Multielectron-Ion Coincidence Spectroscopy of Xe in Extreme Ultraviolet Laser Fields: Nonlinear Multiple Ionization via Double Core-Hole States.

Ultrafast multiphoton ionization of Xe in strong extreme ultraviolet free-electron laser (FEL) fields (91 eV, 30 fs, 1.6×10^{12} W/cm^{2}) has been investigated by multielectron-ion coincidence spectroscopy. The electron spectra recorded in coincidence with Xe^{4+} show characteristic features associated with two-photon absorption to the 4d^{-2} double core-hole (DCH) states and subsequent Auger decay. It is found that the pathway via the DCH states, which has eluded clear identification in previous studies, makes a large contribution to the multiple ionization, despite the long FEL pulse duration compared with the lifetime of the 4d core-hole states.

Element Selectivity in Second-Harmonic Generation of GaFeO_{3} by a Soft-X-Ray Free-Electron Laser.

Nonlinear optical frequency conversion has been challenged to move down to the extreme ultraviolet and x-ray region. However, the extremely low signals have allowed researchers to only perform transmission experiments of the gas phase or ultrathin films. Here, we report second harmonic generation (SHG) of the reflected beam of a soft x-ray free-electron laser from a solid, which is enhanced by the resonant effect. The observation revealed that the double resonance condition can be met by absorption edges for transition metal oxides in the soft x-ray range, and this suggests that the resonant SHG technique can be applicable to a wide range of materials. We discuss the possibility of element-selective SHG spectroscopy measurements in the soft x-ray range.

Ultrafast energy- and momentum-resolved dynamics of magnetic correlations in the photo-doped Mott insulator Sr2IrO4.

Measuring how the magnetic correlations evolve in doped Mott insulators has greatly improved our understanding of the pseudogap, non-Fermi liquids and high-temperature superconductivity. Recently, photo-excitation has been used to induce similarly exotic states transiently. However, the lack of available probes of magnetic correlations in the time domain hinders our understanding of these photo-induced states and how they could be controlled. Here, we implement magnetic resonant inelastic X-ray scattering at a free-electron laser to directly determine the magnetic dynamics after photo-doping the Mott insulator Sr2IrO4. We find that the non-equilibrium state, 2 ps after the excitation, exhibits strongly suppressed long-range magnetic order, but hosts photo-carriers that induce strong, non-thermal magnetic correlations. These two-dimensional (2D) in-plane Néel correlations recover within a few picoseconds, whereas the three-dimensional (3D) long-range magnetic order restores on a fluence-dependent timescale of a few hundred picoseconds. The marked difference in these two timescales implies that the dimensionality of magnetic correlations is vital for our understanding of ultrafast magnetic dynamics.

High-precision x-ray FEL pulse arrival time measurements at SACLA by a THz streak camera with Xe clusters.

The accurate measurement of the arrival time of a hard X-ray free electron laser (FEL) pulse with respect to a laser is of utmost importance for pump-probe experiments proposed or carried out at FEL facilities around the world. This manuscript presents the latest device to meet this challenge, a THz streak camera using Xe gas clusters, capable of pulse arrival time measurements with an estimated accuracy of several femtoseconds. An experiment performed at SACLA demonstrates the performance of the device at photon energies between 5 and 10 keV with variable photon beam parameters.

Real-time monitoring of nitric oxide (NO) and pO2 levels under ischemic conditions associated with small bowel ischemia/reperfusion injury using selective electrodes for NO and oxygen molecules.

The present study demonstrated the feasibility of monitoring nitric oxide (NO) and pO2 levels under ischemic conditions associated with small bowel ischemia/reperfusion (I/R) injury through the use of selective electrodes for NO and oxygen molecules. NO levels gradually increased during ischemia. When reperfusion was started, the NO level decreased suddenly and returned to pre-ischemia values within 10 minutes. After clamping, pO2 decreased rapidly. When reperfusion was started, pO2 increased suddenly, returning to pre-ischemia values within 10 minutes. We concluded that it is feasible to monitor NO and pO2 levels under ischemic conditions of small bowel I/R injury through the use of electrodes selective for NO and oxygen molecules.

