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Bronchiolitis obliterans syndrome (BOS) and idiopathic pneumonia syndrome (IPS) cause high mortality and impaired survival after allogeneic hematopoietic stem-cell transplantation (allo-HSCT). Early recognition of patients at high risk of developing BOS/IPS may lead to improving the outcome of allo-HSCT. We retrospectively analyzed serum surfactant protein A, D (SP-A, -D) and Kerbs von Lungren 6 Ag (KL-6) levels before allo-HSCT in 56 patients who survived more than 90 days after allo-HSCT and compared values of these serum markers and other transplant factors in BOS/IPS patients with those in non-BOS/IPS patients. Five patients developed BOS and two developed IPS at a median interval of 303 and 117 days (range, 100–452 and 95–153) from transplantation. As a result of univariate analysis, pretransplant serum SP-D levels but not SP-A, KL-6 in BOS/IPS patients were significantly lower than those in non-BOS/IPS patients (P=0.03). In multivariate analysis, the patients with lower pretransplant serum SP-D level had a trend toward frequent development of BOS/IPS (P=0.08). Constitutive serum SP-D level before allo-HSCT may be a useful, noninvasive predictor for the development of BOS/IPS.Bone Marrow Transplantation (2008) 42, 43–49; doi:10.1038/bmt.2008.73; published online 17 March 2008 [ABSTRACT FROM AUTHOR]

Idiopathic obliterative bronchiolitis (OB) is a rare disease that usually requires a surgical lung biopsy. A 25-year-old woman with progressive exertional dyspnea for several months showed a severe mixed restrictive and obstructive pattern on spirometry. Chest computed tomography showed a mosaic pattern, and pulmonary ventilation-perfusion scintigraphy showed a matched defect. The bronchoscopic specimens obtained from both the alveolar and bronchiolar regions of the predicted lesion area contributed to the diagnosis of OB. She had no underlying causes of secondary OB, and she was diagnosed with idiopathic OB. Since lung transplantation was indicated, she was referred to a lung transplantation-certified hospital.

Background: MicroRNAs (miRNAs) have been reported to be involved in multiple diseases, including chronic obstructive pulmonary disease (COPD), a progressive disease in which alveolar apoptosis may play a role. We hypothesized that miRNAs are associated with the response to injury. induced by high mobility group box 1 (HMGB1), a cytokine crucial for the development of COPD, and studied the potential link between HMGB1 and miRNAs., Materials and Methods: A549 cells were stimulated with recombinant HMGB1. RNA and protein were extracted and culture supernatants were collected. Molecules downstream of HMGB1 signaling were analyzed by reverse transcription polymerase chain reaction (RT-PCR) and enzyme-linked immunosorbent assay (ELISA). Expression levels of miRNA were analyzed by quantitative RT-PCR. Cellular injury was evaluated by western blotting of relevant proteins. Apoptosis was evaluated by in situ terminal deoxynucleotidyl transferase dUTP nick end-labeling (TUNEL)., Results: HMGB1 treatment of A549 cells resulted in the up-regulation of tumor necrosis factor (TNF)-α and macrophage inflammatory protein (MIP)-2 mRNAs and over expression of matrix metalloprotease (MMP)-7 protein in the supernatant. The miRNA miR-30c was also up-regulated in response to HMGB1 treatment. Cellular injury and apoptosis were observed following HMGB1 treatment, as demonstrated by the oyerexpression of cyclin A2 (CCNA2) and phosphatase and tensin homolog (PTEN) proteins and-b'y decreased levels of pro-caspase-7 protein. The TUNEL assay showed that A549 cells with HMGB1 stimulation underwent apoptosis., Conclusions: Up-regulation of miR-30c and apoptosis of A549 cells were observed following HMGB1 stimulation. Our model demonstrates the potential for utilization of HMGB1 and miR-30c in further studies of alveolar apoptosis in COPD.

