Genetic Background of Iris Melanomas and Iris Melanocytic Tumors of Uncertain Malignant Potential.

Science.gov (United States)

van Poppelen, Natasha M; Vaarwater, Jolanda; Mudhar, Hardeep S; Sisley, Karen; Rennie, Ian G; Rundle, Paul; Brands, Tom; van den Bosch, Quincy C C; Mensink, Hanneke W; de Klein, Annelies; Kiliç, Emine; Verdijk, Robert M

2018-01-19

BAP1 expression as seen in choroidal melanoma. Consequently, iris melanoma is a distinct molecular subgroup of UM. Histologic borderline malignant iris nevi can harbor BAP1 mutations and may be designated iris melanocytic tumors of uncertain malignant potential. Copyright © 2017 American Academy of Ophthalmology. Published by Elsevier Inc. All rights reserved.

Melan-A/Mart-1- or HMB-45-positive melanocytes are not present in calcifying cystic odontogenic tumors (calcifying odontogenic cysts): a study in 13 Caucasian patients.

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Tosios, Konstantinos I; Prountzos, Nikolaos; Katsoulas, Nikolaos; Koutlas, Ioannis G; Sklavounou-Andrikopoulou, Alexandra

2012-03-01

Melanin pigment and melanocytes may be found in odontogenic cysts and tumors, particularly calcifying cystic odontogenic tumor (CCOT). In the present study we investigated the immunohistochemical expression of the Melan-A/Mart-1 and HMB-45 antigens in 13 Caucasians patients with CCOT. Melan-A/Mart-1- and HMB-45-positive melanocytes were not seen in any of the cases. Our findings are in agreement with the assumption that pigmentation in odontogenic lesions may be a racial phenomenon.

Optical Coherence Tomography Angiography Characteristics of Iris Melanocytic Tumors

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Skalet, Alison H.; Li, Yan; Lu, Chen D.; Jia, Yali; Lee, ByungKun; Husvogt, Lennart; Maier, Andreas; Fujimoto, James G.; Thomas, Charles R.; Huang, David

2016-01-01

-injection, cost-effective method for monitoring a variety of tumors including iris melanocytic lesions for growth and vascularity. This could be helpful in evaluating tumors for malignant transformation and response to treatment. Penetration of the OCT beam remains a limitation for highly pigmented tumors, as does the inability to image the entire iris in a single field. PMID:27856029

Malignant Tumor Derived from Skin Melanocytes of a Bovine of Unusual Presentation: A Case Study

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Carlos Alberto Chaves Velásquez

2015-05-01

Full Text Available Melanocytic tumors and melanomas in domestic animals include neoplasms composed of melanin-producing cells. In cattle, these tumors are rare and mostly benign, while malignant tumors are almost non-existent. The article reports the case of a female crossbred cow 38 months of age with a fluctuating mass located between the mandibular border and the left parotid region, about three months duration, with evident growth in the last thirty days. After surgical excision, a sample preserved in buffered formalin (10% was sent to the Laboratory of Pathology (University of Nariño—consisting of a fragment of 7.0 × 10.5 × 8.0 cm, ellipsoid, with skin and hair on one side, irregular surface, blackish brown, semi-soft consistency, and presence of shear translucent slimy content—for processing and inclusion in paraffin, cut to 5 μm thickness and stained with hematoxylin-eosin coloration. The forwarded tissue was classified as a neoplasm of malignant behavior derived from melanocytes, due to its cellular characteristics: growth pattern, pattern of distribution, severe cellular pleomorphism, anisocytosis, megalocytosis, nuclear pleomorphism, anisokaryosis, megalokaryosis, and involvement of blood vessel walls; additionally, the paraffin block was cut for immunohistochemical processing using monoclonal markers (S-100 DAKO® and Melan A DAKO®, contrasted with Mayer’s hematoxylin. Strong immunostaining of neoplastic cells is evident, and it constitutes the first reported case of this disease in Nariño (Colombia.

Serum CA 125, carcinoembryonic antigen, and CA 19-9 as tumor markers in borderline ovarian tumors

NARCIS (Netherlands)

Engelen, MJA; de Bruijn, HWA; Hollema, H; ten Koor, KA; Willemse, PHB; Aalders, JG; van der Zee, AGJ

Objectives. The goals of this study were to analyze preoperative serum levels of CA 125, carcinoembryonic antigen (CEA), and CA 19-9 in patients with borderline ovarian tumors and to investigate if routine assessment of these markers in follow-up may lead to earlier detection of recurrence. Methods.

Fertility preservation in women with borderline ovarian tumors - how does it impact disease outcome? A cohort study.

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Helpman, Limor; Yaniv, Assaf; Beiner, Mario E; Aviel-Ronen, Sarit; Perri, Tamar; Ben-Baruch, Gilad; Hogen Ben-David, Liat; Jakobson-Setton, Ariella; Korach, Jacob

2017-11-01

Borderline ovarian tumors are typically indolent neoplasms. Since many are diagnosed in younger women, fertility conservation is an important consideration and has been advocated based on retrospective data. The objective of this study was to identify features impacting on recurrence and survival in a series of borderline ovarian tumors, and to assess the safety of a fertility-sparing approach. A historical cohort study of consecutive borderline ovarian tumors cases treated at a single institution over 30 years (1981-2011). Data on surgical approach (fertility-sparing or otherwise), disease stage, CA125 levels, histological features, adjuvant treatment and follow-up data were collected. Recurrence and survival were assessed using the Kaplan-Meier method and associations with the variables of interest were evaluated using a multivariate Cox proportional hazards model. 213 patients were included. Of 132 women age 40 years and below at diagnosis, 112 (85%) had a fertility-sparing procedure and 60 (46%) had conservation of an involved ovary. Fifty patients (24%) developed recurrences; fertility preservation (hazard ratio = 2.57; 95% confidence interval 1.1-6; p = 0.029) and advanced stage (hazard ratio = 4.15; 95% confidence interval 2.3-7.6; p Fertility preservation was not associated with compromised survival. Borderline ovarian tumors carry a good prognosis overall. Fertility preservation is associated with a higher risk of disease relapse; however, as most relapses are localized and may be salvaged with surgical treatment, overall survival is not compromised. © 2017 Nordic Federation of Societies of Obstetrics and Gynecology.

Overexpression of hepatoma-derived growth factor in melanocytes does not lead to oncogenic transformation

International Nuclear Information System (INIS)

Sedlmaier, Angela; Wernert, Nicolas; Gallitzendörfer, Rainer; Abouzied, Mekky M; Gieselmann, Volkmar; Franken, Sebastian

2011-01-01

HDGF is a growth factor which is overexpressed in a wide range of tumors. Importantly, expression levels were identified as a prognostic marker in some types of cancer such as melanoma. To investigate the presumed oncogenic/transforming capacity of HDGF, we generated transgenic mice overexpressing HDGF in melanocytes. These mice were bred with mice heterozygous for a defective copy of the Ink4a tumor suppressor gene and were exposed to UV light to increase the risk for tumor development both genetically and physiochemically. Mice were analyzed by immunohistochemistry and Western blotting. Furthermore, primary melanocytes were isolated from different strains created. Transgenic animals overexpressed HDGF in hair follicle melanocytes. Interestingly, primary melanocytes isolated from transgenic animals were not able to differentiate in vitro whereas cells isolated from wild type and HDGF-deficient animals were. Although, HDGF -/- /Ink4a +/- mice displayed an increased number of epidermoid cysts after exposure to UV light, no melanomas or premelanocytic alterations could be detected in this mouse model. The results therefore provide no evidence that HDGF has a transforming capacity in tumor development. Our results in combination with previous findings point to a possible role in cell differentiation and suggest that HDGF promotes tumor progression after secondary upregulation and may represent another protein fitting into the concept of non-oncogene addiction of tumor tissue

Does Melanoma Begin in a Melanocyte Stem Cell

International Nuclear Information System (INIS)

Hoerter, J. D.; Bradley, P.; Casillas, A.; Chambers, D.; Weiswasser, B.; Clements, L.; Gilbert, S.; Jiao, A.

2012-01-01

What is the cellular origin of melanoma? What role do melanocyte stem cells (MSC) and other melanocyte precursors play in the development of melanoma? Are MSCs and other latent melanocyte precursors more susceptible to solar radiation? These and many other questions can be very effectively addressed using the zebra fish model. Zebra fish have a robust regenerative capability, permitting the study of how MSCs are regulated and recruited at specific times and places to generate the pigment pattern following fin amputation or melanocyte ablation. They can be used to determine the effects of environmental radiation on the proliferation, survival, repair, and differentiation of MSCs. Our lab is using zebra fish to investigate how UVA- (320-400nm) and UVB- (290-320nm) induced damage to MSCs may contribute to the development of melanoma. A review is given of MSCs in zebrafish as well as experimental techniques and drugs for manipulating MSC populations. These techniques can be used to design experiments to help answer many questions regarding the role of MSCs or melanocyte precursors in the formation of melanoma stem cells and tumors following exposure to UVA/UVB radiation.

Kinase fusions are frequent in Spitz tumors and spitzoid melanomas

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Esteve-Puig, Rosaura; Botton, Thomas; Yeh, Iwei; Lipson, Doron; Otto, Geoff; Brennan, Kristina; Murali, Rajmohan; Garrido, Maria; Miller, Vincent A.; Ross, Jeffrey S; Berger, Michael F.; Sparatta, Alyssa; Palmedo, Gabriele; Cerroni, Lorenzo; Busam, Klaus J.; Kutzner, Heinz; Cronin, Maureen T; Stephens, Philip J; Bastian, Boris C.

2014-01-01

Spitzoid neoplasms are a group of melanocytic tumors with distinctive histopathologic features. They include benign tumors (Spitz nevi), malignant tumors (spitzoid melanomas), and tumors with borderline histopathologic features and uncertain clinical outcome (atypical Spitz tumors). Their genetic underpinnings are poorly understood, and alterations in common melanoma-associated oncogenes are typically absent. Here we show that spitzoid neoplasms harbor kinase fusions of ROS1 (17%), NTRK1 (16%), ALK (10%), BRAF (5%), and RET (3%) in a mutually exclusive pattern. The chimeric proteins are constitutively active, stimulate oncogenic signaling pathways, are tumorigenic, and are found in the entire biologic spectrum of spitzoid neoplasms, including 55% of Spitz nevi, 56% of atypical Spitz tumors, and 39% of spitzoid melanomas. Kinase inhibitors suppress the oncogenic signaling of the fusion proteins in vitro. In summary, kinase fusions account for the majority of oncogenic aberrations in spitzoid neoplasms, and may serve as therapeutic targets for metastatic spitzoid melanomas. PMID:24445538

Long-term Behavior of Serous Borderline Tumors Subdivided Into Atypical Proliferative Tumors and Noninvasive Low-grade Carcinomas

DEFF Research Database (Denmark)

Vang, Russell; Hannibal, Charlotte G; Junge, Jette

2017-01-01

Ovarian serous borderline tumors (SBTs) have been the subject of considerable controversy, particularly with regard to terminology and behavior. It has been proposed that they constitute a heterogenous group of tumors composed, for the most part, of typical SBTs that are benign and designated...... "atypical proliferative serous tumor (APST)" and a small subset of SBTs with micropapillary architecture that have a poor outcome and are designated "noninvasive low-grade serous carcinoma (niLGSC)". It also has been argued that the difference in behavior between the 2 groups is not due to the subtype...... of the primary tumor but rather the presence of extraovarian disease, specifically invasive implants. According to the terminology of the 2014 WHO Classification, typical SBTs are equivalent to APSTs and SBTs displaying micropapillary architecture are synonymous with niLGSC. In addition, "invasive implants" were...

Malign mural nodules associated with serous ovarian tumor of borderline malignancy: a case report and literature review.

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Gungor, Tayfun; Altinkaya, S Ozlem; Akbay, Serap; Bilge, Umit; Mollamahmutoglu, Leyla

2010-03-01

Cystic tumors of ovary, whether benign, borderline, or malignant may be associated with mural nodule of various types, including sarcomas, sarcoma-like mural nodules (SLMN), and foci of anaplastic carcinoma. Cases of serous borderline ovarian tumor with mural nodules of mixed type are very rare. A 54-year-old woman referred with abdominal swelling. Imaging studies revealed a huge mass localized in pelvis and lower abdomen and grade 1-2 left renal hydronephrosis. Preoperative Ca-125 was 798 U/ml. In exploratory laparotomy there was a 16 cm mass adherent to lateral abdominal wall and intestines. Adhesiolysis and de-bulking surgery were performed including bilateral pelvic, para-aortic lymphadenectomy, appendectomy and omentectomy. Left ureter was found to be dilated because of the infiltration of distal part by the tumor, so distal ureteral resection and neoureterocystostomy were performed. Final pathology revealed borderline serous ovarian tumor with mural nodules which were consisted of SLMNs, multiple and sharply demarcated from the adjacent tumor, and sarcomatous nodules showing infiltrative appearance in metastatic regions. Mural nodules showed a positive reaction for vimentin and SMA but were negative for cytokeratin and also necrosis, hemorrhage, and 10-15 mitoses in 10 high power fields were noted. She had postoperative chemotherapy and follow-up is going on without metastases in her first year. The existence of sarcomatous nodules combined with the SLMN necessitates a careful histologic analysis for treatment and the determination of prognosis. However, too few cases of mixed type mural nodules have been published to warrant a conclusion regarding their prognosis.

Pelvic Inflammatory Disease and the Risk of Ovarian Cancer and Borderline Ovarian Tumors: A Pooled Analysis of 13 Case-Control Studies

Science.gov (United States)

Rasmussen, Christina B.; Kjaer, Susanne K.; Albieri, Vanna; Bandera, Elisa V.; Doherty, Jennifer A.; Høgdall, Estrid; Webb, Penelope M.; Jordan, Susan J.; Rossing, Mary Anne; Wicklund, Kristine G.; Goodman, Marc T.; Modugno, Francesmary; Moysich, Kirsten B.; Ness, Roberta B.; Edwards, Robert P.; Schildkraut, Joellen M.; Berchuck, Andrew; Olson, Sara H.; Kiemeney, Lambertus A.; Massuger, Leon F. A. G.; Narod, Steven A.; Phelan, Catherine M.; Anton-Culver, Hoda; Ziogas, Argyrios; Wu, Anna H.; Pearce, Celeste L.; Risch, Harvey A.; Jensen, Allan

2017-01-01

Inflammation has been implicated in ovarian carcinogenesis. However, studies investigating the association between pelvic inflammatory disease (PID) and ovarian cancer risk are few and inconsistent. We investigated the association between PID and the risk of epithelial ovarian cancer according to tumor behavior and histotype. We pooled data from 13 case-control studies, conducted between 1989 and 2009, from the Ovarian Cancer Association Consortium (OCAC), including 9,162 women with ovarian cancers, 2,354 women with borderline tumors, and 14,736 control participants. Study-specific odds ratios were estimated and subsequently combined into a pooled odds ratio using a random-effects model. A history of PID was associated with an increased risk of borderline tumors (pooled odds ratio (pOR) = 1.32, 95% confidence interval (CI): 1.10, 1.58). Women with at least 2 episodes of PID had a 2-fold increased risk of borderline tumors (pOR = 2.14, 95% CI: 1.08, 4.24). No association was observed between PID and ovarian cancer risk overall (pOR = 0.99, 95% CI: 0.83, 1.19); however, a statistically nonsignificantly increased risk of low-grade serous tumors (pOR = 1.48, 95% CI: 0.92, 2.38) was noted. In conclusion, PID was associated with an increased risk of borderline ovarian tumors, particularly among women who had had multiple episodes of PID. Although our results indicated a histotype-specific association with PID, the association of PID with ovarian cancer risk is still somewhat uncertain and requires further investigation. PMID:27941069

Role of Melanin in Melanocyte Dysregulation of Reactive Oxygen Species

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Noah C. Jenkins

2013-01-01

Full Text Available We have recently reported a potential alternative tumor suppressor function for p16 relating to its capacity to regulate oxidative stress and observed that oxidative dysregulation in p16-depleted cells was most profound in melanocytes, compared to keratinocytes or fibroblasts. Moreover, in the absence of p16 depletion or exogenous oxidative insult, melanocytes exhibited significantly higher basal levels of reactive oxygen species (ROS than these other epidermal cell types. Given the role of oxidative stress in melanoma development, we speculated that this increased susceptibility of melanocytes to oxidative stress (and greater reliance on p16 for suppression of ROS may explain why genetic compromise of p16 is more commonly associated with predisposition to melanoma rather than other cancers. Here we show that the presence of melanin accounts for this differential oxidative stress in normal and p16-depleted melanocytes. Thus the presence of melanin in the skin appears to be a double-edged sword: it protects melanocytes as well as neighboring keratinocytes in the skin through its capacity to absorb UV radiation, but its synthesis in melanocytes results in higher levels of intracellular ROS that may increase melanoma susceptibility.

FISH analysis for diagnostic evaluation of challenging melanocytic lesions.

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Zimmermann, A K; Hirschmann, A; Pfeiffer, D; Paredes, B E; Diebold, J

2010-09-01

The differential diagnosis of malignant melanomas and atypical melanocytic nevi is still a diagnostic challenge. The currently accepted morphologic criteria show substantial interobserver variability, likewise immunohistochemical studies are often not able to discriminate these lesions reliably. Techniques that support diagnostic accuracy are of the greatest importance considering the growing incidence of malignant melanomas and their increase in younger patients. In this study we analyzed the feasibility of fluorescence in situ hybridization (FISH) analysis for the discrimination of malignant and benign melanocytic tumors. A panel of DNA probes was used to detect chromosomal aberrations of chromosomes 6 and 11. On a series of 5 clearly malignant and benign melanocytic tumors we confirmed the applicability of the test. Then we focused on examination of ambiguous melanocytic lesions, where atypical cells are often difficult to relocalize in the 4',6-Diamidino-2-phenylindol (DAPI)-fluorescence stain. FISH analyses were conducted on destained H&E-stained slides. By comparison of the DAPI-image with photos taken from the H&E stain, unambiguous assignment of the FISH results to the conspicuous groups of cells was possible. The results of FISH analysis were consistent with the conventional diagnosis in 11 of 14 small ambiguous lesions. Of the remaining 3 cases, 2 showed FISH-results close to the cut-off level. Comparison of FISH results on thin and thick sections revealed that the cut-off values have to be adapted for 2 microm destained sections. In conclusion, FISH analysis is a useful and applicable tool for assessment of even smallest melanocytic neoplasms, although there will remain unclear cases that cannot be solved even after additional FISH evaluation.

A pilot study to image the vascular network of small melanocytic choroidal tumors with speckle noise-free 1050-nm swept source optical coherence tomography (OCT choroidal angiography).

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Maloca, Peter; Gyger, Cyrill; Hasler, Pascal W

2016-06-01

To visualize and measure the vascular network of melanocytic choroidal tumors with speckle noise-free swept source optical coherence tomography (SS-OCT choroidal angiography). Melanocytic choroidal tumors from 24 eyes were imaged with 1050-nm optical coherence tomography (Topcon DRI OCT-1 Atlantis). A semi-automated algorithm was developed to remove speckle noise and to extract and measure the volume of the choroidal vessels from the obtained OCT data. In all cases, analysis of the choroidal vessels could be performed with SS-OCT without the need for pupillary dilation. The proposed method allows speckle noise-free, structure-guided visualization and measurement of the larger choroidal vessels in three dimensions. The obtained data suggest that speckle noise-free OCT may be more effective at identifying choroidal structures than traditional OCT methods. The measured volume of the extracted choroidal vessels of Haller's layer and Sattler's layer in the examined tumorous eyes was on average 0.982463955 mm(3) /982463956 μm(3) (range of 0.209764406 mm(3) /209764405.9 μm(3)to 1.78105544 mm(3) /1781055440 μm(3)). Full thickness obstruction of the choroidal vasculature by the tumor was found in 18 cases (72 %). In seven cases (18 %), choroidal vessel architecture did not show pronounced morphological abnormalities (18 %). Speckle noise-free OCT may serve as a new illustrative imaging technology and enhance visualization of the choroidal vessels without the need for dye injection. OCT can be used to identify and evaluate the choroidal vessels of melanocytic choroidal tumors, and may represent a potentially useful tool for imaging and monitoring of choroidal nevi and melanoma.

Melanocytic lesions in a private pathology practice. Comparison of histologic features in different tumor types with particular reference to dysplastic nevi.

Science.gov (United States)

Hastrup, N; Hou-Jensen, K

1993-11-01

This study reviews a total of 1000 melanocytic lesions--two separate 500 consecutive sample groupings from 1980 and 1989, respectively--diagnosed in a private non-hospital-associated pathology practice. Lesions were classified as lentigo simplex, congenital nevus, "common" nevus, dysplastic nevus, blue nevus, Spitz's nevus or malignant melanoma. A comparison of the two periods reveals an increase in dysplastic nevi from one in 1980 to nine in 1989. The histologic changes in these nevi were compared to those of the other tumors. Pronounced cytologic atypia was seen in the melanocytes of a few "common" nevi, but more often in the dysplastic nevi and in all of the melanomas. Slight nuclear atypia was usual in "common" nevi and lentigines, and also fibroplasia, lymphocytic infiltration, vessel proliferation and pigment incontinence were seen in both "common" nevi and dysplastic nevi. It is concluded that no single histologic variable was specific for dysplastic nevi.

Coat-sleeve type giant congenital melanocytic nevus with intraoral blue nevus: A rare case report

Directory of Open Access Journals (Sweden)

Lata M Kale

2017-01-01

Full Text Available Congenital melanocytic nevi (CMN are visible hyperpigmented (melanocytic, benign, tumor like proliferations in the skin resulting from faulty development of pigment cell precursors in the embryo, and are composed of an abnormal mixture of skin elements. Giant congenital melanocytic nevus (GCMN is usually defined as a melanocytic lesion present at birth that will reach a larger size in adulthood. GCMN is a rare variety of CMN which is characterized by its size (diameter ≥20 cm and the potential for malignant transformation. It is infrequently associated with other findings, which makes the clinical picture complex. In this case, we report a rare association of GCMN with intraoral blue nevus in a 24-year-old male patient.

MR imaging findings of extraovarian endocervical mucinous borderline tumors arising from pelvic endometriosis

International Nuclear Information System (INIS)

Yeo, Dong Myung; Rha, Sung Eun; Byun, Jae Young; Lee, Ahwon; Kim, Mee Ran

2013-01-01

We report MR imaging findings of a rare case of endocervical mucinous borderline tumor (MBT) involving the cul-de-sac and left fallopian tube arising from extensive pelvic endometriosis with pathologic correlation in a 35-year-old woman presented with vague pelvic pain. Endocervical MBT is a type of endometriosis-associated carcinoma. Imaging findings of endocervical MBT are unilocular or oligolocular cystic lesions with enhancing mural nodules, which are different from those of the more common intestinal type MBT.

MR imaging findings of extraovarian endocervical mucinous borderline tumors arising from pelvic endometriosis

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Yeo, Dong Myung; Rha, Sung Eun; Byun, Jae Young; Lee, Ahwon; Kim, Mee Ran [Seoul St. Mary' s Hospital, The Catholic University of Korea, Seoul (Korea, Republic of)

2013-12-15

We report MR imaging findings of a rare case of endocervical mucinous borderline tumor (MBT) involving the cul-de-sac and left fallopian tube arising from extensive pelvic endometriosis with pathologic correlation in a 35-year-old woman presented with vague pelvic pain. Endocervical MBT is a type of endometriosis-associated carcinoma. Imaging findings of endocervical MBT are unilocular or oligolocular cystic lesions with enhancing mural nodules, which are different from those of the more common intestinal type MBT.

Definition and Management of Borderline Resectable Pancreatic Cancer.

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Denbo, Jason W; Fleming, Jason B

2016-12-01

Patients with localized pancreatic ductal adenocarcinoma seek potentially curative treatment, but this group represents a spectrum of disease. Patients with borderline resectable primary tumors are a unique subset whose successful therapy requires a care team with expertise in medical care, imaging, surgery, medical oncology, and radiation oncology. This team must identify patients with borderline tumors then carefully prescribe and execute a combined treatment strategy with the highest possibility of cure. This article addresses the issues of clinical evaluation, imaging techniques, and criteria, as well as multidisciplinary treatment of patients with borderline resectable pancreatic ductal adenocarcinoma. Copyright © 2016 Elsevier Inc. All rights reserved.

Bilateral Borderline Serous Ovarian Tumor Following Three Cycles of Clomiphene Treatment in 19 Years Old Subfertile Woman with Polycystic Ovaries: A Case Report

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Orhan Gelişen

2006-08-01

We also review published case reports of borderline ovarian tumors following ovulation induction to update the medical literature about this rare yet serious condition may be encountered by physicians providing infertility treatment. A borderline ovarian neoplasm in polycystic ovaries should be considered if a patient develops unforeseen ovarian mass (es following ovulation induction.

Sema4D, the ligand for Plexin B1, suppresses c-Met activation and migration and promotes melanocyte survival and growth.

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Soong, Joanne; Chen, Yulin; Shustef, Elina M; Scott, Glynis A

2012-04-01

Semaphorins are secreted and membrane-bound proteins involved in neural pathfinding, organogenesis, and tumor progression, through Plexin and neuropilin receptors. We recently reported that Plexin B1, the Semaphorin 4D (Sema4D) receptor, is a tumor-suppressor protein for melanoma, which functions, in part, through inhibition of the oncogenic c-Met tyrosine kinase receptor. In this report, we show that Sema4D is a protective paracrine factor for normal human melanocyte survival in response to UV irradiation, and that it stimulates proliferation and regulates the activity of the c-Met receptor. c-Met receptor signaling stimulates melanocyte migration, partly through downregulation of the cell adhesion molecule E-cadherin. Sema4D suppressed activation of c-Met in response to its ligand, hepatocyte growth factor (HGF), and partially blocked the suppressive effects of HGF on E-cadherin expression in melanocytes and HGF-dependent migration. These data demonstrate a role for Plexin B1 in maintenance of melanocyte survival and proliferation in the skin, and suggest that Sema4D and Plexin B1 act cooperatively with HGF and c-Met to regulate c-Met-dependent effects in human melanocytes. Because our data show that Plexin B1 is profoundly downregulated by UVB in melanocytes, loss of Plexin B1 may accentuate HGF-dependent effects on melanocytes, including melanocyte migration.

Oncogenic mutations in melanomas and benign melanocytic nevi of the female genital tract.

Science.gov (United States)

Tseng, Diane; Kim, Julie; Warrick, Andrea; Nelson, Dylan; Pukay, Marina; Beadling, Carol; Heinrich, Michael; Selim, Maria Angelica; Corless, Christopher L; Nelson, Kelly

2014-08-01

The genetic heterogeneity of melanomas and melanocytic nevi of the female genital tract is poorly understood. We aim to characterize the frequency of mutations of the following genes: BRAF, NRAS, KIT, GNA11, and GNAQ in female genital tract melanomas. We also characterize the frequency of BRAF mutations in female genital tract melanomas compared with melanocytic nevi. Mutational screening was performed on the following female genital tract melanocytic neoplasms: 25 melanomas, 7 benign melanocytic nevi, and 4 atypical melanocytic nevi. Of the 25 female genital tract melanoma specimens queried, KIT mutations were detected in 4 (16.0%), NRAS mutations in 4 (16.0%), and BRAF mutations in 2 (8.0%) samples. Two of the tumors with KIT mutations harbored double mutations in the same exon. No GNAQ or GNA11 mutations were identified among 11 melanomas screened. BRAF V600E mutations were detected in 7 of 7 benign melanocytic genital nevi (100%) and 3 of 4 atypical genital nevi (75%). Our study is limited by the small sample size of this rare subset of melanomas. KIT, NRAS, and BRAF mutations are found in a subset of female genital tract melanomas. Screening for oncogenic mutations is important for developing and applying clinical therapies for melanomas of the female genital tract. Copyright © 2014 American Academy of Dermatology, Inc. Published by Mosby, Inc. All rights reserved.

Human melanocytes form a PAX3-expressing melanocyte cluster on Matrigel by the cell migration process.

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Choi, Hyunjung; Jin, Sun Hee; Han, Mi Hwa; Lee, Jinyoung; Ahn, Seyeon; Seong, Minjeong; Choi, Hyun; Han, Jiyeon; Cho, Eun-Gyung; Lee, Tae Ryong; Noh, Minsoo

2014-10-01

The interactions between human epidermal melanocytes and their cellular microenvironment are important in the regulation of human melanocyte functions or in their malignant transformation into melanoma. Although the basement membrane extracellular matrix (BM-ECM) is one of major melanocyte microenvironments, the effects of BM-ECM on the human melanocyte functions are not fully explained at a molecular level. This study was aimed to characterize the molecular and cellular interactions between normal human melanocytes (NHMs) and BM-ECM. We investigated cell culture models of normal human melanocytes or melanoma cells on three-dimensional (3D) Matrigel to understand the roles of the basement membrane microenvironment in human melanocyte functions. Melanogenesis and melanobast biomarker expression in both primary human melanocytes and melanoma cells on 3D Matrigel were evaluated. We found that NHMs migrated and formed reversible paired box 3 (PAX3) expressing cell clusters on three-dimensional (3D) Matrigel. The melanogenesis was significantly decreased in the PAX3 expressing cell cluster. The expression profile of PAX3, SOX10, and MITF in the melanocyte cluster on 3D Matrigel was similar to that of melanoblasts. Interestingly, PAX3 and SOX10 showed an inverse expression profile in NHMs, whereas the inverse expression pattern of PAX3 and SOX10 was disrupted in melanoma MNT1 and WM266-4 cells. The human melanocyte culture on 3D Matrigel provides an alternative model system to study functions of human melanoblasts. In addition, this system will contribute to the elucidation of PAX3-related tumorigenic mechanisms to understand human melanoma. Copyright © 2014 Japanese Society for Investigative Dermatology. Published by Elsevier Ireland Ltd. All rights reserved.

Prognostic impact of normalization of serum tumor markers following neoadjuvant chemotherapy in patients with borderline resectable pancreatic carcinoma with arterial contact.

Science.gov (United States)

Murakami, Yoshiaki; Uemura, Kenichiro; Sudo, Takeshi; Hashimoto, Yasushi; Kondo, Naru; Nakagawa, Naoya; Okada, Kenjiro; Takahashi, Shinya; Sueda, Taijiro

2017-04-01

The survival benefit of neoadjuvant therapy for patients with borderline resectable pancreatic carcinoma has been reported recently. However, prognostic factors for this strategy have not been clearly elucidated. The aim of this study was to clarify prognostic factors for patients with borderline resectable pancreatic carcinoma who received neoadjuvant chemotherapy. Medical records of 66 patients with pancreatic carcinoma with arterial contact who intended to undergo tumor resection following neoadjuvant chemotherapy were analyzed retrospectively. Prognostic factors were investigated by analyzing the clinicopathological factors with univariate and multivariate survival analyses. Gemcitabine plus S-1 was generally used as neoadjuvant chemotherapy. The objective response rate was 24%, and normalization of serum tumor markers following neoadjuvant chemotherapy was achieved in 29 patients (44%). Of the 66 patients, 60 patients underwent tumor resection and the remaining six patients did not due to distant metastases following neoadjuvant chemotherapy. For all 66 patients, overall 1-, 2-, and 5-year survival rates were 87.8, 54.5, and 20.5%, respectively (median survival time, 27.1 months) and multivariate analysis revealed that normalization of serum tumor markers was found to be an independent prognostic factor of better overall survival (P = 0.023). Moreover, for 60 patients who undergo tumor resection, normalization of serum tumor markers (P = 0.005) was independently associated with better overall survival by multivariate analysis. Patients with pancreatic carcinoma with arterial contact who undergo neoadjuvant chemotherapy and experience normalization of serum tumor markers thereafter may be good candidates for tumor resection.

Melanoma and melanocytic nevi in decorative tattoos: three case reports.

Science.gov (United States)

Varga, Erika; Korom, Irma; Varga, János; Kohán, József; Kemény, Lajos; Oláh, Judit

2011-12-01

In response to the demands of style and fashion, the number of decorative tattoos has been increasing worldwide. This has been paralleled by a rising incidence of melanocytic proliferations, including melanoma. The coincidence of various dermatological diseases and skin tumors with tattoos has been documented with some frequency, but reports of melanoma associated with tattoos are exceedingly rare. To date, only 13 cases have been documented in the English language literature. The possibility of an association between melanocytic proliferations and tattoos remains an area for further study. This report presents two cases of melanocytic nevi and one of melanoma occurring in association with a decorative tattoos. At present, the pathogenesis of melanoma developing in a tattoo is unknown. Mere coincidence cannot be ruled out. However, trauma, ultraviolet light exposure, a photoallergic effect, or an inflammatory reaction may promote malignant transformation. Clinicians and histopathologists should be aware of the clinical and pathological features if they are to make a correct diagnosis. Copyright © 2011 John Wiley & Sons A/S.

"Surface epithelial changes" in uterine endometrioid carcinoma mimicking micropapillary serous borderline tumor of ovary: report of two cases and review of the literature

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Quddus M Ruhul

2011-01-01

Full Text Available Abstract We encountered two cases of endometrioid carcinoma of uterus with extensive surface epithelial changes (SECs mimicking serous borderline tumor (SBT of the ovary. The first case was a well-differentiated endometrioid carcinoma arising in a background of complex atypical hyperplasia. The second case was moderately-differentiated endometrioid carcinoma with squamous and mucinous differentiation. The SECs comprised of thin microapapillae without hierarchal branching, lined by cuboidal cells with eosinophilic cytoplasm and mild to moderate nuclear atypia. These areas were reminiscent of SBTs of ovary, micropapillary type. This report expands the existing spectrum of SECs. Serous borderline tumor of ovary like surface epithelial changes could be misleading if present in an endometrial biopsy or curettings. Therefore, knowledge of this morphologic variation is important.

Coffee, tea, and caffeine consumption and risk of epithelial ovarian cancer and borderline ovarian tumors

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Gosvig, Camilla F; Kjaer, Susanne K; Blaakær, Jan

2015-01-01

BACKGROUND: Epidemiological studies that have investigated the association between coffee, tea and caffeine consumption and ovarian cancer risk have produced conflicting results. Furthermore, only few studies have examined the role of coffee and tea consumption separately for borderline ovarian...... tumors. By use of data from a large Danish population-based case-control study, we examined the risk of ovarian tumors associated with coffee, tea, and caffeine consumption with a particular focus on characterizing risks by tumor behavior and histology. MATERIAL AND METHODS: From 1995 through 1999, we....... RESULTS: Both coffee (OR = 0.90; 95% CI 0.84-0.97 per cup/day) and total caffeine consumption from coffee and tea combined (OR = 0.93; 95% CI 0.88-0.98 per 100 mg/day) decreased the risk of ovarian cancer. These associations were significant only for the serous and "other" subtypes of ovarian cancer...

Melanoma cell-derived exosomes promote epithelial-mesenchymal transition in primary melanocytes through paracrine/autocrine signaling in the tumor microenvironment

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Xiao, Deyi; Barry, Samantha; Kmetz, Daniel; Egger, Michael; Pan, Jianmin; Rai, Shesh N; Qu, Jifu; McMasters, Kelly M.; Hao, Hongying

2016-01-01

The tumor microenvironment is abundant with exosomes that are secreted by the cancer cells themselves. Exosomes are nanosized, organelle-like membranous structures that are increasingly being recognized as major contributors in the progression of malignant neoplasms. A critical element in melanoma progression is its propensity to metastasize, but little is known about how melanoma cell-derived exosomes modulate the microenvironment to optimize conditions for tumor progression and metastasis. Here, we provide evidence that melanoma cell-derived exosomes promote phenotype switching in primary melanocytes through paracrine/autocrine signaling. We found that the mitogen-activated protein kinase (MAPK) signaling pathway was activated during the exosome-mediated epithelial-to-mesenchymal transition (EMT)-resembling process, which promotes metastasis. Let-7i, an miRNA modulator of EMT, was also involved in this process. We further defined two other miRNA modulators of EMT (miR-191 and let-7a) in serum exosomes for differentiating stage I melanoma patients from non-melanoma subjects. These results provide the first strong molecular evidence that melanoma cell-derived exosomes promote the EMT-resembling process in the tumor microenvironment. Thus, novel strategies targeting EMT and modulating the tumor microenvironment may emerge as important approaches for the treatment of metastatic melanoma. PMID:27063098

UVB-irradiated keratinocytes induce melanoma-associated ganglioside GD3 synthase gene in melanocytes via secretion of tumor necrosis factor α and interleukin 6

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Miyata, Maiko [Department of Life and Medical Sciences, Chubu University Faculty of Life and Health Sciences, Matsumoto, Kasugai 487-8501 (Japan); Department of Biochemistry II, Nagoya University Graduate School of Medicine, 65 Tsurumai, Showa-ku, Nagoya 466-0065 (Japan); Ichihara, Masatoshi; Tajima, Orie; Sobue, Sayaka; Kambe, Mariko [Department of Life and Medical Sciences, Chubu University Faculty of Life and Health Sciences, Matsumoto, Kasugai 487-8501 (Japan); Sugiura, Kazumitsu [Department of Dermatology, Nagoya University Graduate School of Medicine, 65 Tsurumai, Showa-ku, Nagoya 466-0065 (Japan); Furukawa, Koichi, E-mail: koichi@med.nagoya-u.ac.jp [Department of Biochemistry II, Nagoya University Graduate School of Medicine, 65 Tsurumai, Showa-ku, Nagoya 466-0065 (Japan); Furukawa, Keiko [Department of Life and Medical Sciences, Chubu University Faculty of Life and Health Sciences, Matsumoto, Kasugai 487-8501 (Japan); Department of Biochemistry II, Nagoya University Graduate School of Medicine, 65 Tsurumai, Showa-ku, Nagoya 466-0065 (Japan)

2014-03-07

Highlights: • Melanocytes showed low ST8SIA1 and high B3GALT4 levels in contrast with melanomas. • Direct UVB irradiation of melanocytes did not induce ganglioside synthase genes. • Culture supernatants of UVB-irradiated keratinocytes induced ST8SIA1 in melanocytes. • TNFα and IL-6 secreted from keratinocytes enhanced ST8SIA1 expression in melanocytes. • Inflammatory cytokines induced melanoma-related ST8SIA1 in melanocytes. - Abstract: Although expression of gangliosides and their synthetic enzyme genes in malignant melanomas has been well studied, that in normal melanocytes has been scarcely analyzed. In particular, changes in expression levels of glycosyltransferase genes responsible for ganglioside synthesis during evolution of melanomas from melanocytes are very important to understand roles of gangliosides in melanomas. Here, expression of glycosyltransferase genes related to the ganglioside synthesis was analyzed using RNAs from cultured melanocytes and melanoma cell lines. Quantitative RT-PCR revealed that melanomas expressed high levels of mRNA of GD3 synthase and GM2/GD2 synthase genes and low levels of GM1/GD1b synthase genes compared with melanocytes. As a representative exogenous stimulation, effects of ultraviolet B (UVB) on the expression levels of 3 major ganglioside synthase genes in melanocytes were analyzed. Although direct UVB irradiation of melanocytes caused no marked changes, culture supernatants of UVB-irradiated keratinocytes (HaCaT cells) induced definite up-regulation of GD3 synthase and GM2/GD2 synthase genes. Detailed examination of the supernatants revealed that inflammatory cytokines such as TNFα and IL-6 enhanced GD3 synthase gene expression. These results suggest that inflammatory cytokines secreted from UVB-irradiated keratinocytes induced melanoma-associated ganglioside synthase genes, proposing roles of skin microenvironment in the promotion of melanoma-like ganglioside profiles in melanocytes.

UVB-irradiated keratinocytes induce melanoma-associated ganglioside GD3 synthase gene in melanocytes via secretion of tumor necrosis factor α and interleukin 6

International Nuclear Information System (INIS)

Miyata, Maiko; Ichihara, Masatoshi; Tajima, Orie; Sobue, Sayaka; Kambe, Mariko; Sugiura, Kazumitsu; Furukawa, Koichi; Furukawa, Keiko

2014-01-01

Highlights: • Melanocytes showed low ST8SIA1 and high B3GALT4 levels in contrast with melanomas. • Direct UVB irradiation of melanocytes did not induce ganglioside synthase genes. • Culture supernatants of UVB-irradiated keratinocytes induced ST8SIA1 in melanocytes. • TNFα and IL-6 secreted from keratinocytes enhanced ST8SIA1 expression in melanocytes. • Inflammatory cytokines induced melanoma-related ST8SIA1 in melanocytes. - Abstract: Although expression of gangliosides and their synthetic enzyme genes in malignant melanomas has been well studied, that in normal melanocytes has been scarcely analyzed. In particular, changes in expression levels of glycosyltransferase genes responsible for ganglioside synthesis during evolution of melanomas from melanocytes are very important to understand roles of gangliosides in melanomas. Here, expression of glycosyltransferase genes related to the ganglioside synthesis was analyzed using RNAs from cultured melanocytes and melanoma cell lines. Quantitative RT-PCR revealed that melanomas expressed high levels of mRNA of GD3 synthase and GM2/GD2 synthase genes and low levels of GM1/GD1b synthase genes compared with melanocytes. As a representative exogenous stimulation, effects of ultraviolet B (UVB) on the expression levels of 3 major ganglioside synthase genes in melanocytes were analyzed. Although direct UVB irradiation of melanocytes caused no marked changes, culture supernatants of UVB-irradiated keratinocytes (HaCaT cells) induced definite up-regulation of GD3 synthase and GM2/GD2 synthase genes. Detailed examination of the supernatants revealed that inflammatory cytokines such as TNFα and IL-6 enhanced GD3 synthase gene expression. These results suggest that inflammatory cytokines secreted from UVB-irradiated keratinocytes induced melanoma-associated ganglioside synthase genes, proposing roles of skin microenvironment in the promotion of melanoma-like ganglioside profiles in melanocytes

The value of random biopsies, omentectomy, and hysterectomy in operations for borderline ovarian tumors

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Kristensen, Gitte Schultz; Schledermann, Doris; Mogensen, Ole

2014-01-01

OBJECTIVE: Borderline ovarian tumors (BOTs) are treated surgically like malignant ovarian tumors with hysterectomy, salpingectomy, omentectomy, and multiple random peritoneal biopsies in addition to removal of the ovaries. It is, however, unknown how often removal of macroscopically normal......-appearing tissues leads to the finding of microscopic disease. To evaluate the value of random biopsies, omentectomy, and hysterectomy in operations for BOT, the macroscopic and microscopic findings in a cohort of these patients were reviewed retrospectively. MATERIALS: Women treated for BOT at Odense University.......7%) in International Federation of Gynecology and Obstetrics stage I, 9 (12%) in stage II, and 7 (9.3%) in stage III. The histologic subtypes were serous (68%), mucinous (30.7%), and Brenner type (1.3%). Macroscopically radical surgery was performed in 62 patients (82.7%), and 46 (61.3%) received complete staging...

Growth of melanocytes in human epidermal cell cultures

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Staiano-Coico, L.; Hefton, J.M.; Amadeo, C.; Pagan-Charry, I.; Madden, M.R.; Cardon-Cardo, C.

1990-01-01

Epidermal cell cultures were grown in keratinocyte-conditioned medium for use as burn wound grafts; the melanocyte composition of the grafts was studied under a variety of conditions. Melanocytes were identified by immunohistochemistry based on a monoclonal antibody (MEL-5) that has previously been shown to react specifically with melanocytes. During the first 7 days of growth in primary culture, the total number of melanocytes in the epidermal cultures decreased to 10% of the number present in normal skin. Beginning on day 2 of culture, bipolar melanocytes were present at a mean cell density of 116 +/- 2/mm2; the keratinocyte to melanocyte ratio was preserved during further primary culture and through three subpassages. Moreover, exposure of cultures to mild UVB irradiation stimulated the melanocytes to proliferate, suggesting that the melanocytes growing in culture maintained their responsiveness to external stimuli. When the sheets of cultured cells were enzymatically detached from the plastic culture flasks before grafting, melanocytes remained in the basal layer of cells as part of the graft applied to the patient

Histomorphologic spectrum of BAP1 negative melanocytic neoplasms in a family with BAP1-associated cancer susceptibility syndrome.

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Marušić, Zlatko; Buljan, Marija; Busam, Klaus J

2015-06-01

Multiple BAP1 negative melanocytic neoplasms are a hallmark of familial cancer susceptibility syndrome caused by BAP1 germline mutation. The syndrome is characterized by increased incidence of renal cell carcinoma, mesothelioma, cholangiocarcinoma, cutaneous and uveal melanoma and some other neoplasms. We report histomorphologic characteristics of six cutaneous melanocytic neoplasms with loss of BAP1 expression in two members of a family with BAP1-associated cancer susceptibility syndrome. The neoplasms were dermal melanocytic nevi characterized by a proliferation of large epithelioid (spitzoid) melanocytes, and adipocytic metaplasia. Nuclear pseudoinclusions and multinucleated melanocytes were present in most neoplasms. In two of the cases, a nodular melanoma was found associated with a dermal nevus. None of the melanomas recurred or metastasized after 6 and 3 years of follow up. We report two new cases of melanoma arising in a BAP1-deficient melanocytic nevus in the setting of familial tumor predisposition syndrome. Adipocytic metaplasia and nuclear pseudoinclusions may be additional morphologic clues to a BAP1-deficient nevus. It remains to be seen whether these features are more common in familial than sporadic lesions. © 2015 John Wiley & Sons A/S. Published by John Wiley & Sons Ltd.

Ultraviolet Radiation and the Slug Transcription Factor Induce Proinflammatory and Immunomodulatory Mediator Expression in Melanocytes

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Stephanie H. Shirley

2012-01-01

Full Text Available Despite extensive investigation, the precise contribution of the ultraviolet radiation (UVR component of sunlight to melanoma etiology remains unclear. UVR induces keratinocytes to secrete proinflammatory and immunomodulatory mediators that promote inflammation and skin tumor development; expression of the slug transcription factor in keratinocytes is required for maximal production of these mediators. In the present studies we examined the possibility that UVR-exposed melanocytes also produce proinflammatory mediators and that Slug is important in this process. Microarray studies revealed that both UVR exposure and Slug overexpression altered transcription of a variety of proinflammatory mediators by normal human melanocytes; some of these mediators are also known to stimulate melanocyte growth and migration. There was little overlap in the spectra of cytokines produced by the two stimuli. However IL-20 was similarly induced by both stimuli and the NFκB pathway appeared to be important in both circumstances. Further exploration of UVR-induced and Slug-dependent pathways of cytokine induction in melanocytes may reveal novel targets for melanoma therapy.

Multicystic peritoneal mesothelioma after fertility-sparing surgery for an ovarian tumor of borderline malignancy: A case report

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Hidetaka Nomura

2015-02-01

Full Text Available We report a case of a 19-year-old woman with multicystic peritoneal mesothelioma (MCPM who had previously undergone left adnexectomy due to an ovarian tumor of borderline malignancy at the age of 17 years. Follow-up imaging studies after adnexectomy revealed multiple cystic lesions of increasing size and number, suggesting recurrence of the tumor. Diagnostic laparoscopic surgery was performed, and the cystic lesion was pathologically determined to be MCPM. To our knowledge, this is the first report of MCPM diagnosed and successfully treated by laparoscopic surgery during the course of follow-up for an ovarian tumor. It is important to recognize that MCPM can occur in patients who have previously undergone abdominal surgery, and laparoscopic surgery is recommended for patients of reproductive age, because of the potential risk of infertility associated with extensive pelvic surgery.

Premalignant quiescent melanocytic nevi do not express the MHC class I chain-related protein A

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Mercedes B. Fuertes

2011-08-01

Full Text Available The MHC class I chain-related protein A (MICA is an inducible molecule almost not expressed by normal cells but strongly up-regulated in tumor cells. MICA-expressing cells are recognized by natural killer (NK cells, CD8+ aßTCR and ?dTCR T lymphocytes through the NKG2D receptor. Engagement of NKG2D by MICA triggers IFN-? secretion and cytotoxicity against malignant cells. Although most solid tumors express MICA and this molecule is a target during immune surveillance against tumors, it has been observed that high grade tumors from different histotypes express low amounts of cell surface MICA due to a metalloprotease- induced shedding. Also, melanomas develop after a complex process of neotransformation of normal melanocytes. However, the expression of MICA in premalignant stages (primary human quiescent melanocytic nevi remains unknown. Here, we assessed expression of MICA by flow cytometry using cell suspensions from 15 primary nevi isolated from 11 patients. When collected material was abundant, cell lysates were prepared and MICA expression was also analyzed by Western blot. We observed that MICA was undetectable in the 15 primary nevi (intradermic, junction, mixed, lentigo and congenital samples as well as in normal skin, benign lesions (seborrheic keratosis, premalignant lesions (actinic keratosis and benign basocellular cancer. Conversely, a primary recently diagnosed melanoma showed intense cell surface MICA. We conclude that the onset of MICA expression is a tightly regulated process that occurs after melanocytes trespass the stage of malignant transformation. Thus, analysis of MICA expression in tissue sections of skin samples may constitute a useful marker to differentiate between benign and malignant nevi.

Ultraviolet Radiation and the Slug Transcription Factor Induce Pro inflammatory and Immunomodulatory Mediator Expression in Melanocytes

International Nuclear Information System (INIS)

Shirley, S. H.; Kusewitt, D. F.; Grimm, E. A.

2012-01-01

Despite extensive investigation, the precise contribution of the ultraviolet radiation (UVR) component of sunlight to melanoma etiology remains unclear. UVR induces keratinocytes to secrete pro inflammatory and immunomodulatory mediators that promote inflammation and skin tumor development; expression of the slug transcription factor in keratinocytes is required for maximal production of these mediators. In the present studies we examined the possibility that UVR-exposed melanocytes also produce pro inflammatory mediators and that Slug is important in this process. Micro array studies revealed that both UVR exposure and Slug overexpression altered transcription of a variety of pro inflammatory mediators by normal human melanocytes; some of these mediators are also known to stimulate melanocyte growth and migration. There was little overlap in the spectra of cytokines produced by the two stimuli. However IL-20 was similarly induced by both stimuli and the NFκB pathway appeared to be important in both circumstances. Further exploration of UVR-induced and Slug-dependent pathways of cytokine induction in melanocytes may reveal novel targets for melanoma therapy.

Prostaglandin production by melanocytic cells and the effect of alpha-melanocyte stimulating hormone.

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Nicolaou, Anna; Estdale, Sian E; Tsatmali, Marina; Herrero, Daniel Pascual; Thody, Anthony J

2004-07-16

Prostaglandins are potent mediators of the inflammatory response and are also involved in cancer development. In this study, we show that human melanocytes and FM55 melanoma cells express cyclooxygenase-1 and -2 (COX-1 and -2) and thus have the capability to produce prostaglandins. The FM55 cells produced predominantly PGE2 and PGF2alpha, whereas the HaCaT keratinocyte cell line produced mainly PGE2. The anti-inflammatory peptide, alpha-melanocyte stimulating hormone (alpha-MSH), reduced prostaglandin production in FM55 and HaCaT cells and reversed the effect of the pro-inflammatory cytokine TNF-alpha in the former. These results indicate that melanocytes produce prostaglandins and that alpha-MSH, by inhibiting this response, may play an important role in regulating inflammatory responses in the skin.

Malignant and borderline phyllodes tumor of breast treated with a multi-modality approach in a tertiary cancer care centre in North India

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Supriya Mallick

2016-01-01

Full Text Available Background: Phyllodes tumor (PT of the breast can be categorized into benign, borderline and malignant subgroups depending on various histopathological factors. Although malignant PTs may be indolent and controlled by local excision, they frequently show local and distant relapses. Literature reveals local recurrence to be the predominant pattern of failure and thus emphasizes the importance of adjuvant radiation in these tumors. The role of systemic chemotherapy has remained doubtful. Materials and Methods: We have analyzed details of all patients of PT (n = 33 treated with adjuvant multi-modality approach in our institute since 1994–2009. The demographic data, treatment details, recurrence patterns and salvage treatment options were documented. Results: All patients received adjuvant radiation. Seven patients received adjuvant chemotherapy. The mean survival of the entire cohort was 150.618 months. There was a trend for better overall survival with borderline grade (193.6 vs. 160.2 months; P = 0.08, log rank. The disease free survival (DFS favored borderline grade (193.6 months vs. 82.9 months for high grade; P = 0.02, log rank. The DFS was significantly better in tumors having negative margins on postoperative histopathological examination (DFS rate at 5 years being 100% vs. 69.2% for positive or close margins; P = 0.015. The mode of surgery did not have any impact on survival. Conclusion: Adjuvant Radiation should be discussed taking into account surgical margins, size and various pathological factors of the primary. Adjuvant radiation may be utilized in high risk patients to enhance loco-regional control. Systemic chemotherapy is an option, worth exploring, in cases of systemic failure.

A case of melanocytic cervical adenosquamous carcinoma complicated with Cushing's syndrome.

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Chen, Y; Zhang, Y; Wang, L; Yang, X

2017-01-01

To date, cervical carcinoma complicated with Cushing's syndrome were all diagnosed as small cell carcinoma histo- logically, but not adenosquamous carcinoma. Here the authors present the diagnosis, management, and prognosis of a case of melanocytic cervical adenosquamous carcinoma complicated with Cushing's syndrome. A 28-year-old woman was admitted with the chief complaint of post-coital bleeding for one month. Gynecological examination revealed a nodular yellowish-pigmented vegetation (6x5 cm) on the cervix. Laboratory findings proved the diagnosis of Cushing's syndrome. Histopathological diagnosis showed the adenosquamous carcinoma with melanoma differentiation. Immunohistochemical stainings for melanoma A and anti- adrenocorticotropic hormone (ACTH) were positive in the majority of the tumor cells, which indicated that this melanocytic cervical carcinoma lesion was the source of ectopic ACTH production resulting in Cushing's syndrome. This is a unique case of a rare type of cervical carcinoma.

Effect of surgical staging on 539 patients with borderline ovarian tumors: a Turkish Gynecologic Oncology Group study.

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Guvenal, Tevfik; Dursun, Polat; Hasdemir, Pinar S; Hanhan, Merih; Guven, Suleyman; Yetimalar, Hakan; Goksedef, Behice P; Sakarya, Derya K; Doruk, Arzu; Terek, Mustafa C; Saatli, Bahadir; Guzin, Kadir; Corakci, Aydin; Deger, Emek; Celik, Husnu; Cetin, Ahmet; Ozsaran, Aydin; Ozbakkaloglu, Ayşe; Kolusari, Ali; Celik, Cetin; Keles, Refik; Sagir, Fulya G; Dilek, Saffet; Uslu, Turhan; Dikmen, Yilmaz; Altundag, Ozden; Ayhan, Ali

2013-12-01

The objectives of this study were to examine demographic and clinicopathologic characteristics and to determine the effects of primary surgery, surgical staging and the extensiveness of staging. In a retrospective Turkish multicenter study, 539 patients, from 14 institutions, with borderline ovarian tumors were investigated. Some of the demographic, clinical and surgical characteristics of the cases were evaluated. The effects of type of surgery, surgical staging; complete or incomplete staging on survival rates were calculated by using Kaplan-Meier method. The median age at diagnosis was 40 years (range 15-84) and 71.1% of patients were premenopausal. The most common histologic types were serous and mucinous. Majority of the staged cases were in Stage IA (73.5%). 242 patients underwent conservative surgery. Recurrence rates were significantly higher in conservative surgery group (8.3% vs. 3%). Of all patients in this study, 294 (54.5%) have undergone surgical staging procedures. Of the patients who underwent surgical staging, 228 (77.6%) had comprehensive staging including lymphadenectomy. Appendectomy was performed on 204 (37.8%) of the patients. The median follow-up time was 36 months (range 1-120 months). Five-year survival rate was 100% and median survival time was 120 months. Surgical staging, lymph node sampling or dissection and appendectomy didn't cause any difference on survival. Comprehensive surgical staging, lymph node sampling or dissection and appendectomy are not beneficial in borderline ovarian tumors surgical management. © 2013.

Simulants of malignant melanoma

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Gérald E. Piérard

2015-08-01

Full Text Available During the recent period, dermoscopy has yielded improvement in the early disclosure of various atypical melanocytic neoplasms (AMN of the skin. Beyond this clinical procedure, AMN histopathology remains mandatory for establishing their precise diagnosis. Of note, panels of experts in AMN merely report moderate agreement in various puzzling cases. Divergences in opinion and misdiagnosis are likely increased when histopathological criteria are not fine-tuned and when facing a diversity of AMN types. Furthermore, some AMN have been differently named in the literature including atypical Spitz tumor, metastasizing Spitz tumor, borderline and intermediate melanocytic tumor, malignant Spitz nevus, pigmented epithelioid melanocytoma or animal-type melanoma. Some acronyms have been further suggested such as MELTUMP (after melanocytic tumor of uncertain malignant potential and STUMP (after Spitzoid melanocytic tumor of uncertain malignant potential. In this review, such AMN at the exclusion of cutaneous malignant melanoma (MM variants, are grouped under the tentative broad heading skin melanocytoma. Such set of AMN frequently follows an indolent course, although they exhibit atypical and sometimes worrisome patterns or cytological atypia. Rare cases of skin melanocytomas progress to loco regional clusters of lesions (agminate melanocytomas, and even to regional lymph nodes. At times, the distinction between a skin melanocytoma and MM remains puzzling. However, multipronged immunohistochemistry and emerging molecular biology help profiling any malignancy risk if present.

Melanocyte colonization and pigmentation of breast carcinoma

DEFF Research Database (Denmark)

Mele, Marco; Laurberg, Tinne; Engberg Damsgaard, Tine

2012-01-01

. The pathogenesis by which melanocyte migration takes place is not known, but a breached basement membrane is considered essential. Conclusion. Histological examination and additional staining of skin are essential to differentiate breast cancer melanosis from malignant melanoma.......Introduction. Melanocyte colonization of breast carcinoma by nonneoplastic melanocytes of epidermal origin is a rare and serious condition first described in 1977. We report on the exceptional clinical and pathological features of this migration phenomenon in a 74-year-old patient. Discussion...

Polytomous diagnosis of ovarian tumors as benign, borderline, primary invasive or metastatic: development and validation of standard and kernel-based risk prediction models

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Testa Antonia C

2010-10-01

Full Text Available Abstract Background Hitherto, risk prediction models for preoperative ultrasound-based diagnosis of ovarian tumors were dichotomous (benign versus malignant. We develop and validate polytomous models (models that predict more than two events to diagnose ovarian tumors as benign, borderline, primary invasive or metastatic invasive. The main focus is on how different types of models perform and compare. Methods A multi-center dataset containing 1066 women was used for model development and internal validation, whilst another multi-center dataset of 1938 women was used for temporal and external validation. Models were based on standard logistic regression and on penalized kernel-based algorithms (least squares support vector machines and kernel logistic regression. We used true polytomous models as well as combinations of dichotomous models based on the 'pairwise coupling' technique to produce polytomous risk estimates. Careful variable selection was performed, based largely on cross-validated c-index estimates. Model performance was assessed with the dichotomous c-index (i.e. the area under the ROC curve and a polytomous extension, and with calibration graphs. Results For all models, between 9 and 11 predictors were selected. Internal validation was successful with polytomous c-indexes between 0.64 and 0.69. For the best model dichotomous c-indexes were between 0.73 (primary invasive vs metastatic and 0.96 (borderline vs metastatic. On temporal and external validation, overall discrimination performance was good with polytomous c-indexes between 0.57 and 0.64. However, discrimination between primary and metastatic invasive tumors decreased to near random levels. Standard logistic regression performed well in comparison with advanced algorithms, and combining dichotomous models performed well in comparison with true polytomous models. The best model was a combination of dichotomous logistic regression models. This model is available online

Agreement Between Cytology and Histopathology for Regional Lymph Node Metastasis in Dogs With Melanocytic Neoplasms.

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Grimes, Janet A; Matz, Brad M; Christopherson, Pete W; Koehler, Jey W; Cappelle, Kelsey K; Hlusko, Katelyn C; Smith, Annette

2017-07-01

Melanocytic neoplasms are common in dogs and frequently occur within the oral cavity or in haired skin. The behavior of melanocytic neoplasms is variable and depends on tumor location, size, and histopathologic features. This study compared cytopathology and histopathology of 32 lymph nodes from 27 dogs diagnosed with melanocytic neoplasms. Agreement between the original cytology report, cytology slide review, original histopathology report, and histopathology slide review was determined for each lymph node. A subset of lymph nodes was subjected to immunohistochemistry (Melan-A) and additional histochemical stains/techniques (Prussian blue, bleach) to assist in differentiation of melanocytes and melanophages. Agreement ranged from slight to fair for each of the variables evaluated with weighted kappa (κ w ) or kappa (κ) analysis (original cytology vs cytology review κ w = 0.24; original cytology vs original histopathology κ w = 0.007; original cytology vs histopathology review κ w = 0.23; cytology review vs original histopathology κ w = 0.008; cytology review vs histopathology review κ w = 0.006; and original histopathology vs histopathology review κ = 0.18). The diagnoses (metastatic, equivocal, or negative for metastasis) of the original report and slide review for both cytology and histopathology were not significantly correlated with survival in this population of patients. Overall, agreement between cytology and histopathology was poor even with a single clinical or anatomic pathologist performing slide review. Consensus between routine cytology and histopathology for staging of lymph nodes in patients with melanocytic neoplasms is poor and does not correlate with survival.