Protective effects of MnM2Py4P and Mn-salen against small bowel ischemia/reperfusion injury in rats using an in vivo and an ex vivo electron paramagnetic resonance technique with a spin probe.

BACKGROUND: Reperfusion of ischemic tissues results in the formation of toxic reactive oxygen species (ROS), such as superoxide anion, hydroxyl radicals, hydroperoxide, and peroxynitrite. ROS are potent oxidizing agents, capable of damaging cellular membranes by lipid peroxidation. In the present study, we applied an in vivo electron paramagnetic resonance (EPR)/spin probe and an ex vivo EPR technique to provide direct evidence of ROS following experimentally induced small bowel ischemia/reperfusion (I/R) injury. MATERIALS AND METHODS: We used a rat model of small bowel I/R injury to explore the possibility that MnM2Py4P or Mn-salen can prevent the accumulation of ROS species following experimentally induced I/R injury. We examined the ability of MnM2Py4P and Mn-salen to scavenge radicals in living Sprague-Dawley (SD) rats using an in vivo and an ex vivo EPR technique with a spin probe. RESULTS: The CP decay rates in the MnM2Py4P- and Mn-salen-treated rats were significantly higher than those in the untreated rats and almost equal to those in sham group rats. There were no significant differences between the MnM2Py4P-treated group and the Mn-salen-treated group. Superoxide scavenging activities (SSA) in the MnM2Py4P- and EUK-8-treated group were higher than those in the untreated group and almost equal to the sham group. CONCLUSION: The present study suggested that the protective effects of MnM2Py4P and Mn-salen against small bowel IR injury were mediated by the inhibition of O2, H2O2, and NO production.

Time zero determination for FEL pump-probe studies based on ultrafast melting of bismuth.

A common challenge for pump-probe studies of structural dynamics at X-ray free-electron lasers (XFELs) is the determination of time zero (T0)-the time an optical pulse (e.g., an optical laser) arrives coincidently with the probe pulse (e.g., a XFEL pulse) at the sample position. In some cases, T0 might be extracted from the structural dynamics of the sample's observed response itself, but generally, an independent robust method is required or would be superior to the inferred determination of T0. In this paper, we present how the structural dynamics in ultrafast melting of bismuth can be exploited for a quickly performed, reliable and accurate determination of T0 with a precision below 20 fs and an overall experimental accuracy of 50 fs to 150 fs (estimated). Our approach is potentially useful and applicable for fixed-target XFEL experiments, such as serial femtosecond crystallography, utilizing an optical pump pulse in the ultraviolet to near infrared spectral range and a pixelated 2D photon detector for recording crystallographic diffraction patterns in transmission geometry. In comparison to many other suitable approaches, our method is fairly independent of the pumping wavelength (UV-IR) as well as of the X-ray energy and offers a favorable signal contrast. The technique is exploitable not only for the determination of temporal characteristics of the experiment at the interaction point but also for investigating important conditions affecting experimental control such as spatial overlap and beam spot sizes.

Ultraviolet photochemical reaction of [Fe(III)(C2O4)3](3-) in aqueous solutions studied by femtosecond time-resolved X-ray absorption spectroscopy using an X-ray free electron laser.

Time-resolved X-ray absorption spectroscopy was performed for aqueous ammonium iron(III) oxalate trihydrate solutions using an X-ray free electron laser and a synchronized ultraviolet laser. The spectral and time resolutions of the experiment were 1.3 eV and 200 fs, respectively. A femtosecond 268 nm pulse was employed to excite [Fe(III)(C2O4)3](3-) in solution from the high-spin ground electronic state to ligand-to-metal charge transfer state(s), and the subsequent dynamics were studied by observing the time-evolution of the X-ray absorption spectrum near the Fe K-edge. Upon 268 nm photoexcitation, the Fe K-edge underwent a red-shift by more than 4 eV within 140 fs; however, the magnitude of the redshift subsequently diminished within 3 ps. The Fe K-edge of the photoproduct remained lower in energy than that of [Fe(III)(C2O4)3](3-). The observed red-shift of the Fe K-edge and the spectral feature of the product indicate that Fe(III) is upon excitation immediately photoreduced to Fe(II), followed by ligand dissociation from Fe(II). Based on a comparison of the X-ray absorption spectra with density functional theory calculations, we propose that the dissociation proceeds in two steps, forming first [(CO2 (•))Fe(II)(C2O4)2](3-) and subsequently [Fe(II)(C2O4)2](2-).

