Three-fold Symmetric Doping Mechanism in GaAs Nanowires.

A new dopant incorporation mechanism in Ga-assisted GaAs nanowires grown by molecular beam epitaxy is reported. Off-axis electron holography revealed that p-type Be dopants introduced in situ during molecular beam epitaxy growth of the nanowires were distributed inhomogeneously in the nanowire cross-section, perpendicular to the growth direction. The active dopants showed a remarkable azimuthal distribution along the (111)B flat top of the nanowires, which is attributed to preferred incorporation along 3-fold symmetric truncated facets under the Ga droplet. A diffusion model is presented to explain the unique radial and azimuthal variation of the active dopants in the GaAs nanowires.

Expression and regulation of human neutrophil-derived macrophage inflammatory protein 1 alpha.

Neutrophil (polymorphonuclear leukocyte [PMN]) sequestration is one of the histologic hallmarks of an acute inflammatory response. During the natural evolution of an inflammatory response, PMNs are often replaced by mononuclear cells. This shift in the elicitation of specific leukocyte populations usually occurs as the inflammatory lesion enters either the repair/resolution stage or progresses to a chronic inflammation. To elucidate a potential mechanism for the temporal change from predominantly PMN recruitment to the presence of monocytes, we postulated that PMNs could be a rich source of monocyte chemotactic factors. In our studies, we have identified a dose-dependent induction of monocyte chemotactic activity by PMNs treated with lipopolysaccharide (LPS; 1-100 ng/ml). Interestingly, this monocyte chemotactic activity was significantly attenuated in the presence of neutralizing anti-human macrophage inflammatory protein 1 alpha (MIP-1 alpha) antibodies. Moreover, immunolocalization studies demonstrated the expression of MIP-1 alpha by stimulated PMNs. These findings showed that a significant amount of PMN-derived monocyte chemotactic activity was attributable to MIP-1 alpha. Subsequent characterization of MIP-1 alpha steady-state mRNA and antigen expression demonstrated both a dose- and time-dependent production by LPS-treated PMNs. Granulocyte/macrophage colony-stimulating factor (GM-CSF), a potent PMN activator, failed to induce the expression of MIP-1 alpha over a wide range of concentrations. However, PMNs stimulated in the presence of both LPS and GM-CSF resulted in a synergistic expression pattern for MIP-1 alpha. PMNs stimulated in the presence of both GM-CSF and LPS demonstrated an enhanced and prolonged expression for both MIP-1 alpha mRNA and antigen, as compared with LPS alone. Messenger RNA stabilization analyses demonstrated that MIP-1 alpha mRNA isolated from PMNs stimulated in the presence of GM-CSF and LPS had a prolonged mRNA t1/2, as compared with LPS alone. These findings support the notion that PMNs are capable of producing MIP-1 alpha in the presence of LPS, and that GM-CSF can influence this production through prolongation of MIP-1 alpha mRNA t1/2. The production of PMN-derived MIP-1 alpha, in association with the expression of appropriate adhesion molecules at a site of inflammation, may be one of the central events that contributes to the temporal shift from predominantly PMNs to monocytes during the evolution of inflammation.

A bacterium lipopolysaccharide that elicits Guillain-Barré syndrome has a GM1 ganglioside-like structure.

There is a strong association between Guillain-Barré syndrome (GBS) and Penner's serotype 19 (PEN 19) of Campylobacter jejuni. Sera from patients with GBS after C. jejuni infection have autoantibodies to GM1 ganglioside in the acute phase of the illness. Our previous work has suggested that GBS results from an immune response to cross-reactive antigen between lipopolysaccharide (LPS) of the Gram-negative bacterium and membrane components of peripheral nerves. To clarify the pathogenesis of GBS, we have investigated whether GM1-oligosaccharide structure is present in the LPS of C. jejuni (PEN 19) that was isolated from a GBS patient. After extraction of the LPS, the LPS showing the binding activity of cholera toxin, that specifically recognizes the GM1-oligosaccharide was purified by a silica bead column chromatography. Gas-liquid chromatography-mass spectrometric analysis has shown that the purified LPS contained Gal, GalNAc, and NeuAc, which are sugar components of GM1 ganglioside. 1H NMR methods [Carr-Purcell-Meiboom-Gill (CPMG), total correlation spectroscopy (TOCSY), and nuclear Overhauser effect spectroscopy (NOESY)] have revealed that the oligosaccharide structure [Gal beta 1-3 GalNAc beta 1-4(NeuAc alpha 2-3)Gal beta] protrude from the LPS core. This terminal structure [Gal beta 1-3GalNAc beta 1-4(NeuAc alpha 2-3)Gal beta] is identical to the terminal tetrasaccharide of the GM1 ganglioside. This is the first study to demonstrate the existence of molecular mimicry between nerve tissue and the infectious agent that elicits GBS.

