Determination of the hyperfine coupling tensor in organic conductors κ-(BEDT-TTF)2X (X=Cu[N(CN)2]Br, Cu(NCS)2) on central ¹³C sites.

Although the organic superconductors κ-(BEDT-TTF)2X (X=Cu[N(CN)2]Br and Cu(NCS)2) have been studied by NMR spectroscopy, hyperfine coupling tensors are required to quantify NMR spectra. Angle dependences of NMR spectra were measured to determine hyperfine coupling tensors applicable to further NMR assessments of attractive physical phenomena on κ-salts. The tensors of κ-(BEDT-TTF)2X and ß(')-(BEDT-TTF)2ICl2 salts were compared to determine the hyperfine coupling mechanism in organic metals, with the results indicating that off-site dimer contribution should be considered. We also report the electron correlation of these salts and further application of the tensors.

Regenerative medicine legislation in Japan for fast provision of cell therapy products.

A new legal framework consisting of three laws for cell-based and tissue-based therapies went into effect in November 2014 in Japan. Among the provisions of the laws, the Pharmaceuticals, Medical Devices, and Other Therapeutic Products Act (PMD Act) allows conditional and time-limited approval for regenerative medical products based on the ensured safety and estimated efficacy in small-scale clinical trials. The new legislation is expected to accelerate safe and fast provision of the innovative products to patients with intractable diseases.

Controlling traffic jams by time modulating the safety distance.

The possibility of controlling traffic dynamics by applying high-frequency time modulation of traffic flow parameters is studied. It is shown that the region of the car density where the uniform (free) flow is unstable changes in the presence of time modulation compared with the unmodulated case. This region shrinks when the speed-up of cars does not exceed some critical value and expands in the opposite case. The flux of the time-modulated flow is an increasing function of the amplitude of the modulation for traffic flows whose density is larger than 1/h where h is the safety distance in the nonmodulated case, while it is a decreasing function in the opposite case. In other words, the safety distance time modulation facilitates car propagation in the case when the mean distance between cars in the congestive traffic is less than h and hinders it when the neighboring cars in the flow are well separated. A link between a microscopic description and the macroscopic fundamental diagram is established.

Brain-derived neurotrophic factor/tropomyosin-related kinase B pathway in gastric cancer.

BACKGROUND: Brain-derived neutrophic factor (BDNF) is a member of the neutrophin family that is known to activate the high-affinity tropomyosin-related receptor kinase B (TrkB). This study aimed to clarify the clinical and biological significance of the BDNF/TrkB pathway in gastric cancer. METHODS: We analysed BDNF and TrkB expression in gastric cancer samples by real-time reverse transcription PCR and immunohistochemistry. To investigate the biological role of BDNF/TrkB axis, recombinant human BDNF (rhBDNF) and the Trk antagonist K252a were used for in vitro and in vivo analysis. RESULTS: The BDNF expression at the invasive front of primary tumours was significantly elevated compared with that in the tumour core and adjacent normal mucosa. Increased BDNF expression at the invasive front was significantly correlated with factors reflecting disease progression, and poor prognosis. Increased co-expression of the BDNF/TrkB axis was significantly correlated with poor prognosis. Gastric cancer cells expressed BDNF, and administration of rhBDNF promoted proliferation, migration, invasion, and inhibition of anoikis. These effects were generally inhibited by K252a. In an in vivo assay, BDNF(+)/TrkB(+) gastric cancer cells injected into nude mice established peritoneal dissemination, whereas K252a inhibited tumour growth. CONCLUSION: The BDNF/TrkB pathway might be deeply involved in gastric cancer disease progression.

Relationship between salivary antioxidant capacity and phases of the menstrual cycle.

BACKGROUND AND OBJECTIVE: Reactive oxygen species and free radicals are involved in the pathogenesis of periodontal disease. Previous studies have shown that the stage of the menstrual cycle is associated with the levels of gingival inflammation and discomfort. This study examined changes in salivary antioxidant activities, clinical parameters and bacterial levels during the menstrual cycle. MATERIAL AND METHODS: The study group consisted of 16 women with periodontitis and 12 healthy women. Clinical and bacterial measurements were performed for all subjects during the ovulatory and follicular phases. RESULTS: Salivary antioxidant activity during the ovulatory phase was significantly lower than during the follicular phase in the women with periodontitis. The antioxidant activity in all subjects during the ovulatory phase was negatively correlated with Prevotella intermedia (r = -0.430; p = 0.023) and total bacterial counts (r = -0.496; p = 0.007); however, these correlations were not significant for subjects in the follicular phase. CONCLUSION: This study showed that salivary antioxidant capacity decreased, while bleeding on probing and P. intermedia increased, over the course of the menstrual cycle in women with periodontitis. Antioxidant capacity could be involved in the pathogenesis of periodontitis.

