung than from wild-type mice. Additionally, in vivo and vitro experiments indicated that AQP3 induced the production of some chemokines such as CCL24 and CCL22 through regulating the amount of cellular H2O2 in M2 polarized alveolar macrophages. These results imply a critical role of AQP3 in asthma and AQP3 may be a novel therapeutic target.

Buffalo chest refers to the pleuro-pleural communication that results in a single pleural cavity. Iatrogenic buffalo chest can occur following heart or heart-lung transplantation and other major thoracic surgeries. We present the case of malignant pleural mesothelioma in which iatrogenic buffalo chest after extended thymectomy caused bilateral pneumothoraces and contralateral dissemination of the disease. The free communication between bilateral pleural cavities had facilitated the rapid progression of tumor and the consequent bilateral malignant pleural effusions had made the management of disease much more difficult, leading to the early fatal outcome. To our knowledge, this is the first case of buffalo chest that was associated with bilateral malignant pleural effusions.

Diffuse panbronchiolitis (DPB) is a rare complex genetic disease affecting East Asians and is strongly associated with the class I human leukocyte antigens (HLA)-B54 in Japanese and HLA-A11 in Koreans. We recently showed that an HLA-associated major susceptibility gene for DPB is probably located within the 200 kb in the class I region 300 kb telomeric of the HLA-B locus on the chromosome 6p21.3. We cloned two novel mucin-like genes designated panbronchiolitis related mucin-like 1 and 2 (PBMUCL1 and PBMUCL2) in the candidate region, which form a mucin-like gene cluster together with two adjacent genes, MUC21 and DPCR1. PBMUCL1 gene expression was remarkably upregulated by polyinosine-polycytidylic acid [poly(I:C)] stimulation in normal human bronchial epithelial cells redifferentiated at the air-liquid interface. We found genetic polymorphisms in PBMUCL1 gene which were associated with DPB: the A-allele of the PBMUCL1 intron 2 single nucleotide polymorphism (SNP) was positively associated and variable numbers of tandem repeats (VNTR) polymorphism in exon 3 (1,890-base pair deletion) was negatively associated. Despite a strong association with HLA-B in the Japanese, the mucin-like gene PBMUCL1 is also one of the candidate genes of DPB susceptibility.

We have investigated the nanofabrication for glass-like carbon molds with electron cyclotron resonance oxygen ion beam etching technologies using polysiloxane [-R2SiO-]n as an electron beam mask and a room-temperature imprint resist material. The maximum etching selectivity of polysiloxane film against glass-like carbon was 27, which was obtained with ion energy of 400 eV. It was found that the optimum etching time to fabricate dots of 500 nm in height was 5 min, which was explored according to the computer simulation. The glass-like carbon molds with square pole and cylinder dots were fabricated with 500 nm in width and diameter, respectively. The optimum imprinting pressure and its depth obtained after the press for 5 min were 0.5 MPa and 0.5 μm, respectively. We carried out the room-temperature nanoimprint lithography process using glass-like carbon molds. The resulting width of imprinted polysiloxane patterns was obtained in good agreement with that of the mold.

As an application to the nanoemitter, we investigated the nanofabrication of diamond-like carbon (DLC)-dot arrays by room-temperature curing imprint-liftoff (RTCIL) method using aluminum mask. The DLC film which has excellent properties similar to diamond properties was used as the patterning material. A polished glass like carbon (GC) was used as a mold material. The polysiloxane in the state of sticky liquid at room temperature and stable in air exhibits a negative-exposure characteristics. Therefore, the polysiloxane was used as electron beam (EB) resist and oxide mask material in EB lithography, and also used as RTC-imprint resist material. An aluminum was used as oxide metal mask material of liftoff. We have fabricated the GC mold of dot arrays with 5 µm-square and 500 nm-height. We carried out the RTCIL process using the GC mold under the following optimum imprint conditions: 0.5 MPa-imprinting pressure and 5 min- holding time. Aluminum film on the imprinted polysiloxane was prepared by vacuum evaporation method and its thickness is 20 nm. Finally, the polysiloxane patterns were removed with acetone and aluminum mask patterns were fabricated. We found that the maximum etching selectivity of aluminum film against DLC film was as high as 35, which was obtained under an ion energy of 400 eV. Then we processed the patterned aluminum on DLC film with an ECR oxygen ion shower. We fabricated DLC-dot arrays with 5 µm-square and 400 nm-height with an aspect ratio of 0.08.

