Detecting halfmetallic electronic structures of spintronic materials in a magnetic field.

Band-gap engineering is one of the fundamental techniques in semiconductor technology and also applicable in next generation spintronics using the spin degree of freedom. To fully utilize the spintronic materials, it is essential to optimize the spin-dependent electronic structures in the operando conditions by applying magnetic and/or electric fields. Here we present an advanced spectroscopic technique to probe the spin-polarized electronic structures by using magnetic circular dichroism (MCD) in resonant inelastic soft X-ray scattering (RIXS) under an external magnetic field. Thanks to the spin-selective dipole-allowed transitions in RIXS-MCD, we have successfully demonstrated the direct evidence of the perfectly spin-polarized electronic structures for the prototypical halfmetallic Heusller alloy [Formula: see text]. RIXS-MCD is a promising tool to probe the spin-dependent carriers and band-gap induced in the buried magnetic layers in an element specific way under the operando conditions.

Association study of TRAF1-C5 polymorphisms with susceptibility to rheumatoid arthritis and systemic lupus erythematosus in Japanese.

OBJECTIVE: The primary aim of this study was to investigate the association of polymorphisms of TRAF1-C5, a newly identified rheumatoid arthritis (RA) risk locus in Caucasians, with susceptibility to RA and systemic lupus erythematosus (SLE) in Japanese populations. Gene expression levels of TRAF1 and C5 to assess the functional significance of genotypes were also analysed. METHODS: A multicentre association study consisting of 4 RA case-control series (4397 cases and 2857 controls) and 3 SLE case-control series (591 cases and 2199 shared controls) was conducted. Genotyping was performed using TaqMan genotyping assay for two single nucleotide polymorphisms (SNPs) that showed the best evidence of association in the previous Caucasian studies. Quantifications of TRAF1 and C5 expression were performed with TaqMan expression assay. RESULTS: Significant differences in allele frequency for both SNPs were observed between RA and control subjects (combined odds ratio = 1.09), while no significant difference was detected between patients with SLE and controls. Interestingly, alleles rs3761847 A and rs10818488 G had increased the risk for RA in the present study, while they decreased the risk in the original studies. A significant difference was found between risk allele carriers and non-carriers of rs10818488 for the expression level of TRAF1 in phorbol myristate acetate-stimulated lymphoblastoid cell lines (p = 0.04). CONCLUSION: Association of TRAF1-C5 locus with RA susceptibility was detected in the Japanese populations with modest magnitude, while no significant association was observed for SLE. Significant positive effect of genotype on the expression of TRAF1 might support the genetic association between TRAF1 and RA.

Intractable ulcer caused by Mycobacterium shinshuense: successful identification of mycobacterium strain by 16S ribosomal RNA 3'-end sequencing.

An extremely rare case of intractable ulcer caused by Mycobacterium shinshuense is described. A 59-year-old Japanese woman developed an ulcerated subcutaneous induration on the upper arm. Ziehl-Neelsen staining revealed positive bacilli. Tissue culture isolated Mycobacterium species, but standard identification techniques (including molecular biological approaches such as DNA-DNA hybridization) could not distinguish the precise causative pathogen, although it was narrowed down to three possibilities: Mycobacterium marinum, Mycobacterium ulcerans and M. shinshuense. Finally, a novel 16S rRNA sequencing method enabled the diagnosis of M. shinshuense infection. The epidemiology of the cutaneous infection caused by this mycobacterium has yet to be elucidated, but a review of reported cases indicated that ulcers having some resemblance to those caused by M. ulcerans infection were found in nonendemic areas and that M. shinshuense could be considered as the cause. The approach introduced in this report could provide a powerful tool for the identification of this organism.

The effect of a thymidine phosphorylase inhibitor on angiogenesis and apoptosis in tumors.

