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• Predictors of the invasion level of basal cell carcinomas (BCCs) are unclear. • Tumor thickness showed a significant correlation with tumor diameter. • Invasion level was significantly correlated with anatomical region and tumor diameter. • Our results can help optimize the adequate deep surgical margins in facial BCCs. Basal cell carcinoma (BCC) is the most common skin cancer. While Mohs micrographic surgery is commonly accepted for BCC treatment, surgical excision with free margins is widely considered the best treatment modality for BCCs in Japan. However, little is known about the predictors of the invasion levels of BCCs. To investigate the optimization of deep surgical margins by identifying factors significantly influencing the invasion levels of facial BCCs. The tumor invasion level was defined as the deepest part of a tumor. Tumor thickness was measured from the top of the granular layer to the deepest extension of the tumor or from the ulcer base overlying the deepest point of invasion in ulcerated lesions. Factors independently associated with tumor thickness and invasion level were identified by multivariate analysis. Six variables were tested: age, sex, anatomical region (nose, orbit, others), histologic pattern (aggressive, non-aggressive), presence of pigmentation, and diameter. We included 718 cases of facial BCCs involving 705 Japanese patients. The most frequent anatomical region and histologic pattern were the nose and nodular pattern, respectively. Only tumor diameter showed a correlation with tumor thickness (β = 0.377, P < 0.001). Tumor diameter (AOR = 71.189, 95 % CI: 11.420–430.931, P = 0.01) and the following anatomical regions showed correlations with the invasion level: nose/others: AOR=2.769, 95 % CI: 1.235–6.493, P = 0.01; orbit/others: AOR=6.369, 95 % CI: 2.728–15.429, P < 0.001; orbit/nose: AOR=2.300, 95 % CI: 1.056–4.984, P = 0.04. This study serves as a guide for optimizing deep surgical margins and planning surgery for facial BCCs considering independently associated factors. [ABSTRACT FROM AUTHOR]

Intestinal necrosis associated with cation exchange resin (CER) is considered related to sorbitol, but it has been reported even in patients receiving CER alone. This study was performed to identify the risk factors of CER‐related intestinal necrosis. The pathological database of 61 end‐stage renal disease patients with surgical intervention for intestinal perforation was reviewed. The correlations between CER treatment and clinicopathological factors were studied among three groups: (i) patients administered CER and with CER at the perforation site (n = 23), (ii) patients administered CER with undetected CER at the perforation site (n = 12) and (iii) patients not administered CER (n = 26). The majority of the perforation site in group 1 was in the sigmoid colon (82.6%) with significantly higher average age and more frequent CER adhesion rates to the mucosa around the perforation site than group 2. The laxative administration rate in group 1 was significantly higher than group 3 and tended to be higher than group 2. The incidence of CER‐related intestinal necrosis was estimated at 0.57%. CER should be used with extreme caution in elderly patients with passage disturbance. [ABSTRACT FROM AUTHOR]

Subcutaneous space has been considered an attractive site for islet graft transplantation; however, the oxygen tension and vascularization are insufficient for islet graft survival. We investigated whether subcutaneous pre-implantation of a recombinant peptide (RCP) device with adipose tissue-derived stem cells (ADSCs) enhanced subcutaneous islet engraftment. RCP devices with/without syngeneic ADSCs were pre-implanted into the subcutaneous space of C57BL/6 mice. Syngeneic islets (300 or 120 islet equivalents (IEQs)) were transplanted into the pre-treated space after diabetes induction using streptozotocin. The cure rates of groups in which RCP devices were implanted four weeks before transplantation were significantly better than the intraportal transplantation group when 300 IEQs of islets were transplanted (p < 0.01). The blood glucose changes in the RCP+ADSCs-4w group was significantly ameliorated in comparison to the RCP-4w group when 120 IEQs of islets were transplanted (p < 0.01). Immunohistochemical analyses showed the collagen III expression in the islet capsule of the RCP+ADSCs-4w group was significantly enhanced in comparison to the RCP-4w and RCP+ADSCs-d10 groups (p < 0.01, p < 0.01). In addition, the number of von Willebrand factor-positive vessels within islets in the RCP+ADSCs-4w group was significantly higher than the RCP-4w group. These results suggest that using ADSCs in combination with an RCP device could enhance the restoration of the extracellular matrices, induce more efficient prevascularization within islets, and improve the graft function. [ABSTRACT FROM AUTHOR]

Abstract Nominal values reported for PV Systems are measured at carefully-controlled test conditions. While being strictly standardized to achieve a good benchmarking capability for different, newly manufactured panels; these conditions hardly exist in real-life implementation sites. To add to the problem, highly varying climate, precipitation, scorching sun and freezing snow wear out these systems in the long run. Therefore, actual performance of any PV system is, inevitably, different than those reported under standard test conditions. In order to have a more accurate expectation of power generation over the lifetime of a system, it is important to know the impact of local conditions and the resilience of PV panels to them. To this end, several outdoor performance studies have been reported around the world and the literature is growing. This work reports the impact of Fukushima's weather, which is known to be windy in autumn and have heavy snowfall in the winter, on the installed PV systems. Also, numerous panels belonging to different PV technologies and manufacturers are installed side-by-side to compare the variation in their performances and, thus, benchmark their quality and resilience. To investigate possible impact of micro-climate, or local geographical conditions, two test sites in Fukushima Prefecture are utilized. Finally, a sample PV system calculation is presented to showcase the impacts of these findings on a PV system in planning and operation stages. [ABSTRACT FROM AUTHOR]

