Analysis system of submicron particle tracks in the fine-grained nuclear emulsion by a combination of hard x-ray and optical microscopy.

Analyses of nuclear emulsion detectors that can detect and identify charged particles or radiation as tracks have typically utilized optical microscope systems because the targets have lengths from several µm to more than 1000 µm. For recent new nuclear emulsion detectors that can detect tracks of submicron length or less, the current readout systems are insufficient due to their poor resolution. In this study, we developed a new system and method using an optical microscope system for rough candidate selection and the hard X-ray microscope system at SPring-8 for high-precision analysis with a resolution of better than 70 nm resolution. Furthermore, we demonstrated the analysis of submicron-length tracks with a matching efficiency of more than 99% and position accuracy of better than 5 µm. This system is now running semi-automatically.

Differential expression of mRNAs for sialyltransferase isoenzymes induced in the hippocampus of mouse following kindled seizures.

Sialic acids play important roles in various biological functions. In the brain, evidence suggests that sialylation of glycoproteins and glycolipids affects neural plasticity. While the 18 sialyltransferase isoenzymes (STs) identified to date synthesize individual sialyl-oligosaccharide structures, they each exhibit activity toward more than one substrate and can overlap in their specificity. Therefore, the distribution of STs is a secondary factor in the study of specific sialylation. Here, seven STs; ST3Gal I-IV, ST8Sia IV, ST6Gal I and ST6GalNAc II, the expressions of which were identified in the adult hippocampus by RT-PCR, showed diverse localization patterns in the hippocampus on in situ hybridization, suggesting that the individual cells expressed relevant STS: Furthermore, to assay activity-related changes in ST expression, we used amygdaloid-kindling among models of neural plasticity. Differential expression of the STs participating in the kindling, notably, up-regulation of ST3Gal IV and ST6GalNAc II mRNAs, and down-regulation of ST3Gal I and ST8Sia IV mRNAs, were observed in the hippocampus following kindled seizures. These results indicate that ST expressions are regulated by physiological activity and may play a role in neural plasticity.

Dendritic aberrations in the hippocampal granular layer and the amygdalohippocampal area following kindled-seizures.

Amygdaloid kindling is a model of human temporal lobe epilepsy, in which excitability in limbic structures is permanently enhanced by repeated stimulations. We report here dendritic aberrations occurring in mice following kindled-seizures. Adult mice received a biphasic square wave pulse [495+/-25.5 (S.E.M.) microA 60 Hz, 200 micros duration, for 2 s] unilaterally in the basolateral amygdaloid complex once a day and mice with electrophysiologically and behaviorally verified seizures were used in the experiments. The hippocampus and amygdaloid complex contralateral to the lesions were observed by immunofluorescence histochemistry with a somatodendritic marker, microtubule-associated protein 2 (MAP2), showing that kindled-seizures caused hypertrophy of proximal dendrites in the granule cells of the dentate gyrus and in neurons of the amygdalohippocampal area. To further characterize the morphological changes of the dendrites, electron micrographic analysis was performed on the contralateral side. (1) In the granular layer of the dentate gyrus and the amygdalohippocampal area, kindled-seizures generated an increase in the number of dendrites containing polymerized microtubules and width of dendritic profiles showing the increase was in the range 0.2-3.0 and 0.2-1.4 microm, respectively. (2) In the granular layer, bundles between dendrites separated by the puncta adhaerentia increased. (3) In the granular layer, the seizure-induced dendritic aberration was more severe in the rostral than the caudal region. These results suggested that growth of dendrites with enriched-stable microtubules is part of the structural plasticity in response to seizure activity in specific areas of the adult brain.

X-ray telescope onboard Astro-E: optical design and fabrication of thin foil mirrors.

