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Aim: The aim of this study was to determine the prevalence of anti-liver/kidney microsome autoantibody type 1 (anti-LKM-1) among hepatitis C virus (HCV)-infected Japanese patients at various stages (chronic hepatitis, liver cirrhosis and hepatocellular carcinoma), and to assess the influence of anti-LKM-1 on interferon therapy. Methods: A total of 390 serum samples from 215 HCV-infected patients with chronic hepatitis (HCV-CH), 81 HCV-infected patients with liver cirrhosis (HCV-LC), and 94 HCV-HCC infected patients were subjected to examination. Ninety-one HBsAg-positive patients and 137 healthy subjects served as controls. Anti-liver/kidney microsome autoantibody type 1 was determined by using a newly developed ELISA using recombinant cytochrome P450 IID6 as the antigen. Results: Anti-liver/kidney microsome autoantibody type 1 was detected in six of the 390 (1.5%) chronic HCV-infected patients (four were HCV-CH and two were HCV-LC); in contrast, it was not detected in control groups. Among the 110 HCV-CH patients treated with interferon (IFN), four were positive for anti-LKM-1. No change in anti-LKM-1 immunoreactivity from negative to positive during interferon therapy was observed. Moreover, no increase in the serum alanine aminotransferase level was observed in these four patients with anti-LKM-1. Conclusion: Our study indicates that: (i) anti-LKM-1 does not aggravate the liver disease associated with HCV infection; and (ii) no change in anti-LKM-1 immunoreactivity from negative to positive or no aggravations of liver dysfunction were observed among HCV-CH patients during the IFN therapy for Japanese patients with liver disease.

Brain-derived neurotrophic factor (BDNF) regulates both short-term synaptic functions and activity-dependent synaptic plasticity such as long-term potentiation. In the present study, we investigated the role of BDNF in the spatial reference and working memory in a radial arm maze test. The radial arm maze training resulted in a significant increase in the BDNF mRNA expression in the hippocampus, although the expression in the frontal cortex did not change. When spatial learning was inhibited by treatment with 7-nitroindazole, an inhibitor of brain nitric oxide synthase, the increase in the hippocampal BDNF mRNA did not occur. To clarify the causal relation between BDNF mRNA expression and spatial memory formation, we examined the effects of antisense BDNF treatment on spatial learning and memory. A continuous intracerebroventricular infusion of antisense BDNF oligonucleotide resulted in an impairment of spatial learning, although the sense oligonucleotide had no effect. Treatment with antisense, but not sense, BDNF oligonucleotide was associated with a significant reduction of BDNF mRNA and protein levels in the hippocampus. Furthermore, treatment with antisense BDNF oligonucleotide in rats, which had previously acquired spatial memory by an extensive training, impaired both reference and working memory. There were no differences in locomotor activity, food consumption, and body weight between the antisense and sense oligonucleotide-treated rats. These results suggest that BDNF plays an important role not only in the formation, but also in the retention and/or recall, of spatial memory.

In Aspergillus niger, a cyanide (CN)- and antimycin A-insensitive and salicylhydroxamic acid (SHAM)-sensitive respiratory pathway exists besides the cytochrome pathway and is catalyzed by the alternative oxidase (AOX). In this study, A. niger WU-2223L, a citric acid-producing strain, was cultivated in a medium containing 120 g/l of glucose, which is the concentration usually needed for citric acid production, and the effects of 2% (v/v) methanol, an inducer of citric acid, 2 microM antimycin A, and 1 mM SHAM on AOX activities and citric acid production were investigated. The AOX activity, measured as duroquinol oxidase, was localized in the purified mitochondria regardless of the presence of any additives. When WU-2223L was cultivated with antimycin A or methanol, both citric acid production and citric acid productivity, shown as the ratio of production per mycelial dry weight, increased with the increase of both the activity of AOX and the rate of CN-insensitive and SHAM-sensitive respiration. On the other hand, when WU-2223L was cultivated with SHAM, an inhibitor of AOX, the CN-insensitive and SHAM-sensitive respiration was not detected and the citric acid production and the productivity drastically decreased, although mycelial growth was not affected. These results clearly indicated that the CN-insensitive and SHAM-sensitive respiration catalyzed by AOX, localized in the mitochondria, contributed to citric acid production by A. niger.

Sexual reproduction and auxospore formation of Cocconeis pellucida have been observed using a laboratory culture. This diatom was monoecious. Auxospores occurred at 18°C and 14°C, but not at 5°C. O...