Clinical correlations and prognostic relevance of tissue angiogenic factors in patients with gastric cancer.

AIMS: To evaluate the relationship between vascular endothelial growth factor (VEGF) and hepatocyte growth factor (HGF) levels in gastric cancer tissue and clinicopathological features and to determine whether these factors were correlated with survival. MATERIALS AND METHODS: We analysed tissue samples from 58 patients with gastric cancer and used 24 normal gastric mucosae as controls. Tissue levels of VEGF and HGF were measured in tissue extracts by enzyme-linked immunosorbent assay. RESULTS: HGF and VEGF levels were significantly higher in gastric cancer tissue than in matched normal gastric mucosa. VEGF levels were significantly increased in cancer tissue from cases involving lymphatic invasion. HGF levels were significantly increased according to the disease stage. Patients with high levels of VEGF or HGF showed significantly worse survival rates than patients with low levels. Using multivariate analysis, a high level of VEGF or HGF was an independent factor predicting poor survival. CONCLUSIONS: Intratumoral levels of HGF and VEGF are an important prognostic determinant in gastric cancer. The current findings suggest that high concentrations of HGF and VEGF may induce aggressive tumour growth and metastasis.

Relationship between oral malodor and the menstrual cycle.

BACKGROUND AND OBJECTIVE: Sex hormones have been suggested to be important modifying factors that may influence the pathogenesis of periodontal disease. This study examined changes in volatile sulfur compounds (VSC) levels, clinical parameters and bacterial levels during the menstrual cycle. MATERIAL AND METHODS: The study group consisted of 10 female subjects with periodontitis and 12 periodontally healthy female subjects. Clinical and bacterial measurements were performed for all subjects during the ovulation and follicular phases of the menstrual cycle. RESULTS: Bleeding on probing (BOP) was significantly increased in the ovulation phase in periodontitis subjects but not in healthy subjects. The VSC levels in subjects with periodontitis increased 2.2-fold in the ovulation phase compared with the follicular phase. In the ovulation phase, VSC levels and BOP were significantly higher in subjects with periodontitis than in healthy subjects. The number, and salivary levels, of Prevotella intermedia in subjects with periodontitis were significantly higher in the ovulation phase than in the follicular phase. CONCLUSION: The present study indicated changes in VSC, BOP and P. intermedia during the menstrual cycles of women with periodontitis.

[False-negative cases of axillary ultrasonography: how much size?].

PURPOSE/AIM: 1. To review the sonographic criteria of axillary lymph node status in breast cancer patients. 2. To understand imaging pathologic correlations that the false-negative cases of axillary ultrasonography. CONTENT ORGANIZATION: The sonographic criteria, the accuracy of sonographic axillary ultrasonography, imaging pathologic correlations in false-negative cases, measurement of largest malignant focus size in lymph node, classification of ratio of malignant focus size, ratio of micro metastasis. SUMMARY: 1. Recently, lymph node evaluation that using serial section and immunohistochemical stains makes it difficult to detect imaging modalities. 2. Ultrasonography is limited how to detect the example of sentinel lymph node biopsy non-indications.

Evaluation and treatment for spinal cord tethering in patients with anorectal malformations.

BACKGROUND: It has recently been recognized that there is a close relationship between spinal cord tethering (SCT) and congenital anorectal malformation (ARM). PATIENTS AND METHODS: We evaluated spinal MRI examinations of 28 patients with ARM (14 boys and 14 girls) aged 5 months to 9 years. All patients diagnosed with SCT subsequently underwent operation. Patients were divided into high and low type ARM groups. We reviewed the relationship between SCT and ARM, and evaluated the untethering surgery. RESULTS: We evaluated 14 boys (high, 9; low, 5) and 14 girls (high, 4; low, 10). Of these 28 patients, 13 had SCT on MRI. Five out of 13 patients with high type ARM and 8 out of 15 patients with low type ARM had SCT. Seven out of 10 girls with low type ARM had SCT. Ten of these 13 patients with SCT experienced bowel/urological/orthopedic symptoms. SCT symptoms progressed prior to operation in the 2 patients who underwent untethering surgery a few years after their initial MRI examination. Postoperatively, orthopedic symptoms disappeared completely in all patients, but other symptoms did not. CONCLUSIONS: Based on the results of this study, we recommend routine MRI examination of patients with ARM and early untethering surgery in cases with SCT.

