Inhibition of fibrotic changes in infrapatellar fat pad alleviates persistent pain and articular cartilage degeneration in monoiodoacetic acid-induced rat arthritis model.

OBJECTIVE: We have reported that fibrotic changes in infrapatellar fat pad (IFP) after acute joint inflammation are closely associated with persistent pain in rats. In this study, to examine the effects of anti-fibrotic treatment on persistent pain, we used C-type natriuretic peptides (CNP) at the recovery phase after acute joint inflammation. DESIGN: Thirty-two male Wistar rats were used in this study. Monoiodoacetic acid (MIA) was injected intra-articularly to induce IFP fibrosis and persistent pain. CNP was injected after acute inflammatory phase in the same knee joint. Time-course pain-avoidance behavior tests and histological analyses were performed to examine the effects of CNP. RESULTS: Histological evaluations indicated that intra-articular injection of CNP inhibited fibrotic changes in IFP after acute inflammation. Incapacitance tests indicated that MIA injection into rat knee joint quickly decreased the percent weight on ipsilateral limb. In the vehicle group, the decrease was maintained up to day 28, suggesting that pain persistence occurred after acute inflammation (Day 0/Day 28, Est Dif -8.15, CI -10.78∼-5.53, Linear mixed-effect model). In contrast, the pain was alleviated in the CNP group after day 14 (Day0/Day 14, -0.51, -2.62-1.59). In addition, we observed significant improvement in the degree of articular cartilage degeneration at day 14 in the CNP group (OARSI score: vehicle 16.14 ± 4.37 vs CNP 6.87 ± 3.44, P < 0.01; Wilcoxon rank sum test). CONCLUSION: Fibrotic changes in IFP may play important roles in both persistent pain and articular cartilage degeneration.

Swelling of Doubly Magic

Interaction cross sections for ^{42-51}Ca on a carbon target at 280 MeV/nucleon have been measured for the first time. The neutron number dependence of derived root-mean-square matter radii shows a significant increase beyond the neutron magic number N=28. Furthermore, this enhancement of matter radii is much larger than that of the previously measured charge radii, indicating a novel growth in neutron skin thickness. A simple examination based on the Fermi-type distribution, and mean field calculations point out that this anomalous enhancement of the nuclear size beyond N=28 results from an enlargement of the core by a sudden increase in the surface diffuseness of the neutron density distribution, which implies the swelling of the bare ^{48}Ca core in Ca isotopes beyond N=28.

Displacement of Propagating Squeezed Microwave States.

Displacement of propagating quantum states of light is a fundamental operation for quantum communication. It enables fundamental studies on macroscopic quantum coherence and plays an important role in quantum teleportation protocols with continuous variables. In our experiments, we have successfully implemented this operation for propagating squeezed microwave states. We demonstrate that, even for strong displacement amplitudes, there is no degradation of the squeezing level in the reconstructed quantum states. Furthermore, we confirm that path entanglement generated by using displaced squeezed states remains constant over a wide range of the displacement power.

Microwave down-conversion with an impedance-matched Λ system in driven circuit QED.

By driving a dispersively coupled qubit-resonator system, we realize an "impedance-matched" Λ system that has two identical radiative decay rates from the top level and interacts with a semi-infinite waveguide. It has been predicted that a photon input from the waveguide deterministically induces a Raman transition in the system and switches its electronic state. We confirm this through microwave response to a continuous probe field, observing near-perfect (99.7%) extinction of the reflection and highly efficient (74%) frequency down-conversion. These proof-of-principle results lead to deterministic quantum gates between material qubits and microwave photons and open the possibility for scalable quantum networks interconnected with waveguide photons.

Observation of the three-state dressed states in circuit quantum electrodynamics.

We have investigated the microwave response of a transmon qubit coupled directly to a transmission line. In a transmon qubit, owing to its weak anharmonicity, a single driving field may generate dressed states involving more than two bare states. We confirmed the formation of three-state dressed states by observing all of the six associated Rabi sidebands, which appear as either amplification or attenuation of the probe field. The experimental results are reproduced with good precision by a theoretical model incorporating the radiative coupling between the qubit and the microwave.

Single artificial-atom lasing.

