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Molybdenum(VI) oxide (MoO3) is a promising semiconductor material that can be used in several functional applications. Understanding the structural response of MoO3under high-pressure and high-temperature conditions is important for designing a material used in device applications. An X-ray free electron laser (XFEL) enables the structural response under extreme conditions to be probed at the nanosecond timescale. We describe laser-driven shock compression experiments on MoO3using an XFEL to directly observe the structural evolution of MoO3. When a laser-driven shock wave arrives at a pressure of 61 GPa, MoO3melts immediately and remains in the molten state for a few nanoseconds. Rapid recrystallization to the α-MoO3phase and a high-pressure phase MoO3-II is also observed on nanosecond timescales during pressure release. Our results provide insights into the kinetic and phase transition under shock compression and represent the advancement toward the understanding structural response of MoO3under high-pressure, high-temperature conditions, which has not been studied.

Genome-wide association studies (GWASs) have identified several susceptibility loci for bipolar disorder (BD) and shown that the genetic architecture of BD can be explained by polygenicity, with numerous variants contributing to BD. In the present GWAS (Phase I/II), which included 2964 BD and 61 887 control subjects from the Japanese population, we detected a novel susceptibility locus at 11q12.2 (rs28456, P=6.4 × 10−9), a region known to contain regulatory genes for plasma lipid levels (FADS1/2/3). A subsequent meta-analysis of Phase I/II and the Psychiatric GWAS Consortium for BD (PGC-BD) identified another novel BD gene, NFIX (Pbest=5.8 × 10−10), and supported three regions previously implicated in BD susceptibility: MAD1L1 (Pbest=1.9 × 10−9), TRANK1 (Pbest=2.1 × 10−9) and ODZ4 (Pbest=3.3 × 10−9). Polygenicity of BD within Japanese and trans-European-Japanese populations was assessed with risk profile score analysis. We detected higher scores in BD cases both within (Phase I/II) and across populations (Phase I/II and PGC-BD). These were defined by (1) Phase II as discovery and Phase I as target, or vice versa (for ‘within Japanese comparisons’, Pbest~10−29, R2~2%), and (2) European PGC-BD as discovery and Japanese BD (Phase I/II) as target (for ‘trans-European-Japanese comparison,’ Pbest~10−13, R2~0.27%). This ‘trans population’ effect was supported by estimation of the genetic correlation using the effect size based on each population (liability estimates~0.7). These results indicate that (1) two novel and three previously implicated loci are significantly associated with BD and that (2) BD ‘risk’ effect are shared between Japanese and European populations.

Recent schizophrenia (SCZ) studies have reported an increased burden of de novocopy number variants (CNVs) and identified specific high-risk CNVs, although with variable phenotype expressivity. However, the pathogenesis of SCZ has not been fully elucidated. Using array comparative genomic hybridization, we performed a high-resolution genome-wide CNV analysis on a mainly (92%) Japanese population (1699 SCZ cases and 824 controls) and identified 7066 rare CNVs, 70.0% of which were small (<100 kb). Clinically significant CNVs were significantly more frequent in cases than in controls (odds ratio=3.04, P=9.3 × 10−9, 9.0% of cases). We confirmed a significant association of X-chromosome aneuploidies with SCZ and identified 11 de novoCNVs (e.g., MBD5deletion) in cases. In patients with clinically significant CNVs, 41.7% had a history of congenital/developmental phenotypes, and the rate of treatment resistance was significantly higher (odds ratio=2.79, P=0.0036). We found more severe clinical manifestations in patients with two clinically significant CNVs. Gene set analysis replicated previous findings (e.g., synapse, calcium signaling) and identified novel biological pathways including oxidative stress response, genomic integrity, kinase and small GTPase signaling. Furthermore, involvement of multiple SCZ candidate genes and biological pathways in the pathogenesis of SCZ was suggested in established SCZ-associated CNV loci. Our study shows the high genetic heterogeneity of SCZ and its clinical features and raises the possibility that genomic instability is involved in its pathogenesis, which may be related to the increased burden of de novoCNVs and variable expressivity of CNVs.

AbstractLaser–plasma interaction and hot electrons have been characterized in detail in laser irradiation conditions relevant for direct-drive inertial confinement fusion. The experiment was carried out at the Gekko XII laser facility in multibeam planar target geometry at an intensity of approximately $3\times {10}^{15}$ W/cm2. Experimental data suggest that high-energy electrons, with temperatures of 20–50 keV and conversion efficiencies of $\eta <1\%$ , were mainly produced by the damping of electron plasma waves driven by two-plasmon decay (TPD). Stimulated Raman scattering (SRS) is observed in a near-threshold growth regime, producing a reflectivity of approximately $0.01\%$ , and is well described by an analytical model accounting for the convective growth in independent speckles. The experiment reveals that both TPD and SRS are collectively driven by multiple beams, resulting in a more vigorous growth than that driven by single-beam laser intensity.

