NAD+ overconsumption by poly (ADP-ribose) polymerase (PARP) under oxidative stress induces cytoskeletal disruption in vascular endothelial cell.

Vascular endothelial cytoskeletal disruption leads to increased vascular permeability and is involved in the pathogenesis and progression of various diseases. Oxidative stress can increase vascular permeability by weakening endothelial cell-to-cell junctions and decrease intracellular nicotinamide adenine dinucleotide (NAD+) levels. However, it remains unclear how intracellular NAD+ variations caused by oxidative stress alter the vascular endothelial cytoskeletal organization. In this study, we demonstrated that oxidative stress activates poly (ADP-ribose [ADPr]) polymerase (PARP), which consume large amounts of intracellular NAD+, leading to cytoskeletal disruption in vascular endothelial cells. We found that hydrogen peroxide (H2O2) could transiently disrupt the cytoskeleton and reduce intracellular total NAD levels in human umbilical vein endothelial cells (HUVECs). H2O2 stimulation led to rapid increase in ADPr protein levels in HUVECs. Pharmaceutical PARP inhibition counteracted H2O2-induced total NAD depletion and cytoskeletal disruption, suggesting that NAD+ consumption by PARP induced cytoskeletal disruption. Additionally, supplementation with nicotinamide mononucleotide (NMN), the NAD+ precursor, prevented both intracellular total NAD depletion and cytoskeletal disruption induced by H2O2 in HUVECs. Inhibition of the NAD+ salvage pathway by FK866, a nicotinamide phosphoribosyltransferase inhibitor, maintained H2O2-induced cytoskeletal disruption, suggesting that intracellular NAD+ plays a crucial role in recovery from cytoskeletal disruption. Our findings provide further insights into the potential application of PARP inhibition and NMN supplementation for the treatment and prevention of diseases involving vascular hyperpermeability.

Designing the stripe-ordered cuprate phase diagram through uniaxial-stress.

The ability to efficiently control charge and spin in the cuprate high-temperature superconductors is crucial for fundamental research and underpins technological development. Here, we explore the tunability of magnetism, superconductivity, and crystal structure in the stripe phase of the cuprate La[Formula: see text]Ba[Formula: see text]CuO[Formula: see text], with [Formula: see text] = 0.115 and 0.135, by employing temperature-dependent (down to 400 mK) muon-spin rotation and AC susceptibility, as well as X-ray scattering experiments under compressive uniaxial stress in the CuO[Formula: see text] plane. A sixfold increase of the three-dimensional (3D) superconducting critical temperature [Formula: see text] and a full recovery of the 3D phase coherence is observed in both samples with the application of extremely low uniaxial stress of [Formula: see text]0.1 GPa. This finding demonstrates the removal of the well-known 1/8-anomaly of cuprates by uniaxial stress. On the other hand, the spin-stripe order temperature as well as the magnetic fraction at 400 mK show only a modest decrease under stress. Moreover, the onset temperatures of 3D superconductivity and spin-stripe order are very similar in the large stress regime. However, strain produces an inhomogeneous suppression of the spin-stripe order at elevated temperatures. Namely, a substantial decrease of the magnetic volume fraction and a full suppression of the low-temperature tetragonal structure is found under stress, which is a necessary condition for the development of the 3D superconducting phase with optimal [Formula: see text]. Our results evidence a remarkable cooperation between the long-range static spin-stripe order and the underlying crystalline order with the three-dimensional fully coherent superconductivity. Overall, these results suggest that the stripe- and the SC order may have a common physical mechanism.

Nicotinamide mononucleotide inhibits oxidative stress-induced damage in a SIRT1/NQO-1-dependent manner.

Oxidative stress causes endothelial dysfunction, which is associated with vascular cellular aging and is causally related to cardiovascular disease pathogenesis. Preclinical studies indicate that a nicotinamide adenine dinucleotide (NAD+) precursor, nicotinamide mononucleotide (NMN), alleviates oxidative stress in aged vessels, granting vasoprotective effects. However, the associated cellular mechanism remains largely unclear. In this study, we used human umbilical vein endothelial cells (HUVECs) to demonstrate that NMN inhibits oxidative stress-induced damage by activating the sirtuin 1 (SIRT1)/NAD(P)H: quinone oxidoreductase 1 (NQO-1) axis. We found that NMN inhibited H2O2-induced cytotoxicity and senescence-associated protein expression, such as p16 and p21. Furthermore, NMN prevented H2O2-induced actin cytoskeletal disorganization via inhibiting reactive oxygen species (ROS) production. NMN increased NQO-1 mRNA and protein expression that in turn was abrogated by SIRT1 inhibition, suggesting that NMN-inducible NQO-1 was associated with SIRT1 activity. SIRT1 and NQO-1 inhibition attenuated the inhibitory effect of NMN on H2O2-inducible cytotoxicity, senescence-related protein upregulation, and actin cytoskeletal disorganization. Our findings provide new insights into the mechanism by which NMN exerts protective effects against vascular oxidative stress.

