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Unlabelled: Exchangeable apolipoproteins (ApoA, -C, and -E) have been shown to redundantly participate in the formation of infectious hepatitis C virus (HCV) particles during the assembly process, although their precise role in the viral life cycle is not well understood. Recently, it was shown that the exogenous expression of only short sequences containing amphipathic α-helices from various apolipoproteins is sufficient to restore the formation of infectious HCV particles in ApoB and ApoE double-gene-knockout Huh7 (BE-KO) cells. In this study, through the expression of a small library of human secretory proteins containing amphipathic α-helix structures, we identified the human cathelicidin antimicrobial peptide (CAMP), the only known member of the cathelicidin family of antimicrobial peptides (AMPs) in humans and expressed mainly in bone marrow and leukocytes. We showed that CAMP is able to rescue HCV infectious particle formation in BE-KO cells. In addition, we revealed that the LL-37 domain in CAMP containing amphipathic α-helices is crucial for the compensation of infectivity in BE-KO cells, and the expression of CAMP in nonhepatic 293T cells expressing claudin 1 and microRNA miR-122 confers complete propagation of HCV. These results suggest the possibility of extrahepatic propagation of HCV in cells with low-level or no expression of apolipoproteins but expressing secretory proteins containing amphipathic α-helices such as CAMP., Importance: Various exchangeable apolipoproteins play a pivotal role in the formation of infectious HCV during the assembly of viral particles, and amphipathic α-helix motifs in the apolipoproteins have been shown to be a key factor. To the best of our knowledge, we have identified for the first time the human cathelicidin CAMP as a cellular protein that can compensate for the role of apolipoproteins in the life cycle of HCV. We have also identified the domain in CAMP that contains amphipathic α-helices crucial for compensation and show that the expression of CAMP in nonhepatic cells expressing claudin 1 and miR-122 confers complete propagation of HCV. We speculate that low levels of HCV propagation might be possible in extrahepatic tissues expressing secretory proteins containing amphipathic α-helices without the expression of apolipoproteins., (Copyright © 2016, American Society for Microbiology. All Rights Reserved.)

Background: UVB radiation is the main source of sunburn and skin cancers. Apoptosis eliminates photodamaged cells, and is thus important for preventing epidermal carcinogenesis. The cytoplasmic regulatory protein p62/A170/sequestosome 1 (p62) molecule is involved in a variety of cellular and signaling pathways. p62 is known to be and important in autophagy, but its role in UVB-induced apoptosis remains to be clarified., Objective: To investigate the role of p62 against UVB-induced apoptotic changes, using mouse embryonic fibroblasts (MEFs) derived from p62 homozygous knockout (p62(-/-)) mice., Methods: p62(-/-) and wild-type (p62(+/+)) mice and MEFs were subjected to UVB irradiation, and the resultant apoptosis was analyzed using flow cytometry, quantitative real-time PCR, and western blots., Results: Apoptosis was decreased in the p62(-/-) MEFs compared to p62(+/+) MEFs in response to UVB treatment. Compared with p62(+/+) MEFs, p62(-/-) MEFs expressed significantly more Bcl-2 and less Bax, and showed increased Src and Stat3 phosphorylation. Our results show that p62 regulates apoptotic pathways by modifying critical signaling intermediates such as Src and Stat3., Conclusion: p62 deficiency [corrected] reduces UVB-induced apoptosis by modulating intrinsic apoptotic signaling through Src phosphorylation., (Copyright © 2016 Japanese Society for Investigative Dermatology. Published by Elsevier Ireland Ltd. All rights reserved.)

Scavenger receptor class B type 1 (SR-B1) and low-density lipoprotein receptor (LDLR) are known to be involved in entry of hepatitis C virus (HCV), but their precise roles and their interplay are not fully understood. In this study, deficiency of both SR-B1 and LDLR in Huh7 cells was shown to impair the entry of HCV more strongly than deficiency of either SR-B1 or LDLR alone. In addition, exogenous expression of not only SR-B1 and LDLR but also very low-density lipoprotein receptor (VLDLR) rescued HCV entry in the SR-B1 and LDLR double-knockout cells, suggesting that VLDLR has similar roles in HCV entry. VLDLR is a lipoprotein receptor, but the level of its hepatic expression was lower than those of SR-B1 and LDLR. Moreover, expression of mutant lipoprotein receptors incapable of binding to or uptake of lipid resulted in no or slight enhancement of HCV entry in the double-knockout cells, suggesting that binding and/or uptake activities of lipid by lipoprotein receptors are essential for HCV entry. In addition, rescue of infectivity in the double-knockout cells by the expression of the lipoprotein receptors was not observed following infection with pseudotype particles bearing HCV envelope proteins produced in non-hepatic cells, suggesting that lipoproteins associated with HCV particles participate in the entry through their interaction with lipoprotein receptors. Buoyant density gradient analysis revealed that HCV utilizes these lipoprotein receptors in a manner dependent on the lipoproteins associated with HCV particles. Collectively, these results suggest that lipoprotein receptors redundantly participate in the entry of HCV.

