Search for the Pair Production of Dark Particles X with K_{L}

We present the first search for the pair production of dark particles X via K_{L}^{0}→XX with X decaying into two photons using the data collected by the KOTO experiment. No signal was observed in the mass range of 40-110 MeV/c^{2} and 210-240 MeV/c^{2}. This sets upper limits on the branching fractions as B(K_{L}^{0}→XX)<(1-4)×10^{-7} and B(K_{L}^{0}→XX)<(1-2)×10^{-6} at the 90% confidence level for the two mass regions, respectively.

The bone attachments of the medial collateral and posterior oblique ligaments are defined anatomically and radiographically.

PURPOSE: To define the bony attachments of the medial ligaments relative to anatomical and radiographic bony landmarks, providing information for medial collateral ligament (MCL) surgery. METHOD: The femoral and tibial attachments of the superficial MCL (sMCL), deep MCL (dMCL) and posterior oblique ligament (POL), plus the medial epicondyle (ME) were defined by radiopaque staples in 22 knees. These were measured radiographically and optically; the precision was calculated and data normalised to the sizes of the condyles. Femoral locations were referenced to the ME and to Blumensaat's line and the posterior cortex. RESULTS: The femoral sMCL attachment enveloped the ME, centred 1 mm proximal to it, at 37 ± 2 mm (normalised at 53 ± 2%) posterior to the most-anterior condyle border. The femoral dMCL attachment was 6 mm (8%) distal and 5 mm (7%) posterior to the ME. The femoral POL attachment was 4 mm (5%) proximal and 11 mm (15%) posterior to the ME. The tibial sMCL attachment spread from 42 to 71 mm (81-137% of A-P plateau width) below the tibial plateau. The dMCL fanned out anterodistally to a wide tibial attachment 8 mm below the plateau and between 17 and 39 mm (33-76%) A-P. The POL attached 5 mm below the plateau, posterior to the dMCL. The 95% CI intra-observer was ± 0.6 mm, inter-observer ± 1.3 mm for digitisation. The inter-observer ICC for radiographs was 0.922. CONCLUSION: The bone attachments of the medial knee ligaments are located in relation to knee dimensions and osseous landmarks. These data facilitate repairs and reconstructions that can restore physiological laxity and stability patterns across the arc of knee flexion.

[Cryptorchidism associated with ectopic adrenal cortical tissue in the spermatic cord in a 51-year-old male]. / Un cas de cryptochidie associée à un îlot surrénalien ectopique du cordon spermatique chez un homme de 51ans.

This case report describes an exceptional case of ectopic adrenal cortex tissue (EACT) in the spermatic cord associated with ipsilateral cryptorchidism in an adult. While both EACT and cryptorchidism are fairly common congenital anomalies in boys, adult cases are uncommon. Although the spermatic cord is a known site of EACT, the reports of its association with cryptorchidism have been limited to child cases. During surgery, undescended testis was discovered and incidentally ectopic adrenal tissue along the spermatic cord was also identified. This combination of developmental aberrations in the adult has not been described, and the clinicopathological findings are reported with a brief literature review.

Extremely small-diameter, high-density, radio frequency, plasma sources and central gas feeding for next-generation electrodeless plasma thrusters.

Radio frequency (RF) waves including helicon waves can readily produce high-electron-density (ne up to 1013 cm-3) plasmas with a broad range of external operating parameters. Various featured RF and helicon sources in a wide range of scales are suitable for plasma propulsion schemes. Electrodeless RF plasmas have no direct contact between electrodes and antennas, which enables long-life operation. However, one of the crucial problems is to reduce the plasma size for future applications in nano- and pico-satellites. Diagnostics of the plasma parameters in a small area should also be improved. Furthermore, to increase plasma performance, it is important to consider the radial electron density (ne) profile with an increasing upper limit, observed in high-density helicon sources due to the depletion of neutrals. This problem may be controlled by the location of neutral gas feeding and knowledge of the gas pressure distribution. Here, production of RF plasmas, with extremely small diameters from 3-mm down to 0.5-mm including 1-mm, was demonstrated, and characterization of ne and the electron temperature was performed with a collisional radiative model. Finally, to improve plasma performance such as ne and the thrust force, internal gas feeding was demonstrated using a developed Pirani gauge to measure neutral density.

Spatial measurement in rotating magnetic field plasma acceleration method by using two-dimensional scanning instrument and thrust stand.

