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We propose a new scheme for producing medical 15O isotopes using a water target, for blood flow examination with Positron Emission Tomography. The 15O radioisotopes are produced via the 16O(γ,n)15O reaction in a water target. A simulation study has been carried out to determine the productivity of radioactive [15O]-water using bremsstrahlung γ–rays by a 40 MeV electron beam of 100 μA. The productivity of [15O]-water with an activity of 6.9 GBq was confirmed by a 10-min radiation exposure. Produced [15O]-water is easily and rapidly sent from the production site to a patient site through a transport tube. [ABSTRACT FROM AUTHOR]

The worldwide supply of 99Mo isotopes now encounters a serious crisis due to difficulties in sustainable production by research nuclear reactors. We report the experimental data for the 99mTc and impurity isotopes produced via the natMo(γ, n) reaction with bremsstrahlung γ-rays generated using a 30 MeV electron beam. The supply feasibility of 99mTc isotopes via the natMo(γ, n) reaction is discussed on the basis of the obtained data. [ABSTRACT FROM AUTHOR]

Objective:To compare two strategies to potentiate the effects of placental transfusion in infants born at <29 weeks of gestation.Study design:Twenty infants who received one-time umbilical cord milking after umbilical cord cutting were compared with 20 infants from a previous study group who received multiple-time umbilical cord milking. The primary outcome measurements were the probability of not needing a red blood cell (RBC) transfusion during the hospital stay and the total number of RBC transfusions within 21 days after birth.Result:There was no significant difference in the probability of not needing a transfusion during the hospital stay (P=0.75) and the mean number of RBC transfusions given within the first 21 days of life (1.1±1.8 for the one-time umbilical cord-milking group vs 0.7±1.2 for the multiple-time umbilical cord-milking group, P=0.48).Conclusion:One-time umbilical cord milking after umbilical cord cutting had similar beneficial effects to multiple-time umbilical cord milking before umbilical cord cutting in very premature infants. [ABSTRACT FROM AUTHOR]

p53 is an established tumor suppressor that can activate the transcription of multiple target genes. Recent evidence suggests that p53 may contribute to the regulation of cell invasion and migration. In this study, we show that the forkhead box transcription factor FOXF1 is a novel target of the p53 family because FOXF1 is upregulated by p53, TAp73 and TAp63. We show that FOXF1 is induced upon DNA damage in a p53-dependent manner. Furthermore, we identified a response element located within the FOXF1 gene that is responsive to wild-type p53, TAp73β and TAp63γ. The ectopic expression of FOXF1 inhibited cancer cell invasion and migration, whereas the inactivation of FOXF1 stimulated cell invasion and migration. We also show that FOXF1 regulates the transcriptional activity of E-cadherin (CDH1) by acting on its FOXF1 consensus binding site located upstream of the E-cadherin gene. Collectively, our results show that FOXF1 is a p53 family target gene, and our data suggest that FOXF1 and p53 form a portion of a regulatory transcriptional network that appears to have an important role in cancer cell invasion and migration. [ABSTRACT FROM AUTHOR]

A single human cell contains more than 5.0 × 105 copies of long interspersed element-1 (L1), 80-100 of which are competent for retrotransposition (L1-RTP). Recent observations have revealed the presence of de novo L1 insertions in various tumors, but little is known about its mechanism. Here, we found that 2-amino-1-methyl-6-phenylimidazo[4,5-b]pyridine (PhIP) and 2-amino-3,8-dimethyl-imidazo[4,5-f]quinoxaline (MeIQx), food-borne carcinogens that are present in broiled meats, induced L1-RTP. This induction was dependent on a cellular cascade comprising the aryl hydrocarbon receptor (AhR), a mitogen-activated protein kinase, and CCAAT/enhancer-binding protein β. Notably, these compounds exhibited differential induction of L1-RTP. MeIQx-induced L1-RTP was dependent on AhR nuclear translocator 1 (ARNT1), a counterpart of AhR required for gene expression in response to environmental pollutants. By contrast, PhIP-induced L1-RTP did not require ARNT1 but was dependent on estrogen receptor α (ERα) and AhR repressor. In vivo studies using transgenic mice harboring the human L1 gene indicated that PhIP-induced L1-RTP was reproducibly detected in the mammary gland, which is a target organ of PhIP-induced carcinoma. Moreover, picomolar levels of each compound induced L1-RTP, which is comparable to the PhIP concentration detected in human breast milk. Data suggest that somatic cells possess machineries that induce L1-RTP in response to the carcinogenic compounds. Together with data showing that micromolar levels of heterocyclic amines (HCAs) were non-genotoxic, our observations indicate that L1-RTP by environmental compounds is a novel type of genomic instability, further suggesting that analysis of L1-RTP by HCAs is a novel approach to clarification of modes of carcinogenesis. [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]

Digital tomosynthesis with flat-panel detector radiography is a novel application that allows easy, swift volume data acquisition of any anatomical site of interest with arbitrary patient posture. A single sweep of the X-ray tube provides multiple tomographic images of high resolution. We present the first patient with olecranon fracture who underwent internal fixation and 1-year postoperative follow-up with tomosynthesis. The minimal metallic artifact by this modality successfully provided detailed information regarding the healing process of the fracture. [ABSTRACT FROM AUTHOR]

Chemical composition analysis using inductively coupled plasma spectroscopy and phase identification using X-ray were performed on the extracted residues of 8 pct Cr martensitic steel strengthened by nanoscaled complex oxides, which consist of yttrium, titanium, and oxygen. Some YTiO particles, which were stable during normalizing, decomposed into YO and TiO during tempering. This reaction reversibly occurred between normalizing and tempering. YTiO particles formed in the steel had other constituents in solid solution as compared to the completely stoichiometric YTiO particles synthesized artificially in air. As for the mechanism of the decomposition of YTiO particles in the steel, segregation of oxygen to dislocations induced by normalizing caused the decomposition of YTiO during tempering. In addition to that, the interfacial strain between YO particles or TiO particles within CrC carbides, which are formed by tempering, was lower than the strain between YTiO, which precipitated in CrC carbides or the matrix. This difference in interfacial strain could also promote the decomposition of the YTiO particles in the steel. [ABSTRACT FROM AUTHOR]

