A case of ROS1-rearranged lung adenocarcinoma with osteoblastic bone metastasis.

A 53-year-old woman was referred to our hospital for detailed examination of abnormal chest shadows recognized on CT imaging. Transbronchial lung biopsy of a right S6 nodular shadow led to a diagnosis of lung adenocarcinoma. FDG-PET-CT showed FDG accumulation in the Th11 and L2 vertebral bodies and osteoblastic bone lesions.

Trafficking of newly synthesized surfactant protein B to the lamellar body in alveolar type II cells.

Lung surfactant accumulates in the lamellar body (LB) via not only the secretory (anterograde) pathway but also the endocytic (retrograde) pathway. Our previous studies suggested that the major surfactant components, phosphatidylcholine and surfactant protein A take independent trafficking routes in alveolar type II cells. Thus, trafficking of surfactant protein B (SP-B), a major hydrophobic surfactant apoprotein, should be re-evaluated by a straightforward method.

Mutation and the Lung Phenotype.

is highly expressed in alveolar type II cells, melanocytes, and platelets. These cells are specifically-differentiated cells and contain characteristic intracellular organelles called lysosome-related organelles, i.e.

ADRB2 gene polymorphism and emphysema heterogeneity can modulate bronchodilator response in patients with emphysema.

Background: Genetic variation in the β-adrenergic receptor (ADRB2) gene has been thought to have an important role in the differential response to β-agonist therapy for asthma. However, previous studies have shown little evidence for an association between these ADRB2 variants and the bronchial dilator response (BDR) in chronic obstructive pulmonary disease (COPD) patients. This discrepancy could be explained by differences in the distribution and heterogeneity of pulmonary emphysema in COPD patients, since emphysema distribution and heterogeneity are thought to have a role in pulmonary function in COPD patients.

Exogenous gene transfer of Rab8 small GTPase ameliorates aberrant lung surfactant homeostasis in Ruby rats.

Background: Rab8 small GTPase regulates intracellular transport in melanocytes and alveolar type II epithelial cells. Ruby rats carrying Rab8 and other gene mutations exhibit oculocutaneous albinism, bleeding diathesis, and hence, are a rat model of human Hermansky-Pudlak syndrome (HPS). We previously showed that Long Evans Cinnamon (LEC) rats, one strain of the Ruby rats, developed aberrant lung surfactant homeostasis with remarkably enlarged lamellar bodies in alveolar type II cells.

p53 Signaling Pathway Polymorphisms Associated With Emphysematous Changes in Patients With COPD.

Background: The p53 signaling pathway may be important for the pathogenesis of emphysematous changes in the lungs of smokers. Polymorphism of p53 at codon 72 is known to affect apoptotic effector proteins, and the polymorphism of mouse double minute 2 homolog (MDM2) single nucleotide polymorphism (SNP)309 is known to increase MDM2 expression. The aim of this study was to assess polymorphisms of the p53 and MDM2 genes in smokers and confirm the role of SNPs in these genes in the pathogenesis of pulmonary emphysema.

Sirt1 expression is associated with CD31 expression in blood cells from patients with chronic obstructive pulmonary disease.

Background: Cigarette smoke induced oxidative stress has been shown to reduce silent information regulator 1 (Sirt1) levels in lung tissue from smokers and patients with COPD patients. Sirt1 is known to inhibit endothelial senescence and may play a protective role in vascular cells. Endothelial progenitor cells (EPCs) are mobilized into circulation under various pathophysiological conditions, and are thought to play an important role in tissue repair in chronic obstructive lung disease (COPD).

Lentiviral vector-mediated delivery of lysophosphatidylcholine acyltransferase 1 attenuates airway inflammation in ovalbumin-induced allergic asthmatic mice.

Background: Lysophosphatidylcholine (LPC) is generated through the hydrolysis of phospha-tidylcholine (PC) by phospholipase A2 and is converted back to PC by lysophosphatidylcholine acyltransferase 1 (LPCAT1). Elevated levels of (LPC) are known to play a pathogenic role in the inflammatory injury of asthma. However, the role of LPCAT1 in asthma has not yet been reported.

