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The core light-harvesting complexes (LH1) in bacteriochlorophyll (BChl) b-containing purple phototrophic bacteria are characterized by a near-infrared absorption maximum around 1010 nm. The determinative cause for this ultra-redshift remains unclear. Here, we present results of circular dichroism (CD) and resonance Raman measurements on the purified LH1 complexes in a reaction center-associated form from a mesophilic and a thermophilic Blastochloris species. Both the LH1 complexes displayed purely positive CD signals for their Qy transitions, in contrast to those of BChl a-containing LH1 complexes. This may reflect differences in the conjugation system of the bacteriochlorin between BChl b and BChl a and/or the differences in the pigment organization between the BChl b- and BChl a-containing LH1 complexes. Resonance Raman spectroscopy revealed remarkably large redshifts of the Raman bands for the BChl b C3-acetyl group, indicating unusually strong hydrogen bonds formed with LH1 polypeptides, results that were verified by a published structure. A linear correlation was found between the redshift of the Raman band for the BChl C3-acetyl group and the change in LH1-Qy transition for all native BChl a- and BChl b-containing LH1 complexes examined. The strong hydrogen bonding and π–π interactions between BChl b and nearby aromatic residues in the LH1 polypeptides, along with the CD results, provide crucial insights into the spectral and structural origins for the ultra-redshift of the long-wavelength absorption maximum of BChl b-containing phototrophs. [ABSTRACT FROM AUTHOR]

Summary: We compared the effectiveness of promoting bone healing between two teriparatide preparations for atypical femoral fracture (AFF). A total of 45 AFFs were included in this study, and we compared the duration of bone union. Teriparatide administered by daily injection enhanced bone union more than weekly administration in complete AFFs.Introduction: The efficacy of teriparatide for atypical femoral fracture (AFF) has been recently reported. Although two different teriparatide preparations can be used to treat osteoporosis in Japan, daily or weekly injection, all previous reports on the effectiveness of teriparatide for AFF only examined daily injection formulations. Therefore, we compared the promotion of bone healing between the two teriparatide preparations for AFF.Methods: A total of 45 consecutive AFFs in 43 Japanese patients were included in this study. They received either a daily 20-μg teriparatide injection (daily group; n = 32) or a once-a-week 56.5-μg teriparatide injection (weekly group; n = 13). We compared the clinical background and duration of bone union between these two groups.Results: When all patents were included, the fracture healing time was not significantly different between the two groups. Only patients with complete AFFs had significantly fewer daily bisphosphonate or denosumab injections than the weekly group (P < 0.05). The fracture healing time in the daily group (6.1 ± 4.1 months) was significantly shorter than that in the weekly group (10.1 ± 4.2 months) (P < 0.05). Even if the influence of bisphosphonate or denosumab usage was excluded, a similar significant difference was observed in the fracture healing time (P < 0.05). There was no significant difference between the two groups among patients with incomplete AFFs.Conclusions: Daily teriparatide injections enhance bone union more than weekly injections in complete AFF patients. [ABSTRACT FROM AUTHOR]

Purpose: Radiation-induced oral mucositis is the most common side effect of radiotherapy in head and neck cancer; however, effective modalities for its prevention have not been established. In this study, we evaluated the effectiveness of Hangeshashinto (TJ-14), a Japanese herbal medicine, for preventing radiation-induced mucositis and elucidated its effect on inflammatory responses, including inflammatory cell chemotaxis and cyclooxygenase-2 (COX2) expression, in an animal model. Methods: Syrian hamsters, 8-9 weeks old, were enrolled in this study. Animals were irradiated with a single 40 Gy dose to the buccal mucosa. Hamsters freely received a treatment diet mixed with 2% TJ-14 or a normal diet daily. The therapeutic effect was determined based on the visual mucositis score, body weight, and histological examination of infiltrated neutrophils and COX2 expression. Results: TJ-14 significantly reduced the severity of mucositis. The percentage with severe mucositis (score ≥3) was 100% in the untreated group and 16.7% in the TJ-14 group ( P < 0.05). There was no difference in body weight change between the groups; however, weight gain in the untreated group tended to be suppressed compared to that in the TJ-14 group during the peak period of mucositis. In addition, TJ-14 inhibited the infiltration of neutrophils and COX2 expression in irradiated mucosa ( P < 0.05). Conclusions: TJ-14 reduced the severity of mucositis in an animal model by suppressing the inflammatory response. Because TJ-14 is inexpensive and its safety is established, it is a promising candidate for the standard treatment of radiation-induced mucositis in cancer patients. [ABSTRACT FROM AUTHOR]

Purpose: This retrospective study evaluated the effect of clinical background and treatment line on time to treatment failure (TTF) in advanced/metastatic breast cancer (AMBC) patients receiving F500 in Japan (UMIN 000015168). Methods: Patients who commenced F500 treatment were registered at 16 sites in Japan. Correlations between baseline clinicopathological factors, treatment line, and TTF were investigated by Kaplan-Meier analysis. TTF data were analyzed using univariate analysis and multivariate analysis with a Cox proportional hazards model. Results: Data for 1072 patients were available; 1031 patients (96.2%) were evaluable for efficacy. F500 was administered as first-line treatment in 2.0%, second-line in 22.7%, third-line in 26.7%, and ≥fourth-line in 48.6% patients. Median TTF was 5.4 months. Multivariate analysis found that earlier F500 use (first and second vs. third vs. ≥fourth line; hazard ratio (HR) = 0.80, 95% confidence interval (CI) 0.74-0.86; P < 0.001), longer period from AMBC diagnosis to F500 use (≥3 vs. <3 years; HR 0.60, 95% CI 0.51-0.70; P < 0.001), and no prior palliative chemotherapy administered for unresectable or metastatic breast cancer (no vs. yes; HR 0.69, 95% CI 0.60-0.80; P < 0.001) were associated with significantly longer TTF. Among 691 patients, where information on histologic/nuclear grade was available, a low grade was also associated with a longer TTF, but this finding was not maintained among patients with recurrent breast cancer ( N = 558). Among women with recurrent breast cancer, a longer DFI between a patient's initial breast cancer diagnosis and their recurrence was associated with a longer TTF on F500 therapy. Conclusions: Our study showed that treatment period of F500 was longer when used in earlier-line treatment. For patients on F500, TTF was also longer for patients who had not received prior palliative chemotherapy and for those who had a longer period from their AMBC diagnosis to F500 use. [ABSTRACT FROM AUTHOR]

We give the complete solution to the local diffeomorphism classification problem of generic singularities which appear in tangent surfaces, in as wider situations as possible. We interpret tangent geodesics as tangent lines whenever a (semi-)Riemannian metric, or, more generally, an affine connection is given in an ambient space of arbitrary dimension. Then, given an immersed curve, we define the tangent surface as the ruled surface by tangent geodesics to the curve. We apply the characterization of frontal singularities found by Kokubu, Rossman, Saji, Umehara, Yamada, and Fujimori, Saji, Umehara, Yamada, and found by the first author related to the procedure of openings of singularities. [ABSTRACT FROM AUTHOR]

