Pneumoconiosis with a Sarcoid-Like Reaction Other than Beryllium Exposure: A Case Report and Literature Review.

Background: Chronic beryllium disease (CBD) is a granulomatous disease that resembles sarcoidosis but is caused by beryllium. Clinical manifestations similar to those observed in CBD have occasionally been reported in exposure to dusts of other metals. However, reports describing the clinical, radiographic, and pathological findings in conditions other than beryllium-induced granulomatous lung diseases, and detailed information on mineralogical analyses of metal dusts, are limited. Case presentation: A 51-year-old Japanese man with rapidly progressing nodular shadows on chest radiography, and a 10-year occupation history of underground construction without beryllium exposure, was referred to our hospital. High-resolution computed tomography showed well-defined multiple centrilobular and perilobular nodules, and thickening of the intralobular septa in the middle and lower zones of both lungs. No extrathoracic manifestations were observed. Pathologically, the lung specimens showed 5-12 mm nodules with dust deposition and several non-necrotizing granulomas along the lymphatic routes. X-ray analytical electron microscopy of the same specimens revealed aluminum, iron, titanium, and silica deposition in the lung tissues. The patient stopped smoking and changed his occupation to avoid further dust exposure; the chest radiography shadows decreased 5 years later. Conclusion: The radiological appearances of CBD and sarcoidosis are similar, although mediastinal or hilar lymphadenopathy is less common in CBD and is usually seen in the presence of parenchymal opacities. Extrathoracic manifestations are also rare. Despite limited evidence, these findings are similar to those observed in pneumoconiosis with a sarcoid-like reaction due to exposure to dust other than of beryllium. Aluminum is frequently detected in patients with pneumoconiosis with a sarcoid-like reaction and is listed as an inorganic agent in the etiology of sarcoidosis. It was also detected in our patient and may have contributed to the etiology. Additionally, our case suggests that cessation of dust exposure may contribute to improvement under the aforementioned conditions.

Transbronchial Invasion and Proliferation of Leptospira interrogans in Lung without Inflammatory Cell Infiltration in a Hamster Model.

Leptospirosis caused by pathogenic Leptospira is one of the most common zoonoses in the world. It is believed that humans become infected with it mainly through their skin and mucous membranes by contact with water or soil that is contaminated with urine excreted from infected animals. Recently, outbreaks have frequently occurred in the tropics, especially after flooding, but how leptospires cause mass infection remains poorly understood. In this study, we injected leptospires into the tracheas of hamsters under direct view and prove for the first time that leptospires can infect through the respiratory tract. We determined that a 50% lethal dose (LD50) of the Leptospira interrogans strain UP-MMC-SM (L495) for hamsters in transtracheal infection was 3.2 × 102 cells. The results of culture, macroscopic findings, and histopathological analysis suggested that intratracheally injected leptospires invaded the lung tissue, proliferated in the collagen-rich stroma adjacent to the bronchus and blood vessels, and then spread throughout the body via the bloodstream. In the lung, leptospires continuously infiltrated the alveolar wall without inflammatory cell infiltration, spread throughout the lung, and finally caused pulmonary hemorrhage. Our results revealed that the respiratory tract might be a portal of entry for leptospires. We speculate that some cases of leptospirosis might be caused by transbronchial infection from inhaling infectious aerosols containing leptospires during floods. Leptospira was also confirmed to be a unique pathogen that invades through the bronchus, proliferates in the collagen-rich lung stroma, and spreads through the alveolar interstitium throughout the lung without causing pneumonia.

Molecular and phenotypic characterization of Leptospira johnsonii sp. nov., Leptospira ellinghausenii sp. nov. and Leptospira ryugenii sp. nov. isolated from soil and water in Japan.

In a previous study, 50 of 132 soil samples collected throughout Japan were found to be Leptospira-positive. In the present study, three strains identified in the collected specimens, three, E8, E18 and YH101, were found to be divergent from previously described Leptospira species according to 16S ribosomal RNA gene sequence analysis. These three strains have a helical shape similar to that of typical Leptospira and were not re-isolated from experimental mice inoculated with the cultured strains. Upon 16S ribosomal RNA gene sequence analysis, E8 was found to belong to the intermediate Leptospira species clade and E18 and YH101 to belong to the saprophytic Leptospira species clade. Based on analyses of genome-to-genome distances and average nucleotide identity in silico using whole genome sequences and DNA-DNA hybridization in vitro, these isolates were found to be distinct from previously described Leptospira species. Therefore, these three isolates represent novel species of the genus Leptospira for which the names Leptospira johnsonii sp. nov., (type strain E8 T , = JCM 32515 T = CIP111620 T ), Leptospira ellinghausenii sp. nov., (type strain E18 T , = JCM 32516 T = CIP111618 T ) and Leptospira ryugenii sp. nov., (type strain YH101 T , = JCM 32518 T = CIP111617 T ) are proposed.

