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Aim Repeated psychostimulant drug treatment, including methamphetamine, in rodents readily produces behavioral sensitization, which reflects altered brain function caused by repeated drug exposure. Dendritic remodeling of medium spiny neurons in the nucleus accumbens is thought to be an essential mechanism underlying behavioral sensitization. We recently showed that chronic methamphetamine treatment did not produce behavioral sensitization in serotonin transporter knockout mice. Methods In this study, we report the spine density of medium spiny neurons in the nucleus accumbens after repeated methamphetamine injection to examine morphological alterations in serotonin transporter knockout mice. Results Golgi‐COX staining clearly showed that the spine density of medium spiny neurons in the nucleus accumbens increased following repeated methamphetamine treatment in both wild‐type and serotonin transporter knockout mice. Conclusions Our results suggested that augmented serotonergic neurotransmission produced by serotonin transporter deletion prevents the development of behavioral sensitization in a manner that is independent of dendritic remodeling in the nucleus accumbens.

Sequential permeability and chemical osmosis experiments on Wakkanai mudstones were performed to explore the relationships between the semipermeability of clayey rocks and the hydraulic and diffusion parameters as well as the pore structure characteristics. The wide ranges in osmotic efficiency (0.0004–0.046) and intrinsic permeability (8.92 × 10−20 to 1.24 × 10−17 m2) reflect the variation in the pore size distributions of the Wakkanai mudstones. A regression analysis between osmotic efficiency and permeability shows that the osmotic efficiency is proportional to the inverse of permeability, suggesting that the permeability is indeed indicative of the degree of semipermeability. Osmotic efficiency was determined invariant with the effective diffusion coefficient for the Wakkanai mudstones (3.59–8.36 × 10−11 m2/s) due to their small osmotic efficiencies (≤0.046). The wide variation in osmotic efficiencies and pore structure characteristics of Wakkanai mudstones indicates that the nanoscale pores enable semipermeability in Wakkanai mudstones. However, the pressure evolution caused by chemical osmosis is limited by the connected wide pores that are the main conduits for water, thus dissipating the osmotic pressure buildup induced by the semipermeability of nanoscale pores.

Perpendicularly magnetized magnetic tunnel junctions (MTJs) were fabricated by depositing thin L10-ordered FePt films on MgO(001) substrates using a UHV sputtering system, and the dependence of structural, magnetic, and magnetotransport properties of the junctions on the thickness of the FePt layers was investigated. A full epitaxial structure of MgO(001) sub./Cr/Pt/FePt/MgO/CoPt/Ta was observed. The tunnel magnetoresistance (TMR) ratio was measured to be 6% at room temperature, and magnetization switching was clearly observed in the thin FePt layer. Transmission electron microscopy (TEM) observations revealed that the interface between FePt, MgO, and CoPt layer has strain due to lattice mismatch, which might be a reason for the low TMR ratio.

To obtain reliable diffusion parameters for diffusion testing, multiple experiments should not only be cross-checked but the internal consistency of each experiment should also be verified. In the through- and in-diffusion tests with solution reservoirs, test interpretation of different phases often makes use of simplified analytical solutions. This study explores the feasibility of steady, quasi-steady, equilibrium and transient-state analyses using simplified analytical solutions with respect to (i) valid conditions for each analytical solution, (ii) potential error, and (iii) experimental time. For increased generality, a series of numerical analyses are performed using unified dimensionless parameters and the results are all related to dimensionless reservoir volume (DRV) which includes only the sorptive parameter as an unknown. This means the above factors can be investigated on the basis of the sorption properties of the testing material and/or tracer. The main findings are that steady, quasi-steady and equilibrium-state analyses are applicable when the tracer is not highly sorptive. However, quasi-steady and equilibrium-state analyses become inefficient or impractical compared to steady state analysis when the tracer is non-sorbing and material porosity is significantly low. Systematic and comprehensive reformulation of analytical models enables the comparison of experimental times between different test methods. The applicability and potential error of each test interpretation can also be studied. These can be applied in designing, performing, and interpreting diffusion experiments by deducing DRV from the available information for the target material and tracer, combined with the results of this study.

Various composite devices consisting of nano- and/or microparticles and epoxy resin have been fabricated without heat treatment using a coagulant. The composite including the nanoparticles and the resin showed a rather considerable negative longitudinal magnetoresistance of about -5% compared with the composite including the microparticles. The average tunnel barrier thickness among particles of the composite containing the microparticles was about 2.7 times larger than that of the composite containing the nanoparticles. In both composites containing the micro- and nanoparticles, it was found that the slope of the pressure dependence of the resistance changed suddenly near 20 and 5 MPa in the compression and decompression processes, respectively. This shows that a change in the transport mechanism occurred owing to the pressure. The effects of the dispersion of nano- and/or microparticles and resin in the composite on the transport properties are also discussed.