Proximity of pseudogapped superconductor and commensurate antiferromagnet in a quasi-two-dimensional organic system.

We performed the single-crystal 13C NMR studies on a quasi-two-dimensional system, deuterated kappa-(BEDT-TTF)2Cu[N(CN)(2)]Br, which is just on the border of the Mott transition. The NMR spectra are separated into two parts coming from the metallic (superconducting) and insulating phases due to the phase separation at low temperature. The examination of the separated spectra revealed that the Mott transition in this system is characterized by the first-order transition between the pseudogapped superconductor and the simplest commensurate antiferromagnet with a moment of 0.26 mu(B)/dimer.

Vascular endothelial growth factor mRNA synthesis by peripheral blood mononuclear cells in patients with acute myocardial infarction.

We studied vascular endothelial growth factor (VEGF) mRNA synthesis by peripheral blood mononuclear cells (PBMCs) in 30 patients with acute myocardial infarction (AMI) and 20 healthy individuals. PBMCs were isolated from all patients on days 3 and 14 after the onset of aMI, and from all of control individuals. To prepare samples containing identical amounts of GAPDH cDNA, competitive PCR was performed by co-amplifying serial dilutions of GAPDH mutant templates. Next, to measure VEGF cDNA quantitatively in the samples containing identical amounts of GAPDH, we also used competitive PCR by co-amplifying mutant templates of VEGF. The serum VEGF concentrations on day 14 in patients with aMI were measured by an ELISA method. Higher levels of VEGF mRNA in PBMCs were present on day 14 than either on day 3 or in the control group. Serum VEGF concentrations correlated with the VEGF mRNA levels of PBMCs on day 14. Peak serum CK levels correlated well with VEGF mRNA levels of PBMCs on day 14. The present findings suggest that PBMCs may be one of the candidates responsible for elevated circulatory VEGF protein following aMI. In addition, VEGF mRNA may be overexpressed in PBMCs in response to cardiac muscle damage.

Ferromagnetic and antiferromagnetic fluctuations of pi-d itinerant electrons disclosed by band-selective NMR.

We present a band-selective NMR method to probe the constituent electronic bands separately in the condensed molecular matter. This method is applied to an organic-inorganic pi-d hybrid metal, and its utility to give the static and dynamic spin susceptibilities for the constituent bands is demonstrated. The analysis of the results uncovers an exotic feature; the antiferromagnetic and ferromagnetic correlations are enhanced in separate bands in a single material. This finding provides a novel scope connecting the metal-insulator transitions in this system and the manganese oxides.

HMG-CoA reductase inhibitor mobilizes bone marrow--derived endothelial progenitor cells.

Endothelial progenitor cells (EPCs) have been isolated from circulating mononuclear cells in peripheral blood and shown to incorporate into foci of neovascularization, consistent with postnatal vasculogenesis. These circulating EPCs are derived from bone marrow and are mobilized endogenously in response to tissue ischemia or exogenously by cytokine stimulation. We show here, using a chemotaxis assay of bone marrow mononuclear cells in vitro and EPC culture assay of peripheral blood from simvastatin-treated animals in vivo, that the HMG-CoA reductase inhibitor, simvastatin, augments the circulating population of EPCs. Direct evidence that this increased pool of circulating EPCs originates from bone marrow and may enhance neovascularization was demonstrated in simvastatin-treated mice transplanted with bone marrow from transgenic donors expressing beta-galactosidase transcriptionally regulated by the endothelial cell-specific Tie-2 promoter. The role of Akt signaling in mediating effects of statin on EPCs is suggested by the observation that simvastatin rapidly activates Akt protein kinase in EPCs, enhancing proliferative and migratory activities and cell survival. Furthermore, dominant negative Akt overexpression leads to functional blocking of EPC bioactivity. These findings establish that augmented mobilization of bone marrow-derived EPCs through stimulation of the Akt signaling pathway constitutes a novel function for HMG-CoA reductase inhibitors.