Sekino, Yuko, Kunihiko Obata, Manabu Tanifuji, Makoto Mizuno, and Jin Murayama. Delayed signal propagation via CA2 in rat hippocampal slices revealed by optical recording. J. Neurophysiol. 78: 1662–1668, 1997. Signal propagation from mossy fibers to CA1 neurons was investigated in rat hippocampal slices by a combination of electrical and optical recordings. The slices were prepared by oblique sectioning of the middle part of the hippocampus to preserve fiber connections. The mossy fibers were stimulated to induce population spikes (PSs) and excitatory postsynaptic potentials in the middle part of the CA1 region. Latencies of maximal PSs in CA1 varied widely among slices; they ranged from 7 to 13.5 ms, with two maxima at 9 and 11.5 ms. The fastest PSs probably are evoked by the Schaffer collaterals that connect the CA3 and CA1 regions in the well-known trisynaptic circuit. However, the slower PSs suggest the existence of additional delayed inputs. To determine the source of the delayed input, slices were stained with a voltage-sensitive dye, RH482, and the optical signals relevant to membrane potential changes were detected by a high-resolution optical imaging system. Optical recording of responses to mossy fiber stimulation indicated two distinct types of signal propagation from CA3 to CA1. In preparations evincing the fast type of propagation, signals spread to CA1 within 7.2 ms after the mossy fiber stimulation. During such propagation, activity flowed directly from CA3 to the stratum radiatum of CA1. Other preparations illustrated slow signal propagation, in which optical signals were generated in CA2 before spreading to CA1. During such slow signal transmission, activity persisted in CA2 and its surrounding area for 3 ms before propagating to the strata radiatum and oriens in CA1. In such cases, CA1 activity was detected within 10.8 ms of mossy fiber stimulation. In some slices, a mixture of the fast and slow propagation patterns was observed, indicating that these two transmission modes can coexist. Our data reveal that CA2 neurons can transmit delayed excitatory signals to CA1 neurons. We therefore conclude that consideration of electrical signal propagation through the hippocampus should include flow through the CA2 region in addition to the traditional dentate gyrus–CA3–CA1 trisynaptic circuit.

We analysed the expression of members of the hh gene family in adult ocular tissues of newt, frog and mouse by RT-PCR method. Shh displayed restricted expression in the neural retina that was conserved in each species analyzed. X-bhh, X-chh and mouse Ihh were detected in the iris and in the retinal pigment epithelium, while mouse Dhh was detected additionally in the neural retina and faintly in the cornea. We also found that two types of ptc genes, potential hh targets and receptors, were expressed in these tissues, suggesting the presence of active hh signalling there.

To clarify the cause of delayed fracture of a glasses frame made of Ni-Ti alloy and to establish an appropriate countermeasure against hydrogen embrittlement, the diffusion coefficient of hydrogen DH in a 50 9at%Ni-Ti alloy and changes in the load-elongation curve due to cathodic polarization were investigated. Cathodic polarization introduced large amounts of hydrogen. DH was calculated from the polarization time dependence of the hydrogen content, and the temperature dependence of DH was obtained to be DH=257×10-7(m2/s) exp (-382(kJ/mol)/RT). Cathodic polarization caused hydrogen embrittlement. A marked decrease in elongation occurred as the polarization time and the aging time at room temperature after polarization increased. This is attributed to an increase in the penetration depth of hydrogen.

The present study was undertaken to examine the effects of volume overload on cardiac gene expression and the possible role of angiotensin AT1 receptor in such expression. Cardiac volume overload was prepared by abdominal aortocaval shunt in rats. Rats with aortocaval shunt were treated with 1) vehicle, 2) an angiotensin AT1 receptor antagonist, CS-866 (10mg/kg/d), or 3) an angiotensin-converting enzyme inhibitor, temocapril (10mg/kg/d), for 7 days. Cardiac tissue mRNA was measured by Northern blot analysis with specific probes. Aortocaval shunt not only caused cardiac hypertrophy but also upregulated the gene expression of atrial natriuretic polypeptide, collagen III, and downregulated Ca2+- ATPase expression in the left ventricle. These changes were prevented by treatment with CS-866, while temocapril failed to normalize left ventricular Ca2+-ATPase expression. Unlike the left ventricle, the significant downregulation of α-myosin heavy chain and transforming growth factor-β3 by aortocaval shunt was observed in the right ventricle, and CS-866 normalized this decreased expression of transforming growth factor-β3. The left and right atria showed increased expression of collagen type I as well as of collagen type III and atrial natriuretic polypeptide, and these increases were more effectively prevented by CS-866 than by temocapril. Thus, the effects of cardiac volume overload on cardiac performance-related gene expression differ between the ventricles and atria. Our results suggest that AT1 receptor partially contributed to volume overload-induced changes in cardiac gene expression and that AT1 receptor antagonists and angiotensin-converting enzyme inhibitors have different effects in this model of cardiac hypertrophy. (Hypertens Res 1997; 20: 133-142)

While interferon (IFN) therapy is approved for patients with chronic hepatitis C infection, the effectiveness of IFN therapy for anti-hepatitis C virus (HCV)-positive individuals with normal ALT levels remains poorly understood. Twenty-five individuals (M:F = 9:16; age = 51.8 +/- 15.1 years) who showed a normal alanine aminotransferase (ALT) level (< 30 IU/L) at least 6 months before treatment and were positive for both anti-HCV and serum HCV-RNA by reverse transcription polymerase chain reaction (RT-PCR) were studied. Of these, 16 received IFN therapy for 24 weeks (780 million units total IFN-alpha 2b) and nine were followed for 12 months as controls. The serum HCV-RNA level was determined by bDNA assay and HCV genotype was detected by enzyme immunoassay. All were shown to have chronic hepatitis by liver biopsy. Six (37.5%) of 16 individuals lost serum HCV-RNA by RT-PCR 6 months after cessation of therapy (complete response; CR), while the remaining individuals were defined as non-responders (NR). Of the six individuals in the CR group, five had HCV type 2 infection, compared with none of 10 individuals in the NR group (P < 0.01). There was a trend towards a lower pretreatment viraemia level in the CR group than in the NR group. These data suggest that IFN therapy for individuals with HCV type 2 infection and normal ALT levels was effective.

