Picosecond-Scale Ultrafast Many-Body Dynamics in an Ultracold Rydberg-Excited Atomic Mott Insulator.

We report the observation and control of ultrafast many-body dynamics of electrons in ultracold Rydberg-excited atoms, spatially ordered in a three-dimensional Mott insulator (MI) with unity filling in an optical lattice. By mapping out the time-domain Ramsey interferometry in the picosecond timescale, we can deduce entanglement growth indicating the emergence of many-body correlations via dipolar forces. We analyze our observations with different theoretical approaches and find that the semiclassical model breaks down, thus indicating that quantum fluctuations play a decisive role in the observed dynamics. Combining picosecond Rydberg excitation with MI lattice thus provides a platform for simulating nonequilibrium dynamics of strongly correlated systems in synthetic ultracold atomic crystals, such as in a metal-like quantum gas regime.

Ultrafast Creation of Overlapping Rydberg Electrons in an Atomic BEC and Mott-Insulator Lattice.

We study an array of ultracold atoms in an optical lattice (Mott insulator) excited with a coherent ultrashort laser pulse to a state where single-electron wave functions spatially overlap. Beyond a threshold principal quantum number where Rydberg orbitals of neighboring lattice sites overlap with each other, the atoms efficiently undergo spontaneous Penning ionization resulting in a drastic change of ion-counting statistics, sharp increase of avalanche ionization, and the formation of an ultracold plasma. These observations signal the actual creation of electronic states with overlapping wave functions, which is further confirmed by a significant difference in ionization dynamics between a Bose-Einstein condensate and a Mott insulator. This system is a promising platform for simulating electronic many-body phenomena dominated by Coulomb interactions in the condensed phase.

A case of feline gastrointestinal eosinophilic sclerosing fibroplasia limited to the mesentery.

An entire, female, mixed-breed cat of unknown age was presented with a 6-week history of lethargy, anorexia and vomiting. There was an increase in the number of white blood cells in the blood, including neutrophils and eosinophils; moderate anaemia; ascites; and possible mesenteric peritonitis. Exploratory laparotomy revealed firm, multifocal small nodules in the mesentery. As the nodules were surgically unresectable, they were biopsied. Histologically, the nodules were composed of thin trabeculae of dense collagen fibres mixed with plump fibroblasts and numerous eosinophils, consistent with feline gastrointestinal eosinophilic sclerosing fibroplasia. Bacteria were not detected on histological examination of the nodules and cytology of the ascites. Remission of disease occurred following treatment with prednisolone and ciclosporin A for 22 days and antibiotics for 40 days. After remission, ciclosporin A was administered for 236 days and then discontinued. Eosinophilia also resolved after treatment with ciclosporin A. The cat is still alive and in good condition on day 689. This report describes what may be an atypical case of feline gastrointestinal eosinophilic sclerosing fibroplasia, lacking involvement of the gastrointestinal tract, and was apparently cured by treatment that involved ciclosporin A.

Effects of Granulocyte and Monocyte Adsorptive Apheresis in Renal Transplantation Recipients With Concomitant Cytomegalovirus Infection.

BACKGROUND: Granulocyte and monocyte adsorptive apheresis (GMAA) is widely used as a treatment for active ulcerative colitis (UC) in Japan. Much attention has been paid to the possibility of GMAA for the treatment and control of cytomegalovirus (CMV) reactivation in patients with refractory UC and concomitant CMV infection. In this study, the effects of the combination of GMAA and antiviral therapy were examined in renal transplant recipients with concomitant CMV infection. METHODS: Combination therapy of GMAA and antiviral drugs was performed 9 times in 7 renal transplant recipients with concomitant CMV infection. Four of the cases were positive for CMV-IgG, and 3 were negative. The clinical presentation of CMV infection was viremia in 6 cases and disease (CMV retinitis) in 1 case. CMV infection was diagnosed by using an antigenemia assay (C7-HRP). GMAA session was performed once, and the duration of the session was 120 min. Immediately after the GMAA session, ganciclovir was administered at 5 mg/kg/body weight. CMV infection was monitored based on C7-HRP and CMV-DNA in the peripheral blood samples. RESULTS: All cases became negative for C7-HRP and CMV-DNA within 21 days (median, 14 days; range, 3-21 days) and 17 days (median, 6 days; range, 3-17 days), respectively, after starting the combination therapy. No side effects of GMAA were observed. CONCLUSIONS: This case series found that GMAA in combination with antiviral drugs may shorten the duration of treatment against CMV infection in renal transplant recipients. Further studies in a larger number of patients are required to confirm these results.