The effect of cold-working on hydrogen solubilities in the dilute region (α phase) has been investigated for Pd1-xNix(x≤0.2), Pd1-xPtx(x≤0.19), and Pd1-xNi(1/2)xAg(1/2)x(x≤0.2) alloys by measuring pressure-composition isotherms between 273 and 348 K. The enhancement of hydrogen solubility in Pd-Ni alloys resulting from dislocation-hydrogen interaction tends to increase with increasing Ni content, in contrast to the case of Pd-Ag and Pd-Au alloys. On the other hand, the solubility enhancements in Pd-Pt and Pd-Ni-Ag alloys did not change significantly with alloying metal contents. These results can be qualitatively explained by the interactions between the alloying elements with different sizes and the stress fields of dislocations. The hydrogen trapping at defects such as vacancies was also predicted from the observation of the initial region of the isotherms for cold-worked alloys. It was found that the extent of pressure hysteresis in the isotherm for Pd0.9Ni0.1 alloy which has been initially cold-worked is less than for the well-annealed alloy and in the case of Pd0.85Ni0.075Ag0.075 alloy the hysteresis disappears completely.

The purpose of this communication is to determine whether the solubility enhancements for cold-worked Pd-Ni alloys increase or decrease with atom fraction of Ni. Substitutional Ni atoms contract and Pd lattice, in contrast to the lattice expansion resulting from substitutional Ag in Pd. The Pd-Ni alloy system forms a continuous series of fcc solid solution alloys over the whole composition range. The solubility enhancements will also be determined for a series of homogeneous, ternary Pd[sub 1[minus]x]Ni[sub 1/2x]Ag[sub 1/2x] alloys for x in the range from 0 to 0.2. For this series of ternary alloys the fcc lattice parameters do not change significantly from that of pure Pd. The alloys used in this research were purchased from Tanaka Kikinzoku Kogyo K.K. The detailed experimental procedure has been described previously. The alloys were all deformed by cold-rolling ca 90%. Both the binary and ternary alloys showed only single sets of fcc lattice parameters corresponding to homogeneous fcc solid solutions.

Diffusion anisotropy is a critical property in predicting migration of substances in sedimentary formations with very low permeability. The diffusion anisotropy of sedimentary rocks has been evaluated mainly from laboratory diffusion experiments, in which the directional diffusivities are separately estimated by through-diffusion experiments using different rock samples, or concurrently by in-diffusion experiments in which only the tracer profile in a rock block is measured. To estimate the diffusion anisotropy from a single rock sample, this study proposes an axisymmetric diffusion test, in which tracer diffuses between a cylindrical rock sample and a surrounding solution reservoir. The tracer diffusion between the sample and reservoir can be monitored from the reservoir tracer concentrations, and the tracer profile could also be obtained after dismantling the sample. Semi-analytical solutions are derived for tracer concentrations in both the reservoir and sample, accounting for an anisotropic diffusion tensor of rank two as well as the dilution effects from sampling and replacement of reservoir solution. The transient and steady-state analyses were examined experimentally and numerically for different experimental configurations, but without the need for tracer profiling. These experimental configurations are tested for in- and out-diffusion experiments using Koetoi and Wakkanai mudstones and Shirahama sandstone, and are scrutinized by a numerical approach to identify favorable conditions for parameter estimation. The analysis reveals the difficulty in estimating diffusion anisotropy; test configurations are proposed for enhanced identifiability of diffusion anisotropy. Moreover, it is demonstrated that the axisymmetric diffusion test is efficient in obtaining the sorption parameter from both steady-state and transient data, and in determining the effective diffusion coefficient if isotropic diffusion is assumed. Moreover, measuring reservoir concentrations in an axisymmetric diffusion experiment coupled with tracer profiling may be a promising approach to estimate of diffusion anisotropy of sedimentary rocks.

