A Targeted Genetic Association Study of the Rare Type of Osteomyelitis.

Chronic nonbacterial osteomyelitis is a rare bone disorder that can be found in the jaw. It is often associated with systemic conditions, including autoimmune deficiencies. However, little is known about how the genetic and immunologic background of patients influences the disease. Here, we focus on human leukocyte antigen (HLA), killer cell immunoglobulin-like receptors (KIRs), and their specific combinations that have been difficult to analyze owing to their high diversity. We employed a recently developed technology of simultaneous typing of HLA alleles and KIR haplotype and investigated alleles of the 35 HLA loci and KIR haplotypes composed of centromeric and telomeric motifs in 18 cases and 18 controls for discovery and 472 independent controls for validation. We identified an amino acid substitution of threonine at position 94 of HLA-C in combination with the telomeric KIR genotype of haplotype tA01/tB01 that had significantly higher frequency (>20%) in the case population than in both control populations. Multiple logistic regression analysis based on a dominant model with adjustments for age and sex revealed and validated its statistical significance and high predictive accuracy (C-statistic ≥0.85). Structure-based analysis revealed that the combination of the amino acid change in HLA-C and the telomeric genotype tA01/tB01 could be associated with lower stability of HLA-C. This is the first case-control study of a rare disease that employed the latest sequencing technology enabling simultaneous typing and investigated amino acid polymorphisms at HLA loci in combination with KIR haplotype.

Hypoxic volume evaluated by 18F-fluoromisonidazole positron emission tomography (FMISO-PET) may be a prognostic factor in patients with oral squamous cell carcinoma: preliminary analyses.

Tumour hypoxia can be detected by 18F-fluoromisonidazole positron emission tomography (FMISO-PET). Few studies have assessed the relationships of new PET parameters, including hypoxic volume (HV), metabolic tumour volume (MTV), and total lesion glycolysis (TLG), with 5-year survival of patients treated surgically for oral squamous cell carcinoma (OSCC). This study evaluated the relationships between these PET parameters and 5-year survival in OSCC patients. Twenty-three patients (age 42-84 years; 15 male, eight female) with OSCC underwent FMISO- and 18F-fluoro-2-deoxyglucose (FDG)-PET computed tomography before surgery. All of them underwent radical surgery and were followed up for more than 5 years. The FDG-PET maximum standardized uptake value (SUVmax), HV, MTV, and TLG were measured. The ability of PET parameters to predict disease-free survival (DFS) and loco-regional recurrence (LR) was evaluated using receiver operating characteristic curve analysis. During the follow-up period, five of the 23 patients (22%) died and six (26%) experienced LR. Although FDG-PET SUVmax was not significantly associated with DFS or LR, HV correlated significantly with both DFS and LR. TLG, but not MTV, was significantly associated with DFS; however neither MTV nor TLG was related significantly to LR. In conclusion, tumour HV may predict outcomes in patients with OSCC.

Structural phase transition and magnetic-field effect on the modulated structure in GdBaCo2O5+δ (δ < 0.5).

We investigated the crystal structures of an ordered perovskite-type cobaltate, GdBaCo2O(5+δ) (δ < 0.5), at elevated temperatures by transmission electron microscopy. Above the magnetic ordering temperature, we observed a first-order structural phase transition between the low-temperature tetragonal 3a(p) × 3a(p) and high-temperature orthorhombic 1a(p) × 2a(p) superstructure phases (where a(p) is the perovskite-unit cell). Upon the application of a magnetic field, an incommensurate phase emerges around the structural phase-transition temperature, which indicates a magnetic-field-induced structural phase transition via no magnetic ordering in the ordered perovskite-type cobaltate.

Isomerization dynamics of the 2-phenylazo-1,3-dimethylimidazolium cation photoexcited to the S2 (π, π*) state as studied by transient absorption spectroscopy in the time domain of 10(-13) to 10(3) seconds.

