Feeding Cues and Injected Nutrients Induce Acute Expression of Multiple Clock Genes in the Mouse Liver

The circadian clock is closely associated with energy metabolism. The liver clock can rapidly adapt to a new feeding cycle within a few days, whereas the lung clock is gradually entrained over one week. However, the mechanism underlying tissue-specific clock resetting is not fully understood. To characterize the rapid response to feeding cues in the liver clock, we examined the effects of a single time-delayed feeding on circadian rhythms in the liver and lungs of Per2::Luc reporter knockin mice. After adapting to a night-time restricted feeding schedule, the mice were fed according to a 4, 8, or 13 h delayed schedule on the last day. The phase of the liver clock was delayed in all groups with delayed feeding, whereas the lung clock remained unaffected. We then examined the acute response of clock and metabolism-related genes in the liver using focused DNA-microarrays. Clock mutant mice were bred under constant light to attenuate the endogenous circadian rhythm, and gene expression profiles were determined during 24 h of fasting followed by 8 h of feeding. Per2 and Dec1 were significantly increased within 1 h of feeding. Real-time RT-PCR analysis revealed a similarly acute response in hepatic clock gene expression caused by feeding wild type mice after an overnight fast. In addition to Per2 and Dec1, the expression of Per1 increased, and that of Rev-erbα decreased in the liver within 1 h of feeding after fasting, whereas none of these clock genes were affected in the lung. Moreover, an intraperitoneal injection of glucose combined with amino acids, but not either alone, reproduced a similar hepatic response. Our findings show that multiple clock genes respond to nutritional cues within 1 h in the liver but not in the lung

Correlation between HIV disease and lipid metabolism in antiretroviral-naïve HIV-infected patients in Japan

Antiretroviral therapy alters lipid metabolism in HIV-infected patients. However, interpreting the impact of HIV infection on lipid metabolism is difficult because of various associated factors, including antiretroviral drugs and demographic characteristics. A few studies have associated HIV infection with lipid metabolism in antiretroviral-naïve HIV-infected patients. Because there were no data in this regard from Japan, the present study examined the impact of HIV infection, as well as demographic and clinical features, on lipid metabolism in antiretroviral-naïve HIV-infected patients in Japan. We performed a cross-sectional study to examine the impact of HIV disease, demographic and clinical characteristics on lipid metabolism among 168 HIV-infected Japanese men who were antiretroviral naïve and who did not have hemophilia, including patients who took medication for dyslipidemia. The mean age of the patients was 45.7 years; 0.6% of the patients took medication to dyslipidemia. The mean CD4 lymphocyte count was 289/μL, the mean baseline log10 HIV viral load was 4.2 HIV-1 RNA copies/mL, and 22% of the patients had a history of AIDS-defining events. A higher HDL-C concentration was associated with a higher CD4 lymphocyte count (p = 0.043). Also, a higher LDL-C concentration was associated with a higher CD4 lymphocyte count (p = 0.003). Infection with HIV was associated with dyslipidemia in antiretroviral-naïve patients. More advanced HIV disease was associated with less favorable lipid homeostatic profiles. These results are similar to findings from other countries