The effect of tempering temperature and creep exposure on the microstructure of a modified 9Cr steel was investigated. Creep-interrupted specimens, including the grip portion, were investigated precisely using mainly X-ray and inductively coupled plasma (ICP) spectroscopy. After saturation of precipitation due to creep exposure, the amount of extracted residue decreased once and then increased within a short period (dip). Chemical analysis showed that during the dip, the precipitates temporarily dissolved into the matrix and precipitated again. The size of the Cr23C6 increased gradually during creep, but the growth rate was relatively small, as compared to the Ostwald ripening. The size of the VN particles in the specimens tempered at 800 °C in the early stage of creep was very fine, approximately 20 nm, and tended to decrease further with the progress of creep. The size variations of the precipitates and the dip were explained from the annihilation or migration of precipitation sites, i.e., dislocations and boundaries, during creep. Transient creep for the specimens tempered at 500 °C was controlled by a reduction of the mobile dislocation density. On the other hand, transient creep for 800 °C was due to precipitation hardening of fine VN particles with the progress of creep, which was supported by the increase in both the lattice strain and the activation energy with creep. [ABSTRACT FROM AUTHOR]

Defining apoptosis-regulatory cascades of the epithelium is important for understanding carcinogenesis, since cancer cells are considered to arise as a result of the collapse of the cascades. We previously reported that a novel gene GASDERMIN (GSDM) is expressed in the stomach but suppressed in gastric cancer cell lines. Furthermore, in this study, we demonstrated that GSDM is expressed in the mucus-secreting pit cells of the gastric epithelium and frequently silenced in primary gastric cancers. We found that GSDM has a highly apoptotic activity and its expression is regulated by a transcription factor LIM domain only 1 (LMO1) through a sequence to which Runt-related transcription factor 3 (RUNX3) binds, in a GSDM promoter region. We observed coexpression of GSDM with LMO1, RUNX3 and type II transforming growth factor-β receptor (TGF-βRII) in the pit cells, and found that TGF-β upregulates the LMO1- and GSDM-expression in the gastric epithelial cell line and induces apoptosis, which was confirmed by the finding that the apoptosis induction is inhibited by suppression of each LMO1-, RUNX3- and GSDM expression, respectively. The present data suggest that TGF-β, LMO1, possibly RUNX3, and GSDM form a regulatory pathway for directing the pit cells to apoptosis.Oncogene (2007) 26, 6488–6498; doi:10.1038/sj.onc.1210475; published online 30 April 2007 [ABSTRACT FROM AUTHOR]

Umbilical cord matrix stem (UCMS) cells are unique stem cells derived from Wharton's jelly, which have been shown to express genes characteristic of primitive stem cells. To test the safety of these cells, human UCMS cells were injected both intravenously and subcutaneously in large numbers into severe combined immunodeficiency (SCID) mice and multiple tissues were examined for evidence of tumor formation. UCMS cells did not form gross or histological teratomas up to 50 days posttransplantation. Next, to evaluate whether UCMS cells could selectively engraft in xenotransplanted tumors, MDA 231 cells were intravenously transplanted into SCID mice, followed by intravenous transplantation of UCMS cells 1 and 2 weeks later. UCMS cells were found near or within lung tumors but not in other tissues. Finally, UCMS cells were engineered to express human interferon beta – designated ‘UCMS−IFN-β’. UCMS−IFN-β cells were intravenously transplanted at multiple intervals into SCID mice bearing MDA 231 tumors and their effect on tumors was examined. UCMS−IFN-β cells significantly reduced MDA 231 tumor burden in SCID mouse lungs indicated by wet weight. These results clearly indicate safety and usability of UCMS cells in cancer gene therapy. Thus, UCMS cells can potentially be used for targeted delivery of cancer therapeutics.Cancer Gene Therapy (2007) 14, 828–835; doi:10.1038/sj.cgt.7701077; published online 29 June 2007 [ABSTRACT FROM AUTHOR]

We have been developing a unique system for the downregulation of a gene expression through cutting a specific mRNA by the long form of tRNA 3′-processing endoribonuclease (tRNase ZL) under the direction of small-guide RNA (sgRNA). However, the efficacy of this system and the involvement of tRNase ZL in the living cells were not clear. Here we show, by targeting the exogenous luciferase gene, that the efficacy of the sgRNA/tRNase ZL method can become comparable to that of the RNA interference technology and that the gene silencing is owing to tRNase ZL directed by sgRNA not owing to a simple antisense effect. We also show that tRNase ZL together with sgRNA can downregulate expression of the endogenous human genes Bcl-2 and glycogen synthase kinase-3β by degrading their mRNAs in cell culture. Furthermore, we demonstrate that a gene expression in the livers of postnatal mice can be inhibited by an only seven-nucleotide sgRNA. These data suggest that sgRNA might be utilized as therapeutic agents to treat diseases such as cancers and AIDS.Gene Therapy (2007) 14, 78–85. doi:10.1038/sj.gt.3302841; published online 3 August 2006 [ABSTRACT FROM AUTHOR]

We have succeeded in direct synthesis of single-walled carbon nanotubes (SWNTs) on a conductive substrate coated with a 3D mesoporous silica film, and observed the field emission. Co catalysts for the growth of SWNTs are deposited on the substrate by electroplating. The particle size of the catalyst is well-controlled inside defined space of the mesoporous silica film. Furthermore, the location of Co particles can be controlled in the mesopores by the electroplating method. Mono-dispersed SWNTs are grown along with the mesopores that are normal to the substrate, because Co particles are deposited at the bottom of the mesopores. It is also found that the mesoporous silica film prevents the aggregation of Co catalysts and the distortion of Au layer as the conductive substrate. The field emission measurement shows that the turn-on field is 4.2 V/μm at 10 μA/cm2. The field enhancement factor is about 1500. This approach provides an efficient methodology for fabricating an SWNTs-based field emitters. [ABSTRACT FROM AUTHOR]