Although subcutaneous islet transplantation has many advantages, the subcutaneous space is poor in vessels and transplant efficiency is still low in animal models, except in mice. Subcutaneous islet transplantation using a two-step approach has been proposed, in which a favorable cavity is first prepared using various materials, followed by islet transplantation into the preformed cavity. We previously reported the efficacy of pretreatment using gelatin hydrogel nonwoven fabric (GHNF), and the length of the pretreatment period influenced the results in a mouse model. We investigated whether the preimplantation of GHNF could improve the subcutaneous islet transplantation outcomes in a rat model. GHNF sheets sandwiching a silicone spacer (GHNF group) and silicone spacers without GHNF sheets (control group) were implanted into the subcutaneous space of recipients three weeks before islet transplantation, and diabetes was induced seven days before islet transplantation. Syngeneic islets were transplanted into the space where the silicone spacer was removed. Blood glucose levels, glucose tolerance, immunohistochemistry, and neovascularization were evaluated. The GHNF group showed significantly better blood glucose changes than the control group (p < 0.01). The cure rate was significantly higher in the GHNF group (p < 0.05). The number of vWF-positive vessels was significantly higher in the GHNF group (p < 0.01), and lectin angiography showed the same tendency (p < 0.05). The expression of laminin and collagen III around the transplanted islets was also higher in the GHNF group (p < 0.01). GHNF pretreatment was effective in a rat model, and the main mechanisms might be neovascularization and compensation of the extracellular matrices. [ABSTRACT FROM AUTHOR]

Background: Most patients with head and neck skin tumors present with normal facial nerve function. A common treatment strategy for these patients is facial nerve preservation surgery, although the degree to which the nerve is successfully preserved is still unclear. Data on the incidence and recovery of facial nerve dysfunction are woefully lacking in the field of dermato-oncology. Methods: In 23 patients with normal preoperative facial nerve function, we retrospectively reviewed twenty-six head and neck surgical interventions that included facial nerve exposure and protection, focusing particularly on the differences in outcome between intraparotid and extraparotid exposure of the facial nerve branches. Results: Eleven of the 26 cases (42.4%) developed transient paresis, but only one (3.8%) developed permanent paresis. Of 41 dissected facial nerve branches, 14 developed transient paresis (34.1%) and one, a marginal mandibular branch, developed permanent paresis (2.4%). The branches most susceptible to developing paresis were the temporal (4/6 branches, 66.7%) and marginal mandibular branches (8/17 branches, 47.1%). Although the rate of paresis was higher, and ensuing recovery period slightly longer in the extraparotid dissection group compared to the intraparotid dissection group, there were no statistically significant differences between the two groups. The extraparotid and intraparotid rates of paresis were 48% (11/23 branches) and 21.1% (4/19 branches), respectively, P = 0.139; and the average recovery periods were 10.3 and 9.3 weeks, respectively, P = 0.64. Conclusions: The functional outcome, regardless of the different sites of facial nerve exposure, was almost always either complete facial nerve sparing or transient dysfunction that resolved within 6 months. [ABSTRACT FROM AUTHOR]

Background The number of very elderly patients who require surgery for cutaneous tumors is increasing. However, there is limited information on the safety of cutaneous surgery in such patients. Methods To evaluate the safety of cutaneous surgery in patients 90 years of age and older, we retrospectively reviewed the elderly patients who underwent surgery for cutaneous tumors under local anesthesia. Consecutive patients 90 years of age and older and 75-80 years old were included in the elderly group and the control group. Results The elderly and control groups included 104 and 106 patients, respectively. The mean age of the patients was 93.4 years (range, 90-101 years) in the elderly group and 77.4 years (range, 75-80 years) in the control group. The preoperative performance status was significantly worse in the elderly group than in the control group ( P < 0.001). The surgical time was not significantly different between the two groups ( P = 0.09). The occurrences of intraoperative and postoperative complications were not significantly different between the two groups ( P = 0.19 and P = 0.07, respectively). Conclusions The result of the present study indicates that cutaneous surgery for very elderly patients 90 years of age and older is as safe as for patients ranging in age from 75-80 years old. [ABSTRACT FROM AUTHOR]

Solitary fibrous tumors occasionally present with hypoglycemia because of the excessive release of insulin-like growth factor II. We report the first case of pancreatic solitary fibrous tumor causing ectopic adrenocorticotropic hormone syndrome. An 82-year-old Japanese man presented with lower limb edema, uncontrolled hypertension, hypokalemia, and baseline hypercortisolism. Distal pancreatectomy was performed after the clinical diagnosis of a neuroendocrine tumor with ectopic secretion of adrenocorticotropic hormone. On histological examination, the tumor showed spindle cells in a fascicular arrangement. The diagnosis of the solitary fibrous tumor was confirmed by the identification of the NAB2-STAT6 fusion gene and positive immuno-histochemical staining for STAT6 and CD34. Using quantitative real-time polymerase chain reaction, mRNA that encoded proopiomelanocortin, precursor of adrenocorticotropic hormone, was detected. Proopiomelanocortin production through the demethylation of the promoter region Domain IV was detected. Pancreatic solitary fibrous tumors represent a new cause of ectopic adrenocorticotropic hormone syndrome. [ABSTRACT FROM AUTHOR]

HTTP is recognized as the most widely used protocol on the Internet when applications are being transferred more and more by developers onto the web. Due to increasingly complex computer systems, diversity HTTP automated software (autoware) thrives. Unfortunately, besides normal autoware, HTTP malware and greyware are also spreading rapidly in web environment. Consequently, network communication is not just rigorously controlled by users intention. This raises the demand for analyzing HTTP autoware communication behaviour to detect and classify malicious and normal activities via HTTP traffic. Hence, in this paper, based on many studies and analysis of the autoware communication behaviour through access graph, a new method to detect and classify HTTP autoware communication at network level is presented. The proposal system includes combination of MapReduce of Hadoop and MarkLogic NoSQL database along with xQuery to deal with huge HTTP traffic generated each day in a large network. The method is examined with real outbound HTTP traffic data collected through a proxy server of a private network. Experimental results obtained for proposed method showed that promised outcomes are achieved since 95.1% of suspicious autoware are classified and detected. This finding may assist network and system administrator in inspecting early the internal threats caused by HTTP autoware. [ABSTRACT FROM AUTHOR]