[Significance of retardation of abnormal uptake of iodine-123-beta-methyl-p-iodophenyl-pentadecanoic acid myocardial scintigraphy in patients with vasospastic angina].

OBJECTIVES: This study investigated retardation of abnormal uptake of iodine-123-beta-methyl-p-iodophenyl-pentadecanoic acid(BMIPP) scintigraphy in patients with vasospastic angina. METHODS: Twenty-three patients with vasospastic angina showed abnormal uptake of BMIPP before medical treatment and had coronary vasospasm induced by acetylcholine. The patients were divided into two groups according to uptake of BMIPP after medical treatment: retardation of abnormal uptake of BMIPP(Group R, n = 4) and normal uptake of BMIPP(Group N, n = 19). Frequency of chest pain, medical treatment and autonomic nervous activity were compared between the two groups. Furthermore, the frequency of chest pain and uptake of BMIPP in group R were obtained after intensive medical treatment. Autonomic nervous activity was evaluated by heart rate variability on Holter electrocardiography. Heart rate variability contained high-frequency elements(HF; 0.15-0.4 Hz) and low-frequency elements(LF; 0.04-0.15 Hz). LF/HF was estimated for sympathetic nervous activity and HF was estimated for parasympathetic nervous activity. Daytime and nighttime autonomic nervous activity were compared between the two groups. RESULTS: The frequency of chest pain was higher in Group R than in Group N(p < 0.05). Medical treatment was not different between the two groups. Circadian variation of sympathetic and parasympathetic nervous activity were absent in Group R. During the nighttime, Group R showed higher sympathetic nervous activity(p < 0.05) and lower parasympathetic nervous activity(p < 0.01) than Group N. The frequency of chest pain was significantly lower after intensive medical treatment(p < 0.05), and uptake of BMIPP returned to normal in Group R. We suspected that the disorder in autonomic nervous activity was more severe in Group R, and thus induced coronary vasospasm. CONCLUSIONS: Retardation of abnormal uptake of BMIPP in patients with vasospastic angina indicates poor control of coronary vasospasm. Uptake of BMIPP is useful in the evaluation of coronary vasospasm control in such patients.

Ischemic preconditioning upregulates vascular endothelial growth factor mRNA expression and neovascularization via nuclear translocation of protein kinase C epsilon in the rat ischemic myocardium.

Ischemic preconditioning (IP) exerts cardioprotection through protein kinase C (PKC) activation, whereas myocardial ischemia enhances vascular endothelial growth factor (VEGF) mRNA expression. However, the IP effect or the involvement of PKC on the VEGF expression is unknown in myocardial infarction. We investigated whether IP enhances VEGF gene expression and angiogenesis through PKC activation in the in vivo myocardial infarction model. Sprague-Dawley rats were assigned into the following 3 groups: the sham group; the IP group, which underwent 3 cycles of 3 minutes of ischemia and 5 minutes of reperfusion (IP procedure); and the non-IP group. The latter 2 groups were subsequently subjected to left anterior descending coronary artery occlusion. To examine the involvement of PKC, the PKC inhibitor chelerythrine (5 mg/kg) or bisindolylmaleimide (1 mg/kg) was injected intravenously before the IP procedures. PKCepsilon was translocated to the nucleus after 10 minutes of ischemia after the IP procedure but was not translocated in the non-IP and the sham groups. VEGF mRNA expression 3 hours after infarction was significantly higher in the IP group than in the non-IP and the sham groups. Capillary density in the infarction was significantly higher, whereas the infarct size was smaller in the IP group than in the non-IP group at 3 days of infarction. Chelerythrine but not bisindolylmaleimide blocked all of the IP effects on the nuclear translocation of PKCepsilon, enhancement of VEGF mRNA expression and angiogenesis, and infarct size limitation. These results show that IP may enhance VEGF gene expression and angiogenesis through nuclear translocation of PKCepsilon in the infarcted myocardium.

Therapeutic potential of ex vivo expanded endothelial progenitor cells for myocardial ischemia.