This paper deals with radiative shocks from both theoretical and experimental viewpoints. First, experimental results obtained at Laboratoire d'Utilisation des Lasers Intenses (LULI) at high ($E\sim400-800$J) energies are presented. The modeling of these phenomena is mainly performed through numerical simulations (1D and 2D calculations). We compare simulations given by several radiative hydrodynamics codes and discuss numerical methods employed. The lateral radiative looses are examined. A major point for discussion is the physical data (EOS, ionization, opacities) included in these codes. It is shown that the radiative precursor length depends on the dimensionality of codes and on the opacities employed. Additional quantities (temperature of the shock, electron density in the precursor) are also calculated and good agreement is obtained with the experimental data.

New laser-driven flyer impact experiments have been performed at the LULI laboratory. In these experiments, three types of targets (single Al flyer, multi-layered, and foam-buffered high-Z metal) were used. Impacted conditions in fused quartz were measured with rear-side (two VISARs and SOP) and transverse diagnostics (shadowgraph). In the foam-buffered target, Ta foil was accelerated up to a velocity of 55 km/s. Shock wave accelerated in fused quartz by an Al flyer impact was generated, and the shock wave passing a distinct boundary to a conductive state was directly observed. This method is a way to create unique conditions within the EOS diagram of material.

We present here a summary of various and preliminary experiments performed on the new facility LULI 2000. Four topics in the High Density Energy Physics have been investigated:
a– Equation of State: we studied pre-compressed water, one of most abundant component of Uranus and Neptune's mantle. We used a recent technique based on generating a shock into a diamond anvil cell pre-compressed target. Some new data on EOS surface in the range 2-3 Mbar have been obtained.
b– X-ray Thomson scattering: a strongly coupled and degenerated Aluminum plasma has been produced and probed by Ti He-alpha radiation. By using a curved spectrometer, the scattered spectrum has been measured a Compton shift from electrons has been put in evidence.
c– Astrophysics in the laboratory: A radiative supercritical shock has been produced into a gas cell filled with a low density of Xenon (0.1-0.3 bar). Various diagnostics have been implemented to determine electron density variation, precursor and shock velocities, the 2D shape of the shock at different times and electron temperature.
d– Laser accelerated flyer: different flyer plate targets have been tested. Typical shock loaded material was fused-quartz plate. Flyer velocities up to 55 km/s have been measured.

Subcortical structures, which include the basal ganglia and parts of the limbic system, have key roles in learning, motor control and emotion, but also contribute to higher-order executive functions. Prior studies have reported volumetric alterations in subcortical regions in schizophrenia. Reported results have sometimes been heterogeneous, and few large-scale investigations have been conducted. Moreover, few large-scale studies have assessed asymmetries of subcortical volumes in schizophrenia. Here, as a work completely independent of a study performed by the ENIGMA consortium, we conducted a large-scale multisite study of subcortical volumetric differences between patients with schizophrenia and controls. We also explored the laterality of subcortical regions to identify characteristic similarities and differences between them. T1-weighted images from 1680 healthy individuals and 884 patients with schizophrenia, obtained with 15 imaging protocols at 11 sites, were processed with FreeSurfer. Group differences were calculated for each protocol and meta-analyzed. Compared with controls, patients with schizophrenia demonstrated smaller bilateral hippocampus, amygdala, thalamus and accumbens volumes as well as intracranial volume, but larger bilateral caudate, putamen, pallidum and lateral ventricle volumes. We replicated the rank order of effect sizes for subcortical volumetric changes in schizophrenia reported by the ENIGMA consortium. Further, we revealed leftward asymmetry for thalamus, lateral ventricle, caudate and putamen volumes, and rightward asymmetry for amygdala and hippocampal volumes in both controls and patients with schizophrenia. Also, we demonstrated a schizophrenia-specific leftward asymmetry for pallidum volume. These findings suggest the possibility of aberrant laterality in neural pathways and connectivity patterns related to the pallidum in schizophrenia.

We report an experimental study of the phase diagrams of MgO, MgSiO3, and Mg2SiO4at high pressures. We measured the shock compression response, including pressure‐temperature Hugoniot curves of MgO, MgSiO3, and Mg2SiO4between 0.2–1.2 TPa, 0.12–0.5 TPa, and 0.2–0.85 TPa, respectively, using laser‐driven decaying shocks. A melting signature has been observed in MgO at 0.47 ± 0.04 TPa and 9860 ± 810 K, while no such phase changes were observed either in MgSiO3or in Mg2SiO4. Increases of reflectivity of MgO, MgSiO3, and Mg2SiO4liquids have been detected above 0.55 TPa (12760 K), 0.15 TPa (7540 K), 0.2 TPa (5800 K), respectively. In contrast to SiO2, melting and metallization of these compounds do not coincide, implying the presence of poorly electrically conducting liquids close to the melting lines. This has important implications for the generation of dynamos in super‐Earth's mantles. Magnesium oxides phase diagrams investigated along the Hugoniots between 0.2 and 1.2 TPa with decaying shocks and optical diagnosticsNew MgO experimental melting point proposed at 0.47 ± 0.04 TPa and 9860 ± 810 KNo evidences of phase transition have been found for MgSiO3and Mg2SiO4between 0.12–0.5 TPa and 0.2–0.85 TPa, respectively