Microwave kinetic inductance detector (MKID) is one of the candidates of focal plane detector for future satellite missions such as LiteBIRD. For the space use of MKIDs, the radiation tolerance is one of the challenges to be characterized prior to the launch. Aluminum (Al) MKIDs with 50 nm thickness on silicon substrate and on sapphire substrate were irradiated with a proton beam of 160 MeV at the heavy ion medical accelerator in Chiba. The total water-equivalent absorbed dose was $$\sim $$ 10 krad which should simulate the worst radiation absorption of 5 years observation at the Lagrange point L2. We measured characteristics of these MKIDs before and after the irradiation. We found no significant changes on resonator quality factor, responsivity, and recombination time of quasi-particles. The change on electrical noise equivalent power was also evaluated, and no significant increase was found at the noise level of $$O(10^{-18})$$ W/ $$\sqrt{ \mathrm{Hz} }$$ . [ABSTRACT FROM AUTHOR]

LiSiN crystals are synthesized by direct reaction between LiN and SiN with the molar ratio LiN/SiN of 10:1. Reaction is performed at 1073 K for 1 h under a nitrogen atmosphere of 700 Torr. The lattice constant determined by the X-ray powder diffraction method is 4.718 Å. Four broad Raman peaks are observed at 196, 286, 580, and 750 cm. By analogy with LiMgN, the broad peak at 580 cm with a half width of 140 cm is attributed to homogenously random distribution of Li and Si atoms. The band gap of LiSiN is found to be a direct gap of about 2.5 eV by optical absorption and photoacoustic spectroscopy methods. Comparison with the conventional cathode materials for lithium ion batteries, this gap value is close to d-d transition energy of Mn in LiMnO (1.63 eV or 2.00 eV) and that of Co in LiCoO (2.1 eV), suggesting that LiSiN is a possible cathode material. The 5 × 5 mm-sized lithium secondary battery of LiSiN cathode/propylene carbonate + LiClO electrolyte/Li anode structure shows a discharge capacity of 2.4 μAh cm for a discharge current of 1.0 μA. [ABSTRACT FROM AUTHOR]

Far-upstream element-binding protein-interacting repressor (FIR) is a transcription factor that inhibits c-Myc expression and has been shown to have antitumor effects in some malignancies. Here, we evaluated the antitumor effects of FIR using fusion gene-deleted Sendai virus (SeV/ΔF) as a nontransmissible vector against head and neck squamous cell carcinoma (HNSCC). Using in vitro and in vivo xenograft mouse models, we observed efficient expression of green fluorescent protein (GFP) following transduction with the SeV/ΔF vector encoding GFP (GFP-SeV/ΔF) into HNSCC cells. In vitro and in vivo studies revealed that administration of the FIR-encoded SeV/ΔF (FIR-SeV/ΔF) vector exerted significant antitumor effects, suppressed c-Myc expression and induced apoptosis in HNSCC. Additionally, the antitumor effects of FIR or the expression of GFP following administration of the FIR- or GFP-SeV/ΔF vector, respectively, were dependent on the multiplicity of infection or titer. Furthermore, the SeV/ΔF vector itself had no cytotoxic effects. Therefore, the SeV/ΔF vector may be safe and useful for the treatment of HNSCC, allowing for high-titer SeV/ΔF vector administration for anticancer gene therapy. In addition, SeV/ΔF vector-mediated FIR gene therapy demonstrated effective tumor suppression in HNSCC, suggesting that this therapy may have the potential for clinical use as a novel strategy for HNSCC treatment. [ABSTRACT FROM AUTHOR]

The superconducting fluctuation effect, due to preformed Cooper pairs above the critical temperature Tc, has been generally understood by the standard Gaussian fluctuation theories in most superconductors. The transverse thermoelectric (Nernst) effect is particularly sensitive to the fluctuations, and the large Nernst signal found in the pseudogap regime of the underdoped cuprates has raised much debate. Here we report on the observation of a colossal Nernst signal due to the superconducting fluctuations in the heavy-fermion superconductor URu2Si2. The Nernst coefficient is anomalously enhanced (by a factor of ∼106) as compared with the theoretically expected value of the Gaussian fluctuations. Moreover, contrary to the conventional wisdom, the enhancement is more significant with a reduction of the impurity scattering rate. This unconventional Nernst effect intimately reflects the highly unusual superconducting state of URu2Si2. The results invoke possible chiral or Berry-phase fluctuations associated with the broken time-reversal symmetry of the superconducting order parameter. [ABSTRACT FROM AUTHOR]

The superconducting fluctuation effect, due to preformed Cooper pairs above the critical temperature Tc, has been generally understood by the standard Gaussian fluctuation theories in most superconductors. The transverse thermoelectric (Nernst) effect is particularly sensitive to the fluctuations, and the large Nernst signal found in the pseudogap regime of the underdoped cuprates has raised much debate. Here we report on the observation of a colossal Nernst signal due to the superconducting fluctuations in the heavy-fermion superconductor URu2Si2. The Nernst coefficient is anomalously enhanced (by a factor of ∼106) as compared with the theoretically expected value of the Gaussian fluctuations. Moreover, contrary to the conventional wisdom, the enhancement is more significant with a reduction of the impurity scattering rate. This unconventional Nernst effect intimately reflects the highly unusual superconducting state of URu2Si2. The results invoke possible chiral or Berry-phase fluctuations associated with the broken time-reversal symmetry of the superconducting order parameter. [ABSTRACT FROM AUTHOR]

Tumor-associated B7-H1 molecules inhibit antitumor immunity in some malignancies. We found that B7-H1 expression on patient myeloma cells and human myeloma cell lines (HMCLs) was upregulated by cultivating the cells with autologous stromal cells and the human stromal cell line HS-5. Among major cytokines produced by HS-5 cells, interleukin (IL)-6-induced B7-H1 expression on HMCLs. Moreover, HS-5 cell-mediated B7-H1 expression was downregulated by inhibiting IL-6. B7-H1+ HMCLs were more proliferative and less susceptible to antimyeloma chemotherapy compared with B7-H1− HMCLs. Moreover, the former cells showed higher levels of Bcl-2 and FasL expression than the latter. Finally, B7-H1 molecules on HMCLs induced T-cell apoptosis and anergy of tumor-specific T cells. Consistent with these in vitro observations, patients whose myeloma cells expressed high levels of B7-H1 had higher myeloma cell percentages in the bone marrow (BM) and higher serum lactate dehydrogenase levels compared with other myeloma patients. In addition, B7-H1 expression levels were often upregulated after myeloma patients relapsed or became refractory to therapy. Our data indicate that the BM microenvironment upregulates B7-H1 expression on myeloma cells, which links to the two biological actions of inducing T-cell downregulation and enhancing aggressive myeloma-cell characteristics. Modulating the B7-H1 pathway may be worthwhile in myeloma. [ABSTRACT FROM AUTHOR]