The present study investigated the influence of an auditory tone on the localization of visual objects in the stream/bounce display (SBD). In this display, two identical visual objects move toward each other, overlap, and then return to their original positions. These objects can be perceived as either streaming through or bouncing off each other. In this study, the closest distance between object centers on opposing trajectories and tone presentation timing (none, 0 ms, ± 90 ms, and ± 390 ms relative to the instant for the closest distance) were manipulated. Observers were asked to judge whether the two objects overlapped with each other and whether the objects appeared to stream through, bounce off each other, or reverse their direction of motion. A tone presented at or around the instant of the objects' closest distance biased judgments toward "non-overlapping," and observers overestimated the physical distance between objects. A similar bias toward direction change judgments (bounce and reverse, not stream judgments) was also observed, which was always stronger than the non-overlapping bias. Thus, these two types of judgments were not always identical. Moreover, another experiment showed that it was unlikely that this observed mislocalization could be explained by other previously known mislocalization phenomena (i.e., representational momentum, the Fröhlich effect, and a turn-point shift). These findings indicate a new example of crossmodal mislocalization, which can be obtained without temporal offsets between audiovisual stimuli. The mislocalization effect is also specific to a more complex stimulus configuration of objects on opposing trajectories, with a tone that is presented simultaneously. The present study promotes an understanding of relatively complex audiovisual interactions beyond simple one-to-one audiovisual stimuli used in previous studies.

A 33-year-old man who presented with prolonged epigastric pain was referred to our hospital. He had experienced recurrent epistaxis and had a family history of hereditary hemorrhagic telangiectasia. Computed tomography and magnetic resonance imaging revealed splenomegaly and a 9 cm hypervascular mass in his spleen. Computed tomography also showed a pulmonary arteriovenous malformation and heterogeneous enhancement of the liver parenchyma, suggesting the presence of arteriosystemic shunts and telangiectases. Based on these findings, the patient was definitely diagnosed with hereditary hemorrhagic telangiectasia according to Curaçao criteria. He underwent splenectomy, and his symptoms disappeared after surgery. Pathological examination of the resected specimen revealed that the hypervascular lesion of the spleen was not a tumor but was composed of abnormal vessels associated with hereditary hemorrhagic telangiectasia. Symptomatic splenic involvement may be a rare manifestation of hereditary hemorrhagic telangiectasia but can be revealed by imaging modalities.

A 40-year-old man presented with Cushing's syndrome due to bilateral adrenal hyperplasia with multiple nodules. Computed tomography scan results were atypical demonstrating an enlargement of the bilateral adrenal glands harboring multiple small nodules, but the lesion was clinically diagnosed to be primary pigmented nodular adrenocortical disease (PPNAD) based on both endocrinological test results and his family history. We performed bilateral adrenalectomy and confirmed the diagnosis histologically. An analysis of the patient and his mother's genomic DNA identified a novel mutation in the type Iα regulatory subunit of protein kinase A (PRKAR1A) gene; p.E17X (c.49G>T). This confirmed the diagnosis of PPNAD which is associated with Carney Complex.

Recent neuroimaging studies have investigated the neural substrates involved in the valuation of supraliminally presented targets and the subsequent preference decisions. However, the neural mechanisms of the valuation of subliminally presented targets, which can guide subsequent preference decisions, remain to be explored. In the present study, we determined whether the neural systems associated with the valuation of supraliminally presented faces are involved in the valuation of subliminally presented faces. The subjects were supraliminally and subliminally presented with faces during functional magnetic resonance imaging (fMRI). Following fMRI, the subjects were presented with pairs of faces and were asked to choose which face they preferred. We analyzed brain activation by back-sorting the fMRI data according to the subjects' choices. The present study yielded two main findings. First, the ventral striatum and the ventromedial prefrontal cortex predict preferences only for supraliminally presented faces. Second, the dorsomedial prefrontal cortex may predict preferences for subliminally presented faces. These findings indicate that neural correlates of the preference-related valuation of faces are dissociable, contingent upon whether the subjects consciously perceive the faces., (© 2015 Wiley Periodicals, Inc.)

Objective: To show the efficacy of taxane-based chemotherapy for the treatment of cutaneous angiosarcoma., Methods: A case-control study comparing patients who received taxanes without wide local excision (group A, n = 5) and patients who received conventional surgery-based therapy (group B, n = 8) in one university hospital in eastern Japan. Data were collected from a total of 13 patients with cutaneous angiosarcoma treated from November 1997 through July 2009., Results: Group A received taxanes: four patients received docetaxel, and one patient received paclitaxel. Radiation was used concomitantly in two patients. Marginal local excision was performed in two patients. Group B received wide local excision followed by radiation (six patients), docetaxel (three patients), and interleukin-2 (two patients). No patients in group A had local recurrence, whereas five out of the eight patients in group B did (p < 0.05, chi-square test). Median overall survival was 31 months in group A and 10 months in group B. Estimated overall survival using the Kaplan-Meier method was significantly longer in group A (p < 0.05, log-rank test)., Conclusion: In our series, taxane-based chemotherapy was superior to conventional surgery-based therapy. Our results indicated that taxane regimens without mutilating surgery offered both local control and prevention of metastasis, which led to prolonged survival.

