Axillary lymph-node metabolic activity assessment on 18F-FDG-PET/CT in rheumatoid arthritis patients treated with biologic therapies.

Objective: Recent studies have provided new insights into the role of lymph nodes (LNs) in rheumatoid arthritis (RA). The aim of this study was to evaluate the metabolic activity of the axillary LNs in relation to that of the upper limb joints and the clinical assessment of disease activity in RA patients treated with biologic therapies.Method: 18F-fluorodeoxyglucose-positron emission tomography/computed tomography (18F-FDG-PET/CT) scans were acquired for 64 patients with RA at baseline and after 6 months of biologic therapy, and the patients' clinical status was evaluated. The maximum standardized uptake value (SUVmax), metabolic active volume, and total lesion glycolysis (TLG) were used to assess glucose metabolism in the LNs and 12 joints. Clinical evaluations included serum markers and the Disease Activity Score based on 28-joint count-erythrocyte sedimentation rate (DAS28-ESR).Results: Changes in the SUVmax and TLG for the axillary LNs correlated significantly with those of the ipsilateral wrist joints. There was a positive correlation between the changes in the three metabolic parameters of the axillary LNs and the changes in disease activity after treatment. After 6 months of biologic therapy, all metabolic parameters for the axillary LNs in patients with a DAS28-ESR < 3.2 were significantly lower than those of patients with a DAS28-ESR ≥ 3.2.Conclusion: A relationship between the glucose metabolism of the axillary LNs and the ipsilateral wrist joints was demonstrated by the 18F-FDG-PET/CT parameters. The metabolic activity and active volume of axillary LNs may reflect the therapeutic response to the biologic treatment of RA.

Oral medicine psychiatric liaison clinic: study of 1202 patients attending over an 18-year period.

Patients with orofacial pain and discomfort often suffer from psychiatric disorders. However, few studies involving a large sample have examined the diagnostic results of patients with orofacial pain or discomfort in relation to psychiatric disorders. The purpose of this study was to summarize and clarify the characteristics and demographic data of 1202 patients attending the psychiatric liaison clinic at Aichi Gakuin University Hospital. Psychiatric diagnosis was performed by psychiatrists for all patients, based on the Diagnostic and Statistical Manual of Mental Disorders, fifth edition. Among the 1202 patients, 992 (82.5%) were female. The average age of the patients was 57.2±15.0years. The predominant broad categories of orofacial pain and discomfort seen were burning mouth syndrome (n=484, 40.3%), persistent idiopathic facial pain (n=258, 21.5%), and oral dysesthesia (n=215, 17.9%). The predominant broad categories of psychiatric diagnoses seen were somatic symptoms and related disorders (n=934, 77.7%) and depressive disorders (n=76, 6.3%). Among the 934 patients with somatic symptoms and related disorders, 678 had a somatic symptom disorder with predominant pain. The results confirmed that most patients with orofacial pain and discomfort were middle-aged and elderly women suffering from a somatic symptom disorder with predominant pain.

A MicroRNA Derived from Adenovirus Virus-Associated RNAII Promotes Virus Infection via Posttranscriptional Gene Silencing.

