μ-opioid Receptor-Mediated Alterations of Allergen-Induced Immune Responses of Bronchial Lymph Node Cells in a Murine Model of Stress Asthma

ABSTRACTBackgroundPsychological stress has a recognized association with asthma symptoms. Using a murine model of allergic asthma, we recently demonstrated the involvement of μ-opioid receptors (MORs) in the central nervous system in the stress-induced exacerbation of airway inflammation. However, the involvement of MORs on neurons and immunological alterations in the stress asthma model remain unclear.MethodsMOR-knockout (MORKO) mice that express MORs only on noradrenergic and adrenergic neurons (MORKO/Tg mice) were produced and characterized for stress responses. Sensitized mice inhaled antigen and were then subjected to restraint stress. After a second antigen inhalation, bronchoalveolar lavage cells were counted. Before the second inhalation, bronchial lymph node (BLN) cells and splenocytes from stressed and non-stressed mice were cultured with antigen, and cytokine levels and the proportions of T cell subsets were measured.ResultsStress-induced worsening of allergic airway inflammation was observed in wild-type and MORKO/Tg mice but not MORKO mice. In wild-type stressed mice, IFN-γ/IL-4 ratios in cell culture supernatants and the proportion of regulatory T cells in BLN cell populations were significantly lower than those in non-stressed mice. These differences in BLN cells were not observed between the stressed and non-stressed MORKO mice. Restraint stress had no effect on cytokine production or T cell subsets in splenocytes.ConclusionsRestraint stress aggravated allergic airway inflammation in association with alterations in local immunity characterized by greater Th2-associated cytokine production and a reduced development of regulatory T cells, mediated by MORs

Effect of a Large Dose of Di (2-ethylhexyl) phthalate (DEHP) on Hepatic Peroxisome in Cynomolgus Monkeys (Macaca Fascicularis)

To elucidate the effect of a large dose of di (2-ethylhexyl) phthalate (DEHP), a plasticizer and peroxisome proliferator-activated receptor-α (PPARα) agonist, on hepatic peroxisomes, we orally administered 1,000 mg/kg/day, once daily, to 3 male and 4 female cynomolgus monkeys for 28 days consecutively. Light-microscopic and electron microscopic examinations of the liver were carried out in conjunction with measurement of the hepatic fatty acid β-oxidation system (FAOS), carnitine acetyltransferase (CAT) and carnitine palmitoyltransferase (CPT) activities, which are peroxisomal and/or mitochondrial enzyme activities. Electron microscopically, enlargement of the mitochondria was observed with lamellar orientation of the cristae along the major axis. Although the number of peroxisomes showed a tendency to increase when compared with those in a biopsied specimen before treatment, no abnormality in morphology was observed. A slight increase in CPT activity was noted at termination. No changes were noted in hepatic FAOS or CAT activity. In conclusion, although repeated oral treatment of cynomolgus monkeys with a large dose of DEHP induced a subtle increase in the numbers of peroxisomes with slight enlargements of the mitochondria, this low-sensitivity response to peroxisome proliferators in cynomolgus monkeys was considered to be closer to the response in humans than that in rodents

Is the progression of treatment for patients with hemophilia leading to improvements in school or social life?: A questionnaire survey for mothers of children or adolescents who chiefly receive prophylactic treatment for hemophilia.

【背景】血友病患者の治療は進歩した。そこで治療の進歩による患者の学校・社会生活の詳細を明らかにするために，母親を対象に，若年世代の患者の学校・社会生活，母親の困り事について実態調査した。 【方法】血友病患者の母親を対象に，無記名自記式の質問紙調査を実施した。 【結果】母親27人の回答が得られ，息子である患者は30人だった。定期輸注実施は23人で，そのうち家庭で輸注を行う者は22人だった。通園経験のある者は27人だった。全ての行事に参加させた者が18人だった。宿泊行事中の定期輸注の実施について，中学生までは学校に支援依頼していた。患者８人は自己注射し，高校生以降の患者４人は，自室で一人の時に注射をしたという回答だった。母親の困り事は「血管確保の失敗と焦り」だった。 【結論】治療の進歩は患者の学校・社会生活を改善した。しかし継続的治療を支える家族の負担のもとに成立する。今後必要な医療支援として，患者の宿泊行事中の輸注において，患者が安心して注射できる場所についての助言が示された。Background: Hemostatic treatment for patients with hemophilia（ PWH） has improved. The aim of this study was to clarify school status and social life among young boys with hemophilia, as well as their mothers’ frustrations. Methods: A questionnaire survey was completed anonymously by mothers of hemophilic boys. Results: A total of 27 mothers of 30 PWHs completed the survey. Twenty-three PWHs had received prophylactic treatment, and 22 received home infusion therapy. Twenty-seven PWHs had attended preschool, and 18 had participated in all preschool/school events. When factor concentrates needed to be infused during overnight events, many mothers requested the assistance of medical staff until the PWHs were junior high school students. When they were high school students, eight PWHs were able to infuse themselves. Four PWHs were reported to infuse alone, hiding from the public eye. Mothers’ chief source of frustration was“ infusion failure on busy mornings.” Conclusion: This study indicates that the progress of treatment for PWHs may improve the school or social life of patients. However, these patients’ family support is also essential for the patients’ treatment. Medical support, such as advice about where to self-infuse during overnight events is needed for PWHs