Introduction Cytochrome P450 11B2 (CYP11B2) plays a pivotal role in aldosterone synthesis, while cytochrome P450 11B1 (CYP11B1) and cytochrome P450 17A1 (CYP17) are involved in cortisol synthesis in normal human adrenal glands. However, their detailed distribution in aldosterone-producing adenoma (APA) remains incompletely settled. Materials and methods We examined the status of CYP11B1/CYP11B2 and CYP11B2/CYP17A1 expressions in 27 APA (double staining) cases and 21 APA (triple staining) cases by using immunofluorescence staining and semi-quantitative evaluation. Results Tumor cells co-expressing CYP11B1/B2 (hybrid cell type A), CYP11B2/17 (hybrid cell type B), CYP11B1/17 (hybrid cell type C), and CYP11B1/B2/17 (triple-positive cell) were identified. The area and cell number of these cells were relatively small, but the size of individual hybrid cells were different between three hybrid cell types (A/B/C) and triple-positive cells. Conclusion The presence of hybrid cells indicated the marked intratumoral heterogeneity of steroidogenesis in APAs, particularly in those producing glucocorticoids and mineralocorticoids. [ABSTRACT FROM AUTHOR]

Inguinal lymph node dissection (ILND) for skin cancer is associated with a high incidence of wound complications. The traditional skin approaches are associated with a high risk of wound/flap necrosis of the inguinal skin, which leads to wound dehiscence and wound infection. We report a novel approach for ILND without inguinal skin incision for patients with invasive extramammary Paget disease (EMPD) to minimize the wound complications inherent in conventional ILND. We totally performed this procedure in 3 patients with invasive EMPD with inguinal nodal metastases. No patient had complications, including flap necrosis, wound dehiscence, or wound infection. Our novel surgical approach would retain the vascular supply because there was no inguinal skin incision, preventing postoperative wound complications. In addition, ILND was easily performed with satisfactory exposure of the surgical field. However, the number of patients was small and the follow-up period was short. Further evaluation of a larger case series with longer follow-up is essential to investigate the effect, safety, and indications for this novel approach. [ABSTRACT FROM AUTHOR]

Aldosterone is one of the mineralocorticoids synthesized and secreted by the adrenal glands, and it plays pivotal roles in regulating extracellular fluid volume and blood pressure. Autonomous excessive aldosterone secretion resulting from adrenocortical diseases is known as primary aldosteronism, and it constitutes one of the most frequent causes of secondary hypertension. Therefore, it is important to understand the molecular mechanisms of aldosterone synthesis in both normal and pathological adrenal tissues. Various factors have been suggested to be involved in regulation of aldosterone biosynthesis, and several adrenocortical cell lines have been developed for use as in vitro models of adrenal aldosterone-producing cells, for analysis of the underlying molecular mechanisms. In this review, we summarize the available reports on the regulation of aldosterone biosynthesis in the normal adrenal cortex, in associated disorders, and in in vitro models. [ABSTRACT FROM AUTHOR]

Subcutaneous islet transplantation is a promising treatment for severe diabetes; however, poor engraftment hinders its prevalence. We previously reported that a recombinant peptide (RCP) enhances subcutaneous islet engraftment. However, it is impractical for clinical use because RCP must be removed when transplanting islets. We herein investigated whether a novel bioabsorbable gelatin hydrogel nonwoven fabric (GHNF) could improve subcutaneous islet engraftment. A silicon spacer with or without GHNF was implanted into the subcutaneous space of diabetic mice. Syngeneic islets were transplanted into the pretreated space or intraportally (Ipo group). Blood glucose, intraperitoneal glucose tolerance, immunohistochemistry, CT angiography and gene expression were evaluated. The cure rate and glucose tolerance of the GHNF group were significantly better than in the control and Ipo groups (p < 0.01, p < 0.05, respectively). In the GHNF group, a limited increase of vWF-positive vessels was detected in the islet capsule, whereas laminin (p < 0.05), collagen III and IV were considerably enhanced. TaqMan arrays revealed a significant upregulation of 19 target genes (including insulin-like growth factor-2) in the pretreated space. GHNF markedly improved the subcutaneous islet transplantation outcomes, likely due to ECM compensation and protection of islet function by various growth factors, rather than enhanced neovascularization. [ABSTRACT FROM AUTHOR]

Artifacts in the process of specimen preparation are frequent in ultrastructural evaluation of renal biopsy. We hypothesized that the common practice of wrapping kidney biopsy specimens in saline-soaked gauze to prevent the drying of the specimens could be the major factor of artifacts. In this study, whole kidneys from two male Sprague- Dawley rats were used. Before fixation, fresh small cubes of kidney tissue were macerated in saline ( Saline group) or hypoelectrolytic isoosmotic solution for infusion ( HISI group) ( Sorita T3 or SOLDEM 3A) for 10 or 30 min. Then, the specimens were processed by 1% OsO4 in 0.1 M phosphate buffer ( pH 7.4) and embedded by EPON 812 for ultramicroscopic analysis. In the Saline group, ultrastructural examination revealed swollen podocyte, swollen capillary protuberance of the mesangium into the glomerular capillary loop, tubular cells with swollen mitochondria and microvilli, and the smooth muscle cells in the arteriolar wall with marked vacuolar degeneration were detected after 10 min maceration in saline and these findings become more pronounced after 30 min maceration. However, in the HISI group, these artifacts were not identified or limited within 30 min. It is postulated that HISI solution could prevent the artifacts, and be used for soaking and wrapping instead of physiologic saline solution. [ABSTRACT FROM AUTHOR]

It has become important to evaluate the possible involvement of 3β-hydroxysteroid dehydrogenase type 1 (HSD3B1) and 2 (HSD3B2) isoforms in aldosterone-producing adenoma (APA). In this study, we studied 67 and 100 APA cases using real-time quantitative PCR (qPCR) and immunohistochemistry, respectively. Results of qPCR analysis demonstrated that HSD3B2 mRNA was significantly more abundant than HSD3B1 mRNA ( P  < 0.0001), but only HSD3B1 mRNA significantly correlated with CYP11B2 (aldosterone synthase) mRNA ( P  <   0.0001) and plasma aldosterone concentration (PAC) of the patients ( P  <   0.0001). Results of immunohistochemistry subsequently revealed that HSD3B2 immunoreactivity was detected in the great majority of APA but a significant correlation was also detected between HSD3B1 and CYP11B2 ( P  <   0.0001). In KCNJ5 mutated APA, CYP11B2 mRNA ( P  <   0.0001) and HSD3B1 mRNA ( P  = 0.011) were significantly higher than those of wild type APA. These results suggest that HSD3B1 is involved in aldosterone production, despite its lower levels of expression compared with HSD3B2, and also possibly associated with KCNJ5 mutation in APA. [ABSTRACT FROM AUTHOR]