This study focuses on the verification of test interpretations for different state analyses of diffusion experiments. Part 1 of this study identified that steady, quasi-steady and equilibrium state analyses for the through- and in-diffusion tests with solution reservoirs are generally feasible where the tracer is not highly sorptive. In Part 2 we investigate parameter identifiability in transient-state analysis of reservoir concentration variation using a numerical approach. For increased generality, the analytical models, objective functions and Jacobian matrix necessary for inverse analysis of transient-state data are reformulated using unified dimensionless parameters. In these dimensionless forms, the number of unknown parameters is reduced and a single dimensionless parameter represents the sorption property. The dimensionless objective functions are evaluated for individual test methods and parameter identifiability is discussed in relation to the sorption property. The effects of multiple minima and measurement error on parameter identifiability are also investigated. The main findings are that inverse problems for inlet and outlet reservoir concentration analyses are generally unstable and well-posed, respectively. Where the tracer is sorptive, the inverse problem for the inlet reservoir concentration analysis may have multiple minima. When insufficient measurement data is collected, multiple solutions may result and this should be taken into consideration when inversely analyzing data including that of inlet reservoir concentration. Verification of test interpretation by cross-checking different state analyses is feasible where the tracer is not highly sorptive. In an actual experiment, test interpretation validity is demonstrated through consistency between theory and practice for different state analyses.

The chromium dioxide (CrO2) is a half metallic ferromagnet which has both the metallic and semiconductive spin bands.The tunneling magnetoresistance (TMR) has been measured in single CrO2 deposited on (110) TiO2/vacuum/ Ni80Fe20 film on the AFM cantilever at room temperature. The behavior showed the giant inverse type of the TMR and the values of the TMR ratio from -74% to -63% were estimated using the experimental results, which means the spin polarization of-100% in CrO2. It was estimated that the surface of CrO2 has the insulator layer with the thickness of about 8~10[nm].

We present the performance of a feedforward noise canceller (FNC) for the PR1 [(1+D)] channel combined with an 8/10 DC free code. It appears the PR1 channel can be superior to PR4 [(1-D)(1+D)] and EPR4 [(1-D)(1+D)/sup 2/] for high density magnetic recording due to a characteristic of high frequency suppression. Simulation results show that PR1 with FNC is better than EPR4 for K/spl ges/2.5 [K=PW/sub 50//T]. We adapted PR1 with FNC into an actual DDS3 (Digital Data Storage 3) system and we got an improved result. Applying FNC to DDS3 system can improve the error rate by around 10/sup 2/.

An 800-MHz-band high-power filter using TM/sub 110/-mode dielectric resonators with a 25-MHz bandwidth is described. This elliptic function, six-pole filter has low dissipation characteristics and excellent temperature stability. Under high-power operation, the changes of the filter characteristics are negligible. The size of the filter is 200*140*60 mm (1700 cm/sup 3/), about one-fifth the volume of conventional high-power filters. >

A new planar type dielectric resonator filter, named TE/sub 010/ mode dielectric filter, is proposed for high-speed data communication systems. The filter was manufactured with precise photolithography process on the high-/spl epsiv/ (high-dielectric constant) ceramic substrate. The small filter with low loss and high selectivity characteristic has been realized at 19 GHz.

A TE/sub 010/ mode dielectric resonator is proposed for use in a millimeter-wave filter. The resonators were fabricated on a ceramic substrate and show good performance at 60 GHz. A planar circuit type millimeter-wave filter, using the TE/sub 010/ mode dielectric resonator, has been developed. The filter is applicable to future millimeter-wave communications systems.

Helicobacter pylori eradication markedly improves histological inflammation and decreases peptic ulcer recurrence, but little is known about the subsequent development of gastric mucosal injury.To investigate whether acid suppression treatment after eradication influences the development of gastric erosions.Eighty-one patients (gastritis or peptic ulcer) after successful H. pylori eradication were divided into two groups: 40 received an H2-blocker for 6 months (H2-blocker-positive) and 41 received no treatment (H2-blocker-negative). Endoscopy was performed before, and at 3 and 6 months after completion of eradication.Cumulative prevalence of gastric erosions in the H2-blocker-positive group was significantly lower than in the H2-blocker-negative group, 25% vs. 42%, respectively. In the H2-blocker-negative group but not the H2-blocker-positive group, the cumulative prevalence of gastric erosions after eradication was higher in patients with less severe corpus atrophy or more severe corpus gastritis.Development of gastric erosions after H. pylori eradication may be controlled by acid suppression treatment. Less severe atrophy or more severe gastritis in oxyntic glands before eradication may be involved in the development of gastric erosions. These results support the idea that recovery of acid secretion may be one of factors for development of gastric mucosal erosions after successful eradication.