Piccolo (PCLO) inhibits methamphetamine-induced neuropharmacological effects via modulation of dopamine (DA) uptake and regulation of the transport of synaptic vesicles in neuronal cells. Clinical studies have recently suggested that the single nucleotide polymorphism (SNP) rs13438494 in the intron 24 of the PCLO gene is associated with psychiatric disorder, in the meta-analysis of GWAS. Therefore, in this study, we attempted to evaluate the possible role of the PCLO SNP in the mechanisms of uptake of monoamines. To characterize rs13438494 in the PCLO gene, we constructed plasmids carrying either the C or A allele of the SNP and transiently transfected them into SH-SY5Y cells to analyze genetic effects on the splicing of PCLO mRNA. The C and A allele constructs produced different composition of the transcripts, indicating that the intronic SNP does affect the splicing pattern. We also transfected DA and serotonin (5-hydroxytryptamine; 5- HT) transporters into cells and analyzed their uptakes to elucidate the association to psychiatric disorders. In the cells transfected with the C allele, both the DA and 5-HT uptake were enhanced compared to the A allele. We also conducted a clinical study, in order to clarify the genetic associations. PCLO rs13438494 exhibits a relationship with the symptoms of drug dependence or related parameters, such as the age of first exposure to methamphetamine, eating disorders, tobacco dependence and fentanyl requirement. Our findings suggest that rs13438494 is associated with drug abuse and contributes to the pathogenesis of psychiatric disorders via modulation of neurotransmitter turnover.

In the framework of the Laboratory Astrophysics, we present new radiative shocks experiments performed using the LULI2000 facility. A strong shock is driven in a multi-layered solid target (CH-Ti-CH) which accelerates into a gas cell ($\sim 60$km/s) filled with Xenon at low pressure ($0.1 - 0.3$bar) and produces a radiative supercritical shock [4, 8].
A low power laser beam (8 ns - 532 nm) probes the Xenon gas in the transverse direction and is injected into a VISAR and on two optical framing cameras (GOI). These diagnostics allow to determine electron density variation, to measure both precursor and shock velocities along the shock propagation axis [3, 5] as well as the 2D shape of the shock.
On rear side, the light emitted from the shocked Xenon is imaged onto the slit of a streak camera. An absolute calibration of the optical system allows to determine the brightness temperature [8]. Data were obtained for different laser intensities and gas pressures. Two VISARs on rear side allowed an accurate measurement of the shock conditions in the pusher before the breakout in the Xenon.
Comparison between 1D (MULTI) and 2D (DUED [1, 2]) radiative hydrodynamic codes and measured quantities (shock velocity, shape, radial expansion, and temperature as well as precursor velocity and precursor electron density) are presented.

The regulator of G-protein signaling (RGS) modulates the functioning of heterotrimeric G protein. RGS9-2 is highly expressed in the striatum and plays a role in modulating dopaminergic receptor-mediated signaling cascades. Previous studies suggested that the RGS9 gene might contribute to the susceptibility to psychotic diseases. Therefore, we investigated the association between the RGS9 gene and two related dopamine psychoses, schizophrenia and methamphetamine use disorders. The subjects comprised 487 patients of schizophrenia and 464 age- and sex-matched healthy controls and 220 patients of methamphetamine use disorder and 289 controls. We genotyped two nonsynonymous polymorphisms, rs12452285 (Leu225Ser) and rs34797451 (His498Arg), of the RGS9 gene. Rs34797451 showed monomorphism in the present Japanese population, but rs12452285 showed polymorphism. There were no significant differences in genotypic or allelic distributions of rs12452285 between patients with schizophrenia and the corresponding control or between patients with methamphetamine use disorder and the corresponding control. We also analyzed the clinical features of methamphetamine use disorder. We found a significant association in allelic distribution with the phenotypes of age at first consumption (p0.047). The present study suggested that the RGS9 gene is unlikely to play a major role in schizophrenia and methamphetamine dependence liability and/or the development of methamphetamine induced psychosis, at least in a Japanese population.