A two-dimensional scanning probe instrument has been developed to survey spatial plasma characteristics in our electrodeless plasma acceleration schemes. In particular, diagnostics of plasma parameters, e.g., plasma density, temperature, velocity, and excited magnetic field, are essential for elucidating physical phenomena since we have been concentrating on next generation plasma propulsion methods, e.g., Rotating Magnetic Field plasma acceleration method, by characterizing the plasma performance. Moreover, in order to estimate the thrust performance in our experimental scheme, we have also mounted a thrust stand, which has a target type, on this movable instrument, and scanned the axial profile of the thrust performance in the presence of the external magnetic field generated by using permanent magnets, so as to investigate the plasma captured in a stand area, considering the divergent field lines in the downstream region of a generation antenna. In this paper, we will introduce the novel measurement instrument and describe how to measure these parameters.

Effects of duloxetine on pain and walking distance in neuropathic pain models via modulation of the spinal monoamine system.

BACKGROUND: Approximately 40% of patients with chronic low back pain have a neuropathic component. In this study, we assessed the effects of analgesics on tactile hypersensitivity and walking distance in the rat cauda equina compression (CEC) model of neuropathic low back pain. METHODS: The effects of analgesics on tactile hypersensitivity were examined using the von Frey test in CEC and partial sciatic nerve ligation (pSNL) models. Effects on walking distance were assessed using a treadmill test. Levels of α2δ1 subunit and ATF-3 mRNA in dorsal-root ganglion (DRG) neurons and those of α2δ1 subunit protein in the spinal cord were determined using quantitative RT-PCR and western blotting, respectively. Histological features were assessed using immunohistological methods. RESULTS: Histological changes indicating nerve damage (increase in ATF-3 mRNA, decrease in NF-200 and an increase in CD68 immunoreactivity) were observed in the CEC model. Duloxetine had analgesic effects in both models and improved walking distance in the CEC model. Pregabalin had analgesic effects in both models; however, the effect was weaker in the CEC model than in the pSNL model. α2δ1 subunit expression in DRG neurons and in the spinal cord was unchanged in the CEC model, but significantly increased in the pSNL model. Indomethacin had no analgesic effect in either model. Intrathecal yohimbine inhibited the effects of duloxetine with significant effects on depression. CONCLUSIONS: These findings suggest that the analgesic effects of duloxetine are mainly mediated by the spinal monoamine system, independent of the antidepressant effects of this agent. SIGNIFICANCE: The findings of this study suggest that duloxetine may be an effective treatment of broad neuropathic pain states, including neuropathic low back pain. The analgesic effects of duloxetine might be mediated by alterations of the descending pain modulatory pathways in the spinal cord, independent of the antidepressant effects.

Fine positioning of a poloidal probe array.

Multipoint detection is an essential requirement for investigating plasma turbulence which is a highly nonlinear phenomenon in space and time. We have fabricated an array of 64-channel poloidal probes surrounding the linear cylindrical plasma named LMD-U in order to study turbulence properties, particularly the nonlinear mode couplings, in the domain of poloidal wave number and frequency. However, misalignments of probe tips produce spurious modes, which do not exist in the real plasma, to distort the precise wave number measurements. The paper presents the description of the 64-channel poloidal probe array with means to adjust the probe positions, with discussion on the effects of the misalignments on the wave number measurements.

Difference in voice analysis result by pre- and post- processing of telephone line.

The purpose of this study is to verify the impact of a deterioration of the sound quality of voice by a telephone line on estimating Vitality as the extent of depressive tendency based on voice analysis using MIMOSYS. First, the voices of about 1,000 people recorded using a recorder were prepared. Next, each voice was coded and resampled in preparation for transmission over a phone line. Vitalities obtained by analyzing the voices before and after these processes were compared. The results showed high correlation between the Vitality after coding and Vitality before coding, revealing that using a telephone would be an effective way to obtain voices.

A novel method for assessing bladder-related pain reveals the involvement of nerve growth factor in pain associated with cyclophosphamide-induced chronic cystitis in mice.