The effect of Helicobacter pylori infection on non-steroidal anti-inflammatory drug-induced gastric mucosal injury is controversial.To examine the effect of the interaction between H. pylori and non-steroidal anti-inflammatory drugs on gastric mucosal injury.Mongolian gerbils infected with H. pylori were treated with indometacin at 8 mg/kg for 2 days or 7 days. Mucosal damage was assessed by macroscopic and histological examination, and myeloperoxidase activity was measured as an index of neutrophil infiltration. The expression levels of cyclo-oxygenase proteins were determined by Western blot analysis and cyclo-oxygenase activity.A 2-day course of indometacin did not cause an increase in gastric damage in H. pylori-infected Mongolian gerbils compared to uninfected gerbils, while a 7-day course of indometacin caused additive gastric damage in H. pylori-infected animals. H. pylori infection induced cyclo-oxygenase-2 expression in the stomach. Treatment with indometacin for 2 days did not significantly affect cyclo-oxygenase activity in H. pylori-infected animals, while treatment for 7 days inhibited both cyclo-oxygenase-1 and cyclo-oxygenase-2 activities. Pre-treatment with a selective cyclo-oxygenase-2 inhibitor aggravated mucosal injury in H. pylori-infected animals treated or not treated with indometacin for 2 days.Our results suggest that cyclo-oxygenase-2 protein induced by H. pylori infection may be involved in the defence of the gastric mucosa against damage caused by non-steroidal anti-inflammatory drugs. Therefore, inhibition of cyclo-oxygenase-2 activity may enhance non-steroidal anti-inflammatory drug-caused gastric damage in H. pylori-infected animals.

A 50-year-old woman who had been treated for Parkinson's disease was admitted to our hospital because of exertional dyspnea and weight loss. Her chest computed tomography showed diffuse ground glass opacities in both lung fields. Bronchofiberscopy was performed, and the bronchoalveolar lavage fluid showed an elevated lymphocyte count. The serum Ouchterlony test yielded positive results for parrot droppings as well as for pigeon serum and droppings. She had had a parrot for several years, but no pigeon, and so we diagnosed bird fanciers' disease associated with parrot droppings. This responded well to steroid therapy. This case of bird fanciers' disease was caused by the droppings of only one parrot.

Ultrasound studies have demonstrated the gall bladder wall to consist of two or more (usually three) layers. Gall bladder tumours with neither a thinned nor split outermost hyperechoic layer are confined to the mucosa or muscle layer, or have only invaded the shallow subserosa. Differentiation of these two types of tumour has posed difficulties. We report a case of polypoid gall bladder carcinoma invading the shallow subserosa with a thickened outermost hyperechoic layer but a hypoechoic area in the deeper part of the tumour. Ultrasound and pathological correlation in this case demonstrated that the hypoechoic area represented an adenocarcinoma invading the subserosa accompanied by abundant fibrosis.

We measured the levels of beta-defensin 1 and 2 (HBD-1, 2), novel antimicrobial peptides in plasma and in bronchoalveolar lavage fluid (BALF) from patients with with non-tuberculous mycobacterium infection (NTM). Plasma HBD-2 levels in NTM patients before treatment were higher than those in the controls, while the HBD-1 levels were similar to the control levels. High levels of HBD-2, but not of HBD-1, in BALF were also observed in NTM patients. In NTM, a positive correlation was found between HBD-2 levels in BALF and plasma, and also between HBD-2 and IL-1 beta levels in BALF. NTM patients with cavities or ectasia on chest radiography had higher HBD-2 levels in BALF than those without. Plasma HBD-2 levels in NTM patients were markedly decreased after successful treatment, while those of patients with an intractable mycobacterium infection maintained the same high plasma HBD-2 levels as those before treatment. These findings suggest that HBD-2 may participate in the host defense and plasma HBD-2 levels may reflect disease activity in pulmonary NTM.

A 49-year-old man was admitted to our hospital with a productive cough and bloody sputum. Peripheral blood eosinophil counts and serum IgE values were elevated. Chest radiography and chest computed tomography revealed a solitary nodule with cavitation and satellite lesions in the right middle lobe, in contact with the pleura. The diagnosis of paragonimiasis westermani was confirmed by detection of ova in the sputum and bronchoalveolar lavage fluid (BALF) samples, and by immunoserological examination. The patient was treated with praziquantel for 3 days at a daily dosage of 75 mg/kg. After treatment, his clinical symptoms and radiological abnormalities disappeared. The IL-5 level was high in BALF, but it was undetectable in the plasma, suggesting that IL-5 in inflammatory lesions may be particularly important in mediating eosinophilia in the blood and BALF in paragonimiasis westermani.

