Fumio Kumasawa

Apoptosis signal-regulating kinase 1-mediated signaling pathway regulates lipopolysaccharide-induced tissue factor expression in pulmonary microvasculature.

Sepsis remains a life-threatening event and acute lung injury (ALI) is one of the complications induced by it. ALI is characterized by fibrin deposition, an indication of local activation of the coagulation cascade. Tissue factor (TF) expressed in the microvasculature acts as a critical initiator of blood coagulation in ALI. Lipopolysaccharide (LPS), a component of the outer envelope of all Gram-negative bacteria, is a highly proinflammatory molecule that elicits a wide range of endothelial responses, including the upregulation of TF; however, the molecular mechanism in LPS-induced TF expression in the pulmonary microvasculature has not been determined. We analyzed the role of apoptosis signal-regulating kinase (ASK1), an upstream kinase of p38 mitogen-activated protein kinase (p38 MAPK) and c-Jun N-terminal kinase (JNK), in order to clarify the signaling molecule regulating LPS-induced TF expression. The results showed the following: 1) LPS induces hTF mRNA expression in normal human lung microvascular endothelial cells (HMVEC-L); 2) LPS induces ASK1 phosphorylation in HMVEC-L; 3) LPS-induced TF mRNA expression is depressed in the dominant negative form of ASK1 stably-transfected porcine artery endothelial (PAE) cells; 4) LPS stimulation induces p38 MAPK and JNK phosphorylations in HMVEC-L; 5) LPS-induced p38 MAPK and JNK phosphorylations are depressed in the dominant negative form of ASK1 stably-transfected PAE cells; and 6) SB 203580 as a specific inhibitor of p38 MAPK, but not SP 600125 as a specific inhibitor of JNK cascade, attenuates LPS-induced hTF mRNA expression. These results indicate that the ASK1-p38 MAPK cascade may regulate LPS-induced TF expression in pulmonary microvasculature.

A case of miriplatin-induced lung injury

A 69-year-old man with an 8-year history of hepatocellular carcinoma (HCC) was hospitalized for treatment of recurrent tumour. In 2010, the first transcatheter arterial chemoembolization (TACE) using miriplatin with agents (Lipiodol Ultra-Fluid) was performed and did not occur any adverse events. In 2014, since his HCC recurred, the TACE using miriplatin with agents was performed. Following this therapy, pyrexia occurred on day 3, followed by respiratory failure with cough and dyspnea on day 5. Chest radiography revealed scattered infiltration in the right upper lung fields, and chest computed tomography revealed ground grass attenuations, indicating fibrotic non-specific interstitial pneumonia. These findings progressively deteriorated, and a diagnosis of miriplatin-induced lung injury was made. His respiratory failure also progressively deteriorated. Treatment with pulse methylprednisolone therapy resulted in a dramatic improvement in both patient symptoms and radiological abnormalities.

Serum eosinophil-derived neurotoxin: Correlation with persistent airflow limitation in adults with house-dust mite allergic asthma.

BACKGROUND The serum level of eosinophil-derived neurotoxin (EDN), a protein present in eosinophil granules, correlates with the severity of childhood asthma. However, the relationship between the serum EDN level and the severity of adult asthma has not been sufficiently investigated. OBJECTIVE This study aimed to elucidate the correlation between the serum EDN level and markers of severity in adult asthma. METHODS The subjects comprised 83 adult patients who had asthma and who were undergoing treatment. Of these patients, 40 were positive for house-dust-specific immunoglobulin E (IgE) antibodies; 9 patients with severe adult asthma who were treated with omalizumab were included in the study. We measured the blood eosinophil count, serum EDN, and eosinophil cationic protein levels before investigating the correlations of these parameters with lung function and symptom score. RESULTS There were no significant correlations between the blood eosinophil count or serum EDN or eosinophil cationic protein level with lung function and the symptom score in patients with asthma. However, serum EDN level was inversely correlated with the decrease percentage forced expiratory volume in 1 second (%FEV1) in patients positive for house-dust-specific IgE antibody (R = -0.54; p < 0.05), whereas no such correlation was observed in patients with negative results for house-dust-specific IgE antibody (R = 0.11; p = 0.468). A significant correlation was observed between a decrease in serum EDN level from baseline and lung function improvement after 8 weeks of omalizumab therapy (R = -0.77; p = 0.015). CONCLUSION Serum EDN level may be a useful marker for monitoring persistent airflow limitation in adult patients with asthma who had positive results for house-dust-specific IgE antibodies.

Long-Term Clinical Course of Asthma Recorded by Digital Asthma Diary: A Case Report

Self-management methods for chronic diseases using mobile phone and tablet applications have recently become popular. Although several applications for asthma management are available, there are no reports concerning the long-term treatment effects of inhaled corticosteroid (ICS)/long-acting beta agonist (LABA) treatment on diurnal peak flow variability according to digital asthma diary records or its utility. A 31-year-old female diagnosed with moderate persistent asthma was treated with ICS/LABA. On approximately 2 years after the treatment, we were able to observe that diurnal peak flow variability disappeared gradually and completely when the time axis set that all records can be observed in one screen. Self-monitoring the peak flow using digital asthma diaries is suitable for long-term recording and allows an adequate understanding of long-term asthma state and treatment effects especially for minor diurnal peak flow variability by ICS/LABA.

Successful Combination Therapy with Pulse Methylprednisolone, PMX-DHP and Cyclosporin A for a Patient with Acute Interstitial Pneumonia : Case Report

Successful Combination Therapy with Pulse Methylprednisolone, PMX-DHP and Cyclosporin A for a Patient with Acute Interstitial Pneumonia: Case Report Chika TAKANO1), Fumio KUMASAWA2), Akihiro NODA3), Shuzo NOMURA1), Keiko TAKAHASHI1), Kenichi SUGAYA2), Daisuke KOYAMA2), Yoshitaka SHINTANI2), Hiroko SUZUKI4), Makoto KOGAWA3), Naoki OKAMOTO2), Takashi OHKI2), Masanori ABE4), Shinichi HAYASHI2), Tomoko KOBAYASHI2), Kazuyoshi OKADA4), Noriaki TAKAHASHI2), Kosaku KINOSHITA3), Masayoshi SOMA4), Katsuhisa TANJO3) and Shu HASHIMOTO2) 1)Nihon University School of Medicine 2)Division of Respiratory Medicine, Department of Internal Medicine, Nihon University School of Medicine 3)Division of Emergency and Critical Care Medicine, Department of Acute Medicine, Nihon University School of Medicine 4)Division of Nephrology, Hypertension and Endocrinology, Department of Internal Medicine, Nihon University School of Medicine