Background: Pentraxin-3 (PTX3) is a newly discovered biomarker for various inflammatory conditions. We measured plasma PTX3 levels in patients with febrile neutropenic lung cancer and examined the utility of PTX3 levels as a biomarker for febrile neutropenia., Methods: Fourteen patients with febrile neutropenic lung cancer were enrolled in the study. In addition, 10 untreated lung cancer patients and 12 healthy adults were enrolled as a disease control group and a healthy control group, respectively. On the day of onset of febrile neutropenia (day 1) and days 3 and 7, PTX3 and C-reactive protein (CRP) levels were measured. In the control groups, PTX3 and CRP levels were measured once., Results: On day 1, plasma CRP levels in febrile neutropenia during chemotherapy or chemoradiotherapy for lung cancer (FN/LC) patients (8.11 ± 6.42 mg/dL) were significantly higher than those in healthy controls (HC) and chemotherapy/chemoradiotherapy-naïve lung cancer (CN/LC) patients (p < 0.05). However, CRP levels of the CN/LC group (0.33 ± 0.02 mg/dL) were also significantly higher than those of the HC group (0.07 ± 0.09 mg/dL) (p < 0.05). In contrast, plasma PTX3 levels of the FN/LC group (6.14 ± 5.28 ng/mL) were significantly higher than those of the HC and CN/LC groups on day 1 (p < 0.05), but PTX3 levels of the CN/LC group (1.60 ± 0.64 ng/mL) were not significantly higher than those of the HC group (1.05 ± 0.25 ng/mL). In the FN/LC group, PTX3 levels peaked immediately on day 1., Conclusions: PTX3 may be a useful biomarker for diagnosis of FN in patients with LC.

The aim of this study was to examine defect depths and volumes at the resin composite-dentin (R/D) interface after air polishing with different particles and spray angles. Samples were 54 dentin specimens that were formed in saucer-shaped cavities filled with resin composite. Each specimen was air polished with either sodium bicarbonate (NaHCO3) or one of two glycine (Gly) powders. The air polisher was set at angles of 90° to the interface and at 45° to the interface from both the dentin and resin composite sides. Air polishing with Gly powder produced defects with less depth and volume than NaHCO3 powder (p < 0.05). Air polishing with a spray angle of 45° to the interface from the resin composite side produced fewer defects (p < 0.05) than polishing from the dentin side. Air polishing to the R/D interface from the resin composite side produced fewer defects to the interface because the hardness of the resin composite was higher than that of dentin.

A 44-year-old woman had sustained facial lacerations, loss of several teeth, alveolar bone fracture, and severe vertical bone resorption in conjunction with a shattered alveolar bone and marked loss of intraoral function and facial disfigurement in a car accident. She underwent 9 surgical procedures by plastic surgeons to treat the facial lesions, including hold facial scar formation reduction surgery, reduction of fractures of the nasal and cheek bones, and bone transplants. To restore intraoral function and improve facial appearance, plastic surgeons transplanted a rib into the maxillary sinus while dental surgeons simultaneously inserted 5 dental implants. Eleven months after the dental implant surgery, a complete upper denture and a mandibular gingival ceramometal-casting crown were fitted. After insertion of the final prosthodontics, regular follow-up examinations were performed to check dental occlusion, oral hygiene, and the condition of the gingival tissue. In the years since the upper dental implants were fitted, there have been no bone resorption and no functional problems. Transplantation of rib bones is an effective method for maxillary reconstruction and remains effective even after the insertion of dental implants. The patient is extremely satisfied with the results. A means of maintaining oral health over the long term, and of motivating the patient to maintain oral health, should be established.