Thymidine phosphorylase (TP) is an enzyme involved in the reversible conversion of thymidine to thymine and is identical to an angiogenic factor, platelet-derived endothelial cell growth factor. TP is expressed at higher levels in a wide variety of solid tumors than in the adjacent nonneoplastic tissues. Patients with TP-positive colon and esophageal tumors have a poorer prognosis than those with TP-negative tumors. We have recently synthesized a new TP inhibitor (TPI), 5-chloro-6-[1-(2-iminopyrrolidinyl) methyl] uracil hydrochloride. We investigated the effect of TPI on angiogenesis in KB cells transfected with platelet-derived endothelial cell growth factor cDNA, KB/TP, and a mock transfectant, KB/CV, using the mouse dorsal air sac assay model. We found that KB/TP cells had a higher angiogenic ability than KB/CV cells and that TPI completely suppressed angiogenesis by KB/TP. Furthermore, at a dose of 50 mg/kg/day, TPI considerably decreased the growth rate of KB/TP cells xenografted into nude mice. Microvessel density in KB/TP tumors was higher than that in KB/CV tumors, and TPI did not significantly change the density in either of the tumors. The apoptotic index in KB/TP tumors was significantly lower than that in KB/CV tumors, and TPI significantly increased the apoptotic index in KB/TP tumors but not in KB/CV tumors. These findings, taken together with previous reports, suggest that the expression of TP plays an important role in tumor growth and that TPI suppresses tumor growth by increasing the proportion of apoptotic cells and probably inhibiting angiogenesis.

Hydrogen bonding of flavoprotein. I. Effect of hydrogen bonding on electronic spectra of flavoprotein.

The effect of hydrogen bonding on the transition energy and the oscillator strength of the isoalloxazine nucleus of flavins was studied by the molecular orbital method. Among the possible hydrogen bondings examined, characteristic spectral shifts were found for the hydrogen bondings at N(1) and N(5) of the nucleus. The hydrogen bonding at N(1) resulted in the shift of the first absorption band towards blue and that of the second one towards red. On the other hand, the hydrogen bonding at N(5) resulted in the shifts of both the first and the second band towards red. The spectral characteristics reported on Clostridium MP and Desulfovibrio vulgaris flavodoxin coincided with the calculated results. The application of the calculated results to D-amino acid oxidase (D-amino acid: oxygen oxidoreductase (deaminating), EC 1.4.3.3) led to the conclusion that hydrogen bonding occurs at O(12), N(3)H, O(14) and N(5) of the isoalloxazine nucleus. The occurrence of hydrogen bondings at O(12), N(3)H, and O(14) is favorable for N(5) of the isoalloxazine nucleus to accept electron from an electron donor.

Late persistent expressions of ICAM-1 and VCAM-1 on myocardial tissue in children with lymphocytic myocarditis.

BACKGROUND: Both intercellular adhesion molecule-1 (ICAM-1) and vascular cell adhesion molecule-1 (VCAM-1) have been implicated in cardiac allograft rejection. However, there is little information about the relationship between the expression of these adhesion molecules and myocarditis in children. METHODS AND RESULTS: Immunoreactivities of ICAM-1 and VCAM-1 were examined by enzyme immunoassay in 31 biopsy specimens obtained from 11 pediatric patients with biopsy-proven myocarditis or cardiomyopathy. Five of the 11 patients had clear evidence of acute myocarditis. The other 6 had ECG abnormalities identified by mass screening for heart disease, and subsequently had been histologically diagnosed as having non-specific cardiomyopathy. The period between onset of myocarditis or identification of ECG abnormality and immunohistochemical studies was 23 to 60 days and 8 months to 3 years, respectively. Expression of ICAM-1 and VCAM-1 was assessed by counting ICAM-1 and VCAM-1 positive vessels and dividing by the total number of vessels. ICAM-1 was significantly present on 81% (P < 0.01) of myocardial tissue samples in the 5 patients with healing-stage acute myocarditis, and on 45% (P < 0.05) in the remaining 6 patients with non-specific cardiomyopathy, compared with 24% in control specimens obtained from right ventricular muscle resected at surgery for tetralogy of Fallot. VCAM-1 was also present on 50% (P < 0.05) of the samples from the 5 patients with acute myocarditis, but was not present in those with non-specific cardiomyopathy. CONCLUSION: This persistent expression of ICAM-1 suggests that myocardial cell damage may persist immunologically for a long period in myocarditis. In addition, immunostaining for these adhesion molecules may be diagnostic value in clinically silent lymphocytic myocarditis and chronic cardiomyopathy.

Anti-metastatic efficacy and safety of MMI-166, a selective matrix metalloproteinase inhibitor.

