Analysis of the diagnosis of Japanese patients with primary ciliary dyskinesia using a conditional reprogramming culture.

BACKGROUND: Primary ciliary dyskinesia (PCD) is diagnosed through multiple methods, including transmission electron microscopy (TEM), a high-speed video microscopy analysis (HSVA), immunofluorescence (IF), and genetic testing. A primary cell culture has been recommended to avoid the misdiagnosis of secondary ciliary dyskinesia derived from infection or inflammation and improve diagnostic accuracy. However, primary cells fail to differentiate into ciliated cells through repeated passages. The conditional reprogramming culture (CRC) method, a combination of a Rho-kinase inhibitor and fibroblast feeder cells, has been applied to cystic fibrosis. The goal of this study was to evaluate the value of CRC in diagnosing PCD in Japanese patients. METHODS: Eleven patients clinically suspected of having PCD were included. Airway epithelial cells were obtained from an endobronchial forceps biopsy and cultured at the air-liquid interface (ALI) combined with CRC. Ciliary movement, ultrastructure, and mutated ciliary protein evaluation were performed using HSVA, TEM, and IF, respectively. Genetic testing was performed on some patients. RESULTS: CRC yielded dense and well-differentiated ciliated cells with a high success rate (∼90%). In patients with PCD, the ciliary ultrastructure phenotype (outer dynein arm defects or normal ultrastructure) and IF findings (absence of the mutated ciliary protein) were confirmed after CRC. In DNAH11-mutant cases with normal ultrastructure by TEM, the HSVA revealed stiff and hyperfrequent ciliary beating with low bending capacity in CRC-expanded cells, thereby supporting the diagnosis. CONCLUSIONS: CRC could be a potential tool for improving diagnostic accuracy and contributing to future clinical and basic research in PCD.

Less airway inflammation and goblet cell metaplasia in an IL-33-induced asthma model of leptin-deficient obese mice.

BACKGROUND: Obesity-associated asthma is a phenotype of severe asthma. Late-onset, non-eosinophilic and female-dominant phenotype is highly symptomatic and difficult to treat. Leptin, an adipokine, exerts an immunomodulatory effect. IL-33 associated with innate immunity induces type 2 inflammation and is present in adipose tissue. The purpose of this study was to elucidate the pathogenesis of obesity-associated asthma by focusing on the interaction between leptin and IL-33. METHODS: In leptin-deficient obese (ob/ob) and wild-type mice, IL-33 was instilled intranasally on three consecutive days. In part of the mice, leptin was injected intraperitoneally prior to IL-33 treatment. The mice were challenged with methacholine, and airway hyperresponsiveness (AHR) was assessed by resistance (Rrs) and elastance (Ers) of the respiratory system using the forced oscillation technique. Cell differentiation, IL-5, IL-13, eotaxin, keratinocyte-derived chemokine (KC) in bronchoalveolar lavage fluid (BALF) and histology of the lung were analyzed. For the in vitro study, NCI-H292 cells were stimulated with IL-33 in the presence or absence of leptin. Mucin-5AC (MUC5AC) levels were measured using an enzyme-linked immunosorbent assay. RESULTS: Ob/ob mice showed greater Rrs and Ers than wild-type mice. IL-33 with leptin, but not IL-33 alone, enhanced Ers rather than Rrs challenged with methacholine in ob/ob mice, whereas it enhanced Rrs alone in wild-type mice. IL-33-induced eosinophil numbers, cytokine levels in BALF, eosinophilic infiltration around the bronchi, and goblet cell metaplasia were less in ob/ob mice than in wild-type mice. However, leptin pretreatment attenuated these changes in ob/ob mice. MUC5AC levels were increased by co-stimulation with IL-33 and leptin in vitro. CONCLUSIONS: Ob/ob mice show innate AHR. IL-33 with leptin, but not IL-33 alone, induces airway inflammation and goblet cell metaplasia and enhances AHR involving peripheral airway closure. This is presumably accelerated by mucus in ob/ob mice. These results may explain some aspects of the pathogenesis of obesity-associated asthma.