X-ray telescopes (XRT's) of nested thin foil mirrors are developed for Astro-E, the fifth Japanese x-ray astronomy satellite. Although the launch was not successful, the design concept, fabrication, and alignment procedure are summarized. The main purpose of the Astro-E XRT is to collect hard x rays up to 10 keV with high efficiency and to provide medium spatial resolution in limited weight and volume. Compared with the previous mission, Advanced Satellite for Cosmology and Astrophysics (ASCA), a slightly longer focal length of 4.5-4.75 m and a larger diameter of 40 cm yields an effective area of 1750 cm2 at 8 keV with five telescopes. The image quality is also improved to 2-arc min half-power diameter by introduction of a replication process. Platinum is used instead of gold for the reflectors of one of the five telescopes to enhance the high-energy response. The fabrication and alignment procedure is also summarized. Several methods for improvement are suggested for the reflight Astro-E II mission and for other future missions. Preflight calibration results will be described in a forthcoming second paper, and a detailed study of images will be presented in a third paper.

X-Ray Telescope Onboard Astro-E. II. Ground-Based X-Ray Characterization.

X-ray characterization measurements of the x-ray telescope (XRT) onboard the Astro-E satellite were carried out at the Institute of Space and Astronautical Science (Japan) x-ray beam facility by means of a raster scan with a narrow x-ray pencil beam. The on-axis half-power diameter (HPD) was evaluated to be 1.8?-2.2?, irrespective of the x-ray energy. The on-axis effective areas of the XRTs for x-ray imaging spectrometers (XISs) were approximately 440, 320, 240, and 170 cm(2) at energies of 1.49, 4.51, 8.04, and 9.44 keV, respectively. Those of the x-ray spectrometer (XRS) were larger by 5-10%. The replication method introduced for reflector production significantly improved the imaging capability of the Advanced Satellite for Cosmology and Astrophyics (ASCA) XRT, whose HPD is ~3.6?. The increase in the effective area by a factor of 1.5-2.5, depending upon the x-ray energy, compared with that of the ASCA, was brought about by mechanical scale up and longer focal lengths. The off-axis HPDs were almost the same as those obtained on the optical axis. The field of view is defined as the off-axis angle at which the effective area becomes half of the on-axis value. The diameter of the field of view was ~19? at 1.49 keV, decreasing with increasing x-ray energy, and became ~13? at 9.44 keV. The intensity of stray light and the distribution of this kind of light on the focal plane were measured at the large off-axis angles 30? and 60?. In the entire XIS field of view (25.4 mm x 25.4 mm), the intensity of the stray light caused by a pointlike x-ray source became at most 1% of the same pointlike source that was on the optical axis.

Effect of heat stress on serotonin-2A receptor-mediated intracellular calcium mobilization in rat C6 glioma cells.

This study was conducted to investigate an effect of heat stress at 44 degrees C for 30 min on intracellular Ca2+ signaling system and on heat shock protein (HSP)-70 expression. 5-HT-induced Ca2+ mobilization was reduced 1, 3 and 6 hrs after heat stress, and recovered to the control level 12 and 24 hrs after heat stress. One hr after heat stress, Ca2+ rise was significantly decreased when the cells were stimulated by any concentration of 5-HT. Thrombin-induced Ca2+ increase was also markedly reduced 1 hr after heat stress. HSP-70 level was increased 6 and 9 hr after heat stress. In HSP synthesis inhibitor quercetin-treated cells, HSP-70 expression was not enhanced after heat stress, and Ca2+ rise in response to 5-HT did not return to the control level. However, the Ca2+ rise induced by 5-HT was not restored to the control level after stress in Ac-Asp-Glu-Val-Asp-H (DEVD)-exposed cells while DEVD had little effect on heat stress-induced synthesis of HSP-70. Dexamethasone did not alter the change in HSP-70 expression or Ca2+ response after heat stress. These results indicate that heat stress attenuated 5-HT-induced Ca2+ mobilization and that HSP-70 expression played an important role in recovery from Ca2+ impairment, possibly via protease activity in C6 cells.

Lithium chloride inhibits thrombin-induced intracellular calcium mobilization in C6 rat glioma cells.