Epidermal growth factor (EGF) and its family member neuregulin-1 are implicated in the etiology of schizophrenia. Our recent pharmacological studies indicate that EGF injections to neonatal and adult rats both induce neurobehavioral deficits relevant to schizophrenia. We, however, did not evaluate the genetic impact of EGF transgene on neurobehavioral traits. Here we analyzed transgenic mice carrying the transgene of mouse EGF cDNA. As compared to control littermates, heterozygous EGF transgenic mice had an increase in EGF mRNA levels and showed significant decreases in prepulse inhibition and context-dependent fear learning, but there were no changes in locomotor behaviors and sound startle responses. In addition, these transgenic mice exhibited higher behavioral sensitivity to the repeated cocaine injections. There were neurochemical alterations in metabolic enzymes of dopamine (i.e., tyrosine hydroxylase, dopa decarboxylase, catechol-O-methyl transferase) and monoamine contents in various brain regions of the EGF transgenic mice, but there were no apparent neuropathological signs in the brain. The present findings rule out the indirect influence of anti-EGF antibody production on the reported behavioral deficits of EGF-injected mice. These results support the argument that aberrant hyper-signals of EGF have significant impact on mouse behavioral traits and dopamine metabolism.

A2BP1 is considered to regulate alternative splicing of important neuronal transcripts and has been implicated in a variety of neurological and developmental disorders. A2BP1 was found in neuronal cells and was analyzed biochemically and morphologically. In this study, we prepared a specific antibody against A2BP1, anti-A2BP1, and carried out protein expression and localization analyses of A2BP1 in rat and mouse tissues. By Western blotting, A2BP1 showed tissue-dependent expression profiles and was expressed in a developmental-stage-dependent manner in the brain. A2BP1 was detected at high levels in neocortex and cerebellum in the rat brain. Immunohistochemical analyses demonstrated that A2BP1 was highly expressed in differentiated neurons but not in mitotically active progenitor cells in the cerebral cortex during developmental stages. In cortical neurons, A2BP1 had accumulated mainly in the nucleus and diffusely distributed in the cell body and dendrites. In differentiated primary cultured rat hippocampal neurons, although A2BP1 was enriched in the nucleus and diffusely distributed in the cytoplasm, it was found in a punctate distribution adjacent to synapses. The results suggest that in neuronal tissues A2BP1 plays important roles, which are regulated in a spatiotemporal manner.

A series of imidazole-5-carboxylic acids bearing alkyl, alkenyl, and hydroxyalkyl substituents at the 4-position and their related compounds were prepared and evaluated for their antagonistic activities to the angiotensin II (AII) receptor. Among them, the 4-(1-hydroxyalkyl)-imidazole derivatives had strong binding affinity to the AII receptor and potently inhibited the AII-induced pressor response by intravenous administration. Various esters of these acids showed potent and long-lasting antagonistic activity by oral administration. The most promising compounds were (5-methyl-2-oxo-1,3-dioxol-4-yl)methyl (CS-866) and (pivaloyloxy)-methyl esters of 4-(1-hydroxy-1-methylethyl)-2-propyl-1-[(2'-1H-tetrazol-5- ylbiphenyl-4-yl)-methyl]imidazole-5-carboxylic acid (26c). A study involving stereochemical comparison of 26c with the acetylated C-terminal pentapeptide of AII was also undertaken.

This paper describes a monolithically constructed, flexure-hinged translation mechanism suitable for mechanical scanning stages of very high precision. Two piezoelectric stacks are employed to drive the mechanism ; one piezoelectric stack pushes whilst the other pulls the moving platform. This push-pull drive system is effective for raising the natural frequency of the stage. The mechanism described in this paper functions as both a guide for rectilinear motion and a mechanical amplifier to amplify a limited output displacement of the piezoelectric stack. Static and dynamic characteristics of the mechanism are considered in detail, and design equations are presented. The validity of the design equations is confirmed by experiment. A brief description of the accuracy of motion of the moving platform is included. It is demonstrated that a scan range of 60 μm is achievable with a natural frequency as high as 1175 Hz in the scanning direction.