Using Uniaxial Stress to Probe the Relationship between Competing Superconducting States in a Cuprate with Spin-stripe Order.

We report muon spin rotation and magnetic susceptibility experiments on in-plane stress effects on the static spin-stripe order and superconductivity in the cuprate system La_{2-x}Ba_{x}CuO_{4} with x=0.115. An extremely low uniaxial stress of ∼0.1 GPa induces a substantial decrease in the magnetic volume fraction and a dramatic rise in the onset of 3D superconductivity, from ∼10 to 32 K; however, the onset of at-least-2D superconductivity is much less sensitive to stress. These results show not only that large-volume-fraction spin-stripe order is anticorrelated with 3D superconducting coherence but also that these states are energetically very finely balanced. Moreover, the onset temperatures of 3D superconductivity and spin-stripe order are very similar in the large stress regime. These results strongly suggest a similar pairing mechanism for spin-stripe order and the spatially modulated 2D and uniform 3D superconducting orders, imposing an important constraint on theoretical models.

Elastic constants in orthorhombic hen egg-white lysozyme crystals.

The ultrasonic sound velocities of cross-linked orthorhombic hen egg-white lysozyme (HEWL) crystals, including a large amount of water in the crystal, were measured using an ultrasonic pulse-echo method. As a result, seven elastic constants of orthorhombic crystals were observed to be C11 = 5.24 GPa, C22 = 4.87 GPa, C12 = 4.02 GPa, C33 = 5.23 GPa, C44 = 0.30 GPa, C55 = 0.40 GPa, and C66 = 0.43 GPa, respectively. However, C13 and C23 could not be observed because the suitable crystal planes could not be cut from bulk crystals. We conclude that the observed elastic constants of the cross-linked crystals are coincident with those of the intrinsic crystals without cross-linking. Moreover, the characteristics of the elastic constants in orthorhombic HEWL crystals are due to the fact that the shear elastic constants, C44, C55, and C66, are softer than in tetragonal crystals. That is, the shear components, C44, C55, and C66, are one half of those of the tetragonal crystals.

Development of a method to analyze single cell activity by using dielectrophoretic levitation.

In cell fusion and genetic recombination, although the activity of single cells is extremely important, there is no method to analyze single cell activity. Development of a quick analyzing method for single cell activity is desired in various fields. Dielectrophoresis (DEP) refers to the force exerted on the induced dipole moment of an uncharged dielectric and/or conductive particle by a nonuniform electric field. By applying DEP, we obtained experimentally a relationship between the cell activity and the dielectric property, Re[K(omega)], and examined how to evaluate the single cell activity by measuring Re[K(omega)] of a single cell. A cone and plate electrode geometry was adapted in order to achieve the feedback-controlled DEP levitation. The single cell is exposed to a nonuniform field induced by the cone and plate electrode, and a more polarizable cell is moved to the direction of the cone electrode by the DEP force. The cell settles in the position where the DEP force and gravity are balanced by controlling applied voltage. This settled position, measured on the center axis of the cone electrode, depended on the dielectric constant of the cell. From these results, the relationship between the specific growth rates in cell growth phase and the dielectric properties Re[K(omega)] was obtained. Furthermore, the effect on the cell activity of various stresses, such as concentration of carbon dioxide, temperature, etc., was examined.

Effects of famotidine, mosapride and tandospirone for treatment of functional dyspepsia.

BACKGROUND: An effective therapeutic strategy for functional dyspepsia (FD) has not been well-established. AIM: We investigated and compared the therapeutic effects of famotidine, mosapride and tandospirone for the control of dyspeptic symptoms. METHODS: Fully examined FD patients of outpatient clinics at seven different medical centres were enrolled in the study. They were randomly assigned to three groups based on the type of drug administered: famotidine, mosapride and tandospirone. The effects of treatment over 4 weeks were assessed by visual analogue scales. RESULTS: All of the drugs showed beneficial effects, although famotidine was the most effective for symptom relief, which was significantly greater than tandospirone, while the effect of mosapride was similar to that of famotidine. No subtype of FD showed a better response to a particular type of drug. CONCLUSIONS: For the treatment of FD, famotidine demonstrated the best therapeutic effect, followed by mosapride, while that of tandospirone was significantly lower.

