Serum cell-free DNA levels are a useful marker for extramammary Paget disease.

BACKGROUND: Although carcinoembryonic antigen (CEA) and cytokeratin 19 fragment (CYFRA) are useful markers for extramammary Paget disease (EMPD), serum CEA and CYFRA levels are not elevated in most patients with EMPD without metastasis. Cell-free (cf)DNA has attracted attention as an indicator of clinical conditions in several cancers. OBJECTIVES: To identify further useful biomarkers for the detection of EMPD, including early lesions, and to study the clinical implications of cfDNA in EMPD. METHODS: cfDNA were isolated from serum of patients with EMPD with and without metastasis, and from healthy volunteers. Serum extracts were amplified using polymerase chain reaction. RESULTS: Serum cfDNA levels were significantly elevated in patients with EMPD with or without metastasis compared with those in healthy controls. Serum cfDNA was a better diagnostic marker for the presence of EMPD than serum CYFRA. Moreover, the postoperative serum cfDNA levels were significantly lower than those from the preoperative samples, and the change in serum cfDNA levels reflected the clinical courses of patients with EMPD treated with chemotherapy. CONCLUSIONS: Taking the evidence together, serum cfDNA levels may be a useful marker for diagnosis and disease progression in EMPD. What's already known about this topic? Serum levels of carcinoembryonic antigen (CEA) and cytokeratin 19 fragment (CYFRA) are not elevated in most patients with extramammary Paget disease (EMPD) without metastasis. Cell-free (cf)DNA has attracted attention as an indicator of clinical conditions in several cancers. There are few reports of the clinical implications of cfDNA in dermatology. What does this study add? Serum cfDNA levels were significantly elevated in patients with EMPD with or without metastasis compared with those in healthy controls. Postoperative serum cfDNA levels were significantly lower than those from the preoperative samples. Changes in serum cfDNA levels reflected the clinical courses of patients with EMPD treated with chemotherapy. What is the translational message? Serum cfDNA levels in patients with EMPD are a useful marker for the detection of EMPD, including localized EMPD. Changes in serum cfDNA levels in an individual patient may reflect the clinical course of EMPD.

Detection of current-sheet and bipolar ion flows in a self-generated antiparallel magnetic field of laser-produced plasmas for magnetic reconnection research.

Magnetic reconnection in laser-produced magnetized plasma is investigated by using optical diagnostics. The magnetic field is generated via the Biermann battery effect, and the inversely directed magnetic field lines interact with each other. It is shown by self-emission measurement that two colliding plasmas stagnate on a midplane, forming two planar dense regions, and that they interact later in time. Laser Thomson scattering spectra are distorted in the direction of the self-generated magnetic field, indicating asymmetric ion velocity distribution and plasma acceleration. In addition, the spectra perpendicular to the magnetic field show different peak intensity, suggesting an electron current formation. These results are interpreted as magnetic field dissipation, reconnection, and outflow acceleration. Two-directional laser Thomson scattering is, as discussed here, a powerful tool for the investigation of microphysics in the reconnection region.

Direct observations of pure electron outflow in magnetic reconnection.

Magnetic reconnection is a universal process in space, astrophysical, and laboratory plasmas. It alters magnetic field topology and results in energy release to the plasma. Here we report the experimental results of a pure electron outflow in magnetic reconnection, which is not accompanied with ion flows. By controlling an applied magnetic field in a laser produced plasma, we have constructed an experiment that magnetizes the electrons but not the ions. This allows us to isolate the electron dynamics from the ions. Collective Thomson scattering measurements reveal the electron Alfvénic outflow without ion outflow. The resultant plasmoid and whistler waves are observed with the magnetic induction probe measurements. We observe the unique features of electron-scale magnetic reconnection simultaneously in laser produced plasmas, including global structures, local plasma parameters, magnetic field, and waves.

High-power laser experiment on developing supercritical shock propagating in homogeneously magnetized plasma of ambient gas origin.

