Nemoto (Japan)

Background: Bronchoscopy is a mandatory tool used to diagnose endobronchial tuberculosis (EBTB); however, it is not routinely performed on all patients with pulmonary tuberculosis (PTB) because of the risk of exposure to airborne Mycobacterium tuberculosis. Early diagnosis of EBTB is essential for watchful waiting and treatment planning of residual bronchostenosis. Therefore, physicians need to determine the incidence of EBTB according to the implementation rate of bronchoscopy in each region and identify patients with PTB requiring bronchoscopy on initial evaluation. We evaluated the implementation rate of bronchoscopy among patients with PTB and assessed the incidence and risk factors of concomitant EBTB.

Precise gastrulation is essential for formation of functional bodies in cnidarians and bilaterians. Previously, by using an alk4/5/7-specific inhibitor, we showed that transforming growth factor-beta (TGF-ß)-alk4/5/7 signaling pathway is important for correct gut bending in sea urchin embryos. However, it is still unclear where functional TGF-ß signals are received in embryos for correct gut bending because details of the spatiotemporal expression pattern of alk4/5/7 have not been reported. We revealed that alk4/5/7 are expressed from the 2-cell to early pluteus stage throughout the entire body, including the invaginating gut. To investigate whether TGF-ß signals directly received in endoderm are required for correct gut bending, we made chimeras in which alk4/5/7 translation was inhibited only in endomesoderm lineage. As a result, the gut of the chimeric embryos did not bend precisely, in contrast to the control chimeras. We conclude that direct TGF-ß signaling to the endoderm via alk4/5/7 pathway regulates correct gut bending. However, TGF-ß-alk4/5/7 pathway is not related to mouth opening because the mouth is formed without TGF-ß signaling to the endoderm. This research contributes to understanding the mechanisms leading to the proper positioning of the end of the archenteron for forming a through-gut, which is commonly needed for bilaterians.

Piezoelectric crystals are widely used in many applications such as oscillators, sensors, and actuators. The mechanisms of piezoelectricity could be explained from atomic displacements under a static electric field. However, atomic displacements under a static electric field are usually too small to be detected by conventional Xray diffraction (XRD) measurements. The small atomic displacements can be resonantly amplified by mechanical vibrations under an alternating electric field with the resonant frequency. We have recently succeeded in detecting the small atomic displacements of resonantly vibrating quartz (SiO 2 ) and langasite-type (La 3 Ga 5 SiO 14 and Nd 3 Ga 5 SiO 14 ) piezoelectric crystals by the time-resolved synchrotron radiation XRD measurements under an alternating electric field [1-3].

Hemodynamic compromise identified by cerebrovascular reserve (CVR) and oxygen extraction fraction (OEF) in stroke patients with large artery occlusion is an independent predictor of stroke risk ranging from 27 to 57%. However, comparison of both methods indicates that the sensitivity of CVR is substantially greater than OEF in detecting hemodynamic compromise which may be because CVR includes a vasodilator challenge with acetazolamide as opposed to OEF made in the resting state. We hypothesized that the response of OEF (OEFR) to an acetazolamide challenge would better correlate with CVR than OEF. We examined the correlation between CVR and OEFR to acetazolamide in stroke patients with large artery occlusion. Methods: Stroke patients with large artery occlusion (internal carotid or middle cerebral artery) were studied by positron emission tomography (PET) using H2 15O2 (water) for cerebral blood flow (CBF) and 15O2 (gas) for cerebral metabolic rate for oxygen before and after acetazolamide. CVR was calculated as: CVR (%) = [(CBFa- CBFb)/CBFb] X 100; where: CBFb = CBF before acetazolamide, CBFa = CBF after acetazolamide. OEF response (OEFR) was similarly calculated as: OEFR (%) = [(OEFa-OEFb)/OEFb]X100; for the entire middle cerebral artery territory of each hemisphere. Results: There was a highly significant (P=0.0001) negative linear correlation between CVR and OEFR indicating increasing ischemic stress (Figure). Hemispheres from three patients showed a positive OEFR. Discussion: A positive OEFR in response to a cerebrovascular challenge definitively indicates hemodynamic compromise and eliminates the problem of deciding on the absolute threshold for OEF to signify hemodynamic compromise. A negative OEFR reflects sufficient cerebrovascular reserve relative to oxygen demand.