Tumor-infiltrating CD8+ lymphocytes effect on clinical outcome of muco-cutaneous melanoma

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Mahtab Rahbar

2015-01-01

Full Text Available Background: Recent data have changed our views of prognostic factors in cutaneous melanoma, while some newer methods have yielded better prognostic information. Tumor-infiltrating lymphocytes are believed to represent the immune reaction/response to melanoma cells which is often found in melanocytic cancer. Aim and Objective: We carried out an analysis, aiming to establish pooled estimates for clinical outcomes based on the presence of CD8+ T cell in melanocytic cancer. Materials and Methods: We have included 42 patients with primary cutaneous melanocytic cancer without preoperative treatments in our study. We next analyzed the proliferative activity of CD8+ T cells that infiltrated in tumor cell nests. The intratumoral and adjacent to invasive margin of tumor CD+ T-cell infiltration were analyzed which could also reflect antitumor immunity. Results: The total number of CD8+ cells especially adjacent to invasive margin of tumor was positively correlated with anatomical tumor thickness (P < .001 and not correlated with patient′s age and sex. The stage of tumor which is related to vascular-neural invasion, regional lymph nodes involvement and tumor thickness shows positive correlation with CD8+ infiltration in tumor (P < .004, P < .005, P < .001, respectively. Acral melanoma shows more CD8 lymphocytes infiltration and also recurrence rate of tumor (P < .005. Conclusion: We believe that CD8+ T-cell infiltration in primary cutaneous melanocytic cancer represents the immune reaction/response to melanoma which could be an important new therapy for melanoma although more research is needed on this treatment modality.

Early diagnosis and successful treatment of paraneoplastic melanocytic proliferation.

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Jansen, Joyce C G; Van Calster, Joachim; Pulido, Jose S; Miles, Sarah L; Vile, Richard G; Van Bergen, Tine; Cassiman, Catherine; Spielberg, Leigh H; Leys, Anita M

2015-07-01

Paraneoplastic melanocytic proliferation (bilateral diffuse uveal melanocytic proliferation, BDUMP) is a rare but devastating disease that causes progressive visual loss in patients who usually have an occult malignancy. Visual loss occurs as a result of paraneoplastic changes in the uveal tissue. In a masked fashion, the serum of two patients with BDUMP was evaluated for the presence of cultured melanocyte elongation and proliferation (CMEP) factor using cultured human melanocytes. We evaluated the efficacy of plasmapheresis as a treatment modality early in the disease in conjunction with radiation and chemotherapy. The serum of the first case patient was investigated after plasmapheresis and did not demonstrate proliferation of cultured human melanocytes. The serum of the second case was evaluated prior to treatment with plasmapheresis and did induce this proliferation. These findings are in accordance with the diminution of CMEP factor after plasmapheresis. Treatment with plasmapheresis managed to stabilise the ocular disease progression in both patients. In the past, visual loss due to paraneoplastic melanocytic proliferation was considered progressive and irreversible. We treated two patients successfully with plasmapheresis and demonstrated a relation between CMEP factor in the serum of these patients and proliferation of cultured melanocytes. Published by the BMJ Publishing Group Limited. For permission to use (where not already granted under a licence) please go to http://group.bmj.com/group/rights-licensing/permissions.

Clinical and Pathologic Findings of Spitz Nevi and Atypical Spitz Tumors with ALK Fusions

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Busam, Klaus J; Kutzner, Heinz; Cerroni, Lorenzo; Wiesner, Thomas

2016-01-01

Spitz tumors represent a group of melanocytic neoplasms that typically affects young individuals. Microscopically the lesions are composed of cytologically distinct spindle and epithelioid melanocytes, with a range in the architectural display or the cells, their nuclear features, and secondary epidermal or stromal changes. Recently, kinase fusions have been documented in a subset of Spitz tumors, but there is limited information on the clinical and pathologic features associated with those lesions. Here, we report a series of 17 patients (9 male, 8 female) with spitzoid neoplasms showing ALK fusions (5 Spitz nevi and 12 atypical Spitz tumors). The patients’ ages ranged from 2 years to 35 years (mean = 17; median = 16). Most lesions were located on the lower extremities and presented clinically as polypoid nodules. All tumors were compound melanocytic proliferations with a predominant intradermal growth. Tumor thickness ranged from 1.1 to 6 mm (mean = 2.9 mm; median = 2.5 mm). The most characteristic histopathologic feature of the tumors (seen in all but two lesions) was a plexiform dermal growth of intersecting fascicles of fusiform melanocytes. All but two tumors were amelanotic. All tumors were strongly immunoreactive for ALK. The ALK rearrangements were confirmed in all cases by fluorescence in situ hybridization (FISH) and the fusion partner was determined by quantitative polymerase chain reaction as TPM3 (tropomyosin 3) in 11 cases and DCTN1 (dynactin 1) in 6 cases. None of the eight tumors, which were analyzed by FISH for copy number changes of 6p, 6q, 9p, or 11q met criteria for melanoma. Two patients underwent a sentinel lymph node biopsy, and in both cases melanocytes nests were found in the subcapsular sinus of the node. Array comparative genomic hybridization of these two tumors revealed no chromosomal gains or losses. In conclusion, our study revealed that Spitz nevi/tumors with ALK rearrangement show a characteristic plexiform morphology and that

YY1 regulates melanocyte development and function by cooperating with MITF.

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Juying Li

Full Text Available Studies of coat color mutants have greatly contributed to the discovery of genes that regulate melanocyte development and function. Here, we generated Yy1 conditional knockout mice in the melanocyte-lineage and observed profound melanocyte deficiency and premature gray hair, similar to the loss of melanocytes in human piebaldism and Waardenburg syndrome. Although YY1 is a ubiquitous transcription factor, YY1 interacts with M-MITF, the Waardenburg Syndrome IIA gene and a master transcriptional regulator of melanocytes. YY1 cooperates with M-MITF in regulating the expression of piebaldism gene KIT and multiple additional pigmentation genes. Moreover, ChIP-seq identified genome-wide YY1 targets in the melanocyte lineage. These studies mechanistically link genes implicated in human conditions of melanocyte deficiency and reveal how a ubiquitous factor (YY1 gains lineage-specific functions by co-regulating gene expression with a lineage-restricted factor (M-MITF-a general mechanism which may confer tissue-specific gene expression in multiple lineages.

Complex microcirculation patterns detected by confocal indocyanine green angiography predict time to growth of small choroidal melanocytic tumors: MuSIC Report II.

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Mueller, Arthur J; Freeman, William R; Schaller, Ulrich C; Kampik, Anselm; Folberg, Robert

2002-12-01

Multiple independent laboratories have confirmed the histologic observation that some tumor microcirculation patterns (MCPs) in uveal melanomas are associated strongly with death resulting from metastatic disease. Because these patterns are imageable with confocal indocyanine green angiography (ICG), we designed a prospective study to evaluate whether these angiographically detectable MCPs predict time to tumor growth. Observational case series, prospective, non-randomized. Ninety-eight patients with unilateral, small, choroidal melanocytic tumors. The following information and tumor characteristics were recorded for each patient: demographic parameters, best-corrected visual acuity, intraocular pressure, related visual symptoms, location and dimension of tumor, pigmentation, orange pigment, drusen, tumor-associated hemorrhage, subretinal fluid, and confocal ICG angiographically determined microcirculation patterns-silent (avascularity), normal (preexisting normal choroidal vessels within the tumor), straight vessels, parallel without and with cross-linking, arcs without and with branching, loops, and networks. Time to growth of the tumor, with growth defined as an increase in the maximal apical tumor height of 0.5 mm measured by standardized A-scan ultrasonography, photographic documentation of an increase of the largest basal diameter of at least 1.5 mm, advancement of one tumor border of at least 0.75 mm, or a combination thereof. Twenty-eight of the 98 tumors in this study (29%) met the predetermined criteria for tumor growth. The median time to growth was 127 days (range, 51-625 days). The following tumor characteristics were significantly associated with time to tumor growth: flashes (P = 0.0224), orange pigment (P = 0.012), subretinal fluid (P < 0.001), maximum basal tumor diameter at initial examination (P = 0.015), maximum apical tumor height (P < 0.001), parallel with cross-linking MCP (P < 0.001), arcs with branching MCP (P = 0.006), loops (P < 0

PREFERENTIAL SECRETION OF INDUCIBLE HSP70 BY VITILIGO MELANOCYTES UNDER STRESS

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Mosenson, Jeffrey A.; Flood, Kelsey; Klarquist, Jared; Eby, Jonathan M.; Koshoffer, Amy; Boissy, Raymond E.; Overbeck, Andreas; C.Tung, Rebecca; Poole, I. Caroline Le

2014-01-01

SUMMARY Inducible HSP70 (HSP70i) chaperones peptides from stressed cells, protecting them from apoptosis. Upon extracellular release, HSP70i serves an adjuvant function, enhancing immune responses to bound peptides. We questioned whether HSP70i differentially protects control and vitiligo melanocytes from stress and subsequent immune responses. We compared expression of HSP70i in skin samples, evaluated the viability of primary vitiligo and control melanocytes exposed to bleaching phenols, and measured secreted HSP70i. We determined whether HSP70i traffics to melanosomes to contact immunogenic proteins by cell fractionation, western blotting, electron microscopy and confocal microscopy. Viability of vitiligo and control melanocytes was equally affected under stress. However, vitiligo melanocytes secreted increased amounts of HSP70i in response to MBEH, corroborating with aberrant HSP70i expression in patient skin. Intracellular HSP70i colocalized with melanosomes, and more so in response to MBEH in vitiligo melanocytes. Thus whereas either agent is cytotoxic to melanocytes, MBEH preferentially induces immune responses to melanocytes. PMID:24354861

Targeted deep sequencing of mucinous ovarian tumors reveals multiple overlapping RAS-pathway activating mutations in borderline and cancerous neoplasms

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Mackenzie, Robertson; Kommoss, Stefan; Winterhoff, Boris J.; Kipp, Benjamin R.; Garcia, Joaquin J.; Voss, Jesse; Halling, Kevin; Karnezis, Anthony; Senz, Janine; Yang, Winnie; Prigge, Elena-Sophie; Reuschenbach, Miriam; Doeberitz, Magnus Von Knebel; Gilks, Blake C.; Huntsman, David G.; Bakkum-Gamez, Jamie; McAlpine, Jessica N.; Anglesio, Michael S.

2015-01-01

Mucinous ovarian tumors represent a distinct histotype of epithelial ovarian cancer. The rarest (2-4 % of ovarian carcinomas) of the five major histotypes, their genomic landscape remains poorly described. We undertook hotspot sequencing of 50 genes commonly mutated in human cancer across 69 mucinous ovarian tumors. Our goals were to establish the overall frequency of cancer-hotspot mutations across a large cohort, especially those tumors previously thought to be “RAS-pathway alteration negative”, using highly-sensitive next-generation sequencing as well as further explore a small number of cases with apparent heterogeneity in RAS-pathway activating alterations. Using the Ion Torrent PGM platform, we performed next generation sequencing analysis using the v2 Cancer Hotspot Panel. Regions of disparate ERBB2-amplification status were sequenced independently for two mucinous carcinoma (MC) cases, previously established as showing ERBB2 amplification/overexpression heterogeneity, to assess the hypothesis of subclonal populations containing either KRAS mutation or ERBB2 amplification independently or simultaneously. We detected mutations in KRAS, TP53, CDKN2A, PIK3CA, PTEN, BRAF, FGFR2, STK11, CTNNB1, SRC, SMAD4, GNA11 and ERBB2. KRAS mutations remain the most frequently observed alteration among MC (64.9 %) and mucinous borderline tumors (MBOT) (92.3 %). TP53 mutation occurred more frequently in carcinomas than borderline tumors (56.8 % and 11.5 %, respectively), and combined IHC and mutation data suggest alterations occur in approximately 68 % of MC and as many as 20 % of MBOT. Proven and potential RAS-pathway activating changes were observed in all but one MC. Concurrent ERBB2 amplification and KRAS mutation were observed in a substantial number of cases (7/63 total), as was co-occurrence of KRAS and BRAF mutations (one case). Microdissection of ERBB2-amplified regions of tumors harboring KRAS mutation suggests these alterations are occurring in the same cell

Melanogenesis in dermal melanocytes of Japanese Silky chicken embryos.

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Ortolani-Machado, C F; Freitas, P F; Faraco, C D

2009-08-01

The Japanese Silky chicken (SK) shows dermal and visceral hyperpigmentation. This study characterizes ultrastructurally the melanin granules developing in dermal melanocytes of the dorsal skin of SK, in an attempt to better understand the processes of melanogenesis in these permanently ectopic cells. The steps of melanogenesis are similar to those described for epidermal melanocytes, with melanosomes going from stage I to IV but, in SK, the maturation occurs in the cell body, as well as in the cytoplasmic processes. At stage III, the deposition of melanin is cumulative and can aggregate in rounded structures, which combine to turn into the mature granule. The final destiny of mature melanosomes is still unclear, although it was observed that dermal macrophages can accumulate melanin granules in their phagosomes. Even with the close proximity between melanocytes and other dermal cells, the transference of melanosomes was not observed. Our findings indicate that melanogenesis in dermal melanocytes in SK has the same morphological characteristics found in epidermal melanocytes, but the functional aspect still remains to be elucidated.

Hesperetin induces melanin production in adult human epidermal melanocytes.

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Usach, Iris; Taléns-Visconti, Raquel; Magraner-Pardo, Lorena; Peris, José-Esteban

2015-06-01

One of the major sources of flavonoids for humans are citrus fruits, hesperidin being the predominant flavonoid. Hesperetin (HSP), the aglycon of hesperidin, has been reported to provide health benefits such as antioxidant, anti-inflammatory and anticarcinogenic effects. However, the effect of HSP on skin pigmentation is not clear. Some authors have found that HSP induces melanogenesis in murine B16-F10 melanoma cells, which, if extrapolated to in vivo conditions, might protect skin against photodamage. Since the effect of HSP on normal melanocytes could be different to that observed on melanoma cells, the described effect of HSP on murine melanoma cells has been compared to the effect obtained using normal human melanocytes. HSP concentrations of 25 and 50 µM induced melanin synthesis and tyrosinase activity in human melanocytes in a concentration-dependent manner. Compared to control melanocytes, 25 µM HSP increased melanin production and tyrosinase activity 1.4-fold (p melanin production in human melanocyte cultures could be reproduced on human skin. Copyright © 2015 Elsevier Ltd. All rights reserved.

MicroRNA expression in melanocytic nevi: the usefulness of formalin-fixed, paraffin-embedded material for miRNA microarray profiling.

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Glud, Martin; Klausen, Mikkel; Gniadecki, Robert; Rossing, Maria; Hastrup, Nina; Nielsen, Finn C; Drzewiecki, Krzysztof T

2009-05-01

MicroRNAs (miRNAs) are small, noncoding RNA molecules that regulate cellular differentiation, proliferation, and apoptosis. MiRNAs are expressed in a developmentally regulated and tissue-specific manner. Aberrant expression may contribute to pathological processes such as cancer, and miRNA may therefore serve as biomarkers that may be useful in a clinical environment for diagnosis of various diseases. Most miRNA profiling studies have used fresh tissue samples. However, in some types of cancer, including malignant melanoma, fresh material is difficult to obtain from primary tumors, and most surgical specimens are formalin fixed and paraffin embedded (FFPE). To explore whether FFPE material would be suitable for miRNA profiling in melanocytic lesions, we compared miRNA expression patterns in FFPE versus fresh frozen samples, obtained from 15 human melanocytic nevi. Out of microarray data, we identified 84 miRNAs that were expressed in both types of samples and represented an miRNA profile of melanocytic nevi. Our results showed a high correlation in miRNA expression (Spearman r-value of 0.80) between paired FFPE and fresh frozen material. The data were further validated by quantitative RT-PCR. In conclusion, FFPE specimens of melanocytic lesions are suitable as a source for miRNA microarray profiling.

Parity, infertility, oral contraceptives, and hormone replacement therapy and the risk of ovarian serous borderline tumors

DEFF Research Database (Denmark)

Rasmussen, Emma L Kaderly; Hannibal, Charlotte Gerd; Dehlendorff, Christian

2017-01-01

OBJECTIVE: Few studies have examined the risk of an ovarian serous borderline tumor (SBT) associated with parity, infertility, oral contraceptives (OCs), or hormone replacement therapy (HRT), which was the study aim. METHODS: This nationwide case-control study included all women with an SBT...... diagnosis in Denmark, 1978-2002. SBTs were confirmed by centralized expert pathology review. For each case, 15 age-matched female controls were randomly selected using risk-set sampling. Cases and controls with previous cancer (except for non-melanoma skin cancer) and controls with bilateral oophorectomy...... or salpingo-oophorectomy were excluded. Conditional logistic regression was used to estimate adjusted odds ratios (ORs) and 95% confidence intervals (CIs). RESULTS: We found a strongly decreased risk of SBTs among parous women which decreased with increasing number of children (p

Fascin and EMMPRIN expression in primary mucinous tumors of ovary: a tissue microarray study.

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Alici, Omer; Kefeli, Mehmet; Yildiz, Levent; Baris, Sancar; Karagoz, Filiz; Kandemir, Bedri

2014-12-01

The aim of this study was to compare the expressions of fascin and EMMPRIN in primary malignant, borderline and benign mucinous ovarian tumors, and to investigate the relationship of these markers with tumor progression and their applicability to differential diagnosis. An immunohistochemical study was performed for fascin and EMMPRIN using the tissue microarray technique. Eighty-one cases were included in the study; there were 37 benign, 25 borderline and 19 malignant primary mucinous ovarian tumors. For each case, a total staining score was determined, consisting of scores for extent of staining and intensity of staining. The cases were allocated to negative, weakly positive and strongly positive staining categories, according to the total staining score. Both of the markers were significantly negative in benign tumors as compared with borderline and malignant tumors. There was no significant difference between borderline and malignant groups for both markers. Sixty-eight percent of malignant tumors were stained positive by fascin, while this rate was 40% for borderline mucinous tumors. All malignant tumors were strongly stained positive for EMMPRIN, while this rate was 92% for borderline mucinous tumors. The rest of the cases stained weakly positive. No significant difference in staining score was found between fascin and EMMPRIN expression. In ovarian primary mucinous tumors, fascin and EMMPRIN may play an important role in tumor progression from benign tumor to carcinoma. In that context, EMMPRIN and fascin expression may have potential application in the differential diagnosis of some diagnostically problematic mucinous ovarian tumors. However, the differential diagnostic applicability of EMMPRIN appears to be more limited than that of fascin due to its wide spectrum of staining in mucinous ovarian tumors. Copyright © 2014 Elsevier GmbH. All rights reserved.

Ultraviolet B, melanin and mitochondrial DNA: Photo-damage in human epidermal keratinocytes and melanocytes modulated by alpha-melanocyte-stimulating hormone [version 1; referees: 2 approved

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Markus Böhm

2016-05-01

Full Text Available Alpha-melanocyte-stimulating hormone (alpha-MSH increases melanogenesis and protects from UV-induced DNA damage. However, its effect on mitochondrial DNA (mtDNA damage is unknown. We have addressed this issue in a pilot study using human epidermal keratinocytes and melanocytes incubated with alpha-MSH and irradiated with UVB. Real-time touchdown PCR was used to quantify total and deleted mtDNA. The deletion detected encompassed the common deletion but was more sensitive to detection. There were 4.4 times more mtDNA copies in keratinocytes than in melanocytes. Irradiation alone did not affect copy numbers. Alpha-MSH slightly increased copy numbers in both cell types in the absence of UVB and caused a similar small decrease in copy number with dose in both cell types. Deleted copies were nearly twice as frequent in keratinocytes as in melanocytes. Alpha-MSH reduced the frequency of deleted copies by half in keratinocytes but not in melanocytes. UVB dose dependently led to an increase in the deleted copy number in alpha-MSH-treated melanocytes. UVB irradiation had little effect on deleted copy number in alpha-MSH-treated keratinocytes. In summary, alpha-MSH enhances mtDNA damage in melanocytes presumably by increased melanogenesis, while α-MSH is protective in keratinocytes, the more so in the absence of irradiation.

The slaty mutation affects the morphology and maturation of melanosomes in the mouse melanocytes.

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Hirobe, Tomohisa; Abe, Hiroyuki

2006-10-01

The slaty (Dct(slt)) mutation is known to reduce the activity of dopachrome tautomerase in melanocytes and to reduce the melanin content in skin, hairs and eyes. Although the melanosomes in slaty melanocytes are reported to be eumelanosome-like, detailed melanosome biogenesis is not well studied. To address this point, melanosomes in neonatal epidermal melanocytes from wild-type (Dct+/Dct+) mice at the slaty locus as well as its congenic mouse mutant (Dct(slt)/Dct(slt)) in serum-free primary culture were observed under the electron microscope. Wild-type melanocytes possessed exclusively elliptical melanosomes with internal longitudinal structures, whereas in mutant melanocytes, numerous spherical melanosomes with globular depositions of pigment and elliptical melanosomes as well as mixed type of the two melanosomes were observed. Mature stage IV melanosomes were greatly decreased in mutant melanocytes, whereas immature stage III melanosomes were more numerous than in wild-type melanocytes. These results suggest that the slaty mutation affects the morphology and maturation of melanosomes in mouse melanocytes.

Neurotized congenital melanocytic nevus resembling a pigmented neurofibroma

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Nidhi Singh

2015-01-01

Full Text Available Neurotized congenital melanocytic nevus and pigmented neurofibroma (PNF are close mimics and pose a clinicopathological challenge. We present a case of pigmented hypertrichotic plaque over lumbosacral region and discuss the differential diagnosis and its clinical, histopathological and immunohistochemistry features which may aid in differentiation. We highlight the difficulties faced in differentiating neurotized congenital melanocytic nevus from pigmented neurofibroma.

Giant Congenital Melanocytic Nevus

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Rasmussen, Bo Sonnich; Henriksen, Trine Foged; Kølle, Stig-Frederik Trojahn

2015-01-01

Giant congenital melanocytic nevi (GCMN) occur in 1:20,000 livebirths and are associated with increased risk of malignant transformation. The treatment of GCMN from 1981 to 2010 in a tertiary referral center was reviewed evaluating the modalities used, cosmetic results, associated complications...

Surgical management and perioperative morbidity of patients with primary borderline ovarian tumor (BOT).

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Trillsch, Fabian; Ruetzel, Jan David; Herwig, Uwe; Doerste, Ulrike; Woelber, Linn; Grimm, Donata; Choschzick, Matthias; Jaenicke, Fritz; Mahner, Sven

2013-07-09

Surgery is the cornerstone for clinical management of patients with borderline ovarian tumors (BOT). As these patients have an excellent overall prognosis, perioperative morbidity is the critical point for decision making when the treatment strategy is developed and the primary surgical approach is defined. Clinical and surgical parameters of patients undergoing surgery for primary BOT at our institutions between 1993 and 2008 were analyzed with regard to perioperative morbidity depending on the surgical approach (laparotomy vs. laparoscopy). A total of 105 patients were analyzed (44 with primary laparoscopy [42%], 61 with primary laparotomy [58%]). Complete surgical staging was achieved in 33 patients at primary surgical approach (31.4%) frequently leading to formal indication of re-staging procedures. Tumor rupture was significantly more frequent during laparoscopy compared to laparotomy (29.5% vs. 13.1%, p = 0.038) but no other intraoperative complications were seen in laparoscopic surgery in contrast to 7 of 61 laparotomies (0% vs. 11.5%, p = 0.020). Postoperative complication rates were similar in both groups (19.7% vs. 18.2%, p = 0.848). Irrespective of the surgical approach, surgical management of BOT has acceptable rates of perioperative complications and morbidity. Choice of initial surgical approach can therefore be made independent of complication-concerns. As the recently published large retrospective AGO ROBOT study observed similar oncologic outcome for both approaches, laparoscopy can be considered for staging of patients with BOT if this appears feasible. An algorithm for the surgical management of BOT patients has been developed.

Population-Based Analysis of Histologically Confirmed Melanocytic Proliferations Using Natural Language Processing.

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Lott, Jason P; Boudreau, Denise M; Barnhill, Ray L; Weinstock, Martin A; Knopp, Eleanor; Piepkorn, Michael W; Elder, David E; Knezevich, Steven R; Baer, Andrew; Tosteson, Anna N A; Elmore, Joann G

2018-01-01

Population-based information on the distribution of histologic diagnoses associated with skin biopsies is unknown. Electronic medical records (EMRs) enable automated extraction of pathology report data to improve our epidemiologic understanding of skin biopsy outcomes, specifically those of melanocytic origin. To determine population-based frequencies and distribution of histologically confirmed melanocytic lesions. A natural language processing (NLP)-based analysis of EMR pathology reports of adult patients who underwent skin biopsies at a large integrated health care delivery system in the US Pacific Northwest from January 1, 2007, through December 31, 2012. Skin biopsy procedure. The primary outcome was histopathologic diagnosis, obtained using an NLP-based system to process EMR pathology reports. We determined the percentage of diagnoses classified as melanocytic vs nonmelanocytic lesions. Diagnoses classified as melanocytic were further subclassified using the Melanocytic Pathology Assessment Tool and Hierarchy for Diagnosis (MPATH-Dx) reporting schema into the following categories: class I (nevi and other benign proliferations such as mildly dysplastic lesions typically requiring no further treatment), class II (moderately dysplastic and other low-risk lesions that may merit narrow reexcision with skin biopsies, performed on 47 529 patients, were examined. Nearly 1 in 4 skin biopsies were of melanocytic lesions (23%; n = 18 715), which were distributed according to MPATH-Dx categories as follows: class I, 83.1% (n = 15 558); class II, 8.3% (n = 1548); class III, 4.5% (n = 842); class IV, 2.2% (n = 405); and class V, 1.9% (n = 362). Approximately one-quarter of skin biopsies resulted in diagnoses of melanocytic proliferations. These data provide the first population-based estimates across the spectrum of melanocytic lesions ranging from benign through dysplastic to malignant. These results may serve as a foundation for future

The relationship between Na+/H+ exchanger expression and tyrosinase activity in human melanocytes

International Nuclear Information System (INIS)

Smith, Dustin R.; Spaulding, Deborah T.; Glenn, Hayden M.; Fuller, Bryan B.

2004-01-01

The activity of melanosome-associated tyrosinase in human melanocytes differs based on racial skin type. In melanocytes from Black skin, tyrosinase activity is high while in White melanocytes the activity of the enzyme is low. Recent studies suggest that low tyrosinase activity in White melanocytes may be due to an acidic pH environment within the melanosome. Because sodium/hydrogen (Na + /H + ) exchangers (NHEs) are known to regulate intracellular pH, melanocytes were treated with NHE inhibitors to determine what effect this inhibition might have on tyrosinase activity. Treatment of Black melanocytes with ethyl-isopropyl amiloride (EIPA) caused a rapid dose-dependent inhibition of tyrosinase activity. This inhibition was not due to either direct enzyme inhibition or to a decrease in tyrosinase abundance. In contrast, treatment of White melanocytes with EIPA, cimetidine, or clonidine resulted in little inhibition of tyrosinase activity. Reverse transcriptase-polymerase chain reaction (RT-PCR) and Western blot analysis showed that both Black and White melanocytes expressed mRNA and protein for NHE-1, NHE-3, NHE-5, NHE-6, and NHE-7. Immunohistochemical analysis showed that NHE-7 and NHE-3 co-localized with the melanosomal protein, Tyrosinase Related Protein-1 (TRP-1). In addition, the vesicular proton pump, vesicular ATPase (V-ATPase), was found to be present in both White and Black melanosomes, indicating that organelles from both racial skin types are capable of being acidified. The results suggest that one or more NHEs may help regulate melanosome pH and tyrosinase activity in human melanocytes

Melanocyte pigmentation inversely correlates with MCP-1 production and angiogenesis-inducing potential.

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Adini, Irit; Adini, Avner; Bazinet, Lauren; Watnick, Randolph S; Bielenberg, Diane R; D'Amato, Robert J

2015-02-01

The incidence of certain angiogenesis-dependent diseases is higher in Caucasians than in African Americans. Angiogenesis is amplified in wound healing and cornea models in albino C57 mice compared with black C57 mice. Moreover, mouse and human melanocytes with low pigmentation stimulate endothelial cell (EC) proliferation and migration in vitro more than melanocytes with high pigmentation. This effect is due, in part, to the secretion of an angiogenic protein called fibromodulin (FMOD) from lowly pigmented melanocytes. Herein, we expand upon the mechanism contributing to increased angiogenesis in lighter skin and report that monocyte chemotactic protein-1 (MCP-1) is secreted by nonpigmented mouse melanocytes by 5- to 10-fold more than pigmented melanocytes. MCP-1 protein stimulates EC proliferation and migration in vitro and angiogenesis in vivo. Mechanistic studies determine that FMOD is upstream of MCP-1 and promotes its secretion from both melanocytes and activated ECs via stimulation of NF-κB activity. Mice injected with FMOD-neutralizing antibodies show 2.3-fold decreased levels of circulating MCP-1. Human studies confirmed that, on average, Caucasians have 2-fold higher serum levels of MCP-1 than African Americans. Taken together, this study implicates the FMOD/MCP-1 pathway in the regulation of angiogenesis by local melanocytes and suggests that melanogenic activity may protect against aberrant angiogenic diseases. © FASEB.

Phyllodes malignant mammary tumors:communication of three cases

International Nuclear Information System (INIS)

Beschizza, V.; Rosasco, M.; Episcopo, S.; Dorfman, N.; Centurion, D.

2003-01-01

Three cases of phyllode malignant mammary tumors were studied in the Anatomo-Pathology Chair of the Montevideo, Uruguay.The discussion covered epidemiology, morphologic staging and biological significance of phyllode tumor within the broader spectrum of libro-epithelial breast tumors.An overview of literature shows that histo-pathological criteria recommended by world Health Organization(WHO) are the ones which determine the behaviour of phyllode mammary tumors, wheter bening, malignant of borderline.Prognostic factors of metastases are those involved in stroma overgrowth, anaplasia high mitotic index and infiltrative edge of tumor.None of the clinical aspects,including tumor size, are significant from the viewpoint of prognosis.Efective treatment is broad extended surgical excision (adequate margins),mastectomy being reserved for large tummors that are borderline, malignant or recurrent

Effect of nicotine on melanogenesis and antioxidant status in HEMn-LP melanocytes

International Nuclear Information System (INIS)

Delijewski, Marcin; Beberok, Artur; Otręba, Michał; Wrześniok, Dorota; Rok, Jakub; Buszman, Ewa

2014-01-01

Nicotine is a natural ingredient of tobacco plants and is responsible for the addictive properties of tobacco. Nowadays nicotine is also commonly used as a form of smoking cessation therapy. It is suggested that nicotine may be accumulated in human tissues containing melanin. This may in turn affect biochemical processes in human cells producing melanin. The aim of this study was to examine the effect of nicotine on melanogenesis and antioxidant status in cultured normal human melanocytes HEMn-LP. Nicotine induced concentration-dependent loss in melanocytes viability. The value of EC 50 was determined to be 7.43 mM. Nicotine inhibited a melanization process in human light pigmented melanocytes and caused alterations of antioxidant defense system. Significant changes in cellular antioxidant enzymes: superoxide dismutase and catalase activities and in hydrogen peroxide content were stated. The obtained results may explain a potential influence of nicotine on biochemical processes in melanocytes in vivo during long term exposition to nicotine. - Graphical abstract: Nicotine inhibits melanogenesis and induces oxidative stress in HEMn-LP melanocytes. - Highlights: • Nicotine induces concentration-dependent loss in melanocytes viability. • Nicotine in non-cytotoxic concentrations inhibits melanogenesis. • Nicotine in higher concentrations induces oxidative stress

Effect of nicotine on melanogenesis and antioxidant status in HEMn-LP melanocytes

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Delijewski, Marcin; Beberok, Artur; Otręba, Michał; Wrześniok, Dorota; Rok, Jakub; Buszman, Ewa, E-mail: ebuszman@sum.edu.pl

2014-10-15

Nicotine is a natural ingredient of tobacco plants and is responsible for the addictive properties of tobacco. Nowadays nicotine is also commonly used as a form of smoking cessation therapy. It is suggested that nicotine may be accumulated in human tissues containing melanin. This may in turn affect biochemical processes in human cells producing melanin. The aim of this study was to examine the effect of nicotine on melanogenesis and antioxidant status in cultured normal human melanocytes HEMn-LP. Nicotine induced concentration-dependent loss in melanocytes viability. The value of EC{sub 50} was determined to be 7.43 mM. Nicotine inhibited a melanization process in human light pigmented melanocytes and caused alterations of antioxidant defense system. Significant changes in cellular antioxidant enzymes: superoxide dismutase and catalase activities and in hydrogen peroxide content were stated. The obtained results may explain a potential influence of nicotine on biochemical processes in melanocytes in vivo during long term exposition to nicotine. - Graphical abstract: Nicotine inhibits melanogenesis and induces oxidative stress in HEMn-LP melanocytes. - Highlights: • Nicotine induces concentration-dependent loss in melanocytes viability. • Nicotine in non-cytotoxic concentrations inhibits melanogenesis. • Nicotine in higher concentrations induces oxidative stress.

Usefulness of confocal microscopy in distinguishing between basal cell carcinoma and intradermal melanocytic nevus on the face.

Science.gov (United States)

Gamo, R; Floristan, U; Pampín, A; Caro, D; Pinedo, F; López-Estebaranz, J L

2015-10-01

The clinical distinction between basal cell carcinoma (BCC) and intradermal melanocytic nevus lesions on the face can be difficult, particularly in young patients or patients with multiple nevi. Dermoscopy is a useful tool for analyzing characteristic dermoscopic features of BCC, such as cartwheel structures, maple leaf-like areas, blue-gray nests and dots, and ulceration. It also reveals arborizing telangiectatic vessels and prominent curved vessels, which are typical of BCC, and comma vessels, which are typical of intradermal melanocytic nevi. It is, however, not always easy to distinguish between these 2 conditions, even when dermoscopy is used. We describe 2 facial lesions that posed a clinical and dermoscopic challenge in two 38-year-old patients; confocal microscopy showed separation between tumor nests and stroma and polarized nuclei, which are confocal microscopy features of basal cell carcinoma. Copyright © 2014 Elsevier España, S.L.U. y AEDV. All rights reserved.

Isolation and culture of melanocytes from the arctic fox (Alopex lagopus

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Jiarong Bao

2015-09-01

Full Text Available Coat colour is a phenotypic marker of fur animal species, which was determined by the pigment generated from melanocytes. In this study, we developed and validated a method for isolation, purification and passage culture of melanocytes from the arctic fox (Alopex lagopus. Skin biopsies were harvested from the dorsal region of adult foxes and enzyme digestion by Dispase II. The primary culture of melanocytes from arctic fox skin was obtained by using keratinocyte serum-free medium supplemented with epidermal growth factor and bovine pituitary extract with/without phorbol- 12-myristate-13-acetate, and by carrying out a medium change strategy. After serial passages, it yielded pure population of melanocytes, which become efficient tools for investigating the function of colour genes and unraveling the process of melanin synthesis.

Papillary Tubal Hyperplasia. The Putative Precursor of Ovarian Atypical Proliferative (Borderline) Serous Tumors, Noninvasive Implants and Endosalpingiosis

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Kurman, Robert J.; Vang, Russell; Junge, Jette; Hannibal, Charlotte Gerd; Kjaer, Susanne K.; Shih, Ie-Ming

2011-01-01

In contrast to the controversy regarding the terminology and behavior of ovarian noninvasive low-grade serous tumors (atypical proliferative serous tumor [APST] and serous borderline tumor [SBT]), little attention has been directed to their origin. Similarly, until recently, proliferative lesions in the fallopian tube have not been extensively studied. The recent proposal that ovarian high-grade serous carcinomas are derived from intraepithelial carcinoma in the fallopian tube prompted us to evaluate the possible role of the fallopian tube in the genesis of low-grade serous tumors. We have identified a lesion, designated “papillary tubal hyperplasia (PTH)”, characterized by small rounded clusters of tubal epithelial cells and small papillae, with or without associated psammoma bodies, that are present within the tubal lumen and which are frequently associated with APSTs. Twenty-two cases in this study were selected from a population-based study in Denmark of approximately 1000 patients with low-grade ovarian serous tumors in whom implants were identified on the fallopian tube. Seven additional cases were seen recently in consultation at The Johns Hopkins Hospital (JHH). These 7 cases were not associated with an ovarian tumor. Papillary tubal hyperplasia was found in 20 (91%) of the 22 cases in the Danish study. Based on this association of PTH with APSTs with implants and the close morphologic resemblance of PTH, not only to the primary ovarian APSTs but also to the noninvasive epithelial implants and endosalpingiosis, we speculate that the small papillae and clusters of cells from the fallopian tubes implant on ovarian and peritoneal surfaces to produce these lesions. The 7 JHH cases of PTH that were not associated with an ovarian tumor support the view that PTH is the likely precursor lesion. We propose a model for the development of ovarian and extraovarian low-grade serous proliferations (APST, noninvasive epithelial implants and endosalpingiosis) that

[Effect of Tribulus terrestris extract on melanocyte-stimulating hormone expression in mouse hair follicles].

Science.gov (United States)

Yang, Liu; Lu, Jian-wei; An, Jing; Jiang, Xuan

2006-12-01

To observe the effect of Tribulus terrestris extract on melanocyte stimulating hormone (MSH) expression in C57BL/6J mouse hair follicles, and investigate the role of Tribulus terrestris extract in activation, proliferation, epidermal migration of dormant hair follicle melanocytes. The aqueous extract of Tribulus terrestris was administered orally in specific pathogen-free C57BL/6J mouse at the daily dose equivalent to 1 g/1 kg in adult human, and the expression and distribution of MSH in the mouse hair follicles was observed with immunohistochemistry. The positivity rate of MSH expression in the hair follicle melanocytes was 75% in mice treated with the extract, significantly higher than the rate of only 18.75% in the control group (PTribulus terrestris can significantly increase MSH expression in the hair follicle melanocytes by activating tyrosinase activity and promoting melanocyte proliferation, melanine synthesis, and epidermal migration of dormant melanocytes.

Genetic and biochemical evidence that haploinsufficiency of the Nf1 tumor suppressor gene modulates melanocyte and mast cell fates in vivo.

Science.gov (United States)

Ingram, D A; Yang, F C; Travers, J B; Wenning, M J; Hiatt, K; New, S; Hood, A; Shannon, K; Williams, D A; Clapp, D W

2000-01-03

Neurofibromatosis type 1 (NF1) is a common autosomal-dominant disorder characterized by cutaneous neurofibromas infiltrated with large numbers of mast cells, melanocyte hyperplasia, and a predisposition to develop malignant neoplasms. NF1 encodes a GTPase activating protein (GAP) for Ras. Consistent with Knudson's "two hit" model of tumor suppressor genes, leukemias and malignant solid tumors in NF1 patients frequently demonstrate somatic loss of the normal NF1 allele. However, the phenotypic and biochemical consequences of heterozygous inactivation of Nf1 are largely unknown. Recently neurofibromin, the protein encoded by NF1, was shown to negatively regulate Ras activity in Nf1-/- murine myeloid hematopoietic cells in vitro through the c-kit receptor tyrosine kinase (dominant white spotting, W). Since the W and Nf1 locus appear to function along a common developmental pathway, we generated mice with mutations at both loci to examine potential interactions in vivo. Here, we show that haploinsufficiency at Nf1 perturbs cell fates in mast cells in vivo, and partially rescues coat color and mast cell defects in W(41) mice. Haploinsufficiency at Nf1 also increased mast cell proliferation, survival, and colony formation in response to Steel factor, the ligand for c-kit. Furthermore, haploinsufficiency was associated with enhanced Ras-mitogen-activated protein kinase activity, a major downstream effector of Ras, via wild-type and mutant (W(41)) c-kit receptors. These observations identify a novel interaction between c-kit and neurofibromin in vivo, and offer experimental evidence that haploinsufficiency of Nf1 alters both cellular and biochemical phenotypes in two cell lineages that are affected in individuals with NF1. Collectively, these data support the emerging concept that heterozygous inactivation of tumor suppressor genes may have profound biological effects in multiple cell types.

Major Clinical Impact of Platinum-Based Chemotherapy in a Patient with a Borderline Ovarian Cancer

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Jian Chen

2009-09-01

Full Text Available A patient with extensive and painful chest wall involvement from a metastatic borderline cancer of the ovary was treated with a carboplatin plus paclitaxel chemotherapy regimen. She achieved a rather dramatic improvement of pain control, a significant biochemical response with 75% reduction of the CA-125 antigen level, but only limited radiographic tumor regression. This experience emphasizes the potential clinical utility of platinum-based cytotoxic chemotherapy in the setting of symptomatic advanced borderline ovarian cancer.

Molecular cytogenetics of cutaneous melanocytic lesions - diagnostic, prognostic and therapeutic aspects

NARCIS (Netherlands)

Blokx, Willeke Am M.; van Dijk, Marcory C. R. F.; Ruiter, Dirk J.

This review intends to update current knowledge regarding molecular cytogenetics in melanocytic tumours with a focus on cutaneous melanocytic lesions. Advantages and limitations of diverse, already established methods, such as (fluorescence) in situ hybridization and mutation analysis, to detect

Molecular cytogenetics of cutaneous melanocytic lesions - diagnostic, prognostic and therapeutic aspects.

NARCIS (Netherlands)

Blokx, W.A.M.; Dijk, M.C.R.F. van; Ruiter, D.J.

2010-01-01

This review intends to update current knowledge regarding molecular cytogenetics in melanocytic tumours with a focus on cutaneous melanocytic lesions. Advantages and limitations of diverse, already established methods, such as (fluorescence) in situ hybridization and mutation analysis, to detect

Protective Effect of HemoHIM on Epidermal Melanocytes in Ultraviolet-B irradiated Mice

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Lee, Hae June [Korea Institute of Radiological and Medical Science, Seoul (Korea, Republic of); Kim, Jong Choon; Moon, Chang Jong; Kim, Sung Ho [Chonnam National University, Gwangju (Korea, Republic of); Jung, U Hee; Park, Hae Ran; Jo, Sung Kee [Jeongeup Campus of Korea Atomic Energy Research Institute, Jeongeup (Korea, Republic of); Jang, Jong Sik; Kim, Tae Hwan [Kyungpook National University, Daegu (Korea, Republic of)

2011-06-15

We induced the activation of melanocytes in the epidermis of C57BL/6 mice by ultraviolet-B (UV-B) irradiation, and observed the effect of an herbal preparation (HemoHIM, HH) on the formation, and decrease of UV-B-induced epidermal melanocytes. C57BL/6 mice were irradiated by UV-B 80 mJ:cm{sup -2} (0.5 mW:sec{sup -1}) daily for 7 days, and HH was intraperitoneally, orally or topically applied pre- or post-irradiation. For the estimation of change of epidermal melanocytes, light microscopic observation with dihydroxyphenylalanine (DOPA) stain was performed. Split epidermal sheets prepared from the ear of untreated mice exhibited 13∼15 melanocytes:mm{sup -2}, and one week after UV irradiation, the applied areas showed an increased number of strongly DOPA-positive melanocytes with stout dendrites. But intraperitoneal, oral or topical treatment with HH before each irradiation interrupted UV-B-induced pigmentation and resulted in a marked reduction in the number of epidermal melanocytes as compared to the number found in UV-B-irradiated, untreated control skin. The number and size of DOPA-positive epidermal melanocytes were also significantly decreased in intraperitoneally injected or topically applicated group after irradiation with HH at 3rd and 6th weeks after irradiation. The present study suggests the HH as inhibitor of UV-B-induced pigmentation, and depigmenting agent.

Bilateral diffuse uveal melanocytic proliferation

DEFF Research Database (Denmark)

Klemp, Kristian; Kiilgaard, Jens Folke; Heegaard, Steffen

2017-01-01

cataract formation and uveal melanocytic tumours. The awareness and documentation of BDUMP has increased during the past decade, and the increasing amount of data collected demonstrates the effect of treatment with plasmapheresis and the value of diagnostic tools in BDUMP such as genetic and immunologic...

Is CA-125 an additional help to radiologic findings for differentiation borderline ovarian tumor from stage I carcinoma?

International Nuclear Information System (INIS)

Lee, Eun Joo; Kim, See Hyung; Kim, Young Hwan; Lee, Hee Jung

2011-01-01

Background Borderline ovarian tumors (BOTs) are difficult to differentiate from stage I carcinoma using radiological findings. Little is known about the correlation between CA-125 levels and radiological findings for predicting BOTs or carcinoma. Purpose To assess the role of CA-125, in addition to that of radiological findings, in differentiating BOTs from stage I carcinoma. Material and Methods The study received institutional review board approval, with waiver of informed consent. We evaluated 100 patients (two groups: BOT, 58 patients; stage I carcinoma, 42 patients) using radiological findings, including location and size of each tumor, number and size of septations, papillary projections and vegetations, peritoneal implants, ascites, and preoperative CA-125 levels. The differences in CA-125 levels according to bilateral location, solid components, and thickness of septations between the two groups were evaluated using the McNemar test. Correlations of CA-125 level to size and number of septations were evaluated by the independent sample t test. Results No statistical correlation was found between CA-125 level and location, size, and number of septations between the two groups. Solid components within the tumors were similar in the two groups, but the CA-125 level was significantly higher in stage I carcinoma than in BOTs. The number of septations per tumor was similar in the two groups; thick septations were more frequent in stage I carcinoma than in BOTs, and a significantly higher titer of CA-125 was found in stage I carcinoma. Discriminant analysis of solid components and thickness of septations resulted in accurate diagnosis of 70.6% of the tumors (80.6% of BOTs and 69.7% of stage I carcinomas). Conclusion CA-125 levels for solid components and thickness of septations are lower in BOTs. These may be helpful in predicting the risk of carcinoma, even if BOTs cannot be conclusively differentiated from stage I carcinoma

The Serum CA-125 Concentration Data Assists in Evaluating CT Imaging Information When Used to Differentiate Borderline Ovarian Tumor from Malignant Epithelial Ovarian Tumors

International Nuclear Information System (INIS)

Shin, Ji Eun; Choi, Hyuck Jae; Kim, Mi Hyun; Cho, Kyoung Sik

2011-01-01

We wanted to evaluate the diagnostic value of serum CA-125 concentration, when used in combination with the preoperative contrast-enhanced CT results, to differentiate borderline ovarian tumors (BOTs) from stage I malignant epithelial ovarian tumors (MEOTs). Ninety-eight masses (46 BOTs and 52 stage I MEOTs) from 87 consecutive patients (49 with BOTs and 38 with stage I MEOTs) who had undergone preoperative contrast-enhanced computed tomography (CT) and surgical staging were evaluated retrospectively and independently by two radiologists. The preoperative serum CA-125 concentration was measured in all patients. The utility of analyzing serum CA-125 concentration in combination with the CT results was evaluated by receiver operating characteristic (ROC) curve analysis. An irregular tumor surface and lymphadenopathy were predictive of a MEOT. ROC analysis showed that the combination of CT data and the serum CA-125 level resulted in a higher diagnostic performance than did using the CT alone for differentiating BOTs from MEOTs. The areas under the curves (AUCs) without and with the use of the serum CA-125 level data were 0.67 (95% confidence interval [CI]: 0.57-0.77) and 0.78 (95% CI: 0.68-0.85), respectively, for reader 1 (p = 0.029) and 0.71 (95% CI: 0.61-0.80) and 0.81 (95% CI: 0.72-0.89), respectively, for reader 2 (p = 0.009). The serum CA-125 concentration is of additional diagnostic value when used in conjunction with the CT imaging results for differentiating BOTs from MEOTs.

Association between melanocytic neoplasms and seborrheic keratosis: more than a coincidental collision?

Science.gov (United States)

DeFazio, Jennifer; Zalaudek, Iris; Busam, Klaus J.; Cota, Carlo; Marghoob, Ashfaq

2012-01-01

Clinical observations and an expanding knowledge of cell-to-cell communication have led us to speculate that the finding of a melanocytic nevus in conjunction with a seborrheic keratosis is more than a coincidental collision of two lesions. Here we present five cases demonstrating dermoscopic features of both melanocytic lesions and seborrheic keratoses with corresponding histology. Four cases demonstrate dermoscopic features of a melanocytic nevus and seborrheic keratosis, and the final case a melanoma arising in association with a seborrheic keratosis. PMID:23785597

Tranexamic acid suppresses ultraviolet B eye irradiation-induced melanocyte activation by decreasing the levels of prohormone convertase 2 and alpha-melanocyte-stimulating hormone.

Science.gov (United States)

Hiramoto, Keiichi; Yamate, Yurika; Sugiyama, Daijiro; Takahashi, Yumi; Mafune, Eiichi

2014-12-01

Tranexamic acid (trans-4-aminomethylcyclohexanecarboxylic acid) is a medicinal amino acid used in skin whitening care. This study examined the effects of tranexamic acid on the melanocyte activation of the skin induced by an ultraviolet (UV) B eye irradiation. The eye or ear was locally exposed to UVB at a dose of 1.0 kJ/m(2) using a 20SE sunlamp after covering the remaining body surface with aluminum foil. UVB eye irradiation induced melanocyte activation of the skin, similar to that observed following UVB ear irradiation, which was suppressed by the administration of tranexamic acid treatment. The plasma α-melanocyte-stimulating hormone (α-MSH) content was increased by UVB irradiation of the eye; however, the increase in α-MSH was suppressed by tranexamic acid treatment. In addition, UVB eye irradiation induced the up-regulation of prohormone convertase (PC) 2 in the pituitary gland. Meanwhile, the increase in PC2 induced by UVB eye irradiation was suppressed by tranexamic acid treatment. These results clearly indicate that tranexamic acid decreases the expression of PC2, which cleavages from proopiomelanocortin to α-MSH in the pituitary gland, thereby suppressing melanocyte activation. © 2014 John Wiley & Sons A/S. Published by John Wiley & Sons Ltd.

Microphthalmia-associated transcription factor as the molecular target of cadmium toxicity in human melanocytes

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Chantarawong, Wipa [Department of Molecular Biology and Applied Physiology, Tohoku University School of Medicine, Sendai (Japan); Inter Departmental Multidisciplinary Graduate Program in Bioscience, Faculty of Science, Kasetsart University, Bangkok (Thailand); Takeda, Kazuhisa; Sangartit, Weerapon; Yoshizawa, Miki [Department of Molecular Biology and Applied Physiology, Tohoku University School of Medicine, Sendai (Japan); Pradermwong, Kantimanee [Department of Zoology, Faculty of Science, Kasetsart University, Bangkok (Thailand); Shibahara, Shigeki, E-mail: shibahar@med.tohoku.ac.jp [Department of Molecular Biology and Applied Physiology, Tohoku University School of Medicine, Sendai (Japan)

2014-11-28

Highlights: • In human melanocytes, cadmium decreases the expression of MITF-M and tyrosinase and their mRNAs. • In human melanoma cells, cadmium decreases the expression of MITF-M protein and tyrosinase mRNA. • Expression of MITF-H is less sensitive to cadmium toxicity in melanocyte-linage cells. • Cadmium does not decrease the expression of MITF-H in retinal pigment epithelial cells. • MITF-M is the molecular target of cadmium toxicity in melanocytes. - Abstract: Dietary intake of cadmium is inevitable, causing age-related increase in cadmium accumulation in many organs, including hair, choroid and retinal pigment epithelium (RPE). Cadmium has been implicated in the pathogenesis of hearing loss and macular degeneration. The functions of cochlea and retina are maintained by melanocytes and RPE, respectively, and the differentiation of these pigment cells is regulated by microphthalmia-associated transcription factor (MITF). In the present study, we explored the potential toxicity of cadmium in the cochlea and retina by using cultured human melanocytes and human RPE cell lines. MITF consists of multiple isoforms, including melanocyte-specific MITF-M and widely expressed MITF-H. Levels of MITF-M protein and its mRNA in human epidermal melanocytes and HMV-II melanoma cells were decreased significantly by cadmium. In parallel with the MITF reduction, mRNA levels of tyrosinase, the key enzyme of melanin biosynthesis that is regulated by MITF-M, were also decreased. In RPE cells, however, the levels of total MITF protein, constituting mainly MITF-H, were not decreased by cadmium. We thus identify MITF-M as the molecular target of cadmium toxicity in melanocytes, thereby accounting for the increased risk of disability from melanocyte malfunction, such as hearing and vision loss among people with elevated cadmium exposure.

Microphthalmia-associated transcription factor as the molecular target of cadmium toxicity in human melanocytes

International Nuclear Information System (INIS)

Chantarawong, Wipa; Takeda, Kazuhisa; Sangartit, Weerapon; Yoshizawa, Miki; Pradermwong, Kantimanee; Shibahara, Shigeki

2014-01-01

Highlights: • In human melanocytes, cadmium decreases the expression of MITF-M and tyrosinase and their mRNAs. • In human melanoma cells, cadmium decreases the expression of MITF-M protein and tyrosinase mRNA. • Expression of MITF-H is less sensitive to cadmium toxicity in melanocyte-linage cells. • Cadmium does not decrease the expression of MITF-H in retinal pigment epithelial cells. • MITF-M is the molecular target of cadmium toxicity in melanocytes. - Abstract: Dietary intake of cadmium is inevitable, causing age-related increase in cadmium accumulation in many organs, including hair, choroid and retinal pigment epithelium (RPE). Cadmium has been implicated in the pathogenesis of hearing loss and macular degeneration. The functions of cochlea and retina are maintained by melanocytes and RPE, respectively, and the differentiation of these pigment cells is regulated by microphthalmia-associated transcription factor (MITF). In the present study, we explored the potential toxicity of cadmium in the cochlea and retina by using cultured human melanocytes and human RPE cell lines. MITF consists of multiple isoforms, including melanocyte-specific MITF-M and widely expressed MITF-H. Levels of MITF-M protein and its mRNA in human epidermal melanocytes and HMV-II melanoma cells were decreased significantly by cadmium. In parallel with the MITF reduction, mRNA levels of tyrosinase, the key enzyme of melanin biosynthesis that is regulated by MITF-M, were also decreased. In RPE cells, however, the levels of total MITF protein, constituting mainly MITF-H, were not decreased by cadmium. We thus identify MITF-M as the molecular target of cadmium toxicity in melanocytes, thereby accounting for the increased risk of disability from melanocyte malfunction, such as hearing and vision loss among people with elevated cadmium exposure

The epidermal melanocyte system in individuals of Scandinavian origin, determined by DOPA-staining and TEM

DEFF Research Database (Denmark)

Drzewiecki, K T; Piltz-Drzewiecka, J

1979-01-01

The quantitative evaluation of DOPA-positive epidermal melanocytes in 16 patients of Scandinavian origin showed both individual and regional differences in the melanocyte count. Our data is in agreement with other published studies. The distribution in the number of melanocytes varies significant...

Is Imprint Cytology Useful to Diagnose Malignancy for Brenner Tumors? A Case Series at a Single Institute.

Science.gov (United States)

Minato, Junko; Tokunaga, Hideki; Okamoto, Satoshi; Shibuya, Yusuke; Niikura, Hitoshi; Yaegashi, Nobuo

2017-01-01

The aim of this study was to investigate cytological features of Brenner tumors according to tumor grade using imprint cytology. Between 2004 and 2015, intraoperative imprint cytology was performed on 8 patients with Brenner tumors suspected to be malignant neoplasmas on gross examination because of their large size and solid part. These consisted of 1 benign, 3 borderline, and 4 malignant tumors. In patients with benign and borderline tumors, naked nucleus-like stromal cells and tumor cells in a sheet-like arrangement were observed against a clear background. The nuclei were round to oval-shaped with finely granular chromatin patterns and small nucleoli. Papillary cell clusters and high nucleus-to-cytoplasm ratios were only observed in 1 borderline case. In cases with malignancy, the background was necrotic. The tumor cells occurred in large papillary clusters. The nuclei showed a high degree of nuclear atypia. Nuclear grooves were present in 6 of our 8 cases and they were scant in the malignant cases. Imprint cytology of Brenner tumors provided no characteristic findings to enable a definitive distinction of benign versus borderline tumors, but it enabled discrimination between malignant and other tumors. Imprint cytology can facilitate intraoperative diagnosis and aid in selecting the appropriate surgical procedure. © 2017 S. Karger AG, Basel.

Conjunctival tumors in children: histopathologic diagnosis in 165 cases

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Martin A. Zimmermann-Paiz

2015-12-01

Full Text Available ABSTRACT Purpose: Conjunctival tissue tumors have a varied presentation, and few series studies on pediatric patients have been published. The objective of this paper is to report the histopathologic diagnoses (spanning over 1988-2013 of conjunctival tumors in children younger than 14 years. Methods: We conducted a retrospective, descriptive, and observational study by reviewing the database of all children in whom a conjunctival tumor was surgically removed at Hospital de Ojos y Oídos "Dr. Rodolfo Robles V.," Benemérito Comité Pro Ciegos y Sordos de Guatemala. The data pertaining to gender, age, and histopathologic diagnosis of all cases was collected. The same ocular pathologist made all diagnoses. Results: One hundred sixty-five cases were found, with a mean age of 7.88 years, being 91 (55.15% male subjects. Melanocytic lesions were the most common tumors found (30.91% of cases, with only one case (0.60% being malignant. Conclusions: Melanocytic lesions were the most common tumors found, and of all the cases, only one was malignant; this was in a patient with xeroderma pigmentosum. These findings are consistent with those reported in other studies regarding the frequencies of the histopathology of conjunctival tumors in the pediatric population.

Aberrant expression of HMB-45 in traumatized melanocytic nevi.

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Leleux, Todd M; Prieto, Victor G; Diwan, A Hafeez

2012-09-01

Assessment of histologic and immunohistochemical maturation (with HMB-45 and anti-Ki-67) may be helpful in differentiating benign melanocytic nevi (BMN) from malignant melanoma. Recently, we reported loss of maturation and aberrant immunohistochemical findings in melanocytic nevi after liquid nitrogen cryotherapy (Adeniran et al, J Am Acad Dermatol 2009;61:341-5). Herein we report a similar phenomenon identified in traumatized melanocytic nevi (TMN). We sought to evaluate the histologic and immunohistochemical findings in early and late stages of traumatized nevi. Twenty-four cases of TMN were retrieved from the pathology archives. These were then assessed by two pathologists (T.L. and A.H.D.) using HMB-45 and MIB-1 (for Ki-67) antibodies. TMN showed some of the following findings: epidermal changes (parakeratosis, ulceration, serum crust, flattening of the epidermis) and dermal changes including fibrosis and the presence of melanophages. In some cases, there was architectural disorder of the overlying melanocytes, with crowding in the basal layer, but without significant pagetoid spread. Occasionally, the dermal scar contained larger, more epithelioid-appearing melanocytes than those beneath the scar. Fifty-four percent of TMN lacked obvious immunohistochemical maturation with HMB-45, since nevus cells within the scar or directly beneath it were strongly labeled. None of the TMN showed appreciable labeling for Ki-67. The exact clinical duration between trauma and biopsy could not be determined. Loss of maturation with HMB-45 in TMN can be a diagnostic pitfall in challenging cases. Concurrent evaluation of MIB-1 expression, along with the characteristic histologic features of trauma, should allow the correct diagnosis to be reached. Copyright © 2011 American Academy of Dermatology, Inc. Published by Mosby, Inc. All rights reserved.

PPARalpha/gamma expression and activity in mouse and human melanocytes and melanoma cells.

Science.gov (United States)

Eastham, Linda L; Mills, Caroline N; Niles, Richard M

2008-06-01

We examined the expression of PPARs and the effects of PPARalpha and PPARgamma agonists on growth of mouse and human melanocytes and melanoma cells. PPARalpha,beta, and PPARgamma mRNA qualitative expression in melan-a mouse melanocytes, B16 mouse melanoma, human melanocytes, and A375 and SK-mel28 human melanoma cells was determined by RT-PCR, while quantitative PPARalpha mRNA levels were determined by QuantiGene assay. PPARalpha and PPARgamma protein was assessed by Western blotting. The effect of natural and synthetic PPAR ligands on cell growth was determined by either hemocytometer counting or crystal violet assay. PPAR transcriptional activity was determined by a PPRE-reporter gene assay, while knockdown of PPARalpha expression was achieved by transient transfection of siRNA. Both mouse and human melanoma cells produced more PPARalpha and PPARgamma protein compared to melanocytes. PPARalpha mRNA levels were elevated in human melanoma cells, but not in mouse melanoma cells relative to melanocytes. Silencing of PPARalpha in human melanoma cells did not alter cell proliferation or morphology. PPARgamma-selective agonists inhibited the growth of both mouse and human melanoma cells, while PPARalpha-selective agonists had limited effects. Increased expression of PPARalpha in melanoma relative to melanocytes may be a common occurrence, however its biologic significance remains to be determined. PPARgamma agonists may be useful for arresting the growth of some melanomas.

Expression of cytosolic NADP(+)-dependent isocitrate dehydrogenase in melanocytes and its role as an antioxidant.

Science.gov (United States)

Kim, Ji Young; Shin, Jae Yong; Kim, Miri; Hann, Seung-Kyung; Oh, Sang Ho

2012-02-01

Cytosolic NADP(+)-dependent ICDH (IDPc) has an antioxidant effect as a supplier of NADPH to the cytosol, which is needed for the production of glutathione. To evaluate the expression of IDPc in melanocytes and to elucidate its role as an antioxidant. The knock-down of IDPc expression in immortalized mouse melanocyte cell lines (melan-a) was performed using the short interfering RNA (siRNA)-targeted gene silencing method. After confirming the silencing of IDPc expression with mRNA and protein levels, viability, apoptosis and necrosis, as well as ROS production in IDPc-silenced melanocytes were monitored under conditions of oxidative stress and non-stress. Also, the ratio of oxidized glutathione to total glutathione was examined, and whether the addition of glutathione recovered cell viability, decreased by oxidant stress, was checked. The expression of IDPc in both primary human melanocytes and melan-a cells was confirmed by Western blot and RT-PCR. The silencing of IDPc expression by transfecting IDPc siRNA in melan-a cells was observed by Western blotting and real-time RT-PCR. IDPc knock-down cells showed significantly decreased cell viability and an increased number of cells under apoptosis and necrosis. IDPc siRNA-treated melanocytes demonstrated a higher intensity of DCFDA after the addition of H(2)O(2) compared with scrambled siRNA-treated melanocytes, and a lower ratio of reduced glutathione to oxidized glutathione were observed in IDPc siRNA transfected melanocytes. In addition, the addition of glutathione recovered cell viability, which was previously decreased after incubation with H(2)O(2). This study suggests that decreased IDPc expression renders melanocytes more vulnerable to oxidative stress, and IDPc plays an important antioxidant function in melanocytes. Copyright © 2011 Japanese Society for Investigative Dermatology. Published by Elsevier Ireland Ltd. All rights reserved.

Comparative cytogenetic characterization of primary canine melanocytic lesions using array CGH and fluorescence in situ hybridization.

