Measuring the Energy of Ventilation and Circulation during Human Walking using Induced Hypoxia

Energy expenditure (EE) during walking includes energy costs to move and support the body and for respiration and circulation. We measured EE during walking under three different oxygen concentrations. Eleven healthy, young, male lowlanders walked on a treadmill at seven gait speeds (0.67–1.83 m s−1) on a level gradient under normobaric normoxia (room air, 21% O2), moderate hypoxia (15% O2), and severe hypoxia (11% O2). By comparing the hypoxia-induced elevation in heart rate (HR [bpm]), ventilation (VE [L min−1]) with the change in energy expenditure (EE [W]) at each speed, we were able to determine circulatory and respiratory costs. In a multivariate model combining HR and VE, respiratory costs were 0.44 ± 0.15 W per each L min−1 increase in VE, and circulatory costs were 0.24 ± 0.05 W per each bpm increase in HR (model adjusted r2 = 0.97, p \u3c 0.001). These VE costs were substantially lower than previous studies that ignored the contribution of HR to cardiopulmonary work. Estimated HR costs were consistent with, although somewhat higher than, measures derived from catheterization studies. Cardiopulmonary costs accounted for 23% of resting EE, but less than 5% of net walking costs (i.e., with resting EE subtracted)

Menstrual Abnormalities in Female International Students in Japan : Changes during Pre-Arrival, Difficult, and Current Periods

The number of Japan’s international students has rapidly increased in the last decade. This study examines the relationship between menstrual abnormalities in cycle and symptoms, stress level, and lifestyle of female international students in Japan across three time periods, namely pre-arrival, difficult, and current time periods. A cross-sectional design was employed, and data were collected through a self-administered questionnaire, including the menstrual distress questionnaire (MDQ), between December 2022 and February 2023. The questionnaire was distributed to 56 female international students from two universities in Japan, and a total of 29 valid responses were collected. We found varying menstrual cycle abnormalities and severity of menstrual symptoms across three time periods, with the difficult period after arrival in Japan displaying the highest symptom severity. Higher stress levels were significantly associated with more severe menstrual symptoms. Lifestyle habits such as alcohol consumption were also linked to menstrual symptoms. The current study emphasizes the importance of providing menstrual education, support, and resources to address international students’ unique challenges in managing their menstrual health while studying abroad. By promoting awareness, education, and access to healthcare services, universities may contribute to international students’ well-being and academic success

Two cases of bronchiolitis obliterans organizing pneumonia syndrome after postoperative irradiation for breast cancer

We report two cases of bronchiolitis obliterans organizing pneumonia (BOOP) syndrome that developed after postoperative radiation therapy for breast cancer. In both patients, chest radiographs and computed tomography (CT) showed multiple consolidations outside the irradiation fields after several months of tangential radiation therapy. These patients were diagnosed as having radiation-associated BOOP syndrome, based on their clinical course and the findings on examination. After treatment with a systemic corticosteroid, radiographic consolidations and symptoms improved rapidly. In cases where consolidations appear outside the irradiated field, it is important to consider BOOP syndrome as a pulmonary complication of radiation therapy for breast cancer

Influence of corticosteroid therapy on the serum antibody response to influenza vaccine in elderly patients with chronic pulmonary diseases

Annual influenza vaccination is strongly recommended for patients with chronic pulmonary diseases, such as bronchial asthma, chronic obstructive pulmonary disease (COPD), and interstitial pulmonary diseases. However, many of these patients regularly receive systemic and/or inhaled corticosteroid therapy, and the impact of corticosteroid therapy on influenza vaccine efficacy and safety is unclear. Patients with chronic pulmonary diseases were enrolled in the study and divided into three groups based on their maintenance therapy: (A) without corticosteroid therapy (17 males, three females; mean age, 72.3 ± 7.9), (B) oral corticosteroid therapy (four males, seven females; mean age, 66.1 ± 10.6), and (C) inhaled corticosteroid therapy (eight males, nine females; mean age, 62.4 ± 16.0). All patients received influenza vaccine, and serum hemagglutination inhibition (HI) antibodies against influenza strains A/H1N1, A/H3N2, and B were measured at baseline (before vaccination) and 4-6 weeks after vaccination. Sufficient antibody titers or significant increases were observed after vaccination compared with titers before vaccination in all three groups. No systemic reactions were reported. Long-term oral/inhaled corticosteroid therapy was not associated with vaccination side effects and did not affect the immune response to the influenza vaccine

Significance of MDR1-Gene and P-Glycoprotein (P-gp) Expressions in the Lesional Skin of Psoriasis Vulgaris

We have examined P-gp (P-glycoprotein) and multi-drug resistance 1 (MDR1) gene expressions in the lesional skin of psoriasis vulgaris and atopic dermatitis some of those showed a decreased clinical response to topical corticosteroid ointment during the clinical course. The patients were subdivided into four groups; S (-): responder to topical steroid without steroid ointment for one month at the time of biopsy, S (+): responder to topical steroid and under steroid therapy at the time of biopsy, R (-): low or non- responder to topical steroid without steroid therapy for one month at the time of biopsy, R (+): low-or non-responder to topical steroid and under steroid therapy at the time of biopsy. P-gp was mainly expressed in the cytoplasm of some epidermal keratinocytes and most of infiltrating cells in the dermis of the lesional skin of psoriasis or atopic dermatitis. Scores of P-gp protein-expression was significantly higher in the patients under steroid ointment both in psoriasis vulgaris and atopic dermatitis. While R (+) group showed much more intense expression of P-gp than S (+) group in psoriasis vulgaris but this was not the case for atopic dermatitis. MDR1 gene was expressed in the lesional skin of R (+) psoriasis but not in S (+) psoriasis or normal skin. These results suggest that steroid-resistance occasionally experienced in psoriasis vulgaris might be related to the overexpression of P-gp which is possibly induced after topical steroid ointment. This might provide a new insight for the mechanism of steroid -insensitivity in inflammatory skin disorders especially in psoriasis vulgaris