We aimed to show that a single auditory tone crossmodally affects multiple visual events using a multiple stream/bounce display (SBD), consisting of two disk pairs moving toward each other at equal speeds, coinciding, and then moving apart in a two-dimensional (2-D) display. The temporal offsets were manipulated between the coincidences of the disk pairs (0 to ±240 ms) by staggering motion onset between the pairs. A tone was presented at the coincidence timing of one of the disk pairs on half of the trials. Participants judged whether the disks in each of two pairs appeared to stream through or bounce off each other. Results show that a tone presented at either of the disk pairs' coincidence points promoted bouncing percepts in both disk pairs compared to no-tone trials. Perceived bouncing persisted in the disk-pair whose coincidence was offset 60 ms before and up to more than 120 ms after the audiovisual coincidence timing of the other disk-pair. The temporal window of bounce promotion was comparable to that obtained with a conventional SBD. The interaction of a single auditory event and multiple visual events was also modulated by the kind of experimental task (the stream/bounce or simultaneity judgments). These findings suggest that, using a single auditory cue, the perceptual system resolves the ambiguity of the motion of multiple disk pairs presented within the conventional temporal window of crossmodal interaction., (© 2014 ARVO.)

The transformation of α-acids [in hops (Humulus lupulus L.)] to iso-α-acids (in beer) during the brewing process is well known, but the occurrence and structure of the oxidized α-acids during hop storage are not well documented. Because an understanding of these oxidized compounds is essential to optimize the effects of oxidized hops on the quality of beer, we investigated the autoxidation products of humulone (a representative congener of α-acids) using a simplified autoxidation model. Among the oxidation products, tricyclooxyisohumulones A (1) and B (2), tricycloperoxyisohumulone A (3), deisopropyltricycloisohumulone (4), and the hemiacetal 5 of tricycloperoxyhumulone A (5') were isolated, and their structures were elucidated for the first time. The occurrence of compounds 1-4 in stored hops was verified using LC/MS/MS analysis. We also monitored the levels of compounds 1-4 during hop storage using LC/MS/MS analysis.

B-Myb (Mybl2) is a member of the Myb gene family of transcription factors involved in the control of cell growth, differentiation, and apoptosis. The effects of B-Myb on keratinocyte proliferation and differentiation have not yet been clarified. The present study was performed to examine the role of B-Myb in proliferation and differentiation of the spontaneously immortalized human skin keratinocyte cell line HaCaT and normal human keratinocytes with formation of a stratified epidermoid structure in air-liquid interface three-dimensional culture. B-Myb was expressed specifically in undifferentiated normal keratinocytes and downregulated during differentiation. The constitutive overexpression of B-Myb in HaCaT cells during air exposure-induced differentiation resulted in an undifferentiated phenotype, i.e., thickening of the stratified layers, suppression of differentiation marker expression, and retention of proliferative activity with activation of cell cycle regulatory proteins in the S and G2/M phases. In contrast, suppression of B-Myb caused their downregulation and constrained proliferation with retention of differentiation capacity. These findings suggested that B-Myb plays an important role in maintenance of the undifferentiated phenotype of keratinocytes in the basal epidermal layer.

Previous psychological studies have shown that make-up enhances facial attractiveness. Although neuroimaging evidence indicates that the orbitofrontal cortex (OFC) shows greater activity for faces of attractive people than for those of unattractive people, there is no direct evidence that the OFC also shows greater activity for the face of an individual wearing make-up than for the same face without make-up. Using functional magnetic resonance imaging (fMRI), we investigated neural activity while subjects viewed 144 photographs of the same faces with and without make-up (48 with make-up, 48 without make-up, and 48 scrambled photographs) and assigned these faces an attractiveness rating. The behavioral data showed that the faces with make-up were rated as more attractive than those without make-up. The imaging data revealed that the left OFC and the right hippocampus showed greater activity for faces with make-up than for those without make-up. Furthermore, the activities of the right anterior cingulate cortex, left hippocampus, and left OFC increased with increasing facial attractiveness resulting from cosmetics use. These results provide direct evidence of the neural underpinnings of cosmetically enhanced facial attractiveness., (Copyright © 2014 Elsevier Ireland Ltd. All rights reserved.)