The anti-metastatic efficacy and safety of a newly-developed matrix metalloproteinase (MMP) inhibitor were examined. MMI-166, a N-sulfonylamino acid derivative, inhibited the enzyme activity of MMP-2, 9, and 14 but not MMP-1, 3 or 7. Daily oral administration of MMI-166 resulted in potent inhibition of metastatic lung colonization of Lewis lung carcinoma injected via the tail vein and liver metastasis of C-1H human colon cancer implanted into the spleen at inhibition levels of 43% and 63%, respectively. Daily administration of MMI-166 also resulted in prolonged survival of mice given intraperitoneal implantation of Ma44 human lung cancer cells. The anti-metastatic activity of MMI-166 was as effective as that of other MMP inhibitors with broad inhibitory spectrum. MMI-166 did not affect in vitro tumor cell growth. Neither body weight losses nor hematotoxicity was observed during long-term treatment, indicating the safety of MMI-166 in mice. These results indicate that the selective MMP inhibitor MMI-166 has therapeutic potential as an anti-metastasis agent.

Idebenone improves cerebral mitochondrial oxidative metabolism in a patient with MELAS.

We report a 36-year-old man with MELAS in whom a 5-month course of high-dose oral idebenone, a derivative of coenzyme Q10, increased markedly cerebral metabolic ratio of oxygen and oxygen extraction fraction without increased cerebral blood flow with PET. The results indicate that idebenone improves mitochondrial oxidative metabolism in the brain and suggest a therapeutic potential of idebenone for MELAS.

Apoptosis as a possible cause of wall thinning in end-stage hypertrophic cardiomyopathy.

A 15-year-old boy with hypertrophic cardiomyopathy died of congestive heart failure with progressive left ventricular wall thinning with poor systolic function. Microscopic examination revealed patchy fibrosis in the ventricular myocardium with wall thinning, and immunohistochemical evaluation of apoptosis showed apoptotic cells and bodies in the destroyed myocytes along the border between the fibrotic area and myofibril.

Studies in a model system on the effect of hydrogen bonding at hetero atoms of oxidized flavin on its electron acceptability.

The effect of hydrogen bonding at hetero atoms of oxidized flavin on its electron acceptability was studied by the ab initio molecular orbital method. The calculations were carried out for all possible lumiflavin-H2O complexes and for some lumiflavin-formamide complexes. Calculated data showed that the magnitudes of hydrogen bonding energy at the hetero atoms are in the order of N(3)H greater than N(5) greater than O(12) greater than N(1) greater than O(14). It was found that the atomic orbital coefficient of the lowest unoccupied molecular orbital is the largest at N(5) and that hydrogen bonding at N(1), N(5), O(12), and O(14) increases the electron acceptability of the oxidized flavin at N(5), while hydrogen bonding at N(3)H decreases it.

Alterations in extracellular matrix components and integrins in patients with preeclamptic nephropathy.

The glomerular features of patients with preeclampsia consist of swelling of endothelial cells, subendothelial deposits of incompletely defined material, and thickening of the capillary walls. These abnormalities are thought to resolve in the postpartum period. The distribution of extracellular matrix (ECM) components and integrins was investigated in 10 such patients. Frozen sections and paraffin-embedded sections were stained with antibodies to type IV collagen, laminin (LN), fibronectin (FN), vitronectin (VN), tenascin (TN), fibronectin receptor (FNR), and vitronectin receptor (VNR). In preeclamptic nephropathy, the accumulation of type IV collagen, LN, FN, TN, and FNR was observed in the thickened capillary walls, particularly in the subendothelial layer and, to some extent, in the mesangium. However, deposits of VN were sparse and the distribution of VNR was similar to that in normal kidney. In segmental sclerotic lesions, the amounts of type IV collagen, LN, FN, VN, and TN were increased, whereas those of FNR and VNR were markedly decreased. These results suggest that the materials deposited in the subendothelial space consist of ECM components as well as of plasma-derived proteins, and that the deposition of ECM components and of FNR may be involved in the development and the reparative process of the characteristic glomerular lesions. The formation of sclerotic lesions was linked to the accumulation of ECM components, but not to an interaction with integrins.