A 69-year-old woman visited her physician on October 1 complain of dry cough. However, the chest radiograph revealed no abnormalities. She was later admitted to our hospital because a radiograph taken by another physician on November 26 revealed a massive lesion in the right upper mediastinum. Computed tomographic findings showed a massive lesion containing a branching structure with a few calcifications, suggesting a case of atelectasis of the left upper lobe with mucus plug. Bronchoscopic examination revealed complete obstruction of the orifice of the left upper lobe bronchus, and so a diagnosis of bronchial atresia was made. However, since the patient had a history of tuberculous peritonitis and the mass lesion was somewhat calcified, the possibility that this was an acquired case could not be ruled out. After treatment with oral antibiotics, the size of the atelectasis was decreased. Therefore, we considered that the expansion of the atelectasis could have been due to superimposed bacterial infection.

A 61-year-old man visited a community hospital because of hemosputum. A solitary nodule in the left lower lung field was pointed out on a chest roentgenogram. The patient was treated with antibiotics, but the solitary nodule increased in size. He was referred to our hospital because of high fever and observations of cavity formation and pleural effusion on a chest roentgenogram. The pleural effusion showed no cytologic evidence of malignancy, and cultures were also negative for bacteria. An increased percentage of lymphocytes was detected in the pleural effusion, but slight eosinophilia was found in blood samples. Dot enzyme-linked immunosorbent assay and Ouchterlony's double-diffusion test yielded a diagnosis of pulmonary dirofilariasis. After drainage of the pleural effusion by thoracentesis, spontaneous regression was observed. Cavity formation, pleural effusion, and spontaneous regression are in general rare in patients with pulmonary dirofilariasis.

We report the efficacy of oral clarithromycin and inhaled beclomethasone against severe bronchorrhea in a patient with alveolar cell carcinoma. A 54-year-old man produced about 500 to 900 ml of clear and egg-white-like sputum each day. Anti-cancer chemotherapy and erythromycin therapy did not reduce the volume of sputum. After administration of clarithromycin and inhaled beclomethasone, sputum volume decreased to about 300 nl each day and the patient's ability to perform daily activities improved. Two months later, clarithromycin was stopped and the patient was treated with inhaled beclomethasone alone. Sputum volume did not increase for 6 months, although the chestroentgenographic findings gradually worsened. Then the sputum volume gradually increased. Five months after the sputum volume began to increase, he was producing about 2 liters of sputum each day and died of respiratory failure. Although the levels of CA 19-9, SLX, and CEA in serum were all within the normal range, the sputum contained high levels of CA 19-9 (1,133,620 U/ml), SLX (3,000 U/ml), and CEA (283 ng/ml). In patients with bronchorrhea, measurement of tumor markers in sputum may be useful for the diagnosis of alveolar cell carcinoma.

We measured the concentrations of soluble adhesion molecules in serum obtained from healthy volunteers and from patients with idiopathic pulmonary fibrosis (IPF) and the acute respiratory distress syndrome (ARDS). The concentrations of soluble intercellular adhesion molecule 1 (ICAM-1), vascular cell adhesion molecule 1 (VCAM-1), E-selectin, and P-selectin were significantly higher in serum from the patients than in serum from the healthy volunteers. In patients with IPF, the concentration of soluble ICAM-1 in serum was inversely related to the vital capacity (expressed as a percent of the predicted value). The concentrations of L-selectin in serum from patients with ARDS were significantly lower than those in serum from healthy volunteers and from patients with IPF. These data suggest that serum-soluble adhesion molecules may be useful as markers of disease activity, severity, and prognosis in ARDS and IPF.

A pyrene-labeled ATP (Pyr-ATP) in which a pyrene fluorophore is linked to the ribose moiety of ATP with a butyryl chain has been synthesized, together with the corresponding analog of ADP. The spectroscopic properties of two fluorescent analogs were found to be similar to those of 1-pyrenebutyric acid, making them photostable and highly sensitive probes for detecting changes in conformations around the nucleotide binding sites of proteins. Binding of Pyr-ADP to myosin subfragment-1 (S-1) resulted in a fluorescence quenching of about 70%. This binding was tight, with a dissociation constant (0.9 microM) similar to that of ADP itself. Formation of the stable ternary complex of Pyr-ADP with S-1 and orthovanadate could be monitored from the quench in pyrene fluorescence with a rate constant of 0.01 s-1. The final fluorescence intensity was about 20% of that for Pyr-ADP alone. Pyr-ATP was hydrolyzed by S-1 1.3 times faster than was ATP. Hydrolysis of Pyr-ATP was accompanied by an initial quenching of pyrene fluorescence with a subsequent recovery of the fluorescence. The fluorescence changes could be used to monitor the hydrolysis reaction continuously and measure the turnover rates of the analog. The fluorescence assay was sensitive, particularly under single turnover conditions, allowing hydrolysis reactions to be monitored at concentrations of S-1 and the analog as low as 50 nM.