Adenovector-mediated gene transfer of lysophosphatidylcholine acyltransferase 1 attenuates oleic acid-induced acute lung injury in rats.

Objective: Lysophosphatidylcholine is generated through the hydrolysis of phosphatidylcholine by phospholipase A2 and reversely converted to phosphatidylcholine by lysophosphatidylcholine acyltransferase 1. Although lysophosphatidylcholine is a potent proinflammatory mediator and increased in several types of acute lung injuries, the role of lysophosphatidylcholine acyltransferase 1 has not yet been addressed. We aimed to investigate whether the exogenous expression of lysophosphatidylcholine acyltransferase 1 could attenuate acute lung injury.

A three-microphone acoustic reflection technique using transmitted acoustic waves in the airway.

The acoustic reflection technique noninvasively measures airway cross-sectional area vs. distance functions and uses a wave tube with a constant cross-sectional area to separate incidental and reflected waves introduced into the mouth or nostril. The accuracy of estimated cross-sectional areas gets worse in the deeper distances due to the nature of marching algorithms, i.

[Cytokines and proteases involved in pathogenesis of COPD].

COPD is characterized by persistence of chronic inflammation in small airways and alveoli. Macrophages, neutrophils, and a specialized subset of T lymphocytes orchestrate the mild inflammation. This article focuses on humoral factors such as cytokines and chemokines that recruit these inflammatory and immune cells to the lungs, and proteases/antiproteases that ultimately cause structural derangement in the terminal respiratory zones.

Altered lung surfactant system in a Rab38-deficient rat model of Hermansky-Pudlak syndrome.

Several Long-Evans rat substrains carrying the phenotype of oculocutaneous albinism and bleeding diathesis are a rat model of Hermansky-Pudlak syndrome (HPS). The mutation responsible for the phenotype (Ruby) was identified as a point mutation in the initiation codon of Rab38 small GTPase that regulates intracellular vesicle transport. As patients with HPS often develop life-limiting interstitial pneumonia accompanied by abnormal morphology of alveolar type II cells, we investigated lung surfactant system in Long-Evans Cinnamon rats, one strain of the Ruby rats.

A mutation in Rab38 small GTPase causes abnormal lung surfactant homeostasis and aberrant alveolar structure in mice.

The chocolate mutation, which is associated with oculocutaneous albinism in mice, has been attributed to a G146T transversion in the conserved GTP/GDP-interacting domain of Rab38, a small GTPase that regulates intracellular vesicular trafficking. Rab38 displays a unique tissue-specific expression pattern with highest levels present in the lung. The purpose of this study was to characterize the effects of Rab38-G146T on lung phenotype and to investigate the molecular basis of the mutant gene product (Rab38(cht) protein).

Analysis and expression of Rab38 in oculocutaneous lung disease.

Rab38 is a low-molecular-weight G-protein highly expressed in melanocytes of the skin and alveolar type II cells in the lung. A point mutation in the postulated GTP/GDP-interacting domain of Rab38 has been identified as the genetic lesion responsible for oculocutaneous albinism (OCA) in chocolate (cht) mice. Another point mutation that prevents translation of Rab38 mRNA is the molecular basis of the Ruby gene mutation causing the phenotype of OCA and prolonged bleeding time in Fawn-Hooded and Tester-Moriyama rats.

[Case of broncholithiasis lithoptysis occurring spontaneously after repeated pneumonia].

An abnormal chest shadow was pointed out in a 56-year-old woman in a health check in 2001. She had pulmonary tuberculosis at age 11. Because of repeated fever for the previous 2 years, she visited our hospital in 2003 and right upper lobe pneumonia was detected with a calcified nodule that completely obstructed the right upper lobe bronchus on CT.

Melanocyte differentiation antigen RAB38/NY-MEL-1 induces frequent antibody responses exclusively in melanoma patients.