Background and Objectives: BHR is a clinical feature of asthma and factors crucial to the development of BHR remain to be elucidated. Asymptomatic BHR also occurs in the general population. This study examined the prevalence of asymptomatic BHR in a population of young Japanese atopic individuals to identify whether airway inflammation is present in asthmatic patients but not in asymptomatic subjects with BHR., Methods: Fifty atopic volunteers (aged 18-23 years) without lower respiratory symptoms were recruited and their bronchial responsiveness to methacholine was measured in order to categorize them into two groups, those with BHR (PC(20) below 8 mg/mL) and those without BHR. We evaluated the inflammatory cell profiles and measured IL-5 and IL-13 levels in sputum from subjects of each group by ELISA. Results were compared with those for young adult asthmatic patients., Results: In the young atopic group, 17 subjects (34.0%) exhibited BHR. Compared with asthmatic patients sputum from asymptomatic subjects with BHR contained significantly lower numbers of eosinophils (P < 0.001) and had significantly lower levels of IL-5 (P = 0.088) and IL-13 (P = 0.032). There were no significant differences in each inflammatory parameter between the two asymptomatic groups., Conclusions: In young adult atopic subjects with asymptomatic BHR, airway inflammation does not necessarily play a determining role in the development of BHR to methacholine itself, though it might be an important factor in the onset of asthma.

Background: Hyperinflation is widely accepted as an abnormal state affecting clinical symptoms, activities of daily living and exercise tolerance in chronic obstructive pulmonary disease (COPD). Reducing hyperinflation is an essential theme in COPD treatment. In this study, we let patients with COPD hyperventilate to evoke hyperinflation, and evaluated the effects of tiotropium alone or in combination with salmeterol on hyperventilation-evoked hyperinflation., Methods: Thirty-eight patients with COPD received pulmonary function tests including hyperventilation-evoked hyperinflation testing and the St. George's Respiratory Questionnaire (SGRQ) before treatment, after tiotropium administration for 8 weeks, and after combined therapy with salmeterol for 8 weeks., Results: Before treatment, inspiratory capacity (IC) after hyperventilation decreased significantly in a breathing frequency-dependent manner. After tiotropium administration, forced expiratory volume in one second (FEV1) increased significantly. IC after hyperventilation decreased significantly in a breathing frequency-dependent manner; however, IC was significantly greater than that before treatment (at rest, p=0.001; after hyperventilation at twice the resting respiratory rate, p=0.0009; and after hyperventilation at three times the resting respiratory rate, p<0.0001). The SGRQ score also improved significantly. After combined therapy with salmeterol, FEV1 increased significantly compared with after tiotropium alone. However, there was no significant difference between the IC after tiotropium alone and that after combined therapy, at each stage. However, after combined therapy the SGRQ score significantly improved compared with that after tiotropium alone., Conclusions: Tiotropium improved airflow obstruction and hyperventilation-evoked hyperinflation. In combination with salmeterol, the improvement in airflow obstruction was greater, but hyperventilation-evoked hyperinflation was not further improved.

The use of inhaled corticosteroids in asthma is regarded as first-line therapy. But the efficacy of inhaled corticosteroids in the treatment of chronic obstructive pulmonary disease (COPD) remains controversial. However data from some large studies provide the evidence that regular treatment with inhaled glucocorticosteroids is appropriate for symptomatic COPD patients with an FEVi<50% predicted and repeated exacerbations. In these studies glucocorticosteroids combined with a long-acting beta-agonist was more effective than the individual components. However, additional studies are needed to clarify the effects of inhaled corticosteroids on mortality and to define their long-term adverse effects.