The adenovirus (Ad) serotype 5 genome encodes two noncoding small RNAs (virus-associated RNAs I and II [VA-RNAI and -II]), which are approximately 160-nucleotide (nt) RNAs transcribed by RNA polymerase III. It is well known that VA-RNAI supports Ad infection via the inhibition of double-stranded RNA-dependent protein kinase (PKR), which recognizes double-stranded RNA and acts as an antiviral system. Recent studies revealed that VA-RNAs are processed into VA-RNA-derived microRNAs (miRNAs) (mivaRNAI and -II); however, we and another group recently demonstrated that mivaRNAI does not promote Ad replication. On the other hand, the roles of VA-RNAII and mivaRNAII in Ad replication have remained to be clarified. In this study, we demonstrated mivaRNAII-mediated promotion of Ad replication. Transfection with chemically synthesized 3'-mivaRNAII-138, one of the most abundant forms of mivaRNAII, significantly enhanced Ad replication, while the other species of mivaRNAII did not. We identified 8 putative target genes of 3'-mivaRNAII-138 by microarray analysis and in silico analysis. Among the 8 candidates, knockdown of the cullin 4A (CUL4A) gene, which encodes a component of the ubiquitin ligase complex, most significantly enhanced Ad replication. CUL4A expression was significantly suppressed by 3'-mivaRNAII-138 via posttranscriptional gene silencing, indicating that CUL4A is a target gene of 3'-mivaRNAII-138 and mivaRNAII functions as a viral miRNA promoting Ad infection. It has been reported that CUL4A is involved in degradation of c-Jun, which acts as a transcription factor in the Jun-N-terminal kinase (JNK) signaling cascade. Treatment with JNK inhibitors dramatically suppressed Ad replication, suggesting that mivaRNAII-mediated downregulation of CUL4A enhanced JNK signaling and thereby promoted Ad infection.IMPORTANCE Several types of viruses encode viral miRNAs which regulate host and/or viral gene expression via posttranscriptional gene silencing, leading to efficient viral infection. Adenovirus (Ad) expresses miRNAs derived from VA-RNAs (mivaRNAI and -II); however, recent studies have revealed that processing of VA-RNAI into mivaRNAI inhibits Ad replication. Conversely, we demonstrate here that mivaRNAII significantly promotes Ad replication and that mivaRNAII-mediated suppression of CUL4A expression via posttranscriptional gene silencing induces accumulation of c-Jun, leading to promotion of Ad infection. These results exhibited the significance of VA-RNAII for supporting Ad infection through a mechanism complementary to that of VA-RNAI. These observations could provide important clues toward a new perspective on host-virus interaction. Moreover, Ad is widely used as a basic framework for viral vectors and oncolytic viruses. Our findings will help to regulate Ad infection and will promote the development of novel Ad vectors and oncolytic Ad.

Phase Competition in the Palmer-Chalker XY Pyrochlore Er_{2}Pt_{2}O_{7}.

We report neutron scattering measurements on Er_{2}Pt_{2}O_{7}, a new addition to the XY family of frustrated pyrochlore magnets. Symmetry analysis of our elastic scattering data shows that Er_{2}Pt_{2}O_{7} orders into the k=0, Γ_{7} magnetic structure (the Palmer-Chalker state), at T_{N}=0.38 K. This contrasts with its sister XY pyrochlore antiferromagnets Er_{2}Ti_{2}O_{7} and Er_{2}Ge_{2}O_{7}, both of which order into Γ_{5} magnetic structures at much higher temperatures, T_{N}=1.2 and 1.4 K, respectively. In this temperature range, the magnetic heat capacity of Er_{2}Pt_{2}O_{7} contains a broad anomaly centered at T^{*}=1.5 K. Our inelastic neutron scattering measurements reveal that this broad heat capacity anomaly sets the temperature scale for strong short-range spin fluctuations. Below T_{N}=0.38 K, Er_{2}Pt_{2}O_{7} displays a gapped spin-wave spectrum with an intense, flat band of excitations at lower energy and a weak, diffusive band of excitations at higher energy. The flat band is well described by classical spin-wave calculations, but these calculations also predict sharp dispersive branches at higher energy, a striking discrepancy with the experimental data. This, in concert with the strong suppression of T_{N}, is attributable to enhanced quantum fluctuations due to phase competition between the Γ_{7} and Γ_{5} states that border each other within a classically predicted phase diagram.

Impact of histone demethylase KDM3A-dependent AP-1 transactivity on hepatotumorigenesis induced by PI3K activation.