Photoinduced isomerization of a novel photochromic cation, [2PA-Mmim](+) (2-phenylazo-1,3-dimethylimidazolium cation), was studied by optical spectroscopic methods. The UV-Vis absorption spectra of the [2PA-Mmim](+) cation show two prominent bands starting around 410 and 520 nm, corresponding to the S(0)-S(2) (π, π*) and S(0)-S(1) (n, π*) transitions, respectively. The photoisomerization mechanism is studied by femtosecond time-resolved transient absorption experiments performed after S(0)-S(2) (π, π*) excitation in several solvents with different viscosity, including ionic liquids. The transient absorption signals at two representative wavelengths were fitted by bi-exponential functions, which yield four decay components. The photoisomerization mechanism is discussed in light of the relaxation schemes available for azobenzene. Only one of the components depends on the solvent viscosity and it changes from 1.2 ps (dichloromethane, 0.4 cP) to 5.6 ps ([Bmim][BF(4)], 93 cP). This component is assigned to a molecule at the S(1) state, which is responsible for the "rotational" isomerization. The weak dependence on the solvent viscosity of this component is explained in terms of local change in the viscosity as a result of local heating due to excess energy released at S(2)-S(1) internal conversion. The other three components of ∼0.4, 1.0 and 10 ps are attributed to relaxation processes of the molecule at S(2), S(1) and S(0) states, respectively. The quantum yields for the forward E-Z photoisomerization are ∼0.15 after S(2) excitation. The backward Z-E isomerization is slow with a lifetime of 1 hour and an activation energy of 91 kJ mol(-1) through an "inversion" mechanism.

Postural changes during eye-head movements.

We investigated postural sway in young subjects during eye-head movements. Subjects stood on the force plate wearing a helmet on which a laser spot was attached. Visual targets were presented stepwise at 60 degrees to right and left or 50 degrees to upward and downward of the straight-ahead position. Subjects were asked to look at the targets quickly by directing the laser spot to the target. The anterior-posterior component of centre of pressures (COPs) exhibited the largest changes and shortest latencies during downward movements. Most of the subjects showed COP changes preceding the onset of downward head movements, and these changes were associated with EMG activity of biceps femoris and gastrocnemius. When subjects were asked to look at the target only by eyes, no consistent change was detected in ground reaction forces. These results indicate that the eye-head movements elicited the COP changes that preceded the onset of head movements.

Absolute calibration of imaging plate for GeV electrons.

An imaging plate has been used as a useful detector of energetic electrons in laser electron acceleration and laser fusion studies. The absolute sensitivity of an imaging plate was calibrated at 1 GeV electron energy using the injector Linac of SPring-8. The sensitivity curve obtained up to 100 MeV in a previous study was extended successfully to GeV range.

Direct observation of the bandwidth-disorder induced variation of charge/orbital ordering structure in RE(0.5)(Ca(1-y)Sr(y))(1.5)MnO(4).

Changes in the charge/orbital ordering (CO/OO) structure with the bandwidth of the e(g) band and quenched disorder were investigated in doped manganites RE(0.5)(Ca(1-y)Sr(y))(1.5)MnO(4)(RE = Pr,Eu) with a single-layer perovskite structure. A systematic study of the modulation structure associated with the CO/OO phase demonstrated that the long-range commensurate structure changes to a short-range incommensurate structure with increasing Sr content through the enhancement of the bandwidth and quenched disorder in these systems. At the same time, the transition temperature of CO/OO (T(CO/OO)) decreases. Changes in structure and T(CO/OO) with different A-site combinations reveal that the CO/OO phase is strongly suppressed by the widening of the e(g) band and the stronger quenched disorder in these layered manganites.

Autosomal recessive ataxia with peripheral neuropathy and elevated AFP: novel mutations in SETX.

Mutations in the Senataxin gene (SETX) are associated with autosomal recessive ataxia-ocular apraxia 2 (AOA2) and autosomal dominant juvenile ALS (ALS4). Here, the authors describe novel homozygous missense mutations in SETX, M274I, and R1294C, found in two siblings with ataxia, peripheral neuropathy, and increased serum alpha-fetoprotein level and three other siblings with heterozygous missense mutations who were neurologically asymptomatic. The results demonstrate that the double missense mutations are responsible for AOA2 but not for ALS4.

Observation of magnetic ripple and nanowidth domains in a layered ferromagnet.

