Utility of synthetic MRI in predicting the Ki-67 status of oestrogen receptor-positive breast cancer: a feasibility study.

AIM: To evaluate the utility of synthetic magnetic resonance imaging (MRI) of the breast in predicting the Ki-67 status in patients with oestrogen receptor (ER)-positive breast cancer. MATERIALS AND METHODS: Forty-nine patients with 50 histopathologically proven breast cancers who underwent additional synthetic MRI were enrolled in the present study. Using synthetic MRI images, T1 and T2 relaxation times and their standard deviations (SD) in the breast lesions before (T1-Pre, T2-Pre, PD-Pre, SD of T1-Pre, SD of T2-Pre, SD of PD-Pre) and after (T1-Gd, T2-Gd, PD-Gd, SD of T1-Gd, SD of T2-Gd, SD of PD-Gd) contrast agent injection were obtained. These quantitative values were compared between the low Ki-67 expression (<14%) lesions (low-proliferation group: n=23) and high Ki-67 expression (≥14%) lesions (high-proliferation group: n=27). RESULTS: The univariate analysis showed that the SD of T1-Gd (p<0.001) and T2-Gd (p=0.042) were significantly higher in the high-proliferation group than in the low-proliferation group. Multivariate analysis further showed that the SD of T1-Gd was a significant and independent predictor of Ki-67 expression, with an area under the receiver operating characteristic (AUROC) curve of 0.885. The sensitivity, specificity, and accuracy of the SD of T1-Gd with an optimal cut-off value of 98.5 were 77.8%, 87%, and 82%, respectively. CONCLUSION: The SD of T1-Gd obtained from synthetic MRI was useful to predict Ki-67 status.

Sodium temperature/wind lidar based on laser-diode-pumped Nd:YAG lasers deployed at Tromsø, Norway (69.6°N, 19.2°E).

An Nd:YAG laser-based sodium temperature/wind lidar was developed for the measurement of the northern polar mesosphere and lower thermosphere at Tromsø (69.6N, 19.2E), Norway. Coherent light at 589 nm is produced by sum frequency generation of 1064 nm and 1319 nm from two diode laser end-pumped pulsed Nd:YAG lasers. The output power is as high as 4W, with 4 mJ/pulse at 1000 Hz repetition rate. Five tilting Cassegrain telescopes enable us to make five-direction (zenith, north, south, east, west) observation for temperature and wind simultaneously. This highly stable laser system is first of its kind to operate virtually maintenance-free during the observation season (from late September to March) since 2010.

Correlation between infectious disease and soil radiation in Japan: an exploratory study using national sentinel surveillance data.

We investigated the relationship between epidemics and soil radiation through an exploratory study using sentinel surveillance data (individuals aged <20 years) during the last three epidemic seasons of influenza and norovirus in Japan. We used a spatial analysis method of a geographical information system (GIS). We mapped the epidemic spreading patterns from sentinel incidence rates. We calculated the average soil radiation [dm (µGy/h)] for each sentinel site using data on uranium, thorium, and potassium oxide in the soil and examined the incidence rate in units of 0·01 µGy/h. The correlations between the incidence rate and the average soil radiation were assessed. Epidemic clusters of influenza and norovirus infections were observed in areas with relatively high radiation exposure. A positive correlation was detected between the average incidence rate and radiation dose, at r = 0·61-0·84 (P < 0·01) for influenza infections and r = 0·61-0·72 (P < 0·01) for norovirus infections. An increase in the incidence rate was found between areas with radiation exposure of 0 < dm < 0·01 and 0·15 ⩽ dm < 0·16, at 1·80 [95% confidence interval (CI) 1·47-2·12] times higher for influenza infection and 2·07 (95% CI 1·53-2·61) times higher for norovirus infection. Our results suggest a potential association between decreased immunity and irradiation because of soil radiation. Further studies on immunity in these epidemic-prone areas are desirable.

Gate-Tunable Spin-Charge Conversion and the Role of Spin-Orbit Interaction in Graphene.