Nonadiabatic spin torque investigated using thermally activated magnetic domain wall dynamics.

Using transmission electron microscopy, we investigate the thermally activated motion of domain walls (DWs) between two positions in Permalloy (Ni80Fe20) nanowires at room temperature. We show that this purely thermal motion is well described by an Arrhenius law, allowing for a description of the DW as a quasiparticle in a one-dimensional potential landscape. By injecting small currents, the potential is modified, allowing for the determination of the nonadiabatic spin torque: ßt=0.010±0.004 for a transverse DW and ßv=0.073±0.026 for a vortex DW. The larger value is attributed to the higher magnetization gradients present.

Anti-enolase１antibodies from a patient with systemic lupus erythematosus accompanied by pulmonary arterial hypertension promote migration of pulmonary artery smooth muscle cells.

OBJECTIVE: Pulmonary arterial hypertension (PAH) is an intractable complication in connective tissue diseases, but the pathological mechanisms responsible for progression remain obscure. This study aims to test whether patient IgG possesses biological activity promoting the migration of pulmonary artery smooth muscle cells (PASMCs). METHODS: Cell migration was estimated by lamellipodia formation and by utilizing a Boyden chamber method. The specificity of autoantibodies was established by western blotting, ELISA, and immunocytochemistry. The target antigen was investigated by mass spectrometry. RESULTS: IgG obtained from a patient with systemic lupus erythematosus (SLE) accompanied by PAH was found to promote lamellipodia formation and migration of PASMCs. The IgG bound to a ∼50 kDa protein expressed on the cell membrane, and in the cytoplasm and nucleus. This molecule was identified as enolase 1. Removal of enolase 1-binding antibodies from the IgG fraction, or treatment of the cells with an enolase inhibitor, significantly suppressed the migration of PASMCs. CONCLUSION: Patients with SLE may possess autoantibodies to enolase 1 which stimulate the migration of PASMCs and are likely to play a role in the progression of PAH.

Elevated serum levels of soluble CX3CL1 in patients with microscopic polyangiitis.

OBJECTIVES: To test the hypothesis that CX3CL1 contributes to the pathogenesis of microscopic polyangiitis. METHODS: Serum samples from 18 patients with microscopic polyangiitis (MPA), who fulfilled the revised criteria of the American College of Rheumatology (ACR), were collected during both the newly diagnosed, untreated active disease states and inactive disease states. Also serum was from patients with large vessel vasculitis (LVV), including giant cell arteritis (n=4) and Takayasu arteritis (n=3), and from 52 healthy individuals. Soluble (s)CX3CL1 levels in serum were measured using an enzyme-linked immunosorbent assay. Disease activity was assessed using Birmingham vasculitis activity scores (BVAS). Expression of CX3CR1 was examined by flow cytometry. RESULTS: Serum sCX3CL1 levels were significantly higher in MPA patients than in either LVV group or healthy individuals. The elevated sCX3CL1 levels seen in MPA patients correlated positively with BVAS, as well as with CRP levels and ESR, and similarly increased expression of cell-surface CX3CR1 was seen on peripheral blood CD4 and CD8 T cells from patients with MPA. Notably, sCX3CL1 levels and CX3CR1 expression were diminished during clinical remission following treatment. CONCLUSION: Our findings suggest that CX3CL1 may be involved in the pathogenesis of MPA, and may serve as a useful serologic marker of disease activity in systemic vasculitis.

Magnetic fluctuations in nanosized goethite (α-FeOOH) grains.