BACKGROUND: We investigated the therapeutic potential of ex vivo expanded endothelial progenitor cells (EPCs) for myocardial neovascularization. METHODS AND RESULTS: Peripheral blood mononuclear cells obtained from healthy human adults were cultured in EPC medium and harvested 7 days later. Myocardial ischemia was induced by ligating the left anterior descending coronary artery in male Hsd:RH-rnu (athymic nude) rats. A total of 10(6) EPCs labeled with 1,1'-dioctadecyl-1 to 3,3,3',3'-tetramethylindocarbocyanine perchlorate were injected intravenously 3 hours after the induction of myocardial ischemia. Seven days later, fluorescence-conjugated Bandeiraea simplicifolia lectin I was administered intravenously, and the rats were immediately killed. Fluorescence microscopy revealed that transplanted EPCs accumulated in the ischemic area and incorporated into foci of myocardial neovascularization. To determine the impact on left ventricular function, 5 rats (EPC group) were injected intravenously with 10(6) EPCs 3 hours after ischemia; 5 other rats (control group) received culture media. Echocardiography, performed just before and 28 days after ischemia, disclosed ventricular dimensions that were significantly smaller and fractional shortening that was significantly greater in the EPC group than in the control group by day 28. Regional wall motion was better preserved in the EPC group. After euthanization on day 28, necropsy examination disclosed that capillary density was significantly greater in the EPC group than in the control group. Moreover, the extent of left ventricular scarring was significantly less in rats receiving EPCs than in controls. Immunohistochemistry revealed capillaries that were positive for human-specific endothelial cells. CONCLUSIONS: Ex vivo expanded EPCs incorporate into foci of myocardial neovascularization and have a favorable impact on the preservation of left ventricular function.

Bone marrow as a source of endothelial cells for natural and iatrogenic vascular repair.

Postnatal neovascularization has previously been considered synonymous with angiogenesis, but the finding that circulating endothelial progenitor cells (EPCs) may home to sites of neovascularization and there differentiate into endothelial cells (ECs) is consistent with "vasculogenesis," through which the primordial vascular network is established in the embryo. Our findings suggest that growth and development of new blood vessels in the adult are not restricted to angiogenesis but encompass vasculogenesis as well, although the proportional contributions remain to be clarified. Likewise, augmented or retarded neovascularization probably involves enhancement or impariment of the vasculogenesis process.

Efficacy of adding multiple doses of oxitropium bromide to salbutamol delivered by means of a metered-dose inhaler with a spacer device in adults with acute severe asthma.

BACKGROUND: The efficacy of combination therapy adding multiple doses of anticholinergics to beta(2)-agonists to improve outcome has not been established in adults with acute severe asthma. OBJECTIVE: This study was undertaken to compare the outcome of adults with acute severe asthma treated with 4 puffs of salbutamol (100 microg/actuation) every 20 minutes for 3 doses plus 4 puffs of oxitropium bromide (100 microg/actuation) with each of the 3 salbutamol doses versus salbutamol alone administered by means of a metered-dose inhaler with a spacer device. METHODS: A randomized, single-blind, placebo-controlled study was performed in 74 patients between 18 and 55 years old presenting to the emergency department (ED) for treatment of acute asthma with a peak expiratory flow (PEF) of 50% or less than the normal predicted value. The primary endpoint was improvement in PEF over the course. The secondary endpoint was the need for additional ED treatment at 120 minutes. RESULTS: The increase in PEF over the course was significantly greater in the oxitropium plus salbutamol treatment group (P <.0001). The mean absolute difference in PEF at 120 minutes for combination therapy compared with salbutamol alone was 37.8 L/min (P =.001). In addition, the proportion of need for additional ED treatment was less in the combination group than the group receiving salbutamol alone (odds ratio, 0.32; 95% confidence interval, 0.11-0.90). CONCLUSION: Adding multiple doses of oxitropium bromide to salbutamol delivered by means of a metered-dose inhaler with a spacer device for acute severe asthma produces a significant improvement in lung function and reduces the need for additional ED treatment.

Phylogenic analysis of echovirus type 30 isolated from a large epidemic of aseptic meningitis in Japan during 1997-1998.

During 1997 to 1998, a nationwide epidemic of aseptic meningitis occurred in Japan. More than 4,500 isolates from patients with aseptic meningitis were identified as echovirus type 30. To investigate the character of these isolates, we examined the nucleotide sequences of thirty-seven geographical representatives and compared them with 50 strains isolated during the past 20 years. The phylogenic analysis used partial sequences from either the VP1 or VP4-VP2 region of the viral capsid. This analysis revealed that the isolates were divided into six genomic groups. All isolates identified during 1997-1998 belonged to only two genomic groups; these two groups are thought to be the causative viral agents involved in the recent epidemic.