To clarify the clinical features and outcome of Stenotrophomonas maltophilia infection among hematopoietic SCT (HCT) recipients, we retrospectively reviewed the records of 1085 consecutive HCT recipients and identified 42 episodes in 31 HCT recipients with S. maltophilia infection. We compared these recipients with 30 non-HCT patients with S. maltophilia infection. The mortality rate in HCT recipients was significantly higher than that in non-HCT patients (relative risk 5.7, P=0.04), and we identified seven patients with pulmonary hemorrhage due to S. maltophilia, exclusively in the HCT cohort. Six of these latter seven patients died within 1 day from the onset of hemorrhage and the isolate was identified after death in most cases; one patient, who received empiric therapy for S. maltophilia and granulocyte transfusion, survived for more than 2 weeks. The patients with pulmonary hemorrhage had a more severe and longer duration of neutropenia, persistent fever despite of the use of broad-spectrum antibiotics, complication by pneumonia and higher C-reactive protein levels than those without pulmonary hemorrhage. In conclusion, S. maltophilia was associated with fulminant and fatal pulmonary hemorrhage in HCT recipients. Empiric therapy with antibiotics before the onset of pulmonary hemorrhage may be effective in HCT recipients who carry the conditions identified. [ABSTRACT FROM AUTHOR]

The p53 tumor suppressor belongs to a gene family that includes two other structurally and functionally related members: p73 and p63. The regulation of p53 activity differs significantly from that of p73 and p63. To enhance the tumor suppressive activity of p53, we constructed six recombinant adenoviruses that encode hybrid proteins with three functional domains derived from either p53 or TAp63γ. The potency of these hybrid molecules in suppressing tumorigenesis was evaluated using in vitro and in vivo models. Of the hybrid molecules tested, one hybrid named p63-53O was the most potent activator of apoptosis in human cancer cells. The p63-53O hybrid is composed of the transcriptional activation domain and DNA-binding domain of TAp63γ and the oligomerization domain of p53. The p63-53O hybrid efficiently transactivated p53AIP1. Moreover, silencing of p53AIP1 partially abolished the apoptotic response to p63-53O in human cancer cells. The p53-p63 hybrid molecule is a novel potent anti-proliferative agent for the treatment of cancer. [ABSTRACT FROM AUTHOR]

Objectives: To clarify the changes in organic anion-transporting polypeptide 8 (OATP8) expression and enhancement ratio on gadoxetic acid-enhanced MR imaging in hepatocellular nodules during multistep hepatocarcinogenesis.Methods: In imaging analysis, we focused on 71 surgically resected hepatocellular carcinomas (well, moderately and poorly differentiated HCCs) and 1 dysplastic nodule (DN). We examined the enhancement ratio in the hepatobiliary phase of gadoxetic acid enhanced MR imaging [(1/postcontrast T1 value-1/precontrast T1 value)/(1/precontrast T1 value)], then analysed the correlation among the enhancement ratio, tumour differentiation grade and intensity of immunohistochemical OATP8 expression. In pathological analysis, we focused on surgically resected 190 hepatocellular nodules: low-grade DNs, high-grade DNs, early HCCs, well-differentiated, moderately differentiated and poorly differentiated HCCs, including cases without gadoxetic acid-enhanced MR imaging. We evaluated the correlation between the immunohistochemical OATP8 expression and the tumour differentiation grade.Results: The enhancement ratio of HCCs decreased in accordance with the decline in tumour differentiation (P < 0.0001, R = 0.28) and with the decline of OATP8 expression (P < 0.0001, R = 0.81). The immunohistochemical OATP8 expression decreased from low-grade DNs to poorly differentiated HCCs (P < 0.0001, R = 0.15).Conclusions: The immunohistochemical expression of OATP8 significantly decreases during multistep hepatocarcinogenesis, which may explain the decrease in enhancement ratio on gadoxetic acid-enhanced MR imaging. [ABSTRACT FROM AUTHOR]

Long-term follow-up data on patients who underwent allogeneic hematopoietic stem cell transplantation in our institution between 1990 and 2007 were evaluated for mortality and morbidity beyond 2 years post-transplantation. Follow-up data were obtained annually from medical records or by mail to the relevant hospitals, or to the patients themselves. In total, 369 patients survived more than 2 years, but 72 patients died thereafter. Relapse was the most common cause of death, followed by pulmonary complications and infections. Second malignancy was the cause of death in seven patients. Chronic kidney disease was one of the most serious complications, and seven patients needed regular dialysis or kidney transplantation. Hypertension and diabetes were reported in 19 and 11.2% patients, respectively. Second malignancies were observed in 14 patients beyond 2 years after transplantation, and the oral mucosa, tongue, esophagus and colon were the main organs involved. We recommend that physicians caring for allogeneic hematopoietic stem cell transplant patients should at a minimum examine kidney function and gastrointestinal tract for secondary malignancy, in addition to hematological status. Such information will be useful for optimizing outcomes through the detection and prevention of complications. [ABSTRACT FROM AUTHOR]

Background: a fibroblast growth factor 2 (FGF2)-targeted adenoviral system can alter viral tropism and allow for improved transduction and reduced systemic toxicity. This study is to investigate if the FGF2-targeted adenoviral mutant Nijmegen breakage syndrome 1 (FGF2-Ad-NBS1) gene transfer can enhance cisplatin chemosensitisation not only by targeting DNA repair, but also through the induction of antiangiogenesis, whereas at the same time reducing toxicities in treating head and neck squamous cell carcinoma (HNSCC).Methods: the human HNSCC cell line was treated in vitro and in a nude mouse xenograft model. We conducted verification of binding ability of mutant NBS1 and downregulation of MRN complex, evaluation of transduction efficiency and combined antitumour activities. The antiangiogenesis mechanism was also investigated. Finally, we estimated the distribution of adenoviral vector in the liver.Results: the mutant NBS1 protein retains the binding ability and effectively suppresses the expression level of the MRN in infected cells. Transduction efficiency in vitro and cisplatin chemosensitisation were upregulated. The FGF2-Ad-NBS1 also showed detargeting the viral vectors away from the liver. The downregulation of NF-κB expression was supposed to correlate with increased antiangiogenesis.Conclusions: FGF2-targeted adenoviral system enhances the cisplatin chemosensitisation of mutant NBS1 and may avoid viral-associated liver toxicities. [ABSTRACT FROM AUTHOR]

Preemptive therapy is the standard strategy for preventing CMV disease after allogeneic hematopoietic SCT. In this study, unrelated BMT recipients were randomly assigned to a plasma real-time PCR group or an antigenemia group to compare the value of these monitoring tools for CMV reactivation. Ganciclovir (GCV) was started at 5 mg/kg/day when PCR reached 300 copies per ml or when antigenemia reached three positive cells per two slides. A total of 88 patients were randomized into the antigenemia group (n=45) or the PCR group (n=43). A significantly higher number of patients reached the threshold in the antigenemia group than in the PCR group (73.3 vs 44.2%, P=0.0089). However, only three patients (one in the antigenemia group and two in the PCR group) developed early CMV disease. These patients exclusively had colitis and were successfully treated with GCV or foscarnet. The median number of antigenemia-positive cells at the start of GCV was 47 in the PCR group. These findings suggest that antigenemia assay with the current cutoff was too sensitive and led to unnecessary use of GCV. However, the appropriateness of the threshold may be different by the methodology used, and therefore, it is difficult to generalize. [ABSTRACT FROM AUTHOR]

Background: This technical note introduces diffusion-weighted (DW) MR neurography (MRN) of the sacral plexus with unidirectional motion probing gradients (MPGs).Methods: This is compared with DW MRN with three-directional and six-directional MPGs.Results and Conclusion: This paper indicates that DW MRN of the sacral plexus should be performed with unidirectional MPGs. [ABSTRACT FROM AUTHOR]