Epigenetic gene regulation linked to oncogenic pathways is an important focus of cancer research. KDM3A, a histone H3 lysine 9 (H3K9) demethylase, is known to have a pro-tumorigenic function. Here, we showed that KDM3A contributes to liver tumor formation through the phosphatidylinositol 3-kinase (PI3K) pathway, which is often activated in hepatocellular carcinoma. Loss of Kdm3a attenuated tumor formation in Pik3ca transgenic (Tg) mouse livers. Transcriptome analysis of pre-cancerous liver tissues revealed that the expression of activator protein 1 (AP-1) target genes was induced by PI3K activation, but blunted upon Kdm3a ablation. Particularly, the expression of Cd44, a liver cancer stem marker, was regulated by AP-1 in a Kdm3a-dependent manner. We identified Cd44-positive hepatocytes with epithelial-mesenchymal transition-related expression profiles in the Pik3ca Tg liver and confirmed their in vivo tumorigenic capacity. Notably, the number and tumor-initiating capacity of Cd44-positive hepatocytes were governed by Kdm3a. As a mechanism in Kdm3a-dependent AP-1 transcription, Kdm3a recruited c-Jun to the AP-1 binding sites of Cd44, Mmp7 and Pdgfrb without affecting c-Jun expression. Moreover, Brg1, a component of the SWI/SNF chromatin remodeling complex, interacted with c-Jun in a Kdm3a-dependent manner and was bound to the AP-1 binding site of these genes. Finally, KDM3A and c-JUN were co-expressed in 33% of human premalignant lesions with PI3K activation. Our data suggest a critical role for KDM3A in the PI3K/AP-1 oncogenic axis and propose a novel strategy for inhibition of KDM3A against liver tumor development under PI3K pathway activation.

Associations of sleep bruxism with age, sleep apnea, and daytime problematic behaviors in children.

OBJECTIVES: The aims of this study were to investigate the prevalence of sleep bruxism in children in Japan, and its relationships with sleep-related factors and daytime problematic behavior. SUBJECTS AND METHODS: Guardians of 6023 children aged 2-12 years completed the Japanese Sleep Questionnaire. Multiple regression analysis and structural equation modeling were performed. RESULTS: Sleep bruxism was reported in 21.0% children (n = 1263): the prevalence was highest in the age group of 5-7 years (27.4%). Multiple regression analysis showed that sleep bruxism had significant correlations with age 5-7 years (OR: 1.72; P < 0.0001), 'Moves a lot during sleep' (OR: 1.47; P < 0.0001), 'sleeps with mouth open' (OR: 1.56; P < 0.0001), and 'snores loudly' (OR: 1.80; P < 0.0001). In structural equation modeling, sleep bruxism had a significant but weak direct effect on daytime problematic behavior, while sleep bruxism significantly correlated with obstructive sleep apnea, which had a higher direct effect on daytime problematic behavior. CONCLUSIONS: Sleep bruxism was reported in 21.0% of Japanese children and had independent relationships with age, movements during sleep, and snoring. A comorbidity of sleep-disordered breathing might be related to daytime problematic behavior in children with sleep bruxism.

NF-κB promotes leaky expression of adenovirus genes in a replication-incompetent adenovirus vector.

The replication-incompetent adenovirus (Ad) vector is one of the most promising vectors for gene therapy; however, systemic administration of Ad vectors results in severe hepatotoxicities, partly due to the leaky expression of Ad genes in the liver. Here we show that nuclear factor-kappa B (NF-κB) mediates the leaky expression of Ad genes from the Ad vector genome, and that the inhibition of NF-κB leads to the suppression of Ad gene expression and hepatotoxicities following transduction with Ad vectors. Activation of NF-κB by recombinant tumor necrosis factor (TNF)-α significantly enhanced the leaky expression of Ad genes. More than 50% suppression of the Ad gene expression was found by inhibitors of NF-κB signaling and siRNA-mediated knockdown of NF-κB. Similar results were found when cells were infected with wild-type Ad. Compared with a conventional Ad vector, an Ad vector expressing a dominant-negative IκBα (Adv-CADNIκBα), which is a negative regulator of NF-κB, mediated approximately 70% suppression of the leaky expression of Ad genes in the liver. Adv-CADNIκBα did not induce apparent hepatotoxicities. These results indicate that inhibition of NF-κB leads to suppression of Ad vector-mediated tissue damages via not only suppression of inflammatory responses but also reduction in the leaky expression of Ad genes.

Micromotors working in water through artificial aerobic metabolism.