Background: Exposure of skin to long-wave UV radiation (UVA) increases the cellular levels of reactive oxygen species (ROS), which have been linked to apoptosis induction through the damage of lipids, proteins, and nucleic acids. Peroxiredoxin I (Prx I) is one of a family of antioxidant proteins that plays a protective role against oxidative damage; however the role of Prx I in UVA-induced damage remains to be clarified., Objective: Here we investigated the protective role of Prx I against UVA-induced changes using mouse embryonic fibroblasts (MEFs) derived from Prx I homozygous knockout (Prx I (-/-)) mice., Methods: Prx I (-/-) and wild-type (Prx I (+/+)) MEFs were subjected to UVA irradiation, and the resulting apoptosis was analyzed using flow cytometry, quantitative real-time PCR, and western blotting., Results: Prx I (-/-) MEFs showed enhanced sensitivity to UVA treatment, exhibiting increased apoptosis and ROS production compared to Prx I (+/+) MEFs. Consistent with the increase in apoptosis, p53 expression was significantly higher, while Bcl-2, Bcl-xL, and Nrf2 expressions were all lower in Prx I (-/-) versus (+/+) MEFs. The UVA-induced inflammatory response was upregulated in Prx I (-/-) MEFs, as indicated by increased expressions of IκB, TNFα, and IL-6. Evidence was presented indicating that Prx I impacts these pathways by modifying critical signaling intermediates including p53, IκB, and Nrf2., Conclusion: Our results indicate that Prx I plays a protective role against UVA-induced oxidative damage by controlling ROS accumulation. Both the UVA-induced apoptotic and inflammatory signals were found to be modulated by Prx I., (Copyright © 2013 Japanese Society for Investigative Dermatology. Published by Elsevier Ireland Ltd. All rights reserved.)

A startle reflex to a startle pulse is inhibited when preceded by a prestimulus. We introduced a key-press action (self-action) or an 85 dB noise burst as a prestimulus, followed by a 115 dB noise burst as a startle pulse. We manipulated temporal offsets between the prestimulus and the startle pulse from 30-1,500 ms to examine whether self-action modulates the startle reflex and the temporal properties of the modulatory effect. We assessed eyeblink reflexes by electromyography. Both prestimuli decreased reflexes compared to pulse-alone trials. Moreover, the temporal windows of inhibition were different between the types of prestimuli. A faster maximal inhibition and narrower temporal window in self-action trials suggest that preceding self-action inhibits the startle reflex and allows prediction of the coming pulse in different ways from auditory prestimuli., (Copyright © 2013 Society for Psychophysiological Research.)

Background: Natural orifice specimen extraction (NOSE) has been developed as a means of decreasing the incidence of surgical wound complications. However, NOSE performed using a conventional multiport technique has been reported previously. The current authors performed totally laparoscopic anterior resection with transvaginal specimen extraction (TVSE) using the reduced-port surgery (RPS) technique. The Alexis wound retractor (Applied Medical, Rancho Santa Margarita, CA, USA) and Free Access (Top Corporation, Tokyo, Japan) were attached to the transvaginal route for transvaginal assistance and smooth specimen extraction. The authors documented this simple and safe technique and its short-term results., Methods: Data were prospectively collected for five patients who underwent totally laparoscopic anterior resection with TVSE for colorectal cancer between June 2012 and December 2012. A multiport access device (GelPOINT advanced-access platform; Applied Medical) was inserted into the navel, and a 5-mm port was inserted into the right lower quadrant to be used as a drain site. Transverse transvaginal posterior colpotomy then was performed. One ring of an Alexis ring pair was inserted into the peritoneal cavity through the vagina. The other white ring was placed outside of the vagina and then covered with a Free Access to maintain the pneumoperitoneum for insertion of a 12-mm port. Lymph node dissection and transection of the distal colon were performed with transvaginal assistance. The specimen then was extracted transvaginally. After the Alexis had been removed, the vaginal incision was closed transvaginally. End-to-end colorectal anastomosis was performed using the double-stapling technique., Results: Transvaginal extraction was completed in all five cases. The median operation time was 235 min. One case was complicated by chyloperitoneum. The median hospital stay was 6 days. Only one patient required intravenous analgesics once on postoperative day 1. All the patients remained disease free., Conclusion: Totally laparoscopic anterior resection using TVSE with RPS appears to be feasible, safe, and oncologically acceptable for selected cases.

The patient was a 68-year-old man who had undergone sigmoidectomy 1 year previously. Adjuvant therapy with tegafur- uraci(l UFT) and Leucovorin( UZEL) was administered. Seven months later, the carcinoembryonic antigen( CEA) level increased to 7.5 ng/mL. Enhanced computed tomography (CT) revealed a 4-cm mass in the mesorectum, and the patient was diagnosed as having local recurrence. Chemotherapy with oxaliplatin, 5-fluorouracil, and Leucovorin( mFOLFOX6) and radiation therapy( 60 Gy) were administered. As the tumor could not be detected after chemoradiotherapy, abdominoperineal resection was performed. Pathological examination showed no cancer and indicated a complete response. The patients CEA level has not increased and no recurrence has been detected on enhanced CT for 3.5 years. The tumor could be decreased in size by chemoradiotherapy and the operation could be safely performed without resecting other organs. Although surgery is generally performed for local recurrence, multidisciplinary therapy could be useful in performing such surgery safely.

We describe a female neonate with large flaccid pustules on her trunk and extremities. Cultures were negative, and a Wright-stained smear of pustule contents showed numerous eosinophils (>90%). The pustules resolved without leaving pigmentation after 2 weeks. We diagnosed this case as sterile transient neonatal pustulosis., (© 2012 Wiley Periodicals, Inc.)