The small spin-orbit interaction of carbon atoms in graphene promises a long spin diffusion length and the potential to create a spin field-effect transistor. However, for this reason, graphene was largely overlooked as a possible spin-charge conversion material. We report electric gate tuning of the spin-charge conversion voltage signal in single-layer graphene. Using spin pumping from an yttrium iron garnet ferrimagnetic insulator and ionic liquid top gate, we determined that the inverse spin Hall effect is the dominant spin-charge conversion mechanism in single-layer graphene. From the gate dependence of the electromotive force we showed the dominance of the intrinsic over Rashba spin-orbit interaction, a long-standing question in graphene research.

Polymerization of room-temperature ionic liquid monomers by electron beam irradiation with the aim of fabricating three-dimensional micropolymer/nanopolymer structures.

A novel method for fabricating microsized and nanosized polymer structures from a room-temperature ionic liquid (RTIL) on a Si substrate was developed by the patterned irradiation of an electron beam (EB). An extremely low vapor pressure of the RTIL, 1-allyl-3-ethylimidazolium bis((trifluoromethane)sulfonyl)amide, allows it to be introduced into the high-vacuum chamber of an electron beam apparatus to conduct a radiation-induced polymerization in the nanoregion. We prepared various three-dimensional (3D) micro/nanopolymer structures having high aspect ratios of up to 5 with a resolution of sub-100 nm. In addition, the effects of the irradiation dose and beam current on the physicochemical properties of the deposited polymers were investigated by recording the FT-IR spectra and Young's modulus. Interestingly, the overall shapes of the obtained structures were different from those prepared in our recent study using a focused ion beam (FIB) even if the samples were irradiated in a similar manner. This may be due to the different transmission between the two types of beams as discussed on the basis of the theoretical calculations of the quantum beam trajectories. Perceptions obtained in this study provide facile preparation procedures for the micro/nanostructures.

Fibulin-2 is involved in early extracellular matrix development of the outgrowing mouse mammary epithelium.

Cell-matrix interactions control outgrowth of mammary epithelium during puberty and pregnancy. We demonstrate here that the glycoprotein fibulin-2 (FBLN2) is strongly associated with pubertal and early pregnant mouse mammary epithelial outgrowth. FBLN2 was specifically localized to the cap cells of the terminal end buds during puberty and to myoepithelial cells during very early pregnancy (days 2-3) even before morphological changes to the epithelium become microscopically visible, but was down-regulated thereafter. Exposure to exogenous oestrogen (E2) or E2 plus progesterone (P) increased Fbln2 mRNA expression in the pubertal gland, indicating hormonal control. FBLN2 was co-expressed and co-localised with the proteoglycan versican (VCAN) and co-localised with laminin (LN), while over-expression of FBLN2 in HC-11 cells increased cell adhesion to several extracellular matrix proteins including LN and fibronectin, but not collagens. Mammary glands from Fbln2 knockout mice showed no obvious phenotype but increased fibulin-1 (FBLN1) staining was detected, suggesting a compensatory mechanism by other fibulin family members. We hypothesise that similar to embryonic aortic smooth muscle development, FBLN2 and VCAN expression alters the cell-matrix interaction to allow mammary ductal outgrowth and development during puberty and to enable epithelial budding during pregnancy.

Randomised phase II study comparing dose-escalated weekly paclitaxel vs standard-dose weekly paclitaxel for patients with previously treated advanced gastric cancer.

BACKGROUND: This randomised phase II trial compared dose-escalated weekly paclitaxel (wPTX) vs standard-dose wPTX for patients with previously treated advanced gastric cancer (AGC). METHODS: Ninety patients were randomised to a standard dose of wPTX (80 mg m(-2)) or an escalated dose of wPTX (80-120 mg m(-2)) to assess the superiority of overall survival (OS) with a one-sided alpha error of 0.3 and a power of 0.8. RESULTS: The median OS showed a trend towards longer survival in the dose-escalated arm (11.8 vs 9.6 months; hazard ratio (HR), 0.75; one-sided P=0.12), although it was statistically not significant. The median progression-free survival (PFS) was significantly longer in the dose-escalated arm (4.3 vs 2.5 months, HR, 0.55; P=0.017). Objective response rate was 30.3% with dose escalation and 17.1% with standard dose (P=0.2). The frequency of all grades of neutropenia was significantly higher with dose escalation (88.7% vs 60.0%, P=0.002); however, no significant difference was observed in the proportion of patients experiencing grade 3 or more (40.9% vs 31.1%, P=0.34). CONCLUSION: Dose-escalated wPTX in patients with pretreated AGC met our predefined threshold of primary end point, OS (P<0.3); however, it did not show a significantly longer OS. Progression-free survival was significantly better with dose escalation.