The alpha granules of platelets contain various growth factors, which display in vitro and in vivo activities known to be important in wound healing. Biologically active proteins from platelets include platelet-derived growth factor, transforming growth factor-beta, and insulin-like growth factor, as well as other less well-described angiogenic and differentiated protein factors. The purpose of this study was to evaluate histologically and histometrically the new tissue formation on furcation treatment with platelet-derived factor releasate (PR) in beagle dogs. Class II furcations were created in the mandibular premolars of eight adult male beagle dogs. Periodontal regenerative treatments were then performed using collagen sponge graft material with and without the topical application of PR. PR was prepared fresh from blood drawn from dogs before treatments. A histologic evaluation of the effect on new tissue formation was then performed by comparing periodontal tissue regeneration of sites treated with and without PR. Four and 12 weeks after the flap operations, histologic sections were processed and histologically analyzed. The evaluated parameters were bone, cementum and connective tissue attachment regeneration, length of epithelium, resorption, and ankylosis. Histologically evaluated, the regeneration of new cementum was greater at the collagen sponge with PR sites compared to the control sites throughout the entire research period (P < .01). Four and 12 weeks after the flap operations, the amount of new bone in the sites treated with PR was greater than that in the control group (P < .05). These results suggest that collagen sponge graft material with PR promotes new attachment on the periodontal tissue regeneration treatments.

Angiogenesis is indispensable to guide a regeneration of good periodontal tissue in the wound healing after periodontal surgery. Hepatocyte growth factor is well known for a strong angiogenic factor and it may play important roles in the periodontal tissue during periodontal wound healing. In exploring the promotion of angiogenesis in the periodontal ligament, proliferative and tubulogenic responses of endothelial cells to hepatocyte growth factor and to soluble factors secreted by fibroblasts were investigated. Pavement-shaped cells isolated from a human periodontal ligament were identified as the endothelial cell by their granular immunoreactivity for factor VIII. The proliferation of the endothelial cells was accelerated by the addition of hepatocyte growth factor or fibroblast-conditioned medium, and far more by adding both than either. The endothelial cells seeded on the agar containing both hepatocyte growth factor and fibroblast products formed a dense network in a shorter time than on the agar containing either. The endothelial cells in the dense network took a tube-like structure with lumen and were covered with laminin. These results suggest that hepatocyte growth factor administered into the regenerating periodontal tissue may promote, synergistically with local factors produced by the activated fibroblast, the proliferation and tubulogenesis of the remaining endothelial cells.

Objective: Gemcitabine and docetaxel are non-platinum agents with activity in non-small cell lung cancer (NSCLC). This study was conducted to determine and evaluate the recommended regimen of gemcitabine-docetaxel and evaluated its efficacy and safety in chemonaive Japanese NSCLC patients., Methods: In phase I, patients with stage IIIB/IV NSCLC were randomized and received either gemcitabine on days 1 and 8 plus docetaxel on day 1 or gemcitabine on days 1 and 8 plus docetaxel on day 8. The recommended regimen was the dose level preceding the maximum tolerated dose; once determined, patients were enrolled in phase II. Efficacy and toxicity were evaluated in all patients., Results: Twenty-five patients were enrolled in phase I and six patients were given the recommended regimen; gemcitabine 1000 mg/m(2) on days 1 and 8 plus docetaxel 50 mg/m(2) on day 8. An additional 34 patients were enrolled into phase II and administered with the recommended regimen. The response rate was 32.2% [95% confidence interval (CI) 20.6-45.6%] overall and 30.0% (95% CI 16.6-46.5%) in patients with the recommended regimen (40 patients). Although grade 3 interstitial pneumonia was observed in two patients (5.0%) who received the recommended regimen, both recovered shortly after steroid treatment. No unexpected events were observed throughout this study., Conclusions: Gemcitabine 1000 mg/m(2) on days 1 and 8 plus docetaxel 50 mg/m(2) on day 8 has comparable efficacy and more tolerable toxicities than previously reported platinum-based regimens. These results should be verified by a phase III study.

A 55-year-old man was admitted to our hospital because of progressive dyspnea. Chest radiography showed interstitial shadows in the upper lobe. The pathological diagnosis of lung biopsy specimens obtained from upper and middle lobes by video-assisted thoracoscopy was non-specific interstitial pneumonia, group 2. Administration of glucocorticoids improved the symptoms, the chest radiography findings, and the serum KL-6 level. This patient may belong to the new category of idiopathic interstitial pneumonia, though he exhibited several features of idiopathic pulmonary upper lobe fibrosis originally described by Amitani et al.