[Influence of visual attention upon sound localization].

Previous studies on audio-visual interaction such as the ventriloquism effect have indicated cognitive (or context) factors as well as sensory (or synchronous) factors could make the interaction. In these studies, however, visual attention seems to have been neglected. Thus, it has been still unknown whether the visual attention affects the interaction or not. We investigated the contribution of the attention factors to the audio-visual interaction by comparing the sound localization biases made by attentional factors and those by synchronous factors. Three subjects participated in the localization tasks in horizontal and vertical orientations. As the results, we found small influence of the attentional factors upon the interaction in the horizontal orientation, and no influence in the vertical orientation. On the contrary, the effect of the synchronous factors was larger in the vertical orientation than in the horizontal orientation. We concluded that the visual attention could affect the audio-visual interaction slightly, and that the influences of the attentional factors and the perceptual factors upon the interactions were made in the different processes.

Loss factors of mirrors for a gravitational wave antenna.

Low-loss mirrors fabricated by ion-beam-sputtering machines for possible application in an interferometric gravitational wave antenna were evaluated by use of Nd:YAG laser light (lambda = 1064 nm) with two distinct measurements: a tabletop experiment that used a short cavity with a small beam with a beam waist of approximately 2w(0) = 0.82 mm, and an optical test that used a 20-m prototypical gravitational-wave detector with a large beam with a beam waist of approximately 2w(0) = 4.4 mm. A multilayer coating comprised 29 layers of SiO(2)/Ta(2)O(5) and one protective coating of SiO(2). The best values obtained as a result of these measurements were 16 ppm (parts in 10(6)) and 30 ppm in total loss, respectively. Also, a two-dimensional loss map generated by use of a small beam successfully revealed the existence of a loss structure within the coating surface. These results imply that a high-reflectance multilayer coating has some inhomogeneities and a loss distribution with a typical scale of a few millimeters and that the total measured losses depend on the beam spot size.

Dynamic capture of sound motion by light stimuli moving in three-dimensional space.

A moving light stimulus produced a sensation of motion for a stationary sound stimulus presented simultaneously, which was called the dynamic visual capture by Mateeff, Hohnsbein, and Noack in 1985. The present study examined whether the moving light stimulus might induce a perceptual shift in the velocity, that is, the speed and the direction, of a moving sound stimulus. This type of the visual capture was explored in the directions where the sound stimulus moved along the motion tracks of the light stimulus: first in a horizontal and a vertical orientation and secondly in a depth orientation. Moreover, perceptual distortion of the direction of movement of the sound stimulus was investigated when the direction from which a sound stimulus moved deviated from the motion tracks of a light stimulus. It was found that the dynamic visual capture was inducible in all of three orientations, appearing more strongly in the vertical and the depth orientations than in the horizontal orientation. The perceived direction of the moving sound stimulus was greatly influenced by the direction where the light stimulus moved simultaneously and was often the same as the physical direction of the light stimulus, even when the physical motion directions of those two stimuli were perpendicular or opposite each other.

High-performance liquid chromatographic method for rapid and highly sensitive determination of histidine using postcolumn fluorescence detection with o-phthaldialdehyde.

A high-performance liquid chromatographic method was developed for the rapid and sensitive determination of histidine. The method is based on separation by reversed-phase ion-pair chromatography followed by highly selective fluorescence derivatization of histidine with o-phthaldialdehyde. A linear calibration curve was obtained over the range of 0.25-200 pmol per injection (10 microl) with the coefficient of variation of 0.9% at 2 pmol (n=10) and with the detection limit (SIN=8) of 25 fmol. The method was applicable to the assay of histidine in human serum. Serum histidine values obtained by the present method were in good agreement with values obtained with an amino acid analyzer.

[Long-term administration study of propiverine hydrochloride (BUP-4 tablets) in pollakiuria and urinary incontinence].

