Seiko Nakayama

Clinical Differences Between Interstitial Lung Disease Associated With Clinically Amyopathic Dermatomyositis and Classic Dermatomyositis

BACKGROUND Interstitial lung disease (ILD) associated with clinically amyopathic dermatomyositis (CADM) is a potentially fatal condition in which the clinical features are not well understood. The aim of the present study was to clarify the differences in clinical characteristics and prognosis of patients with ILD associated with CADM (CADM-ILD) and classic dermatomyositis associated with ILD (DM-ILD). METHODS We retrospectively studied consecutive patients with CADM-ILD and classic DM-ILD who were hospitalized between 2001 and 2007 at Nagasaki University Hospital. The study group consisted of 11 patients with CADM-ILD and 16 patients with classic DM-ILD. We compared the clinical features and prognosis between the two forms. RESULTS The Pao(2)/Fio(2) ratio was significantly lower in patients with CADM-ILD than in patients with classic DM-ILD. The lymphocyte subsets ratio in the BAL fluid of patients with CADM-ILD was significantly higher than the corresponding ratio in patients with classic DM-ILD. ILD is classified as acute or chronic, and the acute subtype was more common in patients with CADM-ILD than in those with classic DM-ILD. The mortality rate for patients with CADM-ILD (45%) was much higher than that for patients with classic DM-ILD (6%), and all of the CADM deaths occurred in the group of patients with acute CADM-ILD. CONCLUSION Our data suggest that the higher prevalence of the acute subtype of ILD in patients with CADM results in a higher mortality rate for patients with CADM-ILD.

Differing effects of clarithromycin and azithromycin on cytokine production by murine dendritic cells

The macrolide antibiotics are now well known to have anti‐inflammatory effects. Because dendritic cells (DCs) orchestrate immune responses, we examined the in vitro effects of clarithromycin (CAM), azithromycin (AZM) and midecamycin (MDM) on the expression of co‐stimulatory molecules and production of cytokines [interleukin (IL)‐10, IL‐6, interferon (IFN)‐γ, IL‐12p40, tumour necrosis factor (TNF)‐α] of murine bone marrow‐derived DCs by lipopolysaccharide (LPS) stimulation. A 15‐membered macrolide, AZM, and a 14‐membered macrolide, CAM, significantly enhanced the intensity of a co‐stimulatory molecule, CD80, on DCs but not CD86 and CD40. AZM significantly increased the production of IL‐10 and CAM significantly inhibited the production of IL‐6 by DCs. However, a 16‐membered macrolide, MDM, did not have any significant effect on these surface markers and cytokine productions. Moreover, AZM increased IL‐10 and CAM decreased IL‐2 productions significantly, when naive T cells derived from spleen were co‐cultured with DCs treated in advance with LPS and these macrolides. These findings suggest that 14‐membered and 15‐membered, but not 16‐membered macrolides play as anti‐inflammatory agents, at least in part, through modulating the functions of DCs. However, each macrolide affects them in different ways.

Expression of HSP47 in Usual Interstitial Pneumonia and Nonspecific Interstitial Pneumonia

BackgroundHeat shock protein (HSP) 47, a collagen-specific molecular chaperone, is involved in the processing and/or secretion of procollagens, and its expression is increased in various fibrotic diseases. The aim of this study was to determine whether quantitative immunohistochemical evaluation of the expression levels of HSP47, type I procollagen and α-smooth muscle actin (SMA) allows the differentiation of idiopathic usual interstitial pneumonia (UIP) from UIP associated with collagen vascular disease (CVD) and idiopathic nonspecific interstitial pneumonia (NSIP).MethodsWe reviewed surgical lung biopsy specimens of 19 patients with idiopathic UIP, 7 with CVD-associated UIP and 16 with idiopathic NSIP and assigned a score for the expression of HSP47, type I procollagen and α-SMA in type II pneumocytes and/or lung fibroblasts (score 0 = no; 1 = weak; 2 = moderate; 3 = strong staining).ResultsThe expression level of HSP47 in type II pneumocytes of idiopathic UIP was significantly higher than in CVD-associated UIP and idiopathic NSIP. The expression of HSP47 in fibroblasts was significantly higher in idiopathic UIP and idiopathic NSIP than in CVD-associated UIP. The expression of type I procollagen in type II pneumocytes was significantly higher in idiopathic UIP than in idiopathic NSIP. The expression of type I procollagen in fibroblasts was not different in the three groups, while the expression of α-SMA in fibroblasts was significantly higher in idiopathic UIP than in idiopathic NSIP.ConclusionOur results suggest the existence of different fibrotic pathways among these groups involved in the expression of HSP47 and type I procollagen.