Androstenedione is a common precursor of sex steroids produced and secreted in the human adrenal gland and produced by 3β-hydroxysteroid dehydrogenase (3βHSD), 17β-hydroxylase/17,20-lyase (CYP17) and cytochrome b5 (CYB5A). 3βHSD is expressed in the zona glomerulosa (ZG) and fasciculata (ZF), CYP17 in the ZF and zona reticularis (ZR) and CYB5A in the ZR, respectively. We previously demonstrated the presence of cortical parenchymal cells co-expressing 3βHSD and CYB5A with hybrid features of both ZF and ZR in human adrenal cortex and hypothesized that these cells may play an important role in androstenedione production in human adrenal gland. Age-related morphologic development of these hybrid cells has, however, not been studied. Therefore, in this study, 48 human adrenal specimens from various age groups were retrieved. Double-immunohistochemical analyses were used in order to study the correlation between this hybrid cell type and age. In both male and female adrenal cortex, the means of total adrenocortical area, the area positive for CYB5A and its ratio reached highest peak in the 21-40-year-old (y.o.) group. The greatest overlap between 3βHSD and CYB5A in both total and relative area was present in the 13-20 y.o. group. For all the markers mentioned above, statistically significant differences were detected among the different age groups examined ( p < 0.05). These findings indicated that both area and ratio of 3βHSD and CYB5A double positive cells, which could represent the hybrid cells of ZF and ZR, are correlated with human adrenal development and could subsequently influence age-related serum androstenedione levels. [ABSTRACT FROM AUTHOR]

The sebaceous gland is a major site of steroid synthesis in human skin, but details of the status of steroidogenic enzymes and their regulation in human sebaceous glands under normal and pathological conditions have rarely been reported. Therefore, in this study, we examined the status of steroidogenic enzymes, sex steroid receptors and transcription factors in human sebaceous glands under normal and pathological conditions to explore their possible roles in in situ steroid production in human skin. Immunohistochemical analysis was performed in a total of 59 human skin specimens, including 22 normal human sebaceous glands, 12 with sebaceous nevus, 12 with sebaceous gland hyperplasia, 3 with sebaceoma and 10 with sebaceous carcinoma. Immortalised human SZ95 sebocytes were treated with forskolin or vehicle for 3 h, 6 h, 12 h or 24 h, and the mRNA levels of steroidogenic enzymes were evaluated at each time point using quantitative RT-PCR (qPCR). The results of immunohistochemistry demonstrated the immunoreactivity of 3β-HSD1, CYP11A1, StAR, 17β-HSD5, CYP17A1, 5α-red1, PRB, AR and NGFI-B in normal human sebaceous gland, with lower levels of expression in pathological sebaceous glands. The results of the in vitro study also indicated that the expression levels of 3β-HSD1, CYP11A1, StAR, 5α-red1 and NGFI-B were elevated by forskolin. 3β-HSD1 and other steroidogenic enzymes were expressed in sebaceous glands resulting in in situ androgen and progesterone synthesis and their functions. [ABSTRACT FROM AUTHOR]

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. [ABSTRACT FROM AUTHOR]

The great majority of the cases clinically diagnosed as primary aldosteronism ( PA) have been caused by aldosterone-producing adenoma ( APA) or idiopathic hyperaldosteronism ( IHA). The differential diagnosis of both subtypes of PA is important due to the different therapeutic modes but clinically it is sometimes difficult. It is also important to understand the morphological features of these two subtypes with special emphasis upon differences of the status for aldosterone biosynthesis. In the last decade, molecular mechanisms of PA including the aberrant expression of G-protein coupled receptors ( GPCRs), key regulators of the intracellular calcium signaling pathway and somatic mutations of ion channels, have been revealed and our understanding of the molecular pathways involved in excessive aldosterone production has been markedly advanced. In addition, newly developed monoclonal antibodies specific to the isoform of adrenal steroidogenic enzymes have demonstrated the novel profiles of adrenal steroidogenesis in PA. These novel findings indicate that the molecular mechanisms on the onset and pathophysiology of PA are more complicated than previously considered and further clarification of clinical relevance of these findings is required at this juncture. [ABSTRACT FROM AUTHOR]

Highlights: [•] The monoclonal antibodies of CYP11B1/2 are useful for immunohistochemical evaluation. [•] In APA, CYP11B2 was heterogeneously detected and CYP11B1 diffusely in tumor cells. [•] CYP11B2 may differentiate between hyperplastic ZG of IHA and APA adjacent adrenal. [ABSTRACT FROM AUTHOR]

Oncocytic adrenocortical neoplasm is characterized by abundant eosinophilic cytoplasm containing mitochondria, occasional nuclear atypia and diffuse growth pattern. Oncocytic adrenocortical neoplasm arising in adrenal rest is, however, extremely rare. We report a case of oncocytic adrenocortical neoplasm arising in adrenal rest of the broad ligament with associated marked lipomatous metaplasia. A well circumscribed tumor was accidentally detected in the pelvic cavity of a 29 year old Japanese woman, adjacent to the broad ligament of the uterus. The tumor was composed of large eosinophilic cells associated with diffuse growth pattern and abundant mature adipose tissue admixed with foci of clear cells. Both steroidgenic factor 1 ( SF-1) and alpha-inhibin were immunohistochemically positive in tumor cells. Abundant mitochondria detected by immunohistochemical and electron microscopic examination confirmed the diagnosis of oncocytic adrenocortical neoplasm. The absence of necrosis, capsular and vascular invasion as well as the low mitotic index indicated the benign potential of this tumor. The tumor cells were also positive for dehydroepiandrosteron-sulfotransferase ( DHEA-ST), 17β-hydroxysteroid dehydrogenase type 5 (17β- HSD5), 3β-hydroxysteroid dehydrogenase (3β- HSD) and steroid 17α-hydroxylase (P450-c17), suggesting a possible production of testosterone of this tumor. This is the first reported case of oncocytic adrenocortical adenoma arising in adrenal rest of the broad ligament. [ABSTRACT FROM AUTHOR]