Most catalytic micro/nanomotors that have been developed so far use hydrogen peroxide as fuel, while some use hydrazine. These fuels are difficult to apply because they can cause skin irritation, and often form and store disruptive bubbles. In this paper, we demonstrate a novel catalytic Pt micromotor that does not produce bubbles, and is driven by the oxidation of stable, non-toxic primary alcohols and aldehydes with dissolved oxygen. This use of organic oxidation mirrors living systems, and lends this new motor essentially the same characteristics, including decreased motility in low oxygen environments and the direct isothermal conversion of chemical energy into mechanical energy. Interestingly, the motility direction is reversed by replacing the reducing fuels with hydrogen peroxide. Therefore, these micromotors not only provide a novel system in nanotechnology, but also help in further revealing the underlining mechanisms of motility of living organisms.

Activity levels of cathepsins B and L in tumor cells are a biomarker for efficacy of reovirus-mediated tumor cell killing.

Reovirus has gained much attention as an anticancer agent; however, the mechanism of the tumor cell-specific replication of reovirus is not fully understood. Although Ras activation is known to be crucial for tumor cell-specific replication of reovirus, it remains controversial which cellular factors are required for the reovirus-mediated tumor cell killing. In this study, we systematically investigated which cellular factors determined the efficiencies of reovirus-mediated tumor cell killing in various human cultured cell lines. The efficiency of reovirus-mediated cell killing varied widely among the cell lines. Junction adhesion molecule-A, a reovirus receptor, was highly expressed in almost all cell lines examined. Ras activation levels were largely different between the cell lines; however, there were no apparent correlations among the reovirus-mediated cell killing efficiencies and Ras activation status. On the other hand, activity levels of the cysteine proteases cathepsins B and L, which are crucial for proteolytic disassembly of the outer capsid proteins of reovirus, showed a tendency to be correlated with the efficiency of reovirus-mediated cell killing. These results indicate that the activity of cathepsins B and L is the most suitable as a biomarker for the efficacy of reovirus-mediated oncolysis among the factors examined in this study.

Upregulation of RECK gene expression by small double-stranded RNA targeting the promoter region.

Recent studies have demonstrated that small double-stranded RNAs (dsRNAs) complementary to the promoter region of target genes enhance the expression of those genes following transfection into cells. Here we show that expression of the matrix metalloproteinase (MMP) inhibitor RECK is activated in the cultured tumor cell lines by transfection with dsRNA complementary to the promoter of the RECK gene, leading to suppression of the expression of MMPs and it inhibited tumor cell invasion. These results support the suggestion that dsRNA complementary to the promoter region of tumor suppressor genes would have potential as a novel antitumor agent.

Elastic constants in orthorhombic hen egg-white lysozyme crystals.

The ultrasonic sound velocities of cross-linked orthorhombic hen egg-white lysozyme (HEWL) crystals, including a large amount of water in the crystal, were measured using an ultrasonic pulse-echo method. As a result, seven elastic constants of orthorhombic crystals were observed to be C11 = 5.24 GPa, C22 = 4.87 GPa, C12 = 4.02 GPa, C33 = 5.23 GPa, C44 = 0.30 GPa, C55 = 0.40 GPa, and C66 = 0.43 GPa, respectively. However, C13 and C23 could not be observed because the suitable crystal planes could not be cut from bulk crystals. We conclude that the observed elastic constants of the cross-linked crystals are coincident with those of the intrinsic crystals without cross-linking. Moreover, the characteristics of the elastic constants in orthorhombic HEWL crystals are due to the fact that the shear elastic constants, C44, C55, and C66, are softer than in tetragonal crystals. That is, the shear components, C44, C55, and C66, are one half of those of the tetragonal crystals.

Sex and the clinical value of body mass index in patients with clear cell renal cell carcinoma.

BACKGROUND: An increased body mass index (BMI) is significantly associated with favourable prognosis in renal cell carcinoma (RCC). This study investigated the associations among sex, BMI, and prognosis in clear cell RCC patients. METHODS: We retrospectively analysed 435 patients with clear cell RCC who underwent a nephrectomy. The associations among sex, BMI, clinicopathologic factors, and cancer-specific survival (CSS) were analysed. RESULTS: As a continuous variable, increased BMI was associated with higher CSS rate by univariate analysis in the whole population (hazard ratio, 0.888 per kg m(-2); 95% confidence interval, 0.803-0.982; P=0.021). A sub-population analysis by sex demonstrated that BMI was significantly associated with CSS in men (P=0.004) but not in women (P=0.725). Multivariate analysis revealed BMI to be an independent predictor of CSS in only men. CONCLUSION: Body mass index was significantly associated with clear cell RCC prognosis. However, the clinical value of BMI may be different between men and women.