Serum hepatitis C virus (HCV) RNA level has been shown to be a good predictor of subsequent response to interferon-alpha (IFN) therapy in US patients in whom genotype 1a/1b are both predominant. To determine whether serum HCV RNA level is a predictor of subsequent response to IFN in Japanese patients or not, appropriately collected pre-IFN therapy serum samples from 35 Japanese patients with chronic HCV infection were studied. Serum HCV RNA level and HCV genotype were determined and correlated with the subsequent response to IFN. Response to IFN was defined by serum alanine transaminase level: complete and sustained response (n = 15), complete response followed by relapse (n = 10), and no response (n = 10). Patients with complete and sustained response had lower pre-IFN serum HCV RNA level (median: RT-PCR+, bDNA-) compared to the complete response to relapse group (median: 5.25 x 10(6) genome equivalent/ml [eq/ml], P0.001) and the no response group (median: 10.63 x 10(6) eq/ml, P0.001). Seven (46.7%) of the complete and sustained response patients had HCV genotype 2a and three patients had a mixture of genotypes 1b and 2a. In contrast, all 10 patients in the complete response to relapse group had genotype 1b whereas 8 of 10 patients in the non-response group had genotype 1b and 2 had genotype 2b. The patients with HCV genotype 2a had lower serum HCV RNA level than those with 1b (P = 0.002).(ABSTRACT TRUNCATED AT 250 WORDS)

TiUO 5 and Ti 2 UO 6 were prepared and identified by powder X-ray diffraction analysis. The oxidation states of uranium and titanium in TiUO 5 were found to be basically hexavalent and tetravalent respectively by X-ray photoelectron spectroscopy, but owing to the non-stoichiometry of this compound, a trace of paramagnetic susceptibility was also observed. In Ti 2 UO 6 both uranium and titanium are in the tetravalent state according to X-ray photoelectron spectra. However, the magnetic susceptibility for Ti 2 UO 6 is temperature independent with a superimposed broad peak around 25 K. Considering the structure of Ti 2 UO 6 , this anomalous behaviour is discussed on the basis of crystal field theory and magnetic superexchange interaction between uranium ions.

Sexual reproduction and auxospore formation of Achnanlhes javanica f. subconstricta have been observed in laboratory culture. This monoraphid diatom showed cis-type behavioural anisogamy and produced two auxospores in one of the paired gametangia. This diatom is unique in that the gametes become re-arranged only in the gametangium producing the stationary gametes, not in that producing the active gametes. Its position is thus obscure in the present classifications of sexual reproduction and auxospore formation. Some modification of these classifications is necessary.

High-frequency electrical stimulation in the hippocampus leads to an increase in synaptic efficacy that lasts for many hours. This long-term potentiation (LTP) of synaptic transmission is presumed to play a crucial role in learning and memory in the brain. However, the frequency of stimulation generally used to obtain LTP is beyond the normal physiological range of activity of hippocampal neurons. We found that LTP can be induced by an electrical stimulation whose frequency is comparable to that of the naturally occurring firing activity of hippocampal neurons if the stimulating pulseinterval train has a special time structure. In the present experiment, we compared the magnitude of LTP induced by the four types of stimuli which have the same pulse number and the same mean frequency but different time structure in interstimulus intervals. One type of stimuli has regular intervals, and this served as a control stimulus. In the other three types of stimuli, the adjacent interstimulus interval had the following statistical properties: in type 1, their correlations are positive; in type 2, negative; and in type 3, independent. The magnitude of LTP induced by these four types of stimuli showed clear order relationships: type 3/type 1? control > type 2. Detailed analysis of the evoked potential during a period of temporal pattern stimulation revealed that the amplitude of the population spikes of repetitive firing, especially of the second and third population spikes, had the same order relationship as the LTP. Because 2-amino-5-phosphonovalerate (APV) (50 μM) selectively abolished the second and the third population spikes but not the first, and blocked the formation of LTP, the second and the third peaks which appeared as part of the late component of excitatory postsynaptic potentials (EPSP) must involve LTP formation through the activities of N-methy-D-aspartate (NMDA) channels. From the experimental data, a dynamic induction rule concerning LTP in specific neural networks was derived by which the temporal information of the input stimuli can be extracted and transformed into the weight space of synaptic connections in hippocampal networks (see Fig. 1. CA1).

Imidazoles and pyrroles bearing hydroxymethyl and carboxy groups were prepared, and their AII antagonistic activities were evaluated. The hydroxymethyl substituent at the 4 position and the carboxy substituent at the 5 position in the imidazole nucleus were favorable for the activity.

Although chronic cardiac dysfunction is known to progressively exacerbate renal injury, a condition known as type 2 cardiorenal syndrome (CRS), the mechanism responsible is largely unknown. The present study was undertaken to clarify the mechanism of renal injury in rats with both unilateral nephrectomy (NX) and surgically induced myocardial infarction (MI), corresponding to a model of type 2 CRS. Compared with a control group, rats with both MI and NX (MI+NX) exhibited progressive proteinuria during the experimental period (34 wk after MI surgery), whereas proteinuria was not observed in rats with MI alone and was moderate in rats with NX alone. The proteinuria in rats with MI+NX was associated with renal lesions such as glomerulosclerosis and infiltration of mononuclear cells and upregulation of the renal proinflammatory and -fibrotic cytokine and angiotensin II type 1a receptor (AT1aR) genes. In contrast, plasma renin activity was lowered in rats with MI+NX. Immunohistochemistry revealed that the increased AT1R protein was present mainly in renal interstitial mononuclear cells. Olmesartan medoxomil, an AT1R blocker, markedly reduced the proteinuria and infiltration of mononuclear cells, whereas spironolactone, a mineralocorticoid receptor blocker, did not. The present findings demonstrate the pathogenetic role of renal interstitial AT1R signaling in a model of type 2 CRS, providing evidence that AT1R blockade can be a useful therapeutic option for this syndrome.