Mössbauer spectra of antiferromagnetic goethite (α-FeOOH) particles usually show an asymmetric line broadening, which increases with increasing temperature, although the magnetic anisotropy is expected to be so large that magnetic relaxation effects should be negligible. By use of high resolution transmission electron microscopy we have studied a sample of goethite particles and have found that the particles contain many defects such as low angle grain boundaries, in accordance with previous studies of other samples of goethite particles. Such defects can result in a magnetic mismatch at the grain boundaries between nanometer-sized grains, leading to a weakened magnetic coupling between the grains. We show that the Mössbauer data of goethite can be explained by fluctuations of the sublattice magnetization directions in such weakly coupled grains. It is likely that the influence of defects such as low angle grain boundaries also plays a role with regards to the magnetic properties in other antiferromagnetic nanograin systems. We discuss the results in relation to Mössbauer studies of α-Fe(2)O(3) and α-Fe(2)O(3)/NiO nanoparticles.

Interleukin-10 expression and chemokine regulation during the evolution of murine type II collagen-induced arthritis.

In the enclosed study we have examined the expression and contribution of specific chemokines, macrophage inflammatory protein 1 alpha (MIP-1 alpha) and macrophage inflammatory protein 2 (MIP-2), and interleukin 10 (IL-10) during the evolution of type II collagen-induced arthritis (CIA). Detectable levels of chemotactic cytokine protein for MIP-1 alpha and MIP-2 were first observed between days 32 and 36, after initial type II collagen challenge, while increases in IL-10 were found between days 36 and 44. CIA mice passively immunized with antibodies directed against either MIP-1 alpha or MIP-2 demonstrated a delay in the onset of arthritis and a reduction of the severity of arthritis. On the contrary, CIA mice receiving neutralizing anti-IL-10 antibodies demonstrated an acceleration of the onset and an increase in the severity of arthritis. Interestingly, anti-IL-10 treatment increased the expression of MIP-1 alpha and MIP-2, as well as increased myeloperoxidase (MPO) activity and leukocyte infiltration in the inflamed joints. These data suggest that MIP-1 alpha and MIP-2 play a crucial role in the initiation and maintenance, while IL-10 appears to play a regulatory role during the development of experimental arthritis.

Human hepatoma gangliosides: occurrence of a novel I-type glycolipid with NeuAc alpha 2-6Gal structure.

Gangliosides with NeuAc alpha 2-6Gal structure have been studied in human hepatocellular carcinoma. The gangliosides were purified to homogeneity by a DEAE-Sephadex A-25 column chromatography and by repeated silica beads column chromatography. Three gangliosides containing NeuAc alpha 2-6Gal structure were isolated and were structurally characterized by using monoclonal antibodies, proton nuclear magnetic resonance, fast atom bombardment mass spectrometry, methylation analysis by gas chromatography-mass spectrometry, and exoglycosidase treatments. The first compound was identified as NeuAc alpha 2-6Gal beta 1-4GlcNAc beta 1-3Gal beta 1-4Glc beta 1-1Cer. The structures of 2 other components were concluded to be as follows: [formula: see text] The first compound is a ganglioside that is characteristic of human meconium. The second compound has the same structure as a ganglioside recently found by us (Taki, T., Rokukawa, C., Kasama, T., Kon, K., Ando, S., Abe, T., and Handa, S., J. Biol. Chem., 267: 11811-11817, 1992) in meconium. The third compound is a novel type of ganglioside having blood group I-type structure as the core sequence. In addition to these gangliosides, 5 others were detected, and all except for GM3 were glycolipids with neolacto-series core structure. These results suggest that enzymes for the synthesis of neolacto type and NeuAc alpha 2-6Gal structure of glycolipids are activated in hepatoma.

Identification of two novel amyloid A protein subsets coexisting in an individual patient of AA-amyloidosis.

Amyloid A protein (AA), the major fibril protein in AA-amyloidosis, is an N-terminal cleavage product of the precursor protein, serum amyloid A (SAA). Using mass spectrometry and amino-acid sequencing, we identified and characterized two novel AA protein subsets co-deposited as amyloid fibrils in an patient having AA-amyloidosis associated with rheumatoid arthritis. One of the AA proteins corresponded to positions 2-76 (or 75) of SAA2 alpha and the other corresponded to positions 2-76 (or 75) of known SAA1 subsets, except for position 52 or 57, where SAA1 alpha has valine and alanine and SAA1 beta has alanine and valine in position 52 and 57, respectively, whereas the AA protein had alanine at the both positions. Our findings (1), demonstrate that not only one but two SAA subsets could be deposited together as an AA-amyloid in a single individual and (2), support the existence of a novel SAA1 allotype, i.e., SAA152,57Ala.