Kluyveromyces thermotolerans strain NBRC 1674 was selected for the simultaneous production of sphingolipids and ethanol from beet molasses. The strain gradually synthesized ethanol with fermentation periods and attained a level slightly higher than that of the strain of Saccharomyces cerevisiae usually used for ethanol production. The sphingolipids accumulated in the cells were composed of almost equal amounts of free ceramides and glucosylceramides. The sphingoid bases and fatty acids of the two sphingolipids differed from each other and changed under aerobic and anaerobic growth conditions. Oxygen limitation may cause accumulation of sphinganine by inhibiting sphingolipid desaturases and enhance its proportion in both the sphingolipids. [ABSTRACT FROM AUTHOR]

We evaluated the effects of acute preload reduction with inferior vena cava (IVC) occlusion on myocardial velocities during systole (Sa), early (Ea) and late (Aa) diastole, isovolumic contraction (IVV), and myocardial acceleration (IVA) measured by tissue Doppler imaging (TDI) in pediatric patients. A total of 22 patients (5 ± 3 years) were studied: 9 patients (4 ± 3 years) with Kawasaki disease, 8 patients (6 ± 3 years) with atrial septal defect and right ventricular (RV) volume overload, and 5 patients (5 ± 4 years) with pulmonary stenosis and RV pressure overload. Using TDI, Sa, Ea, Aa, IVV were recorded at the base of the RV free wall from a four-chamber view. IVA was calculated by dividing IVV by the time interval from onset of IVV to the time at peak velocity of this wave. In each group, IVC occlusion caused significant decreases in peak Sa, peak Ea, and peak Aa ( p < 0.05). However, IVV and IVA did not change during acute preload reduction. This study demonstrated the effects of acute preload reduction on TDI velocities. In contrast to peak Sa, peak Ea, and peak Aa, IVV and IVA were unaffected by preload within a physiological range. [ABSTRACT FROM AUTHOR]

In order to form silicon (Si)-on-insulator (SOI) layers with various thicknesses, oxygen implantation with doses between 1.0×1017/cm2 and 6.0×1017/cm2 and at energies between 40 and 240 keV has been carried out into 300 mm diameter (100)Si wafers at a temperature of 560 °C. After implantation, Si wafers are annealed in dry Ar mixed with 1% O2 at a temperature of 1350 °C for 4 h. The quality of buried oxide (BOX) layers and the microstructure in implanted layers before and after annealing is characterized by transmission electron microscopy. The results reveal that the appreciable number of threading dislocations (TDs) is generated in SOI layers implanted at energies above 200 keV under the optimum dose-energy conditions for the continuous BOX layer formation. Whereas, in the case of discontinuous BOX layers, the TD generation is observed in samples implanted at energies above 120 keV. The generation of TDs is discussed with the emphasis on the effect of implantation energy. [ABSTRACT FROM AUTHOR]

To evaluate whether transthoracic Doppler echocardiography can reliably measure coronary flow velocity and coronary flow velocity reserve (CFVR) in the posterior descending coronary artery (PD) in children, we examined 32 patients who had congenital heart disease (ventricular septal defect in 10, tetralogy of Fullot in 6, tricuspid atresia in 3, double-outlet right ventricle in 2, patent ductus arteriosus in 2, and aortic valve stenosis in 2) and 7 patients who had a history of Kawasaki disease without stenosis or aneurysm formation of the coronary artery. Average peak flow velocity (APV) in the PD was measured by transthoracic Doppler echocardiography at the time of intracoronary Doppler study. CFVR was defined as the ratio of hyperemic to basal APV. Clear envelopes of basal and hyperemic APV in the PD were obtained in 23 of 32 patients by transthoracic Doppler echocardiography. APV obtained from transthoracic Doppler echocardiography correlated highly with that from the Doppler guidewire method (r = 0.91). The mean difference between transthoracic Doppler echocardiography and the Doppler guidewire method was 0.1 ± 2.9. There was an excellent correlation between transthoracic Doppler echocardiography and the Doppler guidewire method for the measurements of CFVR (r = 0.84). The mean difference between transthoracic Doppler echocardiography and Doppler guidewire was -0.016 ± 0.198. Noninvasive measurement of coronary flow velocity and CFVR in the PD using transthoracic Doppler echocardiography accurately reflects invasive measurement of coronary flow velocity and CFVR by the Doppler guidewire method in pediatric patients with various heart diseases. [ABSTRACT FROM AUTHOR]

The myocardial performance index (Tei index) determined by the pulsed Doppler method is a simple and noninvasive measurement for assessing global right ventricular (RV) function. This index can also be obtained by tissue Doppler imaging (TDI). The effects of significant pulmonary regurgitation (PR) on the determination of the Tei index by these two methods have not been investigated. We examined 15 patients (6.3 ± 2.2 years) with significant PR after repair of tetralogy of Fallot (TOF) and 24 age-matched healthy children. Myocardial wall motion velocities at the tricuspid annulus were assessed during systole (Sa), early diastole (Ea), and late diastole (Aa) from a four-chamber view. Pulsed Doppler-Tei index and TDI-Tei index were measured as reported previously. The Tei index obtained by the pulsed Doppler method in TOF patients did not differ from that in normal children (0.30 ± 0. 12 vs 0.32 ± 0.07,p= not significant). TDI showed that TOF patients had significantly decreased Ea, Aa, and Sa velocities compared to those of normal children. Both isovolumic contraction time and isovolumic relaxation time in TOF patients were significantly longer than those in normal children (88 ± 18 vs 62 ± 23 msec and 46 ± 11 vs 21 ± 12 msec, respectively;p<0.0001), although the duration of Sa did not differ between the two groups. Consequently, the Tei index as measured by TDI was significantly greater in TOF patients than in normal children (0.48±0.07 vs 0.30 ± 0.07,p<0.0001). The Tei index measured by the pulsed Doppler method is limited in its ability to assess RV function in patients with significant PR. However, the Tei index determined by TDI is a sensitive indicator of RV function in these patients, and it appears to be a promising new means of assessing global RV function in patients with significant PR. [ABSTRACT FROM AUTHOR]

This article presents information on tensile fracture behavior of woven fabric SiC matrix composites. The interface properties of SiC fiber-reinforced SiC matrix composites play important roles on the mechanical performance of the composites. The interface properties of the composites have been controlled by coatings on to the fiber surface. The coating is effective because the method allows wide range of the selection of coating material and thickness, thus enables wide range of interface properties.