Genetic evidence for a novel familial Alzheimer's disease locus on chromosome 14.

Familial Alzheimer's disease (FAD) has been shown to be genetically heterogeneous, with a very small proportion of early onset pedigrees being associated with mutations in the amyloid precursor protein (APP) gene on chromosome 21, and some late onset pedigrees showing associations with markers on chromosome 19. We now provide evidence for a major early onset FAD locus on the long arm of chromosome 14 near the markers D14S43 and D14S53 (multipoint lod score z = 23.4) and suggest that the inheritance of FAD may be more complex than had initially been suspected.

Presenilin-1 mutations downregulate the signalling pathway of the unfolded-protein response.

Missense mutations in the human presenilin-1 (PS1) gene, which is found on chromosome 14, cause early-onset familial Alzheimer's disease (FAD). FAD-linked PS1 variants alter proteolytic processing of the amyloid precursor protein and cause an increase in vulnerability to apoptosis induced by various cell stresses. However, the mechanisms responsible for these phenomena are not clear. Here we report that mutations in PS1 affect the unfolded-protein response (UPR), which responds to the increased amount of unfolded proteins that accumulate in the endoplasmic reticulum (ER) under conditions that cause ER stress. PS1 mutations also lead to decreased expression of GRP78/Bip, a molecular chaperone, present in the ER, that can enable protein folding. Interestingly, GRP78 levels are reduced in the brains of Alzheimer's disease patients. The downregulation of UPR signalling by PS1 mutations is caused by disturbed function of IRE1, which is the proximal sensor of conditions in the ER lumen. Overexpression of GRP78 in neuroblastoma cells bearing PS1 mutants almost completely restores resistance to ER stress to the level of cells expressing wild-type PS1. These results show that mutations in PS1 may increase vulnerability to ER stress by altering the UPR signalling pathway.

Changes of concentrations, shipment amounts and ecological risk of pesticides in river water flowing into Lake Biwa.

A survey of various pesticide contaminations was performed for water in Yanamune River flowing into Lake Biwa from 1988 to 2009. Ten pesticides (diazinon and fenitrothion as insecticides, iprobenfos and isoprothiolane as fungicides and chlornitrofen, thiobencarb, molinate, bromobutide, simetryne and pretilachlor as herbicides) were selected and concentration changes of the pesticides were evaluated based on their shipment amounts. Yearly maximum concentrations of eight of the pesticides in Yanamune River water were compared with their no observed effect concentration and their predicted no effect concentration values and initial ecological risk assessment was conducted for five pesticides (diazinon, fenitrothion, iprobenfos, isoprothiolane and thiobencarb) by their predicted no effect concentration values. All of the diazinon (0.01-0.28 µg/L) and fenitrothion (0.005-0.31 µg/L) concentrations from 1988 to 2007, the iprobenfos (2.7 and 2.4 µg/L) concentrations in 1988 and 1990 and the thiobencarb (0.24-2.7 µg/L) concentrations in 1988, 1992, 1993 and 1995 exceeded their predicted no effect concentration (PNEC) (0.00026, 0.00021, 1.0 and 0.17 µg/L) values.

Seasonal changes of PFOS and PFOA concentrations in Lake Biwa water.

A survey on seasonal concentration changes of perfluorooctane sulfonate (PFOS) and perfluorooctanoic acid (PFOA) was performed for surface water in Lake Biwa (14 sites) from February to November in 2009. The concentrations of PFOS and PFOA were 0.8-1.6 and 7.0-10 ng/L in northern basin of Lake Biwa (eight sites), 0.9-1.7 and 8.3-13 ng/L in southern basin of Lake Biwa except Akanoi Bay (four sites), 1.4-2.8 and 9.1-17 ng/L in Akanoi Bay (8C) and 2.4-5.3 and 12-26 ng/L in Akanoi Bay (168), respectively. Seasonal changes were recognized for both of PFOS and PFOA in the two sites of Akanoi Bay but not in the other sites of the southern and northern basins of Lake Biwa. Monthly detailed surveys in the surface water were performed on the changes of PFOS and PFOA concentrations from June in 2009 to May in 2010 and further on the changes of conductivity values. The changes of PFOS and PFOA concentrations were well consistent with those of conductivity values.

