Disappearance of perihepatic lymph node enlargement after hepatitis C viral eradication with direct-acting antivirals.

Perihepatic lymph node enlargement (PLNE) which has been shown to be negatively associated with hepatocellular carcinoma (HCC) occurrence is frequently observed in chronic liver disease; however, changes in the state of perihepatic lymph nodes after eradication of hepatitis C virus (HCV) have not been investigated yet. We aimed to evaluate this issue. We enrolled 472 patients with chronic HCV infection who achieved viral eradication with direct-acting antivirals (DAA). We investigated whether the status of perihepatic lymph nodes changed before and after HCV eradication (primary endpoint). We also evaluated the association between PLNE and clinical findings such as liver fibrosis or hepatocellular injury before HCV eradication (secondary endpoint). Perihepatic lymph node enlargement was detected in 164 of 472 (34.7%) patients before DAA treatment. Surprisingly, disappearance of PLNE was observed in 23.8% (39 patients) of all PLNE-positive patients after eradication of HCV. Disappearance of PLNE was not associated with baseline clinical parameters or changing rates of clinical findings before and after DAA treatment. At baseline, presence of PLNE was significantly associated with a lower serum HCV-RNA level (P = .03), a higher serum AST level (P = .004) and a higher ALT level (P < .001) after adjustment for sex and age. In conclusion, PLNEs became undetectable after DAA treatment in 23.8% of PLNE-positive patients. Further study with a longer follow-up period is needed to clarify the clinical importance of this phenomenon especially in relationship with the risk of HCC development.

Endocrine Control of Exaggerated Trait Growth in Rhinoceros Beetles.

Juvenile hormone (JH) is a key insect growth regulator frequently involved in modulating phenotypically plastic traits such as caste determination in eusocial species, wing polymorphisms in aphids, and mandible size in stag beetles. The jaw morphology of stag beetles is sexually-dimorphic and condition-dependent; males have larger jaws than females and those developing under optimum conditions are larger in overall body size and have disproportionately larger jaws than males raised under poor conditions. We have previously shown that large males have higher JH titers than small males during development, and ectopic application of fenoxycarb (JH analog) to small males can induce mandibular growth similar to that of larger males. What remains unknown is whether JH regulates condition-dependent trait growth in other insects with extreme sexually selected structures. In this study, we tested the hypothesis that JH mediates the condition-dependent expression of the elaborate horns of the Asian rhinoceros beetle, Trypoxylus dichotomus. The sexually dimorphic head horn of this beetle is sensitive to nutritional state during larval development. Like stag beetles, male rhinoceros beetles receiving copious food produce disproportionately large horns for their body size compared with males under restricted diets. We show that JH titers are correlated with body size during the late feeding and early prepupal periods, but this correlation disappears by the late prepupal period, the period of maximum horn growth. While ectopic application of fenoxycarb during the third larval instar significantly delayed pupation, it had no effect on adult horn size relative to body size. Fenoxycarb application to late prepupae also had at most a marginal effect on relative horn size. We discuss our results in context of other endocrine signals of condition-dependent trait exaggeration and suggest that different beetle lineages may have co-opted different physiological signaling mechanisms to achieve heightened nutrient-sensitive weapon growth.

Ultralow-phase-noise millimetre-wave signal generator assisted with an electro-optics-modulator-based optical frequency comb.

Low-noise millimetre-wave signals are valuable for digital sampling systems, arbitrary waveform generation for ultra-wideband communications, and coherent radar systems. However, the phase noise of widely used conventional signal generators (SGs) will increase as the millimetre-wave frequency increases. Our goal has been to improve commercially available SGs so that they provide a low-phase-noise millimetre-wave signal with assistance from an electro-optics-modulator-based optical frequency comb (EOM-OFC). Here, we show that the phase noise can be greatly reduced by bridging the vast frequency difference between the gigahertz and terahertz ranges with an EOM-OFC. The EOM-OFC serves as a liaison that magnifies the phase noise of the SG. With the EOM-OFC used as a phase noise "booster" for a millimetre-wave signal, the phase noise of widely used SGs can be reduced at an arbitrary frequency f (6 ≦ f ≦ 72 GHz).

Drift transport of helical spin coherence with tailored spin-orbit interactions.