The fabrication of diamond-like carbon (DLC) micro-gear by room temperature curing nanoimprint lithography (RTC-NIL) using glass-like carbon (GC) molds as applications to the DLC-based medical MEMS (Micro Electronic Mechanical Systems) was investigated. The DLC film which has excellent properties similar to chemical vapor deposited (CVD) diamond films was used as the patterning material. We propose GC as mold material because GC has higher etching selectivity than a diamond film. The etching selectivity of polysiloxane film against a GC substrate is about 5 times as high as that of a diamond film. Therefore we fabricated the GC molds that have micro-gear patterns with 30 µm-tip diameter and 500 nm-tooth thickness. We carried out the RTC-NIL process using the GC micro-gear molds under the following optimum conditions. 1 min-time from spin-coating to imprint: t1, 0.5 MPa-imprinting pressure: P and 5 min-holding time: t2, and then the imprinted polysiloxane pattern on DLC film was processed with an electron cyclotron resonance (ECR) oxygen ion shower. However, we were not able to fabricate micro-gear patterns in high accuracy because of a remaining residual layer on the DLC film. Therefore we propose the removing process for the residual layer with trifluoromethane (CHF3) ion shower under the optimum conditions of 300 eV-ion energy and 4 min-etching time. As a result, we succeeded to fabricate concave DLC-based micro-gear patterns in high accuracy which has 30 µm-tip diameter and 1 µm-depth.

The microfabrication technologiesfor organic light-emitting devices (OLEDs) are essential to the fabrication of the next generation of light-emitting devices. The micro-OLEDs fabricated by room-temperature curing nanoimprint lithography (RTC-NIL) using diamond molds have been investigated. However, light emissions from 10 μm-square-dot OLEDs fabricated by the RTC-NIL method have not been uniform. Therefore, we proposed the fabrication of micro-OLEDs by room-temperature curing nanocontact-print lithography (RTC-NCL) using the diamond-like carbon (DLC) mold. The DLC molds used in RTC-NCL were fabricated by an electron cyclotron resonance (ECR) oxygen ion shower with polysiloxane oxide mask in electron beam (EB) lithography technology. The mold patterns are square and rectangle dots which has 10 µm-width, 10 µm-width and50 µm-length, respectively. The height of the patterns is 500 nm. The DLC molds were used to form the insulating layer of polysiloxane in RTC-NCL. We carried out the RTC-NCL process using the DLC mold under the following optimum conditions: 0.1 MPa-pressure for coating DLC mold with polysiloxane film, 2.1 MPa-pressure for transferring polysiloxane from DLC mold pattern to indium tin oxide (ITO) glass substrate. We deposited N, N'-Diphenyl -N, N'-di (m-tolyl)benzidine (TPD) [40 nm-thickness] as hole transport layer / Tris(8-quinolinolato)aluminum (Alq3) [40 nm-thickness] as electron transport layer / Al [200 nm-thickness] as cathode on ITO glass substrateas anode in this order. We succeeded in formation of the insulating layer with square and rectangle dots which has 10 µm-width,10 µm-width and 50 µm-length, and operation of micro-OLEDs by RTC-NIL using DLC molds.