Glimepiride and nateglinide are two common oral hypoglycemic agents currently being used with humans suffering from Type 2 diabetes mellitus. Neither drug has been tested with cats thus far and it is currently unknown whether either of these drugs exert any effect in cats or not. The objective of this study was to determine the effect of glimepiride and nateglinide on glucose and insulin responses in healthy control cats, in order to determine their potential use in diabetic cats. The intravenous glucose tolerance tests was carried out since it is an excellent test for evaluating pancreatic β-cell function for insulin secretion. Alterations in the insulin secretion pattern can be perceived as the earliest sign of β-cell dysfunction in many species, including cats. Nateglinide demonstrated a quick action/short duration type effect with serum glucose nadiring and insulin response peaking at 60 and 20 minutes, respectively. Alternatively, glimepiride is medium-to-long acting with serum glucose nadiring and insulin response peaking at 180 minutes and 60 minutes, respectively. Nateglinide's potency was evident allowing it to induce a 1.5-2 higher preliminary insulin peak (3.7 ± 1.1 pg/ml) than glimepiride's (2.5 ± 0.1 pg/ml), albeit only for a short period of time. Because glimepiride and nateglinide have a shared mode of action, no significant differences in overall glucose AUC (24,435 ± 2,940 versus 24,782 ± 2,354 mg min/dl) and insulin AUC (410 ± 192 versus 460 ± 159) in healthy control cats were observed. These findings may provide useful information when choosing a hypoglycemic drug suited for the treatment of diabetic cats depending on the degree of diabetes mellitus the cat is suffering from. [ABSTRACT FROM AUTHOR]

Background: Several human cancers have been found to contain cancer stem-like cells (CSCs) having cancer-initiating ability. However, only a few reports have shown the existence of CSCs in bone and soft tissue sarcomas. In this study, we identified and characterised side population (SP) cells that showed drug-resistant features in human bone sarcoma cell lines.Methods: In seven osteosarcoma cell lines (OS2000, KIKU, NY, Huo9, HOS, U2OS and Saos2) and in one bone malignant fibrous histiocytoma (MFH) cell line (MFH2003), the frequency of SP cells was analysed. Tumourigenicity of SP cells was assessed in vitro and in vivo. Gene profiles of SP cells and other populations (main population; MP) of cells were characterised using cDNA microarrays.Results: SP cells were found in NY (0.31%) and MFH2003 (5.28%). SP cells of MFH2003 formed spherical colonies and re-populated into SP and MP cells. In an NOD/SCID mice xenograft model, 1 x 10(3) sorted SP cell-induced tumourigenesis. cDNA microarray analysis showed that 23 genes were upregulated in SP cells.Conclusions: We showed that SP cells existed in bone sarcoma cell lines. SP cells of MFH2003 had cancer-initiating ability in vitro and in vivo. The gene profiles of SP cells could serve as candidate markers for CSCs in bone sarcomas. [ABSTRACT FROM AUTHOR]

Purpose: The aim of this study was to evaluate the effect of decreasing the irradiated cardiac volume in breast-conserving therapy (BCT) using breath-adapted radiation therapy (BART).Materials and Methods: The radiation therapy (RT)-computed tomography (CT) of 21 patients with left breast cancer during free breathing (FB), end-inspiration gating (IG) with audio-prompting, and deep inspiration breath-hold (DIBH) were subjected to BART planning analysis. Respiratory movement was monitored during CT scanning with the respiratory-gating system. The opposing tangential fields were planned for each respiratory-gated CT. The dose-volume histograms (DVHs) of the heart, lung, and breast of each respiratory phase were compared.Results: The median respiratory movement of the right chest wall was 5.6 mm with FB CT, 10.9 mm with audioprompting CT, and 21.3 mm from end-inspiration to DIBH. The median left ventricular volume receiving >50% of the prescribed dose was 2.9% for FB, 0.2% for IG, and 0% for DIBH. DIBH led to significant cardiac spattering effect compared with FB or IG (P < 0.01). The median lung volume receiving 20 Gy or more was 5.0% for FB, 4.7% for IG, and 4.3% for DIBH. There were no significant differences between each respiratory phase.Conclusion: We concluded that radiotherapy on the DIBH facilitates a reduction of the irradiated heart volume compared to FB and IG. [ABSTRACT FROM AUTHOR]

The purpose of this study was to assess the value of diffusion-weighted magnetic resonance imaging (DWI) in detecting esophageal cancer and assessing lymph-node status, compared with histopathological results. DWI was prospectively performed in 24 consecutive patients with esophageal cancer, using the diffusion-weighted whole-body imaging with background body signal suppression (DWIBS) sequence. DWIBS images were fused with T2-weighted images, and independently and blindly evaluated by three board-certified radiologists, regarding primary tumor detectability and lymph-node status. Apparent diffusion coefficients (ADCs) of the primary tumor and lymph nodes were also measured. Average primary tumor detection rate was 49.4%, average patient-based sensitivity and specificity for the detection of lymph-node metastasis were 77.8 and 55.6%, and average lymph-node group-based sensitivity and specificity were 39.4 and 92.6%. There were no interobserver differences among the three readers (P < 0.0001). Mean ADC of detected primary tumors was 1.26 +/- 0.29x10(-3) mm(2)/s. Mean ADC of metastatic lymph nodes (1.46 +/- 0.35x10(-3) mm(2)/s) was significantly higher (P < 0.0001) than that of nonmetastatic lymph nodes (1.15 +/- 0.24 mm(2)/s), but ADCs of both groups overlapped. In conclusion, this study suggests that DWI only has a limited role in detecting esophageal cancer and nodal staging. [ABSTRACT FROM AUTHOR]

The low-aspect-ratio ( A) reversed field pinch (RFP) offers attractive properties such as enhanced bootstrap current and simpler MHD mode dynamics. The RELAX (REversed field pinch of Low-Aspect ratio eXperiment) machine with the world’s lowest A of 2 ( R/ a = 0.5 m/0.25 m) has been constructed to explore the RFP properties in low- A regime. In flat-topped low- A RFP discharges in RELAX, plasma current of ~50 kA has been attained with discharge duration of ~2 ms. In round-topped discharges with plasma current of ~70 kA, quasi-periodic growth of a single helical mode has been observed. When the dominant m = 1/ n = 4 mode grows, the toroidal mode spectrum looks like that of the quasi-single helicity (QSH) RFP state with higher amplitude. MHD equilibrium analyses using a reconstruction code have shown that the bootstrap current fraction is lower than ~5% in the present RELAX plasmas, and it will be ~25% if we could achieve the plasma density of 4 × 1019 m−3 and electron temperature of 300 eV at plasma current of ~100 kA. [ABSTRACT FROM AUTHOR]