Improving adenovirus vector-mediated RNAi efficiency by lacking the expression of virus-associated RNAs.

Several studies have reported that short hairpin RNA (shRNA)-mediated RNA interference (RNAi) was competitively inhibited by the expression of adenovirus (Ad)-encoded small RNAs (VA-RNAs), which are expressed from a replication-incompetent Ad vector, as well as a wild-type Ad; however, it remained to be clarified whether an shRNA-expressing Ad vector-mediated knockdown was inhibited by VA-RNAs transcribed from the same Ad vector genome. In this study, we demonstrated that a lack of VA-RNA expression from the Ad vector leads to an increase in knockdown efficiencies of Ad vector-mediated RNAi. In the cells transduced with a first-generation Ad vector (FG-Ad) expressing shRNA (FG-Ad-shRNA), the copy numbers of shRNA and VA-RNAs incorporated into the RNA-induced silencing complex (RISC) was comparable. In contrast, higher amounts of shRNA were found in the RISC when the cells were transduced with an shRNA-expressing helper-dependent Ad (HD-Ad) vector, in which all viral genes, including VA-RNAs, were deleted (HD-Ad-shRNA), compared with FG-Ad-shRNA. HD-Ad vectors expressing shRNA against luciferase and p53 showed 7.4% and 37.3% increases in the knockdown efficiencies compared to the corresponding FG-Ad-shRNA, respectively, following in vitro transduction. Furthermore, higher levels of knockdown efficiencies were also found by the transduction with shRNA-expressing Ad vectors lacking VA-RNA expression (AdΔVR-shRNA) than by transduction with FG-Ad-shRNA. These results indicate that VA-RNAs expressed from an Ad vector inhibit knockdown by the shRNA-expressing Ad vector and that HD-Ad-shRNA and AdΔVR-shRNA are a powerful framework for shRNA-mediated knockdown.

Persistence of ferroelectricity in BaTiO3 through the insulator-metal transition.

The ferroelectric BaTiO(3) is a band-gap insulator. Itinerant electrons can be introduced in this material by doping, for example, with oxygen vacancies. Above a critical electron concentration of n(c) approximately 1 x 10(20) cm(-3), BaTiO(3-delta) becomes metallic. This immediately raises a question: Does metallic BaTiO(3-delta) still retain ferroelectricity? One may expect itinerant electrons to destroy ferroelectricity as they screen the long-range Coulomb interactions. We followed the phase transitions in BaTiO(3-delta) as a function of n far into metallic phase. Although their stability range decreases with n, the low-symmetry phases in metallic BaTiO(3-delta) are still retained up to an estimated concentration of n* approximately 1.9 x 10(21) cm(-3). Moreover, it appears that the itinerant electrons partially stabilize the ferroelectric phases in metallic BaTiO(3-delta) by screening strong crystal field perturbations caused by oxygen vacancies.

Structural, electronic, optical and vibrational properties of nanoscale carbons and nanowires: a colloquial review.