Science.gov (United States)

Poorman, Kelsey; Borst, Luke; Moroff, Scott; Roy, Siddharth; Labelle, Philippe; Motsinger-Reif, Alison; Breen, Matthew

2015-06-01

Melanocytic lesions originating from the oral mucosa or cutaneous epithelium are common in the general dog population, with up to 100,000 diagnoses each year in the USA. Oral melanoma is the most frequent canine neoplasm of the oral cavity, exhibiting a highly aggressive course. Cutaneous melanocytomas occur frequently, but rarely develop into a malignant form. Despite the differential prognosis, it has been assumed that subtypes of melanocytic lesions represent the same disease. To address the relative paucity of information about their genomic status, molecular cytogenetic analysis was performed on the three recognized subtypes of canine melanocytic lesions. Using array comparative genomic hybridization (aCGH) analysis, highly aberrant distinct copy number status across the tumor genome for both of the malignant melanoma subtypes was revealed. The most frequent aberrations included gain of dog chromosome (CFA) 13 and 17 and loss of CFA 22. Melanocytomas possessed fewer genome wide aberrations, yet showed a recurrent gain of CFA 20q15.3-17. A distinctive copy number profile, evident only in oral melanomas, displayed a sigmoidal pattern of copy number loss followed immediately by a gain, around CFA 30q14. Moreover, when assessed by fluorescence in situ hybridization (FISH), copy number aberrations of targeted genes, such as gain of c-MYC (80 % of cases) and loss of CDKN2A (68 % of cases), were observed. This study suggests that in concordance with what is known for human melanomas, canine melanomas of the oral mucosa and cutaneous epithelium are discrete and initiated by different molecular pathways.

A Case of Iris Melanocytoma Demonstrating Diffuse Melanocytic Proliferation with Uncontrolled Intraocular Pressure

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Mami Kusunose

2017-03-01

Full Text Available We report a rare case with histologically proven melanocytoma of the iris that demonstrated diffuse melanocytic proliferation with uncontrolled secondary glaucoma and investigate the etiology of the intraocular pressure elevation. The patient was a 78-year-old man with a history of darkened iris of his left eye. The intraocular pressure was 39 mm Hg. A slit-lamp examination showed a diffuse darkened iris, and a gonioscopic examination revealed open angle with circumferential heavy pigmentation. There was no pigment dispersion of the anterior chamber and no pigment deposition of the cornea. We suspected malignant ring melanoma in the left eye and enucleated it. The globe was examined with light and electron microscopy. Light microscopy revealed the presence of heavily pigmented tumor cells in the iris, ciliary body, trabecular meshwork, and Schlemm’s canal. A bleached preparation showed large tumor cells with central and paracentral nuclei without mitosis. Electron microscopy of the trabecular meshwork revealed melanin-bearing tumor cells invading the intertrabecular spaces, and the melanin granules were not phagocytosed in the trabecular cells. The mechanical obstruction of the aqueous flow by the tumor cells may be a major cause of secondary glaucoma in eyes with iris melanocytoma presenting diffuse proliferation.

Oxidative stress-induced overexpression of miR-25: the mechanism underlying the degeneration of melanocytes in vitiligo

Science.gov (United States)

Shi, Q; Zhang, W; Guo, S; Jian, Z; Li, S; Li, K; Ge, R; Dai, W; Wang, G; Gao, T; Li, C

2016-01-01

Oxidative stress has a critical role in the pathogenesis of vitiligo. However, the specific molecular mechanism involved in oxidative stress-induced melanocyte death is not well characterized. Given the powerful role of microRNAs (miRNAs) in the regulation of cell survival as well as the fact that the generation of miRNAs can be affected by oxidative stress, we hypothesized that miRNAs may participate in vitiligo pathogenesis by modulating the expression of vital genes in melanocytes. In the present study, we initially found that miR-25 was increased in both serum and lesion samples from vitiligo patients, and its serum level was correlated with the activity of vitiligo. Moreover, restoration of miR-25 promoted the H2O2-induced melanocyte destruction and led to the dysfunction of melanocytes. Further experiments proved that MITF, a master regulator in melanocyte survival and function, accounted for the miR-25-caused damaging impact on melanocytes. Notably, other than the direct role on melanocytes, we observed that miR-25 inhibited the production and secretion of SCF and bFGF from keratinocytes, thus impairing their paracrine protective effect on the survival of melanocytes under oxidative stress. At last, we verified that oxidative stress could induce the overexpression of miR-25 in both melanocytes and keratinocytes possibly by demethylating the promoter region of miR-25. Taken together, our study demonstrates that oxidative stress-induced overexpression of miR-25 in vitiligo has a crucial role in promoting the degeneration of melanocytes by not only suppressing MITF in melanocytes but also impairing the paracrine protective effect of keratinocytes. Therefore, it is worthy to investigate the possibility of miR-25 as a potential drug target for anti-oxidative therapy in vitiligo. PMID:26315342

High-definition optical coherence tomography imaging of melanocytic lesions

DEFF Research Database (Denmark)

Boone, Marc A L M; Norrenberg, Sarah; Jemec, Gregor B E

2014-01-01

and cytologic features of melanocytic lesions. All lesions were examined by one observer clinically and using dermoscopy. Cross-sectional HD-OCT images were compared with histopathology. En face HD-OCT images were compared with reflectance confocal microscopy (RCM). Twenty-six melanocytic lesions of 26 patients...... with sufficient resolution and penetration depth to discriminate architectural patterns and cytologic features of pigmented cells in epidermis and dermis. The method appears to offer the possibility of additional three-dimensional structural information complementary to that of RCM, albeit at a slightly lower...

Transmembrane potential of GlyCl-expressing instructor cells induces a neoplastic-like conversion of melanocytes via a serotonergic pathway

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Douglas Blackiston

2011-01-01

Understanding the mechanisms that coordinate stem cell behavior within the host is a high priority for developmental biology, regenerative medicine and oncology. Endogenous ion currents and voltage gradients function alongside biochemical cues during pattern formation and tumor suppression, but it is not known whether bioelectrical signals are involved in the control of stem cell progeny in vivo. We studied Xenopus laevis neural crest, an embryonic stem cell population that gives rise to many cell types, including melanocytes, and contributes to the morphogenesis of the face, heart and other complex structures. To investigate how depolarization of transmembrane potential of cells in the neural crest’s environment influences its function in vivo, we manipulated the activity of the native glycine receptor chloride channel (GlyCl. Molecular-genetic depolarization of a sparse, widely distributed set of GlyCl-expressing cells non-cell-autonomously induces a neoplastic-like phenotype in melanocytes: they overproliferate, acquire an arborized cell shape and migrate inappropriately, colonizing numerous tissues in a metalloprotease-dependent fashion. A similar effect was observed in human melanocytes in culture. Depolarization of GlyCl-expressing cells induces these drastic changes in melanocyte behavior via a serotonin-transporter-dependent increase of extracellular serotonin (5-HT. These data reveal GlyCl as a molecular marker of a sparse and heretofore unknown cell population with the ability to specifically instruct neural crest derivatives, suggest transmembrane potential as a tractable signaling modality by which somatic cells can control stem cell behavior at considerable distance, identify a new biophysical aspect of the environment that confers a neoplastic-like phenotype upon stem cell progeny, reveal a pre-neural role for serotonin and its transporter, and suggest a novel strategy for manipulating stem cell behavior.

Melanoma targeting with alpha-melanocyte stimulating hormone analogs labeled with fac-[99mTc(CO)3]+: effect of cyclization on tumor-seeking properties.

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Raposinho, Paula D; Xavier, Catarina; Correia, João D G; Falcão, Soraia; Gomes, Paula; Santos, Isabel

2008-03-01

Early detection of primary melanoma tumors is essential because there is no effective treatment for metastatic melanoma. Several linear and cyclic radiolabeled alpha-melanocyte stimulating hormone (alpha-MSH) analogs have been proposed to target the melanocortin type 1 receptor (MC1R) overexpressed in melanoma. The compact structure of a rhenium-cyclized alpha-MSH analog (Re-CCMSH) significantly enhanced its in vivo tumor uptake and retention. Melanotan II (MT-II), a cyclic lactam analog of alpha-MSH (Ac-Nle-cyclo[Asp-His-DPhe-Arg-Trp-Lys]-NH2]), is a very potent and stable agonist peptide largely used in the characterization of melanocortin receptors. Taking advantage of the superior biological features associated with the MT-II cyclic peptide, we assessed the effect of lactam-based cyclization on the tumor-seeking properties of alpha-MSH analogs by comparing the pharmacokinetics profile of the 99mTc-labeled cyclic peptide betaAla-Nle-cyclo[Asp-His-D-Phe-Arg-Trp-Lys]-NH2 with that of the linear analog betaAla-Nle-Asp-His-DPhe-Arg-Trp-Lys-NH2 in melanoma-bearing mice. We have synthesized and coupled the linear and cyclic peptides to a bifunctional chelator containing a pyrazolyl-diamine backbone (pz) through the amino group of betaAla, and the resulting pz-peptide conjugates were reacted with the fac-[99mTc(CO)3]+ moiety. The 99mTc(CO)3-labeled conjugates were obtained in high yield, high specific activity, and high radiochemical purity. The cyclic 99mTc(CO)3-labeled conjugate presents a remarkable internalization (87.1% of receptor-bound tracer and 50.5% of total applied activity, after 6 h at 37 degrees C) and cellular retention (only 24.7% released from the cells after 5 h) in murine melanoma B16F1 cells. A significant tumor uptake and retention was obtained in melanoma-bearing C57BL6 mice for the cyclic radioconjugate [9.26 +/- 0.83 and 11.31 +/- 1.83% ID/g at 1 and 4 h after injection, respectively]. The linear 99mTc(CO)3-pz-peptide presented lower values for

Melanocyte biology and function with reference to oral melanin hyperpigmentation in HIV-seropositive subjects.

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Feller, Liviu; Chandran, Rakesh; Kramer, Beverley; Khammissa, Razia A G; Altini, Mario; Lemmer, Johan

2014-09-01

The color of normal skin and of oral mucosa is not determined by the number of melanocytes in the epithelium but rather by their melanogenic activity. Pigmented biopolymers or melanins are synthesized in melanosomes. Tyrosinase is the critical enzyme in the biosynthesis of both brown/black eumelanin and yellow/red pheomelanin. The number of the melanosomes within the melanocytes, the type of melanin within the melanosomes, and the efficacy of the transfer of melanosomes from the melanocytes to the neighboring keratinocytes all play an important role in tissue pigmentation. Melanin production is regulated by locally produced factors including proopiomelanocortin and its derivative peptides, particularly alpha-melanocyte-stimulating hormone (α-MSH), melanocortin 1 receptor (MC1R), adrenergic and cholinergic agents, growth factors, cytokines, and nitric oxide. Both eumelanin and pheomelanin can be produced by the same melanocytes, and the proportion of the two melanin types is influenced by the degree of functional activity of the α-MSH/MC1R intracellular pathway. The cause of HIV oral melanosis is not fully understood but may be associated with HIV-induced cytokine dysregulation, with the medications commonly prescribed to HIV-seropositive persons, and with adrenocortical dysfunction, which is not uncommon in HIV-seropositive subjects with AIDS. The purpose of this article is to discuss some aspects of melanocyte biology and HIV-associated oral melanin hyperpigmentation.

Dermal Squamomelanocytic Tumor: Neoplasm of Uncertain Biological Potential

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Mirsad Dorić

2008-05-01

Full Text Available We report a case of exceedingly rare cutaneous neoplasm with histological features of malignancy and uncertain biological potential. The nodular, darkly pigmented facial tumor with central exulceration, size 12x10x7 mm, of the skin 61-year-old man preauricular left was completely exised.Histologically tumor consists of atypical squamous cells, which express signs of moderate to significant pleomorphism, mitotically active, with foci forming of parakeratotic horn cysts (“pearls”. Characteristically tumor also consists of large number of atypical melanocytes with multifocal pattern, inserted between atypical squamous cells, and which contain large amount of dark brown pigment melanin. Immunohistochemically, squamous cells stain positively with keratin (CK116, melanocytes were stained with S -100 protein, HMB 45, and vimentin, but failed to stain with CK 116.To our knowledge this is the sixth reported case in world literature. The follow-up time of four years no evidence of recurrence or metastasis, similar all reported cases, but it is too short period in estimation to guarantee a benign course. However, it appears that this group of neoplasm may have different prognosis from pure squamous carcinoma or malignant melanoma.

Isolation, Culture, and Motility Measurements of Epidermal Melanocytes from GFP-Expressing Reporter Mice.

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Dagnino, Lina; Crawford, Melissa

2018-03-27

In this article, we provide a method to isolate primary epidermal melanocytes from reporter mice, which also allow targeted gene inactivation. The mice from which these cells are isolated are bred into a Rosa26 mT/mG reporter background, which results in GFP expression in the targeted melanocytic cell population. These cells are isolated and cultured to >95% purity. The cells can be used for gene expression studies, clonogenic experiments, and biological assays, such as capacity for migration. Melanocytes are slow moving cells, and we also provide a method to measure motility using individual cell tracking and data analysis.

Substantial Effect of Melanin Influencing Factors on In vitro Melanogenesis in Muzzle Melanocytes of Differently Colored Hanwoo.

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Amna, Touseef; Park, Kyoung Mi; Cho, In-Kyung; Choi, Tae Jeong; Lee, Seung Soo; Seo, Kang-Seok; Hwang, Inho

2012-07-01

The present study was designed to investigate the effect of α-melanocyte-stimulating hormone (α-MSH), nitric oxide (NO) and L-cysteine on melanin production and expression of related genes MC1R, Tyr, Tyrp-1 and Tyrp-2 in muzzle melanocytes of differently colored three native Hanwoo cattle. Muzzle samples were taken from black, brindle and brown Hanwoo and purified melanocytes were cultured with α-MSH, nitric oxide and L-cysteine at 100 nM, 50 µM and 0.07 mg/ml of media respectively. The amounts of total melanin, eumelanin and mRNA expression at Tyr, Tyrp-1, Tyrp-2 and MC1R levels were quantified. α-MSH and nitric oxide significantly increased (pmuzzle melanocytes. On the contrary, L-cysteine greatly (pmuzzle melanocytes of all three phenotypes. The results of this study revealed nitric oxide and α-MSH contribute hyper-pigmentation by enhancing eumelanogenesis whereas L-cysteine contributes to pheomelanin production in different colored Hanwoo muzzle melanocytes.

Oral melanocytic nevi: Report of two cases with immunohistochemical elaboration of their probable origin and maturation

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Dipti Dutta

2015-01-01

Full Text Available Oral melanocytic nevi are localized developmental tissue malformations of nevus cells in the oral mucosa. Relatively rare in occurrence compared to their dermal counterparts, considerable debate exists in the literature related to their origin, development and maturation, and their relationship to oral melanocytes.We report two cases of oral melanocytic nevi with classical clinical presentation. The histopathology was consistent with the known patterns of oral melanocytic nevi. Special stains such as Masson Fontana, further substantiated the observation. S-100 and HMB-45 were applied to immunohistochemically elaborate the cell population. Interestingly two distinct cell populations were detected in the lesions. "Type A" cells in the center of the lesion were S-100 positive, indicating a neural origin and immaturity in development, while peripheral "type B" cells stained positive with HMB-45, indicating melanocytic origin and mature development.

Borderline Personality in the Medical Setting

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Sansone, Lori A.

2015-01-01

Objective: Individuals with borderline personality disorder in mental health settings tend to present with relationship difficulties, mood instability/dysphoria, and overt self-harm behavior. In contrast, it appears that individuals with borderline personality disorder in medical settings manifest physical symptoms that are medically difficult to substantiate. Through a review of the literature, we examine 2 symptom manifestations among patients with borderline personality in primary care and general medical settings—namely pain sensitivity and multiple somatic complaints. In addition to reviewing the research of others, we also highlight our own investigations into these 2 areas. Data Sources: We conducted a literature search of the PubMed database and a previous version of the PsycINFO search engine (no restrictions). Search terms included borderline personality, borderline personality disorder, personality disorders; chronic pain, pain, pain syndromes; and somatization disorder, Briquet’s syndrome, somatic preoccupation, somatic. Study Selection: Published articles related to borderline personality, pain and somatic symptoms (ie, somatization disorder, somatic preoccupation) were examined. Results: According to our review, the literature indicates higher-than-expected rates of borderline personality disorder among patients in primary care and general medical settings who present with chronic pain conditions and/or somatic preoccupation. Conclusions: Unlike patients with borderline personality disorder in mental health settings, who tend to present with relationship difficulties, mood instability/dysphoria, and overt self-harm behavior, patients with borderline personality disorder in primary care settings tend to present with unsubstantiated chronic pain of various types as well as somatic preoccupation. PMID:26644960

Hepatocyte growth factor/scatter factor-MET signaling in neural crest-derived melanocyte development.

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Kos, L; Aronzon, A; Takayama, H; Maina, F; Ponzetto, C; Merlino, G; Pavan, W

1999-02-01

The mechanisms governing development of neural crest-derived melanocytes, and how alterations in these pathways lead to hypopigmentation disorders, are not completely understood. Hepatocyte growth factor/scatter factor (HGF/SF) signaling through the tyrosine-kinase receptor, MET, is capable of promoting the proliferation, increasing the motility, and maintaining high tyrosinase activity and melanin synthesis of melanocytes in vitro. In addition, transgenic mice that ubiquitously overexpress HGF/SF demonstrate hyperpigmentation in the skin and leptomenigenes and develop melanomas. To investigate whether HGF/ SF-MET signaling is involved in the development of neural crest-derived melanocytes, transgenic embryos, ubiquitously overexpressing HGF/SF, were analyzed. In HGF/SF transgenic embryos, the distribution of melanoblasts along the characteristic migratory pathway was not affected. However, additional ectopically localized melanoblasts were also observed in the dorsal root ganglia and neural tube, as early as 11.5 days post coitus (p.c.). We utilized an in vitro neural crest culture assay to further explore the role of HGF/SF-MET signaling in neural crest development. HGF/SF added to neural crest cultures increased melanoblast number, permitted differentiation into pigmented melanocytes, promoted melanoblast survival, and could replace mast-cell growth factor/Steel factor (MGF) in explant cultures. To examine whether HGF/SF-MET signaling is required for the proper development of melanocytes, embryos with a targeted Met null mutation (Met-/-) were analysed. In Met-/- embryos, melanoblast number and location were not overtly affected up to 14 days p.c. These results demonstrate that HGF/SF-MET signaling influences, but is not required for, the initial development of neural crest-derived melanocytes in vivo and in vitro.

Automatic Classification of Specific Melanocytic Lesions Using Artificial Intelligence.

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Jaworek-Korjakowska, Joanna; Kłeczek, Paweł

2016-01-01

Given its propensity to metastasize, and lack of effective therapies for most patients with advanced disease, early detection of melanoma is a clinical imperative. Different computer-aided diagnosis (CAD) systems have been proposed to increase the specificity and sensitivity of melanoma detection. Although such computer programs are developed for different diagnostic algorithms, to the best of our knowledge, a system to classify different melanocytic lesions has not been proposed yet. In this research we present a new approach to the classification of melanocytic lesions. This work is focused not only on categorization of skin lesions as benign or malignant but also on specifying the exact type of a skin lesion including melanoma, Clark nevus, Spitz/Reed nevus, and blue nevus. The proposed automatic algorithm contains the following steps: image enhancement, lesion segmentation, feature extraction, and selection as well as classification. The algorithm has been tested on 300 dermoscopic images and achieved accuracy of 92% indicating that the proposed approach classified most of the melanocytic lesions correctly. A proposed system can not only help to precisely diagnose the type of the skin mole but also decrease the amount of biopsies and reduce the morbidity related to skin lesion excision.

The unfolded protein response in melanocytes: activation in response to chemical stressors of the endoplasmic reticulum and tyrosinase misfolding.

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Manga, Prashiela; Bis, Sabina; Knoll, Kristen; Perez, Beremis; Orlow, Seth J

2010-10-01

Accumulation of proteins in the endoplasmic reticulum (ER) triggers the unfolded protein response (UPR), comprising three signaling pathways initiated by Ire1, Perk and Atf6 respectively. Unfolded protein response activation was compared in chemically stressed murine wildtype melanocytes and mutant melanocytes that retain tyrosinase in the ER. Thapsigargin, an ER stressor, activated all pathways in wildtype melanocytes, triggering Caspase 12-mediated apoptosis at toxic doses. Albino melanocytes expressing mutant tyrosinase showed evidence of ER stress with increased Ire1 expression, but the downstream effector, Xbp1, was not activated even following thapsigargin treatment. Attenuation of Ire1 signaling was recapitulated in wildtype melanocytes treated with thapsigargin for 8 days, with diminished Xbp1 activation observed after 4 days. Atf6 was also activated in albino melanocytes, with no response to thapsigargin, while the Perk pathway was not activated and thapsigargin treatment elicited robust expression of the downstream effector CCAAT-enhancer-binding protein homologous protein. Thus, melanocytes adapt to ER stress by attenuating two UPR pathways.

Topography of Protein Kinase C βII in Benign and Malignant Melanocytic Lesions.

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Krasagakis, Konstanin; Tsentelierou, Eleftheria; Chlouverakis, Gregory; Stathopoulos, Efstathios N

2017-09-01

Protein kinase C βII promotes melanogenesis and affects proliferation of melanocytic cells but is frequently absent or decreased in melanoma cells in vitro. To investigate PKC-βII expression and spatial distribution within a lesion in various benign and malignant melanocytic proliferations. Expression of PKC-βII was semiquantitatively assessed in the various existing compartments (intraepidermal [not nested], junctional [nested], and dermal) of benign (n = 43) and malignant (n = 28) melanocytic lesions by immunohistochemistry. Melanocytes in the basal layer of normal skin or in lentigo simplex stained strongly for PKC-βII. Common nevi lacked completely PKC-βII. All other lesions expressed variably PKC-βII, with cutaneous melanoma metastases displaying the lowest rate of positivity (14%). In the topographical analysis within a lesion, PKC-βII expression was largely retained in the intraepidermal and junctional part of all other lesions (dysplastic nevus, lentigo maligna, and melanoma). Reduced expression of PKC-βII was found in the dermal component of benign and malignant lesions ( P = .041 vs intraepidermal). PKC-βII expression in the various compartments did not differ significantly between benign and malignant lesions. The current study revealed a significant correlation between PKC-βII expression and spatial localization of melanocytes, with the lowest expression found in the dermal compartment and the highest in the epidermal compartment.

MuSIC report III: tumour microcirculation patterns and development of metastasis in long-term follow-up of melanocytic uveal tumours.

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Klingenstein, Annemarie; Schaumberger, Markus M; Freeman, William R; Folberg, Robert; Mueller, Arthur J; Schaller, Ulrich C

2016-03-01

To statistically determine differences in microcirculation patterns between nevi and uveal melanomas and the influence of these patterns on metastatic potential in the long-term follow-up of 112 patients with melanocytic uveal tumours. In vivo markers indicating malignancy and metastatic potential have implications for treatment decision. Primary diagnosis and work-up included clinical examination, fundus photography, standardized A and B scan echography as well as evaluation of tumour microcirculation patterns via confocal fluorescein and indocyanine green angiography (ICGA). Patient data were collected from the patient files, the tumour registry or personal contact. Statistical analysis was performed with spss 22.0 using chi-square, Fisher's exact test and Kaplan-Meier survival analysis. Forty-three uveal melanocytic lesions remained untreated and were retrospectively classified as benign nevi, whereas 69 lesions were malignant melanomas (T1: 32, T2: 28, T3: 6 and T4: 3). 'Silent' and 'arcs without branching' were found significantly more often in nevi (p = 0.001 and p = 0.010), whereas 'parallel with cross-linking' and 'networks' were significantly more frequent in melanomas (p = 0.022 and p = 0.029). The microcirculation pattern 'parallel with cross-linking' proved significantly more frequent in patients who developed metastases (p = 0.001). Certain microcirculation patterns may guide us in differentiating uveal nevi from malignant melanomas. A non-invasive prognostic marker can be of great value for borderline lesions in which cytology is less likely taken. 'Parallel with cross-linking' did not only indicate malignancy, but it was also associated with later tumour metastasis. © 2015 Acta Ophthalmologica Scandinavica Foundation. Published by John Wiley & Sons Ltd.

Substantial Effect of Melanin Influencing Factors on Melanogenesis in Muzzle Melanocytes of Differently Colored Hanwoo

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Touseef Amna

2012-07-01

Full Text Available The present study was designed to investigate the effect of α-melanocyte-stimulating hormone (α-MSH, nitric oxide (NO and L-cysteine on melanin production and expression of related genes MC1R, Tyr, Tyrp-1 and Tyrp-2 in muzzle melanocytes of differently colored three native Hanwoo cattle. Muzzle samples were taken from black, brindle and brown Hanwoo and purified melanocytes were cultured with α-MSH, nitric oxide and L-cysteine at 100 nM, 50 µM and 0.07 mg/ml of media respectively. The amounts of total melanin, eumelanin and mRNA expression at Tyr, Tyrp-1, Tyrp-2 and MC1R levels were quantified. α-MSH and nitric oxide significantly increased (p<0.05 the amount of total melanin in black and brindle whereas eumelanin production in brown Hanwoo muzzle melanocytes. On the contrary, L-cysteine greatly (p<0.05 depressed the eumelanin production in black color but increased in brown. Simultaneously, up regulation of Tyr by nitric oxide and α-MSH and down regulation of Tyr, Tyrp-2 and MC1R genes by L-cysteine were observed in muzzle melanocytes of all three phenotypes. The results of this study revealed nitric oxide and α-MSH contribute hyper-pigmentation by enhancing eumelanogenesis whereas L-cysteine contributes to pheomelanin production in different colored Hanwoo muzzle melanocytes.

A subpopulation of smooth muscle cells, derived from melanocyte-competent precursors, prevents patent ductus arteriosus.

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Ichiro Yajima

Full Text Available BACKGROUND: Patent ductus arteriosus is a life-threatening condition frequent in premature newborns but also present in some term infants. Current mouse models of this malformation generally lead to perinatal death, not reproducing the full phenotypic spectrum in humans, in whom genetic inheritance appears complex. The ductus arteriosus (DA, a temporary fetal vessel that bypasses the lungs by shunting the aortic arch to the pulmonary artery, is constituted by smooth muscle cells of distinct origins (SMC1 and SMC2 and many fewer melanocytes. To understand novel mechanisms preventing DA closure at birth, we evaluated the importance of cell fate specification in SMC that form the DA during embryonic development. Upon specific Tyr::Cre-driven activation of Wnt/β-catenin signaling at the time of cell fate specification, melanocytes replaced the SMC2 population of the DA, suggesting that SMC2 and melanocytes have a common precursor. The number of SMC1 in the DA remained similar to that in controls, but insufficient to allow full DA closure at birth. Thus, there was no cellular compensation by SMC1 for the loss of SMC2. Mice in which only melanocytes were genetically ablated after specification from their potential common precursor with SMC2, demonstrated that differentiated melanocytes themselves do not affect DA closure. Loss of the SMC2 population, independent of the presence of melanocytes, is therefore a cause of patent ductus arteriosus and premature death in the first months of life. Our results indicate that patent ductus arteriosus can result from the insufficient differentiation, proliferation, or contractility of a specific smooth muscle subpopulation that shares a common neural crest precursor with cardiovascular melanocytes.

A Subpopulation of Smooth Muscle Cells, Derived from Melanocyte-Competent Precursors, Prevents Patent Ductus Arteriosus

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Puig, Isabel; Champeval, Delphine; Kumasaka, Mayuko; Belloir, Elodie; Bonaventure, Jacky; Mark, Manuel; Yamamoto, Hiroaki; Taketo, Mark M.; Choquet, Philippe; Etchevers, Heather C.; Beermann, Friedrich; Delmas, Véronique; Monassier, Laurent; Larue, Lionel

2013-01-01

Background Patent ductus arteriosus is a life-threatening condition frequent in premature newborns but also present in some term infants. Current mouse models of this malformation generally lead to perinatal death, not reproducing the full phenotypic spectrum in humans, in whom genetic inheritance appears complex. The ductus arteriosus (DA), a temporary fetal vessel that bypasses the lungs by shunting the aortic arch to the pulmonary artery, is constituted by smooth muscle cells of distinct origins (SMC1 and SMC2) and many fewer melanocytes. To understand novel mechanisms preventing DA closure at birth, we evaluated the importance of cell fate specification in SMC that form the DA during embryonic development. Upon specific Tyr::Cre-driven activation of Wnt/β-catenin signaling at the time of cell fate specification, melanocytes replaced the SMC2 population of the DA, suggesting that SMC2 and melanocytes have a common precursor. The number of SMC1 in the DA remained similar to that in controls, but insufficient to allow full DA closure at birth. Thus, there was no cellular compensation by SMC1 for the loss of SMC2. Mice in which only melanocytes were genetically ablated after specification from their potential common precursor with SMC2, demonstrated that differentiated melanocytes themselves do not affect DA closure. Loss of the SMC2 population, independent of the presence of melanocytes, is therefore a cause of patent ductus arteriosus and premature death in the first months of life. Our results indicate that patent ductus arteriosus can result from the insufficient differentiation, proliferation, or contractility of a specific smooth muscle subpopulation that shares a common neural crest precursor with cardiovascular melanocytes. PMID:23382837

Development and validation of a simple method for the extraction of human skin melanocytes.

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Wang, Yinjuan; Tissot, Marion; Rolin, Gwenaël; Muret, Patrice; Robin, Sophie; Berthon, Jean-Yves; He, Li; Humbert, Philippe; Viennet, Céline

2018-03-21

Primary melanocytes in culture are useful models for studying epidermal pigmentation and efficacy of melanogenic compounds, or developing advanced therapy medicinal products. Cell extraction is an inevitable and critical step in the establishment of cell cultures. Many enzymatic methods for extracting and growing cells derived from human skin, such as melanocytes, are described in literature. They are usually based on two enzymatic steps, Trypsin in combination with Dispase, in order to separate dermis from epidermis and subsequently to provide a suspension of epidermal cells. The objective of this work was to develop and validate an extraction method of human skin melanocytes being simple, effective and applicable to smaller skin samples, and avoiding animal reagents. TrypLE™ product was tested on very limited size of human skin, equivalent of multiple 3-mm punch biopsies, and was compared to Trypsin/Dispase enzymes. Functionality of extracted cells was evaluated by analysis of viability, morphology and melanin production. In comparison with Trypsin/Dispase incubation method, the main advantages of TrypLE™ incubation method were the easier of separation between dermis and epidermis and the higher population of melanocytes after extraction. Both protocols preserved morphological and biological characteristics of melanocytes. The minimum size of skin sample that allowed the extraction of functional cells was 6 × 3-mm punch biopsies (e.g., 42 mm 2 ) whatever the method used. In conclusion, this new procedure based on TrypLE™ incubation would be suitable for establishment of optimal primary melanocytes cultures for clinical applications and research.

Melanocytes and melanin represent a first line of innate immunity against Candida albicans.

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Tapia, Cecilia V; Falconer, Maryanne; Tempio, Fabián; Falcón, Felipe; López, Mercedes; Fuentes, Marisol; Alburquenque, Claudio; Amaro, José; Bucarey, Sergio A; Di Nardo, Anna

2014-07-01

Melanocytes are dendritic cells located in the skin and mucosae that synthesize melanin. Some infections induce hypo- or hyperpigmentation, which is associated with the activation of Toll-like receptors (TLRs), especially TLR4. Candida albicans is an opportunist pathogen that can switch between blastoconidia and hyphae forms; the latter is associated with invasion. Our objectives in this study were to ascertain whether C. albicans induces pigmentation in melanocytes and whether this process is dependent on TLR activation, as well as relating this with the antifungal activity of melanin as a first line of innate immunity against fungal infections. Normal human melanocytes were stimulated with C. albicans supernatants or with crude extracts of the blastoconidia or hyphae forms, and pigmentation and TLR2/TLR4 expression were measured. Expression of the melanosomal antigens Melan-A and gp100 was examined for any correlation with increased melanin levels or antifungal activity in melanocyte lysates. Melanosomal antigens were induced earlier than cell pigmentation, and hyphae induced stronger melanization than blastoconidia. Notably, when melanocytes were stimulated with crude extracts of C. albicans, the cell surface expression of TLR2/TLR4 began at 48 h post-stimulation and peaked at 72 h. At this time, blastoconidia induced both TLR2 and TLR4 expression, whereas hyphae only induced TLR4 expression. Taken together, these results suggest that melanocytes play a key role in innate immune responses against C. albicans infections by recognizing pathogenic forms of C. albicans via TLR4, resulting in increased melanin content and inhibition of infection. © The Author 2014. Published by Oxford University Press on behalf of The International Society for Human and Animal Mycology. All rights reserved. For permissions, please e-mail: journals.permissions@oup.com.

Malignant Phyllodes Tumor Presenting in Bone, Brain, Lungs, and Lymph Nodes

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Eric D. Johnson

2016-12-01

Full Text Available Introduction: Phyllodes tumors (PTs are rare fibroepithelial tumors of the breast which are classified as benign, borderline, or malignant. Malignant PTs account for <1% of malignant breast tumors, and borderline tumors have potential to progress to malignant tumors. Metastatic recurrences are most commonly documented in bone and lungs. We report an extremely rare presentation of recurrent malignant PTs involving the brain, lung, lymph nodes, and bone. Case: A 66-year-old female presented with a large breast mass. Biopsy identified malignant PT, treated by mastectomy. One year later she presented with acute back pain; imaging showed pathological L4 spinal compression fracture. Core biopsy confirmed PT. Staging identified additional metastases in the lymph nodes, brain, and lung. Discussion: PTs are rare and fast-growing tumors that originate from periductal stromal tissues and are composed of both epithelial and stromal components. Histologically, they are classified as benign, borderline, or malignant. The prognosis of the malignant type is poorly defined, with local recurrence occurring in 10–40% and metastases in 10%. Chemotherapy and radiotherapy are generally ineffective in this tumor type. The most common metastatic sites for malignant cases are the lung and bones, but in rare instances, PTs may metastasize elsewhere. Conclusion: We report a rare presentation of recurrent malignant PT presenting as pathological fracture of the lumbar spine with impingement on the spinal column, along with cerebellar, nodal, and pulmonary metastases. Only 1 similar case has been previously reported.

Heme oxygenase-1 expression protects melanocytes from stress-induced cell death: implications for vitiligo

NARCIS (Netherlands)

Elassiuty, Yasser E.; Klarquist, Jared; Speiser, Jodi; Yousef, Randa M.; El Refaee, Abdelaziz A.; Hunter, Nahla S.; Shaker, Olfat G.; Gundeti, Mohan; Nieuweboer-Krobotova, Ludmila; Caroline Le Poole, I.

2011-01-01

To study protection of melanocytes from stress-induced cell death by heme oxygenases during depigmentation and repigmentation in vitiligo, expression of isoforms 1 and 2 was studied in cultured control and patient melanocytes and normal skin explants exposed to UV or bleaching agent 4-TBP.

Immunohistochemical localization of HE4 in benign, borderline, and malignant lesions of the ovary.

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Georgakopoulos, Penelope; Mehmood, Saira; Akalin, Ali; Shroyer, Kenneth R

2012-11-01

Despite advances in the development of novel methods to improve treatment, ovarian carcinoma is still the leading cause of gynecologic cancer death in the United States and other industrialized nations. Improvements in the clinical outcome of ovarian cancer will be achieved if methods can be developed to enable the detection of these tumors at the earliest possible stage. Thus, it is critically important to identify and validate new biomarkers of ovarian cancer. HE4 expression was defined by immunohistochemical analysis of a wide range of benign, borderline, and malignant ovarian lesions, including serous, endometrioid, mucinous, and clear cell lesions of the ovary and in primary tubal carcinomas and the normal fallopian tube. At the cellular level, HE4 was highly expressed in malignant ovarian tumors and in a wide range of benign and borderline ovarian lesions. In addition, HE4 was highly expressed in primary fallopian tube carcinomas and benign fallopian tubal epithelial cells. These results support the conclusion that HE4 is widely expressed in most benign, borderline, and malignant lesions of the ovary and the fallopian tube. The detection of HE4 expression at high levels in some benign lesions and normal tissues suggests that HE4 could have limited specificity as a marker of ovarian or tubal carcinoma. Furthermore, the relatively weak expression that was observed in many ovarian carcinomas indicates that HE4 could fail to detect some cases of primary or recurrent disease.

Influence of melanocytes in the ex-vivo reconstructed epidermal melanin unit following an acute UV irradiation; Role des melanocytes dans l'unite epidermique de melanisation reconstruite ex-vivo apres une irradiation UV aigue

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Cario-Andre, M

2000-11-15

Influence of melanocytes in skin pigmentation is well documented, however its photo-protective role has given rise to controversy. The role of melanocytes have been investigated on reconstructed epidermis with 100 % of keratinocytes or 95 % of keratinocytes and 5 % of melanocytes. In a first time, the effect of an acute UVB dose has been studied on both reconstructed epidermis, next we have investigated UVA and UVA+B effects on these epidermis. Following irradiation, the presence of melanocytes in reconstructed epidermis protects against apoptosis without protecting significantly against DNA damage formation (CPD, 6-4PP) and protects against UV-induced unbalance of the SOD/catalase ratio (antioxidants enzymes). On the contrary, the presence of melanocytes in reconstructed epidermis amplifies lipids and proteins oxidations but seems to protect against DNA oxidations. Melanocytes differ from keratinocytes by their melanin content and their more important concentration in polyunsaturated fatty acids. To evaluate what is the part of melanin and the part of polyunsaturated fatty acids in epidermal UV responses, reconstructed epidermis with keratinocytes have been supplemented with polyunsaturated fatty acid. This study indicates that polyunsaturated fatty acids are responsible for lipids and proteins oxidations and that melanin protect against DNA oxidation induced by lipid peroxidation. All these studies demonstrate that, model of reconstructed epidermis and epidermis in-vivo have the same behaviour following UV irradiation. In the last part, sunscreens and antioxidants have been tested on reconstructed epidermis and have demonstrated that model of reconstructed epidermis is suitable for photo-protective molecules screening. (author)

Interobserver Variability by Pathologists in the Distinction Between Cellular Fibroadenomas and Phyllodes Tumors

Science.gov (United States)

Lawton, Thomas J.; Acs, Geza; Argani, Pedram; Farshid, Gelareh; Gilcrease, Michael; Goldstein, Neal; Koerner, Frederick; Rowe, J. Jordi; Sanders, Melinda; Shah, Sejal S.; Reynolds, Carol

2015-01-01

Fibroepithelial lesions with cellular stroma are frequently termed cellular fibroadenomas although criteria for distinguishing them from a phyllodes tumor are vague and subjective. However, the clinical implications and surgical management for these 2 lesions may be different. We randomly selected 21 cases of fibroepithelial lesions sent in consultation to the senior author that were challenging to classify as cellular fibroadenoma or phyllodes tumor. One to 2 representative slides of each case along with patient age were sent to 10 pathologists who specialize in breast pathology. The World Health Organization criteria for phyllodes tumors and a diagnosis form were included with the study set. For the purposes of data reporting, fibroadenoma and cellular fibroadenoma are considered together. In only 2 cases was there uniform agreement as to whether the tumor represented a fibroadenoma or phyllodes tumor. Of the remaining 19 cases, if the diagnoses of fibroadenoma and benign phyllodes tumor were combined and separated from borderline and malignant phyllodes tumors, there was 100% agreement in 53% of cases and 90% agreement in 79% of cases. This study highlights the difficulty that exists in distinguishing some cellular fibroadenomas from phyllodes tumors even for pathologists who specialize in breast pathology. However, there appears to be considerable agreement when cellular fibroadenomas and benign phyllodes tumors are distinguished from borderline and malignant phyllodes tumors. Further studies are needed to determine if there is a clinically significant difference between cellular fibroadenomas and benign phyllodes tumors and how to better distinguish them from borderline and malignant phyllodes tumors. PMID:25161205

A reporter mouse model for in vivo tracing and in vitro molecular studies of melanocytic lineage cells and their diseases

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Melissa Crawford

2017-08-01

Full Text Available Alterations in melanocytic lineage cells give rise to a plethora of distinct human diseases, including neurocristopathies, cutaneous pigmentation disorders, loss of vision and hearing, and melanoma. Understanding the ontogeny and biology of melanocytic cells, as well as how they interact with their surrounding environment, are key steps in the development of therapies for diseases that involve this cell lineage. Efforts to culture and characterize primary melanocytes from normal or genetically engineered mouse models have at times yielded contrasting observations. This is due, in part, to differences in the conditions used to isolate, purify and culture these cells in individual studies. By breeding ROSAmT/mG and Tyr::CreERT2 mice, we generated animals in which melanocytic lineage cells are identified through expression of green fluorescent protein. We also used defined conditions to systematically investigate the proliferation and migration responses of primary melanocytes on various extracellular matrix (ECM substrates. Under our culture conditions, mouse melanocytes exhibit doubling times in the range of 10 days, and retain exponential proliferative capacity for 50-60 days. In culture, these melanocytes showed distinct responses to different ECM substrates. Specifically, laminin-332 promoted cell spreading, formation of dendrites, random motility and directional migration. In contrast, low or intermediate concentrations of collagen I promoted adhesion and acquisition of a bipolar morphology, and interfered with melanocyte forward movements. Our systematic evaluation of primary melanocyte responses emphasizes the importance of clearly defining culture conditions for these cells. This, in turn, is essential for the interpretation of melanocyte responses to extracellular cues and to understand the molecular basis of disorders involving the melanocytic cell lineage.

Ecto-mesenchymal stem cells from dental pulp are committed to differentiate into active melanocytes

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F Paino

2010-10-01

Full Text Available Dental pulp stem cells (DPSCs are multipotent stem cells derived from neural crest and mesenchyme and have the capacity to differentiate into multiple cell lineages. It has already been demonstrated that DPSCs differentiate into melanocyte-like cells but only when cultivated in a specific melanocyte differentiating medium. In this study we have shown, for the first time, that DPSCs are capable of spontaneously differentiating into mature melanocytes, which display molecular and ultrastructural features of full development, including the expression of melanocyte specific markers and the presence of melanosomes up to the terminal stage of maturation. We have also compared the differentiating features of DPSCs grown in different culture conditions, following the timing of differentiation at molecular and cytochemical levels and found that in all culture conditions full development of these cells was obtained, although at different times. The spontaneous differentiating potential of these cells strongly suggests their possible applications in regenerative medicine.

A case of collision tumor or transdifferentiation between malignant melanoma and leiomyosarcoma

DEFF Research Database (Denmark)

Ul-Mulk, Jamshaid; Rasmussen, Helle; Breiting, Line

2012-01-01

with a seborrheic keratosis. There have also been occasional reports of rhabdomyosarcomatous differentiation. However, mesenchymal differentiation, and in this case leiomysarcoma, with formation of heterologous elements in melanocytic tumor is very rare. Another plausible explanation may be that malignant melanoma...

Investigating the Correlation of Alexithymia in People with Borderline Tendencies with Impulsivity, Self-Harm and Borderline Personality Traits

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Ahmad Mirgol

2018-03-01

Full Text Available Background and Objectives: The borderline personality disorder includes a cluster of syndromes and symptoms characterized by instable and impulsive behaviors. The aim of the present study was to investigate the correlation of alexithymia in people with borderline tendencies with impulsivity, self-harm and borderline personality traits. Material and Methods: In a descriptive-correlational and cross sectional research approach, 350 students from Tabriz University were selected using random cluster sampling. From this sample, 115 people with a borderline score higher than the cut-off point were chosen and labeled as people with borderline tendencies. Toronto Alexithymia Scale-20, STB, and SHI questionnaires were used to collect data. The data were analyzed using Pearson product-moment correlation and simultaneous multiple regression by SPSS software v.21. Results: The findings indicated that alexithymia has a positive and meaningful relationship with borderline personality traits (r=0.36, p Conclusion: Based on these findings, we can conclude that alexithymia and problems in identifying feelings are the main determinants of borderline personality traits and impulsivity. Also, alexithymia and problems in identifying feelings and problems in describing feelings subscales are the main determinants of self-harm.

Aqueous humor tyrosinase activity is indicative of iris melanocyte toxicity.

Science.gov (United States)

Mahanty, Sarmistha; Kawali, Ankush A; Dakappa, Shruthi Shirur; Mahendradas, Padmamalini; Kurian, Mathew; Kharbanda, Varun; Shetty, Rohit; Setty, Subba Rao Gangi

2017-09-01

Antibiotics such as fluoroquinolones (FQLs) are commonly used to treat ocular infections but are also known to cause dermal melanocyte toxicity. The release of dispersed pigments from the iris into the aqueous humor has been considered a possible ocular side effect of the systemic administration of FQLs such as Moxifloxacin, and this condition is known as bilateral acute iris transillumination (BAIT). Bilateral acute depigmentation of iris (BADI) is a similar condition, with iris pigment released into the aqueous, but it has not been reported as a side effect of FQL. Iris pigments are synthesized by the melanogenic enzyme tyrosinase (TYR) and can be detected but not quantified by using slit-lamp biomicroscopy. The correlation between dispersed pigments in the aqueous and the extent of melanocyte toxicity due to topical antibiotics in vivo is not well studied. Here, we aimed to study the effect of topical FQLs on iris tissue, the pigment release in the aqueous humor and the development of clinically evident iris atrophic changes. We evaluated this process by measuring the activity of TYR in the aqueous humor of 82 healthy eyes undergoing cataract surgery following topical application of FQLs such as Moxifloxacin (27 eyes, preservative-free) or Ciprofloxacin (29 eyes, with preservative) or the application of non-FQL Tobramycin (26 eyes, with preservative) as a control. In addition, the patients were questioned and examined for ocular side effects in pre- and post-operative periods. Our data showed a significantly higher mean TYR activity in the aqueous humor of Ciprofloxacin-treated eyes compared to Moxifloxacin- (preservative free, p iris melanocytes. However, the reduced TYR activity in the aqueous of Moxifloxacin-treated eyes was possibly due to the presence of a higher drug concentration, which inhibits TYR activity. Consistently, immunoblotting analysis of the aqueous humor from both Ciprofloxacin- and Moxifloxacin-treated eyes showed the presence of soluble

Automatic Classification of Specific Melanocytic Lesions Using Artificial Intelligence

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Joanna Jaworek-Korjakowska

2016-01-01

Full Text Available Background. Given its propensity to metastasize, and lack of effective therapies for most patients with advanced disease, early detection of melanoma is a clinical imperative. Different computer-aided diagnosis (CAD systems have been proposed to increase the specificity and sensitivity of melanoma detection. Although such computer programs are developed for different diagnostic algorithms, to the best of our knowledge, a system to classify different melanocytic lesions has not been proposed yet. Method. In this research we present a new approach to the classification of melanocytic lesions. This work is focused not only on categorization of skin lesions as benign or malignant but also on specifying the exact type of a skin lesion including melanoma, Clark nevus, Spitz/Reed nevus, and blue nevus. The proposed automatic algorithm contains the following steps: image enhancement, lesion segmentation, feature extraction, and selection as well as classification. Results. The algorithm has been tested on 300 dermoscopic images and achieved accuracy of 92% indicating that the proposed approach classified most of the melanocytic lesions correctly. Conclusions. A proposed system can not only help to precisely diagnose the type of the skin mole but also decrease the amount of biopsies and reduce the morbidity related to skin lesion excision.

A reporter mouse model for in vivo tracing and in vitro molecular studies of melanocytic lineage cells and their diseases.

Science.gov (United States)

Crawford, Melissa; Leclerc, Valerie; Dagnino, Lina

2017-08-15

Alterations in melanocytic lineage cells give rise to a plethora of distinct human diseases, including neurocristopathies, cutaneous pigmentation disorders, loss of vision and hearing, and melanoma. Understanding the ontogeny and biology of melanocytic cells, as well as how they interact with their surrounding environment, are key steps in the development of therapies for diseases that involve this cell lineage. Efforts to culture and characterize primary melanocytes from normal or genetically engineered mouse models have at times yielded contrasting observations. This is due, in part, to differences in the conditions used to isolate, purify and culture these cells in individual studies. By breeding ROSA mT/mG and Tyr::CreER T2 mice, we generated animals in which melanocytic lineage cells are identified through expression of green fluorescent protein. We also used defined conditions to systematically investigate the proliferation and migration responses of primary melanocytes on various extracellular matrix (ECM) substrates. Under our culture conditions, mouse melanocytes exhibit doubling times in the range of 10 days, and retain exponential proliferative capacity for 50-60 days. In culture, these melanocytes showed distinct responses to different ECM substrates. Specifically, laminin-332 promoted cell spreading, formation of dendrites, random motility and directional migration. In contrast, low or intermediate concentrations of collagen I promoted adhesion and acquisition of a bipolar morphology, and interfered with melanocyte forward movements. Our systematic evaluation of primary melanocyte responses emphasizes the importance of clearly defining culture conditions for these cells. This, in turn, is essential for the interpretation of melanocyte responses to extracellular cues and to understand the molecular basis of disorders involving the melanocytic cell lineage. © 2017. Published by The Company of Biologists Ltd.

Influence of melanocytes in the ex-vivo reconstructed epidermal melanin unit following an acute UV irradiation; Role des melanocytes dans l'unite epidermique de melanisation reconstruite ex-vivo apres une irradiation UV aigue

Energy Technology Data Exchange (ETDEWEB)

Cario-Andre, M

2000-11-15

Influence of melanocytes in skin pigmentation is well documented, however its photo-protective role has given rise to controversy. The role of melanocytes have been investigated on reconstructed epidermis with 100 % of keratinocytes or 95 % of keratinocytes and 5 % of melanocytes. In a first time, the effect of an acute UVB dose has been studied on both reconstructed epidermis, next we have investigated UVA and UVA+B effects on these epidermis. Following irradiation, the presence of melanocytes in reconstructed epidermis protects against apoptosis without protecting significantly against DNA damage formation (CPD, 6-4PP) and protects against UV-induced unbalance of the SOD/catalase ratio (antioxidants enzymes). On the contrary, the presence of melanocytes in reconstructed epidermis amplifies lipids and proteins oxidations but seems to protect against DNA oxidations. Melanocytes differ from keratinocytes by their melanin content and their more important concentration in polyunsaturated fatty acids. To evaluate what is the part of melanin and the part of polyunsaturated fatty acids in epidermal UV responses, reconstructed epidermis with keratinocytes have been supplemented with polyunsaturated fatty acid. This study indicates that polyunsaturated fatty acids are responsible for lipids and proteins oxidations and that melanin protect against DNA oxidation induced by lipid peroxidation. All these studies demonstrate that, model of reconstructed epidermis and epidermis in-vivo have the same behaviour following UV irradiation. In the last part, sunscreens and antioxidants have been tested on reconstructed epidermis and have demonstrated that model of reconstructed epidermis is suitable for photo-protective molecules screening. (author)

MRI appearances of borderline ovarian tumours

Energy Technology Data Exchange (ETDEWEB)

Bent, C.L. [Department of Diagnostic Imaging, St Bartholomew' s Hospital, West Smithfield, London (United Kingdom)], E-mail: clare.bent@bartsandthelondon.nhs.uk; Sahdev, A.; Rockall, A.G. [Department of Diagnostic Imaging, St Bartholomew' s Hospital, West Smithfield, London (United Kingdom); Singh, N. [Department of Pathology, St Bartholomew' s Hospital, West Smithfield, London (United Kingdom); Sohaib, S.A. [Department of Radiology, Royal Marsden Hospital, London (United Kingdom); Reznek, R.H. [Cancer Imaging, St Bartholomew' s Hospital, West Smithfield, London (United Kingdom)

2009-04-15

This review was performed to describe the range of magnetic resonance imaging (MRI) appearances of borderline ovarian tumours. The MRI findings in 26 patients with 31 borderline ovarian tumours (mean age: 40.1 years, range: 14-85 years) were retrospectively reviewed. For each tumour, site, size, MRI characteristics, and enhancement following gadolinium administration were recorded. There were 20 serous and 11 mucinous borderline ovarian subtypes. Nine of 26 patients demonstrated bilateral disease on MRI; synchronous contralateral ovarian disease included three benign, five serous borderline, and one serous invasive tumour. A history of a metachronous mucinous borderline tumour was identified in one patient. MRI appearances were classified into four morphological categories: group 1 (6/31, 19%), unilocular cysts; group 2 (6/31, 19%), minimally septate cysts with papillary projections; group 3 (14/31, 45%), markedly septate lesions with plaque-like excrescences; and group 4 (5/31, 16%), predominantly solid with exophytic papillary projections, all of serous subtype. There was a significant difference in mean volume between serous (841.5 cm{sup 3}) and mucinous (6358.2 cm{sup 3}) subtypes (p = 0.009). All tumours demonstrated at least one MRI feature suggestive of malignancy. The present review demonstrates the variable MRI appearances of borderline ovarian tumours along with imaging features suggestive of tumour subtype. In patients in whom the clinical features are suggestive of a borderline ovarian tumour (young age and normal or minimally elevated CA125), the ability to predict a borderline disease using morphological features observed on MRI would be extremely helpful in surgical planning, with the potential to offer fertility or ovary-preserving surgery. Future studies are required to further this aim.

Image enhancement of optical images for binary system of melanocytes and keratinocytes

Science.gov (United States)

Takanezawa, S.; Baba, A.; Sako, Y.; Ozaki, Y.; Date, A.; Toyama, K.; Morita, S.

2013-05-01

Automatic determination of the cell shapes of large numbers of melanocytes based on optical images of human skin models have been largely unsuccessful (the complexities introduced by dendrites and the melanin pigmentation over the keratinocytes to give unclear outlines). Here, we present an image enhancement procedure for enhancing the contrast of images with removing the non-uniformity of background. The brightness is normalized also for the non-uniform population density of melanocytes.

Genome-wide analyses of borderline personality features

NARCIS (Netherlands)

Lubke, G.H.; Laurin, C.; Amin, N.; Hottenga, J.J.; Willemsen, G.; Grootheest, G.; Abdellaoui, A.; Karssen, L.C.; Oostra, B.A.; van Duijn, C.M.; Penninx, B.W.J.H.; Boomsma, D.I.

2014-01-01

The heritability of borderline personality (BP) features has been established in multiple twin and family studies. Using data from the borderline subscale of the Personality Assessment Inventory Borderline Features Scale (PAI-BOR) collected in two Dutch cohorts (N=7125), the Netherlands Twin

Effect of norfloxacin and moxifloxacin on melanin synthesis and antioxidant enzymes activity in normal human melanocytes.

Science.gov (United States)

Beberok, Artur; Wrześniok, Dorota; Otręba, Michał; Miliński, Maciej; Rok, Jakub; Buszman, Ewa

2015-03-01

Fluoroquinolone antibiotics provide broad-spectrum coverage for a number of infectious diseases, including respiratory as well as urinary tract infections. One of the important adverse effects of these drugs is phototoxicity which introduces a serious limitation to their use. To gain insight the molecular mechanisms underlying the fluoroquinolones-induced phototoxic side effects, the impact of two fluoroquinolone derivatives with different phototoxic potential, norfloxacin and moxifloxacin, on melanogenesis and antioxidant enzymes activity in normal human melanocytes HEMa-LP was determined. Both drugs induced concentration-dependent loss in melanocytes viability. The value of EC50 for these drugs was found to be 0.5 mM. Norfloxacin and moxifloxacin suppressed melanin biosynthesis; antibiotics were shown to inhibit cellular tyrosinase activity and to reduce melanin content in melanocytes. When comparing the both analyzed fluoroquinolones, it was observed that norfloxacin possesses greater inhibitory effect on tyrosinase activity in melanocytes than moxifloxacin. The extent of oxidative stress in cells was assessed by measuring the activity of antioxidant enzymes: SOD, CAT, and GPx. It was observed that norfloxacin caused higher depletion of antioxidant status in melanocytes when compared with moxifloxacin. The obtained results give a new insight into the mechanisms of fluoroquinolones toxicity directed to pigmented tissues. Moreover, the presented differences in modulation of biochemical processes in melanocytes may be an explanation for various phototoxic activities of the analyzed fluoroquinolone derivatives in vivo.

Transtorno borderline: história e atualidade

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Paulo Dalgalarrondo

Full Text Available No presente trabalho é feita uma revisão histórica e psicopatológica do distúrbio borderline. O autor sugere que a categoria clínica introduzida por Kahlbaum, em 1890, “heiboidophenie”, pode ser considerada como um protoconceito na origem do conceito de transtorno borderline. No final dos anos 70 e 80, sob a influência do DMS-III, a esquizofrenia latente ou borderline se transformava em dois subtipos de transtorno de personalidade: borderline e esquizotípico. Alguns aspectos psicopatológicos do Transtorno de Personalidade Borderline são revistos, com especial ênfase sobre os sintomas afetivos e as alterações no plano das relações interpessoais.

The nuclear factor (erythroid-derived 2)-like 2 (NRF2) antioxidant response promotes melanocyte viability and reduces toxicity of the vitiligo-inducing phenol monobenzone.

Science.gov (United States)

Arowojolu, Omotayo A; Orlow, Seth J; Elbuluk, Nada; Manga, Prashiela

2017-07-01

Vitiligo, characterised by progressive melanocyte death, can be initiated by exposure to vitiligo-inducing phenols (VIPs). VIPs generate oxidative stress in melanocytes and activate the master antioxidant regulator NRF2. While NRF2-regulated antioxidants are reported to protect melanocytes from oxidative stress, the role of NRF2 in the melanocyte response to monobenzone, a clinically relevant VIP, has not been characterised. We hypothesised that activation of NRF2 may protect melanocytes from monobenzone-induced toxicity. We observed that knockdown of NRF2 or NRF2-regulated antioxidants NQO1 and PRDX6 reduced melanocyte viability, but not viability of keratinocytes and fibroblasts, suggesting that melanocytes were preferentially dependent upon NRF2 activity for growth compared to other cutaneous cells. Furthermore, melanocytes activated the NRF2 response following monobenzone exposure and constitutive NRF2 activation reduced monobenzone toxicity, supporting NRF2's role in the melanocyte stress response. In contrast, melanocytes from individuals with vitiligo (vitiligo melanocytes) did not activate the NRF2 response as efficiently. Dimethyl fumarate-mediated NRF2 activation protected normal and vitiligo melanocytes against monobenzone-induced toxicity. Given the contribution of oxidant-antioxidant imbalance in vitiligo, modulation of this pathway may be of therapeutic interest. © 2017 John Wiley & Sons A/S. Published by John Wiley & Sons Ltd.

Ultraviolet radiation directly induces pigment production by cultured human melanocytes

International Nuclear Information System (INIS)

Friedmann, P.S.; Gilchrest, B.A.

1987-01-01

In humans the major stimulus for cutaneous pigmentation is ultraviolet radiation (UVR). Little is known about the mechanism underlying this response, in part because of the complexity of interactions in whole epidermis. Using a recently developed culture system, human melanocytes were exposed daily to a physiologic range of UVR doses from a solar simulator. Responses were determined 24 hours after the last exposure. There was a dose-related increase in melanin content per cell and uptake of 14 C-DOPA, accompanied by growth inhibition. Cells from donors of different racial origin gave proportionately similar increases in melanin, although there were approximately tenfold differences in basal values. Light and electron microscopy revealed UVR-stimulated increases in dendricity as well as melanosome number and degree of melanization, analogous to the well-recognized melanocyte changes following sun exposure of intact skin. Similar responses were seen with Cloudman S91 melanoma cells, although this murine cell line required lower UVR dosages and fewer exposures for maximal stimulation. These data establish that UVR is capable of directly stimulating melanogenesis. Because cyclic AMP elevation has been associated in some settings with increased pigment production by cultured melanocytes, preliminary experiments were conducted to see if the effects of UVR were mediated by cAMP. Both alpha-MSH and isobutylmethylxanthine (IBMX), as positive controls, caused a fourfold increase in cAMP level in human melanocytes and/or S91 cells, but following a dose of UVR sufficient to stimulate pigment production there was no change in cAMP level up to 4 hours after exposure. Thus, it appears that the UVR-induced melanogenesis is mediated by cAMP-independent mechanisms

Confocal laser scanning microscopy in vivo for diagnosing melanocytic skin neoplasms

Directory of Open Access Journals (Sweden)

A. A. Kubanova

2014-01-01

Full Text Available The authors discuss the use of confocal laser scanning microscopy in vivo (CLSM for diagnosing melanocytic skin neoplasms and its value for early diagnostics of melanoma. CLSM is an innovation noninvasive visual examination method for real-time multiple and painless examinations of the patient’s skin without injuring the skin integument. The method ensures early diagnostics of skin melanomas with high sensitivity and specificity, which makes it possible to use CLSM for screening melanocytic skin neoplasms for the sake of the early onset of treatment to save patient life and health.

MC1R and the response of melanocytes to ultraviolet radiation

International Nuclear Information System (INIS)

Rouzaud, Francois; Kadekaro, Ana Luisa; Abdel-Malek, Zalfa A.; Hearing, Vincent J.