To evaluate the toxicity and efficacy of an i.v. preparation of BU (12.8 mg/kg), combined with CY (120 mg/kg), a prospective study was performed on 30 Japanese patients (median age, 30 years) with hematologic malignancies undergoing hematopoietic SCT (28 allogeneic transplants from an HLA-matched donor and 2 autologous transplants). There were no significant toxicities, and all but one patient showed evidence of granulocyte engraftment at a median of 14 days for allogeneic and 11 days for autologous transplantation. Grades II–IV acute and chronic GVHD occurred in 9 (9/27, 33%) and 16 patients (16/27, 59%), respectively. Non-relapse mortality at days 100 and 365 was 3 and 17%, respectively. The pharmacokinetics of i.v. BU showed close inter- and intrapatient consistency; the area under the plasma concentration–time curve of the first administration remained at less than 1500 μmol min/l in 27 of the 29 patients (93%), and between 900 and 1350 μmol min/l in 22 patients (73%). As all of the profiles overlap with data from non-Japanese patients, we conclude that racial factors may not seriously influence the bioactivity of i.v. BU.Bone Marrow Transplantation (2009) 43, 611–617; doi:10.1038/bmt.2008.372; published online 17 November 2008 [ABSTRACT FROM AUTHOR]

The muscle-related complications of fasciitis and myositis, caused by chronic GVHD after Allo-SCT are relatively rare, but at times will severely impair a patient's quality of life (QOL). We performed a retrospective analysis in Japanese Allo-SCT recipients to identify the incidence, risk factors and clinical features of fasciitis and myositis. In 1967 patients who underwent Allo-SCT between January 1994 and March 2005 and survived beyond 90 days post transplantation, eight patients developed fasciitis and nine patients developed myositis, with a 5-year cumulative incidence of 0.55% and 0.54%, respectively. The median time from SCT to the development of fasciitis and myositis was 991 and 660 days, respectively. PBSCT was a risk factor for developing fasciitis, but no risk factors were found for myositis. The response to immunosuppressive treatment was better in patients with myositis than fasciitis, and the overall survival after developing these symptoms was better in patients with myositis than those with fasciitis. An early diagnosis by a biopsy, which includes fascia and muscle or magnetic resonance imaging (MRI) and prompt treatment may be important to prevent an impairment of the patient's QOL with persistent disability.Bone Marrow Transplantation (2009) 43, 159–167; doi:10.1038/bmt.2008.297; published online 1 September 2008 [ABSTRACT FROM AUTHOR]

The purpose of our study was to evaluate the usefulness of diffusion-weighted imaging in predicting the responses to neoadjuvant therapy for head and neck squamous cell carcinomas. Diffusion-weighted, T2-weighted, and gadolinium-enhanced T1-weighted images were obtained from 28 patients with untreated head and neck squamous cell carcinomas with histological proof. A blinded radiologist evaluated the quantitative and qualitative signal intensities and apparent diffusion coefficients (ADCs) in the lesions on each sequence. All patients were treated by neoadjuvant therapies, and the post-therapeutic tumor regression rate was determined. Both the quantitative and qualitative signal intensities on diffusion-weighted images showed positive correlations (r = 0.367 and 0.412, p < .05), and the ADCs showed a weak, inversed correlation (r = -0.384, p < .05) with the tumor regression rates. Diffusion-weighted imaging including an assessment by ADCs may be able to predict tumor response to neoadjuvant therapy for head and neck squamous cell carcinomas. [ABSTRACT FROM AUTHOR]

The repulsive guidance molecule (RGM) is a membrane-bound protein that has diverse functions in the developing central nervous system. Identification of neogenin as a receptor for RGM provided evidence of its cell death-inducing activity in the absence of RGM. Here, we show that the serine/threonine kinase death-associated protein kinase (DAPK) is involved in the signal transduction of neogenin. Neogenin interacts with DAPK and reduces DAPK autophosphorylation on Ser308 in vitro. Neogenin-induced cell death is abolished in the presence of RGM or by blocking DAPK. Although neogenin overexpression or RGM downregulation in the chick neural tube in vivo induces apoptosis, coexpression of the dominant-negative mutant or small-interference RNA of DAPK attenuates this proapoptotic activity. Thus, RGM/neogenin regulates cell fate by controlling the DAPK activity.Cell Death and Differentiation (2008) 15, 1593–1608; doi:10.1038/cdd.2008.92; published online 27 June 2008 [ABSTRACT FROM AUTHOR]

RECK is a novel tumour suppressor gene that negatively regulates matrix metalloproteinases (MMPs) and inhibits tumour invasion, angiogenesis and metastasis. In the present study, we investigated the effects of epigallocatechin-3-gallate (EGCG), a major polyphenol in green tea, on the methylation status of the RECK gene and cancer invasion in oral squamous cell carcinoma cell lines. Our results showed that treatment of oral cancer cells with EGCG partially reversed the hypermethylation status of the RECK gene and significantly enhanced the expression level of RECK mRNA. Inhibition of MMP-2 and MMP-9 levels was also observed in these cells after treatment with EGCG. Interestingly, EGCG significantly suppressed cancer cell-invasive ability by decreasing the number of invasive foci (P<0.0001) as well as invasion depth (P<0.005) in three-dimensional collagen invasion model. Although further investigation is required to assess the extent of contribution of RECK on MMPs to the suppression of invasive behaviour, these results support the conclusion that EGCG plays a key role in suppressing cell invasion through multiple mechanisms, possibly by demethylation effect on MMP inhibitors such as RECK. [ABSTRACT FROM AUTHOR]

We tested the ability of two separate nuclear reaction models, the binary cascade and JQMD (Jaeri version of Quantum Molecular Dynamics), to predict the dose distribution in carbon-ion radiotherapy. This was done by use of a realistic simulation of the experimental irradiation of a water target. Comparison with measurement shows that the binary cascade model does a good job reproducing the spread-out Bragg peak in depth-dose distributions in water irradiated with a 290 MeV/u (per nucleon) beam. However, it significantly overestimates the peak dose for a 400 MeV/u beam. JQMD underestimates the overall dose because of a tendency to break a nucleus into lower- Z fragments than does the binary cascade model. As far as shape of the dose distribution is concerned, JQMD shows fairly good agreement with measurement for both beam energies of 290 and 400 MeV/u, which favors JQMD over the binary cascade model for the calculation of the relative dose distribution in treatment planning. [ABSTRACT FROM AUTHOR]

Myelin-associated glycoprotein (MAG) is a well-characterized axon growth inhibitor in the adult vertebrate nervous system. Several signals that play roles in inhibiting axon growth have been identified. Here, we report that soluble MAG induces activation of Rap1 in postnatal cerebellar granule neurons (CGNs) and dorsal root ganglion (DRG) neurons. The p75 receptor associates with activated Rap1 and is internalized in response to MAG. After MAG is applied to the distal axons of the sciatic nerves, the activated Rap1, internalized p75 receptor, and MAG are retrogradely trafficked via axons to the cell bodies of the DRG neurons. Rap1 activity is required for survival of the DRG neurons as well as CGNs when treated with MAG. The transport of the signaling complex containing the p75 receptor and Rap1 may play a role in the effect of MAG.Cell Death and Differentiation (2008) 15, 408–419; doi:10.1038/sj.cdd.4402278; published online 30 November 2007 [ABSTRACT FROM AUTHOR]

We propose a new scenario of gravity-mediated supersymmetry breaking (gravity mediation) in a supersymmetric Randall-Sundrum model, where the gravity mediation takes place at a low scale due to the warped metric. We investigate collider phenomenology involving the hidden sector field, and find a possibility that the hidden sector field can be produced at the LHC and the ILC. The hidden sector may no longer be hidden. [ABSTRACT FROM AUTHOR]