A developing supercritical collisionless shock propagating in a homogeneously magnetized plasma of ambient gas origin having higher uniformity than the previous experiments is formed by using high-power laser experiment. The ambient plasma is not contaminated by the plasma produced in the early time after the laser shot. While the observed developing shock does not have stationary downstream structure, it possesses some characteristics of a magnetized supercritical shock, which are supported by a one-dimensional full particle-in-cell simulation taking the effect of finite time of laser-target interaction into account.

Robustness of large-area suspended graphene under interaction with intense laser.

Graphene is known as an atomically thin, transparent, highly electrically and thermally conductive, light-weight, and the strongest 2D material. We investigate disruptive application of graphene as a target of laser-driven ion acceleration. We develop large-area suspended graphene (LSG) and by transferring graphene layer by layer we control the thickness with precision down to a single atomic layer. Direct irradiations of the LSG targets generate MeV protons and carbons from sub-relativistic to relativistic laser intensities from low contrast to high contrast conditions without plasma mirror, evidently showing the durability of graphene.

High-power laser experiment forming a supercritical collisionless shock in a magnetized uniform plasma at rest.

We present an experimental method to generate quasiperpendicular supercritical magnetized collisionless shocks. In our experiment, ambient nitrogen (N) plasma is at rest and well magnetized, and it has uniform mass density. The plasma is pushed by laser-driven ablation aluminum (Al) plasma. Streaked optical pyrometry and spatially resolved laser collective Thomson scattering clarify structures of plasma density and temperatures, which are compared with one-dimensional particle-in-cell simulations. It is indicated that just after the laser irradiation, the Al plasma is magnetized by a self-generated Biermann battery field, and the plasma slaps the incident N plasma. The compressed external field in the N plasma reflects N ions, leading to counterstreaming magnetized N flows. Namely, we identify the edge of the reflected N ions. Such interacting plasmas form a magnetized collisionless shock.

Mode of action of a new indolocarbazole anticancer agent, J-107088, targeting topoisomerase I.

J-107088 [6-N-(1-hydroxymethyl-2-hydroxy)ethylamino-12,13-dihydro-2,10-dihydroxy- 13-(beta-D-glucopyranosyl)-5H-indolo[2,3-a]-pyrrolo[3,4-c]-carb azo le-5,7(6H)-dione] is a new derivative of NB-506, an indolocarbazole antitumor agent. J-107088 induced single-strand DNA cleavage only in the presence of topoisomerase I (top1) more effectively than NB-506 or camptothecin. The preferable sequences of the DNA cleaved by J-107088 were C/T / G as in the case of NB-506. This base-preference of J-107088 in top1-mediated cleavage was different from that of camptothecin, which was T / G/A. top1 poisons stabilize the complex between DNA and top1 (cleavable complex). This cleavable complex is released on addition of a high concentration of monovalent cation or removal of top1 poisons. The complex induced by J-107088 was quite stable; it was scarcely released on the addition of NaCl or dilution of J-107088, contrary to the case with camptothecin and NB-506. J-107088-inducing complexes were also stable in cultured cells, when the compound was added to the culture medium. These unique in vitro activities of J-107088 on top1 that differed from those of camptothecin and NB-506 may be relevant to its more potent in vivo antitumor efficacy in a human tumor xenographted nude mouse model.

Iodine-123 metaiodobenzylguanidine images reflect intense myocardial adrenergic nervous activity in congestive heart failure independent of underlying cause.

