Sh3bp2 Gain-Of-Function Mutation Ameliorates Lupus Phenotypes in B6.MRL-Faslpr Mice

SH3 domain-binding protein 2 (SH3BP2) is an adaptor protein that is predominantly expressed in immune cells, and it regulates intracellular signaling. We had previously reported that a gain-of-function mutation in SH3BP2 exacerbates inflammation and bone loss in murine arthritis models. Here, we explored the involvement of SH3BP2 in a lupus model. Sh3bp2 gain-of-function (P416R knock-in; Sh3bp2KI/+) mice and lupus-prone B6.MRL-Faslpr mice were crossed to yield double-mutant (Sh3bp2KI/+Faslpr/lpr) mice. We monitored survival rates and proteinuria up to 48 weeks of age and assessed renal damage and serum anti-double-stranded DNA antibody levels. Additionally, we analyzed B and T cell subsets in lymphoid tissues by flow cytometry and determined the expression of apoptosis-related molecules in lymph nodes. Sh3bp2 gain-of-function mutation alleviated the poor survival rate, proteinuria, and glomerulosclerosis and significantly reduced serum anti-dsDNA antibody levels in Sh3bp2KI/+Faslpr/lpr mice. Additionally, B220+CD4-CD8- T cell population in lymph nodes was decreased in Sh3bp2KI/+Faslpr/lpr mice, which is possibly associated with the observed increase in cleaved caspase-3 and tumor necrosis factor levels. Sh3bp2 gain-of-function mutation ameliorated clinical and immunological phenotypes in lupus-prone mice. Our findings offer better insight into the unique immunopathological roles of SH3BP2 in autoimmune diseases

Duration of Electrically Induced Atrial Fibrillation Is Augmented by High Voltage of Stimulus with Higher Blood Pressure in Hypertensive Rats

Objective. Many previous clinical studies have suggested that atrial fibrillation (AF) is closely associated with hypertension. However, the benefits of antihypertensive therapy on AF are still inconsistent, and it is necessary to explore the factors augmenting AF in hypertensive rats. The aim of the present study was to investigate the correlation between arterial pressure or voltage stimulus and to the duration of electrically induced AF in normotensive or hypertensive rats. Methods. AF was reproducibly induced by transesophageal atrial burst pacing in spontaneously hypertensive rats (SHR) and Wistar-Kyoto rats (WKY). We did the burst pacing at high (20 V) or low (5 V) voltage. Results. Duration of AF did not correlate with systolic blood pressure (SBP) and stimulus voltage in WKY. However, only in SHR, duration of AF with high stimulus voltage significantly correlated with SBP and was significantly longer in high than in low voltage stimulus. Discussion and Conclusion. Duration of AF is augmented by high voltage stimulus with higher blood pressure in SHR

Absorption of phenolsulfonphthalein as a model across the mesenteric surface in rats to determine the drug absorption route after intraperitoneal administration

The purpose of this study is to clarify absorption characteristics of a drug across the mesenteric surface which occupies a large area of absorption in the peritoneal cavity in order to determine the drug absorption route after intraperitoneal administration. Absorption of phenolsulfonphthalein (PSP) as a model after application to the mesenteric surface was investigated in rats, by employing a cylindrical diffusion cell attached to the mesentery with or without blood vessels. PSP was absorbed from the rat mesenteric surface, followed by its appearance in the plasma and bile, regardless of blood vessel existence. The absorption ratios of PSP in 6 h were calculated to be 92.1 % and 83.6 % from the mesenteric surface with and without blood vessels, respectively. We then employed an experimental system by sticking a polyethylene cap (PE cap) on the surface of the other side to exclude the influence of absorption of the drug from the other organ surfaces that penetrated across the mesentery. The PE cap-sticking decreased the appearance of PSP in the plasma from the mesenteric surface with blood vessels and eliminated the PSP absorption completely from the mesenteric surface without blood vessels. Accordingly, blood vessels on the mesenteric surface actually play an important role in drug absorption, but the contribution of the mesenteric surface to drug absorption from the peritoneal cavity is unlikely to be significant due to there being a small effective area of blood vessels

