Diffusion Tensor Imaging MRI With Spin-Echo Sequence and Long-Duration Measurement for Evaluation of Renal Fibrosis in a Rat Fibrosis Model.

BACKGROUND: Renal fibrosis (RF) is a well-known marker for chronic kidney disease (CKD) progression, including chronic renal injury after renal transplantation. However, invasive biopsy is an available examination for evaluation of RF. Diffusion MRI was once recognized as a promising option for RF. However, it is now controversial for RF evaluation in a unilateral ureteral obstruction (UUO) model. METHODS: To seek an optimal imaging method applicable for RF in UUO model kidneys, we attempted a series of MRI methods, including proton density-weighted imaging, T1-weighted imaging, T2-weighted imaging, T2*-weighted imaging, diffusion-weighted imaging, and diffusion tensor imaging (DTI). RESULTS: We identified DTI MRI by spin-echo sequence plus a special kidney attachment as the best option for evaluation of renal UUO fibrosis, compared with normal kidney on the opposite side. To confirm these results, we applied this technique to a rat UUO therapeutic model with the anti-fibrotic reagent Fasudil. Fractional anisotropy values calculated from DTI MRI showed statistically significant linear correlation with the RF area measured by use of Sirius red or Masson trichrome staining of the positive area [cortex (r = 0.6397, P = .0283) and outer stripe of the outer medulla (r = 0.7810, P = .0039)]. CONCLUSIONS: By use of the DTI MRI with spin-echo sequence, it may be possible to accurately evaluate RF in CKD.

High flux circularly polarized gamma beam factory: coupling a Fabry-Perot optical cavity with an electron storage ring.

We report and discuss high-flux generation of circularly polarized γ-rays by means of Compton scattering. The γ-ray beam results from the collision of an external-cavity-enhanced infrared laser beam and a low emittance relativistic electron beam. By operating a non-planar bow-tie high-finesse optical Fabry-Perot cavity coupled to a storage ring, we have recorded a flux of up to (3.5 ± 0.3) × 108 photons per second with a mean measured energy of 24 MeV. The γ-ray flux has been sustained for several hours. In particular, we were able to measure a record value of up to 400 γ-rays per collision in a full bandwidth. Moreover, the impact of Compton scattering on the electron beam dynamics could be observed resulting in a reduction of the electron beam lifetime correlated to the laser power stored in the Fabry-Perot cavity. We demonstrate that the electron beam lifetime provides an independent and consistent determination of the γ-ray flux. Furthermore, a reduction of the γ-ray flux due to intrabeam scattering has clearly been identified. These results, obtained on an accelerator test facility, warrant potential scaling and revealed both expected and yet unobserved effects. They set the baseline for further scaling of the future Compton sources under development around the world.

Dextran sodium sulfate alters cytokine production in macrophages in vitro.

Macrophages have been assumed to have a crucial role in the development of inflammatory bowel disease (IBD). However, involvement of intestinal macrophages in IBD onset and functional alterations of macrophages during IBD development has not been clarified. We investigated the effect of exposure of compounds used in the induction of colitis in mice on the immune responses of peritoneal macrophages in mice. 2,4,6- trinitrobenzenesulfonic acid and oxazolone did not affect the production of interleukin (IL)-10 and IL-12 from lipopolysaccharide (LPS)-stimulated peritoneal macrophages from BALB/c mice. A significant increase in IL-10 secretion and decrease in IL-12 production from LPS-stimulated macrophages were observed upon exposure to dextran sodium sulfate (DSS). TNF-α production was enhanced significantly by exposure to DSS and LPS. The level of nitric-oxide production from macrophages was increased slightly by exposure to DSS and LPS. Expression of sphingosine kinase-1 and LIGHT (both of which are specific biomarkers of M2b macrophages) was observed in macrophages upon DSS exposure. Alteration of cytokine production in macrophages was observed upon DSS exposure in the absence of LPS stimulation. Peritoneal macrophages from C57BL/6 mice showed similar responses to peritoneal macrophages from BALB/c mice against DSS. These results suggest that DSS directs the immune response of macrophages towards the M2b phenotype.