Several studies have suggested that the endocannabinoid system plays significant roles in the vulnerability to psychiatric disorders including drug abuse. To examine the possible association of the CNR1 and CNR2 genes, which encode cannabinoid receptors CB1 and CB2, with methamphetamine dependence, we investigated three single nucleotide polymorphisms (SNPs) (rs806379, rs1535255, rs2023239) in intron 2 of the CNR1 gene and a nonsynonymous SNP, Q63R, in the CNR2 gene. The study samples consisted of 223 patients with methamphetamine dependence and 292 age- and sex- matched controls. There were no significant differences between the patients and controls in genotypic or allelic distribution of any SNP of the CNR1 and CNR2 genes. We also analyzed the clinical features of methamphetamine dependence. Rs806379 of the CNR1 gene showed a significant association with the phenotype of latency of psychosis after the first consumption of methamphetamine. Patients with the T allele or T-positive genotypes (T/T or A/T) may develop a rapid onset of psychosis after methamphetamine abuse. The present study suggests a possibility that genetic variants of the CNR1 gene may produce a liability to the complication of psychotic state after abuse of methamphetamine; however, our findings need to be confirmed by future replications.

Experimental studies have demonstrated that not only dopaminergic signaling but also glutamatergic/NMDA receptor signaling play indispensable roles in the development of methamphetamine psychosis. Our recent genetic studies provided evidence that genetic variants of glutamate-related genes such as DTNBP1, GLYT1, and G72, which are involved in glutamate release and regulation of co-agonists for NMDA receptors, conferred susceptibility to methamphetamine psychosis. Serine racemase converts l-serine to d-serine, which is an endogenous co-agonist for NMDA receptors. Three single nucleotide polymorphisms (SNPs) in the promoter region of the serine racemase gene (SRR), rs224770, rs3760229, and rs408067, were proven to affect the transcription activity of SRR. Therefore, we examined these SNPs in 225 patients with methamphetamine psychosis and 291 age- and sex-matched controls. There was no significant association between methamphetamine psychosis and any SNP examined or between the disorder and haplotypes comprising the three SNPs. However, rs408067 was significantly associated with the prognosis for methamphetamine psychosis and multi-substance abuse status. The patients with C-positive genotypes (CC or CG) of rs408067 showed better prognosis of psychosis after therapy and less abuse of multiple substances than the patients with GG genotypes. Because the C allele of rs408067 reduces the expression of SRR, a lower d-serine level or reduced NMDA receptor activation may affect the prognosis of methamphetamine psychosis and multiple substance abuse. Our sample size is, however, not large enough to eliminate the possibility of a type I error, our findings must be confirmed by replicate studies with larger samples.

Several lines of evidence implicate serotonergic dysfunction in diverse psychiatric disorders including anxiety, depression, and drug abuse. Mice with a knock-out of the 5HT1b receptor gene (HTR1B) displayed increased locomotor response to cocaine and elevated motivation to self-administer cocaine and alcohol. Previous genetic studies showed significant associations of HTR1B with alcohol dependence and substance abuse, but were followed by inconsistent results. We examined a case-control genetic association study of HTR1B with methamphetamine-dependence patients in a Japanese population. The subjects were 231 patients with methamphetamine dependence, 214 of whom had a comorbidity of methamphetamine psychosis, and 248 age- and sex-matched healthy controls. The three single nucleotide polymorphisms (SNPs), rs130058 (A-165T), rs1228814 (A-700C) and rs1228814 (A1180G) of HTR1B were genotyped. There was no significant difference in allelic and genotypic distributions of the SNPs between methamphetamine dependence and the control. Genetic associations of HTR1B were tested with several clinical phenotypes of methamphetamine dependence and/or psychosis, such as age at first abuse, duration of latency from the first abuse to onset of psychosis, prognosis of psychosis after therapy, and complication of spontaneous relapse of psychotic state. There was, however, no asscocation between any SNP and the clinical phenotypes. Haplotype analyses showed the three SNPs examined were within linkage disequilibrium, which implied that the three SNPs covered the whole HTR1B, and distribution of estimated haplotype frequency was not different between the groups. The present findings may indicate that HTR1B does not play a major role in individual susceptibility to methamphetamine dependence or development of methamphetamine-induced psychosis.

Endothelial nitric oxide synthase (NOS3) is one of the enzymes influencing nitric oxide (NO) function in the human brain. NO is a gaseous neurotransmitter that is involved in a variety of mechanisms in the central nervous system, such as N-methyl-D-aspartate receptor activation and oxidative stress. The evidence from animal pharmacological studies and postmortem studies supports an association between NO and psychotic disorders. Methamphetamine (METH) use disorder is a known psychotic disorder, and we therefore conducted a gene-based case-control study between tagging single nucleotide polymorphisms (SNPs) (rs2070744, rs1799983) in NOS3 and METH-induced psychosis in Japanese subjects (183 with METH-induced psychosis and 267 controls). Written informed consent was obtained from each subject. No significant association was found between any tagging SNP in NOS3 and METH-induced psychosis in the allele/genotype-wise or haplotype-wise analyses. In conclusion, we suggest that NOS3 might not contribute to the risk of METH-induced psychosis in the Japanese population.