In applying Pressure-Sensitive Paint (PSP) to low-speed flow wind tunnel testing, it is important to minimize any measurement uncertainties. There are various error sources such as camera noise, misalignment of images due to model displacement and temperature distribution over the model. Among these factors, the effects of temperature distribution change during tests on pressure measurement accuracies were studied in the present paper. Pressure and temperature distributions over a simplified car model (1/10 scale Ahmed model) were measured using PSP and Temperature-Sensitive Paint (TSP). Sequential images were acquired at the same intervals over the entire test period, including for the conditions before and after the tunnel run. As a result, it was found that the measurement error caused by temperature distribution over the model could be reduced using a single-point temperature measurement. In addition, by measuring surface temperature distributions on the model using TSP, it was proved that the most accurate pressure measurement could be made by rationing the wind-off image acquired immediately after shutting down the tunnel to the wind-on image acquired immediately before shutting down the tunnel. Using the present measurement technique, complicated pressure fields over the Ahmed model were successfully visualized. [ABSTRACT FROM AUTHOR]

Platelet regeneration represents an important and separate element in the engraftment process for allogeneic stem cell transplantation. Fully automated flow cytometry using blood cell counters now allows reliable quantification of reticulated platelets, expressed as the immature platelet fraction (IPF). We studied the kinetics of IPF in six patients grafted with allogeneic peripheral blood stem cell transplantation (PBSCT), 12 patients with bone marrow transplantation (BMT) and seven patients with cord blood transplantation (CBT). Preconditioning therapy caused an immediate and rapid fall in tri-lineage hematopoiesis. IPF rose transiently above 3% after a mean duration of 11 days post-PBSCT, 18 days post-BMT and 19 days post-CBT. This was 1, 4 and 13 days earlier than platelet engraftment, respectively. A linear correlation model showed a close association between the rise of IPF and tri-lineage engraftment after transplantation. IPF counting may thus provide an accessible measure of thrombopoietic activity, leading to early evaluation of marrow function and allowing monitoring of platelet regeneration.Bone Marrow Transplantation (2007) 39, 501–507. doi:10.1038/sj.bmt.1705623; published online 5 March 2007 [ABSTRACT FROM AUTHOR]

Mitochondrial oxidative phosphorylation (OXPHOS) plays an important role in the pathophysiology of type 2 diabetes. Genes involved in OXPHOS have been reported to be down-regulated in skeletal muscle from patients with type 2 diabetes; however, hepatic regulation is unknown. We analysed expression of genes involved in OXPHOS from the livers of 14 patients with type 2 diabetes and 14 subjects with NGT using serial analysis of gene expression (SAGE) and DNA chip analysis. We evaluated the correlation between expression levels of genes involved in OXPHOS and the clinical parameters of individuals with type 2 diabetes and NGT. Both gene analyses showed that genes involved in OXPHOS were significantly upregulated in the type 2 diabetic liver. In the SAGE analysis, tag count comparisons of mitochondrial transcripts showed that ribosomal RNAs (rRNA) were 3.5-fold over-expressed, and mRNAs were 1.2-fold over-expressed in the type 2 diabetes library. DNA chip analysis revealed that expression of genes involved in OXPHOS, which correlated with several nuclear factors, including estrogen-related receptor-α or peroxisome proliferator-activated receptor-γ, was a predictor of fasting plasma glucose levels, independently of age, BMI, insulin resistance and fasting insulin levels ( p = 0.04). Surprisingly, genes involved in OXPHOS did not correlate with peroxisome proliferator-activated receptor-γ coactivator-1α or nuclear respiratory factor 1. Our results indicate that upregulation of genes involved in OXPHOS in the liver, which are regulated by different mechanisms from genes in the skeletal muscle, is associated with fasting hyperglycaemia in patients with type 2 diabetes. [ABSTRACT FROM AUTHOR]

Single phase (Zn,Fe)1− x O zincite solid solution samples have been prepared by high temperature equilibration in air and in reducing atmospheres, followed by quenching to room temperature. The Fe2+/Fe3+ concentrations in the samples have been determined using wet chemical and XPS techniques. Iron is found to be present in zincite predominantly in the form of Fe3+ ions. The transition from an equiaxed grain morphology to plate-like zincite crystals is shown to be associated with increasing Fe3+ concentration, increasing elongation in <001> of the hexagonal crystals and increasing anisotropic strain along the c-axis. The plate-like crystals are shown to contain planar defects and zincite polytypes at high iron concentrations. [ABSTRACT FROM AUTHOR]

Gangliosides have been proposed as modulators of transmembrane signaling. Recently, GM3, a glycosphingolipid containing monosaialic acids, is thought to be one of the key molecules of signal transduction in mammalian cells. In this study, we used mouse embryonic fibroblast cell lines (MEFs) established from sialyltransferase-I knockout mice (GM3 synthase KO mice) to evaluate the regulation of mitogenic signals by gangliosides. Cell proliferation assay revealed a higher growth potential of GM3 KO MEFs. Immunoblots showed upregulation of Ras/Raf/MEK/ERK pathway in GM3 KO MEFs, and these signals resulted in enhanced translocation of ERK into the nuclei. Further, both exogenous and endogenous add-back of GM3 decreased the activities of MAPK in GM3 KO MEFs. In addition, GM3 KO MEFs formed foci in high-density culture condition, and analyses of cell cycle modulators revealed the resistance of GM3 KO MEFs for entering cell cycle arrest. Finally, sustained expressions of c-Fos in GM3 KO MEFs were shown to correlate with DNA-binding activity between c-Fos and AP-1. These results demonstrate that the deletion of sialyltransferase-I changes the character of MEFs to a highly activated state of the MAPK pathway, indicating the critical role of GM3 as a regulator of membrane-transmitted signals.Oncogene (2006) 25, 3948–3955. doi:10.1038/sj.onc.1209416; published online 20 February 2006 [ABSTRACT FROM AUTHOR]

Study design:Analysis of answers to a new questionnaire.Objective:To examine current practice patterns of physicians in the urological surveillance and management of spinal cord injury (SCI) patients in Japan.Setting:Nationwide questionnaire survey to physicians in Japan.Methods:A Japanese version of the 14-item questionnaire survey carried out in US was mailed to 770 members of the Japanese Neurogenic Bladder Society (JNBS).Results:We received answers to our questionnaire from 333 (43.2%) members of JNBS. The responders were all urologists. For surveillance of the upper urinary tract (UUT), 239 (71.8%) respondents preferred abdominal ultrasound. Cystometry was performed routinely by 174 (52.3%) respondents for the evaluation of vesicourethral function. Cystoscopy was carried out in cases of hematuria (88.0%) and bladder stone (55.3%). Surveillance of the urinary tract was performed every year in 154 (46.2%). For detection of bladder cancer, which 119 (37.9%) respondents have experienced, 94.9% physicians perform cystoscopy, 76.3% urinary cytology, and 60.4% ultrasound. For initial treatment of detrusor-sphincter dyssynergia (DSD), 225 (69.2%) respondents chose α-blocker, and 94 (28.9%) chose clean intermittent catheterization (CIC) with/without anticholinergic agent(s). For initial treatment of overactive bladder, 245 (74.7%) chose anticholinergic agent(s) only and 63 (19.2%) chose anticholinergic agent(s) with CIC. For initial treatment of areflexic bladder, 233 (73.7%) chose CIC and 63 (19.9%) chose Credé maneuver or tapping.Conclusions:This survey shows that there are some differences in urological surveillance and management of SCI patients between Japan and the US. Reasons for the discrepancy should be examined.Spinal Cord (2006) 44, 362–368. doi:10.1038/sj.sc.3101854; published online 6 December 2005 [ABSTRACT FROM AUTHOR]