Structure of a novel phosphocholine-containing aminoglycoglycerolipid of Mycoplasma fermentans.

Mycoplasma fermentans is thought to be a pathogen of rheumatoid arthritis or a cofactor of AIDS (acquired immunodeficiency syndrome). To elucidate the possible involvement of membrane constituents in the pathogenesis of these diseases, we studied its lipid components. Several alkali labile glycophospholipids were detected and named glycoglycerophospholipids (GGPLs). Previously, we purified and determined the structure of one of them as 6'-O-phosphocholine-alpha-glucopyranosyl-(1'-3)-1,2-diacyl-sn-glycerol (GGPL-I). The present paper describes the purification and structural characterization of GGPL-III, the major GGPL of M. fermentans using 1H-, 13C- and 31P-nuclear magnetic resonance spectroscopy, and mass-spectroscopy as 1"-phosphocholine,2"-amino dihydroxypropane-3"-phospho-6'-alpha-glucopyranosyl-(1'-3)-1,2-dia cyl-glycerol.

Sulfatide is expressed in both erythrocytes and platelets of bovine origin.

A novel sulfated glycosphingolipid containing a sulfated galactosyl residue was isolated from bovine erythrocyte ghosts, and purified to homogeneity by column chromatography on DEAE-Sephadex and silica beads. Structural characterization included compositional analyses, permethylation studies, proton nuclear magnetic resonance (NMR) spectroscopy, negative secondary ion mass spectrometry (SIMS), solvolysis and immunostaining on thin-layer chromatogram. As a result, the structure of this glycolipid is proposed as HSO3-Gal beta 1-1 Cer. The ceramide portion contained d18:1, d18:0 and t18:0, and the predominant fatty acid consisted of palmitate and palmitate with a hydroxy group, as deduced by both compositional analysis and negative SIMS mass spectrometry. The component of this glycosphingolipid probably originates from erythrocytes and platelets as indicated by the results of flow cytometry analysis using Sulph I monoclonal antibody. The yield of galactosyl sulfatide was about 0.37 mg/kg wet bovine erythrocyte membranes, about three times that of human kidney. Our results strongly suggest that galactosylceramide sulfate on erythroid cells may play an important biological role in cell to cell interaction and recognition.

Cholestasis induced by lithocholate and its glucuronide: their biliary excretion and metabolism.

We studied the effects of the infusion of lithocholate and lithocholate-3-sulfate and 3-glucuronide in rats (0.29 mumol/min per 100 g body weight for 40 min) on bile flow, together with their biliary excretion and metabolism. Lithocholate-glucuronide had a higher cholestatic effect than lithocholate, whereas lithocholate-sulfate had almost no effect on bile flow. Lithocholate was mainly converted to taurine or glucuronide conjugates in the bile, serum and liver and hydroxylation of the tauro-conjugate proceeded. Lithocholate-sulfate was almost completely excreted in the bile, mainly as tauro-conjugate. Lithocholate-glucuronide was excreted in bile almost without conjugation, while some taurine conjugation occurred in the serum and liver. These results suggest that the poor biotransformation of lithocholate-glucuronide is related to its higher cholestatic potency than lithocholate.

GT1b in human metastatic brain tumors: GT1b as a brain metastasis-associated ganglioside.

We studied ganglioside expression in 12 human metastatic brain tumors metastasized from colon (4), renal (3), lung (2), esophagus (1), pancreas (1), and mammary (1) carcinomas. GM3 was the major common ganglioside expressed in brain metastatic tumor tissues, and GT1b was also present in all the metastatic brain tumor tissues. The latter was identified by TLC-immunostaining and characterized structurally by secondary ion mass spectrometry combined with 'Far-Eastern blot'. The immunohistochemical analysis of frozen tissue sections confirmed localization of GT1b in the tumor cell membrane or cytosol. GT1b was shown to be expressed both in the primary colon carcinoma and the metastasis of a single patient by immunohistochemical procedure. In systemic carcinomas without brain metastasis, GM3 was a common major component, but no GT1b was detected. These findings indicate that GT1b is a brain metastasis-associated ganglioside. We speculate that the presence of GT1b would be a useful marker for estimating metastatic potentials to the brain.