Effects of a vitamin E-modified dialysis membrane on neutrophil superoxide anion radical production.

Activation of neutrophil by the dialysis membrane and peroxidative stress plays an important role on the pathogenesis of complications in hemodialysis (HD) patients. Vitamin E is one of the potent scavengers for reactive oxygen species. Recent studies suggest that a vitamin E-modified multilayer membrane (Excebrane, CL-EE dialyzer) has an inhibitory effect on serum lipids peroxidation in HD patients. To determine the effect of CL-EE on biocompatibility in clinical use, we measured the superoxide anion radical producing ability (SOPA) of polymorphonuclear leukocytes (PMNLs), the plasma hydroxyl radical producing ability (OHPA) and superoxide anion radical scavenging activity (SSA). SOPA was measured after stimulation of PMNLs with phorbol myristate acetate using electron paramagnetic resonance (EPR) method. Plasma OHPA and SSA were also determined using the EPR method. In addition, the plasma concentrations of malondialdehyde (MDA) and oxidized low-density lipoprotein (LDL), as the parameters for lipid peroxidation, were measured. SOPA was decreased in patients who used conventional filter membrane compared with healthy controls. In the patients using the CL-EE membrane, SOPA gradually increased and reached control levels after six months. However, no significant increase was observed in patients who used a conventional filter membrane. OHPA of HD patients was significantly decreased compared with controls. In the CL-EE membrane patient group, OHPA was significantly increased at six months. SSA was significantly higher in the conventional filter membrane group than controls. In the CL-EE membrane patient group, SSA gradually decreased at six months. Plasma MDA and oxidized LDL levels were significantly higher in HD patients compared with controls. These values slowly decreased, and significant differences were found after nine months of using the CL-EE membrane. These findings suggest that activation of PMNLs and plasma OHPA and SSA in HD patients is attenuated by antioxidant effects of the CL-EE.

Mechanism of sodium load-induced hypertension in non-insulin dependent diabetes mellitus model rats: defective dopaminergic system to inhibit Na-K-ATPase activity in renal epithelial cells.

Obesity-related non-insulin dependent diabetes mellitus (NIDDM) is frequently accompanied by hypertension. The present study was designed to clarify this mechanism. We first determined the blood pressure in male Wistar fatty rats (WFR), one of the NIDDM model rats, and in Wistar lean rats (WLR) as the control, with a normal (0.7% NaCl) or high (7% NaCl) salt diet. We observed no difference in systolic and mean blood pressures between WFR and WLR. WFR, however, became extremely hypertensive as a result of ingesting the high salt diet. We next investigated the mechanism for sodium sensitivity in WFR. Although the urinary excretion of dopamine (DA), a potent natriuretic factor, which reflects the ability for renal DA production, was preserved in WFR, the sodium balance with the high salt diet was positive. Moreover, Na-K-ATPase activity in isolated proximal convoluted tubules (PCT) from WFR with a normal salt diet was significantly (p<0.05) higher than that from WLR. A high salt load produced a significant (p<0.05) decrease in Na-K-ATPase activity in WLR but not in WFR. Similarly, Na-K-ATPase activity in WLR with a normal salt diet was significantly (p<0.05) inhibited by DA (10(-5) M), but this was not true in WFR. Furthermore, urinary excretion of norepinephrine in WFR with a high salt diet was the highest among all the groups. These results indicate that WFR tend to develop salt-sensitive hypertension that could be caused by the excessive sodium retention occurring as the results of a defective dopaminergic system in the kidney that fails to inhibit Na-K-ATPase activity. Augmentation of the renal sympathetic nervous system may play some role in this setting.