Most future information processing techniques using electron spins in non-magnetic semiconductors will require both the manipulation and transfer of spins without their coherence being lost. The spin-orbit effective magnetic field induced by drifting electrons enables us to rotate the electron spins in the absence of an external magnetic field. However, the fluctuations in the effective magnetic field originating from the random scattering of electrons also cause undesirable spin decoherence, which limits the length scale of the spin transport. Here we demonstrate the drift transport of electron spins adjusted to a robust spin structure, namely a persistent spin helix. We find that the persistent spin helix enhances the spatial coherence of drifting spins, resulting in maximized spin decay length near the persistent spin helix condition. Within the enhanced distance of the spin transport, the transport path of electron spins can be modulated by employing time-varying in-plane voltages.

High juvenile hormone titre and abdominal activation of JH signalling may induce reproduction of termite neotenics.

Termite castes are a key example of polyphenism, in which reproductive division of labour is clearly seen in colonies. The reproductive castes in termites include primary and neotenic reproductives; primary reproductives found a new colony whereas neotenics succeed them in the reproductive role when the primary reproductives die or become senescent. Neotenics usually differentiate from nymphs or workers by developing functional gonads while retaining juvenile characteristics; however, the developmental mechanism during neotenic differentiation remains poorly understood. Juvenile hormone (JH) mediates a number of aspects of developmental regulation in caste differentiation in termites. In the present study we quantified JH titres in neotenic reproductives of Reticulitermes speratus, and compared these with other developmental stages. In addition, expression changes in JH signalling gene homologues (Methoprene-tolerant [Met], Krüppel-homolog1, Broad-Complex) in the head, thorax and abdomen were investigated during neotenic differentiation. Finally, we examined the function of Met in reproduction of neotenics by RNA interference (RNAi). Our results showed that the JH titres of neotenics were significantly higher than those of nymphs and workers. JH signalling genes were highly expressed in neotenic abdomens, compared with those in workers and nymphs. Met RNAi resulted in the inhibition of vitellogenin gene expression in newly moulted neotenics. These results suggest that the fertility of neotenics might be controlled by a large increase of JH titres and body-part-specific activation of JH signalling pathways.

Heightened condition-dependent growth of sexually selected weapons in the rhinoceros beetle, Trypoxylus dichotomus (Coleoptera: Scarabaeidae).

The exaggerated weapons and ornaments of sexual selection are condition-dependent traits that often grow to exaggerated proportions. The horns of male rhinoceros beetles are extremely sensitive to the larval nutritional environment and are used by rival males in combat over access to females. In contrast to horns, other parts of the body, such as wings, eyes, and legs, scale proportionally with body size, whereas others, such as males' external genitalia, are invariant with body size, regardless of nutrition. We document how body parts of the Asian rhinoceros beetle, Trypoxylus dichotomus, exhibit plasticity and constraint in response to nutritional condition. We discuss the implications of these results for the evolution of condition-dependent and condition-independent traits in animals.

Juvenile hormone titre and related gene expression during the change of reproductive modes in the pea aphid.

Most aphids show reproductive polyphenism, i.e. they alternate their reproductive modes from parthenogenesis to sexual reproduction in response to short photoperiods. Although juvenile hormone (JH) has been considered a likely candidate for regulating the transition from asexual to sexual reproduction after photoperiod sensing, there are few studies investigating the direct relationship between JH titres and the reproductive-mode change. In addition, the sequencing of the pea aphid genome has allowed identification of the genes involved in the JH pathway, which in turn allows us to examine their expression levels in relation to the reproductive-mode change. Using liquid chromatography-mass spectrometry in the pea aphid, JHIII titre was shown to be lower in aphids producing sexual morphs under short-day conditions than in aphids producing parthenogenetic morphs under long-day conditions. The expression levels of genes upstream and downstream of JH action were quantified by real-time quantitative reverse-transcription-PCR across the reproductive-mode change. The expression level of JH esterase, which is responsible for JH degradation, was significantly higher in aphids reared under short-day conditions. This suggests that the upregulation of the JH degradation pathway may be responsible for the lower JHIII titre in aphids exposed to short-days, leading to the production of sexual morphs.

Acoustically induced spin-orbit interactions revealed by two-dimensional imaging of spin transport in GaAs.

Magneto-optic Kerr microscopy was employed to investigate the spin-orbit interactions of electrons traveling in semiconductor quantum wells using surface acoustic waves (SAWs). Two-dimensional images of the spin flow induced by SAWs exhibit anisotropic spin precession behaviors caused by the coexistence of different types of spin-orbit interactions. The dependence of spin-orbit effective magnetic fields on SAW intensity indicates the existence of acoustically controllable spin-orbit interactions resulting from the strain and Rashba contributions induced by the SAWs.