Highlights: [•] Aberrant GnRHR expression is detectable in various types of human adrenal tissues. [•] GnRHR is involved in CYP11B2 expression and aldosterone production in APA. [•] Aldosterone synthesis via GnRHR is regulated by calcium signaling pathway. [ABSTRACT FROM AUTHOR]

Renal epithelioid angiomyolipoma ( EAML) is a potentially malignant tumor type whose characteristics and biomarkers predictive of malignant behavior have not been elucidated. Here, we report three cases of renal EAML with malignant features but without histories of tuberous sclerosis complex. Case 1 involved a 29-year-old man with a 12-cm solid mass in the right kidney who underwent radical right nephrectomy. Case 2 involved a 22-year-old woman with a retroperitoneal mass who underwent radical right nephrectomy and retroperitoneal tumorectomy. Local recurrence was detected 7 years post-surgery. Case 3 involved a 23-year-old man with a 14-cm solid mass in the left kidney who underwent radical left nephrectomy. Microscopically, the tumors in all cases demonstrated proliferation of epithelioid cells with atypia, mitotic activity, necrosis, hemorrhage, and vascular invasion. Epithelioid cells in all cases were immunohistochemically positive for melanocytic and myoid markers and weakly positive for E-cadherin and β-catenin. Immunohistochemistry revealed activation of the mammalian target of rapamycin pathway. Here, we report the morphological and immunohistochemical features of clinically or histologically malignant renal EAML. [ABSTRACT FROM AUTHOR]

Highlights: [•] Glutamate receptors GRM1, GRM3, IGLUR2, and IGLUR3 were detected in human adrenocortical tissues. [•] GRM3 was significantly higher in aldosterone producing adenomas than in the normal adrenal cortex. [•] GRM3 was detected in the zona glomerulosa of normal adrenal and idiopathic aldosteronism. [•] Treatment with the GRM3 agonist LY354740 decreased aldosterone/cortisol production in H295R cells. [•] Forskolin plus LY354740 resulted in decreased CYP11B1 and CYP11B2 mRNA compared to forskolin alone. [ABSTRACT FROM AUTHOR]

Although atrial natriuretic peptide (ANP) is widely used in patients with congestive heart failure (CHF), little is known about its effect on epicardial coronary arteries. Magnetic resonance imaging (MRI) enables precise measurement of coronary vasodilation and flow velocity. In this study, we examined the changes in epicardial coronary artery size and flow velocity in response to intravenous infusion of ANP or nitroglycerin (NTG) by using 3 T MRI in patients with CHF. The study cohort contained a total of 14 subjects: 8 patients with CHF and 6 healthy volunteers as controls, randomly divided into two groups: the ANP group (0.03 μg/kg/min) and the NTG group (0.3 μg/kg/min). Cross-sectional MR angiography and phase-contrast flow velocity of the right coronary artery in the same in-plane slice were obtained at the baseline, during drug infusion, and at two subsequent time points after stopping drug infusion. A significant increase was observed in the coronary cross-sectional area at 15 min after drug infusion in both groups compared with that at baseline; however, a late peak was observed at 15 min after stopping infusion in the ANP group. No significant differences were detected in the flow velocity in both groups. Furthermore, although NTG increased the heart rate, this change was not found in the ANP group. Coronary vasodilation and flow velocity can be measured simultaneously using 3 T MRI. Using this method, we showed that the effects of ANP on the coronary artery vasodilation and flow velocity were not inferior to those of NTG, with no significant alteration in heart rate. [ABSTRACT FROM AUTHOR]

Abstract: Aims: The nuclear hormone receptor estrogen-related receptor α (ERRα) regulates the activation of mitochondrial genes in various human tissues, but its role in the adrenal gland and its disorders has not been defined. Therefore, we examined ERRα expression in both normal adrenal cortex (NAC) and adrenocortical tumor (ACT) in order to study the possible correlation of ERRα with adrenal development and tumor development. Methods: Human adrenal specimens (non-pathological fetal n =7; non-pathological post-birth n =40; aldosterone producing adenoma (APA) n =11; cortisol producing adenoma (CPA) n =11; adrenocortical carcinoma (ACC) n =8) were immunohistochemically examined in this study. NAC (n =13) and ACT (n =28) frozen tissue specimens were also available for studying ERRα mRNA levels. Key findings: In fetal NAC tissues, ERRα labeling index (LI) in fetal zone (FZ) was significantly higher that that in neocortex (NC), and the differences among age groups for overall mean LI was statistically significant when analyzed according to individual cortical layers. ERRα LI was also significantly higher in ACC than in other types of ACT. ERRα mRNA was detected in NAC and all types of ACT. Significance: Results of our present study suggest a possible role of ERRα in adrenal development and ACC. [Copyright &y& Elsevier]

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. [ABSTRACT FROM AUTHOR]

We have performed numerical calculations to analyze the low-frequency properties of a single-junction thermal converter using a modified low-frequency model. A feature of the modified low-frequency model is the incorporation of the heat capacity of the thermocouple and ceramic bead, which had been previously neglected. Since thermocouple and ceramic bead can increase the thermal inertia of the heater, they can modify the thermal time constant, which plays a crucial role at low frequencies. The calculated data using modified low-frequency model for the AC-DC transfer differences correspond better to the experimental data. The difference of the AC-DC transfer difference between calculated and measured data is less than 10 µV/V down to 10 Hz. IEEJ Trans 2012. doi: 10.1002/tee.21739 [ABSTRACT FROM AUTHOR]

Skeletal myoblast transplantation has therapeutic potential for repairing damaged heart. However, the optimal conditions for this transplantation are still unclear. Recently, we demonstrated that satellite cell-derived myoblasts lacking the MyoD gene (MyoD-/-), a master transcription factor for skeletal muscle myogenesis, display increased survival and engraftment compared to wild-type controls following transplantation into murine skeletal muscle. In this study, we compare cell survival between wild-type and MyoD-/- myoblasts after transplantation into infarcted heart. We demonstrate that MyoD2/ 2 myoblasts display greater resistance to hypoxia, engraft with higher efficacy, and show a larger improvement in ejection fraction than wild-type controls. Following transplantation, the majority of MyoD-/- and wild-type myoblasts form skeletal muscle fibers while cardiomyocytes do not. Importantly, the transplantation of MyoD-/- myoblasts induces a high degree of angiogenesis in the area of injury. DNA microarray data demonstrate that paracrine angiogenic factors, such as stromal cell-derived factor-1 (SDF-1) and placental growth factor (PlGF), are up-regulated in MyoD-/- myoblasts. In addition, overexpression and gene knockdown experiments demonstrate that MyoD negatively regulates gene expression of these angiogenic factors. These results indicate that MyoD-/- myoblasts impart beneficial effects after transplantation into an infarcted heart, potentially due to the secretion of paracrine angiogenic factors and enhanced angiogenesis in the area of injury. Therefore, our data provide evidence that a genetically engineered myoblast cell type with suppressed MyoD function is useful for therapeutic stem cell transplantation. [ABSTRACT FROM AUTHOR]