We investigated ferromagnetic domain structures on nanometer to micrometer scale for single crystals of a layered ferromagnet, La(2-2x)Sr(1+2x)Mn2O7 (0.32 < or = x < or = 0.40), as functions of x and temperature by means of Lorentz electron microscopy. We have succeeded in observing the evolution of magnetic ripple structure, dynamically, related to a spin reorientation transition where the magnetization direction switches between parallel and perpendicular to the layers. Our high-resolution magnetic domain imaging revealed that the ripple state is characterized by the evolution of magnetic nanowidth domains.

Ferromagnetic microstructure in double exchange manganites.

Ferromagnetic (FM) microstructures in double-exchange manganites, La0.825Sr0.175MnO3, were examined by low-temperature Lorentz microscopy. It was found that the FM domains with the stripe pattern were in the FM metallic phase of La0.825Sr0.175MnO3. The FM insulator phase induced by the substitution of Al ions for Mn in La0.825Sr0.175MnO3 was characterized as a complex mixture of the characteristic FM domains, which consists of three types of FM domains: the stripe domains, the plate-shaped domains and the complicated wavy domains. It is suggested that this mixture of different types of FM domains breaks the coherence of the electric conductivity and gives rise to the insulating character in Al doped La0.825Sr0.175MnO3.

Ferromagnetic domain structures and nanoclusters in Nd(1/2)Sr(1/2)MnO3.

Magnetic domain structures of Nd(1/2)Sr(1/2)MnO3 were investigated by means of low-temperature Lorentz electron microscopy. On cooling, magnetic domain walls started to appear at 250 K, and they were oriented straight along the [100] and [110] directions. With a further decrease in temperature, the volume of each magnetic domain increased with discontinuous domain-wall jumps. A characteristic granular image was observed at around 140 K, near the charge-ordering transition temperature. We consider that this originated from ferromagnetic nanoclusters that appeared in the antiferromagnetic matrix.

Charge/orbital ordering structure of Pr(1-x)Ca(x)MnO(3)(x = 3/8) examined by low-temperature transmission electron microscopy.

The structural phase transition of Pr(1-x)Ca(x)MnO(3)(x = 3/8) was investigated by means of low-temperature transmission electron microscopy. Superlattice reflection spots with a modulation wave vector q(1) = (0,1/2,0) appeared below 230 K, indicating formation of the d(3x(2-r(2))/d(3y(2)-r(2)) type of charge/orbital ordering. Below 150 K, a new series of superlattice reflection spots with a modulation wave vector q(2) = (1/4,1/4,1/2) appeared, suggesting an additional ordering of excess 1/8 Mn(3+), necessary due to the deviation of x from 1/2, with the occupation of the d(3z(2-r(2)) type of e(g) orbital.

Homozygosity and linkage disequilibrium mapping of autosomal recessive distal myopathy (Nonaka distal myopathy).

Autosomal recessive distal myopathy or Nonaka distal myopathy (NM) is characterized by its unique distribution of muscular weakness and wasting. The patients present with spared quadriceps muscles even in a late stage of the disease. The hamstring and tibialis anterior muscles are affected severely in early adulthood. We have localized the NM gene to the region between markers D9S319 and D9S276 on chromosome 9 by linkage analysis. To further refine the localization of the NM gene, we conducted homozygosity and linkage disequilibrium analysis for 14 patients from 11 NM families using 18 polymorphic markers. All of the patients from consanguineous NM families were found to be homozygous for six markers located within the region between markers D9S2178 and D9S1859. We also provided evidence for significant allelic associations between the NM region and five marker loci. Examination of the haplotype analysis identified a predominant ancestral haplotype comprising the associated alleles 199-160-154-109 (marker order: D9S2179-D9S2180-D9S2181-D9S1804), present in 60% of NM chromosomes and in 0% of parent chromosomes. On the basis of the data obtained in this study, the majority of NM chromosomes were derived from a single ancestral founder, and the NM gene is probably located within the 1.5-Mb region between markers D9S2178 and D9S1791.

Synthesis and antibacterial activity of acylides (3-O-acyl-erythromycin derivatives): a novel class of macrolide antibiotics.

Introduction of an acyl group to the 3-O-position of erythromycin A derivatives instead of L-cladinose led to a novel class of macrolide antibiotics that we named "acylides". The 3-O-nitrophenylacetyl derivative TEA0777 showed significantly potent activity against not only erythromycin-susceptible Gram-positive pathogens but also inducibly macrolides-lincosamides-streptogramin B (MLS(B))-resistant Staphylococcus aureus and efflux-resistant Streptococcus pneumoniae. These results indicated that acylides have potential as next-generation macrolide antibiotics.