Solid-state superconducting circuits are versatile systems in which quantum states can be engineered and controlled. Recent progress in this area has opened up exciting possibilities for exploring fundamental physics as well as applications in quantum information technology; in a series of experiments it was shown that such circuits can be exploited to generate quantum optical phenomena, by designing superconducting elements as artificial atoms that are coupled coherently to the photon field of a resonator. Here we demonstrate a lasing effect with a single artificial atom--a Josephson-junction charge qubit--embedded in a superconducting resonator. We make use of one of the properties of solid-state artificial atoms, namely that they are strongly and controllably coupled to the resonator modes. The device is essentially different from existing lasers and masers; one and the same artificial atom excited by current injection produces many photons.

Path entanglement of continuous-variable quantum microwaves.

Path entanglement constitutes an essential resource in quantum information and communication protocols. Here, we demonstrate frequency-degenerate entanglement between continuous-variable quantum microwaves propagating along two spatially separated paths. We combine a squeezed and a vacuum state using a microwave beam splitter. Via correlation measurements, we detect and quantify the path entanglement contained in the beam splitter output state. Our experiments open the avenue to quantum teleportation, quantum communication, or quantum radar with continuous variables at microwave frequencies.

Secure quantum remote state preparation of squeezed microwave states.

Quantum communication protocols based on nonclassical correlations can be more efficient than known classical methods and offer intrinsic security over direct state transfer. In particular, remote state preparation aims at the creation of a desired and known quantum state at a remote location using classical communication and quantum entanglement. We present an experimental realization of deterministic continuous-variable remote state preparation in the microwave regime over a distance of 35 cm. By employing propagating two-mode squeezed microwave states and feedforward, we achieve the remote preparation of squeezed states with up to 1.6 dB of squeezing below the vacuum level. Finally, security of remote state preparation is investigated by using the concept of the one-time pad and measuring the von Neumann entropies. We find nearly identical values for the entropy of the remotely prepared state and the respective conditional entropy given the classically communicated information and, thus, demonstrate close-to-perfect security.

Finite-time quantum entanglement in propagating squeezed microwaves.

Two-mode squeezing is a fascinating example of quantum entanglement manifested in cross-correlations of non-commuting observables between two subsystems. At the same time, these subsystems themselves may contain no quantum signatures in their self-correlations. These properties make two-mode squeezed (TMS) states an ideal resource for applications in quantum communication. Here, we generate propagating microwave TMS states by a beam splitter distributing single mode squeezing emitted from distinct Josephson parametric amplifiers along two output paths. We experimentally study the fundamental dephasing process of quantum cross-correlations in continuous-variable propagating TMS microwave states and accurately describe it with a theory model. In this way, we gain the insight into finite-time entanglement limits and predict high fidelities for benchmark quantum communication protocols such as remote state preparation and quantum teleportation.

Global genomic changes induced by two-stage carcinogen exposure are precancerous alterations in non-transformed human liver epithelial THLE-3 cells.

Global genomic changes, including DNA aneuploidy, may be necessary for carcinogenesis; however, such genomic changes in precancerous cells have not been studied extensively. To identify early global genotypic changes associated with precancerous lesions, a non-transformed human liver epithelial cell line, THLE-3, was treated with benzo[a]pyrene or N-methyl-N-nitro-N-nitrosoguanidine, then by 12-O-tetradecanoyl-phorbol-13-acetate, resulting in morphological transformation of cells. We examined genotypic changes of the transformed cells by laser scanning cytometry, fluorescence in situ hybridization, and comparative genomic hybridization. Transformed fusiform cells displayed tetraploidy, chromosomal instability, DNA copy number aberrations. Cells with these changes were still in the precancerous stage. However, it is suggested that these global genomic changes including tetraploidization provide cells with genetic alterations leading to cancer.

Ultrastructural changes of synaptic glomeruli following intrathecal injection of distilled water to rats.