Demonstration of the stabilization technique for nonplanar optical resonant cavities utilizing polarization.

Based on our previously developed scheme to stabilize nonplanar optical resonant cavities utilizing polarization caused by a geometric phase in electromagnetic waves traveling along a twisted path, we report an application of the technique for a cavity installed in the Accelerator Test Facility, a 1.3-GeV electron beam accelerator at KEK, in which photons are generated by laser-Compton scattering. We successfully achieved a power enhancement of 1200 with 1.4% fluctuation, which means that the optical path length of the cavity has been controlled with a precision of 14 pm under an accelerator environment. In addition, polarization switching utilizing a geometric phase of the nonplanar cavity was demonstrated.

Development of a real-time loop-mediated isothermal amplification assay for the sensitive and rapid detection of Listeria monocytogenes.

UNLABELLED: A real-time loop-mediated isothermal amplification (RealAmp) assay for the detection of Listeria was developed. The RealAmp assay, using primers specific for the hemolysin-encoding hlyA gene, was verified using Listeria monocytogenes strains (n = 58) from different regions of the world. Both the sensitivity and specificity of the RealAmp assay were high. The RealAmp assay could detect 10(3) CFU ml(-1) within 30 min. A comparative evaluation of the RealAmp assay, the API Listeria assay, and the real-time PCR assay revealed that the RealAmp assay is simpler, faster, and has a higher specificity than the other two assays. SIGNIFICANCE AND IMPACT OF THE STUDY: Conventional culture and molecular detection methods are always time consuming and require a specific laboratory infrastructure, thereby restricting their use for the rapid detection and diagnosis of pathogens. A real-time loop-mediated isothermal amplification (RealAmp) assay performed by ESEtube scanner to rapidly detect Listeria monocytogenes isolated from food was developed. The results showed that the RealAmp assay using the tube scanner was more efficient and precise than the conventional API Listeria assay and the real-time PCR assay.

Cor triatriatum sinister: an incidental finding in a patient with paroxysmal atrial fibrillation.

A 58-year-old male was referred for catheter ablation for atrial fibrillation. He was incidentally diagnosed with cor triatriatum sinister by preoperative transesophageal echocardiography and cardiovascular computed tomography. The patient has since been free from atrial fibrillation for over 24 months following successful electrical pulmonary vein isolation. The rapidly soaring number of cases undergoing catheter ablation for atrial fibrillation and imaging investigation prior to the procedure may increase the incidental detection of asymptomatic congenital heart diseases.

Allogeneic amniotic membrane-derived mesenchymal stromal cell transplantation in a porcine model of chronic myocardial ischemia.

Introduction. Amniotic membrane contains a multipotential stem cell population and is expected to possess the machinery to regulate immunological reactions. We investigated the safety and efficacy of allogeneic amniotic membrane-derived mesenchymal stromal cell (AMSC) transplantation in a porcine model of chronic myocardial ischemia as a preclinical trial. Methods. Porcine AMSCs were isolated from amniotic membranes obtained by cesarean section just before delivery and were cultured to increase their numbers before transplantation. Chronic myocardial ischemia was induced by implantation of an ameroid constrictor around the left circumflex coronary artery. Four weeks after ischemia induction, nine swine were assigned to undergo either allogeneic AMSC transplantation or normal saline injection. Functional analysis was performed by echocardiography, and histological examinations were carried out by immunohistochemistry 4 weeks after AMSC transplantation. Results. Echocardiography demonstrated that left ventricular ejection fraction was significantly improved and left ventricular dilatation was well attenuated 4 weeks after AMSC transplantation. Histological assessment showed a significant reduction in percentage of fibrosis in the AMSC transplantation group. Injected allogeneic green fluorescent protein (GFP)-expressing AMSCs were identified in the immunocompetent host heart without the use of any immunosuppressants 4 weeks after transplantation. Immunohistochemistry revealed that GFP colocalized with cardiac troponin T and cardiac troponin I. Conclusions. We have demonstrated that allogeneic AMSC transplantation produced histological and functional improvement in the impaired myocardium in a porcine model of chronic myocardial ischemia. The transplanted allogeneic AMSCs survived without the use of any immunosuppressants and gained cardiac phenotype through either their transdifferentiation or cell fusion.