During the last ten years, the ability of high power lasers to generate high energy density shocks has made them a reliable tool to study extreme states of matter. These states of matter are relevant in many important physics areas such as astrophysics, planetology and ICF physics. Here, we present some representative studies performed by using a driven laser shock: melting of iron at pressures relevant for geophysics, developments of new techniques to measure the density of highly compressed matter and a study of a radiative shock.

We present here a summary of various and preliminary experiments performed on the new facility LULI 2000. Four topics in the High Density Energy Physics have been investigated:?a? Equation of State: we studied pre-compressed water, one of most abundant component of Uranus and Neptune's mantle. We used a recent technique based on generating a shock into a diamond anvil cell pre-compressed target. Some new data on EOS surface in the range 2-3 Mbar have been obtained.?b? X-ray Thomson scattering: a strongly coupled and degenerated Aluminum plasma has been produced and probed by Ti He-alpha radiation. By using a curved spectrometer, the scattered spectrum has been measured a Compton shift from electrons has been put in evidence.?c? Astrophysics in the laboratory: A radiative supercritical shock has been produced into a gas cell filled with a low density of Xenon (0.1-0.3 bar). Various diagnostics have been implemented to determine electron density variation, precursor and shock velocities, the 2D shape of the shock at different times and electron temperature.?d? Laser accelerated flyer: different flyer plate targets have been tested. Typical shock loaded material was fused-quartz plate. Flyer velocities up to 55 km/s have been measured.?

New laser-driven flyer impact experiments have been performed at the LULI laboratory. In these experiments, three types of targets (single Al flyer, multi-layered, and foam-buffered high-Z metal) were used. Impacted conditions in fused quartz were measured with rear-side (two VISARs and SOP) and transverse diagnostics (shadowgraph). In the foam-buffered target, Ta foil was accelerated up to a velocity of 55 km/s. Shock wave accelerated in fused quartz by an Al flyer impact was generated, and the shock wave passing a distinct boundary to a conductive state was directly observed. This method is a way to create unique conditions within the EOS diagram of material.

This paper deals with radiative shocks from both theoretical and experimental viewpoints. First, experimental results obtained at Laboratoire d'Utilisation des Lasers Intenses (LULI) at high (E?400-800 J) energies are presented. The modeling of these phenomena is mainly performed through numerical simulations (1D and 2D calculations). We compare simulations given by several radiative hydrodynamics codes and discuss numerical methods employed. The lateral radiative looses are examined. A major point for discussion is the physical data (EOS, ionization, opacities) included in these codes. It is shown that the radiative precursor length depends on the dimensionality of codes and on the opacities employed. Additional quantities (temperature of the shock, electron density in the precursor) are also calculated and good agreement is obtained with the experimental data.

In the last few years, high power lasers have demonstrated the possibility to explore a new state of matter, the so-called warm dense matter. Among the possible techniques utilized to generate this state, we present the dynamic compression technique using high power lasers. Applications to planetary cores material (iron) will be discussed. Finally new diagnostics such as proton and hard-x-ray radiography of a shock propagating in a solid target will be presented.

We review the potential of x-ray scattering as a dense plasma diagnostic and present data taken from experiments in which x-ray scattering from dense plasmas is developed as a diagnostic tool. In one type of experiment the scattered photons are detected as a function of angle using direct detection onto a CCD chip. Such experiments are designed primarily to observe the static ion–ion structure factor, which is expected to dominate the scattering for moderate to high Z plasmas at a few electronvolts temperature. In a second type of experiment we have used a curved crystal to observe spectrally resolved x-ray scattering at a fixed angle. This experiment was designed to observe the dynamical structure factor of the plasma.

In the last few years, high power lasers have demonstrated the possibility to explore a new state of matter, the so-called warm dense matter. Among the possible techniques utilized to generate this state, we present the dynamic compression technique using high power lasers. Applications to planetary cores material (iron) will be discussed. Finally new diagnostics such as proton and hard-x-ray radiography of a shock propagating in a solid target will be presented.

We review the potential of x-ray scattering as a dense plasma diagnostic and present data taken from experiments in which x-ray scattering from dense plasmas is developed as a diagnostic tool. In one type of experiment the scattered photons are detected as a function of angle using direct detection onto a CCD chip. Such experiments are designed primarily to observe the static ion-ion structure factor, which is expected to dominate the scattering for moderate to high Zplasmas at a few electronvolts temperature. In a second type of experiment we have used a curved crystal to observe spectrally resolved x-ray scattering at a fixed angle. This experiment was designed to observe the dynamical structure factor of the plasma.