In this study, the authors have demonstrated the effect of lithium, a typical mood stabilizer, on thrombin-evoked Ca2+ mobilization in C6 cells to elucidate the action mechanisms of the drug. Thrombin-induced Ca2 mobilization was reduced 24 hr after 1 or 10 mM lithium chloride (LiCl) pretreatment. The Ca2+ rise was reduced in a time-dependent manner, and the significant inhibition was observed 9 hr pretreatment with 10 mM LiCl. On the other hand, pretreatment of the cells with 10 mM LiCl for 24 hr did not alter the amount of Galphaq/11 significantly. Pretreatment with 10 mM LiCl for 24 hr failed to reduce the 5-HT-induced Ca2+ mobilization or to affect the desensitization of the 5-HT signal. Finally, thrombin-elicited Ca2+ rise was markedly inhibited in the presence of 0.05 U/ml plasmin, however, the Ca2+ rise was not further attenuated in the presence of plasmin in C6 cells pretreated with LiCl for 24 hr. These results indicate that pretreatment with LiCl attenuated thrombin-evoked intracellular Ca2+ mobilization in plasmin sensitive manner in C6 rat glioma cells. Thus, it is important to investigate the effect of lithium on thrombin-induced cellular responses to clarify the action mechanism of lithium in relation to some abnormality in thrombin-evoked Ca2+ rise observed in bipolar disorders.

Risperidone treatment of neuroleptic-induced tardive extrapyramidal symptoms.

Tardive extrapyramidal symptoms (EPS) induced by neuroleptic treatment, and particularly EPS which persist after withdrawal of the drugs, are clinically serious problems. We describe a patient with four types of tardive and persistent EPS such as dystonia, dyskinesia, choreatic movement and myoclonus, induced by haloperidol. These EPS were remarkably inhibited by 3 mg/day risperidone. This is the first published case demonstrating simultaneous development of these four types of tardive EPS induced by a neuroleptic and then reduced by low-dose risperidone treatment. ( Int J Psych Clin Pract 2000; 4: 241 - 243).

Intracellular calcium signaling systems in the pathophysiology of affective disorders.

In this paper, we show the importance of intracellular calcium (Ca2+) signaling systems in the pathophysiology of mood disorders based on our recent work. Patients with affective disorders appear to have an enhanced intracellular Ca2+ rise in response to serotonin. We have observed effects of antidepressant drugs on intracellular Ca2+ signaling in rat cultured neuronal cells and glioma cells, and found that acute application of several classes of antidepressant drugs inhibited intracellular Ca2+ signaling and Ca2+-related signaling. It is important to investigate the role of intracellular Ca2+ signaling system for an understanding of the pathophysiology of affective disorders.

Lipopolysaccharide regulates both serotonin- and thrombin-induced intracellular calcium mobilization in rat C6 glioma cells: possible involvement of nitric oxide synthase-mediated pathway.

To investigate the mechanisms by which lipopolysaccharide (LPS) affects Ca2+ signaling systems, we studied the effects of LPS on the serotonin (5-HT)- or thrombin-induced intracellular Ca2+ ([Ca2+]i) increase in rat C6 glioma cells. Pretreatment of the cells with 1 microg/ml LPS for 24 hr significantly inhibited [Ca2+]i increase induced by 10 microM 5-HT- or 0.5 U/ml thrombin. Its inhibitory effects were both dose- and time-dependent. Treatment with 1 mM dibutyryl cGMP (dbcGMP) for 30 min also significantly inhibited the 5-HT- and thrombin-induced [Ca2+]i increase to approximately 60-70% of control. However, simultaneous pretreatment with LPS and dbcGMP did not show any synergistic inhibition. The simultaneous pretreatment with LPS and the potent cGMP-dependent protein kinase (PKG) inhibitors H-8 and KT5823 for 24 hr significantly antagonized the inhibitory effect of LPS. Pretreatment of the cells with 1 microg/ml LPS for 24 hr significantly enhanced cGMP accumulation, while dexamethasone and NMMA (NOS inhibitors) significantly attenuated the LPS-induced enhancement in cGMP accumulation. In addition, pretreatment of the cells with 100 nM dexamethasone for 24 hr significantly suppressed LPS-induced inducible nitric oxide synthase (iNOS; type II NOS, NOS-II) protein expression. These results indicate that LPS may inhibit both 5-HT- and thrombin-induced [Ca2+]i increase via iNOS expression and PKG activation pathway in rat C6 glioma cells.