Context Although steroid hormones produced by the adrenal gland play critical roles in human physiology, a detailed quantitative analysis of the steroid products has not been reported. The current study uses a single methodology (liquid chromatography-tandem mass spectrometry, LC-MS/MS) to quantify ten corticosteroids in adrenal vein (AV) samples pre- and post-adrenocorticotropic hormone (ACTH) stimulation. Design/methods Three men and six women with a diagnosis of an adrenal aldosterone-producing adenoma (APA) were included in the study. Serum was collected from the iliac vein (IV) and the AV contralateral to the diseased adrenal. Samples were collected, before and after administration of ACTH. LC-MS/MS was then used to quantify serum concentrations of unconjugated corticosteroids and their precursors. Results Prior to ACTH stimulation, the four most abundant steroids in AV were cortisol (90%), cortisone (4%), corticosterone (3%) and 11-deoxycortisol (0·8%). Post-ACTH administration, cortisol remained the major adrenal product (79%); however, corticosterone became the second most abundantly produced adrenal steroid (11%) followed by pregnenolone (2·5%) and 17α-hydroxypregnenolone (2%). ACTH significantly increased the absolute adrenal output of all ten corticosteroids measured ( P < 0·05). The four largest post-ACTH increases were pregnenolone (300-fold), progesterone (199-fold), 17α-hydroxypregnenolone (187-fold) and deoxycorticosterone (82-fold). Conclusion Using LC-MS/MS, we successfully measured 10 corticosteroids in peripheral and AV serum samples under pre- and post-ACTH stimulation. This study demonstrates the primary adrenal steroid products and their response to ACTH. [ABSTRACT FROM AUTHOR]

We reduced the exponentially decreasing thermal drift of a single-junction thermal converter and performed comparison measurements of the ac–dc transfer difference. The thermal converter was mounted on a metal block using a high-thermal-conductance paste; this treatment is crucial to improving the thermal drift. Numerical calculations using a thermal model that includes the temperature increase on the cold side of the thermocouple can explain the measured thermal drift. Our system, which uses a low-drift thermal converter, allows comparison measurements of the ac–dc transfer difference at a few parts in 10^7 with a short measurement time if a sufficiently long waiting time is used. [ABSTRACT FROM PUBLISHER]

Female Wistar rats were given Cd (as CdCl2) at a dose of 0, 1, 2, and 5 mgCd/kg/day by gastric tube daily for 6 consecutive days each week for 10 weeks. After the birth, newborn rats were sacrificed on day 1 and at 4 weeks. Mother rats were sacrificed after 4 weeks of lactation The concentrations of Cd in uterus and placenta, and metallothionein (MT) in the uterus of mother rats were determined. The concentrations of Cd in kidney and liver of newborn rats were also determined. Expression of iso-MT genes (I, II, and III) in the uterus of mother rats was measured using RT-PCR. The Cd concentration in the liver of newborn rats at the first day after birth was higher than in the kidney, while the concentration in the kidney of newborn rats at the fourth week after the birth was significantly higher than in the liver. The uterine MT concentration increased with accumulation of Cd; however, the MT concentration did not increase enough to prevent Cd transport to the fetus. On the other hand, it was considered that more Cd was transported as the chemical form of nonMT-Cd from mother rat, and accumulated in the liver rather than kidney of the fetus. Based on analyses of the Cd distribution in the liver and kidney of newborn rats, we speculate that MT in the uterus and placenta does not play a significant role in preventing Cd transport through the placenta from the uterus to the fetus. [ABSTRACT FROM AUTHOR]

A quadrature bridge, one of the important instruments for National Metrology Institute of Japan capacitance measurement chain based on an ac quantized Hall resistance (QHR), has been developed. The developed quadrature bridge can be used to compare the capacitance and ac QHR at a measurement frequency of 1.592 kHz. At the present stage of development, the bridge can be used to achieve a relative standard uncertainty of 0.030 \times 10^-6 during bridge balancing. [ABSTRACT FROM AUTHOR]

Abstract: Androstenedione is one of several weak androgens produced in the human adrenal gland. 3β-Hydroxysteroid dehydrogenase type 2 (HSD3B2) and cytochrome b5 (CYB5A) are both required for androstenedione production. However, previous studies demonstrated the expression of HSD3B2 within the zona glomerulosa (ZG) and fasciculata (ZF) but low levels in the zona reticularis. In contrast, CYB5A expression increases in the zona reticularis (ZR) in human adrenal glands. Although their colocalization has been reported in gonadal theca and Leydig cells this has not been studied in the human adrenal. Therefore, we immonolocalized HSD3B2 and CYB5A in normal human adrenal glands and first demonstrated their co-expression in the cortical cells located at the border between the ZF and ZR in normal human adrenal. Results of in vitro studies using the human adrenal H295R cells treated with the HSD3B2 inhibitor, trilostane, also demonstrated a markedly decreased androstenedione production. Decreasing CYB5A mRNA using its corresponding siRNA also resulted in significant inhibition of androstenedione production in the H295R cells. These findings together indicate that there are a group of cells co-expressing HSD3B2 and CYB5A with hybrid features of both ZF and ZR in human adrenal cortex, and these hybrid cortical cells may play an important role in androstenedione production in human adrenal gland. [ABSTRACT FROM AUTHOR]