Light element analysis in oxycarbonate superconductors using EELS.

Elemental analysis in an oxycarbonate superconductor ((Cu,N,C)Sr2CaCu2Oy) is conducted using transmission electron microscope-electron energy-loss spectroscopy with detector-gain correction. The gain correction enables highly sensitive elemental analysis and precise measurement of energy-loss near edge structures (ELNESs). It is found that carbon is included as a CO3 group, because the carbon K-edge in the oxycarbonate shows the same ELNES observed from CaCO3. Nitrogen ELNES is similar to that of Sr(NO3)2, so nitrogen is contained as a NO3 group. Although both CO3(2-) and NO3- have similar planar atomic arrangements, the nitrogen ELNES observed is different from that of carbon. EEL spectrum simulation based on DV-Xalpha method is used to interpret the difference.

Synthesis and antibacterial activity of the tricyclic ketolides TE-802 and its analogs.

The novel 6-O-methyl tricyclic ketolides TE-802 and its analogs were synthesized by two successive cyclization reactions, 11,12-cyclic carbamate formation by intramolecular Michael addition and 9,11-diazaheptene ring construction by intramolecular dehydration reaction. These new tricyclic ketolides exhibited good in vitro antibacterial activity against not only erythromycin-susceptible strains but also erythromycin-resistant Staphylococcus aureus and Streptococcus pneumoniae, which are problematic pathogens of nosocomial and community-acquired respiratory tract infections, respectively.

HRTEM study of new series of oxycarbonitrate superconductors (Cu,C,N)Sr2Ca(n - 1)Cu(n)O(y) (n = 1-6).

Arrangements of Cu and anion groups (CO3 and NO3) in the charge-reservoir (CR) blocks of a series of new oxycarbonitrate superconductors (Cu,C,N)Sr2Ca(n - 1)Cu(n)O(y) (n = 1-6) were examined by means of electron diffraction and high-resolution transmission electron microscopy (HRTEM). The first three members with n = 1-3 [Tc = 33 K (n = 1), 91 K (n = 2), 90 K (n = 3)] show the 4a0-type superstructures with periodic arrangements, [-Cu-X-X-X-Cu-X-X-X-Cu-] (X = CO3, NO3), in the CR blocks. The third member (n = 3) partly contains the 2a0-type of superstructure with [-Cu-X-Cu-X-Cu] in the CR blocks. The fourth member with n = 4 (Tc = 113 K) contains only the 2a0-type of superstructure. The higher members, with n = 5 (Tc = 65 K) and n = 6 (Tc = 52 K), show no evidence of ordering in the CR blocks, suggesting random arrangements of Cu and anion groups.

Borate-rhamnogalacturonan II bonding reinforced by Ca2+ retains pectic polysaccharides in higher-plant cell walls

The extent of in vitro formation of the borate-dimeric-rhamnogalacturonan II (RG-II) complex was stimulated by Ca2+. The complex formed in the presence of Ca2+ was more stable than that without Ca2+. A naturally occurring boron (B)-RG-II complex isolated from radish (Raphanus sativus L. cv Aokubi-daikon) root contained equimolar amounts of Ca2+ and B. Removal of the Ca2+ by trans-1,2-diaminocyclohexane-N,N,N',N'-tetraacetic acid induced cleavage of the complex into monomeric RG-II. These data suggest that Ca2+ is a normal component of the B-RG-II complex. Washing the crude cell walls of radish roots with a 1.5% (w/v) sodium dodecyl sulfate solution, pH 6.5, released 98% of the tissue Ca2+ but only 13% of the B and 22% of the pectic polysaccharides. The remaining Ca2+ was associated with RG-II. Extraction of the sodium dodecyl sulfate-washed cell walls with 50 mM trans-1,2-diaminocyclohexane-N, N,N',N'-tetraacetic acid, pH 6.5, removed the remaining Ca2+, 78% of B, and 49% of pectic polysaccharides. These results suggest that not only Ca2+ but also borate and Ca2+ cross-linking in the RG-II region retain so-called chelator-soluble pectic polysaccharides in cell walls.