Stem cell factor contributes to tumorigenesis of mast cells via an autocrine/paracrine mechanism.

Mastocytosis is a disease accompanied by the abnormal expansion and accumulation of mast cells. Although the D816V mutation is detected in most cases of systemic mastocytosis, the mutation is rarely observed in other forms of mastocytosis, such as cutaneous mastocytosis and mast cell leukemia/sarcoma, for which the mechanism of tumorigenesis remains unknown. In this study, we demonstrated a novel mechanism of mast cell tumorigenesis via SCF autocrine/paracrine release. SCF was highly expressed in a WT KIT-expressing HRMC line, contributing to the phosphorylation of KIT. Neutralization of external SCF using a neutralizing antibody or suppression of SCF production by RNA interference inhibited the growth of HRMC cells, indicating the essential role of SCF in cell proliferation. To the best of our knowledge, this is the first report to determine the significant contribution of SCF autoproduction to neoplastic proliferation of mast cells. These results indicate the possibility that targeting SCF production may become a novel treatment for mast cell malignancies.

The interaction between Lyn and FcεRIß is indispensable for FcεRI-mediated human mast cell activation.

BACKGROUND: FcεRIß reportedly functions as an amplifier of the FcεRIγ-mediated activation signal using a reconstitution system. However, the amplification mechanisms in human mast cells (MCs) are poorly understood. We previously reported the hyperexpression of FcεRIß of MCs in giant papillae from vernal keratoconjunctivitis patients, compared with that in conjunctivae from nonallergic conjunctivitis patients. Elucidation of the molecular mechanisms of the amplification induced by FcεRIß should provide new targets for novel therapeutic interventions. The aim is to understand in greater details the function of FcεRIß in human MC FcεRI expression and signaling. METHODS: FcεRIß and Lyn expression was reduced using a lentiviral shRNA silencing technique. Localization of Lyn and FcεRIß in cultured MCs was examined by confocal microscopic analysis. Mediators were measured by ELISAs. RESULTS: The diminution of FcεRIß significantly downregulated cell surface FcεRI expression and FcεRI-mediated mediator release/production. The downregulation of FcεRI-mediated degranulation was not only due to the decrease in FcεRI expression. The diminution of FcεRIß inhibited the redistribution of Lyn within the cell membrane following IgE sensitization. The diminution of Lyn in MCs significantly downregulated FcεRI-mediated degranulation. The recombinant cell-penetrating forms of phosphorylated FcεRIß immunoreceptor tyrosine-based activation motif (ITAM) for intracellular delivery disturbed the interaction between Lyn and phosphorylated endogenous FcεRIß ITAM, resulted in inhibiting IgE-dependent histamine release from MCs in vitro and from giant papillae specimens ex vivo. CONCLUSION: The interaction between Lyn and FcεRIß is indispensable for FcεRI-mediated human MC activation, and specific inhibition of the interaction may represent a new therapeutic strategy for the treatment of human allergic diseases.

A novel NF-κB inhibitor improves glucocorticoid sensitivity of canine neoplastic lymphoid cells by up-regulating expression of glucocorticoid receptors.