Proliferation and differentiation in the epidermis must be tightly regulated. This regulation is known to involve a range of transcription factors, including pituitary tumor transforming gene 1 (PTTG1), a ubiquitously distributed transcription factor that regulates keratinocyte proliferation and differentiation. Psoriasis is a common but refractory skin disorder, the pathophysiology of which is characterized by hyperproliferation and impaired differentiation in the epidermis. The present study was conducted to clarify the less well-known roles of PTTG1 in the pathophysiology of psoriasis, focusing on its relationship with tumor necrosis factor-α (TNF-α), which is a critical mediator of the disease. The levels of PTTG1 expression were increased in the psoriatic epidermis. Overexpression of PTTG1 resulted in the overproduction of TNF-α, and TNF-α itself had an inductive effect on PTTG1 expression, suggesting that their expression may involve autoinduction. Moreover, overexpression of PTTG1 involved augmented the expression of cyclin A and B1 proteins in both cultured keratinocytes and the psoriatic epidermis. Therefore, enhanced expression of PTTG1 in the psoriatic epidermis may result in aberrant regulation of the cell cycle and impaired differentiation via the interplay between PTTG1 and TNF-α.

Mucoepidermoid carcinoma (MEC) usually originates from the salivary glands. However, there has been no report on mucoepidermoid carcinoma of the columella. In this study, we report the case of a high-grade MEC of the columella that was successfully reconstructed after surgical resection with bilateral nasolabial flaps set up in a sandwich shape and an auricular cartilage graft. A 66-year-old man presented with a nodule on the columella. Histological findings were suggestive of a high-grade mucoepidermoid carcinoma. Wide excision was performed, and the defects of the columella and the nasal floor were reconstructed with bilateral nasolabial flaps set up in a sandwich shape and an auricular cartilage graft. The postoperative cosmetic result was good with excellent tissue texture. The reconstructed columella had an appropriate, not bulky, width as well as satisfactory height and depth. This reconstructive technique is particularly useful for correcting the large defect of the columella with nasal septum and/or nasal floor defects., (© 2013 Japanese Dermatological Association.)

Ovalbumin (OVA), a major globular protein in egg white, forms semiflexible fibrillar aggregates during heat-induced gelation. The N-terminal amphiphilic region (pN1-22) of OVA is removed after treatment with pepsin at pH 4 to leave a large OVA fragment (pOVA). The conformation and thermal stability of pOVA and OVA are similar, but the rheological strength of the heat-induced gel of pOVA is much lower compared to that of OVA. The aggregation rate of pOVA, which forms spherical aggregates, was lower than that of OVA. These results suggest that the N-terminal amphiphilic region of OVA facilitates the α-to-β conformational transition, which triggers OVA fibril formation. Heat treatment of OVA in the presence of pN1-22 consistently resulted in the formation of straight fibrils. The strength of OVA and collagen gels was increased when prepared in the presence of pN1-22, suggesting that pN1-22 may be used to control the properties of protein gels.

Graft-versus-host disease (GVHD) is a frequent complication of bone marrow transplantation (BMT) that can be classified as acute or chronic. Characteristic cutaneous manifestations of acute GVHD, which generally occurs within 3 months following BMT, include maculopapular exanthema and perifollicular papular lesions. Psoriasiform skin eruption as a manifestation of acute GVHD is rare. We report the case of a 4-year-old boy who developed a generalized psoriasiform eruption shortly after undergoing an allogeneic BMT. Histologic features of both psoriasis and acute GVHD were present.

To reveal the proteomic background of lymph node metastasis (LNM) in gastric cancer, we performed a proteomic study of tumor and matched nontumor tissues obtained from surgically resected specimens of 22 patients with or without LNM. Using laser microdissection, we recovered specific populations of tumor and nontumor cells. We used two-dimensional difference gel electrophoresis with a large format electrophoresis apparatus to obtain protein expression profiles consisting of 3228 protein spots, and we classified them according to their expression pattern. We found that macrophage-capping protein (CapG) was up-regulated in the tumor tissues of patients with LNM, whereas it showed an equivalent expression level between nontumor and tumor tissues of patients without LNM. It was reported that CapG associated with invasion and metastasis in various malignancies. However, CapG was not investigated in gastric cancer until our study. Western blotting of the laser microdissected tissue samples confirmed up-regulation of CapG in the tumor tissues of patients with LNM. Functional assays demonstrated that CapG promoted tumor cell invasion, but not cell proliferation. The association between CapG expression and LNM is a novel finding in gastric cancer. Further investigation for a prognostic utility of CapG may lead to a risk stratification therapy for gastric cancer.