Characterization of internal transcribed spacer (ITS1)-ITS2 region of ribosomal RNA gene from 25 species of Culicoides biting midges (Diptera: Ceratopogonidae) in Japan.

We determined nucleotide sequences of the nuclear rDNA internal transcribed spacer (ITS)1-5.8S-ITS2a-2S-ITS2 region in 103 individuals of 25 Culicoides species (Diptera: Ceratopogonidae) from 11 locations in Japan. Ribosomal RNA genes, 5.8S and 2S rDNA, were highly conserved among the species with few variations. The ITS2a region showed length variation among species. Both ITS1 and ITS2 showed highly varied sequences among species. The noticeable indel regions among ITS1 sequences are present in some Culicoides species, separating species into two types having long or short ITS1 region. However, Culicoides cylindratus Kitaoka possesses both types of ITS1 in each individual; these results seem to indicate that the ITS1-long type was the prototype and the short type was produced through deletion in many Culicoides species. One species, belonging to subgenus Avaritia, possessed an Avaritia-specific sequence in ITS1 and phylogenetically formed a monophyletic group. Geographical genotypes in a species were not clear. Species-specific sequence features were observed, enabling molecular identification of Culicoides species.

Species-specific mitochondrial gene rearrangements in biting midges and vector species identification.

Partial mitochondrial gene sequences of 16 Culicoides species were determined to elucidate phylogenetic relations among species and to develop a molecular identification method for important virus vector species. In addition, the analysis found mitochondrial gene rearrangement in several species. Sequences of the mitochondrial genome region, cox1-trnL2-cox2 (1940-3785 bp) of 16 Culicoides and additional sequences were determined in some species, including whole mitochondrial genome sequences of Culicoides arakawae. Nine species showed common organization in this region, with three genes cox1-trnL2-cox2 and a small or no intergenic region (0-30 bp) between them. The other seven species showed translocation of tRNA and protein-coding genes and/or insertion of AT-rich non-coding sequences (65-1846 bp) between the genes. The varied gene rearrangements among species within a genus is very rare for mitochondrial genome organization. Phylogenetic analyses based on the sequences of cox1+cox2 suggest a few clades among Japanese Culicoides species. No relationships between phylogenetic closeness and mitochondrial gene rearrangements were observed. Sequence data were used to establish a polymerase chain reaction tool to distinguish three important vector species from other Culicoides species, for which classification during larval stages is not advanced and identification is difficult.

Pesticides in water, fish and shellfish from littoral area of Lake Biwa.

A survey of 29 pesticides were performed for water, fish and shellfish from two littoral areas of Lake Biwa and Yanamune River in 2007. Three insecticides, 5 fungicides and 13 herbicides were detected in the water from the sampling locations, but the insecticides and fungicides were not and the only 9 herbicides were detected in the fish and shellfish from the locations. Bioconcentration factors (BCF) of the 9 herbicides in the fish and shellfish were calculated by the field data obtained from the survey. The average field BCF values of the herbicides in the fish were 8 and 25 for molinate, 5-23 for bromobutide, 4 and 10 for simetryn, 100-214 for esprocarb, 15-41 for pretilachlor, 148 for anilofos, 14 and 79 for mefenacet and 78 for cafenstrole. Those in the shellfish were 6 and 13 for bromobutide, 4 and 8 for simetryn, 67 and 135 for esprocarb, 2 for pretilachlor, 117 for pyributicarb and 57 and 139 for mefenacet. The field BCF data in the fish were evaluated by laboratory BCF data from literatures for molinate, bromobutide, pretilachlor, simetryn and mefenacet.

Pesticides in water and sediment from littoral area of Lake Biwa.