2005-01-01

The constitutive color of our skin plays a dramatic role in our photoprotection from solar ultraviolet radiation (UVR) that reaches the Earth and in minimizing DNA damage that gives rise to skin cancer. More than 120 genes have been identified and shown to regulate pigmentation, one of the key genes being melanocortin 1 receptor (MC1R) that encodes the melanocortin 1 receptor (MC1R), a seven-transmembrane G protein-coupled receptor expressed on the surface of melanocytes. Modulation of MC1R function regulates melanin synthesis by melanocytes qualitatively and quantitatively. The MC1R is regulated by the physiological agonists α-melanocyte-stimulating hormone (αMSH) and adrenocorticotropic hormone (ACTH), and antagonist agouti signaling protein (ASP). Activation of the MC1R by binding of an agonist stimulates the synthesis of eumelanin primarily via activation of adenylate cyclase. The significance of cutaneous pigmentation lies in the photoprotective effect of melanin, particularly eumelanin, against sun-induced carcinogenesis. Epidermal melanocytes and keratinocytes respond to UVR by increasing their expression of αMSH and ACTH, which up-regulate the expression of MC1R, and consequently enhance the response of melanocytes to melanocortins. Constitutive skin pigmentation dramatically affects the incidence of skin cancer. The pigmentary phenotype characterized by red hair, fair complexion, inability to tan and tendency to freckle is an independent risk factor for all skin cancers, including melanoma. The MC1R gene is highly polymorphic in human populations, and allelic variation at this locus accounts, to a large extent, for the variation in pigmentary phenotypes and skin phototypes (SPT) in humans. Several allelic variants of the MC1R gene are associated with the red hair and fair skin (RHC) phenotype, and carrying one of these variants is thought to diminish the ability of the epidermis to respond to DNA damage elicited by UVR. The MC1R gene is considered a

MC1R and the response of melanocytes to ultraviolet radiation

Energy Technology Data Exchange (ETDEWEB)

Rouzaud, Francois [Laboratory of Cell Biology, National Cancer Institute, National Institutes of Health, Building 37, Room 2132, Bethesda, MD 20892 (United States); Kadekaro, Ana Luisa [Department of Dermatology, University of Cincinnati, College of Medicine, Cincinnati, OH 45267 (United States); Abdel-Malek, Zalfa A. [Department of Dermatology, University of Cincinnati, College of Medicine, Cincinnati, OH 45267 (United States); Hearing, Vincent J. [Laboratory of Cell Biology, National Cancer Institute, National Institutes of Health, Building 37, Room 2132, Bethesda, MD 20892 (United States)]. E-mail: hearingv@nih.gov

2005-04-01

The constitutive color of our skin plays a dramatic role in our photoprotection from solar ultraviolet radiation (UVR) that reaches the Earth and in minimizing DNA damage that gives rise to skin cancer. More than 120 genes have been identified and shown to regulate pigmentation, one of the key genes being melanocortin 1 receptor (MC1R) that encodes the melanocortin 1 receptor (MC1R), a seven-transmembrane G protein-coupled receptor expressed on the surface of melanocytes. Modulation of MC1R function regulates melanin synthesis by melanocytes qualitatively and quantitatively. The MC1R is regulated by the physiological agonists {alpha}-melanocyte-stimulating hormone ({alpha}MSH) and adrenocorticotropic hormone (ACTH), and antagonist agouti signaling protein (ASP). Activation of the MC1R by binding of an agonist stimulates the synthesis of eumelanin primarily via activation of adenylate cyclase. The significance of cutaneous pigmentation lies in the photoprotective effect of melanin, particularly eumelanin, against sun-induced carcinogenesis. Epidermal melanocytes and keratinocytes respond to UVR by increasing their expression of {alpha}MSH and ACTH, which up-regulate the expression of MC1R, and consequently enhance the response of melanocytes to melanocortins. Constitutive skin pigmentation dramatically affects the incidence of skin cancer. The pigmentary phenotype characterized by red hair, fair complexion, inability to tan and tendency to freckle is an independent risk factor for all skin cancers, including melanoma. The MC1R gene is highly polymorphic in human populations, and allelic variation at this locus accounts, to a large extent, for the variation in pigmentary phenotypes and skin phototypes (SPT) in humans. Several allelic variants of the MC1R gene are associated with the red hair and fair skin (RHC) phenotype, and carrying one of these variants is thought to diminish the ability of the epidermis to respond to DNA damage elicited by UVR. The MC1R gene is

Azerbaijan-Russia Borderline Security

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Ekaterina V. Arkhipova

2017-03-01

Full Text Available The Azerbaijan-Russia borderline mainly goes by the Caucasian mountain range and close to the Samur riverbed. Main border posts are situated close to the Caspian seashore while the locals living in the Upper Dagestan area have difficulties with crossing borderline. The locals are represented by the so called “divided peoples” whose living area was divided with the state border after 1991. The former inner borders ignored ethnic areas but now they became the lines crossing the ethnic groups of Legins, Avars, Tzakhurs and Rutuls. Certainly, those peoples are interested in specific rules for crossing the border. At the same time, their areas have not got the equipped border offices and they have to spend a lot of time and money for travelling to the neighboring districts via Baku or Vladikavkaz. Such problems arouse the radical demands among locals. The Lezgin movement for an independent Lezgistan is the most famous among them. Its supporters were involved in a terrorist attack in Baku in 1990-s and now they collect files about any problems connected with border issues, including the results of a demarcation process. They attract attention to the facts of all assignments made by Russian representatives. The activity of other ethnic groups was comparatively lower and they could make an agreement with local authorities about division of powers. Obviously, any solution about development of the border infrastructure may stabilize the separatism activity in the area. The author determines the key challenges and threats to cross-border security at Azerbaijan-Russia borderline on the basis of analysis of Federal and regional media, declarations made by representatives of the local and borderline authorities, as well as online activities of national movements. The author reveals the infrastructure factors of ensuring cross-border activity, social and economic conditions of borderline districts development. The suggestion is made on the need to develop

UVA phototransduction drives early melanin synthesis in human melanocytes.

Science.gov (United States)

Wicks, Nadine L; Chan, Jason W; Najera, Julia A; Ciriello, Jonathan M; Oancea, Elena

2011-11-22

Exposure of human skin to solar ultraviolet radiation (UVR), a powerful carcinogen [1] comprising ~95% ultraviolet A (UVA) and ~5% ultraviolet B (UVB) at the Earth's surface, promotes melanin synthesis in epidermal melanocytes [2, 3], which protects skin from DNA damage [4, 5]. UVB causes DNA lesions [6] that lead to transcriptional activation of melanin-producing enzymes, resulting in delayed skin pigmentation within days [7]. In contrast, UVA causes primarily oxidative damage [8] and leads to immediate pigment darkening (IPD) within minutes, via an unknown mechanism [9, 10]. No receptor protein directly mediating phototransduction in skin has been identified. Here we demonstrate that exposure of primary human epidermal melanocytes (HEMs) to UVA causes calcium mobilization and early melanin synthesis. Calcium responses were abolished by treatment with G protein or phospholipase C (PLC) inhibitors or by depletion of intracellular calcium stores. We show that the visual photopigment rhodopsin [11] is expressed in HEMs and contributes to UVR phototransduction. Upon UVR exposure, significant melanin production was measured within one hour; cellular melanin continued to increase in a retinal- and calcium-dependent manner up to 5-fold after 24 hr. Our findings identify a novel UVA-sensitive signaling pathway in melanocytes that leads to calcium mobilization and melanin synthesis and may underlie the mechanism of IPD in human skin. Copyright © 2011 Elsevier Ltd. All rights reserved.

Melanocyte-secreted fibromodulin promotes an angiogenic microenvironment.

Science.gov (United States)

Adini, Irit; Ghosh, Kaustabh; Adini, Avner; Chi, Zai-Long; Yoshimura, Takeru; Benny, Ofra; Connor, Kip M; Rogers, Michael S; Bazinet, Lauren; Birsner, Amy E; Bielenberg, Diane R; D'Amato, Robert J

2014-01-01

Studies have established that pigmentation can provide strong, protective effects against certain human diseases. For example, angiogenesis-dependent diseases such as wet age-related macular degeneration and infantile hemangioma are more common in light-skinned individuals of mixed European descent than in African-Americans. Here we found that melanocytes from light-skinned humans and albino mice secrete high levels of fibromodulin (FMOD), which we determined to be a potent angiogenic factor. FMOD treatment stimulated angiogenesis in numerous in vivo systems, including laser-induced choroidal neovascularization, growth factor-induced corneal neovascularization, wound healing, and Matrigel plug assays. Additionally, FMOD enhanced vascular sprouting during normal retinal development. Deletion of Fmod in albino mice resulted in a marked reduction in the amount of neovascularization induced by retinal vein occlusion, corneal growth factor pellets, and Matrigel plugs. Our data implicate the melanocyte-secreted factor FMOD as a key regulator of angiogenesis and suggest an underlying mechanism for epidemiological differences between light-skinned individuals of mixed European descent and African-Americans. Furthermore, inhibition of FMOD in humans has potential as a therapeutic strategy for treating angiogenesis-dependent diseases.

Investigation of cellular signalling responses to non-ionising radiation in melanocytes by microarray analysis

International Nuclear Information System (INIS)

Boyle, G.M.; Pedley, J.; Martyn, A.C.; Fraser, L.M.; Banducci, K.J.; Parsons, P.G.; Breit, S.N.

2003-01-01

Melanoma is a highly aggressive cancer resulting from the abnormal proliferation and spread of specialised pigment cells in the skin, known as melanocytes. Extensive epidemiological and molecular evidence suggests that a major risk factor for melanoma formation is exposure to non-ionising radiation in the form of solar ultra-violet (UV) light. However, the exact role of solar UV in the development of melanoma is unclear. To elucidate the molecular events that occur in melanocytes following solar UV exposure and determine how they lead to melanoma development, cDNA microarray analysis was used to analyse the gene expression profile of normal melanocytes, melanocytes exposed to simulated solar UV and melanoma cells. The development of cDNA microarray technology has allowed gene expression profiling at the mRNA level to be conducted for many thousands of genes simultaneously by hybridising an array of known sequences with labelled cDNA reverse transcribed form the sample RNA. Gene expression analysis was performed for over 13,000 genes. More than 500 genes were identified as differentially expressed in melanocytes following a single UV exposure, although overall there was a general suppression of transcription. Genes that were up-regulated included oncogenes and cytoskeletal genes; in contrast, genes encoding protein tyrosine kinases and apoptosis effectors were down-regulated. Many of the genes identified as being differentially expressed represent novel UV-regulated targets. Repeated exposure to solar UV resulted in the elevation in expression of a novel member of the transforming growth factor-b (TGF-b) superfamily, the Macrophage Inhibitory Cytokine-1 (MIC-1). Our results have shown that MIC-1 is up-regulated by solar UV in melanocytes, and is highly expressed (>3 fold) in a number of metastatic melanoma cell lines (31/61) in comparison to primary melanocytes. Furthermore functional, dimerised MIC-1 was found to be secreted by melanocytes, and secreted levels were

Transformation of a Silent Adrencorticotrophic Pituitary Tumor Into Central Nervous System Melanoma

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Brandon A. Miller MD, PhD

2013-06-01

Full Text Available Silent adrenocorticotrophic pituitary adenomas are nonfunctioning pituitary adenomas that express adrenocorticotrophic hormone (ACTH but do not cause the clinical or laboratory features of hypercortisolemia. Primary central nervous system (CNS melanoma is well documented, but rarely originates in the sellar region or pituitary gland. Here we report transformation of an aggressive silent adrenocorticotrophic pituitary adenoma that transformed into CNS melanoma and review other presentations of pituitary melanoma. A 37-year-old woman initially presented with apoplexy and an invasive nonfunctioning pituitary macroadenoma for which she underwent transphenoidal surgery. The patient underwent 3 subsequent surgeries as the tumor continued to progress. Pathology from the first 3 operations showed pituitary adenoma or carcinoma. Pathology from the final surgery showed melanoma and the magnetic resonance imaging characteristics of the tumor had changed to become consistent with CNS melanoma. Dermatologic and ophthalmologic examinations did not identify cutaneous or ocular melanoma. The patient’s disease progressed despite aggressive surgical, medical and radiologic treatment. To our knowledge, this is the first report demonstrating transformation of a primary pituitary tumor into melanoma. The mechanism of tumor transformation is unclear, but it is possible that a mutation in the original ACTH-producing tumor lead to increased cleavage of pro-opiomelanocortin or ACTH into α-melanocyte-stimulating hormone, which in turn stimulated the expression of microopthalmia transcription factor, leading to melanocytic phenotype transformation.

Neurochemical alterations associated with borderline personality disorder.

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Atmaca, Murad; Karakoc, Tevfik; Mermi, Osman; Gurkan Gurok, M; Yildirim, Hanefi

2015-01-01

In neuroimaging on borderline personality disorder, prior studies focused on the hippocampus and amygdala, as mentioned above. However, no study investigated whether there were neurochemical changes in the patients with borderline personality disorder. Therefore, in the present study, we aimed to investigate neurochemical change of patients diagnosed with borderline disorder and hypothesized that neurochemicals would change in the hippocampus region of these patients. Seventeen patients and the same number of healthy control subjects were analyzed by using a 1.5 Tesla GE Signa Imaging System. N-acetylaspartate (NAA), choline compounds (CHO), and creatine (CRE) values of hippocampal region were measured. The mean NAA/CRE ratio in the hippocampus region was significantly reduced in the patients with borderline personality disorder compared to that of healthy control subjects, In addition, NAA/CHO ratio of the patients with borderline personality disorder was also significantly reduced when compared to that of healthy subjects. There was no difference in the ratio of CHO/CRE. In summary, we present evidence for reduced NAA in the patients with borderline personality disorder. © 2015, The Author(s).

Molecular Subtyping of Serous Ovarian Tumors Reveals Multiple Connections to Intrinsic Breast Cancer Subtypes

DEFF Research Database (Denmark)

Jönsson, Jenny-Maria; Johansson, Ida; Dominguez-Valentin, Mev

2014-01-01

expressed between benign and malignant serous ovarian tumors, with cell cycle processes enriched in the malignant subgroup. Borderline tumors were split between the two clusters. Significant correlations between the malignant serous tumors and the highly aggressive ovarian cancer signatures, and the basal...

Developmental aspects of borderline personality disorder.

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Reich, D B; Zanarini, M C

2001-01-01

This study examined whether patients with borderline personality disorder and controls with other personality disorders remember their childhoods differently with respect to separation difficulties, evocative memory, temperamental factors such as frustration tolerance and mood reactivity, and onset of symptoms. Two hundred and ninety patients with borderline personality disorder and 72 with other personality disorders were assessed using an instrument to rate memories of separation difficulties, temperamental problems, and onset of symptoms before age 18. Patients with borderline personality disorder remembered more difficulties with separation between ages 6 and 17 years, more mood reactivity and poorer frustration tolerance between ages 6 and 17, and the onset of more symptoms (most prominently sadness, depression, anxiety, and suicidality) before age 18 than did patients with other personality disorders. The groups did not differ in reports of evocative memory before age 18. These results indicate that many of the features of adult patients with borderline personality disorder may initially appear during childhood and adolescence and that these features may be used to differentiate borderline from other personality disorders.

A pigmented calcifying cystic odontogenic tumor associated with compound odontoma: a case report and review of literature

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Borkosky Silvia S

2007-09-01

Full Text Available Abstract Background Pigmented intraosseous odontogenic lesions are rare with only 47 reported cases in the English literature. Among them, pigmented calcifying cystic odontogenic tumor, formerly known as calcifying odontogenic cyst, is the most common lesion with 20 reported cases. Methods A case of pigmented calcifying cystic odontogenic tumor associated with odontoma occurring at the mandibular canine-premolar region of a young Japanese boy is presented with radiographic, and histological findings. Special staining, electron microscopic study and immunohistochemical staining were also done to characterize the pigmentation. Results The pigments in the lesion were confirmed to be melanin by Masson-Fontana staining and by transmission electron microscopy. The presence of dendritic melanocytes within the lesion was also demonstrated by S-100 immunostaining. Conclusion The present case report of pigmented calcifying cystic odontogenic tumor associated with odontoma features a comprehensive study on melanin and melanocytes, including histochemical, immunohistochemical and transmission electron microscopic findings.

[Alpha-melanocyte-stimulating hormone. From bench to bedside].

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Böhm, M; Luger, T A

2010-06-01

Alpha-melanocyte-stimulating hormone (alpha-MSH) is a tridecapeptide that is produced by the skin itself from the precursor proopiomelanocortin. It crucially mediates ultraviolet light-induced tanning after binding to melanocortin-1 receptors (MC-1R) expressed on the surface of epidermal melanocytes. The potent pigment-inducing and also cytoprotective actions of alpha-MSH are the rationale for the performance of first phase II clinical trials with Nle4-D-Phe7-alpha-MSH (NDP-alpha-MSH), a subcutaneously administered synthetic and superpotent alpha-MSH analogue, in patients with photodermatoses such as erythropoietic protoporphyria. Since alpha-MSH has shown promising anti-inflammatory and antifibrotic properties in numerous preclinical studies, it will be most interesting to evaluate these effects in further clinical pilot studies with NDP-alpha-MSH. In addition to alpha-MSH analogues, truncated tripeptides such as KDPT which do not bind to MC-1R but have sustained anti-inflammatory properties are currently emerging as another novel therapeutic strategy in dermatology.

Interleukins 1alpha and 1beta secreted by some melanoma cell lines strongly reduce expression of MITF-M and melanocyte differentiation antigens.

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Kholmanskikh, Olga; van Baren, Nicolas; Brasseur, Francis; Ottaviani, Sabrina; Vanacker, Julie; Arts, Nathalie; van der Bruggen, Pierre; Coulie, Pierre; De Plaen, Etienne

2010-10-01

We report that melanoma cell lines expressing the interleukin-1 receptor exhibit 4- to 10-fold lower levels of mRNA of microphthalmia-associated transcription factor (MITF-M) when treated with interleukin-1beta. This effect is NF-kappaB and JNK-dependent. MITF-M regulates the expression of melanocyte differentiation genes such as MLANA, tyrosinase and gp100, which encode antigens recognized on melanoma cells by autologous cytolytic T lymphocytes. Accordingly, treating some melanoma cells with IL-1beta reduced by 40-100% their ability to activate such antimelanoma cytolytic T lymphocytes. Finally, we observed large amounts of biologically active IL-1alpha or IL-1beta secreted by two melanoma cell lines that did not express MITF-M, suggesting an autocrine MITF-M downregulation. We estimate that approximately 13% of melanoma cell lines are MITF-M-negative and secrete IL-1 cytokines. These results indicate that the repression of melanocyte-differentiation genes by IL-1 produced by stromal cells or by tumor cells themselves may represent an additional mechanism of melanoma immune escape.

Influence of melanocytes in the ex-vivo reconstructed epidermal melanin unit following an acute UV irradiation

International Nuclear Information System (INIS)

Cario-Andre, M.

2000-11-01

Influence of melanocytes in skin pigmentation is well documented, however its photo-protective role has given rise to controversy. The role of melanocytes have been investigated on reconstructed epidermis with 100 % of keratinocytes or 95 % of keratinocytes and 5 % of melanocytes. In a first time, the effect of an acute UVB dose has been studied on both reconstructed epidermis, next we have investigated UVA and UVA+B effects on these epidermis. Following irradiation, the presence of melanocytes in reconstructed epidermis protects against apoptosis without protecting significantly against DNA damage formation (CPD, 6-4PP) and protects against UV-induced unbalance of the SOD/catalase ratio (antioxidants enzymes). On the contrary, the presence of melanocytes in reconstructed epidermis amplifies lipids and proteins oxidations but seems to protect against DNA oxidations. Melanocytes differ from keratinocytes by their melanin content and their more important concentration in polyunsaturated fatty acids. To evaluate what is the part of melanin and the part of polyunsaturated fatty acids in epidermal UV responses, reconstructed epidermis with keratinocytes have been supplemented with polyunsaturated fatty acid. This study indicates that polyunsaturated fatty acids are responsible for lipids and proteins oxidations and that melanin protect against DNA oxidation induced by lipid peroxidation. All these studies demonstrate that, model of reconstructed epidermis and epidermis in-vivo have the same behaviour following UV irradiation. In the last part, sunscreens and antioxidants have been tested on reconstructed epidermis and have demonstrated that model of reconstructed epidermis is suitable for photo-protective molecules screening. (author)

G2 accumulation and melanin overproduction in malignant melanocytes treated with a new nitrosourea.

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Buchdahl, C; Papon, J; Communal, Y; Bourges, M; Madelmont, J C

1998-12-01

Cystemustine (N'-(2-chloroethyl)-N-(2-(methylsulphonyl)ethyl)-N'-nitrosourea), a new anticancer chloroethylnitrosourea (CENU) is being tested in a phase II clinical trial of disseminated melanoma. The antitumour effect of this drug is mainly due to DNA damage in malignant melanocytes. Recently, we have shown that this damage can induce apoptosis in some melanoma cell lines. In others, apoptosis is not clearly observed, although there is a strong cytostatic effect. In this paper, we have characterized the cytological effect of cystemustine on murine malignant melanocytes (B16 cell line) which are resistant to apoptosis induced by this CENU. The results show that 3 days after cystemustine treatment, these melanocytes had accumulated in phase G2 of the cell cycle. There was then a strong morphological modification during a long cytostatic phase up to 30 days after treatment. During this cytostatic phase, there was uncontrolled DNA synthesis and marked swelling. Also, tyrosinase activity, melanin content and the number of mature melanosomes were greatly increased. These results suggest that when malignant melanocytes are not able to undergo apoptosis after treatment with CENU, they accumulate in G2 and this is followed by enhancement of melanogenesis.

Immunopolarization of CD4(+) and CD8(+) T cells to type-1-like is associated with melanocyte loss in human vitiligo

NARCIS (Netherlands)

Wańkowicz-Kalińska, Anna; van den Wijngaard, René M. J. G. J.; Tigges, Bert J.; Westerhof, Wiete; Ogg, Graham S.; Cerundolo, Vincenzo; Storkus, Walter J.; Das, Pranab K.

2003-01-01

Vitiligo is an autoimmune condition characterized by loss of epidermal melanocytes. High frequencies of melanocyte-reactive cytotoxic T cells in the peripheral blood of vitiligo patients and the observed correlation between perilesional T-cell infiltration and melanocyte loss in situ suggest the

Affective disorders among patients with borderline personality disorder.

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Sjåstad, Hege Nordem; Gråwe, Rolf W; Egeland, Jens

2012-01-01

The high co-occurrence between borderline personality disorder and affective disorders has led many to believe that borderline personality disorder should be considered as part of an affective spectrum. The aim of the present study was to examine whether the prevalence of affective disorders are higher for patients with borderline personality disorder than for patients with other personality disorders. In a national cross-sectional study of patients receiving mental health treatment in Norway (N = 36 773), we determined whether psychiatric outpatients with borderline personality disorder (N = 1 043) had a higher prevalence of affective disorder in general, and whether they had an increased prevalence of depression, bipolar disorder or dysthymia specifically. They were compared to patients with paranoid, schizoid, dissocial, histrionic, obsessive-compulsive, avoidant, dependent, or unspecified personality disorder, as well as an aggregated group of patients with personality disorders other than the borderline type (N = 2 636). Odds ratios were computed for the borderline personality disorder group comparing it to the mixed sample of other personality disorders. Diagnostic assessments were conducted in routine clinical practice. More subjects with borderline personality disorder suffered from unipolar than bipolar disorders. Nevertheless, borderline personality disorder had a lower rate of depression and dysthymia than several other personality disorder groups, whereas the rate of bipolar disorder tended to be higher. Odds ratios showed 34% lower risk for unipolar depression, 70% lower risk for dysthymia and 66% higher risk for bipolar disorder in patients with borderline personality disorder compared to the aggregated group of other personality disorders. The results suggest that borderline personality disorder has a stronger association with affective disorders in the bipolar spectrum than disorders in the unipolar spectrum. This association may reflect

Affective disorders among patients with borderline personality disorder.

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Hege Nordem Sjåstad

Full Text Available BACKGROUND: The high co-occurrence between borderline personality disorder and affective disorders has led many to believe that borderline personality disorder should be considered as part of an affective spectrum. The aim of the present study was to examine whether the prevalence of affective disorders are higher for patients with borderline personality disorder than for patients with other personality disorders. METHODS: In a national cross-sectional study of patients receiving mental health treatment in Norway (N = 36 773, we determined whether psychiatric outpatients with borderline personality disorder (N = 1 043 had a higher prevalence of affective disorder in general, and whether they had an increased prevalence of depression, bipolar disorder or dysthymia specifically. They were compared to patients with paranoid, schizoid, dissocial, histrionic, obsessive-compulsive, avoidant, dependent, or unspecified personality disorder, as well as an aggregated group of patients with personality disorders other than the borderline type (N = 2 636. Odds ratios were computed for the borderline personality disorder group comparing it to the mixed sample of other personality disorders. Diagnostic assessments were conducted in routine clinical practice. RESULTS: More subjects with borderline personality disorder suffered from unipolar than bipolar disorders. Nevertheless, borderline personality disorder had a lower rate of depression and dysthymia than several other personality disorder groups, whereas the rate of bipolar disorder tended to be higher. Odds ratios showed 34% lower risk for unipolar depression, 70% lower risk for dysthymia and 66% higher risk for bipolar disorder in patients with borderline personality disorder compared to the aggregated group of other personality disorders. CONCLUSIONS: The results suggest that borderline personality disorder has a stronger association with affective disorders in the bipolar spectrum than

Affective Disorders among Patients with Borderline Personality Disorder

Science.gov (United States)

Sjåstad, Hege Nordem; Gråwe, Rolf W.; Egeland, Jens

2012-01-01

Background The high co-occurrence between borderline personality disorder and affective disorders has led many to believe that borderline personality disorder should be considered as part of an affective spectrum. The aim of the present study was to examine whether the prevalence of affective disorders are higher for patients with borderline personality disorder than for patients with other personality disorders. Methods In a national cross-sectional study of patients receiving mental health treatment in Norway (N = 36 773), we determined whether psychiatric outpatients with borderline personality disorder (N = 1 043) had a higher prevalence of affective disorder in general, and whether they had an increased prevalence of depression, bipolar disorder or dysthymia specifically. They were compared to patients with paranoid, schizoid, dissocial, histrionic, obsessive-compulsive, avoidant, dependent, or unspecified personality disorder, as well as an aggregated group of patients with personality disorders other than the borderline type (N = 2 636). Odds ratios were computed for the borderline personality disorder group comparing it to the mixed sample of other personality disorders. Diagnostic assessments were conducted in routine clinical practice. Results More subjects with borderline personality disorder suffered from unipolar than bipolar disorders. Nevertheless, borderline personality disorder had a lower rate of depression and dysthymia than several other personality disorder groups, whereas the rate of bipolar disorder tended to be higher. Odds ratios showed 34% lower risk for unipolar depression, 70% lower risk for dysthymia and 66% higher risk for bipolar disorder in patients with borderline personality disorder compared to the aggregated group of other personality disorders. Conclusions The results suggest that borderline personality disorder has a stronger association with affective disorders in the bipolar spectrum than disorders in the unipolar

Borderline Personality and the Detection of Angry Faces.

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Johanna Hepp

Full Text Available Many studies have assessed emotion recognition in patients with Borderline Personality Disorder and considerable evidence has been accumulated on patients' ability to categorize emotions. In contrast, their ability to detect emotions has been investigated sparsely. The only two studies that assessed emotion detection abilities found contradictory evidence on patients' ability to detect angry faces.To clarify whether patients with Borderline Personality Disorder show enhanced detection of angry faces, we conducted three experiments: a laboratory study (n = 53 with a clinical sample and two highly powered web studies that measured Borderline features (n1 = 342, n2 = 220. Participants in all studies completed a visual search paradigm, and the reaction times for the detection of angry vs. happy faces were measured.Consistently, data spoke against enhanced detection of angry faces in the Borderline groups, indicated by non-significant group (Borderline vs. healthy control × target (angry vs. happy interactions, despite highly satisfactory statistical power to detect even small effects.In contrast to emotion categorization, emotion detection appears to be intact in patients with Borderline Personality Disorder and individuals high in Borderline features. The importance of distinguishing between these two processes in future studies is discussed.

ALK-FISH borderline cases in non-small cell lung cancer: Implications for diagnostics and clinical decision making.

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von Laffert, Maximilian; Stenzinger, Albrecht; Hummel, Michael; Weichert, Wilko; Lenze, Dido; Warth, Arne; Penzel, Roland; Herbst, Hermann; Kellner, Udo; Jurmeister, Philipp; Schirmacher, Peter; Dietel, Manfred; Klauschen, Frederick

2015-12-01

Fluorescence in-situ hybridization (FISH) for the detection of ALK-rearrangements in non-small cell lung cancer (NSCLC) is based on at first sight clear cut-off criteria (≥15% of tumor cells) for split signals (SS) and single red signals (SRS). However, NSCLC with SS-counts around the cut-off may cause interpretation problems. Tissue microarrays containing 753 surgically resected NSCLCs were independently tested for ALK-alterations by FISH and immunohistochemistry (IHC). Our analysis focused on samples with SS/SRS in the range between 10% and 20% (ALK-FISH borderline group). To better understand the role of these samples in routine diagnostics, we performed statistical analyses to systematically estimate the probability of ALK-FISH-misclassification (false negative or positive) for different numbers of evaluated tumor cell nuclei (30, 50, 100, and 200). 94.3% (710/753) of the cases were classified as unequivocally (FISH-negative (93%; 700/753) or positive (1.3%; 10/753) and showed concordant IHC results. 5.7% (43/753) of the samples showed SS/SRS between 10% and 20% of the tumor cells. Out of these, 7% (3/43; ALK-FISH: 14%, 18% and 20%) were positive by ALK-IHC, while 93% (40/43) had no detectable expression of the ALK-protein. Statistical analysis showed that ALK-FISH misclassifications occur frequently for samples with rearrangements between 10% and 20% if ALK-characterization is based on a sharp cut-off point (15%). If results in this interval are defined as equivocal (borderline), statistical sampling-related ALK-FISH misclassifications will occur in less than 1% of the cases if 100 tumor cells are evaluated. While ALK status can be determined robustly for the majority of NSCLC by FISH our analysis showed that ∼6% of the cases belong to a borderline group for which ALK-FISH evaluation has only limited reliability due to statistical sampling effects. These cases should be considered equivocal and therapy decisions should include additional tests and clinical

Molecular effects of 1-naphthyl-methylcarbamate and solar radiation exposures on human melanocytes.

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Ferrucio, Bianca; Tiago, Manoela; Fannin, Richard D; Liu, Liwen; Gerrish, Kevin; Maria-Engler, Silvya Stuchi; Paules, Richard S; Barros, Silvia Berlanga de Moraes

2017-02-01

Carbaryl (1-naphthyl-methylcarbamate), a broad-spectrum insecticide, has recently been associated with the development of cutaneous melanoma in an epidemiological cohort study with U.S. farm workers also exposed to ultraviolet radiation, the main etiologic factor for skin carcinogenesis. We hypothesized that carbaryl exposure may increase deleterious effects of UV solar radiation on skin melanocytes. This study aimed to characterize human melanocytes after individual or combined exposure to carbaryl (100μM) and solar radiation (375mJ/cm 2 ). In a microarray analysis, carbaryl, but not solar radiation, induced an oxidative stress response, evidenced by the upregulation of antioxidant genes, such as Hemeoxygenase-1 (HMOX1), and downregulation of Microphtalmia-associated Transcription Factor (MITF), the main regulator of melanocytic activity; results were confirmed by qRT-PCR. Carbaryl and solar radiation induced a gene response suggestive of DNA damage and cell cycle alteration. The expression of CDKN1A, BRCA1/2 and MDM2 genes was notably more intense in the combined treatment group, in a synergistic manner. Flow cytometry assays demonstrated S-phase cell cycle arrest, reduced apoptosis levels and faster induction of cyclobutane pyrimidine dimers (CPD) lesions in carbaryl treated groups. Our data suggests that carbaryl is genotoxic to human melanocytes, especially when associated with solar radiation. Copyright © 2016 Elsevier B.V. All rights reserved.

Antimelanogenic Efficacy of Melasolv (3,4,5-Trimethoxycinnamate Thymol Ester) in Melanocytes and Three-Dimensional Human Skin Equivalent.

Science.gov (United States)

Lee, John Hwan; Lee, Eun-Soo; Bae, Il-Hong; Hwang, Jeong-Ah; Kim, Se-Hwa; Kim, Dae-Yong; Park, Nok-Hyun; Rho, Ho Sik; Kim, Yong Jin; Oh, Seong-Geun; Lee, Chang Seok

2017-01-01

Excessive melanogenesis often causes unaesthetic hyperpigmentation. In a previous report, our group introduced a newly synthesized depigmentary agent, Melasolv™ (3,4,5-trimethoxycinnamate thymol ester). In this study, we demonstrated the significant whitening efficacy of Melasolv using various melanocytes and human skin equivalents as in vitro experimental systems. The depigmentary effect of Melasolv was tested in melan-a cells (immortalized normal murine melanocytes), α-melanocyte-stimulating hormone (α-MSH)-stimulated B16 murine melanoma cells, primary normal human melanocytes (NHMs), and human skin equivalent (MelanoDerm). The whitening efficacy of Melasolv was further demonstrated by photography, time-lapse microscopy, Fontana-Masson (F&M) staining, and 2-photon microscopy. Melasolv significantly inhibited melanogenesis in the melan-a and α-MSH-stimulated B16 cells. In human systems, Melasolv also clearly showed a whitening effect in NHMs and human skin equivalent, reflecting a decrease in melanin content. F&M staining and 2-photon microscopy revealed that Melasolv suppressed melanin transfer into multiple epidermal layers from melanocytes as well as melanin synthesis in human skin equivalent. Our study showed that Melasolv clearly exerts a whitening effect on various melanocytes and human skin equivalent. These results suggest the possibility that Melasolv can be used as a depigmentary agent to treat pigmentary disorders as well as an active ingredient in cosmetics to increase whitening efficacy. © 2017 S. Karger AG, Basel.

The gender differences in the inhibitory action of UVB-induced melanocyte activation by the administration of tranexamic acid.

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Hiramoto, Keiichi; Yamate, Yurika; Sugiyama, Daijiro; Takahashi, Yumi; Mafune, Eiichi

2016-05-01

Tranexamic acid has an inhibitory action on ultraviolet (UV) B-induced melanocyte activation. This study examined the sex differences in the inhibitory action of tranexamic acid on UVB-induced melanocyte activation. We irradiated the eye and ear of male and female mice with UVB at a dose of 1.0 kJ/m(2) using a 20SE sunlamp. We orally administered tranexamic acid (750 mg/kg/day) at 30 min before UVB exposure. Tranexamic acid inhibited the UVB-induced epidermal melanocyte activation, and the effect was more remarkable under UVB eye irradiation than under UVB ear irradiation. Furthermore, the melanocyte activity suppression effect was stronger in female mice than in male mice. Following the administration of tranexamic acid, the female displayed increased blood levels of β-endorphin and μ-opioid receptor and estradiol receptor β expression in comparison with the male. Furthermore, the effect of melanocyte activity suppression in the female mice was decreased by the administration of tamoxifen (antagonist of estrogen receptor) or naltrexone (antagonist of μ-opioid receptor). These results suggest that the suppression by tranexamic acid of the UVB-induced melanocyte activation (UVB sensitivity) is stronger in female mice than in male mice and that female hormones and β-endorphin play an important role in this sex difference. © 2015 John Wiley & Sons A/S. Published by John Wiley & Sons Ltd.

Utility of DWI with quantitative ADC values in ovarian tumors: a meta-analysis of diagnostic test performance.

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Pi, Shan; Cao, Rong; Qiang, Jin Wei; Guo, Yan Hui

2018-01-01

Background Diffusion-weighted imaging (DWI) and quantitative apparent diffusion coefficient (ADC) values are widely used in the differential diagnosis of ovarian tumors. Purpose To assess the diagnostic performance of quantitative ADC values in ovarian tumors. Material and Methods PubMed, Embase, the Cochrane Library, and local databases were searched for studies assessing ovarian tumors using quantitative ADC values. We quantitatively analyzed the diagnostic performances for two clinical problems: benign vs. malignant tumors and borderline vs. malignant tumors. We evaluated diagnostic performances by the pooled sensitivity and specificity values and by summary receiver operating characteristic (SROC) curves. Subgroup analyses were used to analyze study heterogeneity. Results From the 742 studies identified in the search results, 16 studies met our inclusion criteria. A total of ten studies evaluated malignant vs. benign ovarian tumors and six studies assessed malignant vs. borderline ovarian tumors. Regarding the diagnostic accuracy of quantitative ADC values for distinguishing between malignant and benign ovarian tumors, the pooled sensitivity and specificity values were 0.91 and 0.91, respectively. The area under the SROC curve (AUC) was 0.96. For differentiating borderline from malignant tumors, the pooled sensitivity and specificity values were 0.89 and 0.79, and the AUC was 0.91. The methodological quality of the included studies was moderate. Conclusion Quantitative ADC values could serve as useful preoperative markers for predicting the nature of ovarian tumors. Nevertheless, prospective trials focused on standardized imaging parameters are needed to evaluate the clinical value of quantitative ADC values in ovarian tumors.

The prevalence of borderline personality symptoms in adolescents.

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Mohammadi, Mohammad Reza; Shamohammadi, Morteza; Salmanian, Maryam

2014-07-01

This study aimed to assess the prevalence of borderline personality symptoms in 16-18 year old adolescents. In this cross sectional - descriptive study, 422 high school students (211 boys, 211 girls) aged 16-18 were selected by cluster random sampling and simple random sampling in 2011-2012. The participants were assessed using the revised diagnostic interview for borderline questionnaire (DIB-R) and demographic questionnaire. Data were analyzed using Pearson correlation coefficient and Spearman correlation coefficient. Of the participants, 0/9% (0/22 % of the 16 year olds, 0.45 % of the 17 year olds and 0/22% of the 18 year olds) were diagnosed with borderline personality symptoms. Also, the prevalence of borderline personality symptoms in boys was 0/45 % of the total sample and it was 0/45 % of the total sample in girls. With respect to the relationship between demographic variables (age, sex, location, parents' occupation, parents' kinship, parents' education and birth order) and borderline personality symptoms, only parents' kinship showed a weak correlation with borderline personality symptoms. In the view of the prevalence of 0.9% of the borderline personality symptoms in adolescents, attention should be paid to the diagnosis and treatment of this disorder. Furthermore, works need to be done to improve the mental health and quality of life of adolescents.

Melanoma Therapy with Rhenium-Cyclized Alpha Melanocyte Stimulating Hormone Peptide Analogs

Energy Technology Data Exchange (ETDEWEB)

Thomas P Quinn

2005-11-22

Malignant melanoma is the 6th most commonly diagnosed cancer with increasing incidence in the United States. It is estimated that 54,200 cases of malignant melanoma will be newly diagnosed and 7,600 cases of death will occur in the United States in the year 2003 (1). At the present time, more than 1.3% of Americans will develop malignant melanoma during their lifetime (2). The average survival for patients with metastatic melanoma is about 6-9 months (3). Moreover, metastatic melanoma deposits are resistant to conventional chemotherapy and external beam radiation therapy (3). Systematic chemotherapy is the primary therapeutic approach to treat patients with metastatic melanoma. Dacarbazine is the only single chemotherapy agent approved by FDA for metastatic melanoma treatment (5). However, the response rate to Dacarbazine is only approximately 20% (6). Therefore, there is a great need to develop novel treatment approaches for metastatic melanoma. The global goal of this research program is the rational design, characterization and validation of melanoma imaging and therapeutic radiopharmaceuticals. Significant progress has been made in the design and characterization of metal-cyclized radiolabeled alpha-melanocyte stimulating hormone peptides. Therapy studies with {sup 188}Re-CCMSH demonstrated the therapeutic efficacy of the receptor-targeted treatment in murine and human melanoma bearing mice (previous progress report). Dosimetry calculations, based on biodistribution data, indicated that a significant dose was delivered to the tumor. However, {sup 188}Re is a very energetic beta-particle emitter. The longer-range beta-particles theoretically would be better for larger tumors. In the treatment of melanoma, the larger primary tumor is usually surgically removed leaving metastatic disease as the focus of targeted radiotherapy. Isotopes with lower beta-energies and/or shorter particle lengths should be better suited for targeting metastases. The {sup 177}Lu

Evaluation of the Melanocytic Pathology Assessment Tool and Hierarchy for Diagnosis (MPATH-Dx) classification scheme for diagnosis of cutaneous melanocytic neoplasms: Results from the International Melanoma Pathology Study Group.

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Lott, Jason P; Elmore, Joann G; Zhao, Ge A; Knezevich, Stevan R; Frederick, Paul D; Reisch, Lisa M; Chu, Emily Y; Cook, Martin G; Duncan, Lyn M; Elenitsas, Rosalie; Gerami, Pedram; Landman, Gilles; Lowe, Lori; Messina, Jane L; Mihm, Martin C; van den Oord, Joost J; Rabkin, Michael S; Schmidt, Birgitta; Shea, Christopher R; Yun, Sook Jung; Xu, George X; Piepkorn, Michael W; Elder, David E; Barnhill, Raymond L

2016-08-01

Pathologists use diverse terminology when interpreting melanocytic neoplasms, potentially compromising quality of care. We sought to evaluate the Melanocytic Pathology Assessment Tool and Hierarchy for Diagnosis (MPATH-Dx) scheme, a 5-category classification system for melanocytic lesions. Participants (n = 16) of the 2013 International Melanoma Pathology Study Group Workshop provided independent case-level diagnoses and treatment suggestions for 48 melanocytic lesions. Individual diagnoses (including, when necessary, least and most severe diagnoses) were mapped to corresponding MPATH-Dx classes. Interrater agreement and correlation between MPATH-Dx categorization and treatment suggestions were evaluated. Most participants were board-certified dermatopathologists (n = 15), age 50 years or older (n = 12), male (n = 9), based in the United States (n = 11), and primary academic faculty (n = 14). Overall, participants generated 634 case-level diagnoses with treatment suggestions. Mean weighted kappa coefficients for diagnostic agreement after MPATH-Dx mapping (assuming least and most severe diagnoses, when necessary) were 0.70 (95% confidence interval 0.68-0.71) and 0.72 (95% confidence interval 0.71-0.73), respectively, whereas correlation between MPATH-Dx categorization and treatment suggestions was 0.91. This was a small sample size of experienced pathologists in a testing situation. Varying diagnostic nomenclature can be classified into a concise hierarchy using the MPATH-Dx scheme. Further research is needed to determine whether this classification system can facilitate diagnostic concordance in general pathology practice and improve patient care. Copyright © 2016 American Academy of Dermatology, Inc. Published by Elsevier Inc. All rights reserved.

Coexistence of borderline ovarian epithelial tumor, primary pelvic hydatid cyst, and lymphoepithelioma-like gastric carcinoma.

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Gungor, Tayfun; Altinkaya, Sunduz Ozlem; Sirvan, Levent; Lafuente, Roberto Alvarez; Ceylaner, Serdar

2011-06-01

Borderline ovarian tumors (BOTs) represent a heterogeneous group of ovarian epithelial neoplasms. Despite a favorable prognosis, 10-20% of BOTs exhibit progressively worsening clinic. Primary involvement of pelvic organs with echinococcus is very rare. Lymphoepithelioma-like gastric carcinoma is a rare neoplasm of the stomach. A 58-year-old woman referred with abdominal swelling and gastric complaints. Imaging studies revealed a huge cystic mass with multiple septations and solid component, another cystic mass with an appearance of cyst hydatid in the pelvis, and thickening of the small curvature of stomach. Gastroscopy revealed an ulcer with a suspicious malignant appearance, and histology of the endoscopic specimen showed severe chronic inflammation and lymphocytic infiltration. No other involvement of hydatid cyst was detected. In the exploration, there was a 25cm cystic lesion with solid components arising from right ovary, another 6cm cyst over the former, 7cm cystic lesion arising from left ovary, and 10cm mass near the small curvature of the stomach. Excision of the masses; total gastrectomy with esophagojejunal anastomosis; total abdominal hysterectomy; bilateral salpingo-oophorectomy; omentectomy; appendectomy; splenectomy; and pelvic, paraaortic, and coeliac lympadenectomy were performed. Final pathology revealed lymphoepithelioma-like gastric carcinoma, bilateral serous BOT, and hydatid cyst. Hydatid cyst should always be considered in the differential diagnosis of abdominopelvic masses in endemic regions of the world. Preoperative diagnosis of primary pelvic hydatid disease is difficult and awareness of its possibility is very important especially in patients residing in or coming from endemic areas. Copyright © 2011. Published by Elsevier B.V.

The prevalence of borderline personality symptoms in adolescents.

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Mohammad Reza Mohammadi

2014-09-01

Full Text Available This study aimed to assess the prevalence of borderline personality symptoms in 16-18 year old adolescents.In this cross sectional - descriptive study, 422 high school students (211 boys, 211 girls aged 16-18 were selected by cluster random sampling and simple random sampling in 2011-2012. The participants were assessed using the revised diagnostic interview for borderline questionnaire (DIB-R and demographic questionnaire. Data were analyzed using Pearson correlation coefficient and Spearman correlation coefficient.Of the participants, 0/9% (0/22 % of the 16 year olds, 0.45 % of the 17 year olds and 0/22% of the 18 year olds were diagnosed with borderline personality symptoms. Also, the prevalence of borderline personality symptoms in boys was 0/45 % of the total sample and it was 0/45 % of the total sample in girls. With respect to the relationship between demographic variables (age, sex, location, parents' occupation, parents' kinship, parents' education and birth order and borderline personality symptoms, only parents' kinship showed a weak correlation with borderline personality symptoms.In the view of the prevalence of 0.9% of the borderline personality symptoms in adolescents, attention should be paid to the diagnosis and treatment of this disorder. Furthermore, works need to be done to improve the mental health and quality of life of adolescents.

Perivascular Epithelioid Cell Tumor in the Stomach

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Sun Ah Shin

2017-07-01

Full Text Available Perivascular epithelioid cell tumors or PEComas can arise in any location in the body. However, a limited number of cases of gastric PEComa have been reported. We present two cases of gastric PEComas. The first case involved a 62-year-old woman who presented with a 4.2 cm gastric subepithelial mass in the prepyloric antrum, and the second case involved a 67-year-old man with a 5.0 cm mass slightly below the gastroesophageal junction. Microscopic examination revealed that both tumors were composed of perivascular epithelioid cells that were immunoreactive for melanocytic and smooth muscle markers. Prior to surgery, the clinical impression of both tumors was gastrointestinal stromal tumor (GIST, and the second case was erroneously diagnosed as GIST even after microscopic examination. Although gastric PEComa is a very rare neoplasm, it should be considered in the differential diagnosis of gastric submucosal lesions.

Diagnosis and staging of female genital tract melanocytic lesions using pump-probe microscopy (Conference Presentation)

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Robles, Francisco E.; Selim, Maria A.; Warren, Warren S.

2016-02-01

Melanoma of the vulva is the second most common type of malignancy afflicting that organ. This disease caries poor prognosis, and shows tendencies to recur locally and develop distant metastases through hematogenous dissemination. Further, there exists significant clinical overlap between early-stage melanomas and melanotic macules, benign lesions that are believed to develop in about 10% of the general female population. In this work we apply a novel nonlinear optical method, pump-probe microscopy, to quantitatively analyze female genitalia tract melanocytic lesions. Pump-probe microscopy provides chemical information of endogenous pigments by probing their electronic excited state dynamics, with subcellular resolution. Using unstained biopsy sections from 31 patients, we find significant differences between melanin type and structure in tissue regions with invasive melanoma, melanoma in-situ and non-malignant melanocytic proliferations (e.g., nevi, melanocytic macules). The molecular images of non-malignant lesion have a well-organized structure, with relatively homogenous pigment chemistry, most often consistent with that of eumelanin with large aggregate size or void of metals, such as iron. On the other hand, pigment type and structure observed in melanomas in-situ and invasive melanomas is typically much more heterogeneous, with larger contributions from pheomelanin, melanins with larger metal content, and/or melanins with smaller aggregate size. Of most significance, clear differences can be observed between melanocytic macules and vulvar melanoma in-situ, which, as discussed above, can be difficult to clinically distinguish. This initial study demonstrates pump-probe microscopy's potential as an adjuvant diagnostic tool by revealing systematic chemical and morphological differences in melanin pigmentation among invasive melanoma, melanoma in-situ and non-malignant melanocytic lesions.

Circulating tumor cells in melanoma patients.

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Gary A Clawson

Full Text Available Circulating tumor cells (CTCs are of recognized importance for diagnosis and prognosis of cancer patients. With melanoma, most studies do not show any clear relationship between CTC levels and stage of disease. Here, CTCs were enriched (∼400X from blood of melanoma patients using a simple centrifugation device (OncoQuick, and 4 melanocyte target RNAs (TYR, MLANA, MITF, and MIF were quantified using QPCR. Approximately one-third of melanoma patients had elevated MIF and MLANA transcripts (p<0.0001 and p<0.001, respectively compared with healthy controls. In contrast, healthy controls had uniformly higher levels of TYR and MITF than melanoma patients (p<0.0001. There was a marked shift of leukocytes into the CTC-enriched fractions (a 430% increase in RNA recovery, p<0.001, and no relationship between CTC levels and stage of disease was found. CTCs were captured on microfabricated filters and cultured. Captured melanoma CTCs were large cells, and consisted of 2 subpopulations, based on immunoreactivity. One subpopulation (∼50% stained for both pan-cytokeratin (KRT markers and the common leukocyte marker CD-45, whereas the second subpopulation stained for only KRT. Since similar cells are described in many cancers, we also examined blood from colorectal and pancreatic cancer patients. We observed analogous results, with most captured CTCs staining for both CD-45/KRT markers (and for the monocyte differentiation marker CD-14. Our results suggest that immature melanocyte-related cells (expressing TYR and MITF RNA may circulate in healthy controls, although they are not readily detectable without considerable enrichment. Further, as early-stage melanomas develop, immature melanocyte migration into the blood is somehow curtailed, whereas a significant proportion of patients develop elevated CTC levels (based on MIF and MLANA RNAs. The nature of the captured CTCs is consistent with literature describing leukocyte/macrophage-tumor cell fusion hybrids

An approach to malignant mammary phyllodes tumors detection

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Ilić Ivan

2009-01-01

Full Text Available Background/Aim. Mammary phyllodes tumors (MPT are uncommon fibroepithelial (biphasic neoplasms whose clinical behavior is difficult to predict on the basis of histological criteria only. They are divided into benign, borderline malignant and malignant groups. Sometimes it appears difficult to distinguish these tumors from other types of soft tissue sarcomas. Because of the relatively scant data on the role of biological markers in MPT histogenesis, we have decided to undertake the following study, trying to shed more light on the issue by investigating the following elements that make up MPT: their histological patterns, biological behavior, enzymohistochemical, histochemical and immunohistochemical characteristics (ICH together with the mast cell analysis. Methods. We examined the biopsy material of 35 MPT in our laboratory. Enzymohistochemistry was performed on frozen sections (method of Crowford, Nachlas and Seligman. The used methods were classical hematoxylin-eosin (H&E; histochemical Massontrichrome, Alcian-blue, Periodic acid Schiff and immunohistochemical LSAB2 method (DacoCytomation. Ki-67, ckit, vimentin, estrogen receptor (ER, progesterone receptor (PR and Her-2 oncoprotein immunohistochemistry was performed on all tumors. Results. The patients were ranged per age from 30-62 years (mean 43.3 years, median 39 years. A total of 35 cases of MPT were included: 20 benign (57%, 6 borderline malignant (17% and 9 malignant (26%. Twenty-two patients (62.8 % underwent segmental mastectomy, while 13 (37.2% had total mastectomies. Twenty-eight patients had negative surgical margins at original resection. The mean size of malignant MPT (7.8 cm was larger than that of benign MPT (4.5 cm. Significant features of the malignant MPT were: stromal cellularity, stromal cellular atypism, high mitotic activity, atypic mitoses, stromal overgrowth, infiltrative tumor contour and heterologous stromal elements. Benign MPT showed strong enzymohistochemical

Giant Congenital Melanocytic Nevus (GCMN - A New Hope for Targeted Therapy?

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Georgi Tchernev

2017-07-01

Full Text Available We present a 6-month-old male patient, who was consulted with dermatologist by his parents, because of a pigmented lesion, present since birth, covering almost the all skin of the back and buttocks.  A sharply bordered, unequally coloured congenital pigmented nevus, measuring approximately 21 cm in diameter was observed in the whole body skin examination. The lesion was affecting the lower 2/3 of the skin of the back and the top half of the gluteus area, extending to the lateral part of the tors, forward the abdomen and the upper lateral part of the hips, composed by multiple darker-pigmented nests and several lighter areas, with single depigmented zones, hairy surface, irregularly infiltrated on palpation. Congenital melanocytic nevi are presented in approximately 1% of newborns, while giant congenital melanocytic nevi (GCMN are the most uncommon subtype of them; with occurrence rate 1 in 50,000 births. They affect 2% of a total body surface or presenting in a diameter larger than 20 cm in older children. Although not common, the possible malignant transformation remains one of the most important considerations related to them, as the related lifetime risk of melanoma is 4% to 10%. Treatment recommendations include non-surgical methods as dermabrasion only within the first two weeks of life, for prevention the possible melanocytic deeper migration, while serial surgical excisions or tissue expanders could be useful treatment tool even in later stages. Nevertheless, cosmetic result is not always satisfactory, and the risk of malignant changes remains, in cases of previous melanocytic migration in deeper layer. Recent article suggests the potential role in the treatment of GCMN with NRAS inhibitor trametinib, approved for treatment of advanced melanoma, associated with underlying NRAS mutations. Although promising, the drug could be useful in paediatric patients, only with associated NRAS gene mutation. It is still unclear whether it could be

Asymmetry and irregularity border as discrimination factor between melanocytic lesions

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Sbrissa, David; Pratavieira, Sebastião.; Salvio, Ana Gabriela; Kurachi, Cristina; Bagnato, Vanderlei Salvadori; Costa, Luciano Da Fontoura; Travieso, Gonzalo

2015-06-01

Image processing tools have been widely used in systems supporting medical diagnosis. The use of mobile devices for the diagnosis of melanoma can assist doctors and improve their diagnosis of a melanocytic lesion. This study proposes a method of image analysis for melanoma discrimination from other types of melanocytic lesions, such as regular and atypical nevi. The process is based on extracting features related with asymmetry and border irregularity. It were collected 104 images, from medical database of two years. The images were obtained with standard digital cameras without lighting and scale control. Metrics relating to the characteristics of shape, asymmetry and curvature of the contour were extracted from segmented images. Linear Discriminant Analysis was performed for dimensionality reduction and data visualization. Segmentation results showed good efficiency in the process, with approximately 88:5% accuracy. Validation results presents sensibility and specificity 85% and 70% for melanoma detection, respectively.

Malignant melanoma arising in congenital melanocytic nevi: clinical and dermoscopic challenges

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Fatma Pelin Cengiz

2017-01-01

Full Text Available Congenital melanocytic nevi (CMN are visible pigmented lesions in the skin that are present at birth. CMN are benign malformations resulting from defective development of melanocyte precursors in the embryo. Six MMs from six patients were analyzed by clinical and dermoscopic examination. Of the patients, 33.3% were female (N = 2 and 66.6% were male (N = 4. Of the MMs, four (66.6% were superficial spreading MM and two (33.3 % were in situ MM. A reticular pattern was present in the MMs of three patients (50%, a homogeneous pattern was present in the other patients (50% at the base of the MMs. Superficial spreading melanomas and in situ melanomas with atypical dots and globules and a blue-white veil were the most common dermoscopic features of MMs found in CMN.

Parental qualities as perceived by borderline personality disorders.

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Goldberg, R L; Mann, L S; Wise, T N; Segall, E A

1985-01-01

This study explores the contribution of parental qualities to the borderline personality disorder. The Parental Bonding Inventory is used to compare four parental qualities (caring mother, caring father, overprotective father, and overprotective mother) across three groups (borderline personality disorders, assorted psychiatric controls and normal controls). The major finding was that the borderline patients perceived their parents to be significantly less caring and more overprotective than both the psychiatric control or nonclinical control groups. This study was verified previous reports that patients diagnosed with an affective illness (in either the borderline group or psychiatric control group) reported no significant differences on the inventory. Pinpointing parental characteristics which antecede mental disorders may be an important first step in devising primary preventive interventions for adult disorders.

Substance abuse in borderline personality disorder: clinical and etiological correlates

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van den Bosch, L. M.; Verheul, R.; van den Brink, W.

2001-01-01

This work examines differences between female borderline patients with and without substance abuse problems and between borderline patients from different treatment settings. A total of 64 female borderline patients were recruited from mental health services (n = 34) and addiction treatment services

Preoperative serum levels of epidermal growth factor receptor, HER2, and vascular endothelial growth factor in malignant and benign ovarian tumors

DEFF Research Database (Denmark)

Dahl Steffensen, Karina; Waldstrøm, Marianne; Jeppesen, Ulla

2008-01-01

, and malignant ovarian tumors. Patients and Methods: Serum from 233 patients (75 serous ovarian/tubal/peritoneal cancers, 24 borderline tumors, 110 benign ovarian tumors, and 24 with normal ovaries) were analyzed for EGFR, HER2, and VEGF using commercially available enzyme-linked immunosorbent assays (ELISA......). Results: The median EGFR serum level in patients with ovarian cancer was 51 ng/mL, and this was significantly lower than the median serum levels in borderline tumors (P =.0054) and benign ovarian tumors (P ovaries (P =.00028). The HER2 median serum level...... as in patients with normal ovaries (P =.00024). Conclusion: Significantly lower serum EGFR levels and higher VEGF levels were noted in patients with ovarian cancer compared with the levels in benign tumors and normal ovaries. Vascular endothelial growth factor and EGFR could have clinical importance as serum...

Clinical status of comorbid bipolar disorder and borderline personality disorder.

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Parker, Gordon; Bayes, Adam; McClure, Georgia; Del Moral, Yolanda Romàn Ruiz; Stevenson, Janine

2016-09-01

The status and differentiation of comorbid borderline personality disorder and bipolar disorder is worthy of clarification. To determine whether comorbid borderline personality disorder and bipolar disorder are interdependent or independent conditions. We interviewed patients diagnosed with either a borderline personality disorder and/or a bipolar condition. Analyses of participants grouped by DSM diagnoses established that those with comorbid conditions scored similarly to those with a borderline personality disorder alone on all key variables (i.e. gender, severity of borderline personality scores, developmental stressors, illness correlates, self-injurious behaviour rates) and differed from those with a bipolar disorder alone on nearly all non-bipolar item variables. Similar findings were returned for groups defined by clinical diagnoses. Comorbid bipolar disorder and borderline personality disorder is consistent with the formal definition of comorbidity in that, while coterminous, individuals meeting such criteria have features of two independent conditions. © The Royal College of Psychiatrists 2016.

Borderline Personality Disorder

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... of a mood disorder—not borderline personality disorder Self-harming behavior, such as cutting Recurring thoughts of suicidal ... symptoms and reduce the number of suicidal or self-harming behaviors. Read more on NIMH’s Psychotherapies health topic ...

Borderline lepromatous leprosy with neurofibromatosis

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Angoori Gnaneshwar

2010-01-01

Full Text Available The coexistence of leprosy with neurofibromatosis is rare both the diseases present with nerve thickening and skin lesions (patches and nodules. The coexistence of neurofibroma with borderline tuberculoid, lepromatous, histoid, and neuritic leprosy has been reported in the past. We report here a case of borderline lepromatous leprosy coexisting with neurofibromatosis in a 60 year-old male, who presented with neurofibromata and nerve thickening. Histopathology of skin biopsy from the leprosy and neurofibroma nodules confirmed the diagnosis of leprosy and neurofibroma.

Role of biological factors in etiopathogenesis of borderline personality disorder

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Jolanta Rabe-Jabłońska

2012-09-01

Full Text Available Emotionally labile personality of borderline type (borderline personality occurs in 1-2% of individuals from general population; 75% of this group are women. Similarly to most of the other mental disorders, the borderline personality results from a combination of biological, social and psychological factors. The subject of this study is a survey of the current knowledge on biological factors of borderline personality. Most researchers are of the opinion that these personality disorders are determined genetically, with such inherited temperamental traits as: dysregulation, impulsivity, and hypersensitivity. Perhaps hereditary is also a defect within the serotonergic system, endogenous opioid system and/or dopaminergic system related to the reward system. Many researchers have recently perceived the dysfunction of endogenous opioid system as an integral component of borderline personality. There is now a lot of evidence showing that this dysfunction as well as that of the reward system may account for most of the borderline personality symptoms which constitute an involuntary attempt of stimulating the inefficient systems. This is how e.g. the presence of reckless sexual behaviours, unstable interpersonal relationships and inability to delay the reward in borderline personality is accounted for. Such observations may in the future constitute an important indication for seeking a more effective pharmacotherapy for patients with borderline personality. It is possible that in some patients the described dysfunctions may be alleviated with time. This is implied by the results of comprehensive prospective studies which show a significant regression of symptoms and improvement in functioning of most patients with borderline personality after at least several years.

Vitiligo inducing phenols activate the unfolded protein response in melanocytes resulting in upregulation of IL6 and IL8

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Toosi, Siavash; Orlow, Seth J.; Manga, Prashiela

2012-01-01

Vitiligo is characterized by depigmented skin patches due to loss of epidermal melanocytes. Oxidative stress may play a role in vitiligo onset, while autoimmunity contributes to disease progression. In this study we sought to identify mechanisms that link disease triggers and spreading of lesions. A hallmark of melanocytes at the periphery of vitiligo lesions is dilation of the endoplasmic reticulum (ER). We hypothesized that oxidative stress results in redox disruptions that extend to the ER, causing accumulation of misfolded peptides, which activates the unfolded protein response (UPR). We used 4-tertiary butyl phenol (4-TBP) and monobenzyl ether of hydroquinone (MBEH), known triggers of vitiligo. We show that expression of key UPR components, including the transcription factor X-box binding protein 1 (XBP1), are increased following exposure of melanocytes to phenols. XBP1 activation increases production of immune mediators interleukin-6 (IL6) and IL8. Co-treatment with XBP1 inhibitors reduced IL6 and IL8 production induced by phenols, while over-expression of XBP1 alone increased their expression. Thus, melanocytes themselves produce cytokines associated with activation of an immune response following exposure to chemical triggers of vitiligo. These results expand our understanding of the mechanisms underlying melanocyte loss in vitiligo and pathways linking environmental stressors and autoimmunity. PMID:22696056

Vitiligo-inducing phenols activate the unfolded protein response in melanocytes resulting in upregulation of IL6 and IL8.