SOS involvement in stress-inducible biofilm formation.

Bacterial biofilm formation can be induced by antimicrobial and DNA damage agents. These agents trigger the SOS response, in which SOS sensor RecA stimulates auto-cleavage of repressor LexA. These observations lead to a hypothesis of a connection between stress-inducible biofilm formation and the RecA-LexA interplay. To test this hypothesis, three biofilm assays were conducted, viz. the standard 96-well assay, confocal laser scanning microscopy, and the newly developed biofilm-on-paper assay. It was found that biofilm stimulation by the DNA replication inhibitor hydroxyurea was dependent on RecA and appeared repressed by the non-cleavable LexA of Pseudomonas aeruginosa. Surprisingly, deletion of lexA led to reduction of both normal and stress-inducible biofilm formation, suggesting that the wild-type LexA contributes to biofilm formation. The decreases was not the result of poor growth of the mutants. These results suggest SOS involvement in hydroxyurea-inducible biofilm formation. In addition, with the paper biofilm assay, it was found that degradation of the biofilm matrix DNA by DNase I appeared to render the biofilms susceptible to the replication inhibitor. The puzzling questions concerning the roles of LexA in DNA release in the biofilm context are discussed.

Quality factor control and lasing characteristics of InAs/InGaAs quantum dots embedded in photonic-crystal nanocavities.

We demonstrate lasing action with a high spontaneous emission factor and temperature insensitivity in InAs/InGaAs quantum dots (QD) embedded in photonic crystal nanocavities. A quality factor (Q) of over 10,000 was achieved by suppressing the material absorption by QDs uncoupled to the cavity mode. High Q cavities exhibited ultra low threshold lasing with a spontaneous emission factor of 0.7. Less frequent carrier escape from the QDs, which was primarily favored by high potential barrier energy, enabled low threshold lasing up to 90 K.

Cavity polaritons in InGaN microcavities at room temperature.

Cavity polaritons are observed in InGaN quantum well (QW) microcavities at room temperature. High-quality microcavities are fabricated by the wafer-bonding of InGaN QW layers and dielectric distributed Bragg reflectors. The anticrossing behavior of strong exciton-photon coupling is confirmed by vacuum-field Rabi splitting obtained from reflection measurements. This strong coupling is also enhanced by increasing the integrated oscillator strength coupled to the cavity mode. The oscillator strength of InGaN QW excitons is 1 order of magnitude larger than that of GaAs QW excitons.

Transgenerational transmission of radiation- and chemically induced tumors and congenital anomalies in mice: studies of their possible relationship to induced chromosomal and molecular changes.

This article provides a broad overview of our earlier studies on the induction of tumors and congenital anomalies in the progeny of X-irradiated or chemically treated mice and our subsequent (published, hitherto unpublished and on-going) investigations aimed at identifying potential relationships between genetic changes induced in germ cells and the adverse effects manifest as tumors and congenital anomalies using cytogenetic and molecular approaches. The earlier studies document the fact that tumors and congenital anomalies can be induced by irradiation or treatment with certain chemicals such as urethane and that these phenotypes are heritable i.e., transmitted to generations beyond the first generation. These findings support the view that transmissible induced genetic changes are involved. The induced rates of congenital abnormalities and tumors are about two orders of magnitude higher than those recorded in the literature from classical mutation studies with specific locus mutations. The cytogenetic studies addressed the question of whether there were any relationships between induced translocations and induced tumors. The available data permit the inference that gross chromosomal changes may not be involved but do not exclude smaller induced genetic changes that are beyond the resolution of the techniques used in these studies. Other work on possible relationship between visible chromosomal anomalies (in bone marrow preparations) and tumors were likewise negative. However, there were indications that some induced cytogenetic changes might underlie induced congenital anomalies, i.e., trisomies, deletions and inversions were observed in induced and transmissible congenital anomalies (such as dwarfs, tail anomalies). Studies that explored possible relationships between induction of minisatellite mutations at the Pc-3 locus and tumors were negative. However, gene expression analysis of tumor (hepatoma)-susceptible offspring of progeny descended from irradiated male mice showed abnormal expression of many genes. Of these, only very few were oncogenes. This lends some support to our hypothesis that cumulative changes in gene expression of many genes, which perform normal cellular functions, may contribute to the occurrence of tumors in the offspring of irradiated or chemically treated mice.