Decreased ciliary beat responsiveness to acetylcholine in the nasal polyp epithelium.

OBJECTIVE: We investigated the difference in ciliary beat responsiveness to acetylcholine in ex vivo and the difference in the expressions of associated molecules (M1/M3 muscarinic receptors, pannexin-1 and P2X7 purinergic receptor) between the nasal polyp and turbinate mucosa. STUDY DESIGN: Laboratorial study. PARTICIPANTS: Nasal polyp and inferior turbinate were collected from patients with hypertrophic rhinitis and/or nasal polyp during endoscopic sinonasal surgery. MAIN OUTCOME MEASURES: The mucosa was cut into thin strips, and ciliary movement was observed under a phase-contrast light microscope equipped with a high-speed digital video camera. The samples were also examined by scanning electron microscopy, fluorescence immunohistochemistry, and quantitative reverse transcription-polymerase chain reaction. RESULTS: Cilia were well preserved in both tissues at the ultrastructural level. The baseline ciliary beat frequency (CBF) was not different between the two tissues. The CBF of the turbinate was significantly increased by stimulation with acetylcholine (P < 0.001), but that of the polyp was not. The ratio of the acetylcholine-stimulated CBF to the baseline CBF was significantly lower in the polyp than in the turbinate (P < 0.001). Immunohistochemical study revealed that immunoreactivities for M3, pannexin-1 and P2X7 were weaker in the polyp than in the turbinate. The mRNA expressions of M1, M3 and P2X7 were significantly lower and that of pannexin-1 tended to be lower in the polyp than in the turbinate. CONCLUSIONS: These results indicate that ciliary beat responsiveness to acetylcholine is decreased in the nasal polyp. This may be explained by the decreased expressions of M3, P2X7 and probably pannexin-1 in this tissue.

Hard Metal Lung Disease with Favorable Response to Corticosteroid Treatment: A Case Report and Literature Review.

Hard metal lung disease (HMLD) is a pneumoconiosis caused by occupational exposure to hard metals such as tungsten carbide and cobalt, but the treatment strategies for HMLD have not been well established. A 68-year-old Japanese man with occupational history as a grinder of hard metals for 18 years referred to our hospital because of dry cough and dyspnea. A chest computed tomography (CT) on admission revealed centrilobular micronodules, ground-glass opacities, and reticular opacities in the peripheral zone of both lungs. Mineralogic analyses of lung tissues detected components of hard metals, such as tungsten, titanium and iron, and the same metals were also detected in the sample of the dust of his workplace. Thus, the patient was diagnosed as having HMLD based on occupational exposure history and radiologic and mineralogic analyses of the lung. Corticosteroid therapy was initiated, which resulted in partial improvements in his symptoms, radiological and pulmonary functional findings. In a review of the 18 case reports of HMLD treated with corticosteroids, including our case, the majority of patients (77.8%) showed favorable responses to corticosteroid treatment. Furthermore, the presence of fibrotic changes, such as reticular opacity, in radiological examinations was associated with the resistance to corticosteroids. In conclusion, the majority of patients with HMLD are expected to favorable response to corticosteroid treatment, whereas chest CT findings such as fibrotic changes may be predictive of the resistance of corticosteroid treatment. Lastly, proper prevention of hard metal exposure is most important as the first step.

Acetylcholine-induced Ciliary Beat of the Human Nasal Mucosa Is Regulated by the Pannexin-1 Channel and Purinergic P2X Receptor.

Background Airway mucociliary transport is an important function for the clearance of inhaled foreign particulates in the respiratory tract. The present study aimed at investigating the regulatory mechanism of acetylcholine (Ach)-induced ciliary beat of the human nasal mucosa in ex vivo. Methods The inferior turbinate mucosa was collected from patients with chronic hypertrophic rhinitis during endoscopic surgery. The mucosa was cut into thin strips, and ciliary movement was observed under a phase-contrast light microscope with a high-speed digital video camera. The sample was alternatively subjected to scanning electron microscopic observation. Results Cilia on the turbinate epithelium were well preserved at the ultrastructural level. The baseline ciliary beat frequency (CBF) was 6.45 ± 0.32 Hz. CBF was significantly increased by stimulation with 100 µM Ach and 100 µM adenosine triphosphate. The Ach-induced CBF increase was completely inhibited by removing extracellular Ca2+. Significant inhibition of the Ach-induced CBF was also observed by the addition of 1 µM atropine, 40 µM 2-aminoethoxydiphenyl borate (inositol trisphosphate [IP3] receptor antagonist), 10 µM carbenoxolone (pannexin-1 blocker), 1 mM probenecid (pannexin-1 blocker), 100 µM pyridoxalphosphate-6-azophenyl-20,40-disulfonic acid (P2X antagonist), and 300 µM flufenamic acid (connexin blocker). Meanwhile, 30 nM bafilomycin A1 (vesicular transport inhibitor) did not inhibit the Ach-induced CBF increase. CONCLUSIONS: These results indicate that the regulatory mechanism of the Ach-induced ciliary beat is dependent on extracellular Ca2+ and involves the muscarinic Ach receptor, IP3 receptor, pannexin-1 channel, purinergic P2X receptor, and connexin channel. We proposed a tentative intracellular signaling pathway of the Ach-induced ciliary beat, in which the pannexin-1-P2X unit may play a central role in ciliary beat regulation.