Different effects of telithromycin on MUC5AC production induced by human neutrophil peptide-1 or lipopolysaccharide in NCI-H292 cells compared with azithromycin and clarithromycin

OBJECTIVES Mucus hypersecretion is a prominent feature in patients with chronic respiratory tract infections such as cystic fibrosis and diffuse panbronchiolitis, and the clinical effectiveness of macrolide antibiotics has been reported in these patients. Because human neutrophil peptide-1 (HNP-1), an antimicrobial peptide in neutrophils, exists in high concentrations in the airway fluid of these patients, we examined the direct effect of HNP-1 on MUC5AC mucin production using NCI-H292 cells. The effects of macrolide antibiotics on the response were also examined. METHODS MUC5AC synthesis was assayed using RT-PCR and ELISA. Phosphorylation of ERK1/2 was determined by western blotting. RESULTS Stimulation with HNP-1 or lipopolysaccharide (LPS) derived from Pseudomonas aeruginosa increases the production of MUC5AC mRNA and protein, and an additive effect was found upon co-stimulation with both HNP-1 and LPS. Azithromycin and clarithromycin had inhibitory effects on overproduction of MUC5AC induced by HNP-1 or LPS stimulation. Telithromycin also had an inhibitory effect on MUC5AC production induced by LPS, but not on production by HNP-1. Phosphorylation of ERK1/2 was induced by HNP-1 or LPS stimulation, and azithromycin, clarithromycin and telithromycin had inhibitory effects on ERK1/2 phosphorylation induced by LPS, but not by HNP-1. CONCLUSIONS These findings suggest that neutrophil-derived defensins as bacterial components contribute to excessive mucus production in patients with respiratory tract infections, and that macrolide and ketolide antibiotics directly inhibit these actions by interfering with intracellular signal transduction. However, the mechanism of telithromycin inhibition of MUC5AC synthesis may differ from the response induced by azithromycin and clarithromycin.

Elevated levels of interferon γ‐inducible protein‐10 and epithelial neutrophil‐activating peptide‐78 in patients with pulmonary sarcoidosis

Objective and background:  Interferon γ‐inducible protein (IP)‐10 and epithelial neutrophil‐activating peptide (ENA)‐78 belong to the CXC chemokine family and are important factors in inflammatory lung diseases. In sarcoidosis, the potential role of IP‐10 to regulate the migration and activation of T‐cells towards sites of sarcoid activity has been suggested.

Effects of smoking cessation on gastric emptying in smokers.

Background Smoking cessation can lead to changes in appetite and weight gain in some patients; thus, smoking cessation may alter gastrointestinal motility. Effects of smoking cessation on gastric emptying in smokers have not been established. Aim This study sought to determine how smoking cessation affects gastric emptying in smokers. Methods Participant group comprised 53 habitual smokers and 12 healthy nonsmokers. Habitual smokers were treated for 2 months with transdermal nicotine patches. Gastric emptying was studied using 13C acetate breath tests at the beginning of the study, and at 1 week and 9 weeks after cessation of patch use. Maximal 13CO2 excretion time (Tmax), 13CO2 excretion half-life (T1/2), and parameters β and κ, representing initial and subsequent gastric-emptying phases, respectively, were determined using conventional formulae. Results Before smoking cessation, Tmax was reached significantly later in smokers (0.94±0.3 h, P=0.014) than in controls (0.89±0.1 h). At 1 week after the end of treatment, Tmax was significantly decreased (from 1.05±0.32 h to 0.72±0.64 h, P=0.003). T1/2 also tended to decrease, but not significantly. Although β was decreased significantly (from 2.46±0.40 to 2.17±0.58, P=0.022), κ was unchanged. However, by 9 weeks after the end of treatment, Tmax (1.28±0.69 h) had increased to levels seen before treatment. Conclusions Smoking cessation temporarily accelerates gastric emptying, and decreases in β suggest that initial-phase gastric emptying accelerates after smoking cessation. The temporary acceleration of gastric emptying after smoking cessation may be involved in the temporary increase in appetite and weight gain seen after smoking cessation.

Interstitial pneumonia caused by inhalation of fumes of nickel and chrome.

Abstract:  Two male industrial painters were admitted to hospital with dry cough and dyspnoea on exertion following a tank coating operation using a high‐temperature spray paint consisting of a nickel‐chromium alloy. Both patients showed hypoxaemia, peripheral leukocytosis, high levels of serum cytokines and bilateral ground‐glass opacities on a chest CT scan. They were diagnosed with interstitial pneumonia caused by inhalation of nickel and chrome fumes and successfully treated with corticosteroid. These are rare cases of interstitial pneumonia associated with nickel/chromium inhalation.

[The booster phenomenon in two-step tuberculin testing of employees in a community hospital].

A study was made to clarify to what degree the booster phenomenon was present when the employees in a community hospital in Japan received two-step tuberculin testing (PPD). Of the seventy-five employees, most of all BCG-vaccinated subjects, twenty-three showed strongly positive of more than 30 mm of induration at the first test (PPD/T1), and the remaining fifty-two subjects received a second (PPD/T2) after 2 weeks. The second PPD showed a marked increase in reactivity, sixteen subjects newly became strongly positive and six of eight who were initially PPD negative (< 10 mm) were converted positive, and the mean reaction size changed from 14.7 +/- 5.6 mm (PPD/T1) to 31.5 +/- 15.5 mm (PPD/T2). The degree of boosting, measured by the change in millimeters induration size between PPD/T1 and PPD/T2 (PPD/T2-PPD/T1), was correlated with neither the size of PPD/T1 nor the age of the study participants, and was not associated with the difference of the position in the hospital. Thus, we could not explain the factor why such a marked boosting was observed in this study. However, these results indicated that the two-step tuberculin testing is an essential means of distinguishing new tuberculous infection from booster phenomenon. We agree with the current recommendation for routine two-step testing of new employees in the hospital.