Expression pattern and immunogenicity are critical issues that define tumor antigens as diagnostic markers and potential targets for immunotherapy. The development of SEREX (serological analysis of recombinant expression libraries) has provided substantial progress in the identification of tumor antigens eliciting both cellular and humoral immune responses in cancer patients. By SEREX, we have previously identified RAB38/NY-MEL-1 as a melanocyte differentiation antigen that is highly expressed in normal melanocytes and melanoma tissues but not in other normal tissues or cancer types.

Stimulation of alveolar epithelial fluid clearance in human lungs by exogenous epinephrine.

Objectives: Because several experimental studies have demonstrated that cyclic adenosine monophosphate generation following beta-adrenoceptor activation can markedly stimulate alveolar fluid clearance, we determined whether the endogenous levels of catecholamines that occur in the pulmonary edema fluid and plasma of patients with acute lung injury are high enough to stimulate alveolar fluid clearance in the human lung.

Design: Observational clinical study.

Setting: Academic university hospital and laboratory.

Pulmonary surfactant transport in alveolar type II cells.

Pulmonary surfactant (PS) is a mixture of several lipids (mainly phosphatidylcholine; PC) and four apoproteins (A, B, C and D). The classical hypothesis of PS transport suggests that PS is synthesized in the endoplasmic reticulum and transported to the lamellar body (LB) via the Golgi apparatus. However, recent studies have raised questions regarding this single route.

Expression and characterization of Rab38, a new member of the Rab small G protein family.

Rab38 is a new member of the Rab small G protein family that regulates intracellular vesicle trafficking. Rab38 is expressed in melanocytes and it has been clarified that a point mutation in the postulated GTP-binding domain of Rab38 is the gene responsible for oculocutaneous albinism in chocolate mice. However, basic information regarding recombinant protein production, intracellular location, and tissue-specific expression pattern has not yet been reported.

[A case of atypical pulmonary carcinoid accompanying skin metastasis].

A 73-year-old woman underwent cranial surgery in 1999 after receiving a diagnosis of suspected malignant meningioma. She began complaining of headache 2 years postoperatively, and around the same time, she noticed a painful skin tumor. She was then transferred to our hospital for further evaluation.

[Implication of oxidant stress in airway inflammation].

There are many species of oxygen radicals in the environment. Inflammatory cells also produce many oxidants in biological tissues. The lung is constantly exposed to highest content of oxygen in the body, and frequently exposed to tobacco smoke, industrially polluted air, and exhausted gas.

[An intra-pulmonary lymphnode resembling typical pulmonary primary adenocarcinoma on high-resolution computed tomographic (HR-CT) chest images].

A 40-year-old man was admitted to our hospital for further evaluation of a pulmonary nodule in chest radiographs. The 8-mm nodular lesion was located in the right anterior basal lobe on a plain chest radiograph, and showed 1) spiculation, 2) pleural indentation and 3) a converging vessel formation in high-resolution computed tomography of the chest. The radiographic findings were highly suggestive of primary pulmonary adenocarcinoma and the patient underwent video-assisted thoracoscopic surgery (VATS) to obtain a precise diagnosis.

Time-dependent effect of pneumonectomy on alveolar epithelial fluid clearance in rat lungs.

Objective: Because pneumonectomy initiates compensatory growth of the remaining lung, we determined the time-dependent effects of pneumonectomy on alveolar fluid clearance capacity.

Methods: Alveolar fluid clearance capacity with the Evans blue-labeled albumin concentration was measured in rats 3 hours, 2 days, 7 days, 14 days, and 28 days after left pneumonectomy. The mechanisms responsible for the increase in alveolar fluid clearance were explored.

[Function of lung surfactant and its deterioration].

Lung surfactant(LS) is a mixture of several lipids and four apolipoproteins(SP-A, -B, -C and -D) and lowers surface tension at air-liquid interface of alveoli. Most of LS is synthesized and secreted by alveolar type II cells. Although lamellar bodies are storage granules of LS, each component appears to take independent intracellular routes to reside in the granules.