[Minimally invasive direct coronary artery bypass in a patient with idiopathic thrombocytopenic purpura; report of a reoperative case].

A 77-year-old man who had undergone coronary artery bypass grafting (CABG) to segment 3, 7 and 12-14 with saphenous vein grafts (SVG) 15 years before, and ligation of coronary arteriovenous (AV) fistula 8 years before was admitted to our hospital, and diagnosed as acute heart failure and idiopathic thrombocytopenic purpura. Coronary angiography showed multiple stenosis of three vessels, and the grafts to segment 3 and 7 were occluded. The area of left anterior descending (LAD) had no viability, but the inferior wall had viability on dobutamine load echocardiography. The platelet count was about 5.0 x 10(4)/mm3. Minimally invasive direct coronary artery bypass (MIDCAB) for right coronary artery (RCA) using right internal thoracic artery (RITA) was performed through right parasternotomy. Operative and postoperative bleeding was slight, and postoperative course was uneventful. Reoperative MIDCAB can be safely performed in a patient with idiopathic thrombocytopenic purpura, and should be considered a viable alternative for highrisk patients.

Magnetic resonance imaging and clinical findings examined in adulthood-studies on three adults with Rett syndrome.

PURPOSE: To clarify magnetic resonance imaging (MRI) findings in three adult patients with Rett syndrome who had been diagnosed with mental retardation and autism. METHOD: Clinical and MRI findings in three adult cases with Rett syndrome were studied. Ages (in years) in three adult cases with Rett Syndrome were 46 in Case 1, 35 in Case 2 and 20 in Case 3. They were able to walk and their convulsions were well controlled. RESULTS: MRI findings in all patients showed mild cerebral atrophy, especially in the frontal and temporal lobes and two of the cases also had mild cerebellar atrophy. One case also showed a narrowing of the brainstem and thinning of the corpus callosum. CONCLUSIONS: These results indicate that abnormalities in MRI imaging, in cases where there is narrowing of the brainstem and thinning of the corpus callosum, may be due to congenital hypoplasia. It was also seen that cerebellar atrophy became more distinct in older cases.

Exciton Rabi oscillation in a single quantum dot.

A spectroscopic method, which enables characterization of a single isolated quantum dot and a quantum wave function interferometry, is applied to an exciton discrete excited state in an InGaAs quantum dot. Long coherence of zero-dimensional excitonic states made possible the observation of coherent population flopping in a 0D excitonic two-level system in a time-domain interferometric measurement. Corresponding energy splitting is also manifested in an energy-domain measurement.

Overexpression of the Wiskott-Aldrich syndrome protein N-terminal domain in transgenic mice inhibits T cell proliferative responses via TCR signaling without affecting cytoskeletal rearrangements.

Wiskott-Aldrich syndrome (WAS) is an X-linked recessive disorder characterized by thrombocytopenia with small platelets, severe eczema, and recurrent infections due to defects in the immune system. The disease arises from mutations in the gene encoding the WAS protein (WASP), which plays a role as an adaptor molecule in signal transduction accompanied by cytoskeletal rearrangement in T cells. To investigate the functional domain of WASP, we developed transgenic mice overexpressing the WASP N-terminal region (exon 1-5) including the Ena/VASP homology 1 (pleckstrin homology/WASP homology 1) domain, in which the majority of mutations in WAS patients have been observed. WASP transgenic mice develop and grow normally under the specific pathogen-free environment, and showed normal lymphocyte development. However, proliferative responses and cytokine production induced by TCR stimulation were strongly inhibited in transgenic mice, whereas Ag receptor capping and actin polymerization were normal. These findings suggest that overexpressed Ena/VASP homology 1 (pleckstrin homology/WASP homology 1) domain of WASP inhibits the signaling from TCR without coupling of cytoskeletal rearrangement. WASP transgenic mice shown here could be valuable tools for further understanding the WASP-mediated processes.

Ulnar deviation after volar subluxation of the proximal interphalangeal joint.

A rare case of irreducible and progressive ulnar deviation after volar subluxation of the proximal interphalangeal joint is presented. An immobilized proximal interphalangeal joint with remaining volar subluxation after improper reduction showed ulnar deviation at 3 weeks after injury. During surgery, the radial collateral ligament was found to be ruptured at its origin, with formation of concomitant scar tissues. There were no apparent lesions at the central slip, lateral band, and volar plate. Interposition of the ruptured ligament and infiltration of the surrounding scar tissues into the proximal interphalangeal joint were identified. Surgical incision of the capsule along the dorsal margin of the radial collateral ligament readily produced successful reduction. The irreducible and progressive ulnar deviation of the proximal interphalangeal joint seemed to result from gradual infiltration of the scar tissues, subsequent to remaining volar subluxation because of interposition of the ruptured collateral ligament.