Background Reconstruction of vulvovaginal defects after tumor excision requires good-quality skin cover because of the cosmetic and functional importance of this region. Although numerous techniques for vulvovaginal reconstruction have been described, an ideal approach has yet to be widely accepted. Methods Seven gluteal-fold flaps advanced in a V-Y fashion were used to cover vulvovaginal defects in five patients who underwent surgical treatment for extramammary Paget's disease or carcinoma of the vulva. Results Each flap survived completely with no complication other than partial dehiscence in one case and temporary postoperative discomfort and pain upon sitting. None of the patients suffered from recurrence of the tumor. Conclusions In our experience, this flap is easily elevated, not bulky, and reliable because it is supplied by the internal pudendal artery and vein perforators without excessive skeletonization of the vascular pedicle, and it has matched local skin quality. In addition, it has minimal donor-site morbidity as the scar is concealed in the gluteal fold. It can cover medium-sized vulvovaginal defects after tumor excision. [ABSTRACT FROM AUTHOR]

Background Tumor lysis syndrome (TLS) is rare in the treatment of solid tumors, but it may occur in myelolymphoproliferative diseases. Methods A 58-year-old man with bulky metastatic melanoma of the liver was treated with transcatheter arterial infusion of cisplatin and embolization therapy. The patient developed classic signs of TLS within 24 h of chemotherapy, including acute renal failure. Results The patient was treated with aggressive hydration, allopurinol, and repeated hemodialysis. He gradually improved and his biochemical markers returned to normal. Conclusion TLS is an uncommon, but potentially life-threatening, complication in melanoma and other solid tumors. It is important for oncologists to recognize this complication and prevent its development if bulky metastatic disease and several pre-existing risk factors, such as multiple and bulky liver metastases, elevated lactate dehydrogenase, and hyperuricemia, are present. [ABSTRACT FROM AUTHOR]

Peroxisome proliferator-activated receptor (PPAR) is a member of the nuclear hormone receptor superfamily of transcription factors. Peroxisome proliferator-activated receptor gamma (PPARγ) plays an important role in the regulation of lipid homeostasis, adipogenesis, insulin resistance, and development of various organs. Agonists of PPARγ have been also reported to inhibit proliferation of prostate carcinoma cells as in other human malignancies, and these synthetic ligands have been used in differentiation-mediated therapy of various human carcinomas associated with high levels of PPARγ. The significance of PPARγ expression, however, was unknown in human prostate carcinoma tissues. The purpose of the present study was therefore to examine the immunolocalization of PPARγ in human prostate cancer tissues (40 cases) and correlate the findings with clinicopathological features of the patients in order to evaluate its possible biological significance. Twenty-nine patients were positive for PPARγ immunoreactivity (73%) and a significant inverse correlation was detected between PPARγ immunoreactivity, pT stage ( P = 0.036), and serum concentration of prostate-specific antigen ( P = 0.0004). In conclusion, PPARγ immunoreactivity is considered to be a new clinicopathological parameter of human prostate cancer. [ABSTRACT FROM AUTHOR]

Abstract: Hormonal regulation of adrenal function occurs primarily through G protein-coupled receptors (GPCR), which may play different roles in fetal vs. adult adrenal glands. In this study, we compared the transcript levels of GPCR between fetal and adult adrenal and found that gonadotropin-releasing hormone receptor (GnRHR), latrophilin 3 receptor, G protein-coupled receptor 37, angiotensin II receptor type 2, latrophilin 2 receptor and melanocortin receptor were expressed at significantly higher levels in fetal adrenal. High GnRHR protein expression was also detected in fetal adrenal using immunohistochemical analysis. To define potential ligand sources for fetal adrenal GnRHR, we demonstrated that GnRH1 mRNA was expressed at high levels in the placenta, while fetal adrenal had high expression of GnRH2. In summary, certain GPCR particularly GnRHR were highly expressed in fetal adrenal and the expression of GnRH mRNA in the placenta and the fetal adrenal raises the possibility of endocrine and/or paracrine/autocrine influences on fetal adrenal function. However, the exact function of GnRHR in fetal adrenal remains to be determined. [Copyright &y& Elsevier]

The article presents a case involving a 79-year-old man with Type 1 extramammary Paget's disease (EMPD), a very rare form of malignancy, involving the glans penis. It describes a new surgical method of tumor resection that does not sacrifice the sinusoids. According to the authors, tumor can be removed with subcutaneous tissue by excision to the fibroelastic layer of the glans penis. They hope that this method will prevent unnecessary excessive surgery.

Abstract: The human adrenal reticularis produces the so-called adrenal androgens, dehydroepiandrosterone (DHEA) and DHEA-sulfate (DHEA-S). As opposed to the cortisol and aldosterone little is known regarding the mechanisms that regulate the production of the adrenal androgens. Several recent studies have shown that type II 3β-hydroxysteroid dehydrogenase (HSD3B2), cytochrome b5 (CYB5), and steroid sulfotransferase (SULT2A1) play an important role in the regulation of adrenal androgen production. Specifically, adrenal production of DHEA-S is correlated with reticularis expression of SULT2A1 and CYB5. In contrast, HSD3B2 has an inverse correlation with adrenal androgen production likely due to its unique ability to remove precursors from the pathway leading to DHEA. Therefore, its expression is limited to the adrenal glomerulosa/fasciculata but not in reticularis. The differential expression of these three proteins appears to be critical for reticularis function. In this review, we focus on studies that have begun to define the mechanisms regulating the transcription of these genes. Understanding the mechanisms controlling differential expression of these proteins should provide novel information about the human adrenal reticularis and its production of DHEA and DHEA-S. [Copyright &y& Elsevier]