Detection of antibody to sialyl-i, a possible antigen in patients with Meniere's disease.

An autoimmune hypothesis for the etiology of Meniere's disease has been proposed. In this study, we focused on gangliosides as potential antigens for autoantibodies in Meniere's disease patients. In an attempt to investigate ganglioside antigens which respond to the serum of patients with Meniere's disease, we analyzed gangliosides of human acoustic neurinomas, and used them as antigens to broadly explore gangliosides that react to serum. All the acoustic neurinoma samples used in the present study showed a similar ganglioside profile on TLC (thin-layer chromatography). For the microscale ganglioside analysis, a newly developed TLC blotting/secondary ion mass spectrometry (SIMS) system together with TLC immunostaining method was employed. Most of the ganglioside bands could be analyzed, and they were identified as GM3, GM2, SPG, GM1a, GD3, S-i (sialyl-i ganglioside) and GD1a. GD1a was the predominant ganglioside and many neolactoseries gangliosides were recognized by immunological analysis. Next, the immune reactivity of serum samples, from patients with Meniere's disease, with the acoustic neurinoma gangliosides was studied by TLC immunostaining. The result showed that five of 11 patients with Meniere's disease and one of eight normal subjects reacted with a specific band, which was identified as S-i by the TLC blotting/SIMS system. The findings of the present study indicate that S-i ganglioside is an autoantigen and possibly involved in the pathogenesis of Meniere's disease.

Effects of cholestanol feeding on corneal dystrophy in mice.

A cholestanol-enriched diet administered for 8 months to BALB/c mice produced in 20% two kinds of corneal opacities resembling calcific band keratopathy and Schnyder's crystalline dystrophy in humans. The concentrations of cholestanol in serum, liver and cornea of the corneal opacity bearing mice were 30-40-times higher than those of normal mice. On the other hand, brain cholestanol level increased only 7-times in the opacity group as compared with that of control group. There was no significant difference in the cholesterol concentrations of serum and several tissues among opacity, non-opacity and the control group. The crystal particles were observed between epithelial basement membrane and superficial stroma by the electron microscopy. Energy dispersive analysis of the particles revealed that the deposits were composed principally of calcium and phosphorus with other crystalline materials, which was presumed to be cholestanol. These results suggest that the cholestanol may deposit in the cornea from elevated serum levels. Deposition of cholestanol in cornea and related area may be a cause of corneal dystrophy in CTX.

Characterization of blood group ABO(H)-active gangliosides in type AB erythrocytes and structural analysis of type A-active ganglioside variants in type A human erythrocytes.

Several monosialogangliosides containing the type A-active epitope have been detected in type A erythrocytes on immunological analysis with a monoclonal antibody, and three of them were purified by repeated silica bead column chromatography and by scraping from the TLC plate. Two of these A-active gangliosides were characterized by methylation analysis by GC/MS, negative SIMS, MALDI-TOF/MS, proton nuclear magnetic resonance spectroscopy, and immunological assays, and their structures were concluded to be as follows. A-active ganglioside I:A-active ganglioside II:The reactivity of the purified gangliosides to the anti-A monoclonal antibodies (mAbs) exhibited enhancement after removal of the sialic acid. Therefore, the sialic residue has been shown to inhibit the binding to the terminal A-active epitope through the formation of an immune complex. To confirm the presence of A- (including S-A-I, -II and -III) and B-active gangliosides, the reactivity of anti-A and -B mAbs were investigated using total gangliosides from type A, -B and -AB erythrocytes on TLC plate. The results were that the gangliosides from types A and AB showed positive reaction to anti-A mAbs, whereas in the anti-B mAbs binding the gangliosides from types B and AB were positive. Thus, it revealed that A-active gangliosides were present in type A and -AB, and B-active gangliosides in types B and AB. As there was no difference in respective gangliosides on type AB erythrocytes of 22 individuals, both A- and B-active gangliosides are equally present in type AB erythrocytes. The biological significance of these A- and B-active ganglioside variants remains vague at present. As these molecules exhibit different reactivities to the anti-A mAbs, it is very likely that they can regulate the antigenicity of the A-epitope on the cell surface.