Fast magnetization precession was observed in L10-FePt thin films with different L10 order parameter values by all optical pump–probe technique. Precession frequency was varied widely for the films with different order parameter, which is due to large difference in perpendicular magnetic anisotropy. Gilbert damping constant (α) was estimated from relaxation time as apparent damping. Clear difference in α was not observed with different perpendicular magnetic anisotropy.

A 71-year-old female presented with posttraumatic occlusion of the anterior cerebral artery (ACA) after a road accident in which she was hit in the mid-frontal region. Initial computed tomography (CT) demonstrated frontal skull fractures and pneumocephalus. High density areas were also identified in the right basal cisterns, suggesting traumatic subarachnoid hemorrhage. She was alert on admission, but with attendant shock due to crush wounds. Her condition rapidly deteriorated and an emergency amputation of her left leg was performed. After aggressive treatment with transfusion and infusion, her systolic pressure increased to 120 mmHg. Her consciousness remained disturbed. Serial CT disclosed hemorrhagic infarction in the entire medial side of the right frontal lobe. Magnetic resonance angiography demonstrated decreased flow voids in the bilateral A1 segments and right ACA, and a basilar artery aneurysm, which was unruptured clinically. Three weeks after the injury, she regained consciousness. Six months later, she had motor aphasia and left upper extremity weakness. The clinicopathological mechanism causing the traumatic occlusion of the ACA in the present case was probably dissecting aneurysm.

Magnetic tunnel junctions (MTJs) of perpendicularly magnetized L10-CoPt/Co2MnSi/MgO/FePt structure were fabricated. In-plane x-ray diffraction measurements and element specific evaluation of magnetic properties using soft x-ray magnetic circular dichroism were carried out to examine quite thin Co2MnSi (CMS) inserted layer between CoPt and MgO interface. Ordered B2-CMS was successfully fabricated onto L10-CoPt as thin as 1 nm thick, and CMS layer shows perpendicular magnetic anisotropy below 3 nm thick via exchange coupling with CoPt layer. In the MTJ-stacking, epitaxial growth was confirmed except for partial misalignment in the upper FePt layer, and coercive field difference clearly appeared between the bottom and the top ferromagnetic electrodes.

Investigations of the structural and magnetic properties of thin Co50-xNixPt50 (x = 0, 10, 15, 37.5) films and fabrication of magnetic tunnel junctions (MTJs) using Co50Pt50 and Co35Ni15Pt50 electrodes were performed. X-ray diffraction analyses revealed that 20-nm-thick CoPt and CoNiPt films were epitaxially grown with (001)-orientation with an L10-chemical order parameter of 0.66–0.82. CoNiPt with various Ni contents magnetized perpendicularly; the saturation magnetization reduced to 157 emu/cm3 when the Ni content was increased to 37.5%. Magnetotransport measurements under a magnetic field applied perpendicular to the film plane revealed a tunnel magnetoresistance ratio of 10% and 1% at 10 K and 300 K, respectively, for MTJ using Co35Ni15Pt50 electrodes.

Perpendicularly magnetized magnetic tunnel junctions (MTJs) were fabricated by depositing thin L10-ordered FePt films on MgO(001) substrates using a UHV sputtering system, and the dependence of structural, magnetic, magnetotransport properties of the junctions on the thickness of the FePt layers was investigated. A full epitaxial structure was observed when the thickness of the L10-ordered FePt film was 4 nm. The tunnel magnetoresistance (TMR) ratio was measured to be 6% at room temperature, and magnetization switching was clearly observed in the thin FePt layer.

The association between idiopathic nephropathy and HLA-class II antigen has been reported in many ethnic groups. We attempted to ascertain the HLA regions more specifically, associated with Japanese idiopathic membranous nephropathy (IMN), IgA nephropathy (IgAN) and minimal change nephrotic syndrome (MCNS), by examining HLA-class II genes. DNA typing of HLA-class II genes showed that IMN was associated with HLA-DRB1*1501-DRB5*0101-DQA1*0102-DQB1*0602, IgA with HLA-DQA1*0301, and MCNS with DQB1*0302. We also found a common epitope of HLA-class II (at 38th amino acid position of HLA-DR beta in IMN, at 55th of HLA-DQ beta in MCNS) in Japanese and Caucasian patients. These particular epitopes seem to be important for the susceptibility to IMN or MCNS.