Organic light-emitting devices (OLEDs) have attracted a lot of attention as a next generation display. In this study, we fabricated the micro-OLEDs by room-temperature curing nanoimprint lithography (RTC-NIL) using diamond molds. The diamond has superior durability and was used as mold material for RTC-NIL. The diamond molds have been fabricated by electron cyclotron resonance (ECR) oxygen ion shower with polysiloxane oxide mask in the electron beam (EB) lithography technology. We fabricated the diamond mold pattern with 10 μm-square dot. The diamond molds have been used to form an insulating layer in micro-OLEDs. The optimum thickness of N,N’-Diphenyl-N,N’-di(m-tolyl)benzidine (TPD) [hole transport layer],Tris(8-quinolinolato)aluminum (Alq3) [electron transport layer] and aluminum (Al) [cathode] were 40 nm, 40 nm and 200 nm, respectively. We succeeded in formation of insulating layer in micro-OLEDs and operation of micro-OLEDs with 10 μm-square-dot by RTC-NIL using diamond molds.

We have proposed the use of glass-like carbon (GC), as mold material because the 27-maximum etching selectivity of polysiloxane film against GC, which was approximately sixtimes larger than that of polysiloxane film against chemical vapor deposited (CVD) diamond film. We have investigated the fabrication of diamond nanopit arrays by room-temperature curing nanoimprint lithography (RTC-NIL) using GC mold, as applications to the emitter and the micro-gear. The polysiloxane has in the state of sticky liquid at room-temperature and negative-exposure characteristic. Therefore, the polysiloxane was used as RTC-imprint resist material, and also used as electron beam (EB) resist (oxide mask) material in EB lithography. We have fabricated the cylindrical GC nanodot mold with 500 nm-diameter, 600 nm-height and 2 μm-pitch. We carried out RTC-NIL using GC mold under the following optimum conditions: time from spin-coating to imprint of 1 min, imprinting pressure of 0.5 MPa and imprinting time of 5min. Then, we have processed the diamond film with an electron cyclotron resonance (ECR) oxygen ion shower. We have fabricated diamond nanopit array with 250 nm-depth and 500 nm-diameter. The diameter of diamond nanopit pattern was in good agreement with that of GC mold. Moreover, the depth of the diamond nanopit patterns fabricated by RTC-NIL using cylindrical GC mold was three times larger than that using conical diamond mold.

We have investigated the nanopatterning of chemical vapor deposited (CVD) diamond films in room-temperature nanoimprint lithography (RT-NIL), using a diamond nanodot mold. We have proposed the use of polysiloxane as an electron beam (EB) mask and RT-imprint resist materials. The diamond molds of cylinder dot using the RT-NIL process were fabricated with polysiloxane oxide mask in EB lithography technology. The dot in minimum diameter is 500 nm. The pitch between the dots is 2 μm, and dot has a height of about 600 nm. It was found that the optimum imprinting conditions for the RT-NIL : time from spin-coating to imprinting t1 of 1 min , pressure time t2 of 5 min, imprinting pressure P of 0.5 MPa. The imprint depth obtained after the press under their conditions was 500 nm. We carried out the RT-NIL process for the fabrication of diamond nanopit arrays, using the diamond nanodot molds that we developed. The resulting diamond nanopit arrays with 500 nm-diameter and 200 nm-depth after the electron cyclotron resonance (ECR) oxygen ion beam etching were fabricated. The diameter of diamond nanopit arrays was in good agreement with that of the diamond nanodot mold.

This paper reports a successful achievement of laser-induced biological cell fusion using an excimer laser excited dye laser. To our knowledge, we examined for the first time the dependence of fusion rate on laser pulse energy, number of laser pulses, and laser wavelength. Maximum fusion rate of approximately 50% was obtained by this laser fusion technology.

A novel type of laser-excited fluorescence microscope system is reported, which, for the first time, realizes excellent sensitivity and spatial resolution in biological and medical applications using an ultra-high sensitivity image camera and digital image processing technique for three-dimensional display of the detected fluorescence intensity across a single cell. Experimental studies are also presented on the fluorescence intensity distribution of Rhodamine 6G adsorbed in an OH gel as a simple cell model and also of a hematoporphyrin-derivative (HpD) taken up by a cultured esophagus cancer cell.