Activations of mitogen-activated protein kinases and regulation of their downstream molecules after rat lung transplantation from donors after cardiac death.

OBJECTIVES: Accepting organs donated after cardiac death (DCD) is an effective approach to the donor shortage. However, lung transplantations from DCD donors show severe rapid pulmonary graft dysfunction (PGD) followed by warm ischemia-reperfusion injury (IRI). This study sought to clarify the molecular mediators in warm IRI, including activation of mitogen-activated protein kinase (MAPK) and the downstream cascades. METHODS: We performed single left lung transplantation using organs from male Sprague-Dawley rats after 0 (CIT group), 30 (30WIT group), or 180 (180WIT group) minutes of warm ischemia time. Pulmonary graft functions were estimated by blood gas analysis. At 1 hour after reperfusion, the phosphorylation status of MAPKs (ERK, p38, and JNK) and the gene expression levels of transcription factors (Egr-1 and ATF-3) and immune mediators (MCP-1, MIP-2, PAI-1, ICAM-1, TNF-α, IL-1ß, IL-6, and COX-2) in the grafts were examined using Western blotting and real-time polymerase chain reaction assays. RESULTS: Severe PGD was observed in the 180WIT group compared with transplanted lungs in the other groups, which exhibited good pulmonary graft function. ERK and JNK activations, as well as mRNA levels of transcription factors (Egr-1 and ATF3) significantly increased with greater warm ischemic times. The pattern of JNK activation correlated with the severity of PGD. MCP-1, ICAM-1, IL-1ß, IL-6, and COX-2 were also up-regulated among the 180WIT group, although MIP-2 and PAI-1 showed no significant differences among the groups. CONCLUSIONS: We suggest that the ERK and JNK pathways may play important roles to induce the injury caused by prolonged warm ischemia followed by reperfusion in the setting of lung transplantation from DCD donors.

Less maintenance immunosuppression in lung transplantation following hematopoietic stem cell transplantation from the same living donor.

Living-donor lobar lung transplantation (LDLLT) is one of the final options for saving patients with pulmonary complications after hematopoietic stem cell transplantation (HSCT). We retrospectively investigated 19 patients who had undergone LDLLT after HSCT in Japan. Eight patients underwent LDLLT after HSCT in which one of the donors was the same living donor as in HSCT (SD group), while 11 received LDLLT from relatives who were not the HSCT donors (non-SD group). In the SD group, three patients underwent single LDLLT. The 5-year survival rate was 100% and 58% in the SD and non-SD groups, respectively. In the SD group, postoperative immunosuppression was significantly lower than in the non-SD group. Two patients died of infection and one died of post-transplant lymphoproliferative disease (PTLD) in the non-SD group, while only one patient died of PTLD 7 years after LDLLT in the SD group. Hematologic malignancy relapsed in two patients in the non-SD group. For the three single LDLLTs in the SD group, immunosuppression was carefully tapered. In our study, LDLLT involving the same donor as for HSCT appeared to have advantages related to lower immunosuppression compared to LDLLT from relatives who were not the HSCT donors.

[Treatment strategy and outcomes of invading apical lung cancer].

Invading apical lung cancers are generally the non-small-cell lung cancers (NSCLCs) which involve the apex of the chest wall. These tumors should be classified into 2 types based on the main location of tumor because of the difference of involved surrounding structures ; (1) the superior sulcus tumor origi nally termed Pancoast tumor which involves posterior region of the apex and (2) the anterior apical tumor which involves anterior region of the apex. Previously, these NSCLCs were considered to be inoperable showing a dismal prognosis. With the development of combined modality therapies for locally advanced NSCLCs, the prognosis of invading apical NSCLCs has been improved, especially since intro duction of the neoadjuvant chemoradiotherapy. Surgical resection for invading apical NSCLCs is 1 of challenging procedures for thoracic surgeons. The point is the anatomical complication of the small apex surrounding vital structures. Several approaches have been developed such as the posterior Paul-son's approach or anterior Masaoka's approach. In particular, the approach from anterior chest has been modified or devised to achieve safe and complete resection of tumors invading anterior structures like subclavian vessels. In this article, we reviewed our 13 cases of invading apical NSCLCs, especially from the view point of surgical approach. Thoracic surgeons should understand the properties of each approach and master them for complete resection avoiding serious complications.