Introduction: Tissue plasminogen activator is used in only 5% of stroke patients because therapeutic window is short (∼3 hr) due to risk of hemorrhage. Rheological modulation of blood flow by nanomolar concentrations of drag-reducing polymers (DRP) improved hemodynamics and survival in animal models of the ischemic myocardium and limb. We previously showed that DRP applied early at 30 min after permanent middle cerebral artery occlusion (pMCAO) restored microvascular perfusion and improved neurologic outcome. We hypothesized that DRP applied after 3 hr delay would be effective in improving recovery. Methods: DRP or saline (control) were i.v. injected 3 hours after pMCAO in rats. Evaluation of the acute DRP effects (5 hours after pMCAO) on microvascular perfusion, hypoxia (NADH) and blood brain barrier (BBB) was done by in-vivo 2-photon laser scanning microscopy (2PLSM) and followed by brain perfusion for Fluoro-Jade staining for neurodegeneration. Cerebral infarction and perfusion were evaluated by MRI at 24 hours, 1 and 3 weeks after pMCAO. Motor function was evaluated by Rotarod test at 1, 2 and 3 weeks after pMCAO. Results: DRP compared to saline, applied after 3 hours following pMCAO, improved impaired microvascular circulation in the penumbra of the parietal cortex (Δ=33 %), reducing hypoxia (Δ=27 %) and BBB damage (Δ=42 %) thereby protecting neurons from neurodegeneration (Fluoro-Jade, Δ=36 %) (n=4, p<0.05). After prolonged recovery, DRP solution compared to saline reduced infarct expansion (Δ=23 %) and increased cerebral blood flow (Δ=31 %) in the penumbra at 24 hours, 1 and 3 weeks after pMCAO as measured by MRI (n=6, p<0.05). Rotarod tests showed that DRP treated rats performed better than saline treated (Δ=35 %) at 1, 2 and 3 weeks after the pMCAO (n=6, p<0.05). Conclusions: Rheological enhancement of cerebral microcirculation by DRP improved neurologic outcome after permanent MCAO without reperfusion even with delayed application after stroke onset. Potential DRP mechanisms involve improved collateral flow and anti-inflammatory effects of the increased shear stress with enhanced microcirculatory flow. DRP may be an effective therapy for ischemic stroke even without reperfusion and after delayed administration following the stroke onset.

To evaluate the effect of a newly developed connecting tube, which generates a spiral flow of saline, on aortic and hepatic contrast enhancement during hepatic-arterial phase (HAP) and portal venous phase (PVP) computed tomography (CT). Eighty patients were randomly assigned to one of two protocols: with a new or a conventional tube. The contrast material (600 mgI/kg) was delivered over 30 s; this was followed by the administration of 25 ml saline solution delivered at the same injection rate as the contrast material. Unenhanced and contrast-enhanced CT images of the upper abdomen were obtained. We calculated the changes in the CT number (∆HU) for the aorta during HAP and PVP, and for the liver during PVP. We compared ∆HU between protocols. The mean ∆HU for the abdominal aorta during HAP was significantly higher with the new tube protocol than with the conventional tube protocol (322 ± 53 vs. 290 ± 53, P < 0.01). There were no significant differences in the mean ∆HU for the abdominal aorta and liver during PVP between the two protocols (P > 0.05). The new connecting tube increased the effect of a saline chaser and significantly improved aortic enhancement during HAP. • Optimal administration of intravenous contrast material is essential for optimal CT quality. • A new connecting tube can generate spiral flow, which improves intravenous administration. • The new connecting tube improved aortic contrast enhancement during the hepatic-arterial phase. • The new connecting tube increased the effect of a saline chaser.