Lymphoid neoplasms including lymphoma and leukemia are one of the most life-threatening disorders in dogs. Many lymphoid malignancies are well-treated with glucocorticoid (GC); however, GC resistance sometimes develops and its mechanism remains uncertain. Since constitutive activation of nuclear factor-κB (NF-κB) has been reported to play roles in lymphoid malignancies, we examined whether inhibition of NF-κB activity with a synthetic inhibitor IMD-0354 affected GC sensitivity of canine neoplastic lymphoid cells, CL-1 and GL-1. Dexamethasone failed to inhibit proliferation of these cells, in which low expression of glucocorticoid receptors (GR) was identified. In the presence of IMD-0354, GR expressions in CL-1 and GL-1 were increased, consequently dexamethasone inhibited their proliferation. These results indicated that GR expression might be down-regulated by spontaneous activation of NF-κB, resulting in GC resistance. Taken together, interference of NF-κB activity may have the synergistic effect in combination chemotherapy with GC for treatment against lymphoid malignancies.

Cell transformation activities of abietic acid and dehydroabietic acid: safety assessment of possible contaminants in paper and paperboard for food contact use.

Abietic acid (AA) and dehydroabietic acid (DHA) have been detected in virgin paper products and recycled paper products used for food packaging. In order to evaluate the cell transformation activities of AA and DHA, the Bhas 42 cell-transformation assay for initiation and promotion was carried out. Tested in the initiation stage, AA and DHA did not significantly increase transformation frequencies. On the other hand, both chemicals induced transformed foci dose dependently at the promotion stage. The highest transformed foci density induced by AA was about 13 foci/well at 60 nmol ml(-1), and that of DHA was about 16 foci/well at 40 nmol ml(-1) (solvent control = 2.3 +/- 1.4 foci/well). The present results suggest that AA and DHA may have tumour-promoting potential.

Static bone cavity in the condylar neck and mandibular notch of the mandible.

This study presents the radiographic findings of two cases of static bone cavity in the inferior aspect of the condylar neck and mandibular notch of the mandible. On plain CT, a soft tissue mass was observed in each cavity. The submandibular gland and the other glands were not found in each cavity. On contrast-enhanced CT, the soft tissue in the cavity in the inferior aspect of the condylar neck had marked linear enhancement and dilated vasculature structure was observed in the cavity. On the contrast-enhanced MRI, the soft tissue in the cavity of the mandibular notch had marked enhancement and flow void was detected in the cavity. In the inferior aspect of the condylar neck, the cavity size had enlarged radiographically over a period of three years. Vascular lesions were found in the cavity located in the inferior aspect of the condylar neck and mandibular notch of the mandible by both CT and MRI. The vascular lesion might explain the enlargement of the static bone cavity.

Vacuum phenomenon in non-open fracture of the mandibular condyle: report of three cases.

Gas in the joint space was observed in three patients with condylar fracture who were referred for CT examinations of the mandible. CT showed that the condylar fractures were non-open fractures. The gas was only observed in the intrajoint capsule of the temporomandibular joint (TMJ). Follow-up CT, 4 days after the initial CT, showed that the gas in the joint space was absorbed in one of three cases. In the non-open condylar fractures, the gas collection in the TMJ was considered to be a vacuum phenomenon due to the intact joint capsule of the TMJ on CT.

Green tea consumption and lung cancer risk: the Ohsaki study.

We examined the risk of lung cancer in relation to green tea consumption in a population-based cohort study in Japan among 41,440 men and women, aged 40-79 years, who completed a questionnaire in 1994 regarding green tea consumption and other health-related lifestyle factors. During the follow-up period of 7 years (from 1995 to 2001), 302 cases of lung cancer were identified, and the Cox proportional hazards regression model was used to estimate the hazard ratios (HRs) and 95% confidence intervals (CIs). The multivariable-adjusted HRs of lung cancer incidence for green tea consumption of 1 or 2, 3 or 4, and 5 or more cups/day as compared to less than 1 cup/day were 1.14 (95% CI: 0.80-1.62), 1.18 (95% CI: 0.83-1.66), and 1.17 (95% CI: 0.85-1.61), respectively (P for trend=0.48). This cohort study has found no evidence that green tea consumption is associated with lung cancer.

Sleep duration and the risk of prostate cancer: the Ohsaki Cohort Study.

