p38 Mitogen-activated Protein Kinase Regulates Oscillation of Chick Pineal Circadian Clock

Extracellular signal-regulated kinase (ERK) and p38 are members of the mitogen-activated protein kinase (MAPK) family, and in some cases these kinases serve for closely related cellular functions within a cell. In a wide range of animal clock structures, ERK plays an important role in the circadian time-keeping mechanism. Here we found that immunoreactivity to p38 protein was uniformly distributed among cells in the chick pineal gland. On the other hand, a constant level of activated p38 was detected over the day, predominantly in the follicular and parafollicular pinealocytes that are potential circadian clock-containing cells. Chronic application of SB203580, a selective and reversible inhibitor of p38, to the cultured chick pineal cells markedly lengthened the period of the circadian rhythm of the melatonin release (up to 28.7 h). Noticeably, despite no significant temporal change of activated p38 level, a 4-h pulse treatment with SB203580 delayed the phase of the rhythm only when delivered during the subjective day. These results indicate a time-of-day-specific role of continuously activated p38 in the period length regulation of the chick pineal clock and suggest temporally separated regulation of the clock by two MAPKs, nighttime-activated ERK and daytime-working p38

Attitudes of Japanese Medical Students towards Disclosure of a Diagnosis of Life-threatening Illness

In this study we investigated the attitudes of Japanese medical students toward being informed of a diagnosis of life-threatening illness. Fourth-year medical students from 20 randomly sampled universities were administered questionnaires that examined their opinion about whether they would welcome disclosure of medical information if they were diagnosed as having an ultimately fatal disease. Data from 1,619 students (male 1,074, female 545, effective collection rate 90.6%) were analyzed. With regard to attitudes about disclosure of a diagnosis of life-threatening illness, 87.7% of the students stated that they would wish to be informed even if there was little chance of recovery, and 11.6% expressed a wish to be informed of their condition only if there was a chance of recovery. Students who did not wish to be informed even if there was a chance of recovery accounted for 0.7% of those surveyed. Our study reveals that medical students are more positive than are members of the general population with regard to being informed of the truth. The proportion of those who wished to be informed even if there was little chance of recovery was higher among students from national and public universities than among those from private universities, and the inter-group difference was statistically significant. Among male students, answers to the survey were significantly correlated with 12-item General Health Questionnaire scores and mental health status, suggesting that mental health status may have affected how this study population viewed being informed of their diagnosis.</p

Leukocyte-depleted terminal blood cardioplegia provides superior myocardial protective effects in association with myocardium-derived nitric oxide and peroxynitrite production for patients undergoing prolonged aortic crossclamping for more than 120 minutes

AbstractObjectivesThis study was designed to examine the myocardial protective effect of leukocyte-depleted terminal blood cardioplegia in association with nitric oxide and peroxynitrite production, especially for patients undergoing prolonged aortic crossclamping.MethodsFifty-four patients (34 men, 20 women, mean age 56.7 ± 12.7 years) undergoing aortic valve replacement were randomly allocated to one of two groups; group LDTC (n = 27) received 10 minutes of leukocyte-depleted terminal blood cardioplegic solution, and group CONT (n = 27) served as controls. Each group was subdivided into 2 groups: aortic crossclamping for less than 120 minutes in groups LDTC-S (n = 13) and CONT-S (n = 14); aortic crossclamping for 120 minutes or more in groups LDTC-L (n = 14) and CONT-L (n = 13).ResultsAfter aortic unclamping, group LDTC-L showed higher incidence of spontaneous defibrillation (78.6% vs 30.8%, P = .0213), higher plasma nitrate + nitrite in the coronary sinus effluent (32.5 ± 4.1 vs 28.7 ± 3.0 μmol/L, P = .0013), lower differences between coronary sinus effluent and arterial blood in the percentage ratio of nitrotyrosine to tyrosine (myocardium-derived peroxynitrite; 2.987% ± 0.576% vs 3.951% ± 0.952%, P = .0036), and plasma polymorphonuclear-elastase (113.9 ± 21.3 vs 155.5 ± 41.6 μg/L, P = .0029) and malondialdehyde (2.75 ± 0.67 vs 4.02 ± 0.96 μmol/L, P = .0005) than group CONT did. Postoperatively, group LDTC-L showed lower human-heart fatty acid–binding protein (111.4 ± 25.2 vs 156.4 ± 38.6 IU/L, P = .0013), lower creatine kinase–muscle and brain (19.2 ± 4.7 vs 24.8 ± 6.5 IU/L, P = .0120), and smaller requirement of catecholamine (5.44 ± 2.29 vs 8.45 ± 3.42 μg · kg−1 · min−1, P = .0122). There were no significant differences in these parameters between groups LDTC-S and CONT-S.ConclusionsThis study demonstrated that leukocyte-depleted terminal blood cardioplegia provided superior myocardial protective effects and regulated myocardial-derived nitric oxide and peroxynitrite production only for patients undergoing aortic crossclamping for more than 120 minutes. The results suggest that prolonged aortic crossclamping deteriorates the tolerance to leukocyte-mediated myocardial injury accompanied by endothelial dysfunction associated with nitric oxide and peroxynitrite production