Loricrin is a major component of the epidermal cornified cell envelope, and is expressed only in terminally differentiated keratinocytes. This cell differentiation-specific expression pattern suggests specific regulatory mechanisms for activation and suppression of loricrin gene transcription in differentiated keratinocytes. Here, we identified a regulatory element in the proximal promoter region of the loricrin gene involved in suppression of its expression in keratinocytes. A database search indicated that this sequence contained a POU transcription factor binding motif. Electrophoretic mobility shift assay revealed that Oct-1, Oct-6, and Oct-11 actually bind to the motif. Constructs with point mutations in the POU-binding motif showed increased reporter activity, indicating that the POU factors negatively regulate loricrin gene transcription. Cotransfection experiments suggested that Oct-6 and Oct-11 suppress loricrin gene transcription in a cooperative manner with AP-1 and Sp1. Furthermore, in vitro experiments indicated that the Oct-6 and Oct-11 can physically associate with both AP-1 factors and Sp1/Sp3. These findings indicate that Oct-6 and Oct-11 contribute to the regulation of loricrin gene transcription via interaction with AP-1 factors and Sp1/Sp3.

The standard technique using lymphoscintigraphy, blue dye and a gamma probe has established a reliable method for sentinel node biopsy for skin cancer. However, the detection rate of cervical sentinel lymph nodes (SLN) is generally lower than that of inguinal or axillary SLN because of the complexity of lymphatic drainage in the head and neck region and the "shine-through" phenomenon. Recently, indocyanine green fluorescence imaging has been reported as a new method to detect SLN. We hypothesized that fluorescence navigation with indocyanine green in combination with the standard technique would improve the detection rate of cervical sentinel nodes. We performed cervical sentinel node biopsies using the standard technique in 20 basins of 18 patients (group A) and using fluorescence navigation in combination with the standard technique in 12 basins of 16 patients (group B). The mean number of sentinel nodes was two per basin (range, 1-4) in group A and three per basin (range, 1-5) in group B. The detection rate of sentinel nodes was 83% (29/35) in group A and 95% (36/38) in group B. The false-negative rate was 6% (1/18 patients) in group A and 0% in group B. Fluorescence navigation with indocyanine green may improve the cervical sentinel node detection rate. However, greater collection of data regarding the usefulness of cervical sentinel node biopsy using indocyanine green is necessary., (© 2013 Japanese Dermatological Association.)

Non-melanoma skin cancer is the most frequently occurring type of cancer worldwide and is caused by epidermal carcinogenesis and malignant progression that involve dysregulated expression of proto-oncogenes and tumor suppressor genes. The proto-oncogene pituitary tumor-transforming gene 1 (PTTG1) is a ubiquitously expressed transcription factor that can promote enhanced proliferation of cultured epidermal keratinocytes. To investigate the potential roles of PTTG1 in epidermal carcinogenesis and malignant progression, the expression of PTTG1 was analysed by immunohistochemistry along with Ki67, keratin 10 (K10) and p53 in tissue samples of cutaneous squamous cell carcinomas (SCC), actinic keratoses (AK) and Bowen's disease (BD). Expression levels of PTTG1 were compared among these disease groups to test for correlations with proliferation, differentiation capacity or the existence of mutated tumor suppressor genes in each disease group. In each disease group, the expression levels of PTTG1 correlated positively with those of Ki67, although the differentiation status, measured by K10 expression, did not show any correlation. In contrast, the existence of mutated p53 proteins showed a positive correlation only in the SCC group. Moreover, the expression levels of PTTG1 in SCC did not correlate with known prognostic factors such as TNM staging or tumor thickness. These results suggest that PTTG1 may represent a proliferation marker associated with mutated p53 proteins but is not an informative predictor of poor clinical outcomes in SCC., (© 2013 John Wiley & Sons A/S.)

We report a case of hyperammonemic encephalopathy related to 5-FU in an aged patient with recurrent colon cancer treated with FOLFIRI therapy. An 80-year-old man underwent right hemicolectomy for cecal cancer. After 10 months, surgical resection was performed for its local recurrence. He was then treated with FOLFIRI therapy, and during the fifth course, he presented with a sudden onset of congestive disturbances. Through radiographic examination and laboratory data, only hyperammonemia was found; he was therefore diagnosed with hyperammonemic encephalopathy. By starting branchedamino acid solutions for its treatment, his consciousness and serum ammonia were promptly improved. Hyperammonemic encephalopathy related 5-FU is caused by increasing ammonia production and its metabolic inhibition, and is worsened by renal dysfunction, dehydration, constipation, infections, or body weight loss. On account of the potential decrease of metabolic function of liver and kidney, an aged person tends to have hyperammonnemia more than a youth. Clinicians should be aware of the adverse events associated with hyperammonemia when then administer a large amount of 5-FU to elderly patients.