We attempted to identify synaptic glomeruli in the spinal substantia gelatinosa of rats by injecting distilled water into the subarachnoid space. The altered synaptic glomeruli were visualized when injecting 1.0 ml of distilled water, though the incidence of degenerative synaptic glomeruli was rare in the case of an injection of 0.5 ml or less. We assume that when the distilled water is injected, there is a sudden change in homeostatic balance in cerebrospinal fluid, following inhibition of nerve impulses in the dorsal root and the altered synaptic glomeruli. Ultrastructurally, the injection of distilled water led to a preferential degeneration of synaptic glomeruli derived from the C-fibers.

Stereoscopic observation of enzyme distribution in lowicryl K4M-embedded specimens by conventional electron microscopy.

The present investigation was undertaken to explore the value of the Lowicryl K4M embedding technique for enzyme histochemical examination of semi-thin sections. The low-temperature embedding procedure with Lowicryl K4M was found to provide favorable conditions for preservation of enzyme activity in tissue samples. We tested the histological effects of various fixatives; the best results were obtained using 4% paraformaldehyde when testing for AcPase, AlPase, TPPase, and Mg-ATPase in the dorsal root ganglion. The three-dimensional cellular fine structure could be clearly seen in stereo pair pictures under stereoscopy.

Alkaline phosphatase activity of the IVth ventricular choroidal epithelium of rats during embryonic and neonatal development.

The cytochemical localization of alkaline phosphatase (AlPase) activity in the developing IVth ventricular choroidal epithelium was investigated in embryonic and neonatal rats. During the initial development of the choroidal primodium the flattened and/or cuboidal epithelial cells of the ventricular roof were changed to columnar cells with well-developed microvilli and apical tight junctions. When compared to AlPase activity on the lateral plasma membranes of the surrounding ependymal cells, these columnar cells of the choroidal primodium revealed activity on the lateral and luminal plasma membranes, but no activity was found on the basal surface of these cells. On the other hand, the epithelial cells in the neonatal choroid plexus showed a continuous morphological alteration from columnar cells with short microvilli to mature cuboidal cells with numerous long microvilli. AlPase activity in immature columnar cells was observed on all plasma membranes, except for the apical junctional area of the lateral surface. With maturing of the choroidal epithelial cells, the activity appeared to be eliminated from the lateral and luminal plasma membranes of the cuboidal cells, and mature choroidal epithelial cells showed activity on the basal surface only. These findings suggest that AlPase may play an important role in the membrane activity of epithelial cells differentiating between the primitive epithelial cells of the ventricular roof and the mature choroidal epithelial cells.

High-voltage electron microscopy of E-PTA-stained synaptic junctions in the rat frontal cortex.

The E-PTA-stained synaptic junctions in the adult rat frontal cortex were examined with high-voltage electron microscopy (HVEM). Perforated whole synaptic junctions were clearly shown in the stereo image. The E-PTA staining procedure provides a useful marker for studies of the 3-dimensional structure of synaptic junctions by means of HVEM.

The protective effects of vitamin E on microcephaly in rats X-irradiated in utero: DNA, lipid peroxide and confronting cisternae.

Fetuses from rats given either water or 0.03% D,L-alpha-tocopherol acetate (vitamin E) as a drinking fluid and X-irradiated with 100 rad on gestational day 13 were examined on gestational day 21. Mean cerebral weight which was significantly reduced by the X-irradiation was increased by vitamin E supplementation but the level did not reach that in sham-irradiated controls. Administration of vitamin E caused an increase in DNA concentration which was significantly reduced by X-irradiation with water treatment. An increase in the mean level of lipid peroxide formation was observed in the water-treated, X-irradiated group in the sample at zero time but not in the vitamin E-treated, X-irradiated group. In the cytoplasm of fetal cerebral neurons from X-irradiated dams with vitamin E supplementation, confronting cisternae were frequently observed between two nuclear envelopes. Confronting cisternae may be considered as a repair mechanism of vitamin E against X-irradiated neuronal damage in the fetal cerebrum. This study provides evidence of the protection by vitamin E of neuronal development in X-irradiated fetuses, through its antioxidant properties, against attacks by free radicals and/or lipid peroxide.

Effects of neonatal capsaicin treatment on thiamine monophosphatase (TMPase) activity in the substantia gelatinosa of the rat spinal cord.