Effect of thyroid statuses on sodium/iodide symporter (NIS) gene expression in the extrathyroidal tissues in mice

<p>Abstract</p> <p>Background</p> <p>Iodide that is essential for thyroid hormone synthesis is actively transported into the thyroid follicular cells via sodium/iodide symporter (NIS) protein in vertebrates. It is well known that NIS expression in thyroid is regulated by the thyroid statuses mainly through thyroid stimulating hormone (TSH). Although <it>NIS </it>mRNA expressions in extrathyroidal tissues have been qualitatively reported, their regulation by thyroid statuses has not been well clarified.</p> <p>Methods</p> <p>Male ICR mice aged four weeks were assigned into three groups (control, hypothyroid, and hyperthyroid). Hypothyroid group of mice were treated with 0.02% methimazole in drinking water and hyperthyroid group of mice received intraperitoneal injection (4 μg _L-T₄twice a week) for four weeks. <it>NIS </it>mRNA expression levels in the tissues were evaluated using Northern blot hybridization and quantitative real-time RTPCR (qPCR). Additionally, end-point RTPCR for the thyroid follicular cell-characteristic genes (TSH receptor, <it>TSHR</it>; thyroid transcription factor-1, <it>TTF1</it>; and paired box gene 8, <it>Pax8</it>) was carried out.</p> <p>Results</p> <p>By Northern blot analysis, <it>NIS </it>mRNA was detected in thyroid and stomach. In addition to these organs, qPCR revealed the expression also in the submandibular gland, colon, testis, and lung. Expression of <it>NIS </it>mRNA in thyroid was significantly increased in hypothyroid and decreased in hyperthyroid group. Trends of <it>NIS </it>mRNA expression in extrathyroidal tissues were not in line with that in the thyroid gland in different thyroid statuses. Only in lung, <it>NIS </it>mRNA was regulated by thyroid statuses but in opposite way compared to the manner in the thyroid gland. There were no extrathyroidal tissues that expressed all three characteristic genes of thyroid follicular cells.</p> <p>Conclusions</p> <p><it>NIS </it>mRNA expression in the thyroid gland was up-regulated in hypothyroid mice and was down-regulated in hyperthyroid mice, suggesting that <it>NIS </it>mRNA in the thyroid gland is regulated by thyroid statuses. In contrast, <it>NIS </it>mRNA expression in extrathyroidal tissues was not altered by thyroid statuses although it was widely expressed. Lack of responsiveness of <it>NIS </it>mRNA expressions in extrathyroidal tissues reemphasizes additional functions of NIS protein in extrathyroidal tissues other than iodide trapping.</p

A chloride capturing system: Via proton-induced structure transformation between opened- and closed-forms of dodecavanadates