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基礎看護学は,看護学の導入部であり,各看護学に発展・応用されるための基礎として身につけられるよう教授してきた。しかし,基礎看護学実習IIが2年次後期の実施であったため,カリキュラムの進度上学生に混乱を招いていた。そこで,今年度の新カリキュラムの開始に伴い,各看護学との調整を図り,1年次に基礎看護学を位置付け実施した。中でも基礎看護学実習IIは,基礎看護学の最終段階で各看護学への移行時期にあり,実習での学習の成果がその後の学習に反映されていく。そのため,旧カリキュラムと新カリキュラムで実施した学生の学びについて把握する必要性を感じ,基礎看護学実習[終了後の学生のレポートを比較検討した。その結果,知識や経験の差が学びの違いとなって現れていたが,1年生では学内で行っている学習と臨床実習との関連が認識され,これまでの学習姿勢を振り返り,今後の学習意欲につながっていた。そして,経験の乏しい中からも看護の役割を考え,看護する事の喜びを感じ,看護する者として様々な人々の生き方や生きる姿勢を学ぶことが必要だと感じることができていた

Absorption characteristics of model compounds with different molecular weights from the serosal caecal surface in rats

The purpose of this study is to clarify the absorption characteristics of drugs across the serosal cecal surface membrane occupying a large absorption area in the peritoneal cavity in rats. Absorptions of phenolsulphonphthalein (PSP) and fluorescein isothiocyanate-dextrans (FDs) as model drugs after application to the rat serosal cecal surface were investigated in rats, employing a cylindrical diffusion cell. PSP was absorbed from the rat serosal cecal surface, followed by appearance in the plasma and bile. The time course of the remaining PSP amount in the diffusion cell obeyed first-order kinetics, and its rate constant Ka was calculated to be 8.01 x 10-3 min-1. No significant difference was seen in the absorption ratio of PSP which was approximately 90 % in 6 h among three doses (0.3, 0.5 and 1 mg), suggesting a linearity of absorption. Moreover, the absorption ratios of FDs from the rat serosal cecal surface at 3 h decreased with an increase in the molecular weight (24.7% for FD-4, 12.8% for FD-10 and 3.4% for FD-40)

Influence of primary and secondary prevention indications on anxiety about the implantable cardioverter-defibrillator

AbstractBackgroundImplantable cardioverter-defibrillators (ICDs) have been established for primary and secondary prevention of fatal arrhythmias. However, little is known about the influence of ICD indications on quality of life (QOL) and psychological disturbances. This study aimed to examine whether there were differences in QOL and psychological distress in patients that have an ICD for primary or secondary prevention of fatal arrhythmias.MethodsA multicenter survey of 179 consecutive outpatients (29.1% primary prevention) with ICD implantations completed the Short Form-8 (SF-8), Beck Depression Inventory (BDI), Impact of Event Scale-Revised (IES-R), State-Trait Anxiety Inventory (STAI), and Worries about ICD (WAICD).ResultsPatients with an ICD for primary prevention had a higher trait anxiety score and worries about ICD score than patients with an ICD for secondary prevention (41.7±12.4 vs. 34.7±12.3, p=0.001 and 39.6±18.0 vs. 30.0±18.9, p=0.002, respectively), even after adjusting for demographic and clinical characteristics. In multivariable analysis of variance, primary prevention ICD recipients reported a poorer QOL on the vitality subscale of the SF-8.ConclusionsIn our study population, which mostly consisted of New York Heart Association (NYHA) class I and II subjects, primary prevention ICD recipients were more prone to experience worries about their ICD, anxiety, and a poorer QOL compared to secondary prevention ICD recipients. In clinical practice, primary prevention ICD patients should be closely monitored. If warranted, they should be offered psychological intervention, as anxiety and low QOL were predictors of mortality

Delivery advantage to the unilateral kidney by direct drug application to the kidney surface in rats and pharmacokinetic verification based on a physiological model