Clinical features of aortic arch anomaly with malalignment ventricular septal defect.

The clinical features and outcome after various surgical procedures on 9 patients with coarctation or interruption of the aortic arch and malalignment ventricular septal defect (group 1) were compared with those of 9 patients with the arch anomaly without malalignment ventricular septal defect (group 2). Cardiomegaly and metabolic acidosis were prominent in group 1. Five of the 9 patients in group 1 died in the immediate postoperative period (56% mortality), but no operative deaths occurred among 8 patients in group 2 (p less than 0.01). The ratio of left ventricular outflow tract to ascending aortic diameter was 0.59 +/- 0.09 in group 1 and 1.03 +/- 0.11 in group 2 (p less than 0.01). Three of 4 patients with a ratio of less than 0.6 died, but no operative deaths occurred among the 6 patients who had a palliative operation and in whom the ratio was more than 0.6. These data suggest that left ventricular outflow tract obstruction is critical when the ratio of left ventricular outflow tract to ascending aortic diameter is 0.6 or less. The presence of severe left ventricular outflow tract obstruction necessitates modification of the present surgical strategy.

Inguinal lymph node metastasis from contralateral testicular origin.

A twenty-eight-year-old man had a testis tumor eighteen years after orchiopexy and inguinal lymph node metastasis in the contralateral side. It is suggested that scrotal surgery may lead to the formation of new lymph channels and alter the pattern of nodal metastases.

Magnetic resonance imaging and brain-stem auditory evoked potentials in neuro-Behçet's disease.

We studied central nervous system lesions in patients with neuro-Behcet's disease using magnetic resonance imaging (MRI) of the brain and recording of brain-stem auditory evoked potentials (BAEPs). MRI revealed abnormal findings in seven of eight patients. MRI studies demonstrated extensive regions with high intensity signal in the brain stem and/or basal ganglia on T2-weighted images obtained during the acute stage of the disease in three patients. One of these patients had a strongly gadolinum-enhanced round lesion in the lower pons. In four of the other five patients with chronic disease, brain-stem atrophy was observed on T1-weighted images. Atrophic changes were more severe in the brain stem than in the cerebellum. Abnormal BAEPs were observed in three patients and consisted of prolongation of interpeak latency of waves III-V and defects of wave III or V. Abnormal BAEPs were recorded in patients with severe inflammatory changes or progression of atrophic changes in the brain stem. Our findings show that MRI and BAEPs are useful in detecting the presence and assessing the degree of neurological involvement in patients with neuro-Behçet's disease.

Recanalisation after coil embolisation of persistent ductus arteriosus.

A 5 year old girl underwent recanalisation after coil embolisation of a persistent ductus arteriosus. Recanalisation is uncommon after coil embolisation and may be related to shrinkage of the coil, a change in its position, and ductal shape.

Spring coil retraction in coil occlusion of persistent ductus arteriosus.

AIMS: To present the short and intermediate term results of coil occlusion of persistent ductus arteriosus and the results of radiographic measurements of spring coils implanted to treat patent ducts. PATIENTS: 22 children underwent coil occlusion. Their ages ranged from 2 years 9 months to 12 years 10 months (mean (SD) age, 6.5 (3.6) years). The duct diameter ranged from 1.0 to 3.5 mm at the narrowest point (mean 2.6 (0.7) mm). In 11 of the children regular coils were implanted using the non-attached system, while in the other 11 the detachable coil embolisation system was used. RESULTS: 12 children (55%) had no significant residual leaks immediately after procedures involving a single coil delivery. The remaining 10 (45%) had residual leaks immediately after the procedure, although no patient with a large duct showed residual leakage 18 months after the procedure. Radiographic measurement of the coils showed that all implanted coils retracted to 65-85% of their original size immediately after occlusion. This retraction was more evident in patients showing spontaneous closure of the residual shunt or having a coil 8 mm in diameter. CONCLUSIONS: Coil embolisation is an acceptable method for occluding persistent ductus arteriosus. Retraction of implanted coils is common in the follow up period. Such retraction may be related to spontaneous closure of residual shunt after embolisation.

Thymidine phosphorylase activity required for tumor angiogenesis and growth.