AbstractPurpose: To study the usefulness of intravitreal injection of triamcinolone acetonide and trypan blue for facilitating visualization and dissection of the posterior vitreous cortex and internal limiting membrane (ILM) during vitrectomy in idiopathic stage 3 macular holes. Methods: Pars plana vitrectomy was performed in 10 eyes of 10 patientswith idiopathic stage 3 macular holes. After core vitrectomy had been performed, triamcinolone acetonide was injected over the posterior pole. After separation of the visualized posterior vitreous cortex, trypan blue was injected over the macular area. Excised specimens were examined by electron microscopy. Results: Upon injection of triamcinolone acetonide, the posterior vitreous cortex and residual vitreous cortex could be visualized in all patients. The posterior vitreous cortex and residual vitreous cortex were completely removed. The ILM of the retina was stained faint blue and was successfully removed in all patients. Electron microscopy revealed that the triamcinolone-acetonide-visualized layer and the trypan-blue-stained layer had different histological features. No complications related to the use of triamcinolone acetonide and trypan blue were encountered. Conclusion: Double visualization of the posterior vitreous cortex and ILM using triamcinolone acetonide and trypan blue during vitrectomy may facilitate separation of the posterior vitreous cortex from the retina and removal of the ILM around the macular hole in patients withidiopathic stage 3 macular holes.Copyright © 2004 S. Karger AG, Basel

AbstractPurpose: To study the usefulness of intravitreal triamcinolone acetonide injection during vitrectomy in highly myopic eyes with retinal detachment due to a macular hole. Methods: Pars plana vitrectomy was performed in 6 patients with retinal detachment resulting from a highly myopic eye with a macular hole. After separation of the posterior hyaloid and removal of any visible epiretinal membrane, triamcinolone acetonide was injected over the posterior pole. Excised specimens were evaluated by transmission electron microscopy. Results: Upon injection of triamcinolone acetonide, the entire epiretinal membrane and residual vitreous cortex could be visualized in all patients. The epiretinal membrane and residual posterior vitreous cortex were completely removed. Successful reattachment was performed without retinal damage in all cases. Electron microscopy revealed a cellular epiretinal membrane within a collagenous matrix lining the smooth internal surface of the internal limiting membrane. No complications related to the use of triamcinolone acetonide were encountered. Conclusion: Intraoperative visualization of the epiretinal membrane and residual posterior vitreous cortex with triamcinolone acetonide was found to be a useful adjunct to vitrectomy. Using triamcinolone acetonide during vitrectomy may facilitate both removal of the epiretinal membrane around the macular hole and separation of the residual vitreous cortex from the retina in highly myopic eyes with retinal detachment.Copyright © 2004 S. Karger AG, Basel

The serotonin 5-HT4 receptor (5-HT4) is implicated in cognitive function, of which impairment is hypothesized as one of the core disturbances of schizophrenia. Linkage analysis shows that 5q33.2, in which HTR4 is located, is schizophrenia-susceptibility loci. We therefore hypothesized that variation in the 5-HT4 receptor gene (HTR4) modifies genetic susceptibility to schizophrenia. HTR4 coding regions and introns that include the branch sites of HTR4 were investigated in 96 unrelated Japanese schizophrenics using denaturing high-performance liquid chromatography analysis. One silent single nucleotide polymorphism (SNP) within the coding region and six intronic SNPs were detected. 353 + 6G > A was located in the branch site that could be effect to RNA splicing. None of the four SNPs, in which rare-allele frequencies were more than 10% was associated with 189 schizophrenics, in comparison to 299 controls. However, a highly significant association between schizophrenia and haplotype A-T (OR = 0.13 [0.03–0.58]) was detected. These findings suggest that haplotype A-T itself may inhibit the occurrence of schizophrenia, or that another susceptible genetic variants may exist within linkage disequilibrium. © 2003 Wiley-Liss, Inc.

Human chorionic gonadotropin (hCG) glycoforms change as pregnancy progresses. We have developed an antibody (B152) which can measure a hyperglycosylated early pregnancy isoform of hCG. This putative hyperglycosylated form of hCG arises very early in pregnancies and is rapidly replaced by an isoform that predominates for the remainder of the pregnancy. The profiles of these hCG glycoforms are measured as a ratio of values of two immunometric assays. The profiles of these ratios differ between pregnancies which persist and those which will experience early failure. In this report, daily urine hCG isoform ratios from donor eggs (no exogenous hCG pretreatment), in vitro fertilization pregnancies were profiled and analyzed from the first day following embryo transfer (ET). Significant differences were found between continuing pregnancy and pregnancy loss throughout days 5-20 post-ET. When hCG isoform ratios were analyzed from the first day of detectable hCG, pregnancy loss could be predicted in the case of a single fetus both during the 5- to 10-day time segment (P=0.018) and the 10- to 15-day time segment (P=0.045). When single and multiple fetus pregnancies were analyzed together significance was approached in the 10- to 15-day time period (P=0.058). In a second population of pregnant women who conceived naturally, in whom urine samples were collected at approximately weekly intervals to either term birth or clinical spontaneous abortion, the ratio could discriminate between miscarriages and normal term pregnancies (P=0.043). In later pregnancy, the ratio of hCG isoforms declined more rapidly in miscarriages than in term pregnancy. Antibody B152 was produced using a choriocarcinoma-derived hCG (C5), which was hyperglycosylated at both N- and O-linked sites and was 100% nicked at position beta(47-48). Western blot analyses supported the assay results showing that early pregnancy urine does not contain nicked C5-like hCG. Also, the early pregnancy hCG appeared to be the same size as later pregnancy hCG as judged by SDS gel electrophoresis. A series of Western blot analyses and immunoassays conducted with the samples either non-reduced or reduced showed that B152 is directed to a linear epitope located in the COOH-terminal peptide region of the beta subunit. This indicated that only the O-glycan groups and not the N-linked glycans are part of the antibody epitope.