Summary. Viral infection is usually initiated by the binding of virus particles to specific receptor molecule(s) on the host cell surface. Blocking of this step prevents the following step, penetration into the cell. In the present study, we investigated the virus-cell interactions of virions of Norwalk virus (NV), a major etiological agent for viral diarrhea. We found that histone was an extremely strong NV-binding protein. Histone H1, a heterologous histone molecule, appeared to be able to interact not only with NV particles, but also with the cell surface. Histone H1 appeared capable of effectively preventing the attachment of NV to intestinal cells, but not of other viruses. No cytotoxic effects of histone were observed under the assay conditions. These results indicate that nonsecretory histone molecules may inhibit the attachment of viruses to cells like lactoferrins. Our results suggest that by searching virus-binding molecules, we might find antiviral agents, even for new viruses. [ABSTRACT FROM AUTHOR]

Jets and winds in pre-main sequence (PMS) stars are often heated and ionized, and understanding their heating mechanism is desired to compare UV-to-IR spectral signatures with models and thus investigate their driving mechanism. We review our results of long-slit spectroscopy and spectro-astrometry for He I 1.083 μm and Hα emission, and investigate the heating mechanisms in the jet in the outer (>10 AU) and inner (<10 AU) regions, respectively. [ABSTRACT FROM AUTHOR]

Dobutamine stress echocardiography has become accepted in the evaluation of cardiac functional reserve. Although the Doppler-derived index of combined systolic/diastolic myocardial performance (Tei index) has been reported to be easily obtainable and useful for predicting left ventricular performance, the effect of dobutamine on the Tei index has not been determined in children. To assess the effect of dobutamine on the Tei index, 8 patients who had undergone surgery for ventricular septal defect and 7 patients who had a history of Kawasaki disease were examined. Echocardiographic recordings were obtained before and after dobutamine infusion (5 mg/kg per minute). Variables measured were transmitral flow velocities (E, A, E/A), rate-corrected mean velocity of circumferential fiber shortening (rate-corrected Vcf), and IMP. We measured isovolumic contraction time (ICT), isovolumic relaxation time (IRT), and ejection time (ET) and then calculated the Tei index using the following formula: Tei index = (ICT + IRT)/ET. Dobutamine infusion increased rate-corrected Vcf (29%, p <0.01), peak E (7%, p <0.05), and peak A (13%, p <0.05). E/A ratio did not change during dobutamine infusion. ET, ICT, and IRT were found to decrease during dobutamine infusion. The magnitude of the change in the ICT (?21%, p <0.01) was greater than those in IRT (?12%, p <0.01) and ET (?8%, p <0.05). The decrease in Tei index (?16%, p <0.01) resulted in a decrease in ICT/ET (?21%, p <0.01) and a slight decrease in IRT/ET (?12%, p <0.05). The Tei index has potential as a sensitive indicator of the effects of inotropic stimilation on global left ventricular function. [ABSTRACT FROM AUTHOR]

Background. Platelet-derived growth factor (PDGF) is an important mediator of mesangial proliferative glomerulonephritis. Little is known about the role of PDGF in the regulation of intraglomerular extracellular matrix turnover. Method. Effects of PDGF on the secretion of matrix metalloproteinase-2 (MMP-2), tissue inhibitor of MMP-2 (TIMP-2), and type IV collagen by cultured human mesangial cells (HMCs) were examined in the present study. Secretion of MMP-2, TIMP-2, and type IV collagen by HMCs was quantified with an enzyme immunoassay. Collagenase activity of HMCs was evaluated by gelatin zymography. Results. Recombinant human PDGF (10–20 ng/ml) stimulated MMP-2 secretion by HMCs in a dose-dependent fashion. PDGF (20 ng/ml) increased TIMP-2 secretion by HMCs to a lesser extent. Enhanced activity of 72-kDa collagenase derived from HMCs incubated with PDGF was demonstrated by zymography. Although PDGF alone did not affect type IV collagen secretion by HMCs, PDGF increased type IV collagen secretion in the presence of TIMP. Conclusions. PDGF may contribute to intraglomerular matrix turnover by up-regulating secretion and activation of MMP-2 by HMCs. [ABSTRACT FROM AUTHOR]

Herpes simplex virus thymidine kinase (HSV-TK) and Escherichia coli cytosine deaminase (CD) are non-mammalian enzymes capable of converting innocuous prodrugs into cytotoxic metabolites. Both enzymes have been utilized independently, as well as together in 'suicide' gene therapy protocols to eliminate tumor cells in vitro and in vivo. We have used a set of replication defective HSV vectors expressing either or both enzymes to compare the efficacies of single and double suicide gene therapies in the 9L gliosarcoma model in vitro and in vivo. In cell culture experiments at high and low multiplicities of infection, combined expression of the two genes by vector TOCD/TK along with exposure to the matching prodrugs (ganciclovir and 5-fluorocytosine) showed increased cytotoxicity compared with exposure to either prodrug alone. However, the two gene combination was inferior to single gene treatments, suggesting that HSVtk and CD are mutually counteractive in the prodrug-dependent killing of glioma cells. In animal experiments, survival was not significantly prolonged by administration of both prodrugs to TOCD/TK-treated animals, while each single gene/prodrug pair resulted in increased survival. These results indicate that single suicide gene systems employing HSVtk or CD may be preferable over combinations of the two. [ABSTRACT FROM AUTHOR]

