Gravitino Dark Matter without R-parity

Cosmological issues are examined when gravitino is the lightest superparticle (LSP) and R-parity is broken. Decays of the next lightest superparticles occur rapidly via R-parity violating interaction, and thus they do not upset the big-bang nucleosynthesis, unlike the R-parity conserving case. The gravitino LSP becomes unstable, but its lifetime is typically much longer than the age of the Universe. It turns out that observations of diffuse photon background coming from radiative decays of the gravitino do not severely constrain the gravitino abundance, and thus the gravitino weighing less than around 1 GeV can be dark matter of the Universe when bilinear R-parity violation generates a neutrino mass which accounts for the atmospheric neutrino anomaly.Comment: 11 pages, 1 figur

Prognostic value of visceral pleural invasion in resected non–small cell lung cancer diagnosed by using a jet stream of saline solution

AbstractObjectiveVisceral pleural invasion caused by non–small cell lung cancer is a factor in the poor prognosis of patients with that disease. We investigated the relationship between the diagnosis of visceral pleural invasion by using a jet stream of saline solution, which was previously reported as a new cytologic method to more accurately detect the presence of visceral pleural invasion, and prognosis.MethodsFrom January 1992 through December 1998, 143 consecutive patients with peripheral non–small cell lung cancer that appeared to reach the visceral pleura underwent a surgical resection at the Department of Thoracic Oncology, National Kyushu Cancer Center. The surface of the visceral pleura in patients undergoing lung cancer resection was irrigated with a jet stream of saline solution. The diagnosis of visceral pleural invasion was determined by means of either a pathologic examination or by means of a jet stream of saline solution. In addition, a cytologic examination of the pleural lavage fluid obtained immediately after a thoracotomy was evaluated.ResultsForty-nine (34%) resected tumors were identified as having visceral pleural invasion. The diagnosis of visceral pleural invasion in 31, 6, and 12 patients was determined by using a jet stream of saline solution alone, pathologic examination alone, or both, respectively. The visceral pleural invasion and positive findings of intrapleural lavage cytology were linked. Although there was no significant difference between the incidence of distant metastases in the patients with visceral pleural invasion and those without visceral pleural invasion, the incidence of local recurrence, especially regarding carcinomatous pleuritis (malignant pleural effusion, pleural dissemination, or both), in the patients with visceral pleural invasion was significantly higher than in those without visceral pleural invasion. The recurrence-free survival of patients with visceral pleural invasion was significantly shorter than that of patients without visceral pleural invasion (P = .004), even patients with stage I disease (P = .02). There was also a significant difference between the patients with or without visceral pleural invasion in the overall survival (P = .02). Visceral pleural invasion was independently associated with a poor recurrence-free survival on the basis of multivariate analyses (P = .03), as were sex (P = .03), age (P = 002), and the stage of the disease (P < .0001).ConclusionsThis study confirmed that the jet stream of saline solution method in addition to ordinary pathologic examination was useful for detecting visceral pleural invasion, which is considered to be one of the causes of local recurrence, especially in carcinomatous pleuritis

Improvement in Frailty in a Patient With Severe Chronic Obstructive Pulmonary Disease After Ninjin'yoeito Therapy: A Case Report

Frailty is a poor prognostic factor in patients with chronic obstructive pulmonary disease (COPD). Although various studies have assessed the effects of conventional treatment with bronchodilators, nutritional support, and pulmonary rehabilitation for frailty in patients with COPD, none have addressed the effects of traditional Japanese medicine (Kampo medicine). Herein, we report the successful management of frailty using Ninjin'yoeito therapy in a 76-year-old patient with COPD. Despite being prescribed multiple bronchodilators, nutritional supplement therapy, patient education, and pulmonary rehabilitation, the patient exhibited unintentional weight loss, low energy, and low physical activity. Ninjin'yoeito was prescribed and these subjective symptoms began to improve 1 month after treatment initiation. In 6 months, the patient reported no frailty, had increased muscle mass, and had achieved an almost normal healthy state. Ninjin'yoeito has been associated with both physical effects, such as improvement in overall physical strength and appetite, and reduction in fatigue, and psychological effects, such as greater motivation and reduction of depression and anxiety symptoms. Physicians have usually treated COPD primarily with organ-specific treatments, such as bronchodilators; however, addressing both the physiological and psychological vulnerability has been difficult. This case report illustrates the potential usefulness of Ninjin'yoeito treatment for frailty in patients with COPD

Inhibitory Effects of Chlorella Extract on Airway Hyperresponsiveness and Airway Remodeling in a Murine Model of Asthma

Chlorella extract （CE） has been shown to induce production of T helper-1 cytokines, and regulate serum IgE levels in animal models of asthma. We aimed to evaluate whether CE could inhibit ovalbumin （OVA）-induced airway hyperresponsiveness （AHR） and airway remodeling in a murine model of asthma. Balb/c mice were allocated to four groups: a control group （no OVA exposure, not given CE）, a CE group （no OVA exposure, given CE）, an asthma group （sensitized/challenged with OVA, not given CE） and a CE＋asthma group （sensitized/challenged with OVA, given CE）. In the asthma and CE＋asthma groups, mice were sensitized with OVA on day 0 and day 12, and then challenged with OVA on three consecutive days. In the CE and CE＋asthma groups, the mice were given feed containing 2％ CE. We assessed AHR to methacholine, and analyzed bronchoalveolar lavage fluid （BALF）, serum, lung tissue and spleen cells. Administration of CE was associated with significantly lower AHR in OVA-sensitized and challenged mice. CE administration was also associated with marked reduction of total cells, eosinophils and T helper-2 cytokines （IL-4, IL-5 and IL-13） in BALF. In addition, administration of CE significantly decreased the numbers of periodic acid-Schiff （PAS）-positive cells in OVA-sensitized and challenged mice. Administration of CE also directly suppressed IL-4, IL-5 and IL-13 production in spleen cells of OVA-sensitized and challenged mice. These results indicate that CE can partly prevent AHR and airway remodeling in a murine model of asthma