Background & Aims:Voltage-dependent Na^+ currents are important determinants of excitability. We hypothesized that gastric inflammation alters Na^+ current properties in primary sensory neurons. Methods:The stomach was surgically exposed in rats to inject theretrograde tracer 1.1'-dioctadecyl-3,3,3,'3-tetramethyl-indocarbocyanine methanesulfonate and saline (control) or 20% acetic acid (ulcer group) into the gastric wall, Nodose or thoracic dorsal root ganglia (DRG) were harvested after 7 days to culture neurons and record Na^+ currents using patch clamp techniques. Results:There were no lesions in the control and 3 +/- 1 ulcers in the ulcer group. Na^+ currents recovered significantly more rapidly from inactivation in nodose and DRG neurons obtained from animals in the ulcer group compared with controls. This was partially a result of an increase in the relative contribution of the tetrodotoxin-resistant to the peak sodium current. In addition, the recovery kinetics of the tetrodotoxin-sensitive current were faster. In DRG neurons, gastric inflammation shifted the voltage-dependence of activation of the tetrodotoxin-resistant current to more hyperpolarized potentials. Conclusions:Gastric injury alters the properties of Na^+ currents in gastric sensory neurons. This may enhance excitability. thereby contributing to the development of dyspeptic symptoms.

Most Japanese pediatric neurologists attempt other treatments before using adrenocorticotropic hormone (ACTH) therapy for West syndrome (WS), and even then, they use only a low-dose synthetic ACTH to avoid serious adverse effects. In this multi-institutional study, the authors analyzed the initial effects, adverse effects, and long-term outcome in patients treated with low-dose synthetic ACTH in Japan.

We have studied electron-irradiation-induced defects created on an electron exit surface of a Si thin film by means of scanning tunneling microscopy (STM). Several electron-irradiated areas with different electron doses are provided for STM observation. Transmission electron microscopy (TEM) observation reveals a number of silicon-surface-nanoholes of 2–3 nm in diameter and about 5 nm apart in an irradiated area whenever it receives the dose larger than 1.5×1024e/cm2, while no distinctive TEM contrast of defects is observed in an area with lower dose. STM observation has shown that electron-irradiated surfaces are rougher than a nonirradiated surface. Examining the depth distribution of the areas with different doses, we have found that each irradiated surface exhibits two depth levels which are attributed to a rough surface and a bottom of surface nanoholes, respectively. Even in an area with the lowest dose (1.5×1022e/cm2) in this experiment we have observed distinctive STM contrasts, the arrangement and sizes of which are similar to those of the well-developed surface nanoholes observable by TEM. This STM observation shows that the arrangement of nanoholes on an electron exit surface is set up at the very early stage, followed by the excavating of nanoholes under prolonged electron irradiation. We suggest that nanoholes exist in the early stage when only a few atomic layers are removed from the initial surface.

Flyer acceleration experiments are carried out using a KrF laser system with a pulse duration of 10–15 ns and an intensity of ~1.0 × 1013 W/cm2. Three-layered targets (aluminum–polyimide–tantalum) are used. First, an average velocity of laser-driven tantalum flyers with a thickness of 4 and 8 μm is estimated. Then, in a collision of a flyer with a copper layer attached to a diamond plate, we measure a transit time of a shock wave in the diamond. The impact velocity is estimated based on the transit time and a numerical simulation. This numerical simulation also shows that the initial peak pressure caused by the impact of a 4-μm-thick flyer is kept at 11 Mbar for 12–13 μm in thickness. Finally, whether this thickness is enough for EOS measurements is discussed.