A dose-escalation study of irinotecan (CPT-11) combined with S-1, an oral dihydropyrimidine dehydrogenase inhibitory fluoropyrimidine, was performed to determine the maximum-tolerated dose (MTD), recommended dose (RD), dose-limiting toxicities (DLTs), and objective response rate (RR) in advanced gastric cancer (AGC). S-1 was administered orally at 80 mg m-2 day-1 from day 1 to 14 of a 28-day cycle and CPT-11 was given intravenously on day 1 and 8 at an initial dose of 70 mg m-2 day-1, stepping up to 100 mg m-2. The treatment was repeated every 4 weeks, unless disease progression was observed. In the phase I portion, the MTD of CPT-11 was presumed to be 100 mg m-2, because 66.6% of patients (two of three) developed DLTs. All three patients at the initial RD of CPT-11 (90 mg m-2) experienced grade 4 haematological or grade 3 nonhaematological toxicities at second course, followed by the dose reduction of CPT-11 from the third course. Considering safety and the ability to continue treatment, the final RD was determined to be 80 mg m-2. In the phase II portion, 42 patients including seven patients in the final RD phase I portion were evaluated. The median treatment course was five (range: 1-13). The incidences of severe (grade 3-4) haematological and nonhaematological toxicities were 19 and 10%, respectively, but all were manageable. The RR was 62% (26 of 42, 95% confidence interval: 47.2-76.6%), and the median survival time was 444 days. Our phase I/II trial showed S-1 combined with CPT-11 is effective for AGC and is well tolerated, with acceptable toxicity. [ABSTRACT FROM AUTHOR]

The spectral density technique is investigated as a basis for measuring turbulent fluxes of CO2 and water vapour over the sea using observations obtained on a well-designed pier of Kyoto University during September 20–22, 2000. By comparing the turbulent fluxes measured by the spectral density technique with those determined by the eddy correlation technique, a set of parameters of the non-dimensional gradient (φ) and Kolmogorov constant (a) was determined. The following parameters are the optimal selection under unstable conditions for the spectral density technique: φ c = φ q = (1 − 16z/L)−1/2; α c = 0.78 and α q = 0.76 Here, subscripts c and q refer to CO2 and water vapour; z is height and L is the Obukhov stability length. The present results demonstrate that with rugged sonic anemometer-thermometer sensors and computers, the spectral density technique applied over the sea has an accuracy comparable to that of the eddy correlation technique. [ABSTRACT FROM AUTHOR]

The predictive values of thymidylate synthase (TS) and dihydropyrimidine dehydrogenase (DPD) gene expressions were retrospectively evaluated in patients with gastric cancer treated by a regimen containing S-1. The study population consisted of 53 patients registered into different two phase II studies for metastatic gastric cancer; 27 patients treated by S-1-alone study: 26 patients treated with S-1 combined with irinotecan (CPT-11). TS and DPD gene expressions in primary tumours were measured by the real-time reverse transcription PCR method. There was no statistical difference in DPD gene expression in terms of response in cases treated with S-1 alone and those treated with S-1 plus CPT-11. TS mRNA of responding tumours was lower than that of nonresponding ones when treated with S-1 (P<0.005). In the S-1-alone group, taking TS cutoff as the median values, the response rate in the low TS group was 50%, but only 8% in the high TS group (P<0.05). Patients with low TS gene expression survived longer than those with high TS gene expression (P<0.0001). However, there was no statistically significant difference in response rate and survival between patients with low TS tumours and those with high TS tumours, when the cutoff was taken as the median value of TS gene expression in the group treated with S-1 plus CPT-11. In conclusion, treatment effects of S-1 monotherapy for gastric cancer were determined by the status of TS gene expression, regardless of DPD gene expression. TS predictive power was overcome by CPT-11 combination therapy with S-1. [ABSTRACT FROM AUTHOR]

The control of Cu precipitation at low temperatures, e.g., bake hardening of Cu bearing steels, has recently attracted considerable attention due to the potential of achieving good formability and high strength. An Fe-1.5 wt pct Cu alloy, solution treated and 10 pct prestrained, exhibits a two- step age-hardening behavior, i.e., a smaller, but substantial hardening around 200°C to 300°C and a major hardening around 500°C, while only the latter hardening occurs in undeformed specimens. The precipitation behavior of nanoscale Cu particles or bcc Cu clusters that plays a major role in age hardening was simulated by Cahn-Hilliard nonclassical nucleation theory and the Langer-Schwartz model. Simulation results are compared with the distribution of Cu particles observed under three-dimensional atom probe field ion microscope (3-D APFIM) and transmission electron microscope (TEM), and age hardening behavior as well. The increase in hardness in prestrained specimens at low temperatures (≤ 400°C) can be ascribed to Cu particles nucleated preferentially at dislocations or to Cu particles that were formed in the matrix as early as at dislocations presumably due to excess vacancies introduced by prestraining. [ABSTRACT FROM AUTHOR]

Presents a study that examined the usefulness of caffeine test in predicting flutamide-induced hepatic injury in patients with prostate cancer. Chromatogram of urine sample after coffee intake; Relationship of alanine aminotransferase and urinary molar ratio after coffee intake in patients treated with flutamide; Summary of clinical data and urinary molar ratio in patients administered with flutamide.

Cimetidine, a H(2) receptor antagonist, has been reported to improve survival in gastrointestinal cancer patients. These effects have largely been attributed to the enhancing effects of cimetidine on the host's antitumour cell-mediated immune response, such as inhibition of suppressor T lymphocyte activity, stimulation of natural killer cell activity and increase of interleukin-2 production from helper T lymphocytes. We conducted an in vitro study on the effects of cimetidine on differentiation and antigen presenting capacity of monocyte-derived dendritic cells from advanced colorectal cancer patients and normal controls. As a result, an investigation of expression of surface molecules associated with dendritic cells by flow cytometric analyses showed that cimetidine had no enhancing effect on differentiation of dendritic cells from cancer patients and normal controls. An investigation of [(3)H]thymidine incorporation by allogeneic mixed lymphocyte reactions revealed that cimetidine increased the antigen presenting capacity of dendritic cells from both materials. Moreover, a higher antigen presenting capacity was observed in advanced cancer patients compared to normal controls. These effects might be mediated via specific action of cimetidine and not via H(2) receptors because famotidine did not show similar effects. Our results suggest that cimetidine may enhance the host's antitumour cell-mediated immunity by improving the suppressed dendritic cells function of advanced cancer patients. [ABSTRACT FROM AUTHOR]