A survey of 29 pesticides was performed for water and sediment from two littoral areas of Lake Biwa in 2007. Two insecticides, 5 fungicides and 13 herbicides in the water and an insecticide, 4 fungicides and 7 herbicides in the sediment were detected from the present survey. Pesticide accumulation potential in the sediment was calculated as "Pesticide concentration ratio" from the results of the survey on water and sediment in Lake Biwa. Correlation was investigated for each of the detected pesticides between sediment ignition loss and pesticide concentration ratio or between sediment particle size and pesticide concentration ratio. The ignition loss correlated well with the pesticide concentration ratio for pyrokiron, simetryn, and isoprothiolane (p < 0.01 to p < 0.001) but did not for molinate, bromobutide and pretilachlor. Further, the <0.025 mm particle size ratio correlated well with the pesticide concentration ratio for pyrokiron, simetryn, flutolanil, isoprothiolane and mefenacet (p < 0.01 to p < 0.001) but did not for bromobutide and pretilachlor. The correlation between <0.025 mm particle size ratio and pesticide concentration ratio had almost the same tendency as that between ignition loss and pesticide concentration ratio, suggesting sediment with higher <0.025 mm particle size ratio had higher weight (%) of ignition loss.

[Early malignant pleural mesothelioma; report of a case].

We report a case who had undergone operation of very early malignant pleural mesothelioma (MPM). A 58-year-old woman admitted to first visited hospital because of pleural effusion of the right side. She received a diagnosis of epithelial type MPM which had been confirmed from a pleural biopsy spacemen obtained by thoracoscopy under local anesthesia. An abnormal change of the pleura could not be detected on chest X-ray and thoracic computed tomography (CT) scan after chest drainage. She was referred to our hospital for surgery, and was undergone an extrapleural pneumonectomy followed by postoperative treatment with cisplatin puls gemcitabine. Pathologically, the disease was diagnosed as stage IA based on the classification of International Mesothelioma Interest Group (IMIG). There is a no evidence of the relapse 9 months after the operation. An early diagnosis of the MPM is very difficult. The thoracoscope with local anesthesia was very effective for early diagnose of a MPM.

Analysis of the functional effects of a mutation in SOD1 associated with familial amyotrophic lateral sclerosis.

Mutations in the Cu, Zn superoxide dismutase (SOD1) gene have been reported in some pedigrees with Familial Amyotrophic Lateral Sclerosis (FALS). We have investigated the functional and structural effects of a Gly-->Ser mutation at codon 41 of SOD1 in a pedigree with FALS and the topography of SOD1 expression in the mammalian CNS. These analyses show that the 41Gly-->Ser mutation causes a 27% reduction in Cu, Zn SOD activity. SOD1 is transcribed at high levels in rat motoneurons and four other types of neurons homologous to upper motoneurons that degenerate in human ALS. However, SOD1 is transcribed at lower levels in other types of neurons, such as cerebellar Purkinje cells, which are not usually involved significantly in human ALS. On the other hand, immunocytochemical studies indicate that most types of rat neurons contain similar levels of Cu, Zn SOD immunoreactive protein. Nevertheless, these results suggest that the essential feature causing this subtype of ALS is either a reduction in Cu, Zn SOD activity in cell types that presumably critically require Cu, Zn SOD for protection against oxidative damage or the fact that the mutation in SOD1 associated with FALS results in a novel gain of function that is particularly deleterious to those cell types expressing SOD1 at high levels.

Congenital anomalies induced by triamcinolone acetonide in murine embryos.

INTRODUCTION: We have studied the morphogenesis of anorectal malformations in mice using retinoids. Several investigators have reported an interaction between glucocorticoids and retinoids. It was supposed that glucocorticoids had some effects on the morphogenesis of murine embryos similar to retinoids. Therefore, we investigated alterations in the morphogenesis of murine embryos after triamcinolone acetonide (TAC) administration. MATERIAL AND METHODS: TAC was administered in a single dose (15 mg/kg or 30 mg/kg body weight) to pregnant ICR-SLC mice on embryonic day 7 (E7), 8, 9, and 10. They were sacrificed on E18, and fetuses were examined for internal and external malformations. Randomly chosen fetuses were embedded in paraffin for immunohistochemical staining of the glucocorticoid receptor (GR). RESULTS: The groups given 15 mg/kg TAC had one peak in the incidence of cleft palate on E9 (100 %) and the groups given 30 mg/kg TAC showed a biphasic pattern in the incidence of cleft palate on E7 and E10. No other anomalies were found. GR expression was marked in the subepithelial layer of palatal processes in the treated specimens. CONCLUSION: The group given 15 mg/kg TAC on E9 provided a good model of cleft palate in ICR-SLC mice, and cleft palate was probably induced by various factors including disturbance of the bone morphogenetic protein (BMP) signaling pathway, shown by GR overexpression.