BACKGROUND/AIMS: The Arthus type allergic reaction is characterised by inflammatory cell infiltration and marked neovascularisation in the cornea. During the healing stages, inflammatory cells and newly formed microvessels gradually disappear. The aim was to establish whether apoptosis affected the regression of inflammatory cells and newly formed microvessels, in order to define more clearly the cellular mechanisms involved in the pathobiology of corneal diseases. METHODS: Albino male rabbits were injected subcutaneously with 5 mg/ml bovine serum albumin (BSA) incorporated in Freund's complete adjuvant twice weekly. Under the anaesthesia, 30 μl of a 0.5 mg/ml BSA solution was injected into the central corneal stroma to induce an Arthus type allergic reaction. The injured corneas were collected at various time points ranging from 3 to 20 days. Apoptotic cells were identified by both light microscopy using in situ TdT-dUTP nick end labelling (TUNEL) method and electron microscopy. RESULTS: With increasing time after induction of the Arthus reaction, marked neovascularisation and infiltrated inflammatory cells such as polymorphonuclear cells (PMNs) and plasma cells were observed in the cornea. Thereafter, the inflammatory cells and newly formed microvessels gradually disappeared. Coincidently, the numbers of microvessel endothelial cells and infiltrated inflammatory cells undergoing apoptosis were increased. Apoptotic bodies were taken up by macrophages, PMNs, as well as myofibroblasts derived presumably from transformation of migrated keratocytes. CONCLUSIONS: These data demonstrate that regression of the cellular infiltrates and microvessel endothelial cells associated with the Arthus reaction in the cornea occurs via apoptosis. This finding adds insights into the cellular mechanisms regulating the pathobiology of corneal diseases.

Opioids are widely and successfully used for control of pain, including pain arising from the viscera. Constipating, sedating, respiratory depressant and other effects of opioids, however, often limit their long-term use in the treatment of a variety of visceral pain states. Accordingly, understanding visceral pain mechanisms and its modulation is important to developing improved strategies for pain control.

Background: Ischemic preconditioning (IPC) is a promising strategy for conferring ischemic tolerance. We confirmed the acquisition of ischemic tolerance in the liver immediately after IPC and the role of adenosine kinetics in this process. Methods: Male Lewis rats were used. IPC was administered with a 10-minute ischemia followed by a 10-minute reperfusion. Ischemic tolerance was tested with a 45-minute ischemia. Changes in the adenosine concentrations in liver tissue were evaluated, and the effects of adenosine A"1 or A"2 receptor agonists or antagonists were examined either in place of or against IPC. Results: The 7-day animal survival was significantly better in the IPC group than in the control group (87% vs 53%; n = 15, P < .05). The release of liver-related enzymes during reperfusion was suppressed better in the IPC group (P < .01). Recovery of adenosine triphosphate levels was faster in the IPC group (P < .01). After IPC, adenosine concentrations in liver tissue immediately increased to 1555 +/- 299 pmol/g wet tissue and were maintained at that level during a subsequent 45-minute ischemia. The ischemic tolerance generated by IPC was mimicked by the administration of adenosine A"2 receptor agonist and opposed by adenosine A"2 receptor antagonist. Conclusions: The ischemic tolerance of the liver immediately after IPC can be supplanted by selective pharmacologic stimulation of adenosine A"2 receptors. (Surgery 1999;126:945-54.)

Summary Cat superior cervical ganglia (SCG) were tetanically stimulatedin vivo at 30–100 Hz until neural transmission was exhausted, and then were allowed to rest and recover. Changes in their cholinergic synapses were examined electrophysiologically and morphologically during the time of tetanic stimulation and during recovery. For morphometric analysis the presynaptic terminal was subdivided into two areas: an area directly over the active zone, termed zone-I, (bounded by a hemicircle with a diameter equivalent to the active zone length), and the remaining preterminal area, termed zone-II. In control ganglia before stimulation synaptic vesicle density in zone-I (SVD-I) averaged 90 µm-2 and the number of vesicles actually attached to the active zone (SVA) averaged about 2.5 per single profile of nerve terminal. Upon stimulation, the postganglionic potential immediately began to decline in amplitude and disappeared after 1 min of stimulation. Simultaneously, SVD-I declined to less than 35 µm-2 and SVA declined to less than 1 per section. Thereafter, stimulation was terminated and the ganglion was allowed to rest. Recovery of the postganglionic potential was monitored by stimulation at 1 Hz. The postganglionic potential reached control levels after only 1 min of rest. Likewise, the structural parameters, SVD-I and SVA, also rapidly recovered, reaching control levels after only 30 sec of rest, slightly faster than the postganglionic potential. This illustrates that stimulation-induced fatigue of transmitter output and depletion of synaptic vesicles recover to the control level at a high rate in synapses of the cat SCG with a normal supply of blood. In fact, morphological recovery may be slightly faster than electrophysiological recovery. Mechanisms of vesicle formation and migration to the presynaptic area are discussed in light of these observations.

The plasma total biopterin and tetrahydrobiopterin (BH4) levels of 24 psychiatric patients were measured in the symptomatic phase, under no influence of psychotropic drugs as long as possible, and were compared with those of normal controls. The significant increase in total biopterin levels was observed only in the plasma of the patients with affective disorders or panic disorder in the depressive mood. A significant decrease in BH4 levels was observed only in the plasma of the patients with depression, and an increase in BH4levels was observed only in the patients with hypomania. The changes of these biopterin levels in plasma could be a disease effect or a phase effect.