BACKGROUND: Pain is a prominent feature of interstitial cystitis/painful bladder syndrome (IC/PBS), but the underlying mechanisms are not fully understood. There is a lack of well-characterized research tools, such as pain evaluation methods and experimental animal models, for investigating non-ulcerative cystitis. We developed a novel method for evaluating bladder pain in mice with cyclophosphamide (CYP)-induced cystitis. METHODS: Cystitis was produced by a single intraperitoneal injection of CYP (300 mg/kg) or repeated injections of CYP (150 mg/kg once daily for 4 days). Blunt stimulation with a cotton probe was applied to the abdominal region, and the thresholds for withdrawal responses were measured quantitatively using an anaesthesiometer. RESULTS: The single injection of CYP provoked acute cystitis with severe bladder inflammation in mice. In these mice, we could detect an increased sensitivity to blunt stimulation, which was abolished by intravesical lidocaine. The stimulation induced phosphorylation of extracellular signal-regulated kinases in bladder-projecting sensory neurons. Chronic treatment with CYP produced persistent pain responses to the blunt stimulus. Although there were few signs of bladder inflammation in these mice, the concentration of nerve growth factor (NGF) was elevated in bladder tissue, and NGF antiserum inhibited the hypersensitivity. CONCLUSIONS: The blunt probe method is useful for evaluating bladder pain signalling in mice, and revealed the involvement of an NGF-sensitive pain pathway in chronic cystitis pain. This assessment method may be useful for studying the pathophysiology of bladder pain and for developing therapeutic strategies for non-ulcerative IC/PBS in patients.

Replica multichannel polymer chips with a network of sacrificial channels sealed by adhesive printing method.

Replica microchips for capillary array electrophoresis containing 10 separation channels (50 microm width, 50 microm depth and 100 microm pitch) and a network of sacrificial channels (100 microm width and 50 microm depth) were successfully fabricated on a poly(methyl methacrylate) (PMMA) substrate by injection molding. The strategy involved development of moving mask deep X-ray lithography to fabricate an array of channels with inclined channel sidewalls. A slight inclination of channel sidewalls, which can not be fabricated by conventional deep X-ray lithography, is highly required to ensure the release of replicated polymer chips from a mold. Moreover, the sealing of molded PMMA multichannel chips with a PMMA cover film was achieved by a novel bonding technique involving adhesive printing and a network of sacrificial channels. An adhesive printing process enables us to precisely control the thickness of an adhesive layer, and a network of sacrificial channels makes it possible to remove air bubbles and an excess adhesive, which are crucial to achieving perfect sealing of replica PMMA chips with well-defined channel and injection structures. A CCD camera equipped with an image intensifier was used to simultaneously monitor electrophoretic separations in ten micro-channels with laser-induced fluorescence detection. High-speed and high-throughput separations of a 100 bp DNA ladder and phi X174 Hae III DNA restriction fragments have been demonstrated using a 10-channel PMMA chip. The current work establishes the feasibility of mass production of PMMA multichannel chips at a cost-effective basis.

Electrophysiological changes in rat hippocampal pyramidal neurons produced by cholecystokinin octapeptide.

Effects of cholecystokinin octapeptide (CCK-8) were investigated in CA1 pyramidal neurons of rat hippocampal slice cultures using the whole-cell patch-clamp technique. In the current-clamp mode, CCK-8 (100 nM) produced slight depolarizaton (2.1 +/- 0.3 mV) and reduced the amplitude of afterhyperpolarization following a train of spikes. CCK-8 (10 nM-1 microM) concentration-dependently reduced the amplitude of afterhyperpolarization. CCK-4, a selective agonist for CCK(B) receptors, also attenuated the amplitude of afterhyperpolarization. CCK-8-induced suppression was completely abolished by (+)L-365,260, a selective CCK(B) receptor antagonist, but not by (-)L-364,718, a selective CCK(A) receptor antagonist. Similarly, CCK-8 reduced the tail currents following a depolarizing pulse. The tail currents were characterized as Ca2+-activated K+ currents. When neurons were held at a holding potential of -40 mV, CCK-8 elicited inward currents with a reduction of membrane conductance. This current had a relatively linear current voltage relationship and was reversed in polarity at membrane potentials close to the K+ equilibrium potential, suggesting that CCK-8 decreases leak K+ currents. Moreover, voltage-activated Ca2+ currents were partially blocked by CCK-8, and this effect was enhanced by intracellular application of GTPgammaS (300 microM) or a protein phosphatase inhibitor, okadaic acid (100 nM), and attenuated by GDPbetaS (300 microM) or a protein kinase inhibitor, staurosporin (400 nM). In acutely-prepared hippocampal slices from neonatal rats, CCK-8 also depolarized CA1 pyramidal neurons and suppressed afterhyperpolarization following a train of action potentials. These results indicate that CCK-8 increases neuronal excitability by suppressing leak K+ currents and Ca2+-activated K+ currents in CA1 pyramidal neurons of the hippocampus through activation of CCK(B) receptors.

Iodine-131 metaiodobenzylguanidine intra- and extravesicular accumulation in the rat heart.