We employed audiovisual stream/bounce displays, in which two moving objects with crossing trajectories are more likely to be perceived as bouncing off, rather than streaming through, each other when a brief sound is presented at the coincidence of the two objects. However, Kawachi and Gyoba (Perception 35:1289-1294, 2006b) reported that the presence of an additional moving object near the two objects altered the perception of a bouncing event to that of a streaming event. In this study, we extended this finding and examined whether alteration of the event perception could be induced by the visual context, such as by occluded object motion near the stream/bounce display. The results demonstrated that even when the sound was presented, the continuous occluded motion strongly biased observers' percepts toward the streaming percept during a short occlusion interval (approximately 100 ms). In contrast, when the continuous occluded motion was disrupted by introducing a spatiotemporal gap in the motion trajectory or by removing occlusion cues such as deletion/accretion, the bias toward the streaming percept declined. Thus, we suggest that a representation of object motion generated under a limited occlusion interval interferes with audiovisual event perception.

Neurofibromatosis type I (NF1) is associated with typical hypervascular tumors, including neurofibroma, glioma, malignant peripheral nerve sheath tumors (MPNST) and glomus tumors. Previously, we and other groups reported that neurofibromas showed high-level expression of vascular endothelial growth factor (VEGF), a potent angiogenic factor involved in neovascularization. However, the molecular mechanism underlying the upregulation of VEGF in neurofibromas remains unclear. In this study, we examined the effects of Nf1 gene silencing on VEGF expression in Schwann cell and non-Schwann cell line and the upstream mTOR-HIF-1α - VEGF pathway in Schwann cell line. The results indicated that Nf1 gene silencing by lentiviral-mediated RNA interference resulted in elevated expression of VEGF, HIF-1α and phosphorylated mTOR at the protein level. The results obtained from Nf1 gene silencing in murine Schwann cell line analogously suggest that NF1 gene haploinsufficiency in human tumor Schwann cells may directly elicit upregulation of VEGF expression without the tumor microenvironment by activation of the mTOR-HIF-1α - VEGF pathway. We also showed that interleukin-6 is upregulated in Nf1 gene knock-down Schwann cells at the protein level., (© 2013 John Wiley & Sons A/S.)

Purposes: Pancreatic cancer still has a poor prognosis even after curative resection because of the high incidence of postoperative liver metastasis. This study prospectively evaluated the feasibility and tolerability of portal vein infusion chemotherapy of gemcitabine (PVIG) as an adjuvant setting after pancreatic resection., Methods: Thirteen patients enrolled in this study received postoperative chemotherapy with PVIG. The patients received intermittent administration of gemcitabine (800 mg/m(2)) via the portal vein on days 1, 8, and 15 after surgery. The tolerability and the toxicity of PVIG were closely monitored., Results: The PVIG was started on an average of 3.1 days after surgery. Complete doses of chemotherapy (three sessions of portal infusion) were accomplished in 11 of the 13 patients. Grade 3 or 4 leukocytopenia was observed in three patients (23 %), and liver dysfunction was found in one patient (7.7 %). Grade 2 sepsis developed in two cases due to bloodstream infection. Liver metastasis was the first site of recurrence in only two patients., Conclusions: PVIG can be administered to the liver with acceptable toxicity, but myelosuppression is similar to the systemic use of gemcitabine. Careful observation is required even for locoregional chemotherapy.

Solid pseudopapillary tumor (SPT) is an uncommon neoplasm of the pancreas. A rare case of spontaneous rupture of SPT is reported. A 13-year-old female felt acute abdominal pain without blunt abdominal trauma. Enhanced computed tomography (CT) revealed a tumor in the pancreas tail with fluid collection around it. The tumor was diagnosed as SPT with hemoperitoneum associated with spontaneous rupture. The bleeding was stopped conservatively and she was referred for surgery at three months after the rupture. At that time, CT revealed a tumor 4 cm in diameter, which protruded from pancreas tail without distant metastases. Since peritoneal dissemination was not seen on intraoperative exploration, laparoscopic enucleation was performed. Pathologically, the tumor was diagnosed as SPT with rupture of the capsule of tumor, and complete resection was confirmed. The patient has been followed up for two years, and she is alive without recurrence.

Loricrin is a major component of the epidermal cornified cell envelope and is expressed only in terminally differentiated keratinocytes. This cell differentiation-specific expression pattern suggests specific regulatory mechanisms for activation of loricrin gene transcription in differentiated keratinocytes. Here, we identified a positive regulatory element in the proximal promoter region of the loricrin gene involved in activation of its expression in differentiated keratinocytes. A database search indicated that this sequence contained a GATA-3 binding motif. Constructs with point mutations in the GATA-3 binding motif showed decreased reporter activity, indicating that GATA-3 positively regulates loricrin gene transcription. Western blotting analysis indicated that GATA-3 is more abundant in differentiated than in undifferentiated keratinocytes. Cotransfection experiments indicated that GATA-3 activates transcription of the loricrin gene in a cooperative manner with c-Fos and Sp1. These findings indicate that GATA-3 contributes to keratinocyte differentiation-specific activation of loricrin gene transcription via interaction with c-Fos and Sp1., (© 2012 John Wiley & Sons A/S.)

Giant congenital blue nevus (GCBN) is rare and usually occurs on the scalp. Malignant blue nevus (MBN) is also rare and has a poor prognosis. We report a case of MBN arising in a GCBN on the back. There have been three previous reports of MBN associated with GCBN on the trunk; our case had the earliest onset of MBN arising in a GCBN., (© 2012 Wiley Periodicals, Inc.)