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Toosi, Siavash; Orlow, Seth J; Manga, Prashiela

2012-11-01

Vitiligo is characterized by depigmented skin patches caused by loss of epidermal melanocytes. Oxidative stress may have a role in vitiligo onset, while autoimmunity contributes to disease progression. In this study, we sought to identify mechanisms that link disease triggers and spreading of lesions. A hallmark of melanocytes at the periphery of vitiligo lesions is dilation of the endoplasmic reticulum (ER). We hypothesized that oxidative stress results in redox disruptions that extend to the ER, causing accumulation of misfolded peptides, which activates the unfolded protein response (UPR). We used 4-tertiary butyl phenol and monobenzyl ether of hydroquinone, known triggers of vitiligo. We show that expression of key UPR components, including the transcription factor X-box-binding protein 1 (XBP1), is increased following exposure of melanocytes to phenols. XBP1 activation increases production of immune mediators IL6 and IL8. Co-treatment with XBP1 inhibitors reduced IL6 and IL8 production induced by phenols, while overexpression of XBP1 alone increased their expression. Thus, melanocytes themselves produce cytokines associated with activation of an immune response following exposure to chemical triggers of vitiligo. These results expand our understanding of the mechanisms underlying melanocyte loss in vitiligo and pathways linking environmental stressors and autoimmunity.

Gene expression analysis of zebrafish melanocytes, iridophores, and retinal pigmented epithelium reveals indicators of biological function and developmental origin.

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Charles W Higdon

Full Text Available In order to facilitate understanding of pigment cell biology, we developed a method to concomitantly purify melanocytes, iridophores, and retinal pigmented epithelium from zebrafish, and analyzed their transcriptomes. Comparing expression data from these cell types and whole embryos allowed us to reveal gene expression co-enrichment in melanocytes and retinal pigmented epithelium, as well as in melanocytes and iridophores. We found 214 genes co-enriched in melanocytes and retinal pigmented epithelium, indicating the shared functions of melanin-producing cells. We found 62 genes significantly co-enriched in melanocytes and iridophores, illustrative of their shared developmental origins from the neural crest. This is also the first analysis of the iridophore transcriptome. Gene expression analysis for iridophores revealed extensive enrichment of specific enzymes to coordinate production of their guanine-based reflective pigment. We speculate the coordinated upregulation of specific enzymes from several metabolic pathways recycles the rate-limiting substrate for purine synthesis, phosphoribosyl pyrophosphate, thus constituting a guanine cycle. The purification procedure and expression analysis described here, along with the accompanying transcriptome-wide expression data, provide the first mRNA sequencing data for multiple purified zebrafish pigment cell types, and will be a useful resource for further studies of pigment cell biology.

Primary Cilia Negatively Regulate Melanogenesis in Melanocytes and Pigmentation in a Human Skin Model.

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Choi, Hyunjung; Shin, Ji Hyun; Kim, Eun Sung; Park, So Jung; Bae, Il-Hong; Jo, Yoon Kyung; Jeong, In Young; Kim, Hyoung-June; Lee, Youngjin; Park, Hea Chul; Jeon, Hong Bae; Kim, Ki Woo; Lee, Tae Ryong; Cho, Dong-Hyung

2016-01-01

The primary cilium is an organelle protruding from the cell body that senses external stimuli including chemical, mechanical, light, osmotic, fluid flow, and gravitational signals. Skin is always exposed to the external environment and responds to external stimuli. Therefore, it is possible that primary cilia have an important role in skin. Ciliogenesis was reported to be involved in developmental processes in skin, such as keratinocyte differentiation and hair formation. However, the relation between skin pigmentation and primary cilia is largely unknown. Here, we observed that increased melanogenesis in melanocytes treated with a melanogenic inducer was inhibited by a ciliogenesis inducer, cytochalasin D, and serum-free culture. However, these inhibitory effects disappeared in GLI2 knockdown cells. In addition, activation of sonic hedgehog (SHH)-smoothened (Smo) signaling pathway by a Smo agonist, SAG inhibited melanin synthesis in melanocytes and pigmentation in a human skin model. On the contrary, an inhibitor of primary cilium formation, ciliobrevin A1, activated melanogenesis in melanocytes. These results suggest that skin pigmentation may be regulated partly by the induction of ciliogenesis through Smo-GLI2 signaling.

Primary Cilia Negatively Regulate Melanogenesis in Melanocytes and Pigmentation in a Human Skin Model.

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Hyunjung Choi

Full Text Available The primary cilium is an organelle protruding from the cell body that senses external stimuli including chemical, mechanical, light, osmotic, fluid flow, and gravitational signals. Skin is always exposed to the external environment and responds to external stimuli. Therefore, it is possible that primary cilia have an important role in skin. Ciliogenesis was reported to be involved in developmental processes in skin, such as keratinocyte differentiation and hair formation. However, the relation between skin pigmentation and primary cilia is largely unknown. Here, we observed that increased melanogenesis in melanocytes treated with a melanogenic inducer was inhibited by a ciliogenesis inducer, cytochalasin D, and serum-free culture. However, these inhibitory effects disappeared in GLI2 knockdown cells. In addition, activation of sonic hedgehog (SHH-smoothened (Smo signaling pathway by a Smo agonist, SAG inhibited melanin synthesis in melanocytes and pigmentation in a human skin model. On the contrary, an inhibitor of primary cilium formation, ciliobrevin A1, activated melanogenesis in melanocytes. These results suggest that skin pigmentation may be regulated partly by the induction of ciliogenesis through Smo-GLI2 signaling.

Autocrine IL-6 mediates pituitary tumor senescence

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Fuertes, Mariana; Ajler, Pablo; Carrizo, Guillermo; Cervio, Andrés; Sevlever, Gustavo; Stalla, Günter K.; Arzt, Eduardo

2017-01-01

Cellular senescence is a stable proliferative arrest state. Pituitary adenomas are frequent and mostly benign, but the mechanism for this remains unknown. IL-6 is involved in pituitary tumor progression and is produced by the tumoral cells. In a cell autonomous fashion, IL-6 participates in oncogene-induced senescence in transduced human melanocytes. Here we prove that autocrine IL-6 participates in pituitary tumor senescence. Endogenous IL-6 inhibition in somatotroph MtT/S shRNA stable clones results in decreased SA-β-gal activity and p16INK4a but increased pRb, proliferation and invasion. Nude mice injected with IL-6 silenced clones develop tumors contrary to MtT/S wild type that do not, demonstrating that clones that escape senescence are capable of becoming tumorigenic. When endogenous IL-6 is silenced, cell cultures derived from positive SA-β-gal human tumor samples decrease the expression of the senescence marker. Our results establish that IL-6 contributes to maintain senescence by its autocrine action, providing a natural model of IL-6 mediated benign adenoma senescence. PMID:27902467

MicroRNA expression in melanocytic nevi: the usefulness of formalin-fixed, paraffin-embedded material for miRNA microarray profiling

DEFF Research Database (Denmark)

Glud, M.; Klausen, M.; Gniadecki, R.

2009-01-01

surgical specimens are formalin fixed and paraffin embedded (FFPE). To explore whether FFPE material would be suitable for miRNA profiling in melanocytic lesions, we compared miRNA expression patterns in FFPE versus fresh frozen samples, obtained from 15 human melanocytic nevi. Out of microarray data, we...

Co-occurrence of dissociative identity disorder and borderline personality disorder.

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Ross, Colin A; Ferrell, Lynn; Schroeder, Elizabeth

2014-01-01

The literature indicates that, among individuals with borderline personality disorder, pathological dissociation correlates with a wide range of impairments and difficulties in psychological function. It also predicts a poorer response to dialectical behavior therapy for borderline personality disorder. We hypothesized that (a) dissociative identity disorder commonly co-occurs with borderline personality disorder and vice versa, and (b) individuals who meet criteria for both disorders have more comorbidity and trauma than individuals who meet criteria for only 1 disorder. We interviewed a sample of inpatients in a hospital trauma program using 3 measures of dissociation. The most symptomatic group was those participants who met criteria for both borderline personality disorder and dissociative identity disorder on the Dissociative Disorders Interview Schedule, followed by those who met criteria for dissociative identity disorder only, then those with borderline personality disorder only, and finally those with neither disorder. Greater attention should be paid to the relationship between borderline personality disorder and dissociative identity disorder.

Treatment of borderline personality disorder and co-occurring anxiety disorders

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Valenstein, Helen R.

2013-01-01

Anxiety disorders are highly prevalent among individuals with borderline personality disorder, with comorbidity rates of up to 90%. Anxiety disorders have been found to reduce the likelihood of achieving remission from borderline personality disorder over time and to increase the risk of suicide and self-injury in this population. Evidence-based treatments for borderline personality disorder have not sufficiently focused on targeting anxiety disorders, and their effects on these disorders are either limited or unknown. Conversely, evidence-based treatments for anxiety disorders typically exclude suicidal, self-injuring, and seriously comorbid patients, thereby limiting their generalizability to individuals with borderline personality disorder. To address these limitations, recent research has begun to emerge focused on developing and evaluating treatments for individuals with co-occurring borderline personality disorder and anxiety disorders, specifically posttraumatic stress disorder (PTSD), with promising initial results. However, there is a need for additional research in this area, particularly studies evaluating the treatment of anxiety disorders among high-risk and complex borderline personality disorder patients. PMID:23710329

Acral melanocytic lesions in the United States: Prevalence, awareness, and dermoscopic patterns in skin-of-color and non-Hispanic white patients.

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Madankumar, Reshmi; Gumaste, Priyanka V; Martires, Kathryn; Schaffer, Panta R; Choudhary, Sonal; Falto-Aizpurua, Leyre; Arora, Harleen; Kallis, Penelope J; Patel, Shailee; Damanpour, Shadi; Sanchez, Margaret I; Yin, Natalie; Chan, Aegean; Sanchez, Miguel; Polsky, David; Kanavy, Holly; Grichnik, James M; Stein, Jennifer A

2016-04-01

Acral lentiginous melanoma has increased mortality compared with other melanoma subtypes and disproportionately affects ethnic minorities. Acral melanocytic lesions have not been well studied in diverse populations of the United States. We sought to assess the prevalence, awareness, and dermoscopic patterns of acral melanocytic lesions in skin-of-color and non-Hispanic white patients. We prospectively examined the palms and soles of 1052 patients presenting to dermatology clinics in New York, NY, and Miami, FL, from October 2013 to April 2015. Acral melanocytic lesions were observed in 36% of our cohort. Skin-of-color patients were more likely to have acral melanocytic lesions than non-Hispanic white patients (P < .01). Acral melanocytic lesions correlated with increased mole counts, particularly on non-Hispanic white patients. The majority of lesions demonstrated benign dermoscopic patterns. We observed 2 lesions with the parallel ridge pattern in our cohort, both found to be atypical nevi on biopsy specimen. Patients often lacked awareness of the presence of their lesions. Interobserver variability in assessing dermoscopic patterns is a limitation. Melanocytic lesions of the palms and soles are common, particularly in a cohort of multiple ethnicities from the United States. Dermoscopy of acral lesions is an important clinical tool for diagnosis and management of these lesions. Copyright © 2015 American Academy of Dermatology, Inc. Published by Elsevier Inc. All rights reserved.

Characterizing somatization, hypochondriasis, and hysteria in the borderline personality disorder.

Science.gov (United States)

Snyder, S; Pitts, W M

1986-03-01

Somatization, hypochondriasis, and hysteria have often been considered as associated features of the borderline personality disorder. This study was designed to characterize these three syndromes in the borderline patient. Inpatients with DSM-III borderline personality disorder were compared with controls with dysthymic disorder. Scales and items from standardized rating instruments which measured the three syndromes were scored and compared between groups. Although the hysteria-obvious and hypochondriasis scales of the MMPI and the Hamilton Depression Scale item measuring hypochondriasis were elevated in the borderline group, there were no significant differences between groups. Scores of dysthymic patients significantly exceeded those of borderline patients on four of five MMPI codetypes measuring the three syndromes. Findings are discussed in light of previous psychodynamic, empirical, and research literature.

Melanome Therapy with Rhenium Cyclized Alpha Melanocyte Stimulating Hormone Peptide Analogs. Final report

International Nuclear Information System (INIS)

Quinn, Thomas P.

2005-01-01

Malignant melanoma is the 6th most commonly diagnosed cancer with increasing incidence in the United States. It is estimated that 54,200 cases of malignant melanoma will be newly diagnosed and 7,600 cases of death will occur in the United States in the year 2003 (1). At the present time, more than 1.3% of Americans will develop malignant melanoma during their lifetime (2). The average survival for patients with metastatic melanoma is about 6-9 months (3). Moreover, metastatic melanoma deposits are resistant to conventional chemotherapy and external beam radiation therapy (3). Systematic chemotherapy is the primary therapeutic approach to treat patients with metastatic melanoma. Dacarbazine is the only single chemotherapy agent approved by FDA for metastatic melanoma treatment (5). However, the response rate to Dacarbazine is only approximately 20% (6). Therefore, there is a great need to develop novel treatment approaches for metastatic melanoma. The global goal of this research program is the rational design, characterization and validation of melanoma imaging and therapeutic radiopharmaceuticals. Significant progress has been made in the design and characterization of metal-cyclized radiolabeled alpha-melanocyte stimulating hormone peptides. Therapy studies with 188 Re-CCMSH demonstrated the therapeutic efficacy of the receptor-targeted treatment in murine and human melanoma bearing mice (previous progress report). Dosimetry calculations, based on biodistribution data, indicated that a significant dose was delivered to the tumor. However, 188 Re is a very energetic beta-particle emitter. The longer-range beta-particles theoretically would be better for larger tumors. In the treatment of melanoma, the larger primary tumor is usually surgically removed leaving metastatic disease as the focus of targeted radiotherapy. Isotopes with lower beta-energies and/or shorter particle lengths should be better suited for targeting metastases. The 177 Lu-DOTA-Re(Arg11)CCMSH and

Comparative cytogenetic characterization of primary canine melanocytic lesions using array CGH and fluorescence in situ hybridization

OpenAIRE

Poorman, Kelsey; Borst, Luke; Moroff, Scott; Roy, Siddharth; Labelle, Philippe; Motsinger-Reif, Alison; Breen, Matthew

2014-01-01

Melanocytic lesions originating from the oral mucosa or cutaneous epithelium are common in the general dog population, with up to 100,000 diagnoses each year in the USA. Oral melanoma is the most frequent canine neoplasm of the oral cavity, exhibiting a highly aggressive course. Cutaneous melanocytomas occur frequently, but rarely develop into a malignant form. Despite the differential prognosis, it has been assumed that subtypes of melanocytic lesions represent the same disease. To address t...

Capaciteitsproblemen grote belemmering: de behandeling van borderline persoonlijkheidsstoornis

NARCIS (Netherlands)

Hermens, M.; van Splunteren, P.; van den Bosch, A.; Verheul, R.

2012-01-01

Barriers to implementing the clinical guideline on borderline personality disorder in the Netherlands. Objective: This study determined the gap between actual care and optimal care (recommended in the clinical guideline) for patients with borderline personality disorder in the Netherlands. Factors

Intracranial melanocytic meningeal tumours and melanosis oculi: case report and literature review

International Nuclear Information System (INIS)

Doglietto, Francesco; Colosimo, Cesare; Lauriola, Libero; Balducci, Mario; De Bonis, Pasquale; Montano, Nicola; Zadeh, Gelareh; Maira, Giulio; Pallini, Roberto

2012-01-01

Melanocytic meningeal tumours are rare extra-axial neoplasms of the nervous system, with only three reported cases in the cavernous sinus. Herein we describe for the first time the association of ocular melanosis and multiple intracranial melanocytic meningeal tumours, with the presenting lesion being in the cavernous sinus. The importance of this association is discussed together with the diagnostic and therapeutic challenges of the case. A 20-year-old man presented with a left sixth cranial nerve deficit; general examination documented only congenital melanosis of the homolateral eye. MRI examination showed a space occupying lesion in the left cavernous sinus, which was followed conservatively for 2 years, until a new space occupying lesion was evident at the level of the right frontal convexity: both lesions presented with neuroradiological characteristics suggestive of melanin content. The frontal convexity lesion was removed: intraoperatively the dura was markedly and diffusely melanotic. Histological examination documented a melanocytic meningeal tumour, with a proliferative index of 3 %. The patient underwent 3D-Conformal Radiation Therapy on the lesion of the cavernous sinus (total dose 5040 cGy), with initial tumour reduction. Three years later, due to a symptomatic growth, he underwent partial removal of the lesion in the cavernous sinus. Histological examination was unchanged. He then received adjuvant Temozolomide with Low Dose Fractionated Radiation Therapy (LD-FRT). Due to further disease progression cisplatin plus fotemustine were administered, concomitant with LD-FRT: after two cycles MRI documented significant disease regression. After a period of apparent disease control, the patient presented with persistent cough and evidence of multiple thoracic metastases, which lead to his death, seven years after presentation. Intracranial melanocytic meningeal tumours are challenging lesions, both from a diagnostic and therapeutic point of view; though rare

Extending extant models of the pathogenesis of borderline personality disorder to childhood borderline personality symptoms: the roles of affective dysfunction, disinhibition, and self- and emotion-regulation deficits.

Science.gov (United States)

Gratz, Kim L; Tull, Matthew T; Reynolds, Elizabeth K; Bagge, Courtney L; Latzman, Robert D; Daughters, Stacey B; Lejuez, C W

2009-01-01

Although research has been conducted on the course, consequences, and correlates of borderline personality disorder (BPD), little is known about its emergence in childhood, and no studies have examined the extent to which theoretical models of the pathogenesis of BPD in adults are applicable to the correlates of borderline personality symptoms in children. The goal of this study was to examine the interrelationships between two BPD-relevant personality traits (affective dysfunction and disinhibition), self- and emotion-regulation deficits, and childhood borderline personality symptoms among 263 children aged 9 to 13. We predicted that affective dysfunction, disinhibition, and their interaction would be associated with childhood borderline personality symptoms, and that self- and emotion-regulation deficits would mediate these relationships. Results provided support for the roles of both affective dysfunction and disinhibition (in the form of sensation seeking) in childhood borderline personality symptoms, as well as their hypothesized interaction. Further, both self- and emotion-regulation deficits partially mediated the relationship between affective dysfunction and childhood borderline personality symptoms. Finally, results provided evidence of different gender-based pathways to childhood borderline personality symptoms, suggesting that models of BPD among adults are more relevant to understanding the factors associated with borderline personality symptoms among girls than boys.

Borderline personality symptoms and work performance: a population-based survey.

Science.gov (United States)

Juurlink, Trees T; Ten Have, Margreet; Lamers, Femke; van Marle, Hein J F; Anema, Johannes R; de Graaf, Ron; Beekman, Aartjan T F

2018-06-19

This study aims to elucidate the interplay between borderline personality symptoms and working conditions as a pathway for impaired work performance among workers in the general population. Cross-sectional data from the Netherlands Mental Health Survey and Incidence Study-2 (NEMESIS-2) were used, including 3672 workers. Borderline personality symptoms were measured with the International Personality Disorder Examination (IPDE) questionnaire. Working conditions (decision latitude, psychological job demands, job security and co-worker support) were assessed with the Job Content Questionnaire (JCQ). Impaired work performance was assessed as total work loss days per month, defined as the sum of days of three types of impaired work performance (inability to work, cut-down to work, and diminished quality at work). These were assessed with the WHO Disability Assessment Schedule (WHO-DAS). Common mental disorders (CMD) were assessed with the Composite International Diagnostic Interview (CIDI). Number of borderline personality symptoms was consistently associated with impaired work performance, even after controlling for type or number of adverse working conditions and co-occurrence of CMD. Borderline personality symptoms were associated with low decision latitude, job insecurity and low co-worker support. The relationship between borderline personality symptoms and work performance diminished slightly after controlling for type or number of working conditions. The current study shows that having borderline personality symptoms is a unique determinant of work performance. This association seems partially explained through the impact of borderline personality symptoms on working conditions. Future studies are warranted to study causality and should aim at diminishing borderline personality symptoms and coping with working conditions.

A Rare Tumor of Nasal Cavity: Glomangiopericytoma

Directory of Open Access Journals (Sweden)

Aysegul Verim

2014-01-01

Full Text Available Glomangiopericytoma is a rare vascular neoplasm characterized by a pattern of prominent perivascular growth. A 72-year-old woman was admitted to our clinic complaining of nasal obstruction, frequent epistaxis, and facial pain. A reddish tumor filling the left nasal cavity was observed on endoscopy and treated with endoscopic excision. Microscopically, closely packed cells interspersed with numerous thin-walled, branching staghorn vessels were seen. Glomangiopericytoma is categorized as a borderline low malignancy tumor by WHO classification. Long-term follow-up with systemic examination is necessary due to high risk of recurrence.

Loss of Oca2 disrupts the unfolded protein response and increases resistance to endoplasmic reticulum stress in melanocytes.

Science.gov (United States)

Cheng, Tsing; Orlow, Seth J; Manga, Prashiela

2013-11-01

Accumulation of proteins in the endoplasmic reticulum (ER) typically induces stress and initiates the unfolded protein response (UPR) to facilitate recovery. If homeostasis is not restored, apoptosis is induced. However, adaptation to chronic UPR activation can increase resistance to subsequent acute ER stress. We therefore investigated adaptive mechanisms in Oculocutaneous albinism type 2 (Oca2)-null melanocytes where UPR signaling is arrested despite continued tyrosinase accumulation leading to resistance to the chemical ER stressor thapsigargin. Although thapsigargin triggers UPR activation, instead of Perk-mediated phosphorylation of eIF2α, in Oca2-null melanocytes, eIF2α was rapidly dephosphorylated upon treatment. Dephosphorylation was mediated by the Gadd34-PP1α phosphatase complex. Gadd34-complex inhibition blocked eIF2α dephosphorylation and significantly increased Oca2-null melanocyte sensitivity to thapsigargin. Thus, Oca2-null melanocytes adapt to acute ER stress by disruption of pro-apoptotic Perk signaling, which promotes cell survival. This is the first study to demonstrate rapid eIF2α dephosphorylation as an adaptive mechanism to ER stress. © 2013 John Wiley & Sons A/S. Published by John Wiley & Sons Ltd.

Melanoma transition is frequently accompanied by a loss of cytoglobin expression in melanocytes: a novel expression site of cytoglobin.

Directory of Open Access Journals (Sweden)

Yoshihiko Fujita

Full Text Available The tissue distribution and function of hemoglobin or myoglobin are well known; however, a newly found cytoglobin (CYGB, which also belongs to the globin family, remains to be characterized. To assess its expression in human malignancies, we sought to screen a number of cell lines originated from many tissues using northern blotting and real time PCR techniques. Unexpectedly, we found that several, but not all, melanoma cell lines expressed CYGB mRNA and protein at much higher levels than cells of other origins. Melanocytes, the primary origin of melanoma, also expressed CYGB at a high level. To verify these observations, immunostaining and immunoblotting using anti-CYGB antibody were also performed. Bisulfite-modified genomic sequencing revealed that several melanoma cell lines that abrogated CYGB expression were found to be epigenetically regulated by hypermethylation in the promoter region of CYGB gene. The RNA interference-mediated knockdown of the CYGB transcript in CYGB expression-positive melanoma cell lines resulted in increased proliferation in vitro and in vivo. Flow cytometric analysis using 2'-, 7'-dichlorofluorescein diacetate (DCFH-DA, an indicator of reactive oxygen species (ROS, revealed that the cellular ROS level may be involved in the proliferative effect of CYGB. Thus, CYGB appears to play a tumor suppressive role as a ROS regulator, and its epigenetic silencing, as observed in CYGB expression-negative melanoma cell lines, might function as an alternative pathway in the melanocyte-to-melanoma transition.

Behandling og håndtering af kongenitte melanocytære naevi

DEFF Research Database (Denmark)

Bahn, Kamille-Amalie; Hædersdal, Merete; Schmidt, Grethe

2016-01-01

Congenital melanocytic naevi (CMN) appear in approximately 2.6% of Caucasians. There is a major demand for treatment but no vital indication. Laser therapy, curettage and excision are available treatment modalities, but there is no ideal treatment with documented long-term effect and without side...

Giant melanocytic nevus with malignant melanoma: a rare disorder in a black African child.

Science.gov (United States)

Katibi, Oludolapo Sherifat; Ogunbiyi, Adebola; Brown, Biobele Jotham; Adeyemi, Oyedeji Oladele

2014-10-01

Giant congenital melanocytic nevus (GCMN) is rare in babies of African descent. Unfortunately, it has an increased potential for malignant transformation. A 3-year-old female child presented with a 6-month history of multiple nodules on an existing giant congenital melanocytic nevus and swelling in the right axilla of four weeks duration. Skin biopsy of the nodular skin lesions was in keeping with a metastatic malignant melanoma (Clark stage 4). She completed a full course of chemotherapy but subsequently died four months after presentation. Patients with large GCMN should be counseled and followed up appropriately to improve and prolong life. © 2014 The International Society of Dermatology.

Treating borderline personality disorder as a trainee psychologist ...

African Journals Online (AJOL)

Clients with borderline personality disorder are viewed as difficult to work with. They also have high drop-out rates and unpredictable treatment outcomes. The characteristics of patients with borderline personality disorder often have a negative effect on the therapeutic process and on clinicians themselves. Challenges are ...

The effect of simultaneous exposure of HEMn-DP and HEMn-LP melanocytes to nicotine and UV-radiation on the cell viability and melanogenesis

International Nuclear Information System (INIS)

Delijewski, Marcin; Wrześniok, Dorota; Beberok, Artur; Rok, Jakub; Otręba, Michał; Buszman, Ewa

2016-01-01

Nicotine is a main compound of tobacco plants and may affect more than a billion people all over the world that are permanently exposed to nicotine from cigarettes, various forms of smoking cessation therapies, electronic cigarettes or second-hand smoke. It is known that nicotine forms complexes with melanin what may lead to accumulation of this alkaloid in tissues of living organisms containing the pigment. This may affect the viability of cells and process of melanin biosynthesis that takes place in melanocytes. Although UV radiation is known to be a particular inductor of melanin biosynthesis, its simultaneous effect with nicotine on this process as well as the viability of human cells containing melanin have not been assessed so far. The aim of this study was to examine the simultaneous impact of nicotine and UV radiation on viability and melanogenesis in cultured normal human melanocytes dark (HEMn-DP) and light (HEMn-LP) pigmented. Nicotine together with UV radiation induced concentration-dependent loss in melanocytes viability. The higher cell loss was observed in dark pigmented melanocytes in comparison to light pigmented cells. Simultaneous exposure of cells to nicotine and UV radiation also caused changes in melanization process in both tested cell lines. The data suggest that simultaneous exposure of melanocytes to nicotine and UV radiation up-regulates melanogenesis and affects cell viability. Observed processes are more pronounced in dark pigmented cells. - Highlights: • Nicotine and UVA induced concentration-dependent loss in melanocytes viability. • Nicotine and UVA modulated melanization process in melanocytes. • Changes in viability and melanization were more pronounced in dark pigmented cells.

The effect of simultaneous exposure of HEMn-DP and HEMn-LP melanocytes to nicotine and UV-radiation on the cell viability and melanogenesis

Energy Technology Data Exchange (ETDEWEB)

Delijewski, Marcin; Wrześniok, Dorota; Beberok, Artur; Rok, Jakub; Otręba, Michał; Buszman, Ewa, E-mail: ebuszman@sum.edu.pl

2016-11-15

Nicotine is a main compound of tobacco plants and may affect more than a billion people all over the world that are permanently exposed to nicotine from cigarettes, various forms of smoking cessation therapies, electronic cigarettes or second-hand smoke. It is known that nicotine forms complexes with melanin what may lead to accumulation of this alkaloid in tissues of living organisms containing the pigment. This may affect the viability of cells and process of melanin biosynthesis that takes place in melanocytes. Although UV radiation is known to be a particular inductor of melanin biosynthesis, its simultaneous effect with nicotine on this process as well as the viability of human cells containing melanin have not been assessed so far. The aim of this study was to examine the simultaneous impact of nicotine and UV radiation on viability and melanogenesis in cultured normal human melanocytes dark (HEMn-DP) and light (HEMn-LP) pigmented. Nicotine together with UV radiation induced concentration-dependent loss in melanocytes viability. The higher cell loss was observed in dark pigmented melanocytes in comparison to light pigmented cells. Simultaneous exposure of cells to nicotine and UV radiation also caused changes in melanization process in both tested cell lines. The data suggest that simultaneous exposure of melanocytes to nicotine and UV radiation up-regulates melanogenesis and affects cell viability. Observed processes are more pronounced in dark pigmented cells. - Highlights: • Nicotine and UVA induced concentration-dependent loss in melanocytes viability. • Nicotine and UVA modulated melanization process in melanocytes. • Changes in viability and melanization were more pronounced in dark pigmented cells.

Ocular Albinism Type 1 Regulates Melanogenesis in Mouse Melanocytes

Directory of Open Access Journals (Sweden)

Tianzhi Chen

2016-09-01

Full Text Available To investigate whether ocular albinism type 1 (OA1 is differentially expressed in the skin of mice with different coat colors and to determine its correlation with coat color establishment in mouse, the expression patterns and tissue distribution characterization of OA1 in the skin of mice with different coat colors were qualitatively and quantitatively analyzed by real-time quantitative PCR (qRT-PCR, immunofluorescence staining and Western blot. The qRT-PCR analysis revealed that OA1 mRNA was expressed in all mice skin samples tested, with the highest expression level in brown skin, a moderate expression level in black skin and the lowest expression level in gray skin. Positive OA1 protein bands were also detected in all skin samples by Western blot analysis. The relative expression levels of OA1 protein in both black and brown skin were significantly higher than that in gray skin, but there was no significant difference between black and brown mice. Immunofluorescence assays revealed that OA1 was mainly expressed in the hair follicle matrix, the inner and outer root sheath in the skin tissues with different coat colors. To get further insight into the important role of OA1 in the melanocytes’ pigmentation, we transfected the OA1 into mouse melanocytes and then detected the relative expression levels of pigmentation-related gene. Simultaneously, we tested the melanin content of melanocytes. As a result, the overexpression of OA1 significantly increased the expression levels of microphthalmia-associated transcription factor (MITF, tyrosinase (TYR, tyrosinase-related protein 1 (TRP1 and premelanosome protein (PMEL. However, the tyrosinase-related protein 2 (TRP2 level was attenuated. By contrast, the level of glycoprotein non-metastatic melanoma protein b (GPNMB was unaffected by OA1 overexpression. Furthermore, we observed a significant increase in melanin content in mouse melanocyte transfected OA1. Therefore, we propose that OA1 may

Maternal empathy, family chaos, and the etiology of borderline personality disorder.

Science.gov (United States)

Golomb, A; Ludolph, P; Westen, D; Block, M J; Maurer, P; Wiss, F C

1994-01-01

Psychoanalytic writers have traced the etiology of borderline personality disorder (BPD) to be a preoedipal disturbance in the mother-child relationship. Despite the prevalence of theories focusing on the role of mothering in the development of BPD, few empirical studies have tested the hypothesis that borderlines were the recipients of unempathic mothering. The current preliminary study compared 13 mothers of borderline adolescents with 13 mothers of normal adolescents. This study found that mothers of borderlines tended to conceive of their children egocentrically, as need-gratifying objects, rather than as individuals with distinct and evolving personalities. This study also found that the mothers of borderlines reported raising their daughters in extremely chaotic families struggling to cope with multiple hardships, including divorce and financial worries. The stressful environmental circumstances reported by the mothers likely affected the borderline daughters directly as well as the mothers' ability to parent effectively and empathically. The results of this study suggest that, as predicted by psychoanalytic theory, a problematic mother-child relationship may play a significant role in the genesis of borderline pathology; however, the life circumstances that contextualize the mother-child relationship also need to be considered when accounting for the etiology of BPD.

Significance of the Melanocortin 1 and Endothelin B Receptors in Melanocyte Homeostasis and Prevention of Sun-Induced Genotoxicity

Directory of Open Access Journals (Sweden)

Zalfa A. Abdel-Malek

2016-08-01

Full Text Available The membrane bound melanocortin 1 receptor (MC1R, and the endothelin B receptor (ENDBR are two G-protein coupled receptors that play important roles in constitutive regulation of melanocytes and their response to ultraviolet radiation (UVR, the main etiological factor for melanoma. The human MC1R is a Gs protein-coupled receptor, which is activated by its agonists α-melanocyte stimulating hormone (α-melanocortin; α-MSH and adrenocorticotropic hormone (ACTH. The ENDBR is a Gq coupled-receptor, which is activated by Endothelin (ET-3 during embryonic development, and ET-1 postnatally. Pigmentation and the DNA repair capacity are two major factors that determine the risk for melanoma. Activation of the MC1R by its agonists stimulates the synthesis of eumelanin, the dark brown photoprotective pigment. In vitro studies showed that α-MSH and ET-1 interact synergistically in the presence of basic fibroblast growth factor (bFGF to stimulate human melanocyte proliferation and melanogenesis, and to inhibit UVR-induced apoptosis. An important function of the MC1R is reduction of oxidative stress and activation of DNA repair pathways. The human MC1R is highly polymorphic, and MC1R variants, particularly those that cause loss of function of the expressed receptor, are associated with increased melanoma risk independently of pigmentation. These variants compromise the DNA repair and antioxidant capacities of human melanocytes. Recently, activation of ENDBR by ET-1 was reported to reduce the induction and enhance the repair of UVR-induced DNA photoproducts. We conclude that α-MSH and ET-1 and their cognate receptors MC1R and ENDBR reduce the risk for melanoma by maintaining genomic stability of melanocytes via modulating the DNA damage response to solar UVR. Elucidating the response of melanocytes to UVR should improve our understanding of the process of melanomagenesis, and lead to effective melanoma chemoprevention, as well as therapeutic strategies.

Experiences of women living with borderline personality disorder ...

African Journals Online (AJOL)

There is limited understanding of the experiences of women living with borderline personality disorder. It was therefore decided to discover how women living with this disorder would tell their life story. For the researcher, who worked in a psychotherapy ward where most women were living with borderline personality ...

(Pheo)melanin photosensitizes UVA-induced DNA damage in cultured human melanocytes

NARCIS (Netherlands)

Wenczl, E.; Schans, G.P. van der; Roza, L.; Kolb, R.M.; Timmerman, A.J.; Smit, N.P.M.; Pavel, S.; Schothorst, A.A.

1998-01-01

The question of whether melanins are photoprotecting and/or photosensitizing in human skin cells continues to be debated. To evaluate the role of melanin upon UVA irradiation, DNA single-strand breaks (ssb) were measured in human melanocytes differing only in the amount of pigment produced by

Mental state decoding impairment in major depression and borderline personality disorder: meta-analysis.

Science.gov (United States)

Richman, Mara J; Unoka, Zsolt

2015-12-01

Patients with major depression and borderline personality disorder are characterised by a distorted perception of other people's intentions. Deficits in mental state decoding are thought to be the underlying cause of this clinical feature. To examine, using meta-analysis, whether mental state decoding abilities in patients with major depression and borderline personality disorder differ from those of healthy controls. A systematic review of 13 cross-sectional studies comparing Reading in the Mind of the Eyes Test (RMET) accuracy performance of patients with major depression or borderline personality disorder and healthy age-matched controls (n = 976). Valence scores, where reported, were also assessed. Large significant deficits were seen for global RMET performance in patients with major depression (d = -0.751). The positive RMET valence scores of patients with depression were significantly worse; patients with borderline personality disorder had worse neutral scores. Both groups were worse than controls. Moderator analysis revealed that individuals with comorbid borderline personality disorder and major depression did better than those with borderline personality disorder alone on accuracy. Those with comorbid borderline personality disorder and any cluster B or C personality disorder did worse than borderline personality disorder alone. Individuals with both borderline personality disorder and major depression performed better then those with borderline personality disorder without major depression for positive valence. These findings highlight the relevance of RMET performance in patients with borderline personality disorder and major depression, and the importance of considering comorbidity in future analysis. © The Royal College of Psychiatrists 2015.

The borderline conditions--an introduction from a Scandinavian perspective

DEFF Research Database (Denmark)

Simonsen, E

1994-01-01

disorder--impulsive or borderline subcategory. This closer demarcation of prototypes in the classification system may facilitate less confusion in future. All Scandinavian countries have contributed a great deal to the research in the field of borderline conditions, especially with regard to genetic...... and nosological issues. A brief summary of these contributions is presented. Some important notions in the phenomenologic and prototypically oriented European tradition of classifying personality disorders are explained in order to understand the rather ambiguous reaction to the borderline concept in European...

Melanocortin 1 receptor genotype: an important determinant of the damage response of melanocytes to ultraviolet radiation

Science.gov (United States)

Kadekaro, Ana Luisa; Leachman, Sancy; Kavanagh, Renny J.; Swope, Viki; Cassidy, Pamela; Supp, Dorothy; Sartor, Maureen; Schwemberger, Sandy; Babcock, George; Wakamatsu, Kazumasa; Ito, Shosuke; Koshoffer, Amy; Boissy, Raymond E.; Manga, Prashiela; Sturm, Richard A.; Abdel-Malek, Zalfa A.

2010-01-01

The melanocortin 1 receptor gene is a main determinant of human pigmentation, and a melanoma susceptibility gene, because its variants that are strongly associated with red hair color increase melanoma risk. To test experimentally the association between melanocortin 1 receptor genotype and melanoma susceptibility, we compared the responses of primary human melanocyte cultures naturally expressing different melanocortin 1 receptor variants to α-melanocortin and ultraviolet radiation. We found that expression of 2 red hair variants abolished the response to α-melanocortin and its photoprotective effects, evidenced by lack of functional coupling of the receptor, and absence of reduction in ultraviolet radiation-induced hydrogen peroxide generation or enhancement of repair of DNA photoproducts, respectively. These variants had different heterozygous effects on receptor function. Microarray data confirmed the observed differences in responses of melanocytes with functional vs. nonfunctional receptor to α-melanocortin and ultraviolet radiation, and identified DNA repair and antioxidant genes that are modulated by α-melanocortin. Our findings highlight the molecular mechanisms by which the melanocortin 1 receptor genotype controls genomic stability of and the mutagenic effect of ultraviolet radiation on human melanocytes.—Kadekaro, A. L., Leachman, S., Kavanagh, R. J., Swope, V., Cassidy, P., Supp, D., Sartor, M., Schwemberger, S., Babcock, G., Wakamatsu, K., Ito, S., Koshoffer, A., Boissy, R. E., Manga, P., Sturm, R. A., Abdel-Malek, Z. A. Melanocortin 1 receptor genotype: an important determinant of the damage response of melanocytes to ultraviolet radiation. PMID:20519635

DMEM enhances tyrosinase activity in B16 mouse melanoma cells and human melanocytes

Directory of Open Access Journals (Sweden)

Panpen Diawpanich

2008-07-01

Full Text Available Media components may affect the activities of cultured cells. In this study, tyrosinase activity was evaluated by using B16-F10 mouse melanoma cell lines (B16-F10 and primary human melanocytes cultured in different media. An optical density measurement and a L-dopa reaction assay were used as the determination of the tyrosinase activity. The study of B16-F10 found the optical density to be 2010, 2246 and 2961 in cells cultured in RPMI Medium 1640 (RPMI1640,Minimum Essential Medium (MEM and Dulbecco’s Modified Eagle Medium (DMEM, respectively. Moreover, compared to RPMI 1640 and MEM, DMEM showed the darkest color of melanin formation in culture media and in cells after the L-dopa reaction assay. Addition of kojic acid showed a significant inhibitory effect on tyrosinase activity in all media.Whereas MCDB153 showed no significant effect on human melanocytes, DMEM caused a dramatic increase in tyrosinase activity after 4 days of cultivation. Addition of kojic acid showed a significant tyrosinase inhibitory effect in DMEM only. Furthermore, an active ingredient in green tea, epigallocathechin gallate (EGCG could inhibit tyrosinase activity in both B16-F10 and human melanocytes cultured in DMEM. In summary, these results suggest that DMEM is a suitable medium that provides high detection sensitivity in a tyrosinase inhibition assay.

Ginsenosides Rb1 and Rg1 Stimulate Melanogenesis in Human Epidermal Melanocytes via PKA/CREB/MITF Signaling

Directory of Open Access Journals (Sweden)

Mao Lin

2014-01-01

Full Text Available Reduced or defective melanin skin pigmentation may cause many hypopigmentation disorders and increase the risk of damage to the skin triggered by UV irradiation. Ginsenosides Rb1 and Rg1 have many molecular targets including the cAMP-response element-binding protein (CREB, which is involved in melanogenesis. This study aimed to investigate the effects of ginsenosides Rb1 and Rg1 on melanogenesis in human melanocytes and their related mechanisms. The effects of Rb1 and Rg1 on cell viability, tyrosinase activity, cellular melanin content and protein levels of tyrosinase, microphthalmia-associated transcription factor (MITF, and activation of CREB in melanocytes were assessed. Results showed that Rb1 or Rg1 significantly increased cellular melanin content and tyrosinase activity in a dose-dependent manner. By contrast, the cell viability of melanocytes remained unchanged. After exposure to Rb1 or Rg1, the protein levels of tyrosinase, MITF, and phosphorylated CREB were significantly increased. Furthermore, pretreatment with the selective PKA inhibitor H-89 significantly blocked the Rb1- or Rg1-induced increase of melanin content. These findings indicated that Rb1 and Rg1 increased melanogenesis and tyrosinase activity in human melanocytes, which was associated with activation of PKA/CREB/MITF signaling. The effects and mechanisms of Rb1 or Rg1 on skin pigmentation deserve further study.

Label-Free Imaging of Female Genital Tract Melanocytic Lesions With Pump-Probe Microscopy: A Promising Diagnostic Tool.

Science.gov (United States)

Robles, Francisco E; Deb, Sanghamitra; Fischer, Martin C; Warren, Warren S; Selim, Maria Angelica

2017-04-01

Melanomas of the female genital tract present a unique clinical challenge. Not only are these lesions in an anatomically sensitive area, but also they tend to be multifocal and have high recurrence rates. Furthermore, several benign melanocytic proliferations resemble early-stage melanoma clinically and/or histopathologically. Thus, there is a significant need for additional tools that can help correctly diagnose and stage these lesions. Here, we quantitatively and nondestructively analyze the chemical composition of melanin in excised pigmented lesions of the female genital tract using pump-probe microscopy, a high-resolution optical imaging technique that is sensitive to many biochemical properties of melanin. Thirty-one thin (~5 μm) tissue sections previously excised from female genital tract melanocytic lesions were imaged with pump-probe microscopy and analyzed. We find significant quantitative differences in melanin type and structure between melanoma and nonmalignant melanocytic proliferations. Our analysis also suggests a link between the molecular signatures of melanins and lesion-specific genetic mutations. Finally, significant differences are found between metastatic and nonmetastatic melanomas. The limitations of this work include the fact that molecular information is restricted to melanin pigment and the sample size is relatively small. Pump-probe microscopy provides unique information regarding the biochemical composition of genital tract melanocytic lesions, which can be used to improve the diagnosis and staging of vulvar melanomas.

NEAR-INFRARED AUTOFLUORESCENCE IN BILATERAL DIFFUSE UVEAL MELANOCYTIC PROLIFERATION ASSOCIATED WITH ESOPHAGEAL CARCINOMA AND CHOROIDAL METASTASIS.

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Golshahi, Azadeh; Bornfeld, Norbert; Weinitz, Silke; Kellner, Ulrich

2016-01-01

To investigate the advantage of near-infrared autofluorescence (787 nm) for the detection of melanocytic lesions in a patient with bilateral diffuse uveal melanocytic proliferation in association with esophageal carcinoma complicated by most likely unilateral choroidal metastasis. In this retrospective case report, a 55-year-old woman referred for the evaluation of sudden visual loss underwent normal ophthalmological evaluation and, in addition, was examined with near-infrared reflectance, near-infrared autofluorescence, fundus autofluorescence (Heidelberg Retina Angiograph II [HRA2; Heidelberg Engineering]), spectral domain optical coherence tomography (Spectralis OCT; Heidelberg Engineering), and multifocal electroretinography (RetiScan; Roland Consult). The patient had been diagnosed with esophageal carcinoma 3 months before the onset of visual symptoms. The visual acuity was 20/40 in the right eye and 20/20 in the left eye. Bilateral patchy melanocytic proliferation was detected on ophthalmoscopy. The extent of lesions was best detected with near-infrared reflectance and near-infrared autofluorescence, whereas fundus autofluorescence and spectral domain optical coherence tomography did not reveal alterations of the outer retina or retinal pigment epithelium in this early stage of bilateral diffuse uveal melanocytic proliferation. The right eye showed in addition to the findings on the left eye choroidal folds in the fovea and an elevated lesion inferotemporal of the fovea suspicious of a choroidal metastasis. In the B-scan ultrasonography, a homogenous lesion was seen. Spectral domain optical coherence tomography demonstrated a mild accumulation of subretinal fluid adjacent to and over the choroidal metastasis. Transretinal biopsy of this elevated lesion revealed a low differentiated carcinoma of squamous epithelium, compatible with choroidal metastasis of the esophageal carcinoma. The choroidal metastasis increased within 3 months after the first visit. The

Infrared A radiation promotes survival of human melanocytes carrying ultraviolet radiation-induced DNA damage.

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Kimeswenger, Susanne; Schwarz, Agatha; Födinger, Dagmar; Müller, Susanne; Pehamberger, Hubert; Schwarz, Thomas; Jantschitsch, Christian

2016-06-01

The link between solar radiation and melanoma is still elusive. Although infrared radiation (IR) accounts for over 50% of terrestrial solar energy, its influence on human skin is not well explored. There is increasing evidence that IR influences the expression patterns of several molecules independently of heat. A previous in vivo study revealed that pretreatment with IR might promote the development of UVR-induced non-epithelial skin cancer and possibly of melanoma in mice. To expand on this, the aim of the present study was to evaluate the impact of IR on UVR-induced apoptosis and DNA repair in normal human epidermal melanocytes. The balance between these two effects is a key factor of malignant transformation. Human melanocytes were exposed to physiologic doses of IR and UVR. Compared to cells irradiated with UVR only, simultaneous exposure to IR significantly reduced the apoptotic rate. However, IR did not influence the repair of UVR-induced DNA damage. IR partly reversed the pro-apoptotic effects of UVR via modification of the expression and activity of proteins mainly of the extrinsic apoptotic pathway. In conclusion, IR enhances the survival of melanocytes carrying UVR-induced DNA damage and thereby might contribute to melanomagenesis. © 2016 John Wiley & Sons A/S. Published by John Wiley & Sons Ltd.

Relative contributions of decay accelerating factor (DAF), membrane cofactor protein (MCP) and CD59 in the protection of melanocytes from homologous complement

NARCIS (Netherlands)

Venneker, G. T.; Vodegel, R. M.; Okada, N.; Westerhof, W.; Bos, J. D.; Asghar, S. S.

1998-01-01

Complement regulatory molecules, membrane cofactor protein (MCP), decay accelerating factor (DAF) and CD59, protect body cells from autologous complement. They have wide tissue distribution but nothing is known about the expression of these molecules on human melanocytes. Since melanocytes are lysed

Shame and implicit self-concept in women with borderline personality disorder.

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Rüsch, Nicolas; Lieb, Klaus; Göttler, Ines; Hermann, Christiane; Schramm, Elisabeth; Richter, Harald; Jacob, Gitta A; Corrigan, Patrick W; Bohus, Martin

2007-03-01

Shame is considered to be a central emotion in borderline personality disorder and to be related to self-injurious behavior, chronic suicidality, and anger-hostility. However, its level and impact on people with borderline personality disorder are largely unknown. The authors examined levels of self-reported shame, guilt, anxiety, and implicit shame-related self-concept in women with borderline personality disorder and assessed the association of shame with self-esteem, quality of life, and anger-hostility. Sixty women with borderline personality disorder completed self-report measures of shame- and guilt-proneness, state shame, anxiety, depression, self-esteem, quality of life, and clinical symptoms. Comparison groups consisted of 30 women with social phobia and 60 healthy women. Implicit shame-related self-concept (relative to anxiety) was assessed by the Implicit Association Test. Women with borderline personality disorder reported higher levels of shame- and guilt-proneness, state shame, and anxiety than women with social phobia and healthy comparison subjects. The implicit self-concept in women with borderline personality disorder was more shame-prone (relative to anxiety-prone) than in women in the comparison groups. After depression was controlled for, shame-proneness was negatively correlated with self-esteem and quality of life and positively correlated with anger-hostility. Shame, an emotion that is prominent in women with borderline personality disorder, is associated with the implicit self-concept as well as with poorer quality of life and self-esteem and greater anger-hostility. Psychotherapeutic approaches to borderline personality disorder need to address explicit and implicit aspects of shame.

[Tattoos and piercings: motives for body modification in women suffering from borderline symptomatology].

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Höhner, Gesche; Teismann, Tobias; Willutzki, Ulrike

2014-02-01

Do women suffering from borderline symptomatology differ from women without these symptoms regarding their motives for body modifications?A sample of 289 women with body modifications were questioned about their tattoos, piercings and motives for body modifications as well as about symptoms of borderline personality disorder. Women with borderline symptomatology were compared to women without borderline symptomatology concerning the extent of and motives for body modification.The 2 groups showed no differences in regard to amount and extent of body modifications. The "borderline"-group considered individuality, coping and management of negative life-events to be more crucial reasons for body modification than the non-borderline females.The degree of a person's body modification is not a feasible indicator for psychopathological strain. Though, for people with borderline tendency body modification may serve as a coping strategy similar to self-injury. © Georg Thieme Verlag KG Stuttgart · New York.

Rab11b mediates melanin transfer between donor melanocytes and acceptor keratinocytes via coupled exo/endocytosis.

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Tarafder, Abul K; Bolasco, Giulia; Correia, Maria S; Pereira, Francisco J C; Iannone, Lucio; Hume, Alistair N; Kirkpatrick, Niall; Picardo, Mauro; Torrisi, Maria R; Rodrigues, Inês P; Ramalho, José S; Futter, Clare E; Barral, Duarte C; Seabra, Miguel C

2014-04-01

The transfer of melanin from melanocytes to keratinocytes is a crucial process underlying maintenance of skin pigmentation and photoprotection against UV damage. Here, we present evidence supporting coupled exocytosis of the melanin core, or melanocore, by melanocytes and subsequent endocytosis by keratinocytes as a predominant mechanism of melanin transfer. Electron microscopy analysis of human skin samples revealed three lines of evidence supporting this: (1) the presence of melanocores in the extracellular space; (2) within keratinocytes, melanin was surrounded by a single membrane; and (3) this membrane lacked the melanosomal membrane protein tyrosinase-related protein 1 (TYRP1). Moreover, co-culture of melanocytes and keratinocytes suggests that melanin exocytosis is specifically induced by keratinocytes. Furthermore, depletion of Rab11b, but not Rab27a, caused a marked decrease in both keratinocyte-stimulated melanin exocytosis and transfer to keratinocytes. Thus, we propose that the predominant mechanism of melanin transfer is keratinocyte-induced exocytosis, mediated by Rab11b through remodeling of the melanosome membrane, followed by subsequent endocytosis by keratinocytes.

The continuum between Bipolar Disorder and Borderline Personality Disorder.

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Elisei, Sandro; Anastasi, Serena; Verdolini, Norma

2012-09-01

Several studies have been carried out regarding the possible overlap between Bipolar Disorder and borderline personality disorder. Up to now, it is not possible to provide a definitive picture. In fact, there is currently significant debate about the relationship between Borderline Personality Disorder and Bipolar Disorder. MEDLINE searches were performed to identify the latest studies of these disorders, considering psychodynamic aspects. Bipolar disorder and borderline personality disorder share common clinical features, namely affective instability and impulsivity which however differ in quality. Consequently, to better understand these aspects, it is necessary to trace the stages of childhood psychological development. It has been claimed that Bipolar Disorder Type II can be divided into two subtypes: one stable and functional between episodes and one unstable between episodes which is related to Borderline Personality Disorder. However, better diagnostic theories, psychiatrist's empathy and patience remain the essential tool to understand and to face human suffering.

Sex Bias in Classifying Borderline and Narcissistic Personality Disorder.

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Braamhorst, Wouter; Lobbestael, Jill; Emons, Wilco H M; Arntz, Arnoud; Witteman, Cilia L M; Bekker, Marrie H J

2015-10-01

This study investigated sex bias in the classification of borderline and narcissistic personality disorders. A sample of psychologists in training for a post-master degree (N = 180) read brief case histories (male or female version) and made DSM classification. To differentiate sex bias due to sex stereotyping or to base rate variation, we used different case histories, respectively: (1) non-ambiguous case histories with enough criteria of either borderline or narcissistic personality disorder to meet the threshold for classification, and (2) an ambiguous case with subthreshold features of both borderline and narcissistic personality disorder. Results showed significant differences due to sex of the patient in the ambiguous condition. Thus, when the diagnosis is not straightforward, as in the case of mixed subthreshold features, sex bias is present and is influenced by base-rate variation. These findings emphasize the need for caution in classifying personality disorders, especially borderline or narcissistic traits.

Preoperative HE4 and ROMA values do not improve the CA125 diagnostic value for borderline tumors of the ovary (BOT) - a study of the TOC Consortium.

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Braicu, Elena Ioana; Van Gorp, Toon; Nassir, Mani; Richter, Rolf; Chekerov, Radoslav; Gasimli, Khayal; Timmerman, Dirk; Vergote, Ignace; Sehouli, Jalid

2014-01-01

Borderline tumors of the ovary (BOT) are a distinct entity of ovarian tumors, characterized by lack of stromal invasion. Recent studies postulated that the presence of invasive implants, incomplete staging, fertility sparing surgery and residual tumor after surgery are major prognostic factors for BOT. There are no biomarkers that can predict BOT or the presence of invasive implants. The aim of our study was to assess the value of CA125 and HE4 alone, or within ROMA score for detecting BOT, and for predicting the presence of invasive implants. Retrospective, monocentric study on 167 women diagnosed with BOT or benign ovarian masses. Serum HE4, CA125 levels and ROMA were assessed preoperatively. Due to low number of BOT with invasive implants, we performed an unmatched analysis (consecutive patients) and a matched analysis (according to age and histology) to compare BOT with invasive implants, BOT without invasive implants and benign disease. There were no significant differences in the HE4 and CA125 expressions in the three groups of patients (p = 0.984 and p = 0.141, respectively). The ROC analysis showed that CA125 alone is superior to ROMA and HE4 in discriminating patients with BOT with invasive implants from patients with benign diseases and BOT without invasive implants. A newly established score, ROMABOT, did not perform better than ROMA. The analysis of the matched groups revealed similar results as the analysis of all samples. Both HE4 and CA125 are not reliable biomarkers for the diagnosis of BOT or for predicting the presence of invasive implants.

[Mentalization based treatment and borderline personality disorder].

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De Oliveira, C; Rahioui, H; Smadja, M; Gorsane, M A; Louppe, F

2017-08-01

The borderline personality disorder is a complex psychiatric disorder that represents a high number of patients in a psychiatric adult service. Even if some therapies have shown to be effective in the therapeutic care of the borderline personality disorder they only target certain symptoms (e.g. anxiety, sadness, self-mutilation). The aim of this paper is to introduce a therapeutic model little known in France: the mentalization based therapy (MBT) developed in 2004 by Bateman and Fonagy. This therapeutic model apprehends the borderline personality disorder in all its complexity and is based on two main concepts: Bowlby's attachment theory and the concept of mentalization. The MBT is based on the hypothesis that a deficit of mentalization leads to the development of borderline disorder. The capacity of mentalization, also known as reflexive function, is acquired in infancy through interpersonal relationships, in particular those of attachment, and is the ability to understand the mental state (emotions, needs, thoughts, etc.) of oneself and others which underlies explicit behaviour. This reflexive capacity is of a better quality when the person has a secure attachment style. Indeed, borderline patients have, mainly, a deficit of mentalization capacity associated with an insecure attachment style. Thus, the main objective of the Bateman and Fonagy approach is to develop and reinforce the mentalization capacity through a therapeutic relationship as a secure base, a group therapy and the concept of insight. Classically, MBT is structured over a period of 18 months divided into 3 distinct phases distributed in two therapeutic axes: group and individual therapy. The initial phase aims to engage the patient in the therapy by evaluating attachment style, mentalization's ability, interpersonal functioning; providing psychoeducation about borderline disorder and establishing a therapeutic contract. To evaluate attachment style, the authors strongly recommend the use of the

Neurobiologien ved borderline-personlighedsforstyrrelse

DEFF Research Database (Denmark)

Simonsen, Erik; Andersen, Rune

2012-01-01

Borderline personality disorder (BPD) is a severe psychiatric disorder characterised by instability of affect regulation, impulse control, interpersonal relationships, and self-image. The aim of this status article is to provide a brief overview of the neurobiological underpinnings of the core...

Blood Supply--Susceptible Formation of Melanin Pigment in Hair Bulb Melanocytes of Mice

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Shogo Maeda, MD

2015-03-01

Conclusions: Melanin pigment formation in the hair bulb melanocytes appeared to be susceptible to the blood supply, and melanocytosis was promoted in the follicles and in the epidermis of Kitl-Tg C57BL/6 mice.

UVB-Stimulated TNFα Release from Human Melanocyte and Melanoma Cells Is Mediated by p38 MAPK

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Visalini Muthusamy

2013-08-01

Full Text Available Ultraviolet (UV radiation activates cell signaling pathways in melanocytes. As a result of altered signaling pathways and UV-induced cellular damage, melanocytes can undergo oncogenesis and develop into melanomas. In this study, we investigated the effect of UV-radiation on p38 MAPK (mitogen-activated protein kinase, JNK and NFκB pathways to determine which plays a major role in stimulating TNFα secretion in human HEM (melanocytes and MM96L (melanoma cells. MM96L cells exhibited 3.5-fold higher p38 activity than HEM cells at 5 min following UVA + B radiation and 1.6-fold higher JNK activity at 15–30 min following UVB+A radiation, while NFκB was minimally activated in both cells. Irradiated HEM cells had the greatest fold of TNFα secretion (UVB: 109-fold, UVA + B: 103-fold & UVB+A: 130-fold when co-exposed to IL1α. The p38 inhibitor, SB202190, inhibited TNFα release by 93% from UVB-irradiated HEM cells. In the UVB-irradiated MM96L cells, both SB202190 and sulfasalazine (NFκB inhibitor inhibited TNFα release by 52%. Although, anisomycin was a p38 MAPK activator, it inhibited TNFα release in UV-irradiated cells. This suggests that UV-mediated TNFα release may occur via different p38 pathway intermediates compared to those stimulated by anisomycin. As such, further studies into the functional role p38 MAPK plays in regulating TNFα release in UV-irradiated melanocyte-derived cells are warranted.

Psychodrama and the Treatment of Narcissistic and Borderline Patients.

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Olsson, Peter A

2018-01-01

Psychiatric clinicians are faced with the challenge of remaining flexible and psychotherapeutically relevant to the broadening scope of patients with severe narcissistic and borderline personality disorders. Diagnostic sophistication among mental health professionals, increased availability of psychotherapy services, and economic pressures combine to cause the public to expect cost-effective, successful, and shorter duration of treatments. These treatment challenges are particularly poignant with the treatment of those narcissistic and borderline patients who have meager capacity for insight and limited verbal skills. This article describes the use of psychodynamically oriented and informed psychodrama for the treatment of narcissistic and borderline patients.

Autobiographical Memory in Borderline Personality Disorder – A Review

DEFF Research Database (Denmark)

Beck, Morten; Elklit, Ask; Simonsen, Erik

2015-01-01

Borderline personality disorder is a severe psychiatric illness. A key feature of the disorder is a disorganized sense of self often referred to as identity diffusion. Autobiographical memory is memory for personal life events. One of the main functions of these memories is to enable us...... to understand who we are by connecting past, present and future experiences. It seems that autobiographical memory is in some way disrupted in individuals with borderline personality disorder. A systematic review is conducted looking at studies that focus on the potential connections. We find that although......, autobiographical memory and borderline personality disorder....

Mutational profile of GNAQQ209 in human tumors.

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Simona Lamba

Full Text Available BACKGROUND: Frequent somatic mutations have recently been identified in the ras-like domain of the heterotrimeric G protein alpha-subunit (GNAQ in blue naevi 83%, malignant blue naevi (50% and ocular melanoma of the uvea (46%. The mutations exclusively affect codon 209 and result in GNAQ constitutive activation which, in turn, acts as a dominant oncogene. METHODOLOGY: To assess if the mutations are present in other tumor types we performed a systematic mutational profile of the GNAQ exon 5 in a panel of 922 neoplasms, including glioblastoma, gastrointestinal stromal tumors (GIST, acute myeloid leukemia (AML, blue naevi, skin melanoma, bladder, breast, colorectal, lung, ovarian, pancreas, and thyroid carcinomas. PRINCIPAL FINDINGS: We detected the previously reported mutations in 6/13 (46% blue naevi. Changes affecting Q209 were not found in any of the other tumors. Our data indicate that the occurrence of GNAQ mutations display a unique pattern being present in a subset of melanocytic tumors but not in malignancies of glial, epithelial and stromal origin analyzed in this study.

Melanotic neuroectodermal tumor of infancy: A rare case report

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E Rajendra Reddy

2013-01-01

Full Text Available Melanotic neuroectodermal tumor of infancy (MNTI is a relatively uncommon osteolytic-pigmented neoplasm that primarily affects the jaws of infants. The early onset and its rapid disfiguring spread necessitate early diagnosis. A 4-month-old male child reported with the complaint of swelling in the right back tooth region of the upper jaw, which rapidly increased in size causing disfigurement of the face. Radiographic examination showed a diffuse osteolytic radiolucent lesion in the right maxilla and displacement and dysmorphic changes in the developing primary tooth buds. Wide surgical excision was performed under general anesthesia. Histopathological report revealed characteristic large pigmented epitheloid cells (melanocyte like cells. The biphasic tumor cell population arranged in a background of fibrous connective tissue stroma is suggestive of MNTI involving the cancellous bone. Early diagnosis and management of such aggressive tumors precludes significant morbidity of the patient.

MMTV-Wnt1 and -DeltaN89beta-catenin induce canonical signaling in distinct progenitors and differentially activate Hedgehog signaling within mammary tumors.