OBJECTIVES: This study was undertaken to assess myocardial adrenergic activity using iodine-123 metaiodobenzylguanidine (MIBG) imaging in patients with heart failure. BACKGROUND: In patients with congestive heart failure, adrenergic nerve activity is accelerated. However, whether myocardial adrenergic nerve activity reflects the severity of heart failure and its relation to the underlying cause have not yet been elucidated. METHODS: Planar MIBG images were obtained from 96 patients with heart failure and compared with images from 9 age-matched healthy subjects. Groups 1 and 2 included 65 patients with heart failure related to impaired myocardial function and whose left ventricular ejection fraction was < 40% (group 1 = 40 patients with dilated cardiomyopathy; group 2 = 25 patients with ischemic cardiomyopathy). Group 3 included 31 patients with heart failure related to a mechanical abnormality and whose left ventricular ejection fraction was > 40% (mitral regurgitation in 16, aortic regurgitation in 9, aortic and mitral regurgitation in 4, ruptured aneurysm of Valsalva in 2). Myocardial uptake of MIBG was calculated as the heart/mediastinal activity ratio. Storage and release of MIBG were calculated as percent myocardial MIBG washout from 15 min to 4 h after isotope injection. RESULTS: The heart/mediastinal activity ratio in the immediate images (15 min) showed a significant decrease only in patients with severe heart failure (groups 1 and 2). The myocardial washout was accelerated in all three heart failure groups. The level of myocardial washout was related to severity of heart failure and correlated well with New York Heart Association functional classification. CONCLUSIONS: In severe heart failure associated with cardiomyopathy, norepinephrine uptake is reduced. In addition, myocardial adrenergic nerve activity is accelerated in proportion to severity of heart failure, independent of the underlying cause.

Augmentation of coronary responsiveness to serotonin at the site of X-ray-induced intimal thickening in miniature pigs.

OBJECTIVE: X-irradiation is known to enhance atherosclerotic change. We tested whether coronary vasoconstrictor responses are augmented at the sites of X-ray-induced intimal thickening in Göttingen miniature pigs. METHODS: In 17 pigs, a major branch of the left coronary artery was denuded with a balloon catheter. In 10 pigs, the denuded portion of the left coronary artery was selectively irradiated with 15 Gy of X-rays twice at 3 and 4 months after denudation (group 1). The remaining 7 pigs were not irradiated (group 2). The effects of intracoronary administration of serotonin, histamine and phenylephrine on the coronary diameter were studied 3 (3M) and 5 months (5M) after denudation. After the angiographical study at 5M, the vessels were isolated and isometric tension was measured in an organ chamber. RESULTS: The percent reduction in coronary diameter evoked with 10 micrograms.kg-1 of serotonin increased from 39(s.e.m. 4)% before X-irradiation (3M) to 75(6)% after X-irradiation (5M) in group 1 (P < 0.01), while it did not differ in group 2 [39(6)% at 3M vs. 33(8)% at 5M[ [39(6)% at 3M vs. 33(8)% at 5M]. In group 1, serotonin-induced coronary constriction was frequently accompanied by ischemic ECG changes. Histamine (10 micrograms.kg-1)-induced vasoconstriction was also augmented but to a smaller degree [47(6)% at 3M vs. 62(4)% at 5M; P < 0.05] in group 1, while it remained unchanged in group 2[52(5)% at 3M vs. 44(7)% at 5M]. Phenylephrine did not cause detectable contraction in either group at 3M or 5M. Methysergide and ketanserin attenuated serotonin-induced hypercontraction in a dose-dependent fashion. In the in vitro studies, endothelium-dependent relaxation to serotonin was impaired at the denuded site with (group 1) and without (group 2) X-irradiation to a similar extent. Isometric tension of medial smooth muscle developed by serotonin was significantly greater at the denuded site with X-irradiation (group 1) than the control site and the denuded site without X-irradiation (group 2) (P < 0.05). Intimal thickening was significantly greater at the denuded sites with X-irradiation [group 1, 238(45) microns] than at the denuded sites without X-irradiation [group 2, 58(5) microns] (P < 0.05). CONCLUSIONS: These results indicate that X-irradiation augments the coronary vasoconstrictor responses to autacoids, predominantly to serotonin, and that this augmentation is accompanied by enhanced intimal thickening. Serotonin-induced hypercontraction after X-irradiation resulted mainly from the hyperreactivity of medial smooth muscle.

Influence of downscatter in simultaneously acquired thallium-201/technetium-99m-PYP SPECT.