Salivary gland extract of Rhipicephalus appendiculatus ticks inhibits in vitro transcription and secretion of cytokines and production of nitric oxide by LPS-stimulated JA-4 cells.

There is increasing evidence that compounds in tick saliva and salivary gland extract (SGE) have a suppressive effect on host immunity and that tick-borne pathogens exploit this situation to their benefit thus causing diseases. We have demonstrated that SGE derived from Rhipicephalus appendiculatus ticks has a suppressive effect on a macrophage like cell line, JA-4, in terms of secretion as well as mRNA transcription of three cytokines. Percent suppression of cytokine secretion by JA-4 cells cultured in the presence of lipopolysaccharide (LPS) and SGE in comparison to JA-4 cells cultured in the presence of LPS alone was 67.8, 89.1 and 82.0% for IL-1alpha, TNF-alpha and IL-10, respectively (P<0.05). A similar pattern of results was demonstrated in terms of mRNA transcription where SGE-induced suppression was 36.9% for IL-1alpha, 25.0% for TNF-alpha and 31.5% for IL-10 (P<0.05). In addition, we have demonstrated that SGE partially inhibited nitric oxide production by JA-4 activated with LPS. The results of the present study suggest that tick salivary gland compounds may exert their effect in vivo by blocking the functions of macrophages in the transcription of cytokines and production of nitric oxide. This SGE-induced immunomodulation may comprise a major gateway in the facilitation of tick feeding and transmission of pathogens in hosts.

Computing the relative gas-phase populations of C60 and C70: beyond the traditional delta H(fo),298 scale.

Computations and experiments have shown that the relative heat of formation (i.e., the heat of formation per carbon atom) of C70 is lower than of C60. Moreover, various computations suggest that this is actually a general trend among fullerene cages. The relationship is particularly important for gas-phase fullerenes. Experiments have shown that C60 is typically more populated than C70 when produced in high-temperature gas-phase synthesis. It is not immediately obvious how to reconcile those two terms, or whether the relative heats of formation and the relative populations are in conflict or in agreement. This article deals with this problem, treating it as a general task of relative stabilities of gas-phase clusters of different dimensions (i.e., nonisomeric clusters) under different types of thermodynamic equilibria. The results are then applied to C60 and C70 and point out that the conventional standard pressure of 1 atm is considerably different from actual fullerene-synthesis conditions. Apparently, we should expect considerably lower cluster pressures in carbon-arc synthesis. At 1 atm, C70 is more populated than C60, but at the conditions of a saturated carbon vapor the stability order is reversed in favor of C60 so that an agreement with experiment is obtained already within the thermodynamic treatment. The pressure effects are modeled using the MNDO, AM1, PM3, and SAM1 quantum-chemical semi-empirical methods as well as the available experimental data. The computations consistently show that, if the pressure effects are considered, C60 becomes more populated than C70. Relationships of the thermodynamic treatment to more sophisticated but impractical kinetic analysis are also discussed.

Pharmacokinetic study of human natural beta-interferon in patients with end-stage renal failure.

AIMS: Although human natural beta-interferon (beta-IFN) is currently used in the treatment of a number diseases, there have been no published studies of the pharmacokinetics and pharmacodynamics of beta-IFN in patients with end-stage renal failure. MATERIALS: Five maintenance hemodialysis patients with chronic hepatitis C (4 men and 1 woman) were enrolled in this study. METHODS: For the pharmacokinetic study, blood samples were obtained from a forearm vein at intervals, before infusion and 0, 3, 5, 10, 20, 30, and 40 minutes after a 15-minute intravenous infusion of human natural beta-IFN (Feron, Toray Industries, Inc., Tokyo) at a dose of 600 MIU. RESULTS: Intravenous beta-IFN was administrated safely to all five patients. The plasma half-life of beta-IFN was found to be 6.91 +/- 2.80 (mean +/- SD) minutes. The initial volume of distribution was found to be 0.49 +/- 0.02 l/kg. CONCLUSION: A 15-minute intravenous infusion of human natural beta-IFN was safely administered to the hemodialysis patients. This pharmacokinetic study showed that it is not necessary to reduce the dosage in patients with end-stage renal failure.