In order to establish the appropriate time for [123I]MIBG human myocardial imaging to assess the adrenergic nerve activity, the time courses of metaiodobenzylguanidine (MIBG) intra- and extravesicular accumulation in the rat heart were estimated by using [131I]MIBG and reserpine. In the heart, the intravesicular accumulation was relatively constant, while the extravesicular accumulation decreased rapidly from 5 min to 6 hr. The intravesicular percentage of the total cardiac tissue concentration reached a plateau value of 50% at 4 hr after i.v. injection of [131I]MIBG. In the spleen, similar time courses were observed as those in the heart, both of these organs being richly innervated by adrenergic nerves. Along with the time activity difference previously observed in the human hearts, these results suggest that at 4 hr post i.v. injection, [123I]MIBG myocardial imaging will best express the neuronal accumulation of the tracer and may be useful for the assessment of adrenergic function in various pathological conditions of the human heart.

Biodistribution and in vivo kinetics of iodine-131 lipiodol infused via the hepatic artery of patients with hepatic cancer.

The biodistribution and in vivo kinetics of [131I]lipiodol infused into the hepatic artery were studied to estimate the potential of internal radiotherapy of hepatic cancer in five patients. It accumulated only in the vascular tumors and adjacent hepatic tissue (AHT) supplied by the infused artery, and to a lesser extent in the lung throughout 8 days imaging sequence. Iodine-131 lipiodol appeared to lead to oil embolization of the tumor and AHT followed by secondary embolization to the lungs and finally the activity was mainly excreted into urine. Four tumors had rapidly and slowly decreasing components, while the AHT activity decreased exponentially from the beginning. The effective half life in tumors was longer with the slow component (mean +/- s.d.: 5.7 +/- 1.2 days) than the AHT (3.7 +/- 0.6 days). The tumor/AHT concentration ratio in three patients at 2 hr was estimated to be 7.5-21. The activity was lower in the lungs than in the AHT in four patients. Iodine-131 lipiodol thus may be used as an intra-arterial infusion agent to treat certain vascular hepatic cancers.

Rapid clearance of iodine-131 MIBG from the heart and liver of patients with adrenergic dysfunction and pheochromocytoma.

Iodine-131 MIBG, a radiolabeled adrenergic neuron-blocking agent, decreased rapidly from the heart and liver of patients with adrenergic dysfunction (n = 3) and pheochromocytoma (n = 2) when compared with eight controls. The 4-hr activity expressed as percentages (mean +/- s.d.) of the 20-min counts were as follows: 80 +/- 3.0% in the controls compared with 60 +/- 7.6% in the patients over the heart (p less than 0.01) and 79 +/- 3.2% in the controls compared with 51 +/- 17% in the patients over the liver (p less than 0.02). However, there was no significant difference in the rate of [131I]MIBG decrease in these organs between controls and patients in the intervals subsequent to 4 hr (p greater than 0.05). These findings suggest that adrenergic neuronal uptake of [131I]MIBG in these organs is smaller in the patients than in the controls. Measurements of time-activity relationships of radioiodinated MIBG may be useful for assessment of adrenergic function of these organs and thus of generalized disorders of adrenergic innervation.

Regulation of cell proliferation using tissue engineering in MIN6 cells.

Pancreatic islet transplantation for patients with diabetes mellitus has been hindered by the problem of donor shortage, as is the case for transplantation of other organs. Among several measures to overcome this problem, cell transplantation using xenogenic cell lines has been considered. For the treatment of diabetic patients, a murine pancreatic beta-cell line MIN6 is a potential source of cell transplant. In order to restrict otherwise unlimited proliferation of transplanted MIN6 cells, cells are rendered to form spheroidal aggregates (SMIN6) on nonadherent culture dishes. SMIN6 stopped its growth around day 7 with a diameter of 220 +/- 40 microm and kept its size almost constant at least until day 28. SMIN6 cells, however, had reduced responsiveness of insulin secretion to glucose concentration compared with MIN6 cells cultured in a monolayer. On the other hand, spheroid MIN6 cells formed in the presence of extracellular matrix gel (SMIN6E) possessed the capacity for glucose-dependent insulin secretion comparable with conventional MIN6 cells. SMIN6E encapsulated in agarose beads (SMIN6E-B) was also viable for at least 1 month in vitro with a constant diameter and favorable glucose responsiveness. The development of spheroid-type MIN6 may contribute to the future clinical application of MIN6 or other beta-cell lines for treatment of diabetes mellitus.

Application of a novel B cell line MIN6 to a mesh-reinforced polyvinyl alcohol hydrogel tube and three-layer agarose microcapsules: an in vitro study.