Expression of vascular endothelial growth factor (VEGF)-C and that of its receptors were assessed in non-small cell lung cancer. Immunohistochemistry revealed positive VEGF-C expression in 38.7% (24/62) of the patients studied. A significant positive correlation was found between VEGF-C in cancer cells and VEGF receptor-3 (VEGFR-3) in vascular endothelial cells, but not between VEGF-C in cancer cells and VEGFR-2 in endothelial cells. In this cohort of lung cancer patients, VEGF-C expression was significantly associated with lymph node metastasis, lymphatic vessel invasion, and worse outcomes after the operation. Although the independent prognostic impact of VEGF-C and VEGFR-3 was not clear, VEGFR-2 expression in endothelial cells retained the independency as the prognostic indicator. In light of these findings, we conclude that VEGF-C plays an important role in lymphatic invasion/metastasis and tumour progression in non-small cell lung cancer. [ABSTRACT FROM AUTHOR]

OBJECTIVE: The purpose of the present study was to determine the effects of weight variability on cardiovascular risk factors (CRF) based on a large sample of community-resident Japanese males and females. METHOD: A total of 3564 men and 1955 women, all Japanese, aged 30-69 y in the baseline year (1987), were followed-up for up to 10 y (end-point in 1996). Height, body weight, systolic and diastolic blood pressure, fasting serum total cholesterol, triglyceride and fasting plasma glucose were measured as an annual health check-up. At least six times in 10 y, body mass index (BMI) mean was calculated as an index of the BMI level of each subject (BMI mean). Direction and magnitude of the change in a subject's BMI was determined by a regression slope of BMI values over time (BMI slope). BMI fluctuation was defined as the root mean square error (BMI RMSE) of a regression line. The slopes of the five CRF were calculated using each regression equation over time. RESULTS: The BMI slope strongly correlated to each CRF slope independent of baseline age, baseline CRF value, smoking habit, BMI mean and BMI RMSE. BMI RMSE did not correlate to any CRF slopes. CONCLUSION: This study indicates that weight gain and weight loss have a much greater effect on CRF change than does weight fluctuation in Japanese middle-aged men and women. [ABSTRACT FROM AUTHOR]

Coronary flow measurement has provided useful clinical and physiologic information. However, there is little information about values for coronary flow in normal neonates, much less neonates with congenital heart disease. The aim of this study was to assess coronary blood flow in normal neonates and to compare the results with those in infants with ventricular septal defect. The study groups consisted of 12 normal neonates and 9 infants with simple ventricular septal defect associated with pulmonary hypertension. Left ventricular dimension, left ventricular mass, and the diameter of the coronary vessel were measured by standard M-mode and two-dimensional echocardiography. Peak flow velocities, flow velocity integrals, and flow volumes in the left anterior descending and circumflex coronary arteries were measured. The flow signals from the left anterior descending and circumflex coronary arteries were recorded in 84% (10/12) and 17% (2/12), respectively, in the normal neonates and 78% (7/9) and 11% (1/9), respectively, in the patients. The left ventricular end diastolic diameter and mass were significantly lower in normal infants than in the infants with ventricular septal defect (1.56 ± 0.11 vs 1.84 ± 0.09 cm and 5.4 ± 1.6 vs 8.8 ± 0.8 g, respectively, p < 0.01). The mean peak diastolic velocity and the flow velocity time integral in the left anterior descending coronary artery were significantly lower in the normal neonates than in the patients (15 ± 4 vs 28 ± 6 cm/sec and 2.3 ± 0.6 vs 5.9 ± 1.5 cm, respectively, p < 0.01). The coronary flow volume was significantly lower in the normal neonates than in the patients (3.1 ± 1.4 vs 7.9 ± 4.7 ml/min, p < 0.05). However, the flow volume of the left anterior descending coronary artery/left ventricular mass did not show any significant difference between the two groups. Our study demonstrated in neonates that it is feasible to detect noninvasively and to evaluate the flow of the left anterior descending coronary artery under physiologic conditions and abnormal hemodynamic situations. Increased flow volume in the left anterior descending coronary artery in patients with ventricular septal defect may be a compensated mechanism for the increase in oxygen demand of hypertrophic myocardium of the left ventricle. [ABSTRACT FROM AUTHOR]

Implantation of retrovirus-producing cells within a tumor has been demonstrated to eliminate malignant brain tumors effectively in animal models. In our previous study, the implantation of high-titer retrovirus-producing fibroblasts into tumors resulted in highly efficient transduction in vivo. The transduced glioma cells migrated far from the implantation site, potentiating the induction of the remarkable bystander effect. It is also possible, however, that the implantation of murine fibroblast-derived virus-producing cells may induce an immune response in patients. In this study, we prepared retroviruses carrying the herpes simplex virus thymidine kinase (HTK) gene with titers of 1.4-2.5 × 10[sup 11] colony-forming units (c.f.u.)/ml, and stereotactically inoculated only 3 µl of the HTK-bearing retroviruses into the brain tumors of mice. Following repetitive ganciclovir (GCV) intraperitoneal injection, effective killing of glioma cells in the mouse brain was observed. The transduction efficiency was nearly as high as that observed for the implantation of high-titer retrovirus-producing fibroblasts. Eighty percent of brain tumor-bearing mice were completely cured by our treatment protocol using concentrated HTK-harboring retroviruses. Our results suggest that repeated inoculations of high-titer retroviruses carrying the HTK gene followed by GCV treatment may be a promising strategy for the clinical treatment of malignant gliomas. [ABSTRACT FROM AUTHOR]