A monolithic translation mechanism driven by two pairs of piezoelectric stacks is described which was devised primarily for the mechanical scanner of STM (scanning tunneling microscope). The layout of the mechanism is symmetrical with respect to the center lines of the base plate. Each pair of piezoelectric stacks is cemented at the outer ends between two movable elements of the flexure-hinged linkage which supports a moving platform, and is also cemented at the center on both sides of aluminium alloy square blocks provided on both ends of the base plate. An X-Y translation stage is readily formed by stacking one translation stage on another. It is possible to improve the accuracy of motion of the moving platform by properly adjusting the applied voltage to each piezoelectric stack. Relationship is examined experimentally between the applied voltage and the accuracy of motion in order to attain a high precision translation mechanism. It is demonstrated that the yaw of the moving platform produced by a 46 μm output displacement of the moving platform is reduced from 0.3 arcsec to less than 0.1 arcsec by adjusting the applied voltage to one of four piezoelectric stacks.

The hepatitis C virus (HCV) core antibody and NS-4 antibody were measured in 25 cases of type C chronic hepatitis after interferon (IFN) treatment. The antibody titres were quantitated and the changes in the antibody titres and the therapeutic effects were compared. The titres of the passive haemagglutination assay (HCV-PHA) before and after IFN administration were also measured and compared with the therapeutic effects. No significant correlation was seen between the core, NS-4 and HCV-PHA titres before IFN administration and the resultant therapeutic effects, but many cases showing excellent effects were seen among those with core antibody titres under 100 U/L and those with HCV-PHA titres less than 2.16 In a study of the changes in the core and NS-4 antibody titres, these titres tended to decrease during IFN administration. In cases showing excellent effects, these decreases continued for a long period after completion of IFN administration and then became negative in some cases. However, in the remaining cases, titres showed increases up to 3 months after completion of IFN administration. HCV-PHA showed reduced titres in many cases of excellent effects before and after IFN administration; and there were also cases showing decreases with two power differences.

SPECIFIC AIMSIn this study, we investigated the hypothesis that a chronic intracerebroventricular (i.c.v.) infusion of amyloid β-peptide (Aβ) into rat can stimulate nitric oxide (NO) production, wh...

Novel protein synthesis is an essential element of various learning paradigms. Although pharmacological and genetic strategies have indicated the importance of translational activation in learning, the specific signaling pathways that are activated in the brain remain unclear. Here, we show that mammalian target of rapamycin (mTOR), a key serine/threonine protein kinase in translational control, is activated in hippocampus of the learning rat as revealed by in vitro kinase assay, Western blotting and immunohistochemistry. The substrates of mTOR, eukaryotic initiation factor 4E-binding protein (4EBP) and p70S6 kinase (p70S6K) are phosphorylated, and total protein synthesis is enhanced, in the learning hippocampus. Furthermore, the inhibition of mTOR by chronic infusion of rapamycin, a specific inhibitor of mTOR, into the ventricle retards the establishment of spatial learning. Thus, mTOR signaling is activated during learning, enhances translation, and plays a crucial role in the spatial learning.

BACKGROUND: Neuregulin-1 (NRG1) is one of the susceptibility genes for schizophrenia and implicated in the neurotrophic regulation of GABAergic and dopaminergic neurons, myelination, and NMDA receptor function. Postmortem studies often indicate a pathologic association of increased NRG1 expression or signaling with this illness. However, the psychobehavioral implication of NRG1 signaling has mainly been investigated using hypomorphic mutant mice for individual NRG1 splice variants. METHODOLOGY/PRINCIPAL FINDINGS: To assess the behavioral impact of hyper NRG1 signaling, we generated and analyzed two independent mouse transgenic (Tg) lines carrying the transgene of green fluorescent protein (GFP)-tagged type-1 NRG1 cDNA. The promoter of elongation-factor 1α gene drove ubiquitous expression of GFP-tagged NRG1 in the whole brain. As compared to control littermates, both heterozygous NRG1-Tg lines showed increased locomotor activity, a nonsignificant trend toward decreasing prepulse inhibition, and decreased context-dependent fear learning but exhibited normal levels of tone-dependent learning. In addition, social interaction scores in both Tg lines were reduced in an isolation-induced resident-intruder test. There were also phenotypic increases in a GABAergic marker (parvalbumin) as well as in myelination markers (myelin basic protein and 2',3'-cyclic nucleotide 3'-phosphodiesterase) in their frontal cortex, indicating the authenticity of NRG1 hyper-signaling, although there were marked decreases in tyrosine hydroxylase levels and dopamine content in the hippocampus. CONCLUSIONS: These findings suggest that aberrant hyper-signals of NRG1 also disrupt various cognitive and behavioral processes. Thus, neuropathological implication of hyper NRG1 signaling in psychiatric diseases should be evaluated with further experimentation.