Dental Technicians' Pneumoconiosis.

A 40-year-old female dental technician visited our hospital for the investigation of a chest X-ray abnormality. Chest computed tomography demonstrated centrilobular nodules and lung volume reduction, and her serum KL-6 level was elevated. A histological analysis of the specimens obtained on a surgical lung biopsy showed peribronchiolar fibrosis with pigmented macrophages and cholesterol clefts. An energy-dispersive X-ray analysis showed that these lung tissues contained some metals, including indium. The serum indium level was also elevated. We diagnosed this patient with pneumoconiosis caused by exposure to sandblasting certain dental metals. This is the first reported case of pneumoconiosis in a dental technician associated with exposure to indium.

Intratracheal administration of fullerene nanoparticles activates splenic CD11b+ cells.

Fullerene nanoparticles ("Fullerenes"), which are now widely used materials in daily life, have been demonstrated to induce elevated pulmonary inflammation in several animal models; however, the effects of fullerenes on the immune system are not fully understood. In the present study, mice received fullerenes intratracheally and were sacrificed at days 1, 6 and 42. Mice that received fullerenes exhibited increased proliferation of splenocytes and increased splenic production of IL-2 and TNF-α. Changes in the spleen in response to fullerene treatment occurred at different time-points than in the lung tissue. Furthermore, fullerenes induced CDK2 expression and activated NF-κB and NFAT in splenocytes at 6 days post-administration. Finally, CD11b(+) cells were demonstrated to function as responder cells to fullerene administration in the splenic inflammatory process. Taken together, in addition to the effects on pulmonary responses, fullerenes also modulate the immune system.

Morphological study of fragmented DNA on touched objects.

In recent years, forensic scientists showed that an individual's genetic profile can be retrieved from touched objects. Degraded DNA is believed to originate from epidermal cells and to be responsible for this phenomenon, yet the mechanism has not been confirmed. In the present study, we carried out a morphological and immunohistochemical investigation of nuclear DNA in differentiating keratinocytes in the skin and also a genetic analysis of DNA on swabs of human skin. Immunoelectron microscope analysis showed that single-stranded DNA was found both in the cornified layer of the skin and in swabs. Real-time-PCR assay proved that the DNA in the swabs was derived from the human DNA. Electron microscopic analysis of shadow-cast showed the presence of small DNA fragments in the swabs. It is conceivable that these DNA fragments on touched objects may originate from the epidermal cells of the cornified layer that are constantly sloughed off and leave for skin surface with sweat.

Finite-difference time-domain simulation of two-dimensional photonic crystal surface-emitting laser.

Using the three-dimensional (3D) finite-difference time-domain (FDTD) method, we have investigated in detail the optical properties of a two-dimensional (2D) photonic crystal (PC) surface-emitting laser having a square-lattice structure. In this study we perform the 3D-FDTD calculation for the structure of an actual fabricated device. The device is based on bandedge resonance, and four band edges are present at the corresponding band edge point. For these band edges, we calculate the quality (Q) factor. The results show that the Q factor of a resonant mode labeled A1 is larger than that of other resonant modes; that is, lasing occurs easily in mode A1. The device can thus achieve single-mode lasing oscillation. To increase the Q factor, we also consider the optimization of device parameters. The results provide important guidelines for device fabrication.

[Treatment of tracheobronchial malignant tumors using a new high power diode contact laser (GaAlAs) system].

We treated ten patients with tracheobronchial malignant tumors using a new high power diode contact laser (GaAlAs) system (DIOMED 25, OLYMPUS) with a flexible bronchofiberscope (OLYMPUS BF IT200 or BF IT240). The total energy of the high power diode laser was 811 J, with a range of 64-3,960 J. With this method 85.7 percent of the symptoms such as dyspnea and hemoptysis were improved, and there was no incidence of massive hemorrhage or serious respiratory failure. The results confirmed the usefulness and safety of this method of treatment for obstructive lesions due to tracheobronchial polypoid malignant tumor and bleeding of the tracheobronchial tree.