In a prospective study of prostate cancer incidence (127 cases), among 22 320 Japanese men, sleep duration was associated with lower risk; the multivariate hazard ratio of men who slept >or=9 h per day compared with those who slept less was 0.48 (95% confidence interval: 0.29-0.79, P for trend=0.02).

Degenerative lumbosacral spondylolisthesis: possible factors which predispose the fifth lumbar vertebra to slip.

We have analysed a number of radiological measurements in an attempt to clarify the predisposing factors for degenerative spondylolisthesis of the lumbosacral junction. We identified 57 patients with a slip and a control group of 293 patients without any radiological abnormality apart from age-related changes. The relative thickness of the L5 transverse process, the sacral table angle and the height of the iliac crest were measured and evaluated. The difference in these measurements between men and women was analysed in the control group. We found that the transverse process of L5 was extremely slender, the sacral table more inclined, and the L5 vertebra was less deeply placed in the pelvis in patients with a slip compared with the control group. The differences in these three parameters were statistically significant. We believe that the L5 vertebra is predisposed to slip when these factors act together on a rigidly-stabilised sacrum. This occurs more commonly in women, probably as a result of constitutional differences in the development of the male and female spine.

Identifying pathogenic genetic background of simplex or multiplex retinitis pigmentosa patients: a large scale mutation screening study.

BACKGROUND AND PURPOSE: More than half of the retinitis pigmentosa (RP) cases are genetically simplex or multiplex. To date, 37 causative genes of RP have been identified; however, the elucidation of gene defects in simplex or multiplex RP patients/families remains problematic. The aim of our study was to identify the genetic causes of RP in patients with unknown or non-Mendelian inheritance. METHODS AND RESULTS: Since 2003, 52 simplex RP patients, 151 patients from 141 multiplex RP families, and six sporadic patients with retinal degeneration were studied. A total of 108 exons of 30 RP-causing genes that harboured the reported mutations were screened by an efficient denaturing high performance liquid chromatography (dHPLC) based assay. Aberrant fragments were subsequently analysed by automatic sequencing. Twenty-six mutations, including two frameshift mutations, one single amino acid deletion, and 23 missense mutations, were identified in 28 probands (14.07%). Eighteen mutations have not been reported to date. Three pairs of combined mutations in different genes were identified in two sporadic cases and one multiplex family, indicating the possibility of novel digenic patterns. Of the 23 missense mutations, 21 were predicted as deleterious mutations by computational methods using PolyPhen, SIFT, PANTHER, and PMut programs. CONCLUSION: We elucidated the mutation spectrum in Japanese RP patients and demonstrated the validity of the mutation detection system using dHPLC sequencing for genetic diagnosis in RP patients independent of familial incidence, which may provide a model strategy for identifying genetic causes in other diseases linked to a wide range of genes.

Giant cell reparative granuloma of the proximal tibia: a case report.

Giant cell reparative granulomas (GCRGs) are non-neoplastic inflammatory lesions, usually of the jaw or gingiva or small bones of the hands and feet. We report one such case in the right proximal tibia of a 45-year-old man. Radiological studies showed a lytic lesion with marginal sclerosis in the epiphysis and metaphysis. After open biopsy, a preliminary diagnosis of a benign giant cell tumour was made. One month after admission, the lesion was curetted and filled with cancellous bone and hydroxyapatite. Based on the histology of the curetted lesion, the diagnosis was changed to a GCRG. The patient had an uneventful postoperative course, with no evidence of local recurrence and metastasis. He died from gastric cancer 2 years later.

Monomeric but not trimeric clathrin heavy chain regulates p53-mediated transcription.