UNLABELLED: Simultaneously acquired dual-isotope imaging is a unique and useful approach in SPECT. Photon spillover, however, is a potential limitation of this technique. METHODS: To investigate the degree of 99mTc downscatter into the 201Tl window in patients, simultaneously acquired dual-isotope 201Tl/99mTc-pyrophosphate imaging was performed in 17 patients with acute myocardial infarction (MI). Thallium-201 SPECT imaging was performed first, with a 201Tl photopeak window after the 201Tl injection (early 201Tl images), followed by 99mTc injection and SPECT acquisition using dual-isotope windows (dual 201Tl images). Twenty-four hours after the 99mTc injection, a third set of 201Tl images was obtained (24-hr 201Tl images). Thallium defect size (extent score) and defect severity (severity score) were calculated from these three sets of 201Tl images to quantify the MI. RESULTS: Technetium-99m accumulation of varying intensity was recognized in all patients. Extent scores and severity scores were identical in early 201Tl images and 24-hr 201Tl images. Both scores, however, in the dual 201Tl images were decreased by 36% and 53%, respectively. CONCLUSION: There in a considerable 99mTc downscatter into the 201Tl window, which prevents precise quantification of MI in simultaneously acquired dual-isotope 201Tl/99mTc-pyrophosphate imaging.

The effect of cycloplegia on measurement of the ocular components.

PURPOSE: The purpose of this study was to examine the effect of cycloplegic agent on the measurement of refractive error and the ocular components. METHODS: We compared two commonly used topical cycloplegic agents, 1% tropicamide and 1% cyclopentolate, for their effect on the measurement of refractive error (by Canon R-1 autorefraction), accommodative response (by Canon R-1 autorefraction and by the conventional, subjective "pushup" method), crystalline lens power (by video phakometry and by calculation), and axial ocular dimensions (by A-scan ultrasonography) in 20 emmetropic to moderately hyperopic children. RESULTS: Comparison of refractive error at each drug's reported time of maximum cycloplegia (30 minutes for tropicamide and 60 minutes for cyclopentolate) showed that distance autorefraction in the vertical meridian differed by +0.20 +/- 0.30 diopters (D) (P = 0.008). The average difference was +0.07 +/- 0.10 mm for anterior chamber depth (P = 0.004), -0.03 +/- 0.05 mm for crystalline lens thickness (P = 0.025), -0.65 +/- 0.69 D for phakometrically measured crystalline lens power (P < 0.001), +0.03 +/- 1.55 D for calculated crystalline lens power (P = 0.94), and -0.09 +/- 0.19 mm for vitreous chamber depth (P = 0.062, all paired t tests; positive signs denote greater values with cyclopentolate). Residual accommodation was 0.47 and 0.67 D greater with tropicamide when measured by autorefraction and the pushup method (P = 0.013 and 0.08 respectively, paired t test). All significant differences were consistently in the direction of poorer cycloplegia with tropicamide. CONCLUSIONS: Although tropicamide, as expected, showed poorer cycloplegia compared to cyclopentolate, the degree of difference appeared to be small, with minimal effect on the measurement of distance refractive error and the ocular optical components.

Structure, tissue distribution, and pharmacological characterization of Xenopus orexins.

We isolated the Xenopus gene encoding prepro-orexin to predict the structures of orexins in submammalian chordates. Putative mature Xenopus orexin-A and -B are highly similar to each mammalian counterpart. Especially, the C-terminal 10 residues were highly conserved among these species and isopeptides. Immunohistochemical examination of Xenopus brain revealed that orexin-containing neurons were highly specifically localized in the ventral hypothalamic nucleus. A rich network of immunoreactive fibers was found in various regions of the Xenopus brain. The distribution was similar to that of mammalian orexins. Xenopus orexin-A and -B specifically bind and activate human orexin receptors expressed in Chinese hamster ovary cells. Of interest, Xenopus orexin-B had several-fold higher affinity to human OX2R compared with human orexins. These results suggest that Xenopus orexin-B might be a useful pharmacological tool as an OX2R selective high-affinity agonist.

Sustained dilatation of large coronary artery by alpha-human atrial natriuretic peptide in conscious dogs: a comparison with nitroglycerin.