The synthesis and biological testing of the fluorescent analog of colcemid, N-(7-nitrobenz-2-oxa-1,3-diazol-4-yl)-colcemid (NBD-colcemid), are here described. NBD-colcemid exhibited a visible absorption maximum at 465 nm and fluoresced in the range of 520-540 nm, highly in environments of low polarity, whereas only slightly in aqueous solution. The addition of NBD-colcemid to bovine brain tubulin was accompanied by a striking enhancement of fluorescence. The fluorescent titration study suggested a stoichiometric binding of NBD-colcemid to tubulin. Assembled microtubules were directly visualized after mixing with NBD-colcemid using a fluorescence microscope. NBD-colcemid reversibly disrupted the metaphase spindles of sea urchin eggs as well as unlabeled colcemid. However, even when the birefringence of spindles was mostly lost, self-quenching properties of the NBD fluorescence allowed tubulin and its oligomers aggregated in higher concentrations in eggs to be visualized under a fluorescence microscope. The results suggest a wide applicability of NBD-colcemid as a fluorescent probe for studying the interactions of colcemid with tubulin and microtubules, as well as for localizing other colcemid-binding structures within cells.

The synthesis of fluorescent derivatives of cAMP and cGMP, by reaction with isatoic anhydride in aqueous solution at mild pH and temperature, yielding 2'-O-anthraniloyl derivatives of cyclic nucleotides, is here described. 2'-O-(N-Methylanthraniloyl) derivatives were also synthesized by reaction with N-methylisatoic anhydride. Upon excitation at 330-350 nm, these derivatives exhibited maximum fluorescence emission at 430-445 nm in aqueous solution with quantum yields of 0.11-0.26. Their fluorescence was sensitive to the polarity of solvent; in N,N-dimethylformamide quantum yields of 0.8-0.95. The major differences between the two fluorophores were the longer wavelength of the emission maximum of the N-methylanthraniloyl group and its greater quantum yield. The derivatives were substrates for beef heart cyclic nucleotide phosphodiesterase, 15-24% as effective as the natural substrate cAMP. When combined with thin layer chromatography techniques, two apparent Km values (3-4 microM and 36-76 microM) for the cAMP derivatives and one value (10-18 microM) for the cGMP derivatives were obtained. The results indicate that these 2'-hydroxyl-modified cAMP and cGMP can be useful fluorescent substrate analogs for cyclic nucleotide phosphodiesterase.

The fluorescent reagent 4-fluoro-7-nitrobenz-2-oxa-1,3-diazole (NBD-F) reacted specifically with 1.9 lysyl residues/mol of the myosin subfragment-1 (S-1) ATPase. When 1.9 lysyl residues were modified, the K+- and Ca2+-ATPase activities were almost completely inhibited, whereas the Mg2+-ATPase activity was increased to 180% of original activity. The actin-activated Mg2+-ATPase activity was decreased to 30% of original activity by this modification. However, affinity of S-1 for actin in the presence of ATP was unchanged. The NBD fluorescence of the modified S-1 was quenched on addition of ATP, suggesting that ATP induced conformational changes around the NBD groups attached to S-1. Tryptic digestion of the modified S-1 revealed that the NBD groups are attached mainly to the 50-kDa peptide of S-1, more precisely the 45-kDa peptide. These results confirm the recent reports that the 50-kDa peptide of S-1 is involved in the myosin ATPase reaction (Korner, M., Thiem, N. V., Cardinaud, R., and Lacombe, G. (1983) Biochemistry 22, 5843-5847; Hiratsuka, T. (1986) Biochemistry 25, in press).

A microwave heating equipment which can automate the press-setting process in pencil manufacture has been developed. This equipment has microwave output power of 4kW maximum and can make 600 to 700 gross of pencils in 8 hours. The quality of these pencils is excellent.