Effect of surface roughness and subsurface damage on grazing-incidence x-ray scattering and specular reflectance.

Grazing-incidence specular reflectance and near-specular scattering were measured at Al-K(alpha) (1.486-keV, 8.34-?) radiation on uncoated dielectric substrates whose surface topography had been measured with a scanning probe microscope and a mechanical profiler. Grazing-incidence specular reflectance was also measured on selected substrates at the Cu-K(alpha) (8.047-keV, 1.54-?) wavelength. Substrates included superpolished and conventionally polished fused silica; SiO(2) wafers; superpolished and precision-ground Zerodur; conventionally polished, float-polished, and precision-ground BK-7 glass; and superpolished and precision-ground silicon carbide. Roughnesses derived from x-ray specular reflectance and scattering measurements were in good agreement with topographic roughness values measured with a scanning probe microscope (atomic force microscope) and a mechanical profiler that included similar ranges of surface spatial wavelengths. The specular reflectance was also found to be sensitive to the density of polished surface layers and subsurface damage down to the penetration depth of the x rays. Density gradients and subsurface damage were found in the superpolished fused-silica and precision-ground Zerodur samples. These results suggest that one can nondestructively evaluate subsurface damage in transparent materials using grazing-incidence x-ray specular reflectance in the 1.5-8-keV range.

Supermirror hard-x-ray telescope.

The practical use of a grazing x-ray telescope is demonstrated for hard-x-ray imaging as hard as 40 keV by means of a depth-graded d-spacing multilayer, a so-called supermirror. Platinum-carbon multilayers of 26 layer pairs in three blocks with a different periodic length d of 3-5 nm were designed to enhance the reflectivity in the energy range from 24 to 36 keV at a grazing angle of 0.3 deg. The multilayers were deposited on thin-replica-foil mirrors by a magnetron dc sputtering system. The reflectivity was measured to be 25%-30% in this energy range; 20 mirror shells thus deposited were assembled into the tightly nested grazing-incidence telescope. The focused hard-x-ray image was observed with a newly developed position-sensitive CdZnTe solid-state detector. The angular resolution of this telescope was found to be 2.4 arc min in the half-power diameter.

Characterization of substrates for use in X-ray multilayer optics.

The optical performance of platinum-carbon multilayers deposited onto different substrates has been examined. Specular reflectivity and non-specular diffuse scattering were measured to study the replication of substrate roughness into the multilayer structure. Surface topography was measured before and after deposition using a scanning probe microscope and a mechanical profiler.

Fabrication and characterization of multilayer supermirrors for hard X-ray optics.

Multilayer supermirrors stacked with three sets of Pt/C combinations have been fabricated on a flat float-glass and conical replica foil mirror using a magnetron DC sputtering system, and applied to X-ray optical systems in the hard X-ray region. The design of the supermirror is optimized to obtain the highest integrated reflectivity in the energy band and at the grazing angle concerned. X-ray reflectivities of 30% in the 25-35 keV band at an incidence angle of 0.3 degrees were obtained.

Benefits of trazodone and mianserin for patients with late-life chronic schizophrenia and tardive dyskinesia: an add-on, double-blind, placebo-controlled study.