This review addresses the field of nanoscience as viewed through the lens of the scientific career of Peter Eklund, thus with a special focus on nanocarbons and nanowires. Peter brought to his research an intense focus, imagination, tenacity, breadth and ingenuity rarely seen in modern science. His goal was to capture the essential physics of natural phenomena. This attitude also guides our writing: we focus on basic principles, without sacrificing accuracy, while hoping to convey an enthusiasm for the science commensurate with Peter's. The term 'colloquial review' is intended to capture this style of presentation. The diverse phenomena of condensed matter physics involve electrons, phonons and the structures within which excitations reside. The 'nano' regime presents particularly interesting and challenging science. Finite size effects play a key role, exemplified by the discrete electronic and phonon spectra of C(60) and other fullerenes. The beauty of such molecules (as well as nanotubes and graphene) is reflected by the theoretical principles that govern their behavior. As to the challenge, 'nano' requires special care in materials preparation and treatment, since the surface-to-volume ratio is so high; they also often present difficulties of acquiring an experimental signal, since the samples can be quite small. All of the atoms participate in the various phenomena, without any genuinely 'bulk' properties. Peter was a master of overcoming such challenges. The primary activity of Eklund's research was to measure and understand the vibrations of atoms in carbon materials. Raman spectroscopy was very dear to Peter. He published several papers on the theory of phonons (Eklund et al 1995a Carbon 33 959-72, Eklund et al 1995b Thin Solid Films 257 211-32, Eklund et al 1992 J. Phys. Chem. Solids 53 1391-413, Dresselhaus and Eklund 2000 Adv. Phys. 49 705-814) and many more papers on measuring phonons (Pimenta et al 1998b Phys. Rev. B 58 16016-9, Rao et al 1997a Nature 338 257-9, Rao et al 1997b Phys. Rev. B 55 4766-73, Rao et al 1997c Science 275 187-91, Rao et al 1998 Thin Solid Films 331 141-7). His careful sample treatment and detailed Raman analysis contributed greatly to the elucidation of photochemical polymerization of solid C(60) (Rao et al 1993b Science 259 955-7). He developed Raman spectroscopy as a standard tool for gauging the diameter of a single-walled carbon nanotube (Bandow et al 1998 Phys. Rev. Lett. 80 3779-82), distinguishing metallic versus semiconducting single-walled carbon nanotubes, (Pimenta et al 1998a J. Mater. Res. 13 2396-404) and measuring the number of graphene layers in a peeled flake of graphite (Gupta et al 2006 Nano Lett. 6 2667-73). For these and other ground breaking contributions to carbon science he received the Graffin Lecture award from the American Carbon Society in 2005, and the Japan Carbon Prize in 2008. As a material, graphite has come full circle. The 1970s renaissance in the science of graphite intercalation compounds paved the way for a later explosion in nanocarbon research by illuminating many beautiful fundamental phenomena, subsequently rediscovered in other forms of nanocarbon. In 1985, Smalley, Kroto, Curl, Heath and O'Brien discovered carbon cage molecules called fullerenes in the soot ablated from a rotating graphite target (Kroto et al 1985 Nature 318 162-3). At that time, Peter's research was focused mainly on the oxide-based high-temperature superconductors. He switched to fullerene research soon after the discovery that an electric arc can prepare fullerenes in bulk quantities (Haufler et al 1990 J. Phys. Chem. 94 8634-6). Later fullerene research spawned nanotubes, and nanotubes spawned a newly exploding research effort on single-layer graphene. Graphene has hence evolved from an oversimplified model of graphite (Wallace 1947 Phys. Rev. 71 622-34) to a new member of the nanocarbon family exhibiting extraordinary electronic properties. Eklund's career spans this 35-year odyssey.

Elastic constants in tetragonal hen egg-white lysozyme crystals containing large amount of water.

Transverse sound velocity of cross-linked tetragonal hen egg-white (HEW) lysozyme crystals containing large amount of water in the crystal was measured using ultrasonic pulse-echo method. All elastic constants of cross-linked crystals were observed to be C11=C22=5.50 GPa, C12=4.33 GPa, C13=C23=3.94 GPa, C33=5.22 GPa, C44=C55=0.68 GPa, and C66=0.84 GPa, respectively. We found that the elastic constants of the cross-linked crystals are identical to those of the intrinsic ones without cross-linking. Moreover, we found that tetragonal HEW lysozyme crystals that enclose large amount of water show decreased elastic constants (softening). In particular, the shear elastic constants C44=C55 and C66 showed more softening effect comparing with other elastic components.

Annexin II represents metastatic potential in clear-cell renal cell carcinoma.