The ribose-modified chromophoric and fluorescent analog of ATP, 2',3'-O-(2,4,6-trinitrocyclohexadienylidene)-ATP (TNP-ATP) (Hiratsuka, T., and Uchida, K. (1973) Biochim. Biophys. Acta 320, 635-647 and Hiratsuka, T. (1976) Biochim. Biophys. Acta 453, 293-297) has been widely used as an ATP analog for various ATPases. Although the corresponding analog of GTP,2',3'-O-(2,4,6-trinitrocyclohexadienylidene)-GTP (TNP-GTP) should be useful for the study of various GTP-requiring enzymes, it is difficult to prepare TNP-GTP by the conventional method. In the present study, we succeeded in the synthesis of TNP-GTP with the use of an alternative method. The analogs of GDP, GMP, and guanyl-5'-yl imidodiphosphate (Gpp(NH)p) were also synthesized. Visible absorption and fluorescent properties of TNP-GTP, TNP-GDP, TNP-GMP, and TNP-Gpp(NH)p were quite similar to those of TNP-ATP. TNP-GTP was found to be able to replace GTP as an inhibitor for bovine liver glutamate dehydrogenase. The enzyme was inhibited by TNP-GTP to a maximum extent of 54% at saturating concentrations of the analog with a KI of 2.7 microM. TNP-Gpp(NH)p and other ribose-modified fluorescent analogs of GTP,3'-O-anthraniloyl-GTP and 3'-O-(N-methylanthraniloyl)-GTP (Hiratsuka, T. (1983) Biochim. Biophys. Acta 742, 496-508), also inhibited the enzymatic activity. Binding of TNP-GTP to the enzyme was characterized by a 5.6-fold enhancement in analog fluorescence. In the presence of NADH, the limiting fluorescence enhancement of the bound analog decreased to 2.7-fold. As determined by fluorometric titration, the maximum number of TNP-GTP binding sites on the enzyme was 1.9 mol/mol of subunit with a KD of 0.66 microM in the absence of NADH and 2.2 mol/mol of subunit with two KD values of 0.11 and 0.71 microM in the presence of NADH. These observations suggest that NADH binding increases the affinity of only 1 mol of the 2 mol of TNP-GTP bound to the enzyme. These spectroscopic and biological properties of TNP-GTP should make this analog useful as a chromophoric and fluorescent probe for studies not only of glutamate dehydrogenase but also of various GTP-requiring enzymes, which have a high specificity for the base moiety of GTP.

An analog of adenosine triphosphate, 2′(or 3′)-O-(2,4,6-trinitrophenyl)adenosine 5′-triphosphate (TNP-ATP), was synthesized as a reporter-labeled substrate of heavy meromyosin ATPase. TNP-ATP was hydrolyzed by heavy meromyosin in the presence of CaCl2 MgCl2 or EDTA. TNP-ATP had absorption maxima at 259 nm, 408 nm and 470 nm at neutral pH. When bound to heavy meromyosin, TNP-ATP underwent the characteristic spectral shift. The difference spectrum resulting from the binding of TNP-ATP to heavy meromyosin at pH 8.0 had positive peaks at 415 nm and 518 nm, and a negative trough at 458 nm. The difference spectrum due to the binding of 2′(or 3′)-O-(2,4,6-trinitrophenyl)adenosine (TNP-adenosine) to heavy meromyosin had small positive peaks at 420 nm and 495 nm. This difference spectrum was similar to that of TNP-ATP or TNP-adenosine produced by 20% (v/v) ethyleneglycol perturbation. The positive peak at 495 nm in the difference spectrum due to the binding of TNP-adenosine to heavy meromyosin shifted toward 505 nm, when pyrophosphate or ATP was added to the reaction mixture. These results suggest that the difference spectrum of TNP-ATP due to the interaction with heavy meromyosin arises not only from the binding of the chromophoric portion of the TNP-ATP molecule but also from that of the phosphate portion.

Two mol of N-methyl-2-anilino-6-naphthalenesulfonyl (Mns) groups was preferentially incorporated into pig cardiac myosin in the absence of divalent metal ions, 1 mol rapidly and 1 mol slowly. In the presence of divalent metal ions. 1 mol was rapidly incorporated but subsequent incorporation was strongly suppressed. No substantial effect of incorporation of Mns groups in the presence or absence of divalent metal ions on the Ca2+- and K+-ATPase activities of myosin was found. However, the fluorescence spectra due to attached Mns groups were different in the two cases. Extensive pronase digestion of labeled myosin indicated that the Mns groups were attached predominantly to lysyl residues, regardless of the labeling conditions. Peptide mapping of the labeled myosin digested with subtilisin, pepsin or trypsin uniformly showed the selective incorporation of an Mns group into essentially one species of peptide. However, the peptide labeled in the absence of divalent metal ions was clearly different from that labeled in their presence. The present results confirm that pig cardiac myosin heavy chains contain two distinct lysyl residues, which are both accessible to labeling with Mns groups only when divalent metal ions are absent. The results also suggest that conformational changes occur around these residues when divalent metal ions are added.