Thymidine phosphorylase (TP) is identical to platelet-derived endothelial cell growth factor (PD-ECGF), and has angiogenic activity. We examined the involvement of TP activity in tumor growth and angiogenesis. KB cells were transfected with wild-type or mutant (L148R) PD-ECGF cDNA, and two sublines with high TP activity, KB/wt4 and KB/wt6, and one subline with no TP activity, KB/L148R, were cloned, respectively. The doubling times of these subclones in vitro were similar to that of KB cells. However, the growth of KB/wt4 and KB/wt6 cells was significantly faster when xenografted into nude mice than that of control cells with no TP activity. The tumors with high TP activity (KB/wt4 and KB/wt6) had significantly more microvessels than those with no TP activity (KB/-, KB/CV and KB/L148R) (P<0.01). These results, taken together with previous reports, suggest that the TP enzyme activity itself is involved in angiogenesis and growth of the KB tumors.

Isotachophoretic separation behavior of rare-earth EDTA chelates and analysis of minor rare-earth elements in an iron ore by bidirectional isotachophoresis-particle-induced X-ray emission.

Mobilities of 16 anions of rare-earth-EDTA 1:1 chelate (RE-EDTAs) were isotachophoretically measured by using two leading electrolytes (pH 3.6 and 6.0) in order to assess their separation behavior. The leading electrolyte was 20 mM hydrochloric acid. The pH of the solution was adjusted to 3.6 by adding beta-alanine and to 6.0 by adding histidine. The obtained mobilities were very close to each other in the range 20.1x10(-5)-21.9x10(-5) cm2 V(-1) s(-1) with the minimum mobilities for Pr-EDTA and Nd-EDTA for pH 3.6 and 6.0, respectively, and pH dependence was hardly observed. On the basis of the above knowledge. minor rare-earth elements in a standard iron ore sample were determined as RE-EDTAs by bidirectional isotachophoresis-particle-induced X-ray emission (PIXE), where the Fe(II) matrix digested by alkali fusion was separated as Fe(II)Phen3(2+) (phen = 1,10-phenanthroline). Since 5% of the total iron was still detected as Fe(III)EDTA- and might disturb PIXE analysis of RE-EDTA-, itaconic acid was used as the spacer for Fe(III)EDTA- and RE-EDTA-. The fractions of RE-EDTA- were successfully analyzed off-line by a multielemental analytical method, PIXE [analytical result (3.62% (w/w) as RE2O3]; the nominal value was 3.37% (w/w) as RExOy.

Cell-surface expression of complement restriction factors and sialyl Lewis antigens in oral carcinoma: relevance to chemo-immunotherapy.

Oral squamous cell carcinomas overexpress tumor-associated antigens, yet these antigens do not induce an immune-mediated anti-tumor response. The absence of an anti-tumor immune response may be due to poor immunogenicity of the tumor antigens or due to presence of factors that restrict immune functions. We have analyzed the expression of the tumor-associated sialyl LewisA (sLeA) and sialyl LewisX (sLeA) antigens, the complement restriction factors (CD59, CD46 and CD55) and the apoptosis associated factors Fas and Fas Ligand. Sialyl Lewis antigens (sLeA and sLeX), are immunogenic in that they elicit complement-fixing IgM antibodies. These antigens are associated with aggressive invasive behavior, tumor progression and poor disease-free survival of patients with human carcinomas. Human oral squamous carcinoma cell lines, SCC12 and SCC71, were analyzed for the density of Sialyl Lewis antigens, CD59, CD46, CD59, Fas and FasL on the cell surface. Expression of these antigens on the cell surface was determined employing a cell-suspension ELISA with monospecific monoclonal antibodies. In both oral carcinoma cell lines, the density of expression of sLeX was higher than that of sLeA and SCC71 had a very low level of sLeA expression. Both cell lines expressed a high density of CD59 and slightly lower levels of CD46 and CD55 on the cell surface, suggesting that even if host antibodies are accessible to the target antigens such as sLeX, they could not mediate complement-dependent cytotoxicity. The SCC lines expressed very low levels of Fas and FasL indicating that there maybe a lack of these signaling molecules for apoptosis. Our data suggests that passive immunotherapy or tumor killing by antibody-complement interaction may require downregulation of complement restriction factors.