A unique case of duodenal stromal tumor In a 51‐year‐old man is reported. The tumor histologically showed spindle cell proliferation and numerous eosinophilic globules. Most globules were composed of ...tangled 45 nm thick fibrils, which were ultrastructurally Identical to ‘skelnoid fibers’. The presence of glycogen granules in the tumor cells and the Immunoreactivity for α‐smooth muscle actin suggested smooth muscle differentiation. Focal ultrastructural findings also supported the smooth muscle nature of this tumor. There were no immunohistochemical and ultra‐structural features indicating neural differentiation. In previous studies, the presence of such ‘skeinoid fibers’ was suggested to be a histological marker for neural differentiation in gastrointestinal stromal tumor. However, the findings In the present case suggest that numerous ‘skeinoid fibers’ can be Identified in duodenal stromal tumor with smooth muscle differentiation, although this condition may be rare.
We report a rare case of primary meningeal malignant melanoma in a 23-year-old female. The patient was admitted to our hospital for sudden onset of consciousness disturbance. Prominent nevi were ...observed on her trunk. From the spinal fluid, a small number of tumor cells, highly suggestive of malignant lymphoma were evident. However, final cytological diagnosis could not be completed. The cells showed no definitive melanin pigment whatsoever. Shortty there after, biopsy specimens taken during decompression surgery revealed a small number of atypical cells in the specimen containing definitive melanin pigment with vivid nucleoli. These findings lead us to a final diagnosis of malignant melanoma. Special staining i.e. Grimelius, Fontana-Masson and immunostains such as NSE, and S-100 protein supported the diagnosis. Ultrastructural study demonstrated abundant mature melanosomes. Finally, autopsy findings revealed neither metastasis nor lesions indicating another primary focus.
A new method of optimal parameter setting for PID control systems with two-degrees-of-freedom is proposed. The method uses a frequency domain performance index, and, hence, can be applied directly ...(without modelling procedure) if the frequency response data of controlled objects are obtained. The performance index used here has close relation to “Time-weighted Integral of Square Error (TISE)”. By using this method, the optimal parameters are calculated for four classes of controlled objects that are first-or second-order lag plus dead time systems without zero point. By simulation, it is assured that these parameters realize less than 20% (12% on average) overshoot, nearly minimum settling time and nearly smallest TISE. The results of simulation also indecates that our method is superior to or, at least, as good as the conventional ones.
Understanding and controlling electrophoretic motions of nanoscopic objects in fluidic channels are a central challenge in developing nanopore technology for molecular analyses. Although progress has ...been made in slowing the translocation velocity to meet the requirement for electrical detections of analytes via picoampere current measurements, there exists no method useful for regulating particle flows in the transverse directions. Here, we report the use of dielectrophoresis to manipulate the single-particle passage through a solid-state pore. We created a trap field by applying AC voltage between electrodes embedded in a low-aspect-ratio micropore. We demonstrated a traffic control of particles to go through center or near side surface via the voltage frequency. We also found enhanced capture efficiency along with faster escaping speed of particles by virtue of the AC-mediated electroosmosis. This method is compatible with nanopore sensing and would be widely applied for reducing off-axis effects to achieve single-molecule identification.
Electrokinetic manipulations of biomolecules using artificial nanostructures within microchannels have proven capability for controlling the dynamics of biomolecules. Because there is an inherent ...spatial size limitation to lithographic technology, especially for nanostructures with a small diameter and high aspect ratio, manipulating a single small biomolecule such as in DNA elongation before nanopore sequencing is still troublesome. Here we show the feasibility for self-assembly of a nanowire array embedded in a microchannel on a fused silica substrate as a means to manipulate the dynamics of a single long T4-DNA molecule and also separate DNA molecules. High-resolution optical microscopy measurements are used to clarify the presence of fully elongated T4-DNA molecules in the nanowire array. The spatial controllability of sublithographic-scale nanowires within microchannels offers a flexible platform not only for manipulating and separating long DNA molecules but also for integrating with other nanostructures to detect biomolecules in methods such as nanopore sequencing.