Hypersensitivity pneumonitis (HP) is an immunologically mediated lung disease of inhaled antigens. HP is not a uniform disease but rather a clinical complex syndrome characterized by varying intensities of responsiveness to different organic antigens. The main aetiological agents include thermophilic bacteria, fungi, animal proteins, and chemical compounds. A combination of host and environmental factors should be considered as a requisite to developing this disease. Although the antigens differ widely, the clinical syndromes that results are very similar. HP occurs mainly in non-smokers, and clinically it may be in acute, subacute, or chronic forms. The diagnosis of HP requires a constellation of clinic, radiographic, physiologic, pathologic, and immunologic criteria. HP is characterized by a diffuse and predominantly mononuclear cell inflammation, a partly granulomatous, immune disorder of alveolar regions that often involves the small airway. A strong evidence supports that delayed cell-mediated hypersensitivity mechanisms play a role in pathogenesis of HP. Studies performed on lung cells have demonstrated that cells bearing suppressor/cytotoxic phenotype characterize the lymphocytic alveolitis in patients with hypersensitivity pneumonitis. And also recently evidence has been provided indicating that a prominent role of T-helper 1 cell-mediated hypersensitivity with an imbalance in T-lymphocyte subsets, although the deposit of immune complex may participate in an acute form of the disease as well as in the early phase of the chronic form., (Copyright 2001 Wiley-Liss, Inc.)

Alterations in polymorphonuclear leukocyte (PMN) functions, such as phagocytosis, chemotaxis, and oxidative burst, play a pivotal role in periodontal pathogenesis. In addition, previous studies have demonstrated a strong relationship between smoking and periodontal disease. In the present study, the effect of cigarette smoking or passive smoking (secondary smoking) on the phagocytic function of salivary PMN (SPMN) was investigated. Twenty volunteers with clinically healthy gingiva (10 smokers, 10 non-smokers) participated in this study. In a small room, the smokers and passive smokers (non-smokers) were instructed to smoke and breathe, respectively, in an identical, specific way for about 4 minutes. SPMN was isolated immediately before and after smoking or passive smoking. PMN was then incubated with fluoresbrite beads for 45 minutes at 37 degrees C and the phagocytic status estimated by using a flow cytometer. Cell viability was determined by trypan blue exclusion (smokers before smoking: 88.3%: smokers after smoking: 89.6%: non-smokers before passive smoking: 89.0%; non-smokers after passive smoking: 89.4%). In both smokers and passive smokers, the proportion of phagocytic cells increased between before and after smoking (smokers before: 33.2%; after: 42.1%: passive smokers before: 36.2%: after: 44.1%). Both increases were statistically significant (P < 0.01). These results demonstrate that the phagocytic activity of SPMN intensifies after smoking and passive smoking. They also suggest that certain substances in cigarette smoke, perhaps nicotine, overstimulate the host response in the oral cavity.

1. In the present study the possible relationship between adrenomedullin (AM) and calcitonin gene-related peptide (CGRP) in the regulation of airway functions in anaesthetized guinea-pigs was examined in vivo. 2. We found that AM significantly inhibited histamine-induced bronchoconstriction in a dose-dependent manner. CGRP or the CGRP receptor antagonist (CGRP [8-37]) alone did not affect pulmonary resistance and pretreatment with CGRP or CGRP [8-37] did not significantly affect histamine-induced bronchoconstriction. However, AM-induced bronchoprotection was significantly inhibited by pretreatment with CGRP or CGRP [8-37] in a dose-dependent manner. 3. It is therefore possible that CGRP may be competitive, at least in part, with binding sites of AM in the guinea-pig airway. Exogenous AM may be useful for the management of bronchial asthma, not only as a potent bronchodilator, but also as a functional antagonist of CGRP.