Multiple infected lung bullae associated with Mycobacterium intracellulare in a Japanese man.

Mycobacterium avium complex (MAC)-infected lung bulla was a rare type of pulmonary non-tuberculous mycobacterial (NTM) infection. A 29-year-old man with a history of tetralogy of Fallot was admitted to our hospital because of a high fever and left chest pain. Chest computed tomography showed two bullae with intrabullous fluid in both the lower lobes and centrilobular small nodular shadow in the right upper lobe and the left lower lobe. Culture of bronchoscopic washing specimen from the right upper lobe bronchus and left lower lobe one and purulent fluid drained from the bulla in the left lower lobe revealed Mycobacterium intracellulare. Percutaneous drainage from the left bulla and anti-NTM treatment were performed. Afterwards, symptoms improved and two intrabullous fluid disappeared. Therefore, a diagnosis of multiple infected lung bullae associated with M. intracellulare was made. This is the first documented case of multiple infected lung bullae associated with MAC.

Multifaceted analysis of Japanese cases of primary ciliary dyskinesia: Value of immunofluorescence for ciliary protein detection in patients with DNAH5 and DNAH11 mutations.

Multifaceted analysis is recommended for the diagnosis of primary ciliary dyskinesia (PCD). A 31-year-old woman had situs inversus, bronchiectasis, family history of PCD, and compound heterozygous mutations in DNAH5. Her cilia were immotile. Defects in the outer dynein arms were revealed by transmission electron microscopy and loss of DNAH5 proteins in the entire length of axonemes using immunofluorescence (IF). A 17-year-old boy had bronchiectasis and heterozygous mutations in DNAH11. His cilia were motile with normal ultrastructure. The loss of DNAH11 proteins at the proximal region of cilia was revealed by IF. IF could be useful to support PCD diagnosis.

Thermal Model and Countermeasures for Future Smart Glasses.

The market for wearable devices such as smart watches and smart glasses continues to grow rapidly. Smart glasses are attracting particular attention because they offer convenient features such as hands-free augmented reality (AR). Since smart glasses directly touch the face and head, the device with high temperature has a detrimental effect on human physical health. This paper presents a thermal network model in a steady state condition and thermal countermeasure methods for thermal management of future smart glasses. It is accomplished by disassembling the state by wearing smart glasses into some parts, creating the equivalent thermal resistance circuit for each part, approximating heat-generating components such as integrated circuits (ICs) to simple physical structures, setting power consumption to the heat sources, and providing heat transfer coefficients of natural convection in air. The average temperature difference between the thermal network model and a commercial thermal solver is 0.9 °C when the maximum temperature is 62 °C. Results of an experiment using the model show that the temperature of the part near the ear that directly touches the skin can be reduced by 51.4% by distributing heat sources into both sides, 11.1% by placing higher heat-generating components farther from the ear, and 65.3% in comparison with all high conductivity materials by using a combination of low thermal conductivity materials for temples and temple tips and high conductivity materials for rims.

A case of Epstein-Barr virus-negative human immunodeficiency virus-related primary effusion lymphoma.

Primary effusion lymphoma (PEL) is a rare subtype of large B-cell lymphoma associated with human herpesvirus-8. Most cases are co-infected with Epstein-Barr virus (EBV). The prognosis of PEL is extremely poor and no optimal treatment regimen has been established. We report a case of EBV-negative PEL in a 49-year-old human immunodeficiency virus-positive man, presenting with massive bilateral pleural effusion.

Diagnosis of imported Ugandan typhoid fever based on local outbreak information: A case report.

Re-emerging multidrug-resistant typhoid fever is becoming a worldwide threat, especially in East Africa. At the beginning of 2015, an outbreak of typhoid fever started in the capital city of Uganda, and 1940 suspected cases were reported by 5 March 2015. In this report, we describe a case of typhoid fever caused by a MDR strain with HIV infection and hemoglobin S-syndrome thalassemia in an Ugandan from Kampala City. It is essential to consider MDR strains of Salmonella enterica serovar Typhi infections, including fluoroquinolone-resistant strains, in patients from Africa and Southeast Asia.