Two psychrophilic strains of unicellular algae were isolated from seawater samples collected in the Antarctic Ocean. The one (strain A) was a species of Cymbella (Bacillariophyceae) and the other (strain B) was a species that belonged to the class Prymnesiophyceae (a prymnesiophyte). Optimum temperatures for growth of both the algae were between 2.5℃ and 5℃. Upper limit temperatures for growth of strain A (Cymbella sp.) and strain B were between 12.5℃ and 15℃ and between 7.5℃ and 10℃, respectively. We suggest that these algae should be categorized into extremely psychrophilic algae from their significantly lower cardinal temperatures for growth.

A 42-year-old male was admitted with subarachnoidal hemorrhage. Dexamethasone 224 mg was used to reduce brain edema. His operation was successful without blood transfusion. No remarkable signs and symptoms were found except HBsAg positive and mild GPT elevation during his admission. He was discharged on the 33rd day. But 2 weeks later, he felt general fatigue and became worse day by day. He was re-admitted on the 75th day. Several therapies were given but he died of hepatic failure on the 85th day. The autopsy showed liver cirrhosis with massive necrosis. We believed that the steroid-withdrawal-phenomenon caused excessive immunological response and this process caused his hepatic failure leading to death.

This paper describes two types of piezo-driven translation mechanisms, which are composed of a flexure-hinged linkage and cut from a monolith. The natural frequency and accuracy of motion of the mechanisms are examined in detail to assess the applicability of both of the mechanisms to the scanner of STM (scanning tunneling microscope). Design formulae of the natural frequency, derived from the strain energy method, are presented to optimize the mechanism design for maximizing the natural frequency. Experimental investigation confirms the validity of the formulae derived. It is demonstrated that a scanning range of 65μm is attained with a parasitic rotation smaller than 0.3 arcsec and natural frequencies amounting to 508 Hz and 2508 Hz in the directions parallel to and perpendicular to the motion of moving platform, respectively.

Abnormal signaling mediated by epidermal growth factor (EGF) or its receptor (ErbB) is implicated in the neuropathology of schizophrenia. Previously, we found that the anthraquinone derivative emodin (3-methyl-1,6,8-trihydroxyanthraquinone) inhibits ErbB1 signaling and ameliorates behavioral deficits of the schizophrenia animal model established by EGF challenge. In the present study, we assessed acute and subchronic effects of its administration on methamphetamine-triggered behavioral hyperactivation in rats. Prior subchronic administration of emodin (50mg/kg/day, 5days, p.o.) suppressed both higher acoustic startle responses and hyperlocomotion induced by acute methamphetamine challenge. In parallel, emodin also attenuated methamphetamine-induced increases in dopamine and its metabolites and decreases in serotonin and its metabolites. Emodin administered alone also had an effect on stereotypic movement but no influence on horizontal or vertical locomotor activity. In contrast to pre-treatment, post-treatment with emodin had no effect on behavioral sensitization to methamphetamine. Administration of emodin in parallel to or following repeated methamphetamine challenge failed to affect hyperlocomotion induced by methamphetamine re-challenges. These findings suggest that emodin has unique pharmacological activity, which interferes with acute methamphetamine signaling and behavior.

The maximal growth rate (μmax) of 19 marine and estuarine diatoms decreased with increasing cell volume (V). The relationship between log μmax (Y) and log V (X) was calculated. Statistical analyses showed that the slope of the equation was not significantly different from those obtained by other researchers and that the 95% confidence intervals of mean μmax at cell volumes of 103–105μm3 were not significantly different from those cited in most studies. A new regression line for diatoms was calculated as follows: log μmax= 0.47–0.14 log V; r =–0.69. The rate of size reduction per generation of the 19 diatom species ranged from 0.03 to 0.87 μm per generation. The rate increased with increasing cell length and cell volume and with decreasing maximum division rate. Statistical analyses showed that the rate was closely related to the cell volume and to the reciprocal of the growth rate. The relationships between maximal growth rate and cell volume and between rate of size reduction and cell volume showed that a diatom with a large volume had a smaller maximal growth rate and a larger rate of size reduction than a diatom with a small volume. The estimates using the equation for the regression line between the rate of size reduction and the reciprocal of maximum division rate indicated that a diatom with a high maximum division rate would need more generation equivalents for a certain size reduction than a diatom with a low maximum division rate, but the periods required for reduction would be approximately equal irrespective of maximum division rate.

We propose a novel 300 MHz embedded flash memory for dual-core microcontrollers targeting shared ROM architecture. One of the features is a three-stage pipeline read operation, which enables reduced access pitch and therefore reduced performance penalty due to shared ROM access conflict. The second feature is a highly sensitive sense amplifier that achieves efficient pipeline operation with two-cycle latency one-cycle pitch because of a shortened sense time of 0.63 ns. The combination of the pipeline architecture and the proposed sense amplifiers achieves significant reduction in access-conflict penalties with shared ROM and enhanced performance of 32-bit RISC dual-core microcontrollers by 30%.