[Bronchoplasty and pulmonary arterioplasty for treatment of lung cancer].

OBJECTIVE: We evaluated the outcomes of bronchoplasty (BP) and pulmonary arterioplasty (PAP) for treatment of patients with lung cancer. SUBJECTS: We studied 33 patients who underwent BP and/or PAP over the previous 7 years at our institution. METHODS: A telescope procedure was utilized for anastomosis of a tubular excision performed in the bronchus. One patient received induction chemoradiotherapy, in whom the anastomosis section was covered with an intercostal muscle flap to assure anastomosis completion, then PAP was performed under heparinization. RESULTS: BP including a sleeve resection was performed in 15 patients, while that with a wedge resection and partial side wall resection was performed in 7 and 1 patient, respectively. PAP was performed in 18 patients, and a combination of BP and PAP was used in 8. The seam was incomplete in 2 patients and stenosis was recognized in the anastomosis section in 1. No local recurrence at the anastomosis site was seen in any of the 33 cases. The survival rate for patients who underwent BP was similar to that of those who underwent a standard resection for primary lung cancer. CONCLUSION: Our results indicate that BP and PAP are safe and useful surgical procedures for patients with lung cancer.

Photosensitization reaction-induced electrical blockade in myocardial tissue.

We proposed the application of photodynamic therapy (PDT) as a new type of atrial fibrillation treatment. PDT is well known as a practical cancer treatment using cytotoxicity of reactive oxygen species generated by the photochemical interaction. We predicted that the photocytotoxic effect induced by PDT might cause electrical blockade in myocardial tissue. We studied the electrical blockade induced by the PDT with talaporfin sodium in vitro, ex vivo, and in vivo. The cell lethality measurement using rat cardiac myocytes confirmed the PDT-induced photocytotoxic effect and its dependence on the loading time of the photosensitizer. In ex vivo experiment using rat right ventricle, the PDT caused a shutdown of the stimulated electrical signal propagation. The long-lasting atrioventricular block induced by the PDT was obtained in vivo experiment with rat heart. These results revealed the possibility of atrial fibrillation treatment with the PDT.

[Surgical technique of displacement and retraction of the heart with a pigtail shaped hook and Tentacles Heart Positioner].

We describe a novel heart retracting system with Tentacles Heart Positioner (Sumitomo Bakelite, Tokyo) during off-pump coronary artery bypass grafting (OPCAB). The heart retracting system is composed of a pigtail shaped hook attached to a flexible Universal Stabilizer Arm (Estech, Minneapolis). After Tentacles suction device is applied on the surface of the heart, the retracting system is fixed on the sternal retracter so that the hook can hang and support the retracting tubes of the sucker. By regulating the shape of the Universal Stabilizer Arm and the position of the hook, the retracting system can lift the heart sufficiently and maintain the optimal position of the heart during OPCAB procedure. Together with Tentacles Heart Positioner, the heart retracting system provides excellent exposure of target coronary arteries with minimal effect on hemodynamics.

Observation and control of transverse energy-transport barrier due to the formation of an energetic-electron layer with sheared ExB flow.

Off-axis electron-cyclotron heating in an axisymmetric barrier mirror produces a cylindrical layer with energetic electrons, which flow through the central cell and into the end region. The layer, producing a localized bumped ambipolar potential Phi(C), forms a strong shear of radial electric fields E(r) and peaked vorticity with the direction reversal of E(r)xB sheared flow near the Phi(C) peak. Intermittent vortexlike turbulent structures near the layer are suppressed in the central cell by this actively produced transverse energy-transport barrier; this results in T(e) and T(i) rises surrounded by the layer.