Glycosphingolipid compositions of human T-lymphotropic virus type I (HTLV-I) and human immunodeficiency virus (HIV)-infected cell lines.

Glycolipid compositions of cells infected by human retroviruses (human immunodeficiency virus, HIV and/or human T-cell lymphotropic virus type I, HTLV-I) have been studied. Eight cell lines, comprising two HTLV-I-infected T-cell lines (MT-2 and MT-4), two HTLV-I-negative T-cell lines (Jurkat and MF), a macrophage cell line (U937), and three HIV-infected counterpart cell lines (MT-4/HIV, Jurkat/HIV and U937/HIV) were used. The neutral glycolipids and gangliosides isolated from these cell lines were compared. Among them, the HTLV-I-infected T-cell lines, MT-2 and MT-4, showed similar patterns for both neutral glycolipids and gangliosides. Neutral glycolipids (GlcCer and LacCer) of MT-2 and MT-4 cells were markedly decreased, and a ganglioside, GM3, of theirs was decreased to only a trace amount compared to that in other cell lines. Gangliosides of MT-4 and MT-4/HIV were further separated on an Iatrobeads column, and were identified as GM2, GM1a and GD1a by methylation and liquid secondary ion mass spectrometric analyses. Since the patterns of neutral glycolipids and gangliosides of MT-2 and MT-4 are unique, as compared to those of HTLV-I-negative cells, it is suggested that these changes are related to HTLV-1 infection. No prominent differences in the ganglioside compositions between HIV-infected and non-infected cell lines could be observed. But it is noteworthy that the contents of asialo-GM2 in Jurkat/HIV and MT-4/HIV cells were increased as compared to those in the parental cell lines.

Identification of 7 alpha-hydroxy-3-oxo-4-cholestenoic acid in chronic subdural hematoma.

We detected a novel kind of bile acid in the content of chronic subdural hematoma. This substance was specifically found in chronic subdural hematoma, and not in subdural hygroma, which is pathologically similar except for the lack of capsular membrane. The compound was identified as 7 alpha-hydroxy-3-oxo-4-cholestenoic acid by high performance liquid chromatography, gas chromatography-mass spectrometry, and nuclear magnetic resonance spectrometry. The structure was confirmed by the comparison with the chemically synthesized compound. The average contents in chronic subdural hematoma were 658.09 +/- 137.53 ng/ml, while those in normal human plasma were 126.27 +/- 17.73 ng/ml. It was not detected in normal cerebrospinal fluid. The higher level in chronic subdural hematoma than human plasma strongly suggests the local, extrahepatic production of this type of C27 bile acids.

Accumulation of isogloboside and ganglio-N-tetraosyl ceramide having blood group B determinant in the hepatomas of female LEC rats.

We have studied the neutral glycolipid composition of spontaneous hepatomas in LEC female rats. Neutral lipid fractions were isolated and purified by column chromatographies on DEAE-Toyopearl 650(M) and Iatrobeads. The neutral glycolipid fraction contained 3.2 to 4.4 micrograms lipid-bound glucose (Glc) per mg protein, and consisted of isogloboside (iso-Gb4, 50.8% of total neutral glycolipids) and IV3Gal, IV2Fuc, GgOse4Cer (asialo-BGM1, 13.5%) as the major neutral glycolipids and Gb3 and iso-Gb3 (9.2%), GlcCer (7.2%), LacCer (6.1%) as the other species. The structure of iso-Gb4 was elucidated by gas-liquid chromatography (GLC), permethylation study, liquid secondary ion (LSI) mass spectrometry, and nuclear Overhauser enhancement spectroscopy (NOESY) and that for asialo-BGM1 by GLC, LSI mass spectrometry, and high-performance thin-layer chromatography (HPTLC)-overlay method using anti-asialo-BGM1 antibody. Isogloboside and asialo-BGM1 which are found in negligible amounts in normal liver tissues may represent excellent markers for studying tumor metastasis and cellular adhesion.