有機薄膜デバイス用n型半導体材料としてのフラーレン誘導体に関する研究

学位の種別:論文博士University of Tokyo(東京大学

Simple method for large-scale production of macrophage activating factor GcMAF

Human group-specific component protein (Gc protein) is a multifunctional serum protein which has three common allelic variants, Gc1F, Gc1S and Gc2 in humans. Gc1 contains an O-linked trisaccharide [sialic acid-galactose-N-acetylgalactosamine (GalNAc)] on the threonine420 (Thr420) residue and can be converted to a potent macrophage activating factor (GcMAF) by selective removal of sialic acid and galactose, leaving GalNAc at Thr420. In contrast, Gc2 is not glycosylated. GcMAF is considered a promising candidate for immunotherapy and antiangiogenic therapy of cancers and has attracted great interest, but it remains difficult to compare findings among research groups because different procedures have been used to prepare GcMAF. Here, we present a simple, practical method to prepare high-quality GcMAF by overexpressing Gc-protein in a serum-free suspension culture of ExpiCHO-S cells, without the need for a de-glycosylation step. We believe this protocol is suitable for large-scale production of GcMAF for functional analysis and clinical testing

Enhanced interleukin-10 signaling with 14-member macrolides in lipopolysaccharide-stimulated macrophages

Immunomodulatory effects of 14-member macrolides, namely erythromycin (EM) and clarithromycin (CAM), have been reported in chronic respiratory infectious diseases. It has been suggested that 14-member macrolides have immunomodulatory effects on various lung cells such as alveolar macrophages. Interleukin (IL)-10 is an immunomodulatory cytokine that performs an irreplaceable role in negatively regulating inflammation, primarily via a mechanism that selectively blocks the expression of pro-inflammatory genes. It activates sig-nal transducer and activator of transcription (STAT)-3, and subsequently induces the suppres-sor of cytokine signaling-3 (SOCS-3), resulting in the resolution of inflammatory response in macrophages. However, it has been still unclear whether 14-member macrolides exert immu-nomodulatory effects via IL-10 signaling pathway. We aimed to evaluate whether 14-member macrolides affect the IL-10 signaling pathway. The RAW264.7 macrophage cell line was pre-treated with EM or CAM, and stimulated with lipopolysaccharide (LPS). The levels of IL-10, IL-10 receptor, phosphorylated (p) STAT-3, and SOCS-3 were determined by RT-PCR, ELISA and immunoblotting. We observed increased levels of IL-10, p-STAT-3 and SOCS-3 in the treated cells. In addition, while the levels of tumor necrosis factor-α 6 h after LPS stimulation was equal between vehicle-treated and CAM-treated macrophage cells, those of CAM-treated cells were repressed 36 h following LPS stimulation, compared with those of the control cells. Therefore, the 14-member macrolides may initiate an early resolution of inflammation, in part, via the enhancement of the IL-10/STAT-3/SOCS-3 pathway

Inactivation of Vibrio vulnificus hemolysin through mutation of the N- or C-terminus of the lectin-like domain

Vibrio vulnificus is an etiological agent causing serious systemic infections in the immunocompromised humans or cultured eels. This species commonly produces a hemolytic toxin consisting of the cytolysin domain and the lectin-like domain. For hemolysis, the lectin-like domain specifically binds to cholesterol in the erythrocyte membrane, and to form a hollow oligomer, the toxin is subsequently assembled on the membrane. The cytolysin domain is essential for the process to form the oligomer. Three-dimensional structure model revealed that two domains connected linearly and the C-terminus was located near to the joint of the domains. Insertion of amino acid residues between two domains was found to cause inactivation of the toxin. In the C-terminus, deletion, substitution or addition of an amino acid residue also elicited reduction of the activity. However, the cholesterol-binding ability was not affected by the mutations. These results suggest that mutation of the C- or N-terminus of the lectin-like domain may result in blockage of the toxin assembly

A complex of rab3A, SNAP-25, VAMP/synaptobrevin-2 and syntaxins in brain presynaptic terminals

AbstractTwo monoclonal antibodies (SPM-1 and SPM-2) immunoprecipitate brain N-type calcium channels. On immunoaffinity chromatography of digitonin extracts of bovine brain membranes on SPM-1- and SPM-2-Sepharose, proteins of 36 (syntaxins A and B), 28 and 19 kDa are specifically retained by both columns. Here we show that the 19 and 28 kDa bands contain VAMP/synaptobrevin-2, and rab3A/smg25A and SNAP-25, respectively. Since SPM-1 and SPM-2 recognize only syntaxins and the 28 kDa band (rab3A/smg25A and SNAP-25), respectively, the results indicate that all these proteins form a complex. Our results suggest tight linkage between the components involved in neurotransmitter release