This study examines the function of a novel B cell line (MIN6) enclosed in hybrid bioartificial pancreas with mesh-reinforced polyvinyl alcohol hydrogel tube (MRPT) or with improved, three-layer agarose microcapsules. MIN6 was established from insulinomas obtained by targeted expression of the simian virus 40 T-antigen gene in transgenic mice. MIN6 retains the ability to secrete insulin in response to physiological glucose concentrations. The MRPT and the three-layer agarose microcapsules, which were developed to act as an artificial pancreas, were readily permeated by insulin, glucose, and other nutrients. Both can immunoisolate enclosed MIN6 cells from the recipient's humoral and cellular immunosystems, which causes a xenogeneic rejection response. MIN6 cells (5.0 x 10(6) or 1.5 x 10(6)) were enclosed in MRPT or in a hundred three-layer microcapsules and subjected to an in vitro perifusion study or a static incubation study to observe the insulin release from each bioartificial pancreas in response to glucose stimulation. In vitro study revealed that the insulin secretion in response to 16.7 mM glucose stimulation was twice that with 3.3 mM glucose stimulation with both MRPT and the three-layer agarose microcapsules. The present study demonstrates that MIN6 effectively functions as a bioreactor for the hybrid bioartificial pancreas. The application of MIN6 cells to the hybrid bioartificial pancreas may offer a solution to the current serious dearth of organs.

Melatonin release from pineal cells of diurnal and nocturnal birds.

Melatonin release from the pineal cells of chicks, pigeons and crows (diurnal birds) in vitro was compared with that from owls (a nocturnal bird). The pineal cells of diurnal birds secreted large amounts of melatonin during the dark period, whereas owl pineal cells released virtually no melatonin over 24 h and did not respond to exogenous stimulant agents. Histological examination revealed that the owl pineal gland is very small and has a poor vascular network. These results suggest that the pineal gland of owls may have degenerated and is not involved in the circadian clock mechanism in this species.

Inhibitory effect of CCK-8 and ceruletide on glutamate-induced rises in intracellular free calcium concentrations in rat neuron cultures.

To study the mechanism by which cholecystokinin octapeptide (CCK-8) and its potent analogue, ceruletide, prevent glutamate-induced neuronal cell death in rat neuron cultures, we examined the effect of both peptides on glutamate-induced increases in the intracellular free calcium concentrations ([Ca2+]i), which are known to be a crucial trigger of the neurodegeneration induced by glutamate. CCK-8 itself did not alter [Ca2+]i in rat neuron cultures. Glutamate increased [Ca2+]i in neuron cultures rapidly and markedly. CCK-8 and ceruletide significantly suppressed the increases in [Ca2+]i induced by glutamate. The maximum inhibitory effects of CCK-8 and ceruletide at 10(-6) M reached 43 and 46% of the response to glutamate, respectively. Gastrin-I and CCK-4 also significantly attenuated the increases in [Ca2+]i induced by glutamate. The inhibitory effect of CCK-8 was completely blocked by the selective antagonist for CCK-B receptors, (+)L-365,260, but not by (-)L-364,718, which is a selective antagonist for CCK-A receptors. CCK-8 significantly suppressed [Ca2+]i response to kainate and high concentrations of extracellular K+, but not to N-methyl-D-aspartate. With cultured astrocytes, CCK-8 did not inhibit the increment of [Ca2+]i induced by glutamate. These findings clearly demonstrated that CCK-8 and ceruletide inhibit glutamate-induced increases in [Ca2+]i in neuron cultures through CCK-B receptors, suggesting that CCK-8 may participate in the central actions of glutamate.

Systemic administration of a cholecystokinin analogue, ceruletide, protects against ischemia-induced neurodegeneration in gerbils.

The neuroprotective action of a cholecystokinin octapeptide analogue, ceruletide, was evaluated in models of cerebral ischemia using Mongolian gerbils. Ceruletide significantly suppressed the hyperactivity and amnesia induced by ischemia when injected s.c. 30 min before 5-min occlusion of the bilateral common carotid arteries at room temperature or immediately after their reperfusion. Ceruletide also reduced behavioral changes in ischemic gerbils whose body temperature was maintained at 37 degrees C during the 3-min occlusion. In these groups, delayed neuronal cell death in the hippocampal CA1 area following ischemia was markedly attenuated by s.c. administration of ceruletide. On the other hand, ceruletide could not inhibit the behavioral changes or the neurodegeneration induced in the hippocampal CA1 area by 5-min occlusion at 37 degrees C. These findings indicate that peripheral injection of ceruletide produces a neuroprotective action against moderate cerebral ischemia, which is the first evidence suggesting the efficacy of ceruletide in neurodegenerative diseases.