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Brigitte Teissedre

Full Text Available Canonical Wnt/beta-catenin signaling regulates stem/progenitor cells and, when perturbed, induces many human cancers. A significant proportion of human breast cancer is associated with loss of secreted Wnt antagonists and mice expressing MMTV-Wnt1 and MMTV-DeltaN89beta-catenin develop mammary adenocarcinomas. Many studies have assumed these mouse models of breast cancer to be equivalent. Here we show that MMTV-Wnt1 and MMTV-DeltaN89beta-catenin transgenes induce tumors with different phenotypes. Using axin2/conductin reporter genes we show that MMTV-Wnt1 and MMTV-DeltaN89beta-catenin activate canonical Wnt signaling within distinct cell-types. DeltaN89beta-catenin activated signaling within a luminal subpopulation scattered along ducts that exhibited a K18(+ER(-PR(-CD24(highCD49f(low profile and progenitor properties. In contrast, MMTV-Wnt1 induced canonical signaling in K14(+ basal cells with CD24/CD49f profiles characteristic of two distinct stem/progenitor cell-types. MMTV-Wnt1 produced additional profound effects on multiple cell-types that correlated with focal activation of the Hedgehog pathway. We document that large melanocytic nevi are a hitherto unreported hallmark of early hyperplastic Wnt1 glands. These nevi formed along the primary mammary ducts and were associated with Hedgehog pathway activity within a subset of melanocytes and surrounding stroma. Hh pathway activity also occurred within tumor-associated stromal and K14(+/p63(+ subpopulations in a manner correlated with Wnt1 tumor onset. These data show MMTV-Wnt1 and MMTV-DeltaN89beta-catenin induce canonical signaling in distinct progenitors and that Hedgehog pathway activation is linked to melanocytic nevi and mammary tumor onset arising from excess Wnt1 ligand. They further suggest that Hedgehog pathway activation maybe a critical component and useful indicator of breast tumors arising from unopposed Wnt1 ligand.

Spontaneous regression of a congenital melanocytic nevus

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Amiya Kumar Nath

2011-01-01

Full Text Available Congenital melanocytic nevus (CMN may rarely regress which may also be associated with a halo or vitiligo. We describe a 10-year-old girl who presented with CMN on the left leg since birth, which recently started to regress spontaneously with associated depigmentation in the lesion and at a distant site. Dermoscopy performed at different sites of the regressing lesion demonstrated loss of epidermal pigments first followed by loss of dermal pigments. Histopathology and Masson-Fontana stain demonstrated lymphocytic infiltration and loss of pigment production in the regressing area. Immunohistochemistry staining (S100 and HMB-45, however, showed that nevus cells were present in the regressing areas.

Melanocytes from patients affected by Ullrich congenital muscular dystrophy and Bethlem myopathy have dysfunctional mitochondria that can be rescued with cyclophilin inhibitors

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Alessandra eZulian

2014-11-01

Full Text Available Ullrich congenital muscular dystrophy and Bethlem myopathy are caused by mutations in collagen VI genes, which encode an extracellular matrix protein; yet mitochondria play a major role in disease pathogenesis through a short circuit caused by inappropriate opening of the permeability transition pore, a high conductance channel which causes a shortage in ATP production. We find that melanocytes do not produce collagen VI yet they bind it at the cell surface, suggesting that this protein may play a trophic role and that its absence may cause lesions similar to those seen in skeletal muscle. We show that mitochondria in melanocytes of Ullrich congenital muscular dystrophy and Bethlem myooathy patients display increased size, reduced matrix density and disrupted cristae, findings that suggest a functional impairment. In keeping with this hypothesis, mitochondria (i underwent anomalous depolarization after inhibition of the F-ATP synthase with oligomycin, and (ii displayed decreased respiratory reserve capacity. The non-immunosuppressive cyclophilin inhibitor NIM811 prevented mitochondrial depolarization in response to oligomycin in melanocytes from both Ullrich congenital muscular dystrophy and Bethlem myopathy patients, and partially restored the respiratory reserve of melanocytes from one Bethlem myopathy patient. These results match our recent findings on melanocytes from patients affected by Duchenne muscular dystrophy (Pellegrini et al., 2013 Melanocytes--a novel tool to study mitochondrial dysfunction in Duchenne muscular dystrophy. J Cell Physiol 228, 1323-1331, and suggest that skin biopsies may represent a minimally invasive tool to investigate mitochondrial dysfunction and to evaluate drug efficacy in collagen VI-related myopathies and possibly in other muscle wasting conditions like aging sarcopenia.

Gene Duplication of the zebrafish kit ligand and partitioning of melanocyte development functions to kit ligand a.

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Keith A Hultman

2007-01-01

Full Text Available The retention of particular genes after the whole genome duplication in zebrafish has given insights into how genes may evolve through partitioning of ancestral functions. We examine the partitioning of expression patterns and functions of two zebrafish kit ligands, kit ligand a (kitla and kit ligand b (kitlb, and discuss their possible coevolution with the duplicated zebrafish kit receptors (kita and kitb. In situ hybridizations show that kitla mRNA is expressed in the trunk adjacent to the notochord in the middle of each somite during stages of melanocyte migration and later expressed in the skin, when the receptor is required for melanocyte survival. kitla is also expressed in other regions complementary to kita receptor expression, including the pineal gland, tail bud, and ear. In contrast, kitlb mRNA is expressed in brain ventricles, ear, and cardinal vein plexus, in regions generally not complementary to either zebrafish kit receptor ortholog. However, like kitla, kitlb is expressed in the skin during stages consistent with melanocyte survival. Thus, it appears that kita and kitla have maintained congruent expression patterns, while kitb and kitlb have evolved divergent expression patterns. We demonstrate the interaction of kita and kitla by morpholino knockdown analysis. kitla morphants, but not kitlb morphants, phenocopy the null allele of kita, with defects for both melanocyte migration and survival. Furthermore, kitla morpholino, but not kitlb morpholino, interacts genetically with a sensitized allele of kita, confirming that kitla is the functional ligand to kita. Last, we examine kitla overexpression in embryos, which results in hyperpigmentation caused by an increase in the number and size of melanocytes. This hyperpigmentation is dependent on kita function. We conclude that following genome duplication, kita and kitla have maintained their receptor-ligand relationship, coevolved complementary expression patterns, and that

Experiences of women living with borderline personality disorder

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N. Ntshingila

2016-10-01

Full Text Available There is limited understanding of the experiences of women living with borderline personality disorder. It was therefore decided to discover how women living with this disorder would tell their life story. For the researcher, who worked in a psychotherapy ward where most women were living with borderline personality disorder, the care of these women was of vital importance, as they were less understood by mental health care providers.The research aimed to explore and describe the experiences of women living with borderline personality disorder. A qualitative, explorative, descriptive and contextual study design was used. Data was collected through in-depth phenomenological interviews that focused on the central question, “Tell me your life story”. Eight participants living with borderline personality disorder were interviewed. Tesch's method for data analysis was used (Creswell, 2009:186, along with an independent coder. Measures to ensure trustworthiness and ethical principles were applied throughout the research. From the findings obtained by means of the interviews of women living with borderline personality disorder, it was evident that there were childhood experiences of living in an unsafe space, related to unhealthy family dynamics, boundary violations and educational challenges. They experienced chronic feelings of emptiness in their relationships with theself. They also presented with a pattern of unstable interpersonal relationships and compromised mental health, which was apparent through the early on set of mental problems, emotional upheaval, looking for emotional escape and having different triggerfactors. Lastly, all these women yearned for facilitated mental health.

Is research on borderline personality disorder underfunded by the National Institute of Health?

Science.gov (United States)

Zimmerman, Mark; Gazarian, Doug

2014-12-30

The relationship between bipolar disorder and borderline personality disorder has generated intense interest. Similar to patients with bipolar disorder, patients with borderline personality disorder are frequently hospitalized, are chronically unemployed, abuse substances, attempt and commit suicide. However, one significant difference between the two disorders is that patients with borderline personality disorder are often viewed negatively by mental health professionals. In the present paper we examined whether this negative bias against borderline personality disorder might be reflected in the level of research funding on the disorder. We searched the National Institute of Health (NIH) Research Portfolio Online Portfolio Reporting Tool (RePORT) for the past 25 years and compared the number of grants funded and the total amount of funding for borderline personality disorder and bipolar disorder. The yearly mean number of grants receiving funding was significantly higher for bipolar disorder than for borderline personality disorder. Results were the same when focusing on newly funded grants. For every year since 1990 more grants were funded for bipolar disorder than borderline personality disorder. Summed across all 25 years, the level of funding for bipolar disorder was more than 10 times greater than the level of funding for borderline personality disorder ($622 million vs. $55 million). These findings suggest that the level of NIH research funding for borderline personality disorder is not commensurate with the level of psychosocial morbidity, mortality, and health expenditures associated with the disorder.

Women’s Views on Their Diagnosis and Management for Borderline Gestational Diabetes Mellitus

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Shanshan Han

2015-01-01

Full Text Available Introduction. Little is known about women’s views relating to a diagnosis of borderline gestational diabetes mellitus (GDM and the subsequent management. This study aimed to explore women’s experiences after being diagnosed with borderline GDM, their attitudes about treatment, and factors important to them for achieving any lifestyle changes. Methods. We conducted face-to-face, semistructured interviews with women diagnosed with borderline GDM. Results. A total of 22 women were interviewed. After a diagnosis of borderline GDM, 14 (64% women reported not being concerned or worried. Management of borderline GDM was thought by 21 (95% women to be very important or important. Eighteen (82% women planned to improve their diet and/or exercise to manage their borderline GDM. The most frequently mentioned enabler for achieving intended lifestyle change was being more motivated to improve the health of their baby and/or themselves (15 women. The most frequent barrier was tiredness and/or being physically unwell (11 women. Conclusions. A diagnosis of borderline GDM caused some concern to one-third of women interviewed. The majority of women believed managing their borderline GDM was important and they planned to improve their lifestyle. Women’s own and their babies’ future health were powerful motivators for lifestyle change.

[Emotional and impulsive dimensions in bipolar disorder and borderline personality disorder].

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Leblanc, A; Jarroir, M; Vorspan, F; Bellivier, F; Leveillee, S; Romo, L

2017-05-01

Studies have shown that patients with borderline personality disorder are often misdiagnosed to have bipolar disorder and conversely. Indeed, a number of characteristics common to both disorders could explain this problem: emotional instability as well as impulsivity represent confounding factors and contribute to the risk of misdiagnosis. However, it appears that these characteristics manifest themselves in different ways according to the pathology. The aim of the study is to show differences between affective lability, emotional intensity and impulsivity dimensions. The clinical aim is to refine bipolar disorder and borderline personality disorder diagnosis, to improve psychological care for these patients in the long-term. We compared the emotional and impulsive dimensions in two groups of patients: a group of 21 patients with bipolar disorder and a group of 19 patients with borderline personality disorder. Tools: ALS, a self-report questionnaire to evaluate affective lability, AIM, a self-report questionnaire to see affective intensity, and UPPS, a self-report questionnaire to measure impulsivity according to several dimensions. The results indicate that borderline patients scored significantly higher than bipolar patients at the ALS and AIM scales. Regarding the UPPS, borderline patients scored significantly higher than bipolar patients for the dimensions "lack of premeditation" and "lack of perseverance"; however, bipolar patients had significantly higher scores than borderline patients for the dimension "negative emergency". This study shows that bipolar disorder and borderline personality can be differentiated thanks to emotional dimensions as well as different dimensions of impulsivity: borderline patients appear to have an affective lability and intensity more important than bipolar patients; it also appears that impulsivity manifests itself differently according to the disorder. Copyright © 2016 L'Encéphale, Paris. Published by Elsevier Masson SAS. All

Prognostic factors in breast phyllodes tumors: a nomogram based on a retrospective cohort study of 404 patients.

Science.gov (United States)

Zhou, Zhi-Rui; Wang, Chen-Chen; Sun, Xiang-Jie; Yang, Zhao-Zhi; Chen, Xing-Xing; Shao, Zhi-Ming; Yu, Xiao-Li; Guo, Xiao-Mao

2018-04-01

The aim of this study was to explore the independent prognostic factors related to postoperative recurrence-free survival (RFS) in patients with breast phyllodes tumors (PTBs). A retrospective analysis was conducted in Fudan University Shanghai Cancer Center. According to histological type, patients with benign PTBs were classified as a low-risk group, while borderline and malignant PTBs were classified as a high-risk group. The Cox regression model was adopted to identify factors affecting postoperative RFS in the two groups, and a nomogram was generated to predict recurrence-free survival at 1, 3, and 5 years. Among the 404 patients, 168 (41.6%) patients had benign PTB, 184 (45.5%) had borderline PTB, and 52 (12.9%) had malignant PTB. Fifty-five patients experienced postoperative local recurrence, including six benign cases, 26 borderline cases, and 22 malignant cases; the three histological types of PTB had local recurrence rates of 3.6%, 14.1%, and 42.3%, respectively. Stromal cell atypia was an independent prognostic factor for RFS in the low-risk group, while the surgical approach and tumor border were independent prognostic factors for RFS in the high-risk group, and patients receiving simple excision with an infiltrative tumor border had a higher recurrence rate. A nomogram developed based on clinicopathologic features and surgical approaches could predict recurrence-free survival at 1, 3, and 5 years. For high-risk patients, this predictive nomogram based on tumor border, tumor residue, mitotic activity, degree of stromal cell hyperplasia, and atypia can be applied for patient counseling and clinical management. The efficacy of adjuvant radiotherapy remains uncertain. © 2018 The Authors. Cancer Medicine published by John Wiley & Sons Ltd.

Renal Cell Carcinoma With Chromosome 6p Amplification Including the TFEB Gene: A Novel Mechanism of Tumor Pathogenesis?

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Williamson, Sean R; Grignon, David J; Cheng, Liang; Favazza, Laura; Gondim, Dibson D; Carskadon, Shannon; Gupta, Nilesh S; Chitale, Dhananjay A; Kalyana-Sundaram, Shanker; Palanisamy, Nallasivam

2017-03-01

Amplification of chromosome 6p has been implicated in aggressive behavior in several cancers, but has not been characterized in renal cell carcinoma (RCC). We identified 9 renal tumors with amplification of chromosome 6p including the TFEB gene, 3 by fluorescence in situ hybridization, and 6 from the Cancer Genome Atlas (TCGA) databases. Patients' ages were 28 to 78 years (median, 61 y). Most tumors were high stage (7/9 pT3a, 2/9 pN1). Using immunohistochemistry, 2/4 were positive for melanocytic markers and cathepsin K. Novel TFEB fusions were reported by TCGA in 2; however, due to a small composition of fusion transcripts compared with full-length transcripts (0.5/174 and 3.3/132 FPKM), we hypothesize that these represent secondary fusions due to amplification. Five specimens (4 TCGA, 1 fluorescence in situ hybridization) had concurrent chromosome 3p copy number loss or VHL deletion. However, these did not resemble clear cell RCC, had negative carbonic anhydrase IX labeling, lacked VHL mutation, and had papillary or unclassified histology (2/4 had gain of chromosome 7 or 17). One tumor each had somatic FH mutation and SMARCB1 mutation. Chromosome 6p amplification including TFEB is a previously unrecognized cytogenetic alteration in RCC, associated with heterogenous tubulopapillary eosinophilic and clear cell histology. The combined constellation of features does not fit cleanly into an existing tumor category (unclassified), most closely resembling papillary or translocation RCC. The tendency for high tumor stage, varied tubulopapillary morphology, and a subset with melanocytic marker positivity suggests the possibility of a unique tumor type, despite some variation in appearance and genetics.

Topical application of dimethylbenz[a]anthracene results in the generation of multiple melanocytic nevi in C3H/HeN mice

International Nuclear Information System (INIS)

Elmets, Craig A.; Yusuf, Nabiha; Hamza, Sate; Iranikakh, Nasser; Smith, Jeffrey; Volk, Andrea L.; Skelton, Henry; Smith, Kathy

2004-01-01

Melanocytic nevi are a common dermatological problem for which there are few in vivo models. It has been postulated that environmental factors contribute to their development. Experiments were therefore conducted to determine whether application of dimethylbenz[a]anthracene (DMBA) to the skin of mice would result in the development of melanocytic nevi. One hundred microliters of a 0.1%, 0.5%, or 1.0% solution of DMBA was applied to the dorsal skin of C3H/HeN mice. The mice were then observed for the appearance of pigmented lesions. Histological examination revealed perifollicular accumulations of nevus cells, which were S-100-protein and HMB-45-positive, confirming their melanocytic origin. Pigmented lesions did not occur in animals treated with vehicle alone. Dose response studies revealed both greater numbers of nevi and lesions with larger diameters as the dose of DMBA was increased from 0.1% to 0.5%. In no instance was an invasive melanoma observed even after 40 weeks. The fact that melanocytic nevi can be produced by topical application of DMBA suggests that xenobiotics may play a previously unrecognized role in the development of this common benign neoplasm. Because this is one of the only animal models for melanocytic nevi, further examination of this model may facilitate identification of the molecular and biochemical mechanisms that lead to the development of pigmented nevi and the factors that promote their evolution into invasive melanomas

Relationship between EDNOS and its subtypes and borderline personality disorder.

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Marino, M F; Zanarini, M C

2001-04-01

The purpose of this study was to assess the prevalence of eating disorder not otherwise specified (EDNOS) and four well-defined subtypes of this disorder found in a sample of female borderline patients. The lifetime prevalence of EDNOS and its various subtypes among 233 female borderline patients and 46 female Axis II comparison subjects was assessed using the Structured Clinical Interview for DSM-III-R Axis I disorders. Thirty-three percent of female borderline patients met DSM-III-R criteria for EDNOS at some point in their lives. Of these 76 women, 20% reported a pattern of restricting without low weight, 37% reported a pattern of binging without purging, 37% reported a pattern of purging without binging, and 33% reported a pattern of low weight without loss of menses. However, less than 25% of these 76 borderline women had ever met criteria for anorexia nervosa or bulimia nervosa. The results of this study suggest that EDNOS is a separate cluster of eating disorders among borderline women, rather than a prodromal or residual form of a more clear-cut case of anorexia or bulimia nervosa. Copyright 2001 by John Wiley & Sons, Inc.

Four factors of impulsivity differentiate antisocial and borderline personality disorders.

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DeShong, Hilary L; Kurtz, John E

2013-04-01

Impulsivity is a shared criterion for the diagnosis of antisocial and borderline personality disorders, and this link may account for the high comorbidity rates between the two disorders. The current study aimed to differentiate between borderline and antisocial personality disorders using the four factors of impulsivity identified by Whiteside and Lynam (2001). Five hundred thirty-six undergraduate participants completed the personality assessment inventory (PAI; Morey, 1991) to assess borderline and antisocial personality features and the NEO personality inventory, third edition (NEO-PI-3; McCrae & Costa, 2010) to assess the four factors of impulsivity. Results indicate that negative urgency and lack of perseverance were significantly and uniquely related to borderline features, while sensation seeking and lack of premeditation were significantly and uniquely related to antisocial features. The implications of these results for improved differential diagnosis are discussed.

Melanosomes are transferred from melanocytes to keratinocytes through the processes of packaging, release, uptake, and dispersion.

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Ando, Hideya; Niki, Yoko; Ito, Masaaki; Akiyama, Kaoru; Matsui, Mary S; Yarosh, Daniel B; Ichihashi, Masamitsu

2012-04-01

Recent studies have described the role of shedding vesicles as physiological conveyers of intracellular components between neighboring cells. Here we report that melanosomes are one example of shedding vesicle cargo, but are processed by a previously unreported mechanism. Pigment globules were observed to be connected to the filopodia of melanocyte dendrites, which have previously been shown to be conduits for melanosomes. Pigment globules containing multiple melanosomes were released from various areas of the dendrites of normal human melanocytes derived from darkly pigmented skin. The globules were then captured by the microvilli of normal human keratinocytes, also derived from darkly pigmented skin, which incorporated them in a protease-activated receptor-2 (PAR-2)-dependent manner. After the pigment globules were ingested by the keratinocytes, the membrane that surrounded each melanosome cluster was gradually degraded, and the individual melanosomes then spread into the cytosol and were distributed primarily in the perinuclear area of each keratinocyte. These results suggest a melanosome transfer pathway wherein melanosomes are transferred from melanocytes to keratinocytes via the shedding vesicle system. This packaging system generates pigment globules containing multiple melanosomes in a unique manner.

Gallium-67 scintigraphy in borderline lepromatous leprosy

International Nuclear Information System (INIS)

Mouratidis, B.; Lomas, F.E.

1993-01-01

A middle aged woman with a pyrexia of unknown origin was shown to have borderline lepromatous leprosy. Early gallium-67 scintigraphy demonstrated increased uptake in the subcutaneous tissues of the face and thighs. As a result of these findings skin biopsy was obtained from the right thigh which gave a diagnosis of borderline lepromatous leprosy. The authors have been unable to find other reports of gallium-67 scintigraphy in leprosy but the pattern of gallium-67 distribution should suggest the diagnosis. 5 refs., 1 fig

Borderline personality disorder and polycystic ovary syndrome: A review of the literature.

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Tan, Raelene Ym; Grigg, Jasmin; Kulkarni, Jayashri

2018-02-01

This review examines the existing evidence for the relationship between borderline personality disorder and polycystic ovary syndrome, and to identify commonalities in etiological mechanisms of borderline personality disorder and polycystic ovary syndrome that might explain the relationship between these seemingly disparate disorders. A search of Medline, EMBASE and Cochrane Central was undertaken on 5 December 2016 to identify studies investigating women with borderline personality disorder and polycystic ovary syndrome (or symptoms and markers specific to polycystic ovary syndrome). Nine studies were identified, including three cross-sectional studies investigating symptoms of polycystic ovary syndrome in women with borderline personality disorder, two cross-sectional and one cohort study examining the prevalence of psychiatric diagnoses in women with polycystic ovary syndrome and three case reports of comorbid borderline personality disorder and polycystic ovary syndrome. Overall, the literature shows women with borderline personality disorder to have higher than expected serum androgen levels and incidence of polycystic ovaries, which can be key features of polycystic ovary syndrome. However, this research is still in its infancy, which limits our understanding of this potential comorbid phenomenon. Given the emerging anecdotal and empirical evidence to date, a theoretical discussion of the potential psychoneuroendocrinological mechanism underlying the borderline personality disorder and polycystic ovary syndrome comorbidity is provided. Further rigorous studies using standardized diagnostic criteria for polycystic ovary syndrome are warranted. Specifically, the use of prospective controlled cohort studies may be able to determine the causality and temporality of observed comorbid borderline personality disorder and polycystic ovary syndrome.

Spectrum of fluorodeoxyglucose-positron emission tomography/computed tomography and magnetic resonance imaging findings of ovarian tumors.

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Kitajima, Kazuhiro; Ueno, Yoshiko; Maeda, Tetsuo; Murakami, Koji; Kaji, Yasushi; Kita, Masato; Suzuki, Kayo; Sugimura, Kazuro

2011-11-01

The purpose of this article is to review fluorodeoxyglucose-positron emission tomography/computed tomography (FDG-PET/CT) and magnetic resonance imaging (MRI) findings in a variety of benign, malignant, and borderline malignant ovarian tumors. It is advantageous to become familiar with the wide variety of FDG-PET/CT findings of this entity. Benign ovarian tumors generally have faint uptake, whereas endometriomas, fibromas, and teratomas show mild to moderate uptake. Malignant ovarian tumors generally have intense uptake, whereas tumors with a small solid component often show minimal uptake.

Borderline organization of personality in adulthood and adolescence

OpenAIRE

Alessandra Mura

2011-01-01

About the middle of the 1950 it was proposed the definition of borderline disorder to classify some of the clinical manifestations that they are not explained by neurosis and psychosis theory. The structural approach of Otto Kernberg has been particular relief to understand the borderline disorder. O. Kernberg has been suggested theborderline organization of personality, to outline a typical permanent pathological functioning underlying string of psychopathologic syndromes associated by a sta...

Tandem duplication of 11p12-p13 in a child with borderline development delay and eye abnormalities: dose effect of the PAX6 gene product?

NARCIS (Netherlands)

Aalfs, C. M.; Fantes, J. A.; Wenniger-Prick, L. J.; Sluijter, S.; Hennekam, R. C.; van Heyningen, V.; Hoovers, J. M.

1997-01-01

We report on a girl with a duplication of chromosome band 11p12-->13, which includes the Wilms tumor gene (WT1) and the aniridia gene (PAX6). The girl had borderline developmental delay, mild facial anomalies, and eye abnormalities. Eye findings were also present in most of the 11 other published

[Childhood traumatization, dissociation and nonsuicidal self-injurious behavior in borderline personality disorder].

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Merza, Katalin; Harmatta, János; Papp, Gábor; Kuritárné Szabó, Ildikó

2017-05-01

Childhood traumatization plays a significant role in the etiology of borderline personality disorder. Studies found a significant association between childhood traumatization, dissociation, and nonsuicidal self-injurious behavior. The aim of our study was to assess dissociation and nonsuicidal self-injury among borderline inpatients and to reveal the association between childhood traumatization, dissociation, and self-injurious behavior. The sample consisted of 80 borderline inpatients and 73 depressed control patients. Childhood traumatization, dissociation and self-injurious behavior were assessed by questionnaires. Borderline patients reported severe and multiplex childhood traumatization. Cumulative trauma score and sexual abuse were the strongest predictors of dissociation. Furthermore, we have found that cumulative trauma score and dissociation were highly predictive of self-injurious behavior. Our results suggest that self-injurious behavior and dissociation in borderline patients can be regarded as indicators of childhood traumatization. Orv Hetil. 2017; 158(19): 740-747.

Pseudomelanocytic nests mimicking atypical melanocytic proliferations: first reported cases in the oral cavity.

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Boros, Audrey L; Handlers, Janice P; Melrose, Raymond J

2014-10-01

The concept of pseudomelanocytic nests has been recently described in the dermatology literature. To our knowledge, this entity has yet to be published in the oral pathology literature. We report 2 cases with features of pseudomelanocytic nests. In both instances, nests of cells suspicious for melanocytes were observed. Interpretation of melan-A was negative. Both cases showed strong and diffuse immunoreactivity of the nested cells to CD68. This immunohistochemical staining pattern is most consistent with a melanophage identity. Pseudomelanocytic nests are a recently described entity that represents a potential diagnostic pitfall. Distinguishing pseudomelanocytic nests from an authentic atypical melanocytic proliferation can be challenging and is important for appropriate patient management. Clinicopathologic correlation with cautious interpretation of immunohistochemistry may be necessary to arrive at the correct diagnosis. These cases represent the first reports of pseudomelanocytic nests in the oral pathology literature. Copyright © 2014 Elsevier Inc. All rights reserved.

False memories and memory confidence in borderline patients.

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Schilling, Lisa; Wingenfeld, Katja; Spitzer, Carsten; Nagel, Matthias; Moritz, Steffen

2013-12-01

Mixed results have been obtained regarding memory in patients with borderline personality disorder (BPD). Prior reports and anecdotal evidence suggests that patients with BPD are prone to false memories but this assumption has to been put to firm empirical test, yet. Memory accuracy and confidence was assessed in 20 BPD patients and 22 healthy controls using a visual variant of the false memory (Deese-Roediger-McDermott) paradigm which involved a negative and a positive-valenced picture. Groups did not differ regarding veridical item recognition. Importantly, patients did not display more false memories than controls. At trend level, borderline patients rated more items as new with high confidence compared to healthy controls. The results tentatively suggest that borderline patients show uncompromised visual memory functions and display no increased susceptibility for distorted memories. Copyright © 2013 Elsevier Ltd. All rights reserved.

Art Therapy for Individuals with Borderline Personality: Using a Dialectical Behavior Therapy Framework

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Drass, Jessica Masino

2015-01-01

Art therapy has shown benefits for people with borderline personality disorder and borderline personality traits by alleviating interpersonal difficulties such as affect regulation, an unstable sense of self, self-injurious behaviors, and suicidal ideation. Borderline personality disorder is currently viewed as a trauma spectrum disorder, because…

Frequency of papillary tubal hyperplasia (PTH), salpingoliths and transition from adenoma to borderline ovarian tumors (BOT): A systematic analysis of 74 BOT with different histologic types.

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Horn, Lars-Christian; Angermann, Karolin; Hentschel, Bettina; Einenkel, Jens; Höhn, Anne Kathrin

2017-04-01

Borderline ovarian tumors (BOT) arise from cystadenomas and represent a transition step within the development of low-grade ovarian carcinomas (Type I tumors). That pathway mirrors the adenoma-to-carcinoma sequence known for colorectal cancer. It has been suggested that papillary tubal hyperplasia (PTH) and salpingoliths may be associated with the development of BOT. To evaluate the frequency of the presence of benign cystadenoma and its transition to BOT in a given patient as well as the presence of PTH and salpingoliths we re-valuated in 74 consecutive cases of BOT with different histologic types. The majority of cases represented serous-BOT (60.8%), followed by mucinous BOT (25.7%), other histologic types were rare. 86.5% showed an adenoma-BOT sequence, which was seen in all mucinous BOT but was missed in 15.6% of serous BOT. Two cases had salpingoliths without associated PTH. PTH was seen in four out of the 74 (5.4%) BOT and occurred only in cases with serous histology. The vast majority of BOT represent a transition from benign cystadenoma to BOT in cases with mucinous and serous histology. Salpingoliths are rarely seen in association with BOT and occurred exclusively in BOT with serous histology. PTH may represent a distinct lesion but is rarely seen in association with BOT, especially in those with non-serous histology. Further studies are needed to evaluate the frequency and pathogenetic association of PTH with BOT. Copyright © 2017 Elsevier GmbH. All rights reserved.

Radiation of different human melanoma cell lines increased expression of RHOB. Level of this tumor suppressor gene in different cell lines

International Nuclear Information System (INIS)

Notcovich, C.; Molinari, B.; Duran, H.; Delgado González, D.; Sánchez Crespo, R.

2013-01-01

Previous results of our group show that a correlation exists between intrinsic radiosensitivity of human melanoma cells and cell death by apoptosis. RhoB is a small GTPase that regulates cytoskeletal organization. Besides, is related to the process of apoptosis in cells exposed to DNA damage as radiation. Also, RhoB levels decrease in a wide variety of tumors with the tumor stage, being considered a tumor suppressor gene due to its antiproliferative and proapoptotic effect. The aim of this study was to analyze the expression of RhoB in different human melanoma cell lines in relation to melanocytes, and evaluate the effect of gamma radiation on the expression of RhoB. We used the A375, SB2 and Meljcell lines, and the derived from melanocytes Pig1. It was found for all three tumor lines RhoB expression levels significantly lower than those of Pig1 (p <0.05), as assessed by semiquantitative RT-PCR . When tumor cells were irradiated to a dose of 2Gyinduction was observed at 3 hours RhoB irradiation. RhoB expression increased in all lines relative to non-irradiated control, showing a greater induction ( p< 0.05) for the more radiosensitive line SB2, consistent with apoptosis in response to radiation. The results allow for the first time in melanoma demonstrate that RhoB, as well as in other tumor types, has a lower expression in tumor cells than their normal counterparts. Moreover, induction in the expression of RhoB in irradiated cells may be associated with the process of radiation-induced apoptosis. The modulation of RhoB could be a new tool to sensitize radioresistant melanoma. (author)

Etiological features of borderline personality related characteristics in a birth cohort of 12-year-old children.

Science.gov (United States)

Belsky, Daniel W; Caspi, Avshalom; Arseneault, Louise; Bleidorn, Wiebke; Fonagy, Peter; Goodman, Marianne; Houts, Renate; Moffitt, Terrie E

2012-02-01

It has been reported that borderline personality related characteristics can be observed in children, and that these characteristics are associated with increased risk for the development of borderline personality disorder. It is not clear whether borderline personality related characteristics in children share etiological features with adult borderline personality disorder. We investigated the etiology of borderline personality related characteristics in a longitudinal cohort study of 1,116 pairs of same-sex twins followed from birth through age 12 years. Borderline personality related characteristics measured at age 12 years were highly heritable, were more common in children who had exhibited poor cognitive function, impulsivity, and more behavioral and emotional problems at age 5 years, and co-occurred with symptoms of conduct disorder, depression, anxiety, and psychosis. Exposure to harsh treatment in the family environment through age 10 years predicted borderline personality related characteristics at age 12 years. This association showed evidence of environmental mediation and was stronger among children with a family history of psychiatric illness, consistent with diathesis-stress models of borderline etiology. Results indicate that borderline personality related characteristics in children share etiological features with borderline personality disorder in adults and suggest that inherited and environmental risk factors make independent and interactive contributions to borderline etiology.

Analytical validation of a melanoma diagnostic gene signature using formalin-fixed paraffin-embedded melanocytic lesions.

Science.gov (United States)

Warf, M Bryan; Flake, Darl D; Adams, Doug; Gutin, Alexander; Kolquist, Kathryn A; Wenstrup, Richard J; Roa, Benjamin B

2015-01-01

These studies were to validate the analytical performance of a gene expression signature that differentiates melanoma and nevi, using RNA expression from 14 signature genes and nine normalization genes that generates a melanoma diagnostic score (MDS). Formalin-fixed paraffin-embedded melanocytic lesions were evaluated in these studies. The overall SD of the assay was determined to be 0.69 MDS units. Individual amplicons within the signature had an average amplification efficiency of 92% and a SD less than 0.5 CT. The MDS was reproducible across a 2000-fold dilution range of input RNA. Melanin, an inhibitor of PCR, does not interfere with the signature. These studies indicate this signature is robust and reproducible and is analytically validated on formalin-fixed paraffin-embedded melanocytic lesions.

[Course of borderline personality disorder: literature review].

Science.gov (United States)

Karaklic, D; Bungener, C

2010-10-01

Borderline personality disorder (BPD) is a serious mental disorder associated with severe emotional, behavioral, cognitive and interpersonal dysfunction, extensive functional impairment and frequent self-destructive behaviour, including deliberate self-harm and suicidal behaviour. For quite some time, BPD has been viewed as a chronic disorder and borderline patients as extremely difficult to treat, doomed to a life of misery. However, those views are changing and there is an increasing recognition that BPD has a far more benign course than previously thought. The purpose of this study is to show how those views changed over time by reviewing longitudinal studies of the course of BPD. We have reviewed the literature published from 1968 to March 2009, using the following key words: borderline personality disorder, outcome, follow-up studies with some additional references. The aim of the longitudinal studies conducted prior to the DSM definition of BPD criteria was to determine whether borderline patients could become psychotic over time, but no such evidence was found even though their functioning was at a relatively low level. The studies conducted after the introduction of BPD in the DSM in 1980 tested the stability and the specificity of BPD diagnosis, concluding that the criteria were relatively stable in the short run since the majority of patients continued to meet them at the follow-up assessments. However, those studies had many methodological drawbacks which limited their generalizability such as small sample sizes, high attrition rates, the absence of comparison groups, etc. Four retrospective studies of the 15-year outcome of borderline patients obtained virtually identical results despite methodological differences, showing that the global functioning of borderline patients improved substantially over time with mean scores of the GAF scale falling within a mild range of impairment. One 27-year retrospective study showed that borderline patients continued

Defense mechanisms in schizotypal, borderline, antisocial, and narcissistic personality disorders.

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Perry, J Christopher; Presniak, Michelle D; Olson, Trevor R

2013-01-01

Numerous authors have theorized that defense mechanisms play a role in personality disorders. We reviewed theoretical writings and empirical studies about defenses in schizotypal, borderline, antisocial, and narcissistic personality disorders, developing hypotheses about these differential relationships. We then examined these hypotheses using dynamic interview data rated for defenses in a study of participants (n = 107) diagnosed with these four personality disorder types. Overall, the prevalence of immature defenses was substantial, and all four disorders fit within the broad borderline personality organization construct. Defenses predicted the most variance in borderline and the least variance in schizotypal personality disorder, suggesting that dynamic factors played the largest role in borderline and the least in schizotypal personality. Central to borderline personality were strong associations with major image-distorting defenses, primarily splitting of self and other's images, and the hysterical level defenses, dissociation and repression. Narcissistic and antisocial personality disorders shared minor image-distorting defenses, such as omnipotence or devaluation, while narcissistic also used splitting of self-images and antisocial used disavowal defenses like denial. Overall, differential relationships between specific defenses and personality disorder types were largely consistent with the literature, and consistent with the importance that the treatment literature ascribes to working with defenses.

Abundance of the benign melanocytic universe: Dermoscopic-histopathological correlation in nevi.

Science.gov (United States)

Woltsche, Nora; Schmid-Zalaudek, Karin; Deinlein, Teresa; Rammel, Katrin; Hofmann-Wellenhof, Rainer; Zalaudek, Iris

2017-05-01

The broad universe of "melanocytic nevi" includes a variety of different subtypes, which can be classified either due to their morphology, epidemiology, genetic alterations or risk for developing melanoma. Regarding morphology, on the one hand macroscopic/clinical and on the other hand histopathological appearance were used to subdivide in the past, often resulting in confusion and poor interobserver agreement, while nowadays dermoscopy presents the clinician's precious bridge between naked-eye examination and histopathological diagnostics, allowing prediction of the lesions' histopathology, follow up and monitoring over time without need of excision. The non-invasive dermoscopic examination relies on the assessment of colors, patterns and the distribution of both within a cutaneous lesion. Until today, the correspondence of certain dermoscopic colors and patterns to certain histopathological correlates has been reported for a huge amount of different cutaneous lesions. Moreover, the correspondence of certain dermoscopic features to certain body sites, age groups and pigmentary traits, but also to specific genetic alterations in lesions, has been broadly investigated. Dermoscopy has led us to a new understanding of melanocytic nevi's biology and evolution and, last but not least, to a new classification system, which we want to present herein. © 2017 Japanese Dermatological Association.

Peritoneal borderline cystoadenocarcinoma

Directory of Open Access Journals (Sweden)

Manoel João Batista Castello Girão

Full Text Available Carcinomas of peritoneal origin represent a seldom diagnosed entity of unknown etiology, with important implications in terms of prophylactic oophorectomy. Initially described in patients belonging to families at high risk for ovarian cancer, it possibly has a pathogeny similar to that of endosalpingiosis and of some cases of endometriosis. We report a case of peritoneal borderline mucinous carcinoma with an anatomopathological diagnosis of normal ovaries.

Phyllodes tumors with and without fibroadenoma-like areas display distinct genomic features and may evolve through distinct pathways.

Science.gov (United States)

Pareja, Fresia; Geyer, Felipe C; Kumar, Rahul; Selenica, Pier; Piscuoglio, Salvatore; Ng, Charlotte K Y; Burke, Kathleen A; Edelweiss, Marcia; Murray, Melissa P; Brogi, Edi; Weigelt, Britta; Reis-Filho, Jorge S

2017-01-01

Breast fibroepithelial lesions (fibroadenomas and phyllodes tumors) are underpinned by recurrent MED12 exon 2 mutations, which are more common in fibroadenomas and benign phyllodes tumors. TERT promoter hotspot mutations have been documented in phyllodes tumors, and found to be more frequent in borderline and malignant lesions. Several lines of evidence suggest that a subset of phyllodes tumors might arise from fibroadenomas. Here we sought to investigate the genetic differences between phyllodes tumors with fibroadenoma-like areas vs. those without. We retrieved data for 16 borderline/ malignant phyllodes tumors, including seven phyllodes tumors with fibroadenoma-like areas and nine phyllodes tumors without fibroadenoma-like areas, which had been previously subjected to targeted capture massively parallel sequencing. Whilst MED12 exon 2 mutations were significantly more frequent in tumors with fibroadenoma-like areas (71 vs. 11%), an enrichment in genetic alterations targeting bona fide cancer genes was found in those without fibroadenoma-like areas, in particular in EGFR mutations and amplifications (78 vs. 14%). No significant difference in the frequency of TERT genetic alterations was observed (71% in cases with fibroadenoma-like areas vs 56% in those without fibroadenoma-like areas). Our data suggest that the development of phyllodes tumors might follow two different evolutionary pathways: a MED12 -mutant pathway that involves the progression from a fibroadenoma to a malignant phyllodes tumor; and a MED12 -wild-type pathway, where malignant phyllodes tumors arise de novo through the acquisition of genetic alterations targeting cancer genes. Additional studies are warranted to confirm our observations and define whether the outcome differs between both pathways.

The five-factor model of personality and borderline personality disorder: a genetic analysis of comorbidity.

Science.gov (United States)

Distel, Marijn A; Trull, Timothy J; Willemsen, Gonneke; Vink, Jacqueline M; Derom, Catherine A; Lynskey, Michael; Martin, Nicholas G; Boomsma, Dorret I

2009-12-15

Recently, the nature of personality disorders and their relationship with normal personality traits has received extensive attention. The five-factor model (FFM) of personality, consisting of the personality traits neuroticism, extraversion, openness to experience, agreeableness, and conscientiousness, is one of the proposed models to conceptualize personality disorders as maladaptive variants of continuously distributed personality traits. The present study examined the phenotypic and genetic association between borderline personality and FFM personality traits. Data were available for 4403 monozygotic twins, 4425 dizygotic twins, and 1661 siblings from 6140 Dutch, Belgian, and Australian families. Broad-sense heritability estimates for neuroticism, agreeableness, conscientiousness, extraversion, openness to experience, and borderline personality were 43%, 36%, 43%, 47%, 54%, and 45%, respectively. Phenotypic correlations between borderline personality and the FFM personality traits ranged from .06 for openness to experience to .68 for neuroticism. Multiple regression analyses showed that a combination of high neuroticism and low agreeableness best predicted borderline personality. Multivariate genetic analyses showed the genetic factors that influence individual differences in neuroticism, agreeableness, conscientiousness, and extraversion account for all genetic liability to borderline personality. Unique environmental effects on borderline personality, however, were not completely shared with those for the FFM traits (33% is unique to borderline personality). Borderline personality shares all genetic variation with neuroticism, agreeableness, conscientiousness, and extraversion. The unique environmental influences specific to borderline personality may cause individuals with a specific pattern of personality traits to cross a threshold and develop borderline personality.

Borderline personality pathology in young people at ultra high risk of developing a psychotic disorder.

Science.gov (United States)

Ryan, Jaymee; Graham, Anne; Nelson, Barnaby; Yung, Alison

2017-06-01

The association between borderline personality disorder and the ultra high risk (UHR) for psychosis state is unclear. The following study aimed to investigate the type of attenuated psychotic symptoms and prevalence of borderline personality pathology in a sample of UHR young people. Additionally, the study aimed to explore whether borderline personality pathology influenced the transition rate to psychosis. Medical records from Orygen Youth Health between 2007 and 2009 were examined. There were 180 patients who met UHR criteria and were included for analysis. Most patients were females (62.8%) and age ranged from 15 to 24 years. A quarter (25.2%) of UHR patients endorsed items consistent with borderline personality pathology. UHR patients with borderline personality pathology experienced a range of attenuated psychotic symptoms and could not be statistically differentiated from UHR patients with less significant or without borderline personality pathology. Borderline personality pathology did not increase or decrease the risk of developing a psychotic disorder. The absence of depression was the only predictor of psychosis. Many UHR patients present with concurrent borderline personality features. The psychotic experiences reported by UHR patients with borderline personality features were not limited to paranoid ideation, supporting the idea that borderline personality disorder may include a wider range of psychotic symptoms than previously thought. It is further possible that the psychotic symptoms experienced in this group could also be indicative of an emerging psychotic disorder. © 2015 Wiley Publishing Asia Pty Ltd.

C-kit expression in canine mucosal melanomas.

Science.gov (United States)

Newman, S J; Jankovsky, J M; Rohrbach, B W; LeBlanc, A K

2012-09-01

The c-kit receptor is responsible for transmission of promigration signals to melanocytes; its downregulation may be involved in malignant progression of human melanocytic neoplasms. Expression of this receptor has not been examined in normal or neoplastic melanocytes from dogs. In this study, 14 benign dermal and 61 malignant mucosal melanocytic tumors were examined for c-kit (KIT) expression. Sites of the mucosal melanomas were gingiva (not further specified; n = 30), buccal gingiva (n = 6), soft palate (n = 4), hard palate (n = 5), tongue (n = 7), lip (n = 6), and conjunctiva (n = 3). Melan A was expressed in all 14 dermal melanocytomas and in 59 of 61 (96.7%) tumors from oral or conjunctival mucosa, confirming melanocytic origin. C-kit receptor expression was strong and diffuse throughout the cytoplasm in all 14 dermal melanocytomas and was identified in basilar mucosal melanocytes over submucosal neoplasms (27 of 61, 44.3%), junctional (neoplastic) melanocytes (17 of 61, 27.9%), and, less commonly, neoplastic melanocytes of the subepithelial tumors (6 of 61, 9.8%). KIT expression anywhere within the resected melanomas correlated with significantly longer survival. These results suggest that c-kit receptor expression may be altered in canine melanomas and may have potential as a prognostic indicator for mucosal melanomas.

FAMILY HISTORY STUDY OF THE FAMILIAL COAGGREGATION OF BORDERLINE PERSONALITY DISORDER WITH AXIS I AND NON-BORDERLINE DRAMATIC CLUSTER AXIS II DISORDERS

OpenAIRE

Zanarini, Mary C.; Barison, Leah K.; Frankenburg, Frances R.; Reich, D. Bradford; Hudson, James I.

2009-01-01

The purpose of this study was to assess the familial coaggregation of borderline personality disorder (BPD) with a full array of axis I disorders and four axis II disorders (antisocial personality disorder, histrionic personality disorder, narcissistic personality disorder, and sadistic personality disorder) in the first-degree relatives of borderline probands and axis II comparison subjects. Four hundred and forty-five inpatients were interviewed about familial psychopathology using the Revi...

Stereological quantification of tumor volume, mean nuclear volume and total number of melanoma cells correlated with morbidity and mortality

DEFF Research Database (Denmark)

Bønnelykke-Behrndtz, Marie Louise; Sørensen, Flemming Brandt; Damsgaard, Tine Engberg

2008-01-01

potential indicators of prognosis. Sixty patients who underwent surgery at the Department of Plastic Surgery, Aarhus University Hospital, from 1991 to 1994 were included in the study. Total tumor volume was estimated by the Cavalieri technique, total number of tumor cells by the optical dissector principle...... showed a significant impact on both disease-free survival (p=0.001) and mortality (p=0.009). In conclusion, tumor volume and total number of cancer cells were highly reproducible but did not add additional, independent prognostic information regarding the study population.......Stereological quantification of tumor volume, total number of tumor cells and mean nuclear volume provides unbiased data, regardless of the three-dimensional shape of the melanocytic lesion. The aim of the present study was to investigate whether these variables are reproducible and may represent...

The effects of oxytocin on social cognition in borderline personality disorder.

Science.gov (United States)

Servan, A; Brunelin, J; Poulet, E

2018-02-01

Deficits in social cognition and interpersonal difficulties are key features in borderline personality disorder. Social cognition refers to the function of perceiving and adequately dealing with social signals, leading to the establishment and maintenance of healthy and positive social relationships. Evidence suggests that oxytocin (OT) may improve social cognition and human social behavior. Recently, several studies have highlighted the beneficial effects of oxytocin in several psychiatric conditions involving social cognition deficits such as schizophrenia, autism or social phobia. However, despite growing interest, the effects of oxytocin in patients with borderline personality disorder are far from being clearly demonstrated. The objective of this work was to review and discuss studies investigating the interest of oxytocin in alleviating social cognition deficits in patients with borderline personality disorder (recognition of emotion, trust and cooperation, affective and cognitive empathy, emotional expression and social problem-solving). A systematic review of the literature was conducted up to September 31, 2016 on the Pubmed, Science direct, Medline and Scopus databases using "borderline personality disorder" and "oxytocin" as keywords. To be included, studies were to include patients with borderline personality disorder; to investigate social cognition and to investigate the effect of oxytocin on social cognition in patients with TPB. The initial search yielded 52 articles. Among them, 11 studies were selected according to the PRISMA criteria. The effect of oxytocin on social cognition in patients with borderline personality disorder was mainly investigated in relation to recognition of emotions and trust and cooperation. We did not find any studies investigating the effect of oxytocin on affective and cognitive empathy, emotional expression or social problem-solving abilities. In patients with borderline personality disorder, oxytocin had a beneficial

Borderline Personality Disorder and Religion: A perspective from a Muslim country.

Directory of Open Access Journals (Sweden)

Sina Hafizi

2014-09-01

Full Text Available There are still many unanswered questions about psychological and social factors that may affect the development and treatment of borderline personality disorder (BPD. Religion/spirituality (R/S is a factor that could influence the lives of people with BPD.The aim of this study was to evaluate the relationship between religiosity, religious attendance and borderline personality traits.Four hundred twenty- nine medical students of Tehran University of medical sciences participated in this study, and their information on demographics, responses to the Duke University Religion Index (DUREL, and the Structured Clinical Interview for DSM-IV Axis II Disorders (the self-administered section on BPD was obtained.The total score of SCID-II questionnaire and the number of positive borderline personality characteristics on the SCID-II were inversely related with the DUREL total score and individual DUREL items. Those with higher levels of borderline personality traits had lower total DUREL score and lower DUREL subscale scores.Religiosity and religious attendance are negatively correlated with borderline personality traits, especially with anger, instability of mood, feeling of emptiness and self-harming behaviors. These findings are important for understanding the causes of BPD and in developing treatments for this disorder.

Childhood maltreatment and its link to borderline personality disorder features in children: A systematic review approach.

Science.gov (United States)

Ibrahim, Jeyda; Cosgrave, Nicola; Woolgar, Matthew

2018-01-01

Borderline personality disorder has repeatedly been associated with a history of maltreatment in childhood; however, research on maltreatment and its link to borderline features in children is limited. The aim of this review is to synthesise the existing data on the association between maltreatment and borderline features in childhood. In total, 10 studies were included in this systematic review. Studies indicated that children with borderline features were more likely to have a history of maltreatment, and that children who had been maltreated were more likely to present with borderline features. Other risk factors such as cognitive and executive functioning deficits, parental dysfunction and genetic vulnerability were also identified across studies. This review adds to the literature by highlighting maltreatment as a risk factor for borderline features in childhood. Longitudinal research is required to establish the link between childhood borderline features and adult borderline features. Implications for early identification, prevention and intervention services are discussed.

Constitutive activation of the ERK pathway in melanoma and skin melanocytes in Grey horses.

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Jiang, Lin; Campagne, Cécile; Sundström, Elisabeth; Sousa, Pedro; Imran, Saima; Seltenhammer, Monika; Pielberg, Gerli; Olsson, Mats J; Egidy, Giorgia; Andersson, Leif; Golovko, Anna

2014-11-21

Constitutive activation of the ERK pathway, occurring in the vast majority of melanocytic neoplasms, has a pivotal role in melanoma development. Different mechanisms underlie this activation in different tumour settings. The Grey phenotype in horses, caused by a 4.6 kb duplication in intron 6 of Syntaxin 17 (STX17), is associated with a very high incidence of cutaneous melanoma, but the molecular mechanism behind the melanomagenesis remains unknown. Here, we investigated the involvement of the ERK pathway in melanoma development in Grey horses. Grey horse melanoma tumours, cell lines and normal skin melanocytes were analyzed with help of indirect immunofluorescence and immunoblotting for the expression of phospho-ERK1/2 in comparison to that in non-grey horse and human counterparts. The mutational status of BRAF, RAS, GNAQ, GNA11 and KIT genes in Grey horse melanomas was determined by direct sequencing. The effect of RAS, RAF and PI3K/AKT pathways on the activation of the ERK signaling in Grey horse melanoma cells was investigated with help of specific inhibitors and immunoblotting. Individual roles of RAF and RAS kinases on the ERK activation were examined using si-RNA based approach and immunoblotting. We found that the ERK pathway is constitutively activated in Grey horse melanoma tumours and cell lines in the absence of somatic activating mutations in BRAF, RAS, GNAQ, GNA11 and KIT genes or alterations in the expression of the main components of the pathway. The pathway is mitogenic and is mediated by BRAF, CRAF and KRAS kinases. Importantly, we found high activation of the ERK pathway also in epidermal melanocytes, suggesting a general predisposition to melanomagenesis in these horses. These findings demonstrate that the presence of the intronic 4.6 kb duplication in STX17 is strongly associated with constitutive activation of the ERK pathway in melanocytic cells in Grey horses in the absence of somatic mutations commonly linked to the activation of this

Human Adipose Mesenchymal Cells Inhibit Melanocyte Differentiation and the Pigmentation of Human Skin via Increased Expression of TGF-β1.

Science.gov (United States)

Klar, Agnes S; Biedermann, Thomas; Michalak, Katarzyna; Michalczyk, Teresa; Meuli-Simmen, Claudia; Scherberich, Arnaud; Meuli, Martin; Reichmann, Ernst

2017-12-01

There is accumulating evidence that interactions between epidermal melanocytes and stromal cells play an important role in the regulation of skin pigmentation. In this study we established a pigmented dermo-epidermal skin model, melDESS, of human origin to investigate the effects of distinct stromal cells on melanogenesis. melDESS is a complex, clinically relevant skin equivalent composed of an epidermis containing both melanocytes and keratinocytes. Its dermal compartment consists either of adipose tissue-derived stromal cells, dermal fibroblasts (Fbs), or a mixture of both cell types. These skin substitutes were transplanted for 5 weeks on the backs of immuno-incompetent rats and analyzed. Gene expression and Western blot analyses showed a significantly higher expression of transforming growth factor-β1 by adipose tissue-derived stromal cells compared with dermal Fbs. In addition, we showed that melanocytes responded to the increased levels of transforming growth factor-β1 by down-regulating the expression of key melanogenic enzymes such as tyrosinase. This caused decreased melanin synthesis and, consequently, greatly reduced pigmentation of melDESS. The conclusions are of utmost clinical relevance, namely that adipose tissue-derived stromal cells derived from the hypodermis fail to appropriately interact with epidermal melanocytes, thus preventing the sustainable restoration of the patient's native skin color in bioengineered skin grafts. Copyright © 2017 The Authors. Published by Elsevier Inc. All rights reserved.

Effects of Extremely Low Frequency Electromagnetic Fields on Melanogenesis through p-ERK and p-SAPK/JNK Pathways in Human Melanocytes

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Yu-Mi Kim

2017-10-01

Full Text Available This study evaluated frequency-dependent effects of extremely low frequency electromagnetic fields (ELF-EMFs on melanogenesis by melanocytes in vitro. Melanocytes were exposed to 2 mT EMFs at 30–75 Hz for 3 days before melanogenesis was examined. Exposure to ELF-EMFs at 50 and 60 Hz induced melanogenic maturation without cell damage, without changing cell proliferation and mitochondrial activity. Melanin content and tyrosinase activity of cells exposed to 50 Hz were higher than in controls, and mRNA expression of tyrosinase-related protein-2 was elevated relative to controls at 50 Hz. Phosphorylated cyclic adenosine monophosphate response element-binding protein (p-CREB levels were higher than controls in cells exposed to ELF-EMFs at 50–75 Hz. Immunohistochemical staining showed that melanocyte-specific markers (HMB45, Melan-A were strongly expressed in cells exposed to EMFs at 50 and 60 Hz compared to controls. Thus, exposure to ELF-EMFs at 50 Hz could stimulate melanogenesis in melanocytes, through activation of p-CREB and p-p38 and inhibition of phosphorylated extracellular signal-regulated protein kinase and phosphorylated stress-activated protein kinase/c-Jun N-terminal kinase. The results may form the basis of an appropriate anti-gray hair treatment or be applied in a therapeutic device for inducing repigmentation in the skin of vitiligo patients.

[Pharmacotherapy in the treatment of borderline personality disorder].

Science.gov (United States)

Alliani, Daniela; Tarantelli, Silvia

2009-01-01

The aim of this study is to bring together the previous studies on pharmacotherapy of borderline disorder from the oldest to the recent ones, mainly focusing on atypical antipsychotic, whose success has been underlined in recent medical literature with peculiar reference to olanzapine. Since the '80 the pharmacotherapy in borderline personality disorder has been playing an increasing role in the interest of scientific community and in the medical practice as indicated by APA guidelines (2000). Nowadays the pharmacological approach, supported by some experimental outcomes, follow a so called "dimensional" standard. The targets of this standard drug approach are specific psychopathological "dimensions" of the disorder and related neurotransmitters' changes in particular linked to serotoninergic and dopaminergic systems, both supported by experimental outcomes. The psychopathological dimensions to which pharmacological approach is more suitable are: impulsiveness and emotional dysregulation. During the last past years, effectiveness of atypical antipsychotic drugs became of major interest in medical treatment of borderline disorder, mainly related to their action toward the serotoninergic and dopaminergic systems.

Significance of aggressive surgery for an invasive carcinoma derived from an intraductal papillary mucinous neoplasm diagnosed preoperatively as borderline resectable.

Science.gov (United States)

Aimoto, Takayuki; Mizutani, Satoshi; Kawano, Youichi; Suzuki, Hideyuki; Uchida, Eiji

2013-01-01

We investigated the clinicopathological features of borderline resectable invasive carcinomas (BRICs) derived from intraductal papillary mucinous neoplasms (IPMNs) and examined the significance of the aggressive "surgery first" approach compared with the treatment of conventional borderline resectable pancreatic ductal adenocarcinomas (BRPDAs). We retrospectively studied 7 patients with BRICs derived from IPMNs and 14 patients with conventional BRPDAs. Several factors were reviewed: initial symptoms, preoperative imaging, serum level of CA19-9, perioperative factors, pathological findings, adjuvant chemotherapy, and outcome. All BRICs derived from IPMN were huge tumors (more than 3 cm in diameter) suspected to involve BRICs derived from IPMNs were larger than those of conventional BRPDAs (pBRICs derived from IPMN less frequently metastasized to lymph nodes (pBRICs derived from IPMNs (100%) than for conventional BRPDAs (19%, pBRICs derived from an intestinal or gastric IPMN are less aggressive than conventional BRPDAs and have a more favorable prognosis. In addition, aggressive "surgery first" approach may contribute to this better prognosis.

A rare case of unilateral diffuse melanocytic proliferation

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Guruprasad Ayachit

2018-01-01

Full Text Available A 67-year-old woman presented with metamorphopsia in the right eye. Leopard mottling was seen temporal to the fovea oculus dexter with corresponding hyper- and hypo-autofluorescent lesions on fundus autofluorescence. Spectral domain-optical coherence tomography revealed hyperreflective dots in the retinal pigment epithelium and choroid with subretinal fluid (SRF. Intravitreal bevacizumab was administered with which SRF resolved, albeit with increase in the areas of mottling. The patient was diagnosed to have metastatic ductal carcinoma of the right breast. It is important to bear in mind that the well-known entity of bilateral diffuse uveal melanocytic proliferation can rarely present unilaterally.

Mutations in c10orf11, a melanocyte-differentiation gene, cause autosomal-recessive albinism.

Science.gov (United States)

Grønskov, Karen; Dooley, Christopher M; Østergaard, Elsebet; Kelsh, Robert N; Hansen, Lars; Levesque, Mitchell P; Vilhelmsen, Kaj; Møllgård, Kjeld; Stemple, Derek L; Rosenberg, Thomas

2013-03-07

Autosomal-recessive albinism is a hypopigmentation disorder with a broad phenotypic range. A substantial fraction of individuals with albinism remain genetically unresolved, and it has been hypothesized that more genes are to be identified. By using homozygosity mapping of an inbred Faroese family, we identified a 3.5 Mb homozygous region (10q22.2-q22.3) on chromosome 10. The region contains five protein-coding genes, and sequencing of one of these, C10orf11, revealed a nonsense mutation that segregated with the disease and showed a recessive inheritance pattern. Investigation of additional albinism-affected individuals from the Faroe Islands revealed that five out of eight unrelated affected persons had the nonsense mutation in C10orf11. Screening of a cohort of autosomal-recessive-albinism-affected individuals residing in Denmark showed a homozygous 1 bp duplication in C10orf11 in an individual originating from Lithuania. Immunohistochemistry showed localization of C10orf11 in melanoblasts and melanocytes in human fetal tissue, but no localization was seen in retinal pigment epithelial cells. Knockdown of the zebrafish (Danio rerio) homolog with the use of morpholinos resulted in substantially decreased pigmentation and a reduction of the apparent number of pigmented melanocytes. The morphant phenotype was rescued by wild-type C10orf11, but not by mutant C10orf11. In conclusion, we have identified a melanocyte-differentiation gene, C10orf11, which when mutated causes autosomal-recessive albinism in humans. Copyright © 2013 The American Society of Human Genetics. Published by Elsevier Inc. All rights reserved.

Malignant hepatic perivascular epithelioid cell tumor (PEComa)- Case report and a brief review

International Nuclear Information System (INIS)

Abhirup, B.; Kaushal, K.; Ganesh, N.; Sanket, M.

2015-01-01

Perivascular epithelioid cell tumors (PEComas) are rare mesenchymal neoplasms which can arise from almost any location in the body. Diagnosing them pre-operatively is difficult as they mimic features of other hepatic neoplasms including hepatocellular carcinoma (HCC), fibrolamellar HCC, and focal nodular hyperplasia (FNH) among others. The unique feature of these tumors is the coexpression of muscle and melanocytic markers. These are identified immunohistochemically by the expression of Human Melanin Black-45 (HMB-45), Melan-A and Smooth Muscle Antigen (SMA) which are seen in the majority of tumors. The liver is uncommonly associated with a PEComa and the approach to a patient with hepatic PEComa is not well described. There is no consensus regarding the neo-adjuvant/adjuvant therapy in these patients. The natural history of this condition is not well documented making it an unpredictable disease. Here we have discussed a case and reviewed the literature concerning these rare tumors.

Expression patterns of emmprin and monocarboxylate transporter-1 in ovarian epithelial tumors.