The safety and efficacy of one-year administration of propiverine hydrochloride (BUP-4 tablets) were assessed in facilities affiliated with the Department of Urology of Yokohama City University School of Medicine. Changes in subjective symptoms showed significant improvement in mean frequency of urination in the daytime from 10.3 +/- 4.0 times before administration to 7.1 +/- 2.9 times 1 year after the start of administration, in mean frequency of voiding at night from 4.2 +/- 1.7 times to 2.1 +/- 1.1 times and in mean incidence of urinary incontinence from 2.9 +/- 2.1 times to 0.7 +/- 1.0 times. The final degree of overall improvement rate was 82.0% (41/50 cases). Adverse effects were observed 26 times in 22 patients, the incidence being 15.6% (22/141 cases). They consisted of digestive symptoms in 9.9% (6 events of dry mouth, 4 of constipation, 2 of abdominal discomfort, 2 of diarrhea and 1 of gastritis), urinary tract symptoms in 3.5% (4 of dysuria and 1 of residual urine), abnormal laboratory findings in 1.4% (increase in glutamic-oxaloacetic transaminase, glutamic-pyruvic transaminase or lactate dehydrogenase levels) and others (1.4%). These results provide further evidence of the safety and efficacy of propiverine hydrochloride (BUP-4 tablets) even when administered for a long-term in the treatment of patients with pollakiuria and urinary incontinence.

Correlation between serum pepsinogen concentration and gastric acidity measured by 24 h pH monitoring.

The relationship between the intragastric pH measured by 24 h pH monitoring system and the serum pepsinogen I/II ratio was studied in 68 cases. When pepsinogen I/II ratio was compared with pH 3.0 holding time (the percentage time during which the gastric pH is above 3.0), there was a negative correlation between these two parameters (correlation coefficient r = -0.62, P < 0.001). Furthermore, there was also a strong negative correlation between the early morning (from 03.00 to 06.00 h) gastric pH and pepsinogen I/II ratio (r = -0.76, P < 0.001). Accordingly, by simply measuring serum pepsinogen I and II, it may be possible to infer gastric acidity and to obtain the information concerning the early morning intragastric pH.

Ultralow-loss mirror of the parts-in-10(6) level at 1064 nm.

We describe an ultralow-loss and high-reflectance mirror at 1064 nm. A Fabry-Perot cavity is fabricated with two mirrors to measure the finesse and the transmission efficiency on resonance. The finesse was cross checked by two different methods: measurements of the cavity decay time and of the frequency-response function. As a result, a loss of 6 +/- 6 x 10(-6) (6 +/- 6 parts in 10(6), scatter and absorption) and a finesse of 2236 +/- 54 were measured during the cavity decay time. This result coincides with that of the response function within accuracies cited above. To our knowledge, the loss is the lowest obtained at 1064 nm.

[A case of advanced cancer of the renal pelvis effectively treated by continuous infusion of 5-fluorouracil].

We obtained a partial response to a transitional cell carcinoma (TCC) of the renal pelvis with multiple metastasis following a 24-hour continuous injection of 5-FU (5 fluorouracil) over a period of 8 weeks. After treatment we could successfully remove the primary lesion. After removal of the primary lesion, the patient lived for three months. Because the effects of this treatment, compared to those of combination chemotherapy, are mild, it is useful for elderly patients with progressive TCC.

[A case of ureteritis with a course of rapidly progressing stricture].

Rapidly progressing stricture of the ureter with non-specific ureteritis is very rare and neither pathogenesis nor reliable treatment is known. We report a case of ureteritis in a 51-year-old woman with a stricture rapidly progressing over a course of 2 months. She was sent to us for left hydronephrosis. Retrograde pyelography (RP) revealed a 5 cm stricture in the left ureter. CT showed no abnormal mass in the retroperitoneum. Gastro-intestinal and gynecological inspection revealed no abnormalities. As a second RP showed 9 cm stricture 2 months later, we performed a biopsy of the ureter and examined it pathologically. There was no evidence of malignancy, but we performed a left nephroureterectomy, because of the stricture in the entire left ureter. Pathological study of the kidney and the ureter showed a non-specific inflammation of the entire urothelium without malignancy. There has been no recurrence in the right ureter.

Incidence of fundic gland polyps in patients without familial adenomatous polyposis.

The incidence of fundic gland polyps was evaluated using a high-resolution videoendoscope. In 1388 upper gastrointestinal endoscopic studies, 26 cases of fundic gland polyps (1.9% of the studied cases) were found. None of these patients had evidence of familial adenomatous polyposis. Fifteen of these patients (58%) had a solitary polyp in the gastric body, most of which were small sessile polyps of less than 2 mm in diameter. The results of this study indicated that a small solitary fundic gland polyp is not a rare gastric lesion and that little relationship exists between these solitary fundic gland polyps and familial adenomatous polyposis.