The effect of ephedrine and phenylephrine on BIS values during propofol anaesthesia.

BACKGROUND: The purpose of this study was to evaluate the effect of ephedrine and phenylephrine on propofol concentrations and bispectral index during propofol anesthesia. METHODS: General anaesthesia was induced with propofol and was maintained with propofol (4 mg kg-1 h-1) and fentanyl. Vecuronium was used to facilitate the artificial ventilation of the lungs. Patients with systolic blood pressure > 90 mmHg were defined as the control group (n = 16). Patients who had to be treated for larger decreases in arterial blood pressure (systolic blood pressure 60, whereas no patient in the control or phenylephrine groups had bispectral index >60. There were no significant differences in propofol concentrations or cardiac output relative to baseline at 3 or 10 min after the administration of ephedrine or phenylephrine. CONCLUSIONS: Ephedrine increases bispectral index values without decreasing propofol concentrations during general anesthesia.

Observation of the effects of radially sheared electric fields on the suppression of turbulent vortex structures and the associated transverse loss in GAMMA 10.

Vortexlike turbulent structures in hot-ion mode plasmas with several keV are observed in the case with a radially produced weak shear of electric fields E(r). However, a strong E(r) shear formation due to a high ion-confining potential phi(c) production clears up these vortices together with plasma-confinement improvement and disappearance of both drift-wave and turbulencelike Fourier spectral signals. These findings are based on three-time progress in phi(c) in comparison to phi(c) attained 1992-2002. The significant advance of phi(c) is well extended in line with proposed potential-formation physics scalings.

A viral envelope as a vehicle for tracer, drug, and gene delivery: initial biodistribution study using PET imaging.

Viral envelopes can be used as an effective vehicle to deliver imaging tracers as well as therapeutic drugs and genes. However, the current methods for in vivo tracking of viral envelopes are limited. This purpose of this study is to investigate dynamically the in vivo biodistribution of viral envelopes using positron emission tomography (PET) imaging. The hemagglutinating virus of Japan envelope (HVJ-E) was labeled with radioactive fluorine (F-18) for tracking with PET imaging. Due to the low molecular weight of F-18, the encapsulation process by HVJ-E was optimized using the cationic agent poly-L-lysine (PLL, MW 66.7 kDa) and Feridex, a magnetic resonance imaging tracer. After labeling, HVJ-Es were injected intravenously into the normal rat and followed for 2 h using high resolution PET imaging. Region of interest analysis showed a significant increase in average liver accumulation based on radioactivity as compared to all control subjects. Average brain uptake showed a significant increase in radioactivity as compared to control subjects receiving F-18-PLL complexes or F-18 alone. Control subjects showed F-18 uptake primarily in the bones. These results demonstrate a molecular imaging technique that can be used to monitor drug and gene delivery and evaluate potential targeting mechanisms.

A Viral Envelope as a Vehicle for Tracer, Drug, and Gene Delivery: Initial Biodistribution Study Using PET Imaging.

Viral envelopes can be used as an effective vehicle to deliver imaging tracers as well as therapeutic drugs and genes. However, the current methods for in vivo tracking of viral envelopes are limited. This purpose of this study is to investigate dynamically the in vivo biodistribution of viral envelopes using positron emission tomography (PET) imaging. The hemagglutinating virus of Japan envelope (HVJ-E) was labeled with radioactive fluorine (F-18) for tracking with PET imaging. Due to the low molecular weight of F-18, the encapsulation process by HVJ-E was optimized using the cationic agent poly-L-lysine (PLL, MW 66.7 kDa) and Feridex, a magnetic resonance imaging tracer. After labeling, HVJ-Es were injected intravenously into the normal rat and followed for 2 h using high resolution PET imaging. Region of interest analysis showed a significant increase in average liver accumulation based on radioactivity as compared to all control subjects. Average brain uptake showed a significant increase in radioactivity as compared to control subjects receiving F-18-PLL complexes or F-18 alone. Control subjects showed F-18 uptake primarily in the bones. These results demonstrate a molecular imaging technique that can be used to monitor drug and gene delivery and evaluate potential targeting mechanisms.