It is extremely rare that swelling of pelvic lymph nodes is found when inguinal lymph nodes contain only a microscopic amount of disease without enlargement. A 69-year-old woman with malignant melanoma of the heel was treated with a wide, local excision. About four years after the initial operation, a left common iliac node was enlarged although all lymph nodes in the obturator, external iliac and inguinal regions were not enlarged. Rapid pathological examination of the resected swollen lymph nodes revealed involvement of malignant melanoma, and left pelvic and groin dissection was undertaken. Histologically, multiple lymph node metastases were found in the common iliac, obturator, external iliac and inguinal regions. This case indicates that sentinel lymph node biopsy may be worth considering even for stage IA malignant melanoma of the lower extremity.

With few exceptions, the sound-induced bias toward bouncing characteristic of the stream/bounce effect has been demonstrated via subjective responses, leaving open the question whether perceptual factors, decisional factors, or some combination of the two underlie the illusion. We addressed this issue directly, using a novel stimulus and signal detection theory to independently characterize observers' sensitivity (d') and criterion (c) when discriminating between objective streaming and bouncing events in the presence or absence of a brief sound at the point of coincidence. We first confirmed that sound-induced motion reversals persist despite rendering the targets visually distinguishable by differences in texture density. Sound-induced bouncing persisted for targets differing by as many as nine just-noticeable-differences (JNDs). We then exploited this finding in our signal detection paradigm in which observers discriminated between objective streaming and bouncing events. We failed to find any difference in sensitivity (d') between sound and no-sound conditions, but we did observe a significantly more liberal criterion (c) in the sound condition than the no-sound condition. The results suggest that the auditory-induced bias toward bouncing in this context is attributable to a sound-induced shift in criterion implicating decisional processes rather than perceptual processes determining responses to these displays.

The epidermis is a self-renewing tissue, the homeostasis of which is dependent upon the tight balance between proliferation and differentiation based on appropriate regulation of the cell cycle. The cell cycle regulation is dependent on the interactions among a number of cell cycle regulatory molecules, including the pituitary tumor-transforming gene 1 (PTTG1), also known as securin, a regulator of sister chromatid separation and transition from metaphase to anaphase. This study was conducted to clarify the less-known functions of PTTG1 in the epidermis by the use of keratinocytes cultured under two-dimensional (2D) or three-dimensional (3D) conditions. Forced overexpression of PTTG1 caused upregulation of cyclin B1, cyclin-dependent kinase 1 (CDK1), and c-Myc, resulting in enhanced proliferation and suppression of early differentiation without apparent alterations in terminal differentiation, and the exogenous PTTG1 was downregulated in association with cell cycle exit. In contrast, depletion of PTTG1 caused their downregulation and constrained proliferation with retention of differentiation capacity. These findings suggested that PTTG1 could alter the proliferation status by modulating the expression levels of the other cell cycle regulatory proteins, and excess PTTG1 primarily affects early differentiation of keratinocytes under the stability regulation associated with cell cycle exit.

Background and Objectives: Although sentinel lymph node (SLN) biopsy using radioisotope (RI) and blue dye (BD) achieved a high detection rate, approximately 5% of melanomas with negative SLNs develop nodal metastasis. We tested a new lymphatic navigation method using indocyanine green fluorescence imaging (ICG-FI) to detect such "occult" SLNs., Methods: Thirty-four skin cancer patients received SLN biopsy with the following three methods: RI (99Tc-tin colloid), BD (2% patent blue), and ICG (0.5% indocyanine green). Lymph nodes detected by any of the three methods were counted as SLNs., Results: ICG-FI detected more SLNs in 8 out of the 34 cases (24%). The average numbers of SLNs detected by ICG-FI, RI, and BD were 2.18, 1.76, and 1.73, respectively. Interestingly, ICG-FI not only detected more SLNs in one basin (ICG-FI: 1.64, RI: 1.50, and BD: 1.51 SLNs per basin), but also detected additional SLNs in other basins (ICG-FI: 1.32, RI: 1.18, and BD: 1.15 basins per case)., Conclusion: ICG-FI detected SLNs more efficiently than did the conventional methods, and these "occult" SLNs may offer an explanation for some false-negative cases. We recommend using ICG-FI in addition to a conventional method to reduce the risk of overlooking these "occult" SLNs., (Copyright © 2012 Wiley Periodicals, Inc.)

Subcutaneous panniculitis-like T-cell lymphoma is an uncommon form of CD8-positive cytotoxic T-cell lymphoma of the skin that predominantly affects the subcutaneous tissue and is extremely rare in early childhood (<3 yrs). Here, we present an early pediatric case with an indolent form of subcutaneous panniculitis-like T-cell lymphoma occurring at 12 months old. The subcutaneous nodules gradually disappeared spontaneously, and the girl showed excellent prognosis with no aggressive treatment., (© 2012 Wiley Periodicals, Inc.)