Herpes simplex virus (HSV)-mediated delivery of the HSV thymidine kinase (tk) gene to tumor cells in combination with ganciclovir (GCV) administration may provide an effective suicide gene therapy for destruction of malignant glioblastomas. However, because HSV is a highly cytotoxic agent, gene expression from the virus is short-rived which may limit the effectiveness of HSVtk/GCV therapy. Using different replication-defective HSVtk gene vectors, we compared HSV vector backgrounds for their cytotoxic activity on infection of 9L gliosarcoma cells in culture and brain tumors in rats and evaluated the impact of vector toxicity on the effectiveness of tk/GCV-mediated suicide gene therapy. As reported previously for other cell lines, a vector deleted for both copies of the immediate-early (IE) gene ICP4 (SOZ.1) was highly toxic for 9L cells in culture while a vector deleted in addition for the ICP22 and ICP27 IE genes (T.1) reduced or arrested 9L cell proliferation with more limited cell killing. Nevertheless, both vectors supported widespread killing of uninfected cells in the presence of GCV following low multiplicity infections, indicating that vector cytotoxicity did not preempt the production of vector-encoded TK enzyme necessary for the killing of uninfected cells by the HSV-tk/GCV bystander effect. Although an SOZ.1-related vector (SHZ.2) caused tumor cell necrosis in vivo, injection of SHZ.2 at multiple coordinates thoughout the tumor followed by GCV administration failed to prolong markedly the survival of tumorbearing rats. In contrast, a single injection of T.1 produced a life-extending response to GCV. These results indicate that vector cytotoxicity can limit the efficacy of HSV-tk/GCV treatment in vivo, which may be due to premature termination of tk gene expression with attendant abortion of the bystander effect. [ABSTRACT FROM AUTHOR]

In almond, gametophytic self-incompatibility is controlled by a single multiallelic locus (S-locus). In styles, the products of S-alleles are ribonucleases, the S-RNases. Cultivated almond in California have four predominant S-alleles (Sa, Sb, Sc, Sd). We previously reported the cDNA cloning of three of these alleles, namely Sb, Sc and Sd. In this paper we report the cloning and DNA sequence analysis of the Sa allele. The Sa-RNase displays approximately 55% similarity at the amino-acid level with other almond S-RNases (Sb, Sc, and Sd) and this similarity was lower than that observed among the Sb, Sc and Sd-RNases. Using the cDNA sequence, a PCR-based identification system using genomic DNA was developed for each of the S-RNase alleles. Five almond cultivars with known self-incompatibility (SI) geno-types were analyzed. Common sequences among four S-alleles were used to create four primers, which, when used as sets, amplify DNA bands of unique size that corresponded to each of the four almond S-alleles; Sa (602 bp), Sb (1083 bp), Sc (221 bp) and Sd (343 bp). All PCR products obtained from genomic DNA isolated from the five almond cultivars were cloned and their DNA sequence obtained. The nucleotide sequence of these genomic DNA fragments matched the corresponding S-allele cDNA sequence in every case. The amplified products obtained for the Sa- and Sb-alleles were both longer than that expected for the coding region, revealing the presence of an intron of 84 bp in the Sa-allele and 556 bp in the Sb-allele. Both introns are present within the site of the hypervariable region common in S-RNases from the Rosaceae family and which may be important for S specificity. The exon portions of the genomic DNA sequences were completely consistent with the cDNA sequence of the corresponding S-allele. A useful application of these primers would be to identify the S-genotype of progeny in a breeding program, new varieties in an almond nursery, or new grower selections at the seedling stage. [ABSTRACT FROM AUTHOR]

Experimental and modeling studies on tensile fracture behavior of notched unidirectional Si-Ti-C-O (Tyranno fiber) reinforced BMAS (barium magnesium aluminosilicate) glass matrix composite were carried out. The longitudinal crack arose at the tip of the transverse notch before overall fracture. The critical energy release rate around at initiation of the longitudinal cracking was estimated to be nearly 100 J/m2 by application of the present model to the experimentally observed relation between the stress of the composite in the very early stage of longitudinal cracking and the notch size. The notched strength was higher than that predicted by the fracture mechanical criterion due to the blunting arising from the premature longitudinal cracking, but it was lower than that predicted by the net stress criterion due to the constraint effect arising from the bridging of the fibers and the spalling of the segmented matrix into the longitudinal crack. [ABSTRACT FROM AUTHOR]

For glioma- and glioblastoma-specific gene expression, we utilized a nestin regulatory element whose activity was evaluated by the reporter gene lacZ. Nestin is a 38-kDa intermediate filament protein, and is expressed specifically in the neuroepithelial stem cells. Nestin is detected in gliomas and glioblastomas, but not in normal brain tissue. We constructed a nestin gene regulator by placing nestin's second intron before the 5' upstream region (2iNP). To obtain enhanced expression of this tissue-specific regulator, we utilized the adenovirus double-infection method with a Cre-loxP on/off switching system. We constructed a 'regulator' vector, Ax2iNPNCre, which expresses Cre recombinase under the control of the nestin regulatory element, 2iNP. A 'reporter' vector, AxCALNLNZK, expresses lacZ under the control of a strong CAG promoter when the stuffer sequence has been removed by Cre recombinase at a pair of loxP sites. We used seven human glioma/glioblastoma cell lines: U251, KG-1C, NGM5, U87 MG, LN-Z308, NP-2 and T98G. Of these, nestin was expressed highly in U251 and KG-1C, less in NGM5, and undetectably in the other four lines. With the use of the two adenovirus vectors, we found X-gal staining and high nestin regulator-promoted β-galactosidase activities in four of the seven glioma/glioblastoma cell lines. Staining was strong in U251, KG-1C and NGM5, and less in U87 MG. LacZ expression was nearly undetectable in the non-glioma cell line, HeLa, but a little in COS-7. The adenovirus double-infection method, which uses a nestin regulator, is applicable for glioma/glioblastoma-specific expression. [ABSTRACT FROM AUTHOR]