Kisspeptins, including metastin, are encoded by the KISS- 1 gene and play an important role in regulating the hypothalamic gonadotropin-releasing hormone (GnRH) system via G protein-coupled receptor 54 (GPR54, also called KISS- 1R). Normally, metastin (also called Kp-54) levels are quite low, except during pregnancy, when levels increase 1000-fold over those found in men and nonpregnant women. However, the potential hormonal role of metastin in the fetal and maternal circulation is unknown. In this study, the authors examine the levels of GPR54 mRNA expression in human adult and fetal adrenals using quantitative real-time reverse-transcriptase polymerase chain reaction (R T-PCR). In addition, they examine the effects of metastin on steroidogenesis and steroidogenic enzyme mRNA levels in fetal adrenal cells and in the H295R adrenocortical cell line using enzyme immunoassay and RT-PCR techniques. The authors demonstrate that GPR54 mRNA is significantly higher (50-fold) in human fetal adrenals than in adult adrenals. Immunohistochemical studies have demonstrated that the GPR54 protein is predominantly expressed in the neocortex of human fetal adrenals in the third trimester. Metastin increases aldosterone production (approximately 2-fold) in both fetal neocortex adrenal cells and H295R adrenal cells, with a maximal increase seen at 100 nM. In addition, metastin increased angiotensin H (Ang II)-stimulated aldosterone production by approximately 1.5-fold. Metastin also increased the ability of the H295R cells to metabolize exogenously added pregnenolone to aldosterone but had no effect on the expression of aldosterone synthase (CYP11B2). These results suggest that the high fetal/maternal levels of metastin seen during pregnancy may affect adrenal production of aldosterone. [ABSTRACT FROM AUTHOR]

To describe the changes in the magnetic resonance (MR) signal of the perianterior horn structure (PAS) with increasing age, we studied 69 infants and children aged between 3 days and 9.4 years (average: 2.8 years) without any neurological deficits. T1- and T2-weighted images and FLAIR (fluid attenuation inversion recovery) images were obtained in the axial plane. Based on a comparison of the intensity of the PAS with that of the cortex in each sequence (T1-WI/FLAIR/T2-WI), we classified the signal-intensity patterns into four types: I, low/low/high; II, low/high/high; III, iso/high/high; IV, high/low/low. Signal-intensity types I, II, III and IV were seen in 22, 8, 17, and 22 subjects, respectively, with younger subjects showing type I or II intensity patterns and older subjects showing type III or IV. In addition, T1-weighted and FLAIR images of subjects with a type I intensity pattern showed a rim of an isointensity component around the PAS that histologically coincided with migrating glial cells. The low-intensity area on FLAIR and T2-WI images of subjects with a type IV intensity pattern may represent myelinated fibers of the subcallosal fasciculus (ScF). The intensity of the MR signals of the PAS changes with increasing age, and this change may reflect histological features. A better understanding of these characteristics may help us to clarify myelination abnormalities, particularly those related to the ScF in the frontal lobe in infants and children. [ABSTRACT FROM AUTHOR]

The article presents the clinical case of a 22-year-old man diagnosed with a mass in the right lower chest. Reportedly, the mass in the right lower chest had grown gradually and become painful over two years. The patient has undergone ultrasound examination, where a well-circumscribed homogeneous solid mass between the external oblique and external intercostal muscle was found. Furthermore, the clinical findings had revealed schwannoma or a hemangioma.

The article presents the case report of a 28-year-old woman with an elastic and firm subcutaneous tumor. The article mentions that the clinical studies comprising computed tomography and magnetic resonance imaging were suggestive of a neural tumor. However, the pathology and immunohistochemistry diagnosed the lesion as a solitary fibrous tumor (SFT). It is discussed that surgical excision of the tumor is a typical treatment option.

Previous studies of epidermal-specific gene promoters suggested that a limited set of transcription factors regulate keratinocyte-specific and differentiation-specific gene expression in the epidermis. In the present study, we investigated the functional importance of AP-1- and Sp1-binding elements in the determination of cell type-specific and differentiation-specific gene expression by transient transfection into undifferentiated and differentiated keratinocytes as well as into various non-epidermal cell lines. Synthesized short AP-1- and/or Sp1-binding elements were inserted into a minimal reporter vector, and the artificial promoter containing both AP-1 and Sp1 elements showed high levels of transcriptional activity only when transfected into differentiated keratinocytes. Promoters containing either the AP-1 or the Sp1 motif alone showed little activity in any of the cells examined. We also found that close proximity of the Sp1 and AP-1 sites is essential for transcriptional activity, suggesting that the physical interaction between Sp1 and AP-1 factors is important for functional activity. These results clearly demonstrate that the combination of ubiquitously expressed transcription factors AP-1 and Sp1 confers keratinocyte specificity and differentiation specificity on the gene expression. Our findings also provide a simple model of the mechanisms underlying regulation of cell type-specific and cell differentiation-specific gene expression by ubiquitously expressed transcription factors. [ABSTRACT FROM AUTHOR]

We report a patient with gastric small cell carcinoma (SCC) who showed a marked response to neoadjuvant chemotherapy. The patient was a 72-year-old Japanese man who was admitted because of epigastralgia. Subsequent examination revealed the presence of advanced gastric carcinoma in the lesser curvature of the lower body of the stomach, with multiple abdominal lymph node metastases. Endoscopic biopsy specimens from the tumor revealed SCC with moderately differentiated adenocarcinoma. The patient received neoadjuvant chemotherapy consisting of carboplatin (400 mg/m2, for 1 day), epirubicin (27 mg/m2, for 1 day), etoposide (70 mg/m2, for 3 days), and 5-fluorouracil (330 mg/m2, for 11 days). Clinically, the primary tumor and lymph node metastases were markedly reduced. Subsequently the patient underwent curative surgery and was alive without recurrence for more than 3 years after the surgery. [ABSTRACT FROM AUTHOR]

Tubulin beta II (Tub-II) is widely distributed in the developing neuronal axons and dendrites. Recent studies have demonstrated that Tub-II is also important in the early development of the human brain, and Tub-II represents a marker for progenitor and neural stem cells. To elucidate the correlation between the developing brain and neuroepithelial tumors (NETs), the present study assessed Tub-II expression by NETs and normal brain tissue using immunohistochemical and immunoblot analyses. In the gliomas, decreased numbers and staining intensities of Tub-II-positive cells tended to be associated with increased differentiation. Conversely, neuronal neoplasms displayed high percentages and strong staining intensities among the Tub-II-positive cells, irrespective of differentiation. In neuronal neoplasms and neoplasms with neuronal differentiation, Tub-II staining was far more intense and more homogeneous than Tub-II staining in gliomas. These results indicate that the expression of Tub-II in NETs may reflect architectural changes in the developing brain and may support the hypothesis that neuroepithelial tumors originate from glioneuronal progenitor cells capable of generating astrocytic, and neuronal cell types. [ABSTRACT FROM AUTHOR]