The objective of this study was to evaluate the drug delivery advantage to the unilateral kidney by direct drug application to the rat kidney surface based on a physiological pharmacokinetic model. Under anesthesia, a cylindrical diffusion cell (i.d. 6 mm, area 0.28 cm(2)) was attached to the right kidney surface in rats. Phenolsulfonphthalein (PSP), an organic anion chosen as a model compound, was added into the diffusion cell. The free PSP concentration in the right (applied) kidney after application to the right kidney surface at a dose of 1 mg was significantly higher than that of the left (non-applied) kidney until 60 min after application. Similarly, the urinary excretion rate of free PSP from the applied kidney was much faster than that from the non-applied kidney, with a 2.6 times larger excreted amount in 240 min. These results imply the possibility that a considerable drug delivery advantage to the unilateral kidney could be obtained after direct absorption from the kidney surface. This tendency was also observed at the other application doses of 0.3 and 1.5 mg. On the other hand, fluorescein isothiocyanate dextran (Mw 4400, FD-4) was equally excreted into the urine from each kidney and the renal concentrations in the applied and non-applied kidneys were almost the same, possibly due to the involvement of passive transport for the absorbed FD-4, i.e. glomerular filtration. The computer simulations of free PSP concentrations in the plasma and each kidney based on a physiological model after kidney surface application were consistent with the respective experimental data. Moreover, the delivery advantage of kidney surface application of PSP was verified by its comparison with other routes such as i.v. and i.a. administrations

The Hayabusa Spacecraft Asteroid Multi-Band Imaging Camera: AMICA

The Hayabusa Spacecraft Asteroid Multiband Imaging Camera (AMICA) has acquired more than 1400 multispectral and high-resolution images of its target asteroid, 25143 Itokawa, since late August 2005. In this paper, we summarize the design and performance of AMICA. In addition, we describe the calibration methods, assumptions, and models, based on measurements. Major calibration steps include corrections for linearity and modeling and subtraction of bias, dark current, read-out smear, and pixel-to-pixel responsivity variations. AMICA v-band data were calibrated to radiance using in-flight stellar observations. The other band data were calibrated to reflectance by comparing them to ground-based observations to avoid the uncertainty of the solar irradiation in those bands. We found that the AMICA signal was linear with respect to the input signal to an accuracy of << 1% when the signal level was < 3800 DN. We verified that the absolute radiance calibration of the AMICA v-band (0.55 micron) was accurate to 4% or less, the accuracy of the disk-integrated spectra with respect to the AMICA v-band was about 1%, and the pixel-to-pixel responsivity (flatfield) variation was 3% or less. The uncertainty in background zero-level was 5 DN. From wide-band observations of star clusters, we found that the AMICA optics have an effective focal length of 120.80 \pm 0.03 mm, yielding a field-of-view (FOV) of 5.83 deg x 5.69 deg. The resulting geometric distortion model was accurate to within a third of a pixel. We demonstrated an image-restoration technique using the point-spread functions of stars, and confirmed that the technique functions well in all loss-less images. An artifact not corrected by this calibration is scattered light associated with bright disks in the FOV.Comment: 107 pages, 22 figures, 9 tables. will appear in Icaru

Impact of administering umbilical cord-derived mesenchymal stem cells to cynomolgus monkeys with endometriosis

Purpose: This study aimed to explore whether umbilical cord-derived mesenchymal stem cells (UC-MSCs) could be used as a therapeutic resource for endometriosis. Methods: Of seven cynomolgus monkeys with endometriosis, five were administered UC-MSCs (intervention group) and two were administered saline (control group). First, intravenous US-MSC treatment was administered for three months. Second, weekly intravenous US-MSC administration combined with monthly intraperitoneal US-MSC administration was conducted for 3 months. Finally, weekly intraperitoneal US-MSC administration was conducted for 3 months. The dose of UC-MSCs was set to 2 × 106 cells/kg for all administration routes. Laparoscopic findings and serum cancer antigen 125 (CA125) levels were also evaluated. The Revised American Society for Reproductive Medicine classification was used for laparoscopic evaluation. Results: Laparoscopic findings showed exacerbation of endometriosis after intraperitoneal UC-MSC administration, although no changes were observed in the control group. Intravenous UC-MSC administration decreased the level of CA125 in all monkeys; however, the difference was not significant. Intraperitoneal UC-MSC administration significantly exacerbated endometriosis compared with intravenous administration (p = 0.02). Conclusions: This study revealed that intraperitoneal UC-MSC administration exacerbates endometriosis in a nonhuman primate model of the disease.journal articl