This paper investigates the interaction between consumer learning and advertising using a simulation model. Consumers use advertising to estimate the quality change, but learn advertising's trustworthiness through their consumption experience. Firms spend on not only advertising but also RD in this sense, advertising misleads consumers. When learning is fast or when consumers do not rely on advertising at all, advertising is unlikely to mislead them. Easy imitation of rival products also prevents advertising from being misleading. These results are consistent with existing empirical findings on advertising-quality relationships.

A planar linkage is described which was devised primarily for micropositioning stages. It functions both as a magnifying or reducing mechanism and a guidance system for a rectilinear motion. Two input bars, which are coupled to a driving element such as a piezoelectric stack, two output bars, one of which is mounted on a base plate and the other performs the function of a moving platform, and four connecting bars, eight bars in total are connected together by flexure pivots. A displacement amplification or reduction is effected according as the angle between the input and connecting bars is larger or less than 45°. Design formulae are given for the linearity between the input and output displacements and a decrease in magnification caused by an elongation of the flexure pivot. A differential linkage, which combines a pair of linkages, is presented for improving the linearity. Description of the experiments performed for evaluat-ing the validity of design formulae, is included.

The effects of hyperdynamic therapy on patients with cerebral vasospasm following subarachnoid hemorrhage (SAH), under normal blood pressure (BP) and normal blood volume conditions, are reported. Forty-four patients, who underwent surgery for aneurysms in acute stage, received hydroxyethyl starch (500 ml/day) postoperatively to prevent dehydration. Twenty-four of the 44 patients with prominent SAH on the computed tomographic (CT) scan, anticipating to develop cerebral ischemia due to vasospasm, were given dobutamine (DOB). The BP was maintained within the normal range, and the heart rate was kept below 130/min. In the 24 patients treated with DOB, cerebral blood flow (CBF) was measured repeatedly by the 133Xe intravenous injection method. In 8 of these 24 patients, the cardiovascular function was monitored with Swan-Ganz (S-G) catheters. Twelve of the 44 patients (27%) developed delayed neurological deficits associated with cerebral vasospasm. The neurological deficits were reversed by the administration of DOB, at a dose of 8-25 (average 12.4) micrograms/kg/min. In 43 patients, the ischemic lesions associated with vasospasm did not appear on CT scan and the patients were of normal condition at discharge. However, one patient showed multiple low-density lesions on CT scan. This was because of the failure of hyperdynamic therapy due to pulmonary complications. No case of pulmonary edema or heart failure due to volume overload was noted. In the 24 patients with prominent SAH, CBF increased significantly by up to 20% following DOB administration, although the BP stayed in the normal range.(ABSTRACT TRUNCATED AT 250 WORDS)

Numerous clinical classification systems have been developed for patients with ruptured intracranial aneurysms. However, most systems do not take age into account and are less reliable in elderly than in younger patients in terms of indications for early surgery and predicting the clinical outcome. The authors have studied this problem using our clinical classification system and, present here the results of 38 elderly patients (greater than or equal to 65 years of age) who underwent neck clipping and implementation of continuous ventricular drainage within 3 days of aneurysm rupture. The clinical outcome at 1 year after onset was considered "good" if the patient was able to function independently and "poor" if he or she was partially or fully dependent or had died. The preoperative level of consciousness was not significantly correlated with the outcome according to Spearman's nonparametric statistical analysis. Age, however, was a significant factor: the incidence of poor outcome was significantly higher in patients over age of 70 years than in those between 65 and 70 (p less than 0.05). Postoperative complications, which were previously found to be significantly related to the outcome in elderly patients, were significantly more common in patients who had a history of cardiac, pulmonary, hepatic, and/or renal disease than in those without such a history (p less than 0.005). The authors found that the prognostic accuracy of clinical classification systems, based on preoperative level of consciousness, is improved in geriatric cases if one point is added for patients over age of 70 years or those with a history of systemic diseases. Additional relevant factors included computed tomographic findings and pre-existing cerebral dysfunction.

Ligands for epidermal growth factor (EGF) receptor (ErbB1), such as EGF, transforming growth factor alpha (TGFalpha), and epiregulin, are enriched in body fluids and blood and regulate development of various peripheral organs. It remains however how such circulating polypeptide growth factors influence brain development and function. Here, we performed peripheral injections of TGFalpha and epiregulin to mouse neonates and evaluated immediate physical and neurochemical development and later behavioral consequences. Subcutaneous administration of TGFalpha and epiregulin increased phosphorylation of brain ErbB1, suggesting their effects on brain development. Repeated their injections similarly enhanced physical development of eyelid opening and tooth eruption during early postnatal stage and resulted in abnormal behavioral traits in the adult stage. Acoustic startle responses of mice treated with these growth factors as neonates were enhanced and prepulse inhibition was decreased without an apparent correlation between prepulse inhibition level and startle intensity. Locomotor activity and fear-learning performance with tone and context cues were not altered, however. These results suggest that circulating ErbB1 ligands in the periphery of neonates have some common influences on later behavioral traits. Abnormal ErbB1 ligand production at neonatal and potentially prenatal stages might therefore associate with neurodevelopmental disorders such as schizophrenia.