Science.gov (United States)

Fukuoka, Miyoko; Hamasaki, Makoto; Koga, Kaori; Hayashi, Hiroyuki; Aoki, Mikiko; Kawarabayashi, Tatsuhiko; Miyamoto, Shingo; Nabeshima, Kazuki

2012-10-01

Emmprin is a transmembrane glycoprotein known as a matrix metalloproteinase inducer and is highly up-regulated in malignant cancer cells. The monocarboxylate transporters (MCTs) are responsible for H(+)-linked transport of monocarboxylates across the cell membrane. It was recently demonstrated that proper plasma membrane localization and activity of MCTs require the presence of emmprin as a chaperone and that MCT-1 also acts as chaperone for emmprin. The objectives of this study were to clarify emmprin and MCT-1 expression patterns in ovarian epithelial tumors and to elucidate the clinicopathological significance of co-localization of the two molecules. Immunohistochemical analysis of 205 epithelial tumors indicated that emmprin is always localized in cell membranes but its distribution differs according to tumor type: in lateral membranes in 89 % of adenomas, in lateral and basal membranes in 76 % of borderline tumors, and in membranes surrounding the entire cell in 98 % of carcinomas. Most carcinomas in situ also showed a lateral and basal expression pattern. In only 21 % of the carcinomas, the cells expressing membranous MCT-1 showed co-localized emmprin expression. Poor co-localization of the two molecules was more frequently found in serous carcinomas. However, the overall survival was not significantly different for the good and poor co-localization carcinoma groups. These findings indicate that the emmprin expression pattern might discriminate between invasive carcinomas and borderline tumors including carcinoma in situ. Moreover, there may be an as yet unidentified regulatory mechanism(s), for localization of MCT-1 and emmprin in cell membranes in vivo.

Sexual Orientation and Borderline Personality Disorder Features in a Community Sample of Adolescents.

Science.gov (United States)

Reuter, Tyson R; Sharp, Carla; Kalpakci, Allison H; Choi, Hye J; Temple, Jeff R

2016-10-01

Empirical literature demonstrates that sexual minorities are at an increased risk of developing psychopathology, including borderline personality disorder (BPD). The specific link between sexual orientation and BPD has received significantly less attention in youth, and it remains unclear what drives this relation. Given that there are higher rates of psychopathology in both sexual minorities and individuals with BPD, the present study aimed to determine if sexual orientation uniquely contributes to borderline personality pathology, controlling for other psychopathology. An ethnically diverse sample of 835 adolescents completed self-report measures of borderline features, depression, anxiety, and sexual orientation. Sexual minorities scored higher on borderline features compared to heterosexual adolescents. When controlling for depression and anxiety, sexual orientation remained significantly associated with borderline features. The relation between sexual orientation and BPD cannot fully be explained by other psychopathology. Future research is necessary to understand potential mechanisms underlying this relation.

Stimulation of cyclic GMP efflux in human melanocytes by hypergravity generated by centrifugal acceleration

NARCIS (Netherlands)

Ivanova, Krassimira; Zadeh, Nahid Hamidi; Block, Ingrid; Das, Pranab K.; Gerzer, Rupert

2004-01-01

Gravity alteration (micro- and hypergravity) is known to influence cell functions. As guanosine 3',5'-cyclic monophosphate (cGMP) plays an important role in human melanocyte functions and different guanylyl cyclase isoforms are responsible for cGMP synthesis in human non-metastatic and metastatic

Mutations in c10orf11, a melanocyte-differentiation gene, cause autosomal-recessive albinism

DEFF Research Database (Denmark)

Grønskov, Karen; Dooley, Christopher M; Østergaard, Elsebet

2013-01-01

in an individual originating from Lithuania. Immunohistochemistry showed localization of C10orf11 in melanoblasts and melanocytes in human fetal tissue, but no localization was seen in retinal pigment epithelial cells. Knockdown of the zebrafish (Danio rerio) homolog with the use of morpholinos resulted...

Borderline Personality Disorder in the perinatal period: early infant and maternal outcomes.

Science.gov (United States)

Blankley, Gaynor; Galbally, Megan; Snellen, Martien; Power, Josephine; Lewis, Andrew J

2015-12-01

This study examines pregnancy and early infant outcomes of pregnant women with a clinical diagnosis of Borderline Personality Disorder presenting for obstetric services to a major metropolitan maternity hospital in Victoria, Australia. A retrospective case review of pregnancy and early infant outcomes on 42 women who had been diagnosed with Borderline Personality Disorder via psychiatric assessment using DSM-IV-R criteria was undertaken. Outcomes were compared with a control group of 14,313 consisting of women and infants of non-affected women from the same hospital over the same period of time. Women presenting for obstetric services with a clinical diagnosis of Borderline Personality Disorder experienced considerable psychosocial impairment. They anticipated birth as traumatic and frequently requested early delivery. High comorbidity with substance abuse was found and high rates of referral to child protective services. Mothers with Borderline Personality Disorder were significantly more likely to have negative birth outcomes such as lowered Apgar scores, prematurity and special care nursery referral when compared with controls. These findings offer preliminary evidence to be considered by clinicians in developing treatments and services for the perinatal care of women with Borderline Personality Disorder and their infants. Further research is required in order to develop evidence informed clinical guidelines for the management of women with Borderline Personality Disorder and their infants. © The Royal Australian and New Zealand College of Psychiatrists 2015.

Association among self-compassion, childhood invalidation, and borderline personality disorder symptomatology in a Singaporean sample.

Science.gov (United States)

Keng, Shian-Ling; Wong, Yun Yi

2017-01-01

Linehan's biosocial theory posits that parental invalidation during childhood plays a role in the development of borderline personality disorder symptoms later in life. However, little research has examined components of the biosocial model in an Asian context, and variables that may influence the relationship between childhood invalidation and borderline symptoms. Self-compassion is increasingly regarded as an adaptive way to regulate one's emotions and to relate to oneself, and may serve to moderate the association between invalidation and borderline symptoms. The present study investigated the association among childhood invalidation, self-compassion, and borderline personality disorder symptoms in a sample of Singaporean undergraduate students. Two hundred and ninety undergraduate students from a large Singaporean university were recruited and completed measures assessing childhood invalidation, self-compassion, and borderline personality disorder symptoms. Analyses using multiple regression indicated that both childhood invalidation and self-compassion significantly predicted borderline personality disorder symptomatology. Results from moderation analyses indicated that relationship between childhood invalidation and borderline personality disorder symptomatology did not vary as a function of self-compassion. This study provides evidence in support of aspects of the biosocial model in an Asian context, and demonstrates a strong association between self-compassion and borderline personality disorder symptoms, independent of one's history of parental invalidation during childhood.

A Non-linear Predictive Model of Borderline Personality Disorder Based on Multilayer Perceptron.

Science.gov (United States)

Maldonato, Nelson M; Sperandeo, Raffaele; Moretto, Enrico; Dell'Orco, Silvia

2018-01-01

Borderline Personality Disorder is a serious mental disease, classified in Cluster B of DSM IV-TR personality disorders. People with this syndrome presents an anamnesis of traumatic experiences and shows dissociative symptoms. Since not all subjects who have been victims of trauma develop a Borderline Personality Disorder, the emergence of this serious disease seems to have the fragility of character as a predisposing condition. Infect, numerous studies show that subjects positive for diagnosis of Borderline Personality Disorder had scores extremely high or extremely low to some temperamental dimensions (harm Avoidance and reward dependence) and character dimensions (cooperativeness and self directedness). In a sample of 602 subjects, who have had consecutive access to an Outpatient Mental Health Service, it was evaluated the presence of Borderline Personality Disorder using the semi-structured interview for the DSM IV-TR personality disorders. In this population we assessed the presence of dissociative symptoms with the Dissociative Experiences Scale and the personality traits with the Temperament and Character Inventory developed by Cloninger. To assess the weight and the predictive value of these psychopathological dimensions in relation to the Borderline Personality Disorder diagnosis, a neural network statistical model called "multilayer perceptron," was implemented. This model was developed with a dichotomous dependent variable, consisting in the presence or absence of the diagnosis of borderline personality disorder and with five covariates. The first one is the taxonomic subscale of dissociative experience scale, the others are temperamental and characterial traits: Novelty-Seeking, Harm-Avoidance, Self-Directedness and Cooperativeness. The statistical model, that results satisfactory, showed a significance capacity (89%) to predict the presence of borderline personality disorder. Furthermore, the dissociative symptoms seem to have a greater influence than

A Non-linear Predictive Model of Borderline Personality Disorder Based on Multilayer Perceptron

Directory of Open Access Journals (Sweden)

Nelson M. Maldonato

2018-04-01

Full Text Available Borderline Personality Disorder is a serious mental disease, classified in Cluster B of DSM IV-TR personality disorders. People with this syndrome presents an anamnesis of traumatic experiences and shows dissociative symptoms. Since not all subjects who have been victims of trauma develop a Borderline Personality Disorder, the emergence of this serious disease seems to have the fragility of character as a predisposing condition. Infect, numerous studies show that subjects positive for diagnosis of Borderline Personality Disorder had scores extremely high or extremely low to some temperamental dimensions (harm Avoidance and reward dependence and character dimensions (cooperativeness and self directedness. In a sample of 602 subjects, who have had consecutive access to an Outpatient Mental Health Service, it was evaluated the presence of Borderline Personality Disorder using the semi-structured interview for the DSM IV-TR personality disorders. In this population we assessed the presence of dissociative symptoms with the Dissociative Experiences Scale and the personality traits with the Temperament and Character Inventory developed by Cloninger. To assess the weight and the predictive value of these psychopathological dimensions in relation to the Borderline Personality Disorder diagnosis, a neural network statistical model called “multilayer perceptron,” was implemented. This model was developed with a dichotomous dependent variable, consisting in the presence or absence of the diagnosis of borderline personality disorder and with five covariates. The first one is the taxonomic subscale of dissociative experience scale, the others are temperamental and characterial traits: Novelty-Seeking, Harm-Avoidance, Self-Directedness and Cooperativeness. The statistical model, that results satisfactory, showed a significance capacity (89% to predict the presence of borderline personality disorder. Furthermore, the dissociative symptoms seem to have a

Evaluation of changes in prescription medication use after a residential treatment programme for borderline personality disorder.

Science.gov (United States)

Broadbear, Jillian H; Nesci, Julian; Thomas, Rosemary; Thompson, Katherine; Beatson, Josephine; Rao, Sathya

2016-12-01

Residential patients diagnosed with borderline personality disorder were evaluated to determine whether borderline personality disorder-focused psychotherapy reduced prescribing, personality disorder and co-morbid symptom severity. Psychotropic prescriptions were measured at admission, discharge and 1 year later in 74 female participants with one or more personality disorder diagnosis and co-morbid mood disorders. Changes in pharmacotherapy were examined in the context of improvements in borderline personality disorder and/or co-morbid disorder symptom severity. Residential treatment included individual and group psychotherapy for borderline personality disorder. The Structured Clinical Interview for DSM-IV was used to confirm the borderline personality disorder diagnosis and associated co-morbid conditions. The Beck Depression Inventory was completed at each time point. A significant reduction in the incidence and severity of self-rated depression as well as clinician assessed personality disorder, including borderline personality disorder, was accompanied by a reduction in prescription of psychoactive medications. Three to six months of intensive borderline personality disorder-specific psychotherapy showed lasting benefit with regard to symptom severity of personality disorders (borderline personality disorder in particular) as well as depressive symptoms. This improvement corresponded with a reduction in prescriptions for psychoactive medications, which is consistent with current thinking regarding treatment for borderline personality disorder. © The Royal Australian and New Zealand College of Psychiatrists 2016.

[Anorexia and borderline personality disorder : bonds pathology].

Science.gov (United States)

Cayn, Delphine; Pham-Scottez, Alexandra

Comorbidity with a borderline personality disorder is far from rare in patients suffering from eating disorders. Clinically, this presents as chronic instability in many areas: interpersonal relationships, self-image, emotions, mood and acting out. Treatment is mainly based on a containing and reassuring therapeutic framework. A care plan may be put in place that incorporates reducing impulsive harmful, eating and self-harming behaviours. Dialectical behaviour therapy is intended in particular to prevent suicide risk in borderline personality disorder patients. Copyright © 2016 Elsevier Masson SAS. All rights reserved.

Ultraviolet Radiation-Induced Cytogenetic Damage in White, Hispanic and Black Skin Melanocytes: A Risk for Cutaneous Melanoma

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Dasgupta, Amrita [Hampton University Skin of Color Research Institute, Hampton, VA 23668 (United States); Katdare, Meena, E-mail: mkatdare@gmail.com [Hampton University Skin of Color Research Institute, Hampton, VA 23668 (United States); Department of Dermatology, Eastern Virginia Medical School, Norfolk, VA 23507 (United States)

2015-08-14

Cutaneous Melanoma (CM) is a leading cause of cancer deaths, with reports indicating a rising trend in the incidence rate of melanoma among Hispanics in certain U.S. states. The level of melanin pigmentation in the skin is suggested to render photoprotection from the DNA-damaging effects of Ultraviolet Radiation (UVR). UVR-induced DNA damage leads to cytogenetic defects visualized as the formation of micronuclei, multinuclei and polymorphic nuclei in cells, and a hallmark of cancer risk. The causative relationship between Sun exposure and CM is controversial, especially in Hispanics and needs further evaluation. This study was initiated with melanocytes from White, Hispanic and Black neonatal foreskins which were exposed to UVR to assess their susceptibility to UVR-induced modulation of cellular growth, cytogenetic damage, intracellular and released melanin. Our results show that White and Hispanic skin melanocytes with similar levels of constitutive melanin are susceptible to UVR-induced cytogenetic damage, whereas Black skin melanocytes are not. Our data suggest that the risk of developing UVR-induced CM in a skin type is correlated with the level of cutaneous pigmentation and its ethnic background. This study provides a benchmark for further investigation on the damaging effects of UVR as risk for CM in Hispanics.

Ultraviolet Radiation-Induced Cytogenetic Damage in White, Hispanic and Black Skin Melanocytes: A Risk for Cutaneous Melanoma

International Nuclear Information System (INIS)

Dasgupta, Amrita; Katdare, Meena

2015-01-01

Cutaneous Melanoma (CM) is a leading cause of cancer deaths, with reports indicating a rising trend in the incidence rate of melanoma among Hispanics in certain U.S. states. The level of melanin pigmentation in the skin is suggested to render photoprotection from the DNA-damaging effects of Ultraviolet Radiation (UVR). UVR-induced DNA damage leads to cytogenetic defects visualized as the formation of micronuclei, multinuclei and polymorphic nuclei in cells, and a hallmark of cancer risk. The causative relationship between Sun exposure and CM is controversial, especially in Hispanics and needs further evaluation. This study was initiated with melanocytes from White, Hispanic and Black neonatal foreskins which were exposed to UVR to assess their susceptibility to UVR-induced modulation of cellular growth, cytogenetic damage, intracellular and released melanin. Our results show that White and Hispanic skin melanocytes with similar levels of constitutive melanin are susceptible to UVR-induced cytogenetic damage, whereas Black skin melanocytes are not. Our data suggest that the risk of developing UVR-induced CM in a skin type is correlated with the level of cutaneous pigmentation and its ethnic background. This study provides a benchmark for further investigation on the damaging effects of UVR as risk for CM in Hispanics

Mammalian melanocytes and radiations

International Nuclear Information System (INIS)

Hirobe, Tomohisa

2008-01-01

Melanocytes (M) decide the skin and hair color through the synthesis of melanine pigment, which is transported via their melanosome to keratinocytes (K) for body color expression in animals. This paper describes mainly author's studies of M concerning effects of ultraviolet (UV), ionizing radiation and heavy ion (carbon ion) beam on their development and differentiation together with its mechanism. In vitro, studies of UV effect on proliferation and differentiation of M and melanoblast (MB) have been greatly advanced since their culturing in serum-free media became possible using cells from author's black-mouse (C57BL/10JHir strain): Their mixed culture with K firstly revealed that their proliferation and differentiation were enhanced by UV irradiation. The important K's factor to regulate M/MB cells was identified to be GMCSF (granulocyte-macrophage colony-stimulating factor). In vivo studies of the skin color of the black-mouse before and after birth were performed using radiations like 60 Co gamma ray and high linear energy transfer (LET) carbon ion beam and have revealed that abnormal proliferation and differentiation of M/MB, which were expressed as white spot formation, death and mal-differentiation of M/MB, were induced dose-, LET- and developmental stage-dependently. (R.T.)

[Psychological Treatments for Borderline Personality Disorder: A Review of Cognitive-Behavioral Oriented Therapies].

Science.gov (United States)

Marques, Sofia; Barrocas, Daniel; Rijo, Daniel

2017-04-28

Borderline personality disorder is the most common personality disorder, with a global prevalence rate between 1.6% and 6%. It is characterized by affective disturbance and impulsivity, which lead to a high number of self-harm behaviors and great amount of health services use. International guidelines recommend psychotherapy as the primary treatment for borderline personality disorder. This paper reviews evidence about the effects and efficacy of cognitive-behavioral oriented psychological treatments for borderline personality disorder. A literature review was conducted in Medline and PubMed databases, using the following keywords: borderline personality disorder, cognitive-behavioral psychotherapy and efficacy. Sixteen randomized clinical trials were evaluate in this review, which analyzed the effects of several cognitive-behavioral oriented psychotherapeutic interventions, namely dialectical behavioral therapy, cognitive behavioral therapy, schema-focused therapy and manual-assisted cognitive therapy. All above stated treatments showed clinical beneficial effects, by reducing borderline personality disorder core pathology and associated general psychopathology, as well as by reducing the severity and frequency of self-harm behaviors, and by improving the overall social, interpersonal and global adjustment. Dialectical behavioral therapy and schema-focused therapy also caused a soaring remission rate of diagnostic borderline personality disorder criteria of 57% and 94%, respectively. Although there were differences between the psychotherapeutic interventions analysed in this review, all showed clinical benefits in the treatment of borderline personality disorder. Dialectical behavioral therapy and schema-focused therapy presented the strongest scientific data documenting their efficacy, but both interventions are integrative cognitive-behavioral therapies which deviate from the traditional cognitive-behavioral model. In summary, the available studies support

Incision and stress regulation in borderline personality disorder: neurobiological mechanisms of self-injurious behaviour.

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Reitz, Sarah; Kluetsch, Rosemarie; Niedtfeld, Inga; Knorz, Teresa; Lis, Stefanie; Paret, Christian; Kirsch, Peter; Meyer-Lindenberg, Andreas; Treede, Rolf-Detlef; Baumgärtner, Ulf; Bohus, Martin; Schmahl, Christian

2015-08-01

Patients with borderline personality disorder frequently show non-suicidal self-injury (NSSI). In these patients, NSSI often serves to reduce high levels of stress. Investigation of neurobiological mechanisms of NSSI in borderline personality disorder. In total, 21 women with borderline personality disorder and 17 healthy controls underwent a stress induction, followed by either an incision into the forearm or a sham treatment. Afterwards participants underwent resting-state functional magnetic resonance imaging while aversive tension, heart rate and heart rate variability were assessed. We found a significant influence of incision on subjective and objective stress levels with a stronger decrease of aversive tension in the borderline personality disorder group following incision than sham. Amygdala activity decreased more and functional connectivity with superior frontal gyrus normalised after incision in the borderline personality disorder group. Decreased stress levels and amygdala activity after incision support the assumption of an influence of NSSI on emotion regulation in individuals with borderline personality disorder and aids in understanding why these patients use self-inflicted pain to reduce inner tension. © The Royal College of Psychiatrists 2015.

Rhododenol and raspberry ketone impair the normal proliferation of melanocytes through reactive oxygen species-dependent activation of GADD45.

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Kim, Minjeong; Baek, Heung Soo; Lee, Miri; Park, Hyeonji; Shin, Song Seok; Choi, Dal Woong; Lim, Kyung-Min

2016-04-01

Rhododenol or rhododendrol (RD, 4-(4-hydroxyphenyl)-2-butanol) occurs naturally in many plants along with raspberry ketone (RK, 4-(4-hydroxyphenyl)-2-butanone), a ketone derivative, which include Nikko maple tree (Acer nikoense) and white birch (Betula platyphylla). De-pigmenting activity of RD was discovered and it was used as a brightening ingredient for the skin whitening cosmetics. Recently, cosmetics containing RD were withdrawn from the market because a number of consumers developed leukoderma, inflammation and erythema on their face, neck and hands. Here, we explored the mechanism underlying the toxicity of RD and RK against melanocytes using B16F10 murine melanoma cells and human primary epidermal melanocytes. Treatment with RD or RK resulted in the decreased cell viability in a dose-dependent manner which appeared from cell growth arrest. Consistently, ROS generation was significantly increased by RD or RK as determined by DCF-enhanced fluorescence. An antioxidant enzyme, glutathione peroxidase was depleted as well. In line with ROS generation, oxidative damages and the arrest of normal cell proliferation, GADD genes (Growth Arrest and DNA Damage) that include GADD45 and GADD153, were significantly up-regulated. Prevention of ROS generation with an anti-oxidant, N-acetylcysteine (NAC) significantly rescued RD and RK-suppressed melanocyte proliferation. Consistently, up-regulation of GADD45 and GADD153 was significantly attenuated by NAC, suggesting that increased ROS and the resultant growth arrest of melanocytes may contribute to RD and RK-induced leukoderma. Copyright © 2016 Elsevier Ltd. All rights reserved.

PHYLLODES TUMOR OF THE BREAST : A CLINICOPATHOLOGICAL ANALYSIS FROM A SINGLE INSTITUTION

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Naoual Benhmidou

2017-07-01

Full Text Available The aim of our study is to examine the clinical and pathological features of patients with breast phyllodes tumors and to determine features that are correlated to outcome. Forty four phyllodes tumors were assessed. There were 11 benign, 11 borderline and 22 malignant tumors. 10 of 44 patients (22.72 % relapsed at any site. Seven patients (15.9 % had a local recurrence and 3 patients experienced local and metastatic relapse. The 5-year and 10-year survival rates are 97% and 95 % respectively. The 5 years and 10 years DFS are 81% and 77% respectively. Grade, histological size, margin involvement impacted disease free survival. Adjuvant radiation therapy improved local control in high grade tumors although it didn’t reach significance.

Clinical and histological responses of congenital melanocytic nevi after single treatment with Q-switched lasers

NARCIS (Netherlands)

Grevelink, JM; vanLeeuwen, RL; Anderson, RR; Byers, HR

Background: Laser irradiation of congenital melanocytic nevi is a controversial treatment. Recurrence of lesions after laser treatment appears to be the rule, and the effects of laser irradiation on cellular biological behavior and the possible mutagenic responses of nevomelanocytes that have

Rectal malignant melanoma mistaken for thrombotic hemorrhoids - rare tumor with poor prognosis

International Nuclear Information System (INIS)

Kovacova, E.; Hvizdakova, A.; Vyskocil, M.; Kinova, S.; Sesovsky, V.; Kobzova, D.; Palkovic, M.

2011-01-01

Rectal malignant melanoma originates in the melanocytes of the anorectal area. Represent less than 1 % of all melanomas, and 4 % of all malignant tumors of the rectum and anus. The most common clinical manifestation is bleeding, the clinical examination may be mistaken for benign lesions or hemorrhoids. Given the rarity of the diagnosis are not well-defined therapeutic procedures. Prognosis for patient is poor. The authors present a case of 70-year old patient with rectal melanoma diagnosed at an advanced stage of disease, initially with diagnosis a thrombotic hemorrhoid. (author)

Autobiographical memory in borderline personality disorder-A systematic review.

Science.gov (United States)

Bech, Morten; Elklit, Ask; Simonsen, Erik

2015-05-01

Borderline personality disorder is a severe psychiatric illness. A key feature of the disorder is a disorganized sense of self often referred to as identity diffusion. Autobiographical memory is memory for personal life events. One of the main functions of these memories is to enable us to understand who we are by connecting past, present and future experiences. It seems that autobiographical memory is in some way disrupted in individuals with borderline personality disorder. A systematic review is conducted looking at studies that focus on the potential connections. We find that although a number of studies have been published results remain inconsistent. Furthermore, we find that many of the studies suffer from inadequate designs particularly regarding the reported measures of autobiographical memory. We discuss potential links between personality functioning, identity diffusion, autobiographical memory and borderline personality disorder. Copyright © 2015 John Wiley & Sons, Ltd.

Early Intervention for Borderline Personality Disorder: Psychodynamic Therapy in Adolescents.

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Salzer, Simone; Cropp, Carola; Streeck-Fischer, Annette

2014-01-01

Borderline personality disorder (BPD) should be understood as a disorder of development (Streeck-Fischer 2008, 2013) that has its first manifestation in late childhood and adolescence. There are only few treatment studies of adolescents meeting the diagnostic criteria of borderline personality disorder, although early interventions for these patients are urgently needed (see Chanen & McCutcheon 2013). We examined the effectiveness of an inpatient psychodynamic therapy (PDT). Twenty-eight adolescents fulfilling the DSM-IV diagnostic criteria of borderline personality disorder were treated with psychodynamic therapy. The mean duration of treatment was 29.87 weeks (SD = 15.88). Outcomes were remission rates, GAF, GSI, SDQ, IIP and BPI scores. Assessments were made at admission and after treatment. Pre-post comparisons and comparisons with normative data were conducted. At the end of treatment 39.29% of the patients were remitted. We found significant improvements for the GAF, GSI, SDQ, IIP (all p0.001) and the BPI (p = 0.006). These clinically relevant improvements demonstrate the effectiveness of psychodynamic therapy in adolescents with borderline personality disorder and stress the usefulness of an early intervention for these patients.

BORDERLINE PERSONALITY DISORDER IN THE MEDICAL SETTING: Suggestive Behaviors, Syndromes, and Diagnoses.

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Sansone, Randy A; Sansone, Lori A

2015-01-01

Borderline personality disorder is a personality dysfunction that is characterized by disinhibition and impulsivity, which oftentimes manifest as self-regulation difficulties. Patients with this disorder have always been present in medical settings, but have been described as "difficult patients" rather than patients with borderline personality disorder. According to empirical findings, a number of behaviors and medical syndromes/diagnoses are suggestive of borderline personality disorder. Suggestive behaviors in the medical setting may include aggressive or disruptive behaviors, the intentional sabotage of medical care, and excessive healthcare utilization. Suggestive medical syndromes and diagnoses in the medical setting may include alcohol and substance misuse (including the abuse of prescription medications), multiple somatic complaints, chronic pain, obesity, sexual impulsivity, and hair pulling. While not all-inclusive or diagnostic, these behaviors and syndromes/diagnoses may invite further clinical evaluation of the patient for borderline personality disorder.

Examining the Relationship between Childhood Sexual Abuse and Borderline Personality Disorder: Does Social Support Matter?

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Elzy, Meredith B.

2011-01-01

The relationship between childhood sexual abuse and borderline personality disorder is a prominent issue in the etiological research on borderline personality disorder. This study further explored the relationship between childhood sexual abuse and the development of borderline personality features while evaluating the moderating role of a primary…

Familial resemblance of borderline personality disorder features: genetic or cultural transmission?

Directory of Open Access Journals (Sweden)

Marijn A Distel

Full Text Available Borderline personality disorder is a severe personality disorder for which genetic research has been limited to family studies and classical twin studies. These studies indicate that genetic effects explain 35 to 45% of the variance in borderline personality disorder and borderline personality features. However, effects of non-additive (dominance genetic factors, non-random mating and cultural transmission have generally not been explored. In the present study an extended twin-family design was applied to self-report data of twins (N = 5,017 and their siblings (N = 1,266, parents (N = 3,064 and spouses (N = 939 from 4,015 families, to estimate the effects of additive and non-additive genetic and environmental factors, cultural transmission and non-random mating on individual differences in borderline personality features. Results showed that resemblance among biological relatives could completely be attributed to genetic effects. Variation in borderline personality features was explained by additive genetic (21%; 95% CI 17-26% and dominant genetic (24%; 95% CI 17-31% factors. Environmental influences (55%; 95% CI 51-60% explained the remaining variance. Significant resemblance between spouses was observed, which was best explained by phenotypic assortative mating, but it had only a small effect on the genetic variance (1% of the total variance. There was no effect of cultural transmission from parents to offspring.

Borderline personality disorder and the emerging field of developmental neuroscience.

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Crowell, Sheila E; Kaufman, Erin A

2016-10-01

Over the past 2 decades there has been a dramatic shift in understanding of personality disorders, such as borderline personality disorder (BPD). What was historically viewed as an entrenched pattern of antagonistic, interpersonally dependent, and uncorrectable conduct is now seen as the outcome of complex-yet modifiable-developmental processes. The borderline label, which once inspired such harsh opprobrium in clinical communities that early diagnosis was considered taboo, is now increasingly applied to adolescents who are receiving effective treatment and desisting from a borderline trajectory. Research examining the developmental origins and early manifestations of BPD is increasing rapidly, making it an appropriate time to take stock of current developmental research and articulate an agenda for the future. We identify 4 challenges that continue to impede innovative research on borderline personality development: (a) inadequate attention to continuity and discontinuity across development, (b) medical and diagnostic systems that localize personality pathology within the individual, (c) the lingering belief that biological research is antithetical to contextual/interpersonal understandings of psychopathology (and vice versa), and (d) reluctance to reach across disciplinary and developmental boundaries to identify creative paradigms and foster innovative discovery. In order to overcome these challenges, we propose an approach to future research on adolescent borderline pathology that integrates developmental psychopathology, social and affective neuroscience, and personality theory perspectives. This intersection-the developmental neuroscience of personality pathology-offers theoretical and methodological advantages over disciplinary isolation and is fertile ground for generating novel hypotheses on the development and prevention of BPD. (PsycINFO Database Record (c) 2016 APA, all rights reserved).

Orbital melanocytoma: When a tumor becomes a relieving surprise

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Haytham E. Nasr

2018-06-01

Full Text Available Purpose: Melanocytomas are rare pigmented tumors that arise form melanocytes and have been reported in the central nervous system. Orbital melanocytomas “also known as blue nevus” are rarely reported. The occurrence of choroidal melanoma and orbital melanocytomas has never been described. Observations: This is a case of orbital melanocytoma in a 34 year old female who presented with left proptosis and ecchymosis. She has the right eye enucleated to treat a large choroidal melanoma, 6 years earlier. Orbital metastasis was suspected. After orbital imaging and systemic evaluation, incisional biopsy was planned yet the mass could be totally excised and it turned out to be melanocytoma. The condition was not associated with nevus of Ota and the patient is not known to have any predisposing condition for melanocytic lesions. Conclusion and importance: Melanocytoma and malignant melanoma share the same cell of origin. The benign course, the well differentiated cells, absence of anaplasia and the positive reaction to Human Melanoma Black-45 (HMB-45 and S-100 proteins established the diagnosis of the former. Such diagnosis was a relief for this one eyed patient.(HMB-45:human melanoma black-45. Keywords: Orbit, Melanocytoma, Choroidal melanoma, HMB-45, S-100

Risk for borderline ovarian tumours after exposure to fertility drugs

DEFF Research Database (Denmark)

Bjørnholt, Sarah Marie; Kjaer, Susanne Krüger; Nielsen, Thor Schütt Svane

2015-01-01

numbers. To obtain information on use of fertility drugs, hospital files and medical records of infertility-associated visits to all Danish fertility clinics were collected and supplemented with information from the Danish IVF register. We used case-cohort techniques to calculate rate ratios (RRs......STUDY QUESTION: Do fertility drugs increase the risk for borderline ovarian tumours, overall and according to histological subtype? SUMMARY ANSWER: The use of any fertility drug did not increase the overall risk for borderline ovarian tumours, but an increased risk for serous borderline ovarian...... tumours was observed after the use of progesterone. WHAT IS KNOWN ALREADY: Many epidemiological studies have addressed the connection between fertility drugs use and risk for ovarian cancer; most have found no strong association. Fewer studies have assessed the association between use of fertility drugs...

Premalignant quiescent melanocytic nevi do not express the MHC class I chain-related protein A Los nevos melanocíticos premalignos quiescentes no expresan la molécula MHC class I chain-related protein A

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Mercedes B. Fuertes

2011-08-01

Full Text Available The MHC class I chain-related protein A (MICA is an inducible molecule almost not expressed by normal cells but strongly up-regulated in tumor cells. MICA-expressing cells are recognized by natural killer (NK cells, CD8+ aßTCR and ?dTCR T lymphocytes through the NKG2D receptor. Engagement of NKG2D by MICA triggers IFN-? secretion and cytotoxicity against malignant cells. Although most solid tumors express MICA and this molecule is a target during immune surveillance against tumors, it has been observed that high grade tumors from different histotypes express low amounts of cell surface MICA due to a metalloprotease- induced shedding. Also, melanomas develop after a complex process of neotransformation of normal melanocytes. However, the expression of MICA in premalignant stages (primary human quiescent melanocytic nevi remains unknown. Here, we assessed expression of MICA by flow cytometry using cell suspensions from 15 primary nevi isolated from 11 patients. When collected material was abundant, cell lysates were prepared and MICA expression was also analyzed by Western blot. We observed that MICA was undetectable in the 15 primary nevi (intradermic, junction, mixed, lentigo and congenital samples as well as in normal skin, benign lesions (seborrheic keratosis, premalignant lesions (actinic keratosis and benign basocellular cancer. Conversely, a primary recently diagnosed melanoma showed intense cell surface MICA. We conclude that the onset of MICA expression is a tightly regulated process that occurs after melanocytes trespass the stage of malignant transformation. Thus, analysis of MICA expression in tissue sections of skin samples may constitute a useful marker to differentiate between benign and malignant nevi.MHC class I chain-related protein A (MICA es una molécula casi ausente en células normales pero sobre-expresada por células tumorales, que promueve el reconocimiento por células citotóxicas naturales (natural killer o NK y por

Etiological features of borderline personality related characteristics in a birth cohort of 12 year old children

NARCIS (Netherlands)

Belsky, D.; Caspi, A.; Arseneault, L.; Bleidorn, W.; Fonagy, P.; Goodman, M.; Houts, R.; Moffitt, T.

2012-01-01

It has been reported that borderline personality related characteristics can be observed in children, and that these characteristics are associated with increased risk for the development of borderline personality disorder. It is not clear whether borderline personality related characteristics in

Monoclonal origin of peritoneal implants and lymph node deposits in serous borderline ovarian tumors (s-BOT) with high intratumoral homogeneity.

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Horn, Lars-Christian; Höhn, Anne K; Einenkel, Jens; Siebolts, Udo

2014-11-01

Molecular studies have shown that the most prevalent mutations in serous ovarian borderline tumors (s-BOT) are BRAF and/or KRAS alterations. About one third of s-BOT represent peritoneal implants and/or lymph node involvement. These extraovarian deposits may be monoclonal or polyclonal in origin. To test both the hypotheses, mutational analyses using pyrosequencing for BRAF codon 600 and KRAS codon 12/13 and 61 of microdissected tissue was performed in 15 s-BOT and their invasive and noninvasive peritoneal implants. Two to 6 implants from different peritoneal sites were examined in 13 cases. Lymph node deposits were available for the analysis in 3 cases. Six s-BOT showed mutation in exon 2 codon 12 of the KRAS proto-oncogen. Five additional cases showed BRAF p.V600E mutation representing an overall mutation rate of 73.3%. Multiple (2-6) peritoneal implants were analyzed after microdissection in 13 of 15 cases. All showed identical mutational results when compared with the ovarian site of the disease. All lymph node deposits, including those with multiple deposits in different nodes, showed identical results, suggesting high intratumoral mutational homogeneity. The evidence presented in this study and the majority of data reported in the literature support the hypothesis that s-BOT with their peritoneal implants and lymph node deposits show identical mutational status of BRAF and KRAS suggesting a monoclonal rather than a polyclonal disease regarding these both tested genetic loci. In addition, a high intratumoral genetic homogeneity can be suggested. In conclusion, the results of the present study support the monoclonal origin of s-BOT and their peritoneal implants and lymph node deposits.

Silencing of GPNMB by siRNA Inhibits the Formation of Melanosomes in Melanocytes in a MITF-Independent Fashion

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Zhu, Cansheng; Yuan, Xiaoying; Li, Dongguang; Gu, Weijie; Ma, Huimin; Xie, Xin; Gao, Tianwen

2012-01-01

Background Melanosomes are specialized membrane-surrounded organelles, which are involved in the synthesis, storage and transport of melanin. Glycoprotein (transmembrane) non-metastatic melanoma protein b (GPNMB), a melanosome-specific structural protein, shares significant amino acid sequence homology with Pmel-17. Proteomic analysis demonstrated that GPNMB is present in all stages (I-IV) of melanosomes. However, little is known about the role of GPNMB in melanosomes. Methodology/Principal Findings Using real-time quantitative PCR, Western blotting and immunofluorescence analysis, we demonstrated that the expression of GPNMB in PIG1 melanocytes was up-regulated by ultraviolet B (UVB) radiation. Transmission electron microscopy analysis showed that the total number of melanosomes in PIG1 melanocytes was sharply reduced by GPNMB-siRNA transfection. Simultaneously, the expression levels of tyrosinase (Tyr), tyrosinase related protein 1 (Trp1), Pmel17/gp100 and ocular albinism type 1 protein (OA1) were all significantly attenuated. But the expression of microphthalmia-associated transcription factor (MITF) was up-regulated. Intriguingly, in GPNMB silenced PIG1 melanocytes, UVB radiation sharply reduced MITF expression. Conclusion Our present work revealed that the GPNMB was critical for the formation of melanosomes. And GPNMB expression down-regulation attenuated melanosome formation in a MITF-independent fashion. PMID:22912767

The psychodynamics of borderline psychopathology.

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Corradi, Richard B

2015-01-01

The concept of borderline personality disorder (BPD) remains problematic despite psychiatrists' general familiarity with its DSM diagnostic criteria. The diagnosis of BPD is frequently based simply on the DSM checklist of traits and symptoms without knowledge of their origins or significance. Misdiagnosis is common, as is lack of recognition of the full complexity of this severe personality disorder and the nature of the vulnerabilities that underlie its myriad forms of pathology. The stresses of ordinary life are often too much for people with BPD. Knowledge of the nature and origins of their stress points, such as their great fear of loss or rejection, is necessary for adequate diagnosis and treatment. The author addresses how signature features of the disorder relate to psychosocial development, how they correlate with failed developmental milestones, and how they can be understood psychodynamically. This is essential knowledge for psychotherapists because the pathological interpersonal relationships of the borderline patient will be repeated and acted out in the transference, whatever the modality or intensity of treatment.

Early inflammatory response in epithelial ovarian tumor cyst fluids

International Nuclear Information System (INIS)

Kristjánsdóttir, Björg; Partheen, Karolina; Fung, Eric T; Yip, Christine; Levan, Kristina; Sundfeldt, Karin

2014-01-01

Mortality rates for epithelial ovarian cancer (EOC) are high, mainly due to late-stage diagnosis. The identification of biomarkers for this cancer could contribute to earlier diagnosis and increased survival rates. Given that chronic inflammation plays a central role in cancer initiation and progression, we selected and tested 15 cancer-related cytokines and growth factors in 38 ovarian cyst fluid samples. We used ovarian cyst fluid since it is found in proximity to the pathology and mined it for inflammatory biomarkers suitable for early detection of EOC. Immunoprecipitation and high-throughput sample fractionation were obtained by using tandem antibody libraries bead and mass spectrometry. Two proteins, monocyte chemoattractant protein-1 (MCP-1/CCL2) and interleucin-8 (IL-8/CXCL8), were significantly (P < 0.0001) higher in the malignant (n = 16) versus benign (n = 22) tumor cysts. Validation of MCP-1, IL-8, and growth-regulated protein-α (GROα/CXCL1) was performed with ELISA in benign, borderline, and malignant cyst fluids (n = 256) and corresponding serum (n = 256). CA125 was measured in serum from all patients and used in the algorithms performed. MCP-1, IL-8, and GROα are proinflammatory cytokines and promoters of tumor growth. From 5- to 100-fold higher concentrations of MCP-1, IL-8 and GROα were detected in the cyst fluids compared to the serum. Significant (P < 0.001) cytokine response was already established in borderline cyst fluids and stage I EOC. In serum a significant (P < 0.01) increase of IL-8 and GROα was found, but not until stage I and stage III EOC, respectively. These findings confirm that early events in tumorigenesis can be analyzed and detected in the tumor environment and we conclude that ovarian cyst fluid is a promising source in the search for new biomarkers for early ovarian tumors

Mentalization-based treatment for patients with borderline personality disorder: an overview Terapia de mentalização para pacientes com transtorno de personalidade borderline: uma atualização

Directory of Open Access Journals (Sweden)

Mariana Eizirik

2009-03-01

Full Text Available OBJECTIVE: To describe the concept of mentalization, and its application in understanding the development of psychopathology in patients with borderline personality disorder; to give an account of the main features of mentalization-based treatment; to summarise the evidence supporting its effectiveness. DISCUSSION: Mentalization is a predominantly preconscious mental activity that enables the individual to understand him/herself and others in terms of subjective states and mental processes. Psychological trauma in childhood is associated with deficits in mentalization and with the development of borderline personality disorder. Mentalization-based treatment is a psychodynamically-oriented manualized psychotherapy for borderline personality disorder that aims to develop a therapeutic process in which the patient's capacity for mentalization becomes the focus of treatment. Randomized controlled trials have demonstrated the effectiveness of this treatment for patients with borderline personality disorder. CONCLUSIONS: The development of a psychodynamically-oriented therapeutic intervention that specifically targets the deficits involved in the psychopathology of borderline personality disorder is a crucial step in increasing the effectiveness of treatment. Mental health professionals should be adequately prepared to deliver effective interventions to their patients, such as mentalization-based treatment.OBJETIVO: Descrever o conceito de mentalização e sua aplicação no entendimento do desenvolvimento da psicopatologia em pacientes com transtorno de personalidade borderline; descrever as principais características da terapia de mentalização; sumarizar as evidências que demonstram sua efetividade. DISCUSSÃO: Mentalização é uma atividade mental predominantemente pré-consciente que capacita o indivíduo a compreender a si mesmo e aos outros em termos de estados subjetivos e processos mentais. Trauma psicológico na infância está associado

First evidence of a prospective relation between avoidance of internal states and borderline personality disorder features in adolescents.

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Sharp, Carla; Kalpakci, Allison; Mellick, William; Venta, Amanda; Temple, Jeff R

2015-03-01

At least two leading developmental models of borderline personality disorder (BPD) emphasize the role of accurate reflection and understanding of internal states as significant to the development of BPD features (Fonagy, Int J Psycho-Anal 72:639-656, 1991; Linehan, Cognitive-behavioral treatment of borderline personality disorder, 1993). The current study used the construct of experiential avoidance (EA) to operationalize avoidance of internal states and sought to examine (1) the concurrent relations between EA and borderline features in a large and diverse community sample; and (2) the prospective relation between EA and borderline features over a 1-year follow-up, controlling for baseline levels of borderline features. N = 881 adolescents recruited from public schools in a large metropolitan area participated in baseline assessments and N = 730 completed follow-up assessments. Two main findings were reported. First, EA was associated with borderline features, depressive, and anxiety symptoms at the bivariate level, but when all variables were considered together, depression and anxiety no longer remained significantly associated with borderline features, suggesting that the relations among these symptom clusters may be accounted for by EA as a cross-cutting underlying psychological process. Second, EA predicted levels of borderline symptoms at 1-year follow-up, controlling for baseline levels of borderline symptoms, and symptoms of anxiety and depression. Results are interpreted against the background of developmental theories of borderline personality disorder.

Borderline personality disorder in the primary care setting.

Science.gov (United States)

Dubovsky, Amelia N; Kiefer, Meghan M

2014-09-01

Borderline personality disorder is estimated to be present in approximately 6% of outpatient primary care settings. However, the time and energy spent on this population can greatly exceed what primary care doctors are able to spend. This article gives an overview of borderline personality disorder, including the clinical characteristics, epidemiology, and comorbidities, as well as pharmacologic and most important behavioral management. It is our hope that, with improved understanding of the disorder and skills for managing this population, caring for patients with the disorder can be more satisfying and less taxing for both primary care doctors and their patients. Copyright © 2014 Elsevier Inc. All rights reserved.

Refractometry of melanocyte cell nuclei using optical scatter images recorded by digital Fourier microscopy.

Science.gov (United States)

Seet, Katrina Y T; Nieminen, Timo A; Zvyagin, Andrei V

2009-01-01

The cell nucleus is the dominant optical scatterer in the cell. Neoplastic cells are characterized by cell nucleus polymorphism and polychromism-i.e., the nuclei exhibits an increase in the distribution of both size and refractive index. The relative size parameter, and its distribution, is proportional to the product of the nucleus size and its relative refractive index and is a useful discriminant between normal and abnormal (cancerous) cells. We demonstrate a recently introduced holographic technique, digital Fourier microscopy (DFM), to provide a sensitive measure of this relative size parameter. Fourier holograms were recorded and optical scatter of individual scatterers were extracted and modeled with Mie theory to determine the relative size parameter. The relative size parameter of individual melanocyte cell nuclei were found to be 16.5+/-0.2, which gives a cell nucleus refractive index of 1.38+/-0.01 and is in good agreement with previously reported data. The relative size parameters of individual malignant melanocyte cell nuclei are expected to be greater than 16.5.

The mediating role of mentalizing capacity between parents and peer attachment and adolescent borderline personality disorder

DEFF Research Database (Denmark)

Beck, Emma; Sharp, Carla; Poulsen, Stig

2017-01-01

Background: Insecure attachment is a precursor and correlate of borderline personality disorder. According to the mentalization-based theory of borderline personality disorder, the presence of insecure attachment derails the development of the capacity to mentalize, potentially resulting in borde......Background: Insecure attachment is a precursor and correlate of borderline personality disorder. According to the mentalization-based theory of borderline personality disorder, the presence of insecure attachment derails the development of the capacity to mentalize, potentially resulting...... personality features. Our findings suggest that in a simple mediational model, mentalizing capacity mediated the relation between attachment to peers and borderline features. In the case of attachment to parents, the mediational model was not significant. Conclusions: The current study is the first...... to evaluate this mediational model with parent and peer attachment as separate concepts and the first to do so in a sample of adolescents who meet full or sub-threshold criteria for borderline personality disorder. Findings incrementally support that mentalizing capacity and attachment insecurity, also...

Borderline personality disorder and emotional intelligence

NARCIS (Netherlands)

Peter, M.; Schuurmans, H.; Vingerhoets, A.J.J.M.; Smeets, G.; Verkoeijen, P.; Arntz, A.

2013-01-01

The present study investigated emotional intelligence (EI) in borderline personality disorder (BPD). It was hypothesized that patients with BPD (n = 61) compared with patients with other personality disorders (PDs; n = 69) and nonpatients (n = 248) would show higher scores on the ability to perceive

Different Serotonergic Expression in Nevomelanocytic Tumors

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Naimi-Akbar, Clara; Ritter, Markus; Demel, Sasika; El-Nour, Husameldin; Hedblad, Mari-Anne [Dermatology and Venereology Unit, Department of Medicine, Solna, Karolinska Institutet, Karolinska University Hospital, Solna (Sweden); Azmitia, Efrain C. [Department of Biology and Psychiatry, New York University, NY (United States); Nordlind, Klas, E-mail: klas.nordlind@karolinska.se [Dermatology and Venereology Unit, Department of Medicine, Solna, Karolinska Institutet, Karolinska University Hospital, Solna (Sweden)

2010-06-07

The neuromediator serotonin (5-hydroxytryptamine; 5-HT) has been proposed to play a role in tumor progression. Thus, the aim of the present investigation was to determine whether alterations in the serotonergic system occur in nevomelanocytic tumors. For this purpose, paraffin-embedded biopsies of superficial spreading malignant melanoma (SSM), dysplastic compound nevi (DN) and benign compound nevi (BCN) were characterized with regard to their expression of 5-HT, the 5-HT1A and 5-HT2A receptors, and the serotonin transporter protein (SERT), by immunohistochemical analysis. Melanocytes in the region surrounding the tumor were found to express both the 5-HT1A and 5-HT2A receptors. Tumor cells that immunostained positively for the different serotonergic markers were observed in the suprabasal epidermis of DN tissue and, to an even greater extent, in the case of SSM. Furthermore, some of these latter cells expressed both 5-HT1AR and 5-HT2AR. The level of expression of 5-HT1AR at the junctional area was lower for SSM than for DN or BCN. As the degree of atypia increased, the intensity of tumor cell staining in the dermis for 5-HT1AR and SERT declined. Vessel immunoreactivity for 5-HT2A was more intense in SSM than in BCN tissue. Round-to-dendritic cells that expressed both SERT and 5-HT1AR were seen to infiltrate into the dermal region of the tumor, this infiltration being more evident in the case of DN and SSM. These latter cells were also tryptase-positive, indicating that they are mast cells. Thus, alterations in serotonergic system may be involved in nevomelanocytic tumors and mast cells may play an important role in this connection.

Towards a "free radical theory of graying": melanocyte apoptosis in the aging human hair follicle is an indicator of oxidative stress induced tissue damage.

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Arck, Petra Clara; Overall, Rupert; Spatz, Katharina; Liezman, Christiane; Handjiski, Bori; Klapp, Burghard F; Birch-Machin, Mark A; Peters, Eva Milena Johanne

2006-07-01

Oxidative stress is generated by a multitude of environmental and endogenous challenges such as radiation, inflammation, or psychoemotional stress. It also speeds the aging process. Graying is a prominent but little understood feature of aging. Intriguingly, the continuous melanin synthesis in the growing (anagen) hair follicle generates high oxidative stress. We therefore hypothesize that hair bulb melanocytes are especially susceptible to free radical-induced aging. To test this hypothesis, we subjected human scalp skin anagen hair follicles from graying individuals to macroscopic and immunohistomorphometric analysis and organ culture. We found evidence of melanocyte apoptosis and increased oxidative stress in the pigmentary unit of graying hair follicles. The "common" deletion, a marker mitochondrial DNA-deletion for accumulating oxidative stress damage, occurred most prominently in graying hair follicles. Cultured unpigmented hair follicles grew better than pigmented follicles of the same donors. Finally, cultured pigmented hair follicles exposed to exogenous oxidative stress (hydroquinone) showed increased melanocyte apoptosis in the hair bulb. We conclude that oxidative stress is high in hair follicle melanocytes and leads to their selective premature aging and apoptosis. The graying hair follicle, therefore, offers a unique model system to study oxidative stress and aging and to test antiaging therapeutics in their ability to slow down or even stop this process.

Induction of autocrine factor inhibiting cell motility from murine B16-BL6 melanoma cells by alpha-melanocyte stimulating hormone.

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Murata, J; Ayukawa, K; Ogasawara, M; Watanabe, H; Saiki, I

1999-03-15

We have previously reported that neuropeptide alpha-melanocyte stimulating hormone (alpha-MSH) successfully inhibited Matrigel invasion and haptotactic migration of B16-BL6 melanoma cells towards both fibronectin and laminin without affecting their growth. In the present study, we investigated the inhibitory mechanism of tumor cell motility by alpha-MSH. Alpha-MSH significantly blocked the autocrine motility factor (AMF)-enhanced cell motility. However, alpha-MSH did neither prevent the secretion of AMF from B16-BL6 cells nor alter the expression level of AMF receptor (gp78). On the other hand, alpha-MSH induced the secretion of the motility inhibitory factor(s) from B16-BL6 cells in a concentration- and time-dependent manner. The induction of the motility inhibitor(s) was proportional to increasing levels of intracellular cAMP induced by alpha-MSH as well as forskolin, and the activity was abolished by an adenylate cyclase inhibitor, 2',5'-dideoxyadenosine (DDA). The motility-inhibiting activity in conditioned medium (CM) from alpha-MSH-treated B16-BL6 cells was found to have a m.w. below 3 kDa after fractionation. This activity was abolished by boiling but insensitive to trypsin. The treatment of tumor cells with cycloheximide reduced the activity in alpha-MSH-stimulated CM. Our results suggest that alpha-MSH inhibited the motility of B16-BL6 cells through induction of autocrine factor(s).

Longitudinal transmission pathways of borderline personality disorder symptoms: from mother to child?

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Reinelt, Eva; Stopsack, Malte; Aldinger, Maren; Ulrich, Ines; Grabe, Hans Jörgen; Barnow, Sven

2014-01-01

There is evidence that the borderline symptomatology of the mother longitudinally predicts the number of borderline criteria met by the children. However, possible underlying mechanisms have rarely been examined. In line with transactional models of borderline personality disorder (BPD), we analyzed a broad concept of maladaptive mother-child interactions of mothers with BPD symptoms towards their children, including insensitive parenting and mother-child discrepancies, in reporting the child's psychopathological behavior. SAMPLING/METHODS: The sample was drawn from the population-based Greifswald Family Study and consisted of 295 children and their biological mothers. Both were examined at two points in time, first when the children were about 15 years old (T0) and again 5 years later (T1), using path analyses. Maladaptive mother-child interactions (especially an overprotective and rejecting parenting style and high discrepancies regarding internalizing problems) mediate the longitudinal transmission of borderline symptoms from mother to child. Furthermore, our data revealed that this result is consistent for various youth symptoms which are associated with BPD such as impulsivity or dissociation. The data of the current study imply that the transmission of borderline symptoms from mother to child is mediated by maladaptive mother-child interactions. For this reason early and professional support may be useful to prevent these children from developing severe psychopathology. Copyright © 2012 S. Karger AG, Basel.

Childhood adversity and borderline personality disorder: a focus on adolescence.

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Newnham, Elizabeth A; Janca, Aleksandar

2014-01-01

This article explores recent research in the field of childhood exposure to trauma and the development of borderline personality disorder in adolescence. Adolescence is a critical period of development. Exposure to trauma, specifically sexual abuse, prior to and during puberty has specific implications for personality development and heightens risk for borderline personality disorder. Elevated symptom levels in adolescence are likely to decline across adulthood, but social and vocational impairments remain. Impulsivity, difficulties in emotion regulation, and suicidality may characterize adolescent expression of borderline personality disorder, whereas negative affect and functional impairment are more stable features of the disorder. Preliminary findings in treatment models for adults have potential for benefit among adolescence. Further research is required to examine treatment effectiveness and efficiency. Greater attention to low-income and middle-income nations, which are disproportionately affected by adversity, is needed to determine cross-cultural validity and the impact of trauma in adolescent populations.

Vulnerability, Borderline Personality Disorders. Clinical and ...

African Journals Online (AJOL)

Borderline personality disorder and vulnerability are difficult to assess and are rather elusive to define. A case study material is presented from a cognitive analytical model. An attempt of the dominant features of cognitive analytical therapy and discussion of vulnerability in relation to personality disorder is provided.

Generation borderline: Insecurity of family bondings and the world of addiction

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Nicolò Terminio

2014-09-01

Full Text Available The article concerns of the psychopathology of drug addiction, with an emphasis on the phenomenology of borderline personality disorder. The attention is focused on setting up of family ties in subjects with substance abuse disorders. In particular the anthropological frame of trauma is studied which presents itself as the core on which the therapeutic work is based. Keywords:Addiction; Borderline personality disorder; Trauma

Effect of Novel Marine Nutraceuticals on IL-1α-Mediated TNF-α Release from UVB-Irradiated Human Melanocyte-Derived Cells

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Visalini Muthusamy

2011-01-01

Full Text Available UV-induced inflammation and reactive oxygen species formation are involved in the development of melanoma. Natural products like 5β-scymnol and CO2-supercritical fluid extract (CO2-SFE of mussel oil contain anti-inflammatory and antioxidant properties that may aid in reducing the deleterious effects of UV radiation. Therefore, their effect on the release of the proinflammatory cytokine, tumour necrosis factor-α (TNF-α, from UVB-irradiated human melanocytic cells was examined. Human epidermal melanocytes (HEM and MM96L melanoma cells were exposed to UVB radiation and IL-1α. Cell viability and TNF-α levels were determined 24 hours after-irradiation while p38 mitogen-activated protein kinase (MAPK activation was observed at 15 min after-irradiation. When α-tocopherol, CO2-SFE mussel oil, and 5β-scymnol were added to the UVB-irradiated HEM cells treated with IL-1α, TNF-α levels fell by 53%, 65%, and 76%, respectively, while no inhibition was evident in MM96L cells. This effect was not due to inhibition of the intracellular p38 MAPK signalling pathway. These compounds may be useful in preventing inflammation-induced damage to normal melanocytes.

A single-center experience and review of the literature: 64 cases of phyllodes tumors to better understand risk factors and disease management.

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Lightner, Amy L; Shurell, Elizabeth; Dawson, Nicole; Omidvar, Yasaman; Foster, Nova

2015-03-01

Phyllodes tumors of the breast are rare fibroepithelial tumors that are characterized as benign, borderline, or malignant based on cellular characteristics such as stromal overgrowth and number of mitoses. Currently, there is a lack of consensus on risk factors and management of patients with phyllodes tumors, which has led to variation in treatment patterns as well as patient outcomes across many institutions. This study seeks to understand the clinicopathologic features, risk factors for local and metastatic recurrence, and clinical outcomes of patients with phyllodes tumors to better define optimal treatment patterns.

Reducing renal uptake of 9Y- and 177Lu-labeled alpha-melanocyte stimulating hormone peptide analogues

International Nuclear Information System (INIS)

Miao Yubin; Fisher, Darrell R.; Quinn, Thomas P.

2006-01-01

Objective: The purpose of this study was to improve the tumor-to-kidney uptake ratios of 9 Y- and 177 Lu-[1,4,7,10-tetraazacyclododecane-1,4,7,10-tetraacetic acid-Re-Cys 3,4,1 , D-Phe 7 , Arg 11 ]α-melanocyte stimulating hormone 3-13 {DOTA-Re(Arg 11 )CCMSH} through coupling a negatively charged glutamic acid (Glu) to the peptide sequence. Methods: A new peptide of DOTA-Re(Glu 2 , Arg 11 )CCMSH was designed, synthesized and labeled with 9 Y and 177 Lu. Pharmacokinetics of 9 Y- and 177 Lu-DOTA-Re(Glu 2 , Arg 11 )CCMSH was determined in B16/F1 murine melanoma-bearing C57 mice. Results: 9 Y- and 177 Lu-DOTA-Re(Glu 2 , Arg 11 )CCMSH exhibited significantly (P 9 Y- and 177 Lu-DOTA-Re(Arg 11 )CCMSH at 30 min and at 2, 4 and 24 h after dose administration. The renal uptake values of 9 Y- and 177 Lu-DOTA-Re(Glu 2 , Arg 11 )CCMSH were 28.16% and 28.81% of those of 9 Y- and 177 Lu-DOTA-Re(Arg 11 )CCMSH, respectively, at 4 h postinjection. 9 Y- and 177 Lu-DOTA-Re(Glu 2 , Arg 11 )CCMSH displayed higher tumor-to-kidney uptake ratios than 9 Y- and 177 Lu-DOTA-Re(Arg 11 )CCMSH at 30 min and at 2, 4 and 24 h after dose administration. The tumor-to-kidney uptake ratio of 9 Y- and 177 Lu-DOTA-Re(Glu 2 , Arg 11 )CCMSH was 2.28 and 1.69 times of 9 Y- and 177 Lu-DOTA-Re(Arg 11 )CCMSH, respectively, at 4 h postinjection. The 9 Y- and 177 Lu-DOTA-Re(Glu 2 , Arg 11 )CCMSH activity accumulation was low in normal organs except for kidney. Conclusions: Coupling a negatively charged amino acid (Glu) to the CCMSH peptide sequence dramatically reduced the renal uptake values and increased the tumor-to-kidney uptake ratios of 9 Y- and 177 Lu-DOTA-Re(Glu 2 , Arg 11 )CCMSH, facilitating their potential applications as radiopharmaceuticals for targeted radionuclide therapy of melanoma

Differences in mental health among young adults with borderline personality symptoms of various severities

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Wei-Hsin Lu

2018-04-01

Full Text Available Purpose: This study examined the differences in mental health and behavioral problems among young adults with borderline personality symptoms of various severities. Methods: 500 college students participated in this study. Borderline personality symptoms were evaluated using the Taiwanese version of the Borderline Symptom List (BSL-23. Mental health problems were assessed using the Symptom Checklist-90-Revised Scale. Suicidality and other behavioral problems were assessed using questions from the epidemiological version of the Kiddie Schedule for Affective Disorders and Schizophrenia and BSL-23 Supplement. According to the distribution of BSL-23 scores at the 25th, 50th, and 75th percentiles, the participants were divided into 4 groups: No/Mild, Moderate, Severe, and Profound. Analysis of variance and the chi-square test were used to compare mental health and behavioral problems among the 4 groups. Results: All mental health problems differed significantly among the 4 groups. The severity of nearly all mental health problems increased with that of borderline personality symptoms. The proportions of most behavioral problems differed significantly among the 4 groups. The Profound group was more likely to have behavioral problems than the other 3 groups. Conclusion: Young adults who had more severe borderline personality symptoms had more severe mental health and behavioral problems. Keywords: Borderline personality, Mental health, Suicidality

Grandiose and Vulnerable Narcissism in Borderline Personality Disorder.

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Euler, Sebastian; Stöbi, Dominik; Sowislo, Julia; Ritzler, Franziska; Huber, Christian G; Lang, Undine E; Wrege, Johannes; Walter, Marc

2018-02-21

Little is known about narcissistic traits in borderline personality disorder (BPD). This exploratory study aimed to illustrate the associations between total, grandiose, and vulnerable narcissism and gender, diagnostic features of BPD and narcissistic personality disorder (NPD), and psychopathology in BPD patients. The Pathological Narcissism Inventory and psychometric measures for impulsivity, anger, borderline symptom severity, personality organization, depression, and rejection sensitivity were completed by 65 BPD patients. Statistical analyses were conducted using the t test, Pearson correlation, and multivariate regression analyses. Male BPD patients displayed higher narcissistic scores than females (p personality disorders. Future studies are advised to apply complementary measures and take new diagnostic approaches of DSM-5 and ICD-11 into account. © 2018 S. Karger AG, Basel.

The neural correlates of anomalous habituation to negative emotional pictures in borderline and avoidant personality disorder patients.