Fully implantable VAD and TAH are eager to be developed as destination therapy for the severe heart failure patients who do not be candidate of heart transplantation. We have been developing fully implantable VAD and TAH using undulation pump(UP) under multi-institutional cooperative project supported by the Program for Promotion of Fundamental Studies in Health Sciences of the Pharmaceuticals and Medical Device Agency(PMDA). The objective of this presentation is to introduce the present status of their development.

During the past 15 years, the concept of dysembryoplastic neuroepithelial tumors has continued to evolve. We present an interesting case of dysembryoplastic neuroepithelial tumor that showed rapid growth during a short period of time. A 9-year-old boy had been experiencing intractable complex partial seizures since the age of 7 years. Magnetic resonance imaging scans demonstrated a well-demarcated 3.5-cm lesion with a 1.5-cm ring-enhanced core in the left temporal lobe. One month later, the lesion had rapidly grown to occupy three times more space than on the first evaluation, with the ring-enhanced core reaching approximately five times its initial volume. A combined tumor removal and epileptogenic focus resection surgery was performed immediately. In the pathological examination, the presence of the specific glioneuronal element with a Ki-67 labeling index of lower than 1%, as well as the glial component with a Ki-67 labeling index of 8%, led to a postoperative diagnosis of dysembryoplastic neuroepithelial tumor, complex form. No adjuvant therapy was performed. Five years after surgery, there is no evidence of any recurrence and the boy continues to be seizure free without antiepileptic drugs. The lesion did not behave as a stable benign entity as it is generally accepted, and is, therefore, presented as an argument in favor of an early and complete resection.

TJ-8117 (Onpi-to) is a herbal medicine extracted from mixture of five crude drugs (Rhei Rhizoma, Glycyrrhizae Radix, Ginseng Radix, Zingiberis Rhizoma and Aconiti Tuber), which has been developed as a drug for chronic renal failure. (-)Epicatechin 3-O-gallate (ECG), one of the active compounds of TJ-8117, was labeled with tritium and spiked to TJ-8117. Effects of food, renal failure and repeated administration to pharmacokinetics of ECG-related radioactivity in the plasma were investigated after oral administration of TJ-8117 containing [3H]ECG ([3H]TJ-8117) in male rats. After oral administration of [3H]TJ-8117, the radioactivity in the plasma in non-fasted rats was higher than that in fasted rats. AUC(0-72 h) and Cmax in the non-fasted was 123% and 248% of those in the fasted. After oral administration of [3H]TJ-8117, the radioactivity in the plasma in 5/6 nephrectomized rats was higher than that in sham-operated rats. AUC(0-72 h) and Cmax in 5/6 nephrectomized was 332% and 236% of those in sham-operated. After repeated administration of TJ-8117 for 6 days, [3H]TJ-8117 was administered on 7th day. Radioactivity in plasma in first day was similar to that in 7th day. The pharmacokinetic parameters were not significantly different between single and repeated administration.

The europium(II) sites in Sr4Al 14O25 ∶ Eu phosphor with blue emission were examined by means of high frequency (90 and 180 GHz) EPR spectroscopy. The ions occupy two low symmetry sites in the Sr4Al 14O25 lattice with |D| = 0.100 and 0.0907 cm−1 respectively; the ratio |E/D | is estimated to be 1/3 regardless of the substitution site. This implies that the crystal field surrounding europium(II) ions has non-axial symmetry. EPR spectral simulation suggests that the europium( II) ions preferentially occupy the site with the larger |D | when they substitute for strontium ions. Comparison of the EPR spectra of Sr4Al14O25 ∶ Eu and SrAl2O4 ∶ Eu,Dy phosphors shows that the Sr4Al14O25 ∶ Eu is present as an impurity in the non-stoichiometric SrAl2O 4 ∶ Eu,Dy when prepared with excess amounts of Al 2O3. Such materials have been found to have long phosphorescent characteristics.