Seismometric Observations of Matsushiro Swarm Earthquakes

This paper is the report of seismometric observations of Matsushiro swarm earthquakes made by Abuyama Seismological Observatory and Disaster Prevention Research Institute, independently or co-operatively. Continuous observation at Shinko has been carried out to investigate the time variation of the seismic activity since the joint observation of ultramicro-earthquakes at the end of 1965. As the seismicity became active, continuous observation was started at Sanada, too, on June, 1966, with the main purpose of investigating the "Ishimoto-Iida's relation" and the time variation of seismic activity, but it was abandoned on September, 1966 because of overlapping the station with that of the Earthquake Research Institute. For studying the attenuation of seismic wave in short hypocentral distance and formulating the equation for calculating the magnitude of an earthquake, the Matsushiro swarm earthquakes are a very good source observations. On the basis of this idea, we picked out four observation points on the array line from Matsushiro to Komoro, and installed completely equipped low magnification seismographs of displacement type. The observations were begun on June, 1966. Further, on November the same year, the array line turned about 90 degrees for the first line which was extended from Matsushiro to Toyoshina through Akashina. The observations are still being continued at present. As had been planned in the earthquake prediction program in Japan, mobile observations were carried out three times from June to November, 1966, for the purpose of investigating the field problems of this observation system and the seismic activity outside the so-called seismic region of Matsushiro swarm earthquakes. Although this is a simple method by which only the frequency distribution of S-P duration times were observed, notwithstanding its simplicity the mobile observation system for the purpose of surveying the seismic activity was proved useful in the region where the dense observation network had not then been set up. Though the idea that the earthquakes are almost always generated in the vicinity of the fault is exceedingly Americanized, we carried out the observation of ultramicro-earthquakes by the seismometer-array, with an expectation that some relation between the cracks around Mt. Minakami and ultramicro-earthquakes may exist. However this expectation has been proved completely to the contrary

Influence of smoking on HIV infection among HIV-infected Japanese men

AbstractWe performed a cross-sectional study that included 100 HIV-infected Japanese men without hemophilia to examine the influence of smoking on HIV infection. History of smoking was obtained using a questionnaire. The percentage of current smokers was 40% and was the highest (50%) among men in their forties. The mean Brinkman index (BI, number of cigarettes smoked per day multiplied by years of smoking) was 450. The percentage of patients with a BI ≥600 was significantly higher in patients with an AIDS-defining event than in those without an AIDS-defining event. A BI ≥600 was associated with an AIDS-defining event. Reducing smoking appears to be critical to enhancing disease management efforts in Japanese men with HIV

Chloride-sensitive nature of the histamine-induced Ca2+ entry in cultured human aortic endothelial cells

Whole-cell currents and intracellular Ca2+ concentration ([Ca2+]i) were recorded in cultured human aortic endothelial cells (HAECs) to study the mechanisms underlying Cl−-sensitive Ca2+ entry.In the absence of histamine the membrane potential ranged between -90 and +5 mV and showed bimodal distribution with peaks at -17.8 and -67.5 mV.Histamine (1-100 μm) activated an outward current, followed by a sustained inward current at -50 mV. The reversal potential (Vrev) was more negative than -60 mV for the initial outward current, and approximately -30 mV for the sustained inward current with normal Tyrode solution and internal solution containing 30 mM Cl−.Vrev of the sustained inward current was hardly affected by varying the external concentrations of K+, Na+ and Ca2+, but was greatly changed by varying the external Cl− concentration ([Cl−]o). The relationship between Vrev and log[Cl−]o showed a slope of -44.8 mV per tenfold increase of [Cl−]o.The Cl− channel blockers 9-anthracene carboxylic acid (1 mM), N-phenylanthranilic acid (0.1 mM) and niflumic acid (0.1 mM) all depressed the histamine-induced inward current. The non-selective cation channel blocker Gd3+ (10 μm) was without effect on the current.In the absence of histamine, [Ca2+]i was not affected by varying the membrane potential. During the continuous presence of histamine, however, hyperpolarization increased and depolarization decreased [Ca2+]i, indicating that Ca2+ entry through the plasma membrane was activated by histamine.Vrev of the histamine-induced Cl− current, measured by the gramicidin-perforated patch clamp method, was -28.4 ± 6.6 mV (n = 8), which gave an intracellular Cl− concentration of approximately 34 mM. Under the current clamp condition, the membrane potential varied from cell to cell in the control, but application of histamine induced either depolarization or hyperpolarization, depending on the membrane potential before histamine application, and the membrane potential became stable near the equilibrium potential for Cl−.We conclude that the histamine-induced inward current is carried mainly by Cl−. Although Ca2+ entry was also activated, we consider that its amplitude was too small to be resolved by the patch clamp method. The Cl− current may play a functional role in the sustained [Ca2+]i elevation by providing a constant driving force for Ca2+ entry in the presence of histamine