Chloride-incorporated dodecavanadates show two distinct structures of the monoprotonated-form [HV12O32(Cl)]4- (closed-V12) with a spherical closed-structure and the opened-form [V12O32(Cl)]5- (opened-V12). The reaction of closed-V12 with a stoichiometric amount of ethylenediamine drives the structure transformation reaction to opened-V12, quantitatively. From time dependent observations of 51V NMR, a tube-type intermediate [V12O32(Cl)]5- (tube-V12) was observed in the transformation process. Isolation of the intermediate was achieved by the deprotonation reaction of closed-V12 with diethylamine, and the structure transformation was confirmed by using the isolated intermediate. The reverse transformation from opened-V12 to closed-V12 was also achieved by addition of trifluoroacetic acid. The geometrical difference between closed-V12 and opened-V12 is reflected in the reactivity difference to the external reagents, and this was demonstrated by examining the chloride removal reaction by using a silver cation. The incorporated chloride was preserved in the closed-V12 cage even in the presence of a silver cation. In contrast, the chloride in opened-V12 was removed as AgCl by the silver cation. In addition, by the reaction of chloride-free opened-V12 with a quantitative amount of {Et4N}Cl retrieved opened-V12, showing the capability of opened-V12 to recapture a guest chloride in the cavity. This transformation between two isomeric dodecavanadate structures is regarded as the movement of a molecular mitt to catch a ball and secure it. © 2016 The Royal Society of Chemistry.Embargo Period 12 month

Patient affect and caregiver burden in dementia

BACKGROUND: Numerous studies focusing on the burden of caregivers of dementia patients have been published. However, there have been few studies focusing on positive affect as an important factor affecting the caregiver burden, and only a few studies comparing the caregiver burden between different dementia diseases have been reported. METHODS: Three hundred and thirty-seven consecutive caregivers of people with dementia participated in this study. The caregiver burden was evaluated by the short version of the Japanese version of the Zarit Burden Interview. RESULTS: Positive affect scores had a significant relationship with the scores of the short version of the Zarit Burden Interview. Caregivers for patients with dementia with Lewy bodies or frontotemporal dementia suffered from a greater burden than those for patients with Alzheimer's disease dementia. CONCLUSIONS: The caregiver burden differed between people caring for patients with different dementia diseases. Positive affect of dementia patients has a significant relationship with caregiver burden, independently from neuropsychiatric symptoms of patients

Intestinal Tuberculosis with Hoarseness as a Chief Complaint due to Mediastinal Lymphadenitis

A 68-year-old woman was admitted to our hospital complaining of hoarseness. A chest X-ray detected an abnormal shadow on the upper right lung. Bronchoscopic examination revealed that the left vocal cord was fixed in the paramedian position, and therefore left recurrent nerve paralysis was suspected. Lymphadenopathy was found in the left supraclavicular area. Chest computed tomography showed that the pretracheal and subaortic lymph nodes were swollen. Gastroendoscopy showed a 2-cm protruding lesion with ulceration on the upper esophagus. Histological examination of the supraclavicular lymph nodes and biopsy specimens from the esophagus revealed non-specific inflammation. PET-CT showed abnormal accumulations not only on the upper right lung but also on the lower right of the abdomen. Colonoscopy was performed and multiple erosions on the terminal ileum were found. Polymerase chain reaction analysis of a specimen biopsied from the erosion of the terminal ileum was positive for Mycobacterium tuberculosis and intestinal tuberculosis was diagnosed. The patient was then treated with anti-tuberculous therapy. After treatment, the erosions on the terminal ileum, the swelling of the mediastinal lymphadenopathy, and the esophageal ulcer were all improved. The hoarseness was subsequently relieved. This is the first report of intestinal tuberculosis with hoarseness as a chief complaint due to mediastinal lymphadenitis

DME-Fired Water-Tube Boiler - A R&D Study

Increasing attention has been given to the development of low-NOx combustion technology for DME (Dimethyl Ether). The present paper describes the R&D study for water-tube boiler carried out in Kansai University and Hirakawa Guidam Co., Ltd. under the support of DME project from METI. The major problem in DME use is the difficulty in the application of premixed flame due to its low ignition temperature and rather high burning velocity. However, the previously developed tube-nested combustor, i.e. water-tubes installed in the empty furnace, becomes effective means together with the flue-gas recirculation to overcome such difficulty in achieving low-NOx combustion. This paper begins with a brief review of the R&D study of the tube-nested combustor specifically designed for city gas. Then the further development for DME-fired water-tube boiler is described