The objective of the present study was to evaluate the efficacy of mianserin and trazodone as antidepressants with serotonin 2 antagonist properties on negative symptoms and tardive dyskinesia in elderly patients with chronic schizophrenia. In this double-blind, placebo-controlled study the dose of each drug was increased gradually, from 20 mg/day mianserin to 60 mg/day, and from 50 mg/day trazodone to 200 mg/day. Symptoms were assessed using the Brief Psychiatric Rating Scale, the Scale for Assessment of Negative Symptoms and the Abnormal Involuntary Movement Scale every week for 5 weeks. A total of 38 patients (23 men and 15 women) completed the trial. Mianserin (n = 13) and trazodone (n = 12) did not alter the Brief Psychiatric Rating Scale positive symptom factor over the 5 weeks. In the mianserin group, the Scale for Assessment of Negative Symptoms total score decreased significantly after 5 weeks. Scores of 'affective flattening and blunting' and 'alogia' scores on the Scale for assessment of Negative Symptoms decreased significantly in both treatment groups. In the trazodone group, the decrease in the Abnormal Involuntary Movement Scale total score was statistically significant at weeks 2 and 3. Results indicate that serotonergic antidepressants, when used in conjunction with neuroleptics, are safe and effective for treating negative symptoms in elderly patients with chronic schizophrenia. Results also indicated a possible beneficial effect of trazodone in treating tardive dyskinesia.

Modulation of endothelin-induced intracellular Ca2+ mobilization by interleukin-1 beta and lipopolysaccharide in C6 rat glioma cells.

We have investigated the effects of interleukin (IL)-1 beta and lipopolysaccharide (LPS) on endothelin (ET)-induced intracellular Ca2+ rise in C6 rat glioma cells in order to study the mechanisms of their effects on Ca2+ signaling systems. Pretreatment with IL-1 beta (10(3) U/mL) and LPS (1 microgram/mL) for 24 h significantly inhibited 100 nM ET-1-induced increase in intracellular Ca2+ either in the presence or absence of external Ca2+. Their inhibitory effects were in dosedependent (IL-1 beta; 50-1000 U/mL, LPS; 10-1000 ng/mL) and time-dependent (12-24 h) manners. A tyrosine kinase antagonist genistein (50 microM) but not a protein kinase C inhibitor H7 (30 microM) prevented the inhibition of the ET response by IL-1 beta and LPS. These results suggest that activation of tyrosine kinase may be essential for the inhibition of the ET receptor-mediated Ca2+ signaling systems by IL-1 beta and LPS.

Transient and intermittent oral dyskinesia appearing in a young woman ten days after neuroleptic treatment.

A 22-year-old woman was admitted to our hospital because she showed psychomotor excitement and signs of schizophrenia following psychological stress. Nine days after neuroleptic medication, she could not eat and exhibited high fever, diaphoresis, excessive salivation, and severe extrapyramidal signs with cogwheel rigidity and resting tremor of the upper extremities. The next day, bucco-linguomasticatory dyskinesia, which is quite similar to tardive dyskinesia, appeared. The dyskinesia lasted intermittently for 6 days. The present case shows that buccolingual dyskinesia can occur even after early neuroleptic exposure in certain patients.

Nitric oxide is involved in the inhibitory action of cholecystokinin octapeptide (CCK-OP) on proximal colonic motility.

To determine whether nitric oxide (NO) is a possible mediator in the inhibitory action of CCK-octapeptide (CCK-OP) on circular muscle contractions of the rat proximal colon, contractile activities of the circular muscle were recorded in the proximal colon of unrestrained conscious rats in the fasting state using a miniature strain gauge force transducer and an implantable telemetry system. Regular and rhythmic phasic contractions were observed during the fasted condition, similar to the myoelectric migrating complex seen in intestinal contractions of the fasting dog. These phasic contractions were almost completely inhibited after intraperitoneal (i.p.) administration of CCK-OP at a dose of 15 microg/kg body weight. N(omega)-nitro-arginine, methyl ester (L-NAME), at doses of 20 and 200 mg/kg i.p. administered prior to i.p. injection of CCK-OP, prevented the inhibitory action on the fasting phasic contractions. The degree of prevention was dose-dependent. 100 mg/kg body weight i.p. injection of L-arginine inhibited the circular muscle contractions. The same dose of D-arginine had no action on contractions of the circular muscle of the proximal colon in the fasted rat. From these data, we conclude that NO is one possible mediator in the inhibitory mechanism of CCK-OP on smooth muscle motor activity of the rat proximal colon in vivo.