Lateral charge distribution in nitride of split-gate type semiconductor-oxide-nitride-oxide-semiconductor (SONOS) memories has been determined by well-controlled experimental devices in which nanometer-size nitride piece was located at various positions for monitoring trapped charge. We found that electron distribution is created by two different hot-electron-injection mechanisms. Based on this new finding, the way to improve the matching of electron and hole distributions is investigated.

Brain-derived neurotrophic factor (BDNF) is involved in synaptic development and plasticity, and alterations in BDNF expression or signaling are implicated in drug addiction and psychiatric diseases, such as depression and schizophrenia. In this study, we administered phencyclidine to postnatal and adult rats with different time schedules, and determined the correlations between BDNF expression and the behavioral effects. Both single and repeated phencyclidine injections into adult rats induced BDNF up-regulation in the corticolimbic system and a decrease in prepulse inhibition, both of which were transient. In contrast, subchronic postnatal administration increased BDNF protein and mRNA levels in the hippocampus and entorhinal cortex, which were sustained until 8 weeks of age. In parallel, the postnatal rats treated with phencyclidine developed a persistent decrease in prepulse inhibition at the adult stage. The chronic BDNF increase appeared to contribute to the prepulse inhibition abnormality, as subchronic BDNF infusion into the hippocampus of normal rats mimicked the prepulse inhibition deficits. This study suggests that phencyclidine exposure during brain development induces sustained BDNF up-regulation in the limbic system with a biological link to sensorimotor gating deficits.

We propose a new method of collision prediction, which is effective in the situation that any object including ego is able to be under the state of motion or stillness. A new concept named as "binocular velocity pair" is introduced in order to achieve a purpose that robot arrives at a goal without coming into collision with a moving or stationary object. The moving distance deltaL on the left camera image and deltaR on the right camera image i.e. "binocular velocity pair" are extracted at each corresponding pixels. Then, the 3D relative direction of the object, the collision location on the robot and the collision time are calculated directly. Simple neural network can execute the calculation. The effectiveness of the proposed method is checked by using a stereo video camera of View Plus Ltd and a moving platform produced by Tokyo Seiki Ltd

To reveal the underlying cellular mechanisms of the noise tolerance in the discrimination of the direction of visual flow, we analyzed both response behaviors of directionally selective cells in the d-MST of the macaque and discrimination properties of human subjects for visual flow by using large-field texture flow. The stimulus was a 32/spl times/32-pixel random checker pattern refreshed at every 16 msec in which coherency of the motion of the texture was systematically controlled by a special purpose computer. The discrimination performance of the human observers showed a high degree of tolerance for directional noise. Field-type D-cells in d-MST also showed response properties which closely resembled human discrimination performance. These results strongly suggest that cells in d-MST area play a crucial role in the generation of signals for perception of global motion.

Long-term potentiation (LTP) in the CA1 area of hippocampus is highly sensitive to the higher order statistical characteristics of the stimulus (correlation between successive pairs of inter-stimulus intervals) (Tsukada, 1990, 1992; Aihara, 1991, 1992). The temporal-pattern sensitivity in LTP was identified in a slice preparation by using the optical imaging method. In this experiment, the authors found that the spatial pattern of LTP in the CA1 area differed depending on the temporal pattern of the stimulus; positively correlated sequences were much more effective (large area) in producing LTP, while negatively correlated sequences were ineffective (small area). The spatial pattern of LTP, was closely related to the position where the repetitive firing of population spikes was evoked during the period of temporal-pattern stimuli. These results suggest that there is a transformation from the temporal pattern into the spatial pattern in the coding process of the hippocampal learning system.

Epidermal growth factor (EGF) is a member of a structurally related family containing heparin-binding EGF-like growth factor (HB-EGF) and transforming growth factor alpha (TGFalpha) that exerts neurotrophic activity on midbrain dopaminergic neurons. To examine neurotrophic abnormality in Parkinson's disease (PD), we measured the protein content of EGF, TGFalpha, and HB-EGF in post-mortem brains of patients with Parkinson's disease and age-matched control subjects. Protein levels of EGF and tyrosine hydroxylase were decreased in the prefrontal cortex and the striatum of patients. In contrast, HB-EGF and TGFalpha levels were not significantly altered in either region. The expression of EGF receptors (ErbB1 and ErbB2, but not ErbB3 or ErbB4) was down-regulated significantly in the same forebrain regions. The same phenomenon was mimicked in rats by dopaminergic lesions induced by nigral 6-hydroxydopamine infusion. EGF and ErbB1 levels in the striatum of the PD model were markedly reduced on the lesioned side, compared with the control hemisphere. Subchronic supplement of EGF in the striatum of the PD model locally prevented the dopaminergic neurodegeration as measured by tyrosine hydroxylase immunoreactivity. These findings suggest that the neurotrophic activity of EGF is maintained by afferent signals of midbrain dopaminergic neurons and is impaired in patients with Parkinson's disease.