Abstract To investigate X-chromosome inactivation (XCI) in human trophoblasts during early pregnancy, trophoblast genomic DNA was extracted and analyzed for a Bst XI restriction endonuclease site polymorphism in the X-linked phosphoglycerate kinase gene, after digestion with methylation-sensitive Hpa II (control samples were digested instead with Afa I). Six villous trophoblast DNA samples were informative for the polymorphism (ie, heterozygous) and were derived from women homozygous for the polymorphism. These samples were then evaluated for XCI. In five of the six samples with Hpa II predigestion, the sizes of the two heterozygous band peaks differed; maternal X-chromosome (X[sup M])-derived alleles showed smaller peak sizes than paternal X-chromosome (X[sup P])-derived alleles, but the differences varied in degree. In samples obtained by microdissection from formalin-fixed, paraffin-embedded tissues (30 samples from different anchoring villi, and 38 samples from different branch villi), monoclonal band patterns of X[sup P]-derived alleles were observed more frequently than those of X[sup M]-derived alleles, but almost half of the samples showed polyclonal patterns. Our results suggest that a skewing of XCI exists in the human trophoblast; however, the degree of nonrandomness due to predominant X[sup P] inactivation appears to be restricted. It is probable that transcription of the X inactivation center (XIC) begins earlier in mice than in humans. [ABSTRACT FROM AUTHOR]

The intracranial migration of transduced glioma cells was investigated in order to improve the treatment of malignant glioma by gene therapy using retroviral vectors. In this study, about half the volume of the tumor mass could be transduced in 14 days after only a single implantation of 3 × 105 retrovirus-producing cells into a tumor mass with a diameter of 5 mm. Moreover, we were able to follow the migration of glioma cells transduced by the lacZ-harboring retroviruses originating from the high-titer retrovirus-producing cells. Besides the importance of using a high-titer retroviral vector system, our results also indicate that the implantation site of the virus-producing cells and the interval between the implantation of the virus-producing cells and the subsequent administration of ganciclovir are important factors for the efficient killing of glioma cells. [ABSTRACT FROM AUTHOR]

Multilayered thermal barrier coatings (TBC) with different functions were proposed for the hot section components of land-based gas turbines. This article describes a multilayered TBC with an oxidation resistant layer. A conventional duplex TBC and a triplex TBC, in which an aluminized layer was added to the conventional duplex TBC to increase oxidation resistance, were prepared. It was confirmed by a burner rig test that the triplex TBC with the aluminized layer is resistant to oxidation and shows high durability in a thermal cycle test, compared with the conventional duplex TBC. The spalling in the thermal cycle test of each TBC specimen occurred at the same position, when the thickness of the oxidation layer was 11 to 13 µm. The mechanism of spalling of the coating in the thermal cycle test was discussed in terms of stress in the coating. Stress in the direction of spalling occurred by an uneven interface between the bond and top coat and increased with growth of the oxidation layer. It is thought that the high durability of the triplex TBC in the thermal cycle test is derived from suppressing the growth of the oxidation layer and decreasing the stress due to the addition of the aluminized layer. [ABSTRACT FROM AUTHOR]

Abstract. Gas temperatures deduced from one-line and two-line laser-induced fluorescence (LIF) measurements of NO seeded into low-pressure methane flames are compared with those determined from LIF measurements of OH rotational distribution. The purpose is to make a quantitative assesment of the accuracy of one- and two-line LIF temperature strategies. Temperature determination from NO LIF intensity from a single transition must accurately account for any variation in the mole fraction of seeded NO. In the hot post-flame region, this added NO is diluted by the thermal equilibrium of radical species and incomplete combustion; this dilution depends on gas temperature and fuel/air stoichiometry. Chemical reactions of the NO produce an even larger variation in the NO mole fraction. Reburning of NO in the flame front (via reaction with CH) reduces the added NO by as much as 16% in the burnt gases of a slightly fuel-rich (PHI = 1.07) methane/air flame. The size of the reduction depends on both the amount of NO addition and the fuel/air stoichiometry. This effect can alter the apparent temperature determined from one-line NO LIF by as much as 25%. Two-line LIF strategies for gas temperature avoid these complications. Temperatures determined from all throe LIF methods show good agreement in low-pressure flames, when a detailed model of the chemistry is used to correct the one-line NO temperature. However, in reactive systems where a model of the chemistry cannot be applied, one-line LIF strategies for gas temperature from seeded NO are not reliable. [ABSTRACT FROM AUTHOR]

Abstract. Cross-sectional transmission electron microscope observations have been carried out to clarify the formation, evolution and dissolution of secondary defects in the region below the amorphous/crystalline interface formed in Si (100) by low-energy (10, 20, and 30keV) implantation of a 5 x 10[sup 14]/cm[sup 2] dose of As ions followed by both isochronal and isothermal annealing. The elementary defects generated first during solid-phase epitaxial recovery of implantation-induced amorphous layers at temperatures of 550 Celsius and/or 600 Celsius are {311} defects 2-3 nm long. They are considered to be transformed into {111} and {100} defects alter annealing at temperatures higher than 750 Celsius. These secondary defects show the opposite annealing behavior to the dissolution and growth by the difference of their depth positions at 800 Celsius. This phenomenon is explained by the diffusion of self-interstitials contained in defects. With regard to the formation and dissolution of defects, there is no significant difference between the effects of rapid thermal annealing (950 Celsius for 10 s) and furnace annealing (800 Celsius for 10 min). [ABSTRACT FROM AUTHOR]

High-resolution cross-sectional and conventional plan-view transmission electron microscope observations have been carried out for molecular beam epitaxially grown GaAs films on vicinal Si (0 0 1) before and after annealing as a function of film thicknesses and observation directions between two orthogonal <110> directions. Two groups of misfit dislocations are characterized at the interface regions between GaAs and Si by analyzing whether their extra half planes exist in the film or the substrate side. Group I misfit dislocations due to stress caused by a lattice misfit between GaAs and Si consist of partial dislocations and 60° and 90° complete dislocations in an as-grown state. With an increase in the film thickness, partial dislocations decrease and complete dislocations increase. After annealing, partial dislocations almost completely disappear and 90° perfect dislocations are predominantly observed. Group II misfit dislocations due to thermal-expansion misfit-induced stress are all 60°-type complete dislocations regardless of film thicknesses and annealing treatment. [ABSTRACT FROM AUTHOR]