BACKGROUND: Annexin II (ANX2) is a multi-functional protein involved in cell proliferation and membrane physiology and is related to cancer progression. The purpose of this study was to assess ANX2 expression in clear-cell (cc) renal cell carcinoma (RCC). METHODS: The ANX2 expression in 18 primary ccRCCs was examined by real-time reverse transcriptase (RT)-PCR and western blot analyses. Furthermore, immunohistochemical study was performed using paraffin section of 154 primary ccRCCs and 24 metastases. The association between ANX2 expression and the clinicopathological factors and prognosis was analysed. RESULTS: The ANX2 was upregulated at both mRNA and protein levels in 14 of 18 primary ccRCCs. Immunohistochemical analysis showed that ANX2 was positive in 73 (47.4%) of 154 primary ccRCC and in 21 (87.5%) of 24 metastatic tumours. The ANX2 expression in the primary tumours showed significant associations with a higher stage, a higher nuclear grade. In patients without metastasis, the 5-year metastasis-free rate in patients with ANX2-positive tumour was significantly lower than that in those with ANX2-negative tumour (63.0% vs 90.1%; P<0.0001). Multivariate analysis showed that ANX2 expression is an independent predictor for metastasis. CONCLUSION: Our findings suggest that ANX2 expression might be a novel predictor of the metastatic potential of ccRCC.

Ectopic (subcutaneous) Paragonimus miyazakii infection in a dog.

Ectopic infection with Paragonimus miyazakii was determined to be the cause of a subcutaneous inguinal mass in a 15-month-old, male, boar-hunting dog. On histologic examination, the mass comprised granulomatous panniculitis, intralesional adult trematodes and eggs, and lymphadenitis. Extrapulmonary paragonimosis in animals is rare. This appears to be the first report in a dog of ectopic P. miyazakii infection with mature trematodes and eggs that involved the inguinofemoral lymphocenter and surrounding subcutis.

Activation of peroxisome proliferator-activated receptor gamma suppresses mast cell maturation involved in allergic diseases.

BACKGROUND: Mast cells play a central role in allergic and inflammatory diseases. Several reports indicated role of peroxisome proliferator-activated receptor gamma (PPARgamma) on mast cell function. However, there is no report about the role of PPARgamma on differentiation of mast cells from the progenitors. In this study, we investigated the role of PPARgamma in regulating bone marrow-derived mast cell maturation and the therapeutic implications for mast cell-related diseases such as atopic or contact dermatitis. METHODS: We used in vitro cell culture system for mast cell differentiation from bone marrow-progenitors using specific ligands and lentiviral-mediated short hairpin RNA of PPARgamma, and in vivo murine dermatitis models. RESULTS: Activation of PPARgamma inhibited the maturation of bone marrow progenitors into connective tissue-type mast cells (CTMCs) through up-regulation of GATA-4 and GATA-6 resulting in a decrease in expression of histidine decarboxylase and mast cell histamine content. In comparison, the differentiation of bone marrow progenitors into CTMCs was significantly accelerated by the knockdown of PPARgamma expression by lentiviral-mediated short hairpin RNA. Peroxisome proliferator-activated receptor gamma ligand administration to mice inhibited the maturation of mast cells resulting in attenuation of atopic and contact dermatitis via diminishment of the number of mature mast cells. CONCLUSION: Our results indicate that PPARgamma is one of master regulators on mast cell maturation and potentially useful for the therapy in various disorders involving mast cell activation.

Robotic-assisted laparoscopic radical prostatectomy: initial 15 cases in Japan.

Recently, we have introduced robotic-assisted laparoscopic radical prostatectomy (RALP) in Japan. This article describes the details of a training program to shorten the learning curve in the absence of an urologist with expertise in robotic surgery. Five months after a 2-day training course of robotic surgery, RALP was first performed in Japan, and a total of 15 cases were performed in the subsequent 4 months. Our training program consisted of: (1) image training using surgical operation videos, (2) dry lab training using a sham pelvic cavity model, and (3) intraoperative mentoring. The operative procedure was divided into five consecutive stages, and time required to complete each stage was recorded. Robotic radical prostatectomy was completed in all patients without conversion to open surgery, except for the first patient in whom a restriction to a 2-h operation had been imposed by the ethics committee. The mean console time and the mean intraoperative blood loss (including urine) reduced from 264.2 min and 459.4 ml, respectively, in the first 11 cases, to 151 min and 133.3 ml, respectively, in the last three cases. With direct intraoperative guidance by the mentor during cases 13 and 14, the operation time was reduced at all five stages of the operative procedure. Our training program proved remarkably effective in reducing the learning curve of RALP in Japan, where there is no person with expertise in robotic surgery.