A Subaru Search for Lyman-Alpha Emitters at z=5.8 with an Intermediate-Band Filter

We present the results of a survey for Ly-alpha emitters at z ~ 5.8 using a new intermediate-band filter centered at lambda_c = 8275 AA with Delta-lambda_FWHM = 340 AA (i.e., the spectroscopic resolution is R ~ 23) with a combination with a traditional narrow-band centered at lambda_c = 8150 AA with Delta-lambda_FWHM = 120 AA (R ~ 68). Our observations were made with use of the Subaru Prime Focus Camera, Suprime-Cam, on the 8.2 m Subaru telescope in a sky area surrounding the high redshift quasar, SDSSp J104433.04-012522.2 at z=5.74, covering an effective sky area with ~ 720 arcmin^2. In this survey, we have found four Ly-alpha-emitter candidates from the intermediate-band image (z \~ 5.8 with Delta z ~ 0.3). Combined with our previous results based on the NB816 imaging, we discuss the star formation activity in galaxies between z ~ 5.7 and z ~ 5.9.Comment: 8 pages, 8 figures. Accepted for publication in PAS

Isoform-specific potentiation of stem and progenitor cell engraftment by AML1/RUNX1

Background: AML1/RUNX1 is the most frequently mutated gene in leukaemia and is central to the normal biology of hematopoietic stem and progenitor cells. However, the role of different AML1 isoforms within these primitive compartments is unclear. Here we investigate whether altering relative expression of AML1 isoforms impacts the balance between cell self-renewal and differentiation in vitro and in vivo. Methods and Findings: The human AML1a isoform encodes a truncated molecule with DNA-binding but no transactivation capacity. We used a retrovirus-based approach to transduce AML1a into primitive haematopoietic cells isolated from the mouse. We observed that enforced AML1a expression increased the competitive engraftment potential of murine long-term reconstituting stem cells with the proportion of AML1a-expressing cells increasing over time in both primary and secondary recipients. Furthermore, AML1a expression dramatically increased primitive and committed progenitor activity in engrafted animals as assessed by long-term culture, cobblestone formation, and colony assays. In contrast, expression of the full-length isoform AML1b abrogated engraftment potential. In vitro, AML1b promoted differentiation while AML1a promoted proliferation of progenitors capable of short-term lymphomyeloid engraftment. Consistent with these findings, the relative abundance of AML1a was highest in the primitive stem/progenitor compartment of human cord blood, and forced expression of AML1a in these cells enhanced maintenance of primitive potential both in vitro and in vivo. Conclusions: These data demonstrate that the "a" isoform of AML1 has the capacity to potentiate stem and progenitor cell engraftment, both of which are required for successful clinical transplantation. This activity is consistent with its expression pattern in both normal and leukaemic cells. Manipulating the balance of AML1 isoform expression may offer novel therapeutic strategies, exploitable in the contexts of leukaemia and also in cord blood transplantation in adults, in whom stem and progenitor cell numbers are often limiting. © 2007 Tsuzuki et al

A Shock-Induced Pair of Superbubbles in the High-Redshift Powerful Radio Galaxy MRC 0406-244

We present new optical spectroscopy of the high-redshift powerful radio galaxy MRC 0406$-$244 at redshift of 2.429. We find that the two extensions toward NW and SE probed in the rest-frame ultraviolet image are heated mainly by the nonthermal continuum of the active galactic nucleus. However, each extension shows a shell-like morphology, suggesting that they are a pair of superbubbles induced by the superwind activity rather than by the interaction between the radio jet and the ambient gas clouds. If this is the case, the intense starburst responsible for the formation of superbubbles could occur $\sim 1 \times 10^9$ yr ago. On the other hand, the age of the radio jets may be of the order of $\sim 10^6$ yr, being much shorter than the starburst age. Therefore, the two events, i.e., the starburst and the radio-jet activities, are independent phenomena. However, their directions of the expanding motions could be governed by the rotational motion of the gaseous component in the host galaxy. This idea appears to explain the alignment effect of MRC 0406$-$244.Comment: 4 pages (emulateapj.sty), Fig. 1 (jpeg) + Fig.2 (eps). Accepted for publications in ApJ (Letters