Effects of edaravone on experimental brain injury in view of free radical reaction.

The purpose of this study is to clarify the influence of a novel free radical scavenger edaravone on experimental brain injury. Male Wistar rats were anesthetized with 1-2% halothane. Brain injury was produced using a controlled cortical impact injury device. Experimental rats were divided into 2 groups. In the edaravone group, edaravone (3 mg/kg) was twice administered intravenously for 30 minutes. In the saline group, saline solution was administered in the same way. This administration of edaravone or saline solution made it possible to evaluate the relative effects of edaravone by assessment of free radical reaction and water content. As a result, the level of oxygen free radicals at 50 minutes after brain injury was significantly lower in the edaravone group than in the saline group. The water content in the injured brain at 180 minutes was significantly lower in the edaravone group than in the saline group. Therefore, we propose that edaravone may be effective for treatment in head injury.

Recent aspects in the genetic renal mechanisms involved in hypertension.

The kidney plays an important role in the blood pressure regulation primarily by modulating tubular sodium reabsorption. Various hormones, vasoactive peptides, autacoids and transporters or channels in renal tubules are involved in this process. Genes associated with renal tubular sodium handling are possibly related to the development of hypertension. Genes of the renin-angiotensin-aldosterone system are thought to be especially important as causal genes of hypertension. Na-K-ATPase, biochemically equal to Na pump, exists on the basolateral membrane of renal epithelial cells. It plays a central role in Na reabsorption and creates a driving force for transepithelial transport. Na-K-ATPase activity is regulated by adducin, a membrane-bound skeletal protein, as well as by several hormones such as dopamine, endogenous ouabain-like factor or cytochrome P450 metabolites. Genes of these factors involved in Na-K-ATPase regulation should be related to the development of hypertension. The endothelin system, atrial natriuretic peptide and nitric oxide regulate the tonus of blood vessels as well as renal sodium excretion. Several reports have indicated that genes of these substances are crucial in the pathogenesis of hypertension.

Hyperosmotic stimuli induces recruitment of aquaporin-1 to plasma membrane in cultured rat peritoneal mesothelial cells.

Aquaporin-1 (AQP-1) has been reported to play an important role in peritoneal dialysis. To determine the precise mechanism involved, we used cultured rat peritoneal mesothelial cells (RPMCs) to examine the translocation of AQP-1 to the plasma membrane induced by hyperosmotic stimuli. Cultured RPMCs obtained from male Sprague-Dawley rats were incubated at room temperature in Dulbecco modified Eagle medium/F12 (DMEM/F12) with and without glucose or mannitol as the hyperosmotic stimulus. The plasma membrane was then extracted by the Percoll gradient method. Finally, the abundance AQP-1 molecules in the membrane fraction was determined by Western blot analysis. Significant enhancement of AQP-1 abundance (p < 0.05) was observed within 2.5 minutes of the addition of 5% glucose to the medium. The increase was sustained in its abundance through 15 minutes. Abundance of AQP-1 was also increased (p < 0.05) by the addition of 5% mannitol. These results suggest that hyperosmotic stimuli could generate increased AQP-1 abundance in the plasma membrane by translocation of AQP-1 protein from recycling endosomes or early endosomes to the plasma membrane, rather than by protein synthesis via newly expressed mRNA. The latter mechanism would be expected to take more time.

[A case of Fabry's disease with chronic renal failure].