The development of heart failure is tightly correlated with a decrease in the stoichiometric ratio for FKBP12.6 binding to the ryanodine receptor (RyR) in the sarcoplasmic reticulum (SR). We report ...that a new drug, the 1,4-benzothiazepine derivative JTV519, reverses this pathogenic process. JTV519 is known to have a protective effect against Ca2+ overload-induced myocardial injury.
Heart failure was produced by 4 weeks of rapid right ventricular pacing, with or without JTV519; SR were then isolated from dog left ventricular (LV) muscles. First, in JTV519-treated dogs, no signs of heart failure were observed after 4 weeks of chronic right ventricular pacing, LV systolic and diastolic functions were largely preserved, and LV remodeling was prevented. Second, JTV519 acutely inhibited both the FK506-induced Ca2+ leak from RyR in normal SR and the spontaneous Ca2+ leak in failing SR. Third, there was no abnormal Ca2+ leak in SR vesicles isolated from JTV519-treated hearts. Fourth, in JTV519-treated hearts, both the stoichiometry of FKBP12.6 binding to RyR and the amount of RyR-bound FKBP12.6 were restored toward the values seen in normal SR. Fifth, in JTV519-untreated hearts, RyR was PKA-hyperphosphorylated, whereas it was reversed in JTV519-treated hearts, returning the channel phosphorylation toward the levels seen in normal hearts.
During the development of experimental heart failure, JTV519 prevented the amount of RyR-bound FKBP12.6 from decreasing. This in turn reduced the abnormal Ca2+ leak through the RyR, prevented LV remodeling, and led to less severe heart failure.
Novel experimental techniques allow for the manipulation and interrogation of biomolecules between metallic probes immersed in micro/nanofluidic channels. The behavior of ions in response to applied ...fields is a major issue in the use of these techniques in sensing applications. Here, we experimentally and theoretically elucidate the behavior of background currents in these systems. These large currents have a slowly decaying transient response, as well as noise that increases with ionic concentration. Using mechanically controllable break junctions (MCBJ), we study the ionic response in nanogaps with widths ranging from a few nanometers to millimeters. Moreover, we obtain an expression for the ionic current by solving time-dependent Nernst–Planck and Poisson equations. This expression shows that after turning on an applied voltage, ions rapidly respond to the strong fields near the electrode surface, screening the field in the process. Ions subsequently translocate in the weak electric field and slowly relax within the diffusion layer. Our theoretical results help to explain the short- and long-time behavior of the ionic response found in experiments, as well as the various length scales involved.
In heart failure, protein kinase A-mediated hyperphosphorylation of ryanodine receptors (RyRs) in sarcoplasmic reticulum (SR) causes dissociation of FKBP12.6 from RyRs. This results in an abnormal ...Ca2+ leak through RyRs, possibly leading to cardiac dysfunction. In the present study, we assess whether beta-blockers can correct this defect in RyR in tachycardia-induced heart failure and thereby improve cardiac function.
SRs were isolated from dog left ventricular muscles (normal group, 4 weeks of rapid right ventricular pacing with or without propranolol P(+) or P(-)). End-diastolic and end-systolic diameters both increased less in P(+) than P(-), associated with a smaller decrease in fractional shortening in P(+). In SR from P(-), a prominent Ca2+ leak was observed, and FK506 (which dissociates FKBP12.6 from RyR) did not induce an additional Ca2+ leak. However, there was no appreciable Ca2+ leak in SR from P(+), although FK506 induced a Ca2+ leak as in normal SRs. In SR from P(+), an FK506-induced conformational change in RyR, which was virtually absent in SR from P(-), was observed as in normal SRs. Both the stoichiometry of FKBP12.6 versus RyR, assessed by 3HFK506 and 3Hryanodine binding assays, and the protein expression of FKBP12.6, assessed by Western blot analysis, were restored by propranolol toward the levels seen in normal SRs.
Low-dose propranolol corrects the defective interaction of FKBP12.6 with RyR (restoration of RyR conformational change and prevention of Ca2+ leak from RyR), apparently resulting in an attenuation of intracellular Ca2+ overload and hence preventing the development of left ventricular remodeling in heart failure.
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