The effects of alpha-human atrial natriuretic peptide (alpha-hANP) on the coronary circulation were compared with those of nitroglycerin in 16 conscious dogs chronically instrumented with a pair of miniature sonomicrometers and an electromagnetic flow probe placed on the left circumflex coronary artery. alpha-hANP (1 and 10 micrograms) and nitroglycerin (0.1, 1 and 10 micrograms) were administered intracoronarily via a cannula implanted in the proximal left circumflex coronary artery. Both alpha-hANP and nitroglycerin dose dependently increased the coronary diameter and coronary blood flow. Although alpha-hANP (10 micrograms) and nitroglycerin (1 microgram) dilated the large coronary artery to almost the same extent (92 +/- 10 vs. 98 +/- 8 microns), the time course of the dilating action differed; the peak dilatation occurred at 5.6 +/- 0.8 and 0.9 +/- 0.07 min (P less than 0.01), and full recovery occurred at 31.5 +/- 3.8 and 5.5 +/- 1.3 min (P less than 0.01) after alpha-hANP and nitroglycerin, respectively. Topical application of alpha-hANP (50 micrograms) to the epicardial coronary artery of three anesthetized open-chest dogs did not affect the coronary diameter and coronary blood flow, while nitroglycerin (50 micrograms) increased both variables. Thus, intracoronary alpha-hANP dilates the large coronary artery more gradually and more sustainedly than nitroglycerin does.

Clinical characteristics and long-term prognosis of patients with variant angina. A comparative study between western and Japanese populations.

To determine the factors influencing the prognosis of variant angina, the clinical characteristics and long-term prognosis of 158 consecutive Japanese patients were examined and compared with those in previous major western studies (Pisa, Montreal, and Duke studies). The Japanese patients were characterized by relatively low prevalences of coronary risk factors, significant coronary stenoses and previous myocardial infarction. Survival and survival without myocardial infarction for the entire group or for the subpopulation with significant coronary artery disease were significantly better in the Japanese population than in the western populations; however, in the subpopulation without significant coronary artery disease, the prognosis was excellent in all four studies. If the prevalence of coronary artery disease was corrected for the Japanese population, there would be no difference in the prognosis between the Japanese and the western populations. It is concluded: (1) the overall prognosis of variant angina may be better in Japanese patients, and (2) coronary artery disease appears to be the strongest prognostic factor for assessing the differences in the prognosis between the Japanese and the western populations.

Pathogenicity of bacteria using a simulated root canal system.

The purpose of this study was to investigate the reliability of an implantation test using Teflon-simulated root canals for evaluating the pathogenicity of root canal bacteria. Models including suspensions of lyophilized strains (Actinomyces israelii, Streptococcus faecalis, and Porphyromonas asaccharolyticus) were implanted in rat subcutaneous tissue for 1 wk, and histological changes were observed. Severe inflammation occurred around the models. Among them, P. asaccharolyticus induced the severest inflammatory response. Further study using P. asaccharolyticus was conducted to compare the implantation test's ability to evaluate pathogenicity with that of an injection test at 1, 2, or 4 wk. Tissue injected with a bacterial suspension showed no clear response through the experimental periods, whereas tissue around implantation sites showed a severe response at 1 wk. However, the inflammatory response subsided at later stages. Consequently, further improvement is needed to investigate pathogenicity for long periods.

Relationship between the electrical resistivity of enamel and the relative humidity.

The present study was carried out to investigate the relationship between the relative humidity and the electrical resistivity of enamel in vitro. The electrical resistivity of enamel samples was measured in a thermo-hygrostat where the relative humidity varied between 60% and 90%, with the measurements carried out first in a descending direction and then in an ascending direction. When the electrical resistivity was measured from a low to high relative humidity in an ascending direction, a higher value of electrical resistivity was always obtained in comparison to that when measured in the reverse descending direction. The difference between the mean electrical resistivity in an ascending and a descending direction increased in proportion to the relative humidity. These findings suggest that the diffusion of electrolytes and water in enamel is sensitive to changes in the relative humidity.