Fabry's disease is a genetic disorder caused by the absence of alpha-galactosidase (alpha-Gal), the gene of which is carried on the long arm of the X chromosome. This enzymatic defect leads to an accumulation of glycosphingolipids in the plasma and lysosomes of endothelial, perithelial, and smooth muscle cells, especially involving those of the cardiovascular, renal and cerebrovascular systems. We report one male case of Fabry's disease with renal deterioration. A 36-year-old man who was a classic case with acroparesthesia, angiokeratoma, and hypohidrosis from 10 years of age, was diagnosed to be a hemizygote of Fabry's disease at 27 years as a result of severe decreased alpha-Gal activity of his peripheral white blood cells. This patient was found to have a point mutation of a G to A transition in exon 1. In May, 1989, he was reported to have proteinuria with normal renal function and admitted to our hospital due to renal deterioration in September, 1993. Laboratory examinations revealed a serum urea nitrogen of 65 mg/dl and creatinine value of 6.9 mg/dl. Urinary protein excretion was 3.9 g/day and urinary sugar was negative. On the renal biopsy specimens, light microscopic examinations revealed multiple sclerosing and collaptic lesions in glomeruli without severe tubulo-interstitial damage, but with stenotic change of the small arteries and arterioles. Electron microscopic examinations revealed a large number of electron dense deposits in the tubules. We diagnosed this case as Fabry's disease with chronic renal failure, however the pathogenesis of this renal progressive deterioration remained obscure. In this case, degenerative changes in the renal vessels due to Fabry's disease may be associated with rapid deterioration in renal function.

[A case report of advanced breast cancer effectively treated with etoposide, adriamycin and cis-platinum combination therapy].

A 61-year-old woman with left advanced breast cancer (T3a, N2, M0, Stage IIIa) underwent preoperative chemotherapy. The regimen consisted of etoposide 70 mg/m2 (day 4, 5, 6 i.v.), adriamycin 20 mg/m2 (day 1, 7 i.v.) and cis-platinum 40 mg/m2 (day 2, 8 i.v.). By the third week of administration, the size of the breast tumor reduced markedly, with the rate of 97%, resulting in partial response. Following preoperative combination-chemotherapy, a left extended radical mastectomy was performed. Histological findings of the resected specimen showed sufficient effects of chemotherapy; degeneration of tumor cells, infiltration of histiocytes and fibrosis of stroma. After operation, chemotherapy with the same dosage and sequential irradiation were undergone. As the side effect of this chemotherapy, slight nausea, vomiting and leucocytopenia were observed. The result of this case suggested that combination-chemotherapy with etoposide, adriamycin and cisplatinum was an effective chemotherapy for advanced breast cancer.

[Intra-arterial infusion chemotherapy for recurrent cervical lymph nodes after surgery in esophageal cancer].

We attempted intra-arterial infusion chemotherapy using a reservoir system in recurrent cervical lymph nodes after surgery for esophageal cancer, and obtained favorable results. Intra-arterial infusion chemotherapy (75 mg of cisplatin and 5 mg of peplomycin) was performed using a reservoir system connected with a catheter inserted into the left subclavian artery, because recurrent lymph nodes developed in the left supraclavicular fossa. The therapy was effective for 6 months and the quality of life was improved without side effects.

[A clinical study of immunological status in patients with gastric cancer: with special reference to T-cell subsets, interleukin-2 in the lymphocytes of peripheral blood].

Peripheral blood lymphocytes of 63 patients with gastric cancer were studied by using different monoclonal antibodies and flow cytometry. Used monoclonal antibodies were OKT3 (total T cell), OKT4 (helper/inducer), OKT8 (suppressor/cytotoxic), Leu 7 and Leu 11 (NK/K cell). Interleukin-2 was measured by tritium-labelled thymidine CTLL assay on the supernatant of peripheral blood lymphocytes after 24 hours stimulation with phytohemagglutinin. Interleukin-2 receptor was also studied by using monoclonal antibody (for Tac antigen) and flow cytometry. The results were as follows: among peripheral blood lymphocytes; 1. the number of OKT3, OKT4 cells and the percentage of OKT4 cells decreased significantly with more advanced stage of cancer. 2. production of interleukin-2 also decreased with the progression of the cancer. 3. decreases in the OKT4/OKT8 ratio were found with cancer progression. 4. the percentage and the number of OKT8 cells increased. 5. the percentage and the number of Leu 11 cells and the number of Leu 7 cells were increased significantly in the stage III (moderately advanced cancer). These results suggested that the activated helper T cells decreased, the induction capability of cytotoxic T cells decreased and the suppressor T cells increased with the progression of cancer. Quantitative and qualitative change in T-cell subsets in advanced stage may be one factor responsible for immunosuppression.