The histological diagnosis and proliferative potential measured by bromodeoxyuridine (BrdU) labelling index (LI) were corelated with preoperative CT and contrast-enhanced, MRI, 18F-flurodeoxyglucose positron emission tomography (PET) and 201T1 single photon emission computed tomography (SPECT) in 43 patients with various grades of glioma. 201T1 SPECT had slightly higher sensitivity to tumours with BrdU LI N 5 % (showing 10/10) than 18F-FDG PET (7/8 tumours). 18F-FDG PET was better for identifying tumours of BrdU LI < 1 % (13/15) than 201T1 SPECT (13/22). Accumulation of 201T1 in the tumour was slightly different from contrast enhancement on CT and/or MRI, and gave “false-postive” results in some low-grade gliomas. However, 201T1 SPECT, which is available in many hospitals and may cost less, provided useful information to supplement that from CT and MRI. [ABSTRACT FROM AUTHOR]

Two cases of recurrent pilocytic astrocytoma with leptomeningeal dissemination (LMD) are described. A 6-year-old boy presented with a cerebellar tumor, which was subtotally removed. Tumor recurrence with LMD occurred 4 years later. Reoperation for tumor removal followed by craniospinal irradiation stabilized the LMD over 5 years. A 4-year-old girl presented with a chiasmatic-hypothalamic tumor. Partial removal of the tumor was followed by radiation therapy. Tumor regrowth with LMD occurred 4 years later and was managed by reoperation, chemotherapy and radiotherapy. Tumor recurrence with LMD can be stabilized by multimodal treatment without tumor progression. [ABSTRACT FROM AUTHOR]

Three pediatric cases of temporal lobe seizure due to calcified glioma of amygdalo-hippocampal region are described. Computed tomography and magnetic resonance imaging showed dense calcification with no postcontrast enhancement in the amygdalo-hippocampal region. Positron emission tomography showed low oxygen metabolism, low glucose metabolism, hypermetabolism of amino acids, and low regional cerebral blood flow in the tumors. Single photon emission computed tomography showed a high accumulation ofTl chloride andI-isopropyl iodoamphetamine in one tumor, but otherwise low radioisotope uptake. These studies indicated lowgrade malignancies. The patients were treated by partial tumor removal and radiotherapy. Histological examination of the tumor specimens showed astrocytoma with interstitial calcification. One patient died due to tumor recurrence, while the others are doing well with minimal seizure. We recommended temporal lobectomy in similar cases to achieve complete remission. [ABSTRACT FROM AUTHOR]

A mixed glioma and sarcoma in a 3-month-old infant is presented as a rare case of gliosarcoma with a good response to treatment. This congenital case is quite different from those in adults: the tumor cells were mainly composed of sarcomatous elements; glial components were not anaplastic without obvious endothelial hyperplasia, but presented as reticulin-free islands, mimicking a reactive glioma in a sarcoma. It may be termed 'sarcoglioma' to distinguish from a classic gliosarcoma. The origin of the rare mixed tumor may be related to a dysgenesis of both mesenchymal and glial elements. [ABSTRACT FROM AUTHOR]

The prognosis of recurrent IV-ventricle ependymoma in children is poor. Three cases of recurrent ependymoma were treated with combination chemotherapy using cis-diamine dichloro platinum (II) (CDDP) and methyl-6-(3-(2-chloroethyl)-3-nitrosoureido)-6-deoxy-α- d-glucopyranoside (MCNU). The patients were 2-, 3-, and 6-year-old boys. The interval between the first operation with irradiation and recurrence was 1 year and 5 months to 2 years. Two cases showed a recurrence at the original site; in the other case, a right sylvian tumor deposit was found via computed tomography. The therapeutic regimen for recurrnt ependymomas was as follows: (1) the tumor was debulked if possible; (2) additional local irradiation of 30 Gy was administered; (3) combined treatment of 100 mg/m CDDP and 80 mg/m MCNU over 24 h was given 5 times with an interval of 6 weeks between treatments. The patients tolerated the therapy well with only mild side effects. Remission lasted 1 year in two patients and has lasted for 8 months in one. [ABSTRACT FROM AUTHOR]

A successful transplantation of soybean agglutinin (SBA) and sheep red blood cell (SRBC)-fractionated, maternal marrow in a patient with severe combined immunodeficiency (SCID) is reported. The engraftment of HLA-haplotype mismatched marrow cells was obtained without apparent graft versus host disease (GVHD). With immunological reconstitution the patient recovered from a BCG infection, which might have been caused by a BCG inoculation before his bone marrow transplantation. [ABSTRACT FROM AUTHOR]

The clinical and neuro-endocrinological aspects of 17 suprasellar germinoma patients treated between 1972-1991 are reported. Surgical extirpation was not initially attempted, but all patients received irradiation with or without a biopsy. Sixteen of those have led useful lives with appropriate hormonal replacement therapy during a mean follow up of 8 years. Seven tumours at diagnosis were less than 2 cm in diameter (type 1), nine tumours more than 2 cm (type 2), and one double midline tumour was of unknown size. All 7 type 1 patients required 1-deamino-8-D-arginine-vasopressin (DDAVP) to control diabetes insipidus (DI), but only 2 of the 9 type 2 patients have needed DDAVP since completion of the treatment. Patients with smaller tumours required more DDAVP following tumour disappearance, than those with larger tumours. The prognostic indicators for the post-treatment course of DI and retarded growth appeared to be the tumour size and the age at diagnosis. We also emphasize the absence of metastasis in unoperated cases and the use of tumour markers as a diagnostic criterion which obviates surgical acquisition of tissue to make the diagnosis. Possible reasons are discussed and the literature reviewed. [ABSTRACT FROM AUTHOR]