Tumor suppressor p53 protein is the transcription factor responsible for various genes including DNA repair, growth arrest, apoptosis and antiangiogenesis. Recently, we showed that clathrin heavy chain (CHC), which was originally identified as a cytosolic protein regulating endocytosis, is present in nuclei and functions as a coactivator for p53. Here, we determined the detailed p53-binding site of CHC and a CHC deletion mutant containing this region (CHC833-1406) behaved as a monomer in cells. Monomeric CHC833-1406 still had a higher ability to transactivate p53 than wild-type CHC although this CHC mutant no longer had endocytic function. Moreover, similar to wild-type CHC, monomeric CHC enhances p53-mediated transcription through the recruitment of histone acetyltransferase p300. Immunofluorescent microscopic analysis exhibited that CHC833-1406 is predominantly localized in nuclei, suggesting that there may be a certain regulatory domain for nuclear export in the C-terminus of CHC. Thus, the trimerization domain of CHC is not necessary for the transactivation of p53 target genes and these data provide further evidence that nuclear CHC plays a role distinct from clathrin-mediated endocytosis.

Genetic analysis of high-metastatic clone of RCT sarcoma in mice, and its growth regression in vivo in response to angiogenesis inhibitor TNP-470.

Genetic analysis of a high-metastatic clone of RCT sarcoma (HM-RCT) was the aim of the study. HM-RCT was developed by the lung passage as well as limiting dilution method from the original RCT sarcoma, in which a tumor was spontaneously developed in a C3H/He mouse. HM-RCT expressed enhanced POU domain (class 2, associating factor 1), adenylate cyclase 7, procollagen type III (alpha), A kinase anchor protein 4 and Ehm (expressed on high-metastatic cells) and 11 expressed sequence tags (ESTs). compared with the original clone of RCT. Eighteen specific genes and 14 ESTs were underexpressed in HM-RCT. We investigated the effects of angiogenesis inhibitor TNP-470 on tumor growth and metastasis of this HM-RCT in vivo. In an experimental group, mice received TNP-470 (30 mg/kg) intraperitoneally every other day. After 5 weeks, the growth of the TNP-470-treated tumor was significantly suppressed in vivo, but did not affect the metastasis. The proportion of positive PCNA-stained cells and cellular telomerase activity was significantly low in response to TNP-470.

CT and MRI findings of intraosseous schwannoma of the mandible: a case report.

We report the radiographical findings of a rare case of intraosseous schwannoma of the mandible. The tumour that presented as a unilocular, well-defined, radiolucent lesion on plain radiography was located in the molar region. On CT, the tumour was a well-demarcated mass with no periosteal reaction and no destruction of the bone cortex. Destructive changes in the cortical wall of the mandibular canal by the tumour were observed on CT, but no evidence of dilatation and shift in the inferior mandibular canal was seen. MR imaging revealed that the mandibular canal was encased by the tumour as a solid mass without cystic parts. The signal intensity of the tumour was non-specific on MRI. Characteristics of intraosseous schwannoma in the mandible are the encasement of the canal by a well-demarcated tumour without periosteal reaction and the destruction of mandibular bone cortex. The destructive change of the inferior mandibular canal can be observed on CT and MRI. However, a biopsy is necessary to make the final diagnosis because of the non-specificity of the findings.

Validity and utility of the Japanese version of the WHO-Five Well-Being Index in the context of detecting suicidal ideation in elderly community residents.

OBJECTIVE: The aim of this study is to evaluate the validity and the utility of the Japanese version of the WHO-Five Well-Being Index (WHO-5-J) in the context of detecting suicidal ideation in elderly community residents. METHODS: A sample of 696 subjects aged 70 years or over who completed a set of questionnaires was examined. RESULTS: Cronbach's alpha was 0.87 and Loevinger's coefficient was 0.64. The total score was significantly correlated with the number of cohabitants, the number of physical illnesses, physical functioning, instrumental activities of daily living, and depressive symptoms. Subjects with suicidal ideation had significantly lower scores on the WHO-5-J. The receiver-operating characteristic curve analysis indicated that the scale significantly discriminated the subjects with suicidal ideation. When combined with the assessment of a lack of perceived social support (PSS), a standard cut-off criterion of "a total score < or = 12 or answering 0 or 1 to any of the five items" more appropriately identified elderly subjects with suicidal ideation: sensitivity = 87%, specificity = 75%, negative predictive value = 99%, and positive predictive value = 10%. CONCLUSIONS: In combination with PSS, the scale has predictive utility to detect suicidal ideation in elderly community residents.