Open-label clinical trial of bezafibrate treatment in patients with fatty acid oxidation disorders in Japan

IntroductionFatty acid oxidation disorders (FAODs) are rare diseases caused by defects in mitochondrial fatty acid oxidation (FAO) enzymes. While the efficacy of bezafibrate, a peroxisome proliferator-activated receptor agonist, on the in vitro FAO capacity has been reported, the in vivo efficacy remains controversial. Therefore, we conducted a clinical trial of bezafibrate in Japanese patients with FAODs.Materials and methodsThis trial was an open-label, non-randomized, and multicenter study of bezafibrate treatment in 6 patients with very long-chain acyl-CoA dehydrogenase (VLCAD) deficiency and 2 patients with carnitine palmitoyltransferase-II (CPT-2) deficiency (median age, 8.2 years; ranging from 5.8 to 26.4 years). Bezafibrate was administered for 6 months following a 6-month observation period. The primary endpoint was the frequency of myopathic attacks, and the secondary endpoints were serum acylcarnitines (ACs, C14:1 or C16 + C18:1), creatine kinase (CK) levels, degree of muscle pain (VAS; visual analog scale) during myopathic attacks, and quality of life (QOL; evaluated using validated questionnaires).ResultsThe frequency of myopathic attacks after bezafibrate administration decreased in 3 patients, increased in 3, and did not change in 2. The CK, AC, and VAS values during attacks could be estimated in only three or four patients, but a half of the patients did not experience attacks before or after treatment. Changes in CK, AC, and VAS values varied across individuals. In contrast, three components of QOL, namely, physical functioning, role limitation due to physical problems (role physical), and social functioning, were significantly elevated. No adverse drug reactions were observed.ConclusionIn this study, the frequency of myopathic attacks and CK, AC, and VAS values during the attacks could not be evaluated due to several limitations, such as a small trial population. Our findings indicate that bezafibrate improves the QOL of patients with FAODs, but its efficacy must be examined in future investigations

Tumor Necrosis Factor-alpha and Transforming Growth Factor-beta Synergistically Upregulate Endothelin-1 Expression in Human Bronchial Epithelial Cells BEAS-2B

Endothelin-1 is a peptide with many functions including bronchoconstriction and the stimulation of fibroblasts, and myofibroblasts, and airway smooth muscle cell proliferation. These functions are related to airway remodeling and endothelin-1 is known to be upregulated in the epithelium of patients with severe asthma. We thus sought to elucidate the mechanisms underlying endothelin-1 expression in bronchial epithelial cells in vitro. The human bronchial epithelial cell line BEAS-2B was grown in culture and then treated with tumor necrosis factor-alpha (TNF-α), interleukin-4 (IL-4), interleukin-13 (IL-13), and transforming growth factor-beta (TGF-β). Expression of endothelin-1 mRNA and protein was quantified by real-time polymerase chain reaction and enzyme-linked immunosorbent assay, respectively. We also repressed expression of the key transcription factor in the pathogenesis of severe asthma, nuclear factor-kappa B (NF-κB), using small interfering RNA (siRNA). TNF-α and TGF-β significantly increased the release of endothelin-1 protein into the culture medium of BEAS-2B cells at 24 h after treatment compared to untreated cells; however, the Th2 cytokines, IL-4 and IL-13, had no effect. Endothelin-1 mRNA expression was also upregulated by TNF-α and TGF-β with a peak time point at 4 h after stimulation. Finally, the combination of TNF-α and TGF-β synergistically increased both endothelin-1 protein secretion and mRNA expression, and this upregulation was significantly suppressed in cells transfected with siRNA to repress NF-κB expression. TNF-α and TGF-β synergistically upregulate the expression of endothelin-1 in human bronchial epithelial cells, possibly via the activity of NF-κB. Our findings thus suggest NF-κBa as a potential therapeutic target for the regulation of airway remodeling

Long-term follow-up of production of IgM and IgG antibodies against SARS-CoV-2 among patients with COVID-19

The patients diagnosed with coronavirus disease 2019 （COVID-19） produce IgM and IgG antibodies against severe acute respiratory syndrome coronavirus 2 （SARS-CoV-2）. However, the frequency and duration of antibody production still need to be fully understood. In the present study, we investigated the duration of antibody production after SARS-CoV-2 infection. The patients diagnosed with COVID-19 were monitored over twelve months for the production of SARS-CoV-2 IgM and IgG antibodies, and the characteristics of these patients were examined. Forty-five patients diagnosed with COVID-19 were enrolled, and thirty-four patients were followed up until they tested negative for SARS-CoV-2 IgM and IgG antibodies or up to twelve months after the date of a negative SARS-CoV-2 polymerase chain reaction （PCR） result. The positivity rates of SARS-CoV-2 IgM and IgG antibodies were 27.3％ and 68.2％ when SARS-CoV-2 PCR was negative, 20.6％ and 70.6％ after one month, 8.8％ and 52.9％ after three months, and 0.0％ and 14.7％ after six months, respectively. Moreover, we compared patients with milder conditions who did not require oxygen administration with those with severe conditions which required oxygen administration. The positivity rate of SARS-CoV-2 IgG antibodies was significantly higher in patients with severe conditions than in those with milder conditions on the date of a negative SARS-CoV-2 PCR result and after one month and three months, but not after six months. Patients with more severe COVID-19 produced more SARS-CoV-2 IgG antibodies. Moreover, it is suggested that the duration of IgG antibody production is independent of COVID-19 severity