The present study investigated changes in gelatinosal TMPase activity following capsaicin treatment. The gelatinosal TMPase activity was positive around postnatal day 3, and the activity disappeared when newborn rats were treated with capsaicin on postnatal days 2 or 3. The absence of TMPase activity was still observed four months after treatment. The possibility that TMPase is associated with nociception has to be considered.

Fetal alcohol effects: decreased synaptic formations in the field CA3 of fetal hippocampus.

The effects of prenatal ethanol exposure on the synaptic formation in the field CA3 of the hippocampus of fetal rats have been investigated on gestational day 21. Significantly decreased number of synaptic junctions was observed in the fetus showing decreasing cerebral weight either with or without decreasing body weight. The administration of 0.01% zinc with ethanol or 0.02% alpha-tocopherol acetate with ethanol during pregnancy resulted in an increased cerebral weight, but did not result in an increased synaptic formation compared to ethanol alone. This result indicates that one of the most vulnerable factors in rat fetus exposed to ethanol in utero is the synaptic formation in the hippocampus. In conclusion, ethanol exposure in utero during a period of brain development roughly equivalent to the first and second human trimesters can produce consistent dysforming effect of synapses and may be associated with the functional impairement of the central nervous system in the fetal alcohol effects.

Decreased density of synaptic formation in the frontal cortex of neonatal rats exposed to ethanol in utero.

We examined the developing synaptic junctions in the rat frontal cortex in cases of fetal alcohol syndrome, the objective being to determine the synapse-mental retardation relationship. On day 21 of gestation, the ultrastructural synaptic junction revealed no obvious differences between the ethanol-exposed and control rats; however, the number of synapses in ethanol-exposed rats was one third that of the controls. The possible relationship between synaptic density in the frontal cortex and mental development has to be considered.

Role of parotid amylase in starch digestion in the gastro-intestinal tracts of diabetic rats.

In order for the role of parotid amylase in starch digestion in the gastro-intestinal tracts of diabetic rats to be clarified, this study investigated the effect of parotid-duct ligation on both amylase secretion from the parotid glands and pancreas into the gastro-intestinal tract and on starch digestion in the gastro-intestinal contents during feedings. In both diabetic rats and control rats, parotid-duct ligation reduced amylase activity in both the parotid glands during fasting and in the gastric contents after feeding. The amylase activity in the intestinal contents after feeding was reduced by parotid-duct ligation in the diabetic rats. Starch digestion in the gastro-intestinal tract after feeding was reduced by parotid-duct ligation in the diabetic rats. The results suggest that most of the amylase activity in the gastric contents and a large part of the amylase activity in the intestinal contents are derived from the parotid glands, and that parotid amylase plays an important role in starch digestion in the gastro-intestinal tracts of diabetic rats.

Usefulness of quick intraoperative measurements of intact parathyroid hormone in the surgical management of hyperparathyroidism.

We investigated the use of quick measurement of intraoperative intact parathyroid hormone (I-PTH) to predict the outcome of parathyroidectomy. We examined intraoperative monitoring of I-PTH in 34 consecutive primary hyperparathyroidism (pHPT) patients operated on between April and December 1999. The average patient age was 56 +/- 13 years, and all but one were women. Four had a history of thyroidectomy. Blood samples were drawn before excision of enlarged parathyroid gland(s) and at 2, 5, 10, and 15 minutes afterward. Plasma I-PTH was measured by a two-site immunochemiluminometric assay. Twenty-three patients were shown to have single gland disease, and ten had multiglandular disease. All patients, except one, underwent successful parathyroidectomies. The plasma I-PTH value 15 minutes after removal of enlarged gland(s) had dropped to 26 +/- 10% of pre-excision I-PTH value. In one patient with a previous history of thyroidectomy for thyroid papillary cancer, no gland enlargement was found in the area where the lesion had been suggested by both ultrasonography and 99mTc sestamibi scanning. In this case, intraoperative measurements of I-PTH in the bilateral internal jugular veins identified an ectopic parathyroid tumor, which was successfully removed. We conclude that quick measurement of intraoperative I-PTH is a valuable tool for decision-making, especially for reoperative parathyroid surgery, for patients with previous history of thyroidectomy, and for patients in whom unilateral neck exploration or a single-gland approach is scheduled based upon preoperative localization.