Effect of dantrolene on KCl- or NMDA-induced intracellular Ca2+ changes and spontaneous Ca2+ oscillation in cultured rat frontal cortical neurons.

Dantrolene has been known to affect intracellular Ca2+ concentration ([Ca2+]i) by inhibiting Ca2+ release from intracellular stores in cultured neurons. We were interested in examining this property of dantrolene in influencing the [Ca2+]i affected by the NMDA receptor ligands, KCl, L-type Ca2+ channel blocker nifedipine, and two other intracellular Ca2(+)-mobilizing agents caffeine and bradykinin. Effect of dantrolene on the spontaneous oscillation of [Ca2+]i was also examined. Dantrolene in microM concentrations dose-dependently inhibited the increase in [Ca2+]i elicited by NMDA and KCl. AP-5, MK-801 (NMDA antagonists), and nifedipine respectively reduced the NMDA and KCl-induced increase in [Ca2+]i. Dantrolene, added to the buffer solution together with the antagonists or nifedipine, caused a further reduction in [Ca2+]i to a degree similar to that seen with dantrolene alone inhibiting the increase in [Ca2+]i caused by NMDA or KCl. At 30 microM, dantrolene partially inhibited caffeine-induced increase in [Ca2+]i whereas it has no effect on the bradykinin-induced change in [Ca2+]i. The spontaneous oscillation of [Ca2+]i in frontal cortical neurons was reduced both in amplitude and in base line concentration in the presence of 10 microM dantrolene. Our results indicate that dantrolene's mobilizing effects on intracellular Ca2+ stores operate independently from the influxed Ca2+ and that a component of the apparent increase in [Ca2+]i elicited by NMDA or KCl represents a dantrolene-sensitive Ca2+ release from intracellular stores. Results also suggest that dantrolene does not affect the IP3-gated release of intracellular Ca2+ and that the spontaneous Ca2+ oscillation is, at least partially, under the control of Ca2+ mobilization from internal stores.

Methicillin-resistant Staphylococcus aureus and Candida albicans on denture surfaces.

Infectious diseases caused by methicillin-resistant Staphylococcus aureus, MRSA, and Candida albicans are often serious in compromised hosts. We enumerated MRSA and C. albicans on denture surfaces and in saliva samples from 29 adults. Staphylococcus species, MRSA, and methicillin-resistant Staphylococcus epidermidis, MRSE, were detected on 17, 3, and 1 of the 29 denture surfaces, respectively. C. albicans were detected on 22 denture surfaces. All saliva samples from patients whose dentures carried Staphylococcus species and C. albicans were also found to contain both microorganisms. Adherence of isolated 3H labeled cells of MRSA and C. albicans to resin beads and saliva-coated resin beads was examined. Cells of both microorganisms adhered in significantly higher numbers to saliva-coated resin beads than to resin beads. The hydrophobicity of the MRSA isolated from denture surfaces varied from strain to strain; that of C. albicans strains was moderately high. The zeta potentials of MRSA isolates and of C. albicans isolates determined in KCI buffer were significantly low. The potential of the resin beads decreased after treatment with saliva. Two out of 5 MRSA strains were found to be inhibited in growth by oral Streptococcus, Actinomyces, and gram-negative bacterial strains, suggesting that some oral bacterial species play a role in inhibiting the colonization of Staphylococcus species. No isolates of C. albicans were inhibited in their growth by any of the oral bacteria tested. Isolates of MRSA and C. albicans coaggregated with Porphyromonas gingivalis and Fusobacterium nucleatum strains. Using denture cleaners every night for 2 weeks did not reduce numbers of Staphylococcus species or C. albicans organisms in saliva.