To investigate the clinical significance of circulating angiogenic factors, especially in association with early relapse of osteosarcoma, we quantified pre-therapeutic levels of vascular endothelial growth factor, basic fibroblast growth factor and placenta growth factor in the sera of 16 patients with osteosarcoma using an enzyme-linked immunosorbent assay. After a 1-year follow-up, the serum level of angiogenic factors was analysed with respect to microvessel density of the biopsy specimen and clinical disease relapse. The serum vascular endothelial growth factor levels were positively correlated with the microvessel density with statistical significance (P=0.004; Spearman rank correlation) and also significantly higher in seven patients who developed pulmonary metastasis than the remaining nine patients without detectable disease relapse (P=0.0009; The Mann-Whitney U-test). In contrast, the serum levels of basic fibroblast growth factor or placenta growth factor failed to show significant correlation with the microvessel density or relapse of the disease. Although there was no significant correlation between serum vascular endothelial growth factor levels and the tumour volume, the serum vascular endothelial growth factor levels were significantly higher in patients with a vascular endothelial growth factor-positive tumour than those with a vascular endothelial growth factor-negative tumour. These findings suggest that the pre-therapeutic serum vascular endothelial growth factor level reflects the angiogenic property of primary tumour and may have a predictive value on early disease relapse of osteosarcoma. [ABSTRACT FROM AUTHOR]

From propionate-containing solutions of Np(V), the crystalline compounds NpO2OOCC2H5· nH2O with n = 1 or 2 and M(NpO2)2(OOCC2H5)3·H2O with M = NH4 or Cs were separated. Their X-ray powder patterns were recorded and behavior at heating was studied. The IR and electronic absorption spectra suggest that, in these compounds, the NpO2 + ions are coordinated with each other to form cation-cation bonds involving all “yl” oxygen atoms. [ABSTRACT FROM AUTHOR]

Membrane conductance of cultured rabbit articular chondrocytes was characterized by means of the patch-clamp technique. The resting membrane potential of the articular chondrocytes was about ?42 mV. The membrane potential shifted in accordance with the prediction by the Nernst equation for Cl? when intracellular and extracellular concentrations of Cl? were changed. On the other hand, change in extracellular concentration of K+ produced no shift in the membrane potential of chondrocytes. The Cl? channel blocker 4-acetamido-4?-isothiocyanatostilbene-2?2-disulfonic acid (SITS) depolarized the membrane potential. These findings suggest that the membrane potential of the chondrocytes is determined mainly by Cl? conductance. Using the cell-attached patch-clamp method, a large unitary conductance of 217 pS was observed in the articular chondrocytes. The unitary current was reversibly blocked by SITS. Therefore, the unitary current was carried by Cl?. The Cl? channel showed voltage-dependent activation and the channels exhibited long-lasting openings. Therefore, the membrane potential of rabbit cultured articular chondrocytes was mainly determined by the activities of the large-conductance and voltage-dependent Cl? channels. [ABSTRACT FROM AUTHOR]

Osteocalcin is a noncollagenous protein that is abundant in mineralized bone matrix. Mice have a gene cluster of osteocalcin that consists of OG1, OG2, and ORG. We established a new method to directly analyze the expression levels of OG1, OG2, and ORG mRNAs relative to total osteocalcin mRNA. They were amplified as 371-bp fragments by reverse transcription-polymerase chain reaction (RT-PCR) at the same time using common primers, digested with ApaLI, and separated in a polyacrylamide gel. ApaLI digestion did not affect the mobility of the OG1-derived 371-bp fragment, whereas both 371-bp fragments, derived from OG2 and ORG, were digested into 350 bp. Total RNA prepared from mouse bone was then subjected to RT-PCR followed by ApaLI digestion. OG1 and OG2 mRNAs were found to be expressed at ratios of 80%-86% and 14%-20%, respectively, to the total osteocalcin mRNA in mouse bone. The ratios were almost constant in various bones in vivo, independent of the animal's genetic background, age, or gender, or different parts of bone. RT-PCR using specific primers revealed that mouse bone tissues strongly expressed osteocalcin mRNA derived from OG1 and OG2, but not ORG. In contrast, cells cultured in vitro showed different expression ratios of osteocalcin mRNA: 53%-65% for OG1 and 35%-47% for OG2 to the total osteocalcin mRNA in the osteoblast cell line and primary osteoblasts in culture even though they formed many mineralized bone nodules. Similar results were obtained in both KS483 osteoblasts and C2C12 myoblasts, when they were cultured with bone morphogenetic protein-2 (BMP-2) to induce osteocalcin mRNA. Taken together, these findings indicate that OG1 is the predominant transcript among the three osteocalcin genes in mouse bone in vivo. It is also suggested that the expression of OG1 and OG2 is regulated differently in bone tissues and osteoblast cultures. [ABSTRACT FROM AUTHOR]

Glutamine:fructose-6-phosphate amidotransferase (GFAT1) is the rate-limiting enzyme in the hexosamine biosynthetic pathway, which plays an important role in hyperglycemia-induced insulin resistance. To evaluate the role of GFAT1 expression, we analyzed the expression profiles of GFAT1 mRNA in various human tissues using reverse transcriptase-polymerase chain reaction. We report here the identification and cDNA cloning of a novel GFAT1 splice variant expressed abundantly in skeletal muscle and heart. This subtype, designated GFAT1-L, contains a 54-bp insertion within the GFAT1 coding sequence. Recombinant GFAT1-L protein possessed functional GFAT activities and biochemical characteristics similar to GFAT1. Previously, GFAT1 was considered a simplex enzyme. The identification of a novel GFAT1 subtype possessing functional enzymatic activity and tissue-specific expression should provide additional insight into the mechanism of skeletal muscle insulin resistance and diabetes complications. [ABSTRACT FROM AUTHOR]

To clarify the pharmacokinetic properties of idarubicin (IDA) in Japanese patients and to clarify the relationship between the pharmacokinetic parameters of IDA or idarubicinol (IDAol), an active metabolite of IDA, and leukocytopenia or neutropenia, we examined the pharmacokinetics of IDA in patients with malignant lymphoma. Nine of 21 patients registered in an early phase II study of IDA were enrolled in the pharmacokinetic study. IDA (12 or 15 mg/m2) was administered by intravenous infusion for 5 minutes. The elimination half lives (t 1/2) of IDA were 11.0 hours and 12.5 hours after administration of 12 and 15 mg/m2 IDA, respectively. IDAol appeared rapidly both in plasma and in blood cells, and its concentrations exceeded those of IDA within 4 hours. IDAol had a very long t 1/2 (69.2 hours and 70.0 hours for 12 and 15 mg/m2, respectively). The areas under the concentration curves of IDAol in plasma were 3.4 and 5.8 times higher than those of IDA after administration of 12 and 15 mg/m2 IDA, respectively. The t 1/2 of IDAol in plasma correlated significantly with the nadir of neutrophils, and the steady-state volume of distribution of IDA in plasma and in blood cells correlated significantly with the nadirs of white blood cells and neutrophils. These results suggest that both IDA and IDAol play an important role in leukocytopenia or neutropenia. No substantial differences between Japanese and Caucasian people in the pharmacokinetics of IDA were apparent. [ABSTRACT FROM AUTHOR]