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Koenigsberg, Harold W; Denny, Bryan T; Fan, Jin; Liu, Xun; Guerreri, Stephanie; Mayson, Sarah Jo; Rimsky, Liza; New, Antonia S; Goodman, Marianne; Siever, Larry J

2014-01-01

Extreme emotional reactivity is a defining feature of borderline personality disorder, yet the neural-behavioral mechanisms underlying this affective instability are poorly understood. One possible contributor is diminished ability to engage the mechanism of emotional habituation. The authors tested this hypothesis by examining behavioral and neural correlates of habituation in borderline patients, healthy comparison subjects, and a psychopathological comparison group of patients with avoidant personality disorder. During fMRI scanning, borderline patients, healthy subjects, and avoidant personality disorder patients viewed novel and repeated pictures, providing valence ratings at each presentation. Statistical parametric maps of the contrasts of activation during repeated versus novel negative picture viewing were compared between groups. Psychophysiological interaction analysis was employed to examine functional connectivity differences between groups. Unlike healthy subjects, neither borderline nor avoidant personality disorder patients exhibited increased activity in the dorsal anterior cingulate cortex when viewing repeated versus novel pictures. This lack of an increase in dorsal anterior cingulate activity was associated with greater affective instability in borderline patients. In addition, borderline and avoidant patients exhibited smaller increases in insula-amygdala functional connectivity than healthy subjects and, unlike healthy subjects, did not show habituation in ratings of the emotional intensity of the images. Borderline patients differed from avoidant patients in insula-ventral anterior cingulate functional connectivity during habituation. Unlike healthy subjects, borderline patients fail to habituate to negative pictures, and they differ from both healthy subjects and avoidant patients in neural activity during habituation. A failure to effectively engage emotional habituation processes may contribute to affective instability in borderline

Inhibition of systemic inflammation by central action of the neuropeptide alpha-melanocyte- stimulating hormone.

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Delgado Hernàndez, R; Demitri, M T; Carlin, A; Meazza, C; Villa, P; Ghezzi, P; Lipton, J M; Catania, A

1999-01-01

The neuropeptide alpha-melanocyte stimulating hormone (alpha-MSH) reduces fever and acute inflammation in the skin when administered centrally. The aim of the present research was to determine whether central alpha-MSH can also reduce signs of systemic inflammation in mice with endotoxemia. Increases in serum tumor necrosis factor-alpha and nitric oxide, induced by intraperitoneal administration of endotoxin, were modulated by central injection of a small concentration of alpha-MSH. Inducible nitric oxide synthase (iNOS) activity and iNOS mRNA in lungs and liver were likewise modulated by central alpha-MSH. Lung myeloperoxidase activity, a marker of neutrophil infiltration, was increased in endotoxemic mice; the increase was significantly less in lungs of mice treated with central alpha-MSH. Intraperitoneal administration of the small dose of alpha-MSH that was effective centrally did not alter any of the markers of inflammation. In experiments using immunoneutralization of central alpha-MSH, we tested the idea that endogenous peptide induced within the brain during systemic inflammation modulates host responses to endotoxic challenge in peripheral tissues. The data showed that proinflammatory agents induced by endotoxin in the circulation, lungs, and liver were significantly greater after blockade of central alpha-MSH. The results suggest that anti-inflammatory influences of neural origin that are triggered by alpha-MSH could be used to treat systemic inflammation.

Perivascular Epithelioid Cell Tumor (PEComa of the Uterine Cervix in a Patient with Tuberous Sclerosis Complex: A Literature Review

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Handan ÇELİK

2018-01-01

Full Text Available Perivascular epithelioid cell tumors (PEComa are a rare type of mesenchymal tumor arising from perivascular epithelial cells. These tumor cells are a co-expression of both melanocytic and myogenic antigens, such as HMB 45 and smooth muscle actin, and at least in some patients, are located around vessels. PEComas has been reported at various sites, including visceral organs, soft tissue, the prostate gland and broad ligaments. In the female reproductive system, the uterine corpus is the most common site of involvement. Some cases are related to tuberous sclerosis complex. Cervical PEComa with tuberous sclerosis complex is presented in the case of a 41 year-old and the literature is reviewed. There have been only eight cases of cervical PEComas and only one other case associated with tuberous sclerosis complex reported to date.

Clinical management of borderline tumours of the ovary - experience from the "Berlin online tumour conference for gynaecological malignancies".

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Sehouli, Jalid; Oskay-Oezcelik, Guelten; Pietzner, Klaus; Chen, Frank; Coumbos, Alexandra; Darb-Esfahani, Silvia; Schuback, Beatrix; Heinrich, Georg; Kronenberger, Christel; Lorsbach, Michael; Lichtenegger, Werner; Chekerov, Radoslav

2010-05-01

Borderline ovarian tumour (BOT) represents a rare and special tumour entity. Despite a generally favourable prognosis for patients with BOT, the presence of invasive peritoneal implants decreases the survival rate to 30-50%. In contrast to ovarian cancer, only few data exist concerning the current clinical management of patients with BOT. For this reason, the present analyses were performed for patients with BOT who were admitted into our online tumor conference for patients with gynaecological malignancies. Based on the results discussed in this article, the current aspects and problems regarding the diagnostic, surgical and conservative treatment and aftercare management of patients with BOT are considered.

The Effect of Attending Good Psychiatric Management (GPM) Workshops on Attitudes Toward Patients With Borderline Personality Disorder.

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Keuroghlian, Alex S; Palmer, Brian A; Choi-Kain, Lois W; Borba, Christina P C; Links, Paul S; Gunderson, John G

2016-08-01

The effect that attending a 1-day workshop on Good Psychiatric Management (GPM) had on attitudes about borderline personality disorder (BPD) was assessed among 297 clinicians. Change was recorded by comparing before and after scores on a 9-item survey previously developed to assess the effects of workshops on Systems Training for Emotional Predictability and Problem Solving (STEPPS). Participants reported decreased inclination to avoid borderline patients, dislike of borderline patients, and belief that BPD's prognosis is hopeless, as well as increased feeling of competence, belief that borderline patients have low self-esteem, feeling of being able to make a positive difference, and belief that effective psychotherapies exist. Less clinical experience was related to an increased feeling of competence and belief that borderline patients have low self-esteem. These findings were compared to those from the STEPPS workshop. This assessment demonstrates GPM's potential for training clinicians to meet population-wide needs related to borderline personality disorder.

Functional expression of TWEAK and the receptor Fn14 in human malignant ovarian tumors: possible implication for ovarian tumor intervention.

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Liying Gu

Full Text Available The aim of this current study was to investigate the expression of the tumor necrosis factor (TNF-like weak inducer of apoptosis (TWEAK and its receptor fibroblast growth factor-inducible 14 (Fn14 in human malignant ovarian tumors, and test TWEAK's potential role on tumor progression in cell models in-vitro. Using immunohistochemistry (IHC, we found that TWEAK and its receptor Fn14 were expressed in human malignant ovarian tumors, but not in normal ovarian tissues or in borderline/benign epithelial ovarian tumors. High levels of TWEAK expression was detected in the majority of malignant tumors (36 out of 41, 87.80%. Similarly, 35 out of 41 (85.37% malignant ovarian tumors were Fn14 positive. In these malignant ovarian tumors, however, TWEAK/Fn14 expression was not corrected with patients' clinical subtype/stages or pathological features. In vitro, we demonstrated that TWEAK only inhibited ovarian cancer HO-8910PM cell proliferation in combination with tumor necrosis factor-α (TNF-α, whereas either TWEAK or TNF-α alone didn't affect HO-8910PM cell growth. TWEAK promoted TNF-α production in cultured THP-1 macrophages. Meanwhile, conditioned media from TWEAK-activated macrophages inhibited cultured HO-8910PM cell proliferation and invasion. Further, TWEAK increased monocyte chemoattractant protein-1 (MCP-1 production in cultured HO-8910PM cells to possibly recruit macrophages. Our results suggest that TWEAK/Fn14, by activating macrophages, could be ovarian tumor suppressors. The unique expression of TWEAK/Fn14 in malignant tumors indicates that it might be detected as a malignant ovarian tumor marker.

On the role of oxytocin in borderline personality disorder.

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Brüne, Martin

2016-09-01

Interpersonal dysfunction is central to borderline personality disorder (BPD). Recent research has focused on the role of oxytocin (OT) in BPD, particularly regarding associations of OT activity with symptoms, genetic polymorphisms of the oxytocin receptor coding gene (OXTR) in BPD, and experimental modification of interpersonal core problems of patients with BPD such as hypervigilance towards threat detection, mistrust, and non-verbal behaviour during social interaction by intranasal application of OT. A literature ('medline') review was performed using the keywords 'oxytocin' and 'borderline personality disorder'. Secondary literature on trauma and attachment in relation to OT was also considered relevant. Together, findings suggest that in BPD OT is associated with enhanced defensive mechanisms and avoidance behaviour. Moreover, gene-environment interaction concerning polymorphic variations of the OXTR gene and childhood adversity in BPD suggests that these genes convey developmental flexibility or 'differential susceptibility' to environmental contingencies, whereby BPD resides at the poor outcome end of the spectrum. In view of the conflicting literature, it needs to be studied carefully whether OT can serve as a therapeutic agent given adjunct to psychotherapy in BPD. More research about the role of OT is also required with regard to the prevention of the non-genetic intergenerational transmission of BPD. Clarifying the role of OT in BPD may also benefit from research in non-human animals targeting the interaction between early adversity and OT availability more directly. The study of oxytocin can contribute to the understanding of the neurobiology of borderline personality disorder. Oxytocin is critically involved in attachment security, and methylation of the oxytocin receptor may play a role in the epigenetic modulation of early adversity. The intranasal application of oxytocin may be a useful therapeutic adjunct to psychotherapy. Insecure attachment and

Borderline organization of personality in adulthood and adolescence

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Alessandra Mura

2011-12-01

Full Text Available About the middle of the 1950 it was proposed the definition of borderline disorder to classify some of the clinical manifestations that they are not explained by neurosis and psychosis theory. The structural approach of Otto Kernberg has been particular relief to understand the borderline disorder. O. Kernberg has been suggested theborderline organization of personality, to outline a typical permanent pathological functioning underlying string of psychopathologic syndromes associated by a standard and specific structural pathology of Ego that it is based on mechanism of split. Recently there is a build-up the theory about adolescence disorders, where its diagnosis is complicated by lack structural identity and about symptoms that they show the effects of typical change of adolescence.

Contemporary Management of Borderline Resectable and Locally Advanced Unresectable Pancreatic Cancer.

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Shaib, Walid L; Ip, Andrew; Cardona, Kenneth; Alese, Olatunji B; Maithel, Shishir K; Kooby, David; Landry, Jerome; El-Rayes, Bassel F

2016-02-01

Adenocarcinoma of the pancreas remains a highly lethal disease, with less than 5% survival at 5 years. Borderline resectable pancreatic cancer (BRPC) and locally advanced unresectable pancreatic cancer (LAPC) account for approximately 30% of newly diagnosed cases of PC. The objective of BRPC therapy is to downstage the tumor to allow resection; the objective of LAPC therapy is to control disease and improve survival. There is no consensus on the definitions of BRPC and LAPC, which leads to major limitations in designing clinical trials and evaluating their results. A multimodality approach is always needed to ensure proper utilization and timing of chemotherapy, radiation, and surgery in the management of this disease. Combination chemotherapy regimens (5-fluorouracil, leucovorin, irinotecan, oxaliplatin, and gemcitabine [FOLFIRINOX] and gemcitabine/nab-paclitaxel) have improved overall survival in metastatic disease. The role of combination chemotherapy regimens in BRPC and LAPC is an area of active investigation. There is no consensus on the dose, modality, and role of radiation therapy in the treatment of BRPC and LAPC. This article reviews the literature and highlights the areas of controversy regarding management of BRPC and LAPC. Pancreatic cancer is one of the worst cancers with regard to survival, even at early stages of the disease. This review evaluates all the evidence for the stages in which the cancer is not primarily resectable with surgery, known as borderline resectable or locally advanced unresectable. Recently, advancements in radiation techniques and use of better combination chemotherapies have improved survival and tolerance. There is no consensus on description of stages or treatment sequences (chemotherapy, chemoradiation, radiation), nor on the best chemotherapy regimen. The evidence behind the treatment paradigm for these stages of pancreatic cancer is summarized. ©AlphaMed Press.

Emotion Regulation Training for Adolescents With Borderline Personality Disorder Traits : A Randomized Controlled Trial

NARCIS (Netherlands)

Schuppert, H. Marieke; Timmerman, Marieke E.; Bloo, Josephine; van Gemert, Tonny G.; Wiersema, Herman M.; Minderaa, Ruud B.; Emmelkamp, Paul M. G.; Nauta, Maaike H.

2012-01-01

Objective: To evaluate the effectiveness of Emotion Regulation Training (ERT), a 17-session weekly group training for adolescents with borderline personality disorder (BPD) symptoms. Method: One hundred nine adolescents with borderline traits (73% meeting the full criteria for BPD) were randomized

Emotion regulation training for adolescents with borderline personality disorder traits: a randomized controlled trial

NARCIS (Netherlands)

Schuppert, H.M.; Timmerman, M.E.; Bloo, J.; van Gemert, T.G.; Wiersema, H.M.; Minderaa, R.B.; Emmelkamp, P.M.G.; Nauta, M.H.

2012-01-01

Objective: To evaluate the effectiveness of Emotion Regulation Training (ERT), a 17-session weekly group training for adolescents with borderline personality disorder (BPD) symptoms. Method: One hundred nine adolescents with borderline traits (73% meeting the full criteria for BPD) were randomized

A biosocial developmental model of borderline personality: Elaborating and extending Linehan's theory.

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Crowell, Sheila E; Beauchaine, Theodore P; Linehan, Marsha M

2009-05-01

Over the past several decades, research has focused increasingly on developmental precursors to psychological disorders that were previously assumed to emerge only in adulthood. This change in focus follows from the recognition that complex transactions between biological vulnerabilities and psychosocial risk factors shape emotional and behavioral development beginning at conception. To date, however, empirical research on the development of borderline personality is extremely limited. Indeed, in the decade since M. M. Linehan initially proposed a biosocial model of the development of borderline personality disorder, there have been few attempts to test the model among at-risk youth. In this review, diverse literatures are reviewed that can inform understanding of the ontogenesis of borderline pathology, and testable hypotheses are proposed to guide future research with at-risk children and adolescents. One probable pathway is identified that leads to borderline personality disorder; it begins with early vulnerability, expressed initially as impulsivity and followed by heightened emotional sensitivity. These vulnerabilities are potentiated across development by environmental risk factors that give rise to more extreme emotional, behavioral, and cognitive dysregulation. (PsycINFO Database Record (c) 2009 APA, all rights reserved).

Inpatient management of borderline personality disorder at Helen ...

African Journals Online (AJOL)

Inpatient management of borderline personality disorder at Helen Joseph Hospital, Johannesburg. ... South African Journal of Psychiatry ... to the acute inpatient psychiatric assessment unit at the Helen Joseph Hospital, in Johannesburg, over ...

Psychosocial morbidity associated with bipolar disorder and borderline personality disorder in psychiatric out-patients: comparative study.

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Zimmerman, Mark; Ellison, William; Morgan, Theresa A; Young, Diane; Chelminski, Iwona; Dalrymple, Kristy

2015-10-01

The morbidity associated with bipolar disorder is, in part, responsible for repeated calls for improved detection and recognition. No such commentary exists for the improved detection of borderline personality disorder. Clinical experience suggests that it is as disabling as bipolar disorder, but no study has directly compared the two disorders. To compare the levels of psychosocial morbidity in patients with bipolar disorder and borderline personality disorder. Patients were assessed with semi-structured interviews. We compared 307 patients with DSM-IV borderline personality disorder but without bipolar disorder and 236 patients with bipolar disorder but without borderline personality disorder. The patients with borderline personality disorder less frequently were college graduates, were diagnosed with more comorbid disorders, more frequently had a history of substance use disorder, reported more suicidal ideation at the time of the evaluation, more frequently had attempted suicide, reported poorer social functioning and were rated lower on the Global Assessment of Functioning. There was no difference between the two patient groups in history of admission to psychiatric hospital or time missed from work during the past 5 years. The level of psychosocial morbidity associated with borderline personality disorder was as great as (or greater than) that experienced by patients with bipolar disorder. From a public health perspective, efforts to improve the detection and treatment of borderline personality disorder might be as important as efforts to improve the recognition and treatment of bipolar disorder. © The Royal College of Psychiatrists 2015.

The mediating role of mentalizing capacity between parents and peer attachment and adolescent borderline personality disorder.

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Beck, Emma; Sharp, Carla; Poulsen, Stig; Bo, Sune; Pedersen, Jesper; Simonsen, Erik

2017-01-01

Insecure attachment is a precursor and correlate of borderline personality disorder. According to the mentalization-based theory of borderline personality disorder, the presence of insecure attachment derails the development of the capacity to mentalize, potentially resulting in borderline pathology. While one prior study found support for this notion in adolescents, it neglected a focus on peer attachment. Separation from primary caregivers and formation of stronger bonds to peers are key developmental achievements during adolescence and peer attachment warrants attention as a separate concept. In a cross-sectional study, female outpatients (M age 15.78=, SD = 1.04) who fulfilled DSM-5 criteria for BPD ( N  = 106) or met at least 4 BPD criteria ( N  = 4) completed self-reports on attachment to parents and peers, mentalizing capacity (reflective function) and borderline personality features. Our findings suggest that in a simple mediational model, mentalizing capacity mediated the relation between attachment to peers and borderline features. In the case of attachment to parents, the mediational model was not significant. The current study is the first to evaluate this mediational model with parent and peer attachment as separate concepts and the first to do so in a sample of adolescents who meet full or sub-threshold criteria for borderline personality disorder. Findings incrementally support that mentalizing capacity and attachment insecurity, also in relation to peers, are important concepts in theoretical approaches to the development of borderline personality disorder in adolescence. Clinical implications are discussed.

Suicide attempts and self-injurious behaviours in adolescent and adult patients with borderline personality disorder.

Science.gov (United States)

Goodman, Marianne; Tomas, Irene Alvarez; Temes, Christina M; Fitzmaurice, Garrett M; Aguirre, Blaise A; Zanarini, Mary C

2017-08-01

Prevalence data on self-mutilation and suicide attempts for adolescent borderline personality disorder (BPD) are currently not available. The purpose of this paper was to determine the frequency and methods of two forms of physically self-destructive acts (i.e. self-mutilation and suicide attempts) reported by adolescent borderline inpatients in one of the largest samples to date and to compare these results with a similarly diagnosed and assessed group of adult borderline inpatients. A total of 104 adolescent inpatients with BPD and 290 adult inpatients with BPD were interviewed about their lifetime history of physically self-destructive acts. The overall rates of self-mutilation (about 90%) and suicide attempts (about 75%) were similar during index admission for both adolescent and adult borderline patients. However, adolescents reported significantly higher rates of extreme levels of lifetime self-mutilation (e.g. >25 and >50 episodes) and cutting in particular, as compared with adult BPD. In contrast, borderline adults were significantly more likely to report a history of numerous (five or more) suicide attempts than adolescents with BPD. Self-mutilation and suicide attempts among adolescent borderline patients are prevalent and serious. Taken together, these results suggest that extreme levels of self-mutilation distinguish adolescent BPD from adults with BPD. Copyright © 2017 John Wiley & Sons, Ltd. Copyright © 2017 John Wiley & Sons, Ltd.

[Transference Focused Psychotherapy for Borderline-Adolescents in a Day Clinic Treatment Program].

Science.gov (United States)

Krischer, Maya; Ponton-Rodriguez, Tamara; Gooran, Ghazal Rostami; Bender, Stephan

2017-07-01

Transference Focused Psychotherapy for Borderline-Adolescents in a Day Clinic Treatment Program This paper focuses on the concept of transference focused psychotherapy (TFP) modified for juvenile borderline patients. Adolescents with borderline developmental personality disorder (bpd) have an essential deficit in their personality structure that leads to oscillations in their self-esteem and in a "split" perception of the world. They suffer from a variety of symptoms and severe impairments on their own and their families' quality of life. Their fragmented perception of themselves and others make relationships almost unbearable for them. Relationships are mostly marked by severe anxiety of resentment and rejection. For these patients this causes intolerable trouble at school where every day conflicts take place. Self-mutilation and suicidal thoughts often seem the only way out. By now, there is an agreement that an early specialized assessment and treatment is necessary in order to stop the typical consequences of their self-mutilative and dysfunctional behavior. Still, in contrast to adult age, empirical evidence is missing which proves the effectiveness of treating adolescent borderline patients. In this paper we present a research project on the effectiveness of transference focused psychotherapy with adolescent borderline patients (TFP-A) in a day clinic setting, combining TFP with group skills training as known from dialectic behavior therapy (DBT). Furthermore, we give first results on analyzing the effectiveness of our day clinic treatment program based on TFP-A, focusing on improving core symptoms such as affective problems, aggressive behavior against self and others and interpersonal problems.

SSRI treatment of borderline personality disorder: A randomized, placebo-controlled clinical trial for female patients with borderline personality disorder

NARCIS (Netherlands)

Rinne, Thomas; van den Brink, Wim; Wouters, Luuk; van Dyck, Richard

2002-01-01

Objective: Selective serotonin reuptake inhibitors (SSRIs) are recommended for treatment of affect lability, impulsivity, and aggression in patients with borderline personality disorder. This recommendation is based on positive findings in at least 10 open studies and one small double-blind study of

Identifying classes of persons with mild intellectual disability or borderline intellectual functioning: a latent class analysis.

Science.gov (United States)

Nouwens, Peter J G; Lucas, Rosanne; Smulders, Nienke B M; Embregts, Petri J C M; van Nieuwenhuizen, Chijs

2017-07-17

Persons with mild intellectual disability or borderline intellectual functioning are often studied as a single group with similar characteristics. However, there are indications that differences exist within this population. Therefore, the aim of this study was to identify classes of persons with mild intellectual disability or borderline intellectual functioning and to examine whether these classes are related to individual and/or environmental characteristics. Latent class analysis was performed using file data of 250 eligible participants with a mean age of 26.1 (SD 13.8, range 3-70) years. Five distinct classes of persons with mild intellectual disability or borderline intellectual functioning were found. These classes significantly differed in individual and environmental characteristics. For example, persons with a mild intellectual disability experienced fewer problems than those with borderline intellectual disability. The identification of five classes implies that a differentiated approach is required towards persons with mild intellectual disability or borderline intellectual functioning.

Borderline personality features in childhood: the role of subtype, developmental timing, and chronicity of child maltreatment.

Science.gov (United States)

Hecht, Kathryn F; Cicchetti, Dante; Rogosch, Fred A; Crick, Nicki R

2014-08-01

Child maltreatment has been established as a risk factor for borderline personality disorder (BPD), yet few studies consider how maltreatment influences the development of BPD features through childhood and adolescence. Subtype, developmental timing, and chronicity of child maltreatment were examined as factors in the development of borderline personality features in childhood. Children (M age = 11.30, SD = 0.94), including 314 maltreated and 285 nonmaltreated children from comparable low socioeconomic backgrounds, provided self-reports of developmentally salient borderline personality traits. Maltreated children had higher overall borderline feature scores, had higher scores on each individual subscale, and were more likely to be identified as at high risk for development of BPD through raised scores on all four subscales. Chronicity of maltreatment predicted higher overall borderline feature scores, and patterns of onset and recency of maltreatment significantly predicted whether a participant would meet criteria for the high-risk group. Implications of findings and recommendations for intervention are discussed.

Borderline Personality Features in Childhood: The Role of Subtype, Developmental Timing and Chronicity of Child Maltreatment

Science.gov (United States)

Hecht, Kathryn F.; Cicchetti, Dante; Rogosch, Fred A.; Crick, Nicki

2014-01-01

Child maltreatment has been established as a risk factor for borderline personality disorder (BPD), yet few studies consider how maltreatment influences the development of BPD features through childhood and adolescence. Subtype, developmental timing and chronicity of child maltreatment were examined as factors in the development of borderline personality features in childhood. Children (M age = 11.30, SD = 0.94), including 314 maltreated and 285 nonmaltreated children from comparable low socioeconomic backgrounds, provided self-reports of developmentally salient borderline personality traits. Maltreated children had higher overall borderline feature scores, higher scores on each individual subscale and were more likely to be identified as at high risk for development of BPD through raised scores on all 4 subscales. Chronicity of maltreatment predicted higher overall borderline feature scores and patterns of onset and recency of maltreatment significantly predicted whether a participant would meet criteria for the high-risk group. Implications of findings and recommendations for intervention are discussed. PMID:25047300

S-100 protein in the diagnosis of tuberculoid borderline tuberculoidleprosy

International Nuclear Information System (INIS)

Khan, A.R.

1998-01-01

A definitive diagnosis of tuberculoid and borderline tuberculoid leprosyis based on a demonstration of either acid-fast bacilli or nerve elementswithin the granulomas. On routine hematoxylin and eosin stains, the nervefibers are not easily identifiable. In this study, we used S-100 protein tohighlight the nerve elements and to count their numbers in leprosy andnon-leprosy granulomas. Skin biopsy specimens from 15 cases oftuberculoid/borderline tuberculoid leprosy and 14 cases belonging to othergranulomatous disease of the skin were stained with S-100 protein. Thesurface area of all the biopsies was calculated and the numbers of nervebundles stained with S-100 protein were counted in each specimen. The nervebundles were 15 per cm2 in leprosy cases, and 9.2 per cm2 in non-leprosycases. In addition, the leprosy cases showed longer nerve twigs that wereperpendicularly oriented to the skin surface. Immunostaining with S-100facilitated detection of nerve elements in tuberculoid/borderline tuberculoidleprosy. Also, an increased number of nerve elements were found in leprosygranulomas when compared with non-leprosy granulomas (P=<0.05). (author)

Comprehensive expression profiling of tumor cell lines identifies molecular signatures of melanoma progression.

Directory of Open Access Journals (Sweden)

Byungwoo Ryu

2007-07-01

Full Text Available Gene expression profiling has revolutionized our ability to molecularly classify primary human tumors and significantly enhanced the development of novel tumor markers and therapies; however, progress in the diagnosis and treatment of melanoma over the past 3 decades has been limited, and there is currently no approved therapy that significantly extends lifespan in patients with advanced disease. Profiling studies of melanoma to date have been inconsistent due to the heterogeneous nature of this malignancy and the limited availability of informative tissue specimens from early stages of disease.In order to gain an improved understanding of the molecular basis of melanoma progression, we have compared gene expression profiles from a series of melanoma cell lines representing discrete stages of malignant progression that recapitulate critical characteristics of the primary lesions from which they were derived. Here we describe the unsupervised hierarchical clustering of profiling data from melanoma cell lines and melanocytes. This clustering identifies two distinctive molecular subclasses of melanoma segregating aggressive metastatic tumor cell lines from less-aggressive primary tumor cell lines. Further analysis of expression signatures associated with melanoma progression using functional annotations categorized these transcripts into three classes of genes: 1 Upregulation of activators of cell cycle progression, DNA replication and repair (CDCA2, NCAPH, NCAPG, NCAPG2, PBK, NUSAP1, BIRC5, ESCO2, HELLS, MELK, GINS1, GINS4, RAD54L, TYMS, and DHFR, 2 Loss of genes associated with cellular adhesion and melanocyte differentiation (CDH3, CDH1, c-KIT, PAX3, CITED1/MSG-1, TYR, MELANA, MC1R, and OCA2, 3 Upregulation of genes associated with resistance to apoptosis (BIRC5/survivin. While these broad classes of transcripts have previously been implicated in the progression of melanoma and other malignancies, the specific genes identified within each class

A Biosocial Developmental Model of Borderline Personality: Elaborating and Extending Linehan’s Theory

Science.gov (United States)

Crowell, Sheila E.; Beauchaine, Theodore P.; Linehan, Marsha M.

2009-01-01

Over the past several decades, research has focused increasingly on developmental precursors to psychological disorders that were previously assumed to emerge only in adulthood. This change in focus follows from the recognition that complex transactions between biological vulnerabilities and psychosocial risk factors shape emotional and behavioral development beginning at conception. To date, however, empirical research on the development of borderline personality is extremely limited. Indeed, in the decade since M. M. Linehan initially proposed a biosocial model of the development of borderline personality disorder, there have been few attempts to test the model among at-risk youth. In this review, diverse literatures are reviewed that can inform understanding of the ontogenesis of borderline pathology, and testable hypotheses are proposed to guide future research with at-risk children and adolescents. One probable pathway is identified that leads to borderline personality disorder; it begins with early vulnerability, expressed initially as impulsivity and followed by heightened emotional sensitivity. These vulnerabilities are potentiated across development by environmental risk factors that give rise to more extreme emotional, behavioral, and cognitive dysregulation. PMID:19379027

Gestalt psychotherapy in the outpatient treatment of borderline ...

African Journals Online (AJOL)

): ... psychotic reactions as well as self-destructive behaviour could also be experienced. ... level graduate program, moved out of her parents' home and bought her own ... effectiveness of cognitive behavior therapy for borderline personality ...

Borderline Personality Disorder Features Are Associated with Concurrent Pain-Related Disability in a Chronic Pain Sample.

Science.gov (United States)

Reynolds, Caleb J; Tragesser, Sarah L

2018-04-03

To determine whether core features of borderline personality disorder are associated with increased rates of being on disability benefits due to chronic pain conditions. A total of 147 patients currently in treatment for chronic pain at a multimodal chronic pain clinic. We tested for a concurrent relationship between borderline personality disorder features and employment status using self-report measures. Borderline personality disorder features were associated with increased likelihood of currently being on disability due to pain conditions (odds ratio [OR] = 23.13, 95% confidence interval [CI] = 1.68-318.73), on disability due to other conditions (OR = 33.65, 95% CI = 2.15-526.13), and unemployed (OR = 20.14, 95% CI = 1.38-294.93), even while controlling for pain severity and interference, depression, and trait anxiety. A follow-up analysis revealed that these associations were due to the negative relationships facet of borderline personality disorder features. Borderline personality disorder features, particularly negative relationships, are associated with increased rates of pain disability, general disability, and unemployment in a chronic pain sample. Future research should examine mechanisms by which the maladaptive interpersonal behaviors and cognitions of borderline personality disorder might result in worse long-term employment outcomes of chronic pain.

Parameterization using Fourier series expansion of the diffuse reflectance of human skin to vary the concentration of the melanocytes

Science.gov (United States)

Narea, J. Freddy; Muñoz, Aarón A.; Castro, Jorge; Muñoz, Rafael A.; Villalba, Caroleny E.; Martinez, María. F.; Bravo, Kelly D.

2013-11-01

Human skin has been studied in numerous investigations, given the interest in knowing information about physiology, morphology and chemical composition. These parameters can be determined using non invasively optical techniques in vivo, such as the diffuse reflectance spectroscopy. The human skin color is determined by many factors, but primarily by the amount and distribution of the pigment melanin. The melanin is produced by the melanocytes in the basal layer of the epidermis. This research characterize the spectral response of the human skin using the coefficients of Fourier series expansion. Simulating the radiative transfer equation for the Monte Carlo method to vary the concentration of the melanocytes (fme) in a simplified model of human skin. It fits relating the Fourier series coefficient a0 with fme. Therefore it is possible to recover the skin biophysical parameter.

Microscopic endometrial perivascular epithelioid cell nodules: a case report with the earliest presentation of a uterine perivascular epithelioid cell tumor

Directory of Open Access Journals (Sweden)

Fang Chia-Lang

2012-09-01

Full Text Available Abstract Perivascular epithelioid cell (PEC tumors (PEComas are a family of related mesenchymal tumors composed of PECs which co-express melanocytic and smooth muscle markers. Although their distinctive histologic, immunohistochemical, ultrastructural, and genetic features have been clearly demonstrated, their histogenesis and normal counterpart remain largely unknown. Precursor lesions of PEComas have rarely been reported. We herein describe a tuberous sclerosis patient with microscopic PEC nodules in the endometrium of adenomyosis, pelvic endometriosis, an ovarian endometriotic cyst, and the endometrium of the uterine cavity. The nodules showed a mixture of spindle-shaped and epithelioid cells concentrically arranged around small arteries. The cells exhibited uniform nuclei, light eosinophilic cytoplasm, and immunoreactivity with HMB-45 and CD10. Some nodules revealed continuity with a PEComa in the myometrium. These findings support microscopic endometrial PEC nodules possibly being precursor lesions of uterine PEComas. The wide distribution of the nodules in the pelvis may be related to the multicentricity of PEComas in tuberous sclerosis patients. Owing to the immunoreactivity with CD10, microscopic endometrial PEC nodules may be misinterpreted as endothelial stromal cells unless melanocytic markers are stained. To the best of our knowledge, this is a case with the earliest manifestation of PEC lesions occurring in the endometrium. Virtual Slides The virtual slide(s for this article can be found here: http://www.diagnosticpathology.diagnomx.eu/vs/9658280017862643

Attention and impulse control in children with borderline intelligence with or without conduct disorder.

NARCIS (Netherlands)

van der Meere, Jaap; van der Meer, Dirk-Jan; Borger, Norbert; Pirila, Silja

2008-01-01

This study was designed to investigate attention and impulse control in 21 boys with dual diagnoses of conduct disorder and borderline intelligence and in 19 boys with borderline intelligence only. Using the Continuous Performance Test A-not-X, it appeared that children with the dual diagnosis made

A diagnostic algorithm for atypical spitzoid tumors: guidelines for immunohistochemical and molecular assessment.

Science.gov (United States)

Cho-Vega, Jeong Hee

2016-07-01

Atypical spitzoid tumors are a morphologically diverse group of rare melanocytic lesions most frequently seen in children and young adults. As atypical spitzoid tumors bear striking resemblance to Spitz nevus and spitzoid melanomas clinically and histopathologically, it is crucial to determine its malignant potential and predict its clinical behavior. To date, many researchers have attempted to differentiate atypical spitzoid tumors from unequivocal melanomas based on morphological, immonohistochemical, and molecular diagnostic differences. A diagnostic algorithm is proposed here to assess the malignant potential of atypical spitzoid tumors by using a combination of immunohistochemical and cytogenetic/molecular tests. Together with classical morphological evaluation, this algorithm includes a set of immunohistochemistry assays (p16(Ink4a), a dual-color Ki67/MART-1, and HMB45), fluorescence in situ hybridization (FISH) with five probes (6p25, 8q24, 11q13, CEN9, and 9p21), and an array-based comparative genomic hybridization. This review discusses details of the algorithm, the rationale of each test used in the algorithm, and utility of this algorithm in routine dermatopathology practice. This algorithmic approach will provide a comprehensive diagnostic tool that complements conventional histological criteria and will significantly contribute to improve the diagnosis and prediction of the clinical behavior of atypical spitzoid tumors.

Borderline Personality Disorder is Associated with Lower Confidence in Perception of Emotional Body Movements

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Morten eKaletsch

2014-11-01

Full Text Available Much recent research has shown that personality disorders are associated with an altered emotion perception. Whereas most of this research was conducted with stimuli such as faces, the present study examined possible differences in the perception of emotions expressed via body language and body movements. 30 patients with borderline personality disorder and 30 non-patients observed video scenes of emotional human interactions conveyed by point–light displays, rated the depicted valence, and judged their confidence in this rating. Patients with borderline personality disorder showed no altered emotion perception (i.e., no biased perception in either a negative or a positive direction. They did not perceive and evaluate depicted emotions as being more extreme than healthy controls. However, patients with borderline personality disorder showed less confidence in their perception of depicted emotions, especially when these were difficult to identify. The findings extend insights on altered emotion perception in persons with borderline personality disorder to include the field of body movements.

Self-Esteem and Anger in Borderline Patients With Self-Injury Behavior.

Science.gov (United States)

Almeida, Carla Maria; Horta, Maria Purificação

2018-04-01

Anger and low self-esteem characterize borderline individuals, yet little is known about their role and impact in the presence or absence of self-injury behavior. The present study aimed to investigate the impact of anger and self-esteem in borderline patients and whether these variables distinguish these patients with and without self-injury. Patients were recruited from a psychiatric service and were evaluated for self-esteem and anger. Additionally, impulsivity and symptoms were assessed. Two groups were compared, one with self-injurious behavior (n = 18) and another one without it (n = 23). Those who injure themselves seem to have a lower self-esteem (p < 0.001), yet the strengthening of self-esteem seems to have different outcomes, according to the presence or absence of self-injury. Anger and self-esteem seem to influence the severity of diagnosis, but only in patients who self-injure. Anger and self-esteem may influence borderline patients differently according to the presence or absence of self-injury.

Parenting, relational aggression, and borderline personality features: associations over time in a Russian longitudinal sample.

Science.gov (United States)

Nelson, David A; Coyne, Sarah M; Swanson, Savannah M; Hart, Craig H; Olsen, Joseph A

2014-08-01

Crick, Murray-Close, and Woods (2005) encouraged the study of relational aggression as a developmental precursor to borderline personality features in children and adolescents. A longitudinal study is needed to more fully explore this association, to contrast potential associations with physical aggression, and to assess generalizability across various cultural contexts. In addition, parenting is of particular interest in the prediction of aggression or borderline personality disorder. Early aggression and parenting experiences may differ in their long-term prediction of aggression or borderline features, which may have important implications for early intervention. The currrent study incorporated a longitudinal sample of preschool children (84 boys, 84 girls) living in intact, two-parent biological households in Voronezh, Russia. Teachers provided ratings of children's relational and physical aggression in preschool. Mothers and fathers also self-reported their engagement in authoritative, authoritarian, permissive, and psychological controlling forms of parenting with their preschooler. A decade later, 70.8% of the original child participants consented to a follow-up study in which they completed self-reports of relational and physical aggression and borderline personality features. The multivariate results of this study showed that preschool relational aggression in girls predicted adolescent relational aggression. Preschool aversive parenting (i.e., authoritarian, permissive, and psychologically controlling forms) significantly predicted aggression and borderline features in adolescent females. For adolescent males, preschool authoritative parenting served as a protective factor against aggression and borderline features, whereas authoritarian parenting was a risk factor for later aggression.

Alpha-Melanocyte Stimulating Hormone Protects against Cytokine-Induced Barrier Damage in Caco-2 Intestinal Epithelial Monolayers.

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Judit Váradi

Full Text Available Alpha-melanocyte-stimulating hormone (α-MSH is a potent anti-inflammatory peptide with cytoprotective effect in various tissues. The present investigation demonstrates the ability of α-MSH to interact with intestinal epithelial cell monolayers and mitigate inflammatory processes of the epithelial barrier. The protective effect of α-MSH was studied on Caco-2 human intestinal epithelial monolayers, which were disrupted by exposure to tumor necrosis factor-α and interleukin-1β. The barrier integrity was assessed by measuring transepithelial electric resistance (TEER and permeability for marker molecules. Caco-2 monolayers were evaluated by immunohistochemistry for expression of melanocortin-1 receptor and tight junction proteins ZO-1 and claudin-4. The activation of nuclear factor kappa beta (NF-κB was detected by fluorescence microscopy and inflammatory cytokine expression was assessed by flow cytometric bead array cytokine assay. Exposure of Caco-2 monolayers to proinflammatory cytokines lowered TEER and increased permeability for fluorescein and albumin, which was accompanied by changes in ZO-1 and claudin-4 immunostaining. α-MSH was able to prevent inflammation-associated decrease of TEER in a dose-dependent manner and reduce the increased permeability for paracellular marker fluorescein. Further immunohistochemistry analysis revealed proinflammatory cytokine induced translocation of the NF-κB p65 subunit into Caco-2 cell nuclei, which was inhibited by α-MSH. As a result the IL-6 and IL-8 production of Caco-2 monolayers were also decreased with different patterns by the addition of α-MSH to the culture medium. In conclusion, Caco-2 cells showed a positive immunostaining for melanocortin-1 receptor and α-MSH protected Caco-2 cells against inflammatory barrier dysfunction and inflammatory activation induced by tumor necrosis factor-α and interleukin-1β cytokines.

Psychopathology in offspring of mothers with borderline personality disorder: a pilot study.

Science.gov (United States)

Weiss, M; Zelkowitz, P; Feldman, R B; Vogel, J; Heyman, M; Paris, J

1996-06-01

Children of mothers with borderline personality disorder (BPD) were hypothesized to be at greater risk for psychopathology, particularly impulse spectrum disorders, than children of mothers with other personality disorders. Twenty-one index children were compared with 23 children of mothers with a nonborderline personality disorder. Diagnoses were obtained using the Kiddie Schedule for Affective Disorders and Schizophrenia-Episodic Version (KSADS-E) and the Child Diagnostic Interview for BPD (CDIB), and functioning was rated with the Child Global Assessment Schedule (CGAS). Physical, sexual, and verbal abuse, as well as family violence and placements, were also assessed. The children of the borderline mothers, as compared with controls, had more psychiatric diagnoses, more impulse control disorders, a higher frequency of child BPD, and lower CGAS scores. There were no differences between the groups for trauma. The offspring of borderline mothers are at high risk for psychopathology.

alpha-Melanocyte-stimulating-hormone precursors in the pig pituitary

DEFF Research Database (Denmark)

Fenger, M

1986-01-01

The occurrence of intermediates from the processing of ACTH-(1-39) [adrenocorticotropic hormone-(1-39)] to alpha-melanocyte-stimulating hormone was investigated in normal pig pituitaries by the use of sensitive and specific radioimmunoassays for ACTH-(1-13), ACTH-(1-14), ACTH-(1-13)-NH2 and ACTH-(1......) were detected in lower amounts in both the intermediate lobe and the anterior lobe. ACTH-(1-17), ACTH-(1-13) and their acetylated analogues could not be detected in the anterior lobe or the intermediate lobe. The results suggest that an endopeptidase initially cleaves ACTH-(1-39) at the Lys-16-Arg-17...... bond. ACTH-(1-16) is then processed by a pituitary carboxypeptidase to ACTH-(1-14) and ACTH-(17-39) by the aminopeptidase to ACTH-(18-39)....

Fostering Self-Compassion and Loving-Kindness in Patients With Borderline Personality Disorder: A Randomized Pilot Study.

Science.gov (United States)

Feliu-Soler, Albert; Pascual, Juan Carlos; Elices, Matilde; Martín-Blanco, Ana; Carmona, Cristina; Cebolla, Ausiàs; Simón, Vicente; Soler, Joaquim

2017-01-01

The aim of this randomized pilot study is to investigate the effects of a short training programme in loving-kindness and compassion meditation (LKM/CM) in patients with borderline personality disorder. Patients were allocated to LKM/CM or mindfulness continuation training (control group). Patients in the LKM/CM group showed greater changes in Acceptance compared with the control group. Remarkable changes in borderline symptomatology, self-criticism and self-kindness were also observed in the LKM/CM group. Mechanistic explanations and therapeutic implications of the findings are discussed. Three weeks of loving-kindness and compassion meditations increased acceptance of the present-moment experience in patients with borderline personality disorder. Significant improvements in the severity of borderline symptoms, self-criticism, mindfulness, acceptance and self-kindness were observed after the LKM/CM intervention. LKM/CM is a promising complementary strategy for inclusion in mindfulness-based interventions and Dialectical Behavioural Therapy for treating core symptoms in borderline personality disorder. Copyright © 2016 John Wiley & Sons, Ltd. Copyright © 2016 John Wiley & Sons, Ltd.

Emotion Regulation Training for Adolescents with Borderline Personality Disorder Traits: A Randomized Controlled Trial

Science.gov (United States)

Schuppert, H. Marieke; Timmerman, Marieke E.; Bloo, Josephine; van Gemert, Tonny G.; Wiersema, Herman M.; Minderaa, Ruud B.; Emmelkamp, Paul M. G.; Nauta, Maaike H.

2012-01-01

Objective: To evaluate the effectiveness of Emotion Regulation Training (ERT), a 17-session weekly group training for adolescents with borderline personality disorder (BPD) symptoms. Method: One hundred nine adolescents with borderline traits (73% meeting the full criteria for BPD) were randomized to treatment as usual only (TAU) or ERT + TAU.…

International consensus on definition and criteria of borderline resectable pancreatic ductal adenocarcinoma 2017.

Science.gov (United States)

Isaji, Shuji; Mizuno, Shugo; Windsor, John A; Bassi, Claudio; Fernández-Del Castillo, Carlos; Hackert, Thilo; Hayasaki, Aoi; Katz, Matthew H G; Kim, Sun-Whe; Kishiwada, Masashi; Kitagawa, Hirohisa; Michalski, Christoph W; Wolfgang, Christopher L

2018-01-01

This statement was developed to promote international consensus on the definition of borderline resectable pancreatic ductal adenocarcinoma (BR-PDAC) which was adopted by the National Comprehensive Cancer Network (NCCN) in 2006, but which has changed yearly and become more complicated. Based on a symposium held during the 20th meeting of the International Association of Pancreatology (IAP) in Sendai, Japan, in 2016, the presenters sought consensus on issues related to BR-PDAC. We defined patients with BR-PDAC according to the three distinct dimensions: anatomical (A), biological (B), and conditional (C). Anatomic factors include tumor contact with the superior mesenteric artery and/or celiac artery of less than 180° without showing stenosis or deformity, tumor contact with the common hepatic artery without showing tumor contact with the proper hepatic artery and/or celiac artery, and tumor contact with the superior mesenteric vein and/or portal vein including bilateral narrowing or occlusion without extending beyond the inferior border of the duodenum. Biological factors include potentially resectable disease based on anatomic criteria but with clinical findings suspicious for (but unproven) distant metastases or regional lymph nodes metastases diagnosed by biopsy or positron emission tomography-computed tomography. This also includes a serum carbohydrate antigen (CA) 19-9 level more than 500 units/ml. Conditional factors include the patients with potentially resectable disease based on anatomic and biologic criteria and with Eastern Cooperative Oncology Group (ECOG) performance status of 2 or more. The definition of BR-PDAC requires one or more positive dimensions (e.g. A, B, C, AB, AC, BC or ABC). The present definition acknowledges that resectability is not just about the anatomic relationship between the tumor and vessels, but that biological and conditional dimensions are also important. The aim in presenting this consensus definition is also to highlight

Echinococcus cysticus of the liver - sonographic pattern suggestive of solid tumor

International Nuclear Information System (INIS)

Grosser, G.; Hauenstein, K.H.; Henke, W.

1985-01-01

In a patient with Hodgkin's disease, an intrahepatic echodense mass was diagnosed incidentally by ultrasonography. The sonographic pattern suggested a solid tumor. Despite negative or borderline serology, computed tomography establised the diagnosis of echinococcus cysticus by documentation of one ''daughter'' cyst; this diagnosis was confirmed by surgery. The criteria of echinococcus cysticus in modern imaging methods like sonography and computed tomography are summarized and the diagnostic value of various procedures including diagnostic procedure in seronegative cases are discussed. (orig.) [de

Family Study of Borderline Personality Disorder and Its Sectors of Psychopathology

Science.gov (United States)

Gunderson, John G.; Zanarini, Mary C.; Choi-Kain, Lois W.; Mitchell, Karen S.; Jang, Kerry L.; Hudson, James I.

2011-01-01

Context The familiality of borderline personality disorder (BPD) and its sectors of psychopathology are incompletely understood. Objectives To assess the familial aggregation of BPD and its 4 major sectors (affective, interpersonal, behavioral, and cognitive) and test whether the relationship of the familial and nonfamilial associations among these sectors can be accounted for by a latent BPD construct. Design Family study, with direct interviews of probands and relatives. Setting A psychiatric hospital (McLean Hospital) and the Boston-area community. Participants A total of 368 probands (132 with BPD, 134 without BPD, and 102 with major depressive disorder) and 885 siblings and parents of probands. Main Assessments The Diagnostic Interview for DSM-IV Personality Disorders and the Revised Diagnostic Interview for Borderlines (DIB-R) were used to assess borderline psychopathology, and the Structured Clinical Interview for DSM-IV was used to assess major depressive disorder. Results Borderline personality disorder meeting both DSM-IV and DIB-R criteria showed substantial familial aggregation for BPD in individuals with a family member with BPD vs those without a family member with BPD, using proband-relative pairs (risk ratio, 2.9; 95% confidence interval, 1.5–5.5) as well as using all pairs of family members (3.9; 1.7–9.0). All 4 sectors of BPD psychopathology aggregated significantly in families, using both DSM-IV and DIB-R definitions (correlation of traits among all pairs of family members ranged from 0.07 to 0.27), with the affective and interpersonal sectors showing the highest levels; however, the level of familial aggregation of BPD was higher than that of the individual sectors. The relationship among the sectors was best explained by a common pathway model in which the sectors represent manifestations of a latent BPD construct. Conclusions Familial factors contribute to BPD and its sectors of psychopathology. Borderline personality disorder may arise

Randomized Controlled Trial of Web-Based Psychoeducation for Women With Borderline Personality Disorder.

Science.gov (United States)

Zanarini, Mary C; Conkey, Lindsey C; Temes, Christina M; Fitzmaurice, Garrett M

2017-07-11

To determine if internet-based psychoeducation for borderline personality disorder is effective in reducing symptom severity and improving psychosocial functioning. Eighty women who met DSM-IV criteria for borderline personality disorder were randomly assigned either to the internet-based psychoeducation treatment group (n = 40) or to the internet-based control group with no psychoeducation (n = 40). Recruitment was conducted from July 2013 to March 2015. Subjects participated in 15 assessment periods that were divided into an acute phase (weeks 1-12) and a maintenance phase (months 6, 9, and 12). Main outcomes were assessed using the Zanarini Rating Scale for Borderline Personality Disorder. In the acute phase, women in the treatment group were found to have a significant decline in their scores on all 10 outcomes studied, while women in the control group had a significant decline on 7 of these outcomes. Two between-group differences were found to be significant-those in the treatment group reported a significantly greater decline in their impulsivity (z = -1.98, P = .048) and a significantly greater increase in their psychosocial functioning (z = -1.97, P = .049) than those in the control group. In the maintenance phase, those in the treatment group were found to have a significant decline in their scores on 9 of the 10 outcomes studied, while those in the control group had a significant decline in 3 of these outcomes. In terms of between-group differences, those in the treatment group reported a significantly greater decline in all 5 studied areas of borderline psychopathology: affective symptoms (z = -2.31, P = .021), cognitive symptoms (z = -3.20, P = .001), impulsivity (z = -2.44, P = .015), interpersonal difficulties (z = -2.15, P = .032), and overall borderline personality disorder symptoms (z = -2.11, P = .035). Taken together, these results suggest that internet-based psychoeducation is an effective form of early treatment for reducing the symptom

The course of eating disorders in patients with borderline personality disorder: a 10-year follow-up study.

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Zanarini, Mary C; Reichman, Charlotte A; Frankenburg, Frances R; Reich, D Bradford; Fitzmaurice, Garrett

2010-04-01

The purpose of this study was to describe the longitudinal course of eating disorders in patients with borderline personality disorder. The SCID I was administered to 290 borderline inpatients and 72 participants with other axis II disorders during their index admission and at five contiguous 2-year follow-up periods. The prevalence of anorexia, bulimia, and eating disorder not otherwise specified (EDNOS) declined significantly over time for those in both study groups but the prevalence of EDNOS remained significantly higher among borderline patients. While over 90% of borderline patients meeting criteria for anorexia, bulimia, or EDNOS at baseline experienced a stable remission by the time of the 10-year follow-up, diagnostic migration was common, particularly for those with anorexia or bulimia. In addition, both recurrences (52%) and new onsets (43%) of EDNOS were more common among borderline patients than recurrences and new onsets of anorexia (28% and 4%) and bulimia (29% and 11%). The results of this study suggest that the prognosis for both anorexia and bulimia in borderline patients is complicated, with remissions being stable but migrations to other eating disorders being common. The results also suggest that EDNOS may be the most prevalent and enduring of the eating disorders in these patients.

Philosophy and the Disciplines: The Borderlines | Minimah ...

African Journals Online (AJOL)

This work examines the borderlines of philosophy in relation to the central concern of other disciplines. As a preliminary step towards our examination, we attempt to uncover the specific nature of philosophy on the basis of its subject matter. We argue that while philosophy asks 'second order' questions about the totality of ...

Cutaneous lasers and skin camouflage make-up: a useful alternative intervention for periorbital hairy congenital melanocytic naevus.

Science.gov (United States)

Townley, William A; Bragg, Thomas W H; Wright, Philip A; Cole, Richard P

2013-12-01

Periorbital congenital melanocytic naevi can be very disfiguring and difficult to treat effectively. Although surgical excision and reconstruction is the most widely accepted treatment strategy, we describe a case in which cutaneous lasers treatment followed by the application of cosmetic skin camouflage make-up provided an alternative solution delivering a good cosmetic improvement.

The co-occurrence of autistic traits and borderline personality disorder traits is associated to increased suicidal ideation in nonclinical young adults.

Science.gov (United States)

Chabrol, Henri; Raynal, Patrick

2018-04-01

The co-occurrence of Autism Spectrum Disorder (ASD) and Borderline Personality Disorder (BPD) is not rare and has been linked to increased suicidality. Despite this significant comorbidity between ASD and BPD, no study had examined the co-occurrence of autistic traits and borderline personality disorder traits in the general population. The aim of the present study was to examine the co-occurrence of autistic and borderline traits in a non-clinical sample of young adults and its influence on the levels of suicidal ideation and depressive symptomatology. Participants were 474 college students who completed self-report questionnaires. Data were analysed using correlation and cluster analyses. Borderline personality traits and autistic traits were weakly correlated. However, cluster analysis yielded four groups: a low traits group, a borderline traits group, an autistic traits group, and a group characterized by high levels of both traits. Cluster analysis revealed that autistic and borderline traits can co-occur in a significant proportion of young adults. The high autistic and borderline traits group constituted 17% of the total sample and had higher level of suicidal ideation than the borderline traits group, despite similar levels of depressive symptoms. This result suggests that the higher suicidality observed in patients with comorbid ASD and BPD may extent to non-clinical individuals with high levels of co-occurrent autistic and borderline traits. Copyright © 2018 Elsevier Inc. All rights reserved.

Gruppemusikterapi med patienter med borderline-personlighedsforstyrrelse i dagbehandlingsregi

DEFF Research Database (Denmark)

Hannibal, Niels

2008-01-01

Denne artikel er første redegørelse for de erfaringer, som er gjort med gruppemusikterapi (GMT) for patienter med borderline-personlighedsforstyrrelse (BPF) i dagbehandlingsregi på Aalborg Psykiatriske Sygehus. Artiklen indeholder både konkrete anvisninger til aktiviteter og interventioner, liges...

Similarities and differences in borderline and organic personality disorder.

Science.gov (United States)

Mathiesen, Birgit B; Simonsen, Erik; Soegaard, Ulf; Kvist, Kajsa

2014-01-01

Previous research has shown that brain injury patients with Organic Personality Disorder (OPD) may display "borderline" traits due to prefrontal damage, and their personality structure may be unstable and close to a borderline personality organisation. They may have few general neuropsychological dysfunctions but specific executive deficits. Similar deficits have been found in patients with Borderline Personality Disorder (BPD). The objective of this study was to identify differences and similarities between the neuropsychological and personality profiles of BPD and OPD patients. Twenty BPD patients and 24 OPD patients were assessed with the Structured Clinical Interview for DSM-IV Axis II Disorders (SCID-II), the Karolinska Psychodynamic Profile (KAPP), and a comprehensive neuropsychological test battery. Very few neuropsychological differences were found between the two patient groups. However, the verbal fluency, verbal intelligence, verbal memory, and immediate auditory memory/attention of the BPD patients were significantly poorer than the OPD patients'. The KAPP profiles of the BPD patients showed significantly poorer functioning in three areas: frustration tolerance, the body as a factor of self-esteem, and overall personality organisation. These results support our clinical experience and expectations concerning the severity of symptoms of both patient groups. We suggest considering in depth assessments of both neuropsychological and personality-related problems for each of these patients in order to inform treatment.

[Epistemic and historical elucidation of the borderline personality disorder].

Science.gov (United States)

Londoño Paredes, Diego Enrique

2015-01-01

The particularities of those that have been considered "hard cases" in the clinical field, and their relationship with personality disorders, are discussed together with their quintessential conceptual and diagnostic model: the borderline personalities. The aim of the study is to historically and epistemologically rebuild their origins within psychiatry and psychoanalysis. From a classical epistemological and historical study, a brief tour is made through the nineteenth century alienism and the postulate of "partial insanity". Next, a passage is spawned through the concepts that emerged from this postulate: "monomania" and "moral insanity", up to mid-century Kraepelin and the "fundamental states" of manic-depressive insanity as pathological constitutional forms or characters, and reaching the twentieth century with characterology and psychopathic personalities. Finally, psychoanalysis is analyzed as the main source of borderline personality disorders arising from the problems encountered in analytical treatments and the development of the notion of "character neurosis". Borderline personality disorders are the result of the conjunction of a number of factors, heirs of the notion of "partial insanity", of the fundamental states of manic-depression insanity, of characterology, of the idea of constitutions and pathological personalities, together with the emerging concerns of psychoanalysis in the early twentieth century. Copyright © 2014 Asociación Colombiana de Psiquiatría. Publicado por Elsevier España. All rights reserved.

Differentiating risk for mania and borderline personality disorder: The nature of goal regulation and impulsivity.

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Fulford, Daniel; Eisner, Lori R; Johnson, Sheri L

2015-06-30

Researchers and clinicians have long noted the overlap among features and high comorbidity of bipolar disorder and borderline personality disorder. The shared features of impulsivity and labile mood in both disorders make them challenging to distinguish. We tested the hypothesis that variables related to goal dysregulation would be uniquely related to risk for mania, while emotion-relevant impulsivity would be related to risk for both disorders. We administered a broad range of measures related to goal regulation traits and impulsivity to 214 undergraduates. Findings confirmed that risk for mania, but not for borderline personality disorder, was related to higher sensitivity to reward and intense pursuit of goals. In contrast, borderline personality disorder symptoms related more strongly than did mania risk with threat sensitivity and with impulsivity in the context of negative affect. Results highlight potential differences and commonalities in mania risk versus borderline personality disorder risk. Copyright © 2015 Elsevier Ireland Ltd. All rights reserved.

Experiences of women in secure care who have been prescribed clozapine for borderline personality disorder.

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Dickens, Geoffrey L; Frogley, Catherine; Mason, Fiona; Anagnostakis, Katina; Picchioni, Marco M

2016-01-01

Clozapine is an atypical antipsychotic medicine which can cause significant side-effects. It is often prescribed off-license in severe cases of borderline personality disorder contrary to national treatment guidelines. Little is known about the experiences of those who take clozapine for borderline personality disorder. We explored the lived-experience of women in secure inpatient care who were prescribed clozapine for borderline personality disorder. Adult females ( N  = 20) participated in audio-taped semi-structured interviews. Transcripts were subject to thematic analysis. The central themes related to evaluation, wellbeing, understanding and self-management; for many, their subjective wellbeing on clozapine was preferred to prior levels of functioning and symptomatology, sometimes profoundly so. The negative and potentially adverse effects of clozapine were explained as regrettable but relatively unimportant. When psychological interventions are, at least initially, ineffective then clozapine treatment is likely to be evaluated positively by a group of women with borderline personality disorder in secure care despite the potential disadvantages.

Theory of mind in women with borderline personality disorder or schizophrenia: differences in overall ability and error patterns

Directory of Open Access Journals (Sweden)

Anja eVaskinn

2015-08-01

Full Text Available Although borderline personality disorder and schizophrenia are notably different mental disorders, they share problems in social cognition – or understanding the feelings, intentions and thoughts of other people. To date no studies have directly compared the social cognitive abilities of individuals with these two disorders. In this study, the social cognitive subdomain theory of mind was investigated in females with borderline personality disorder (n = 25, females with schizophrenia (n = 25 and healthy females (n = 25. An ecologically valid video-based measure (Movie for the Assessment of Social Cognition was used. For the overall score, females with schizophrenia performed markedly below both healthy females and females with borderline personality disorder, whereas females with borderline personality disorder did not perform significantly different compared to the healthy control group. A statistically significant error type x group interaction effect indicated that the groups differed with respect to kind of errors. Whereas females with borderline personality disorder made mostly overmentalizing errors, females with schizophrenia in addition committed undermentalizing errors. Our study suggests different magnitude and pattern of social cognitive problems in borderline personality disorder and schizophrenia.

[Methylation of selected tumor-supressor genes in benign and malignant ovarian tumors].

Science.gov (United States)

Cul'bová, M; Lasabová, Z; Stanclová, A; Tilandyová, P; Zúbor, P; Fiolka, R; Danko, J; Visnovský, J

2011-09-01

To evaluate the usefullness of examination of methylation status of selected tumor-supressor genes in early diagnosis of ovarian cancer. Prospective clinical study. Department of Gynecology and Obstetrics, Department of Molecular Biology, Jessenius Medical Faculty, Commenius University, Martin, Slovak Republic. In this study we analyzed hypermethylation of 5 genes RASSF1A, GSTP, E-cadherin, p16 and APC in ovarian tumor samples from 34 patients - 13 patients with epithelial ovarian cancer, 2 patients with border-line ovarian tumors, 12 patients with benign lesions of ovaries and 7 patients with healthy ovarian tissue. The methylation status of promoter region of tumor-supressor genes was determined by Methylation Specific Polymerase Chain Reaction (MSP) using a nested two-step approach with bisulfite modified DNA template and specific primers. Gene methylation analysis revealed hypermethylation of gene RASSF1A (46%) and GSTP (8%) only in malignant ovarian tissue samples. Ecad, p16 and APC genes were methylated both in maignant and benign tissue samples. Methylation positivity in observed genes was present independently to all clinical stages of ovarian cancer and to tumor grades. However, there was observed a trend of increased number and selective involvement of methylated genes with increasing disease stages. Furthermore, there was no association between positive methylation status and histological subtypes of ovarian carcinomas. RASSF1A and GSTP promoter methylation positivity is associated with ovarian cancer. The revealed gene-selective methylation positivity and the increased number of methylated genes with advancing disease stages could be considered as a useful molecular marker for early detection of ovarian cancer. However, there is need to find diagnostic approach of specifically and frequently methylated genes to determining a methylation phenotype for early detection of ovarian malignancies.

Twenty-five-year-old Woman with Bilateral Borderline Ovarian Tumour Desiring to Preserve Fertility - Case Report and Literature Review on the Current State of Fertility Preservation in Women with Borderline Ovarian Tumours.

Science.gov (United States)

Findeklee, S; Lotz, L; Heusinger, K; Hoffmann, I; Dittrich, R; Beckmann, M W

2016-11-01

Borderline ovarian tumours are semimalignant tumours occurring unilaterally or bilaterally with a peak incidence among women of reproductive age. Since the affected women often wish to preserve fertility, particular precautions must be taken when counselling the patient and obtaining consent prior to planning an individual treatment. Options for preserving fertility include an organ-sparing surgical procedure and cryopreservation of oocytes and/or ovarian tissue. In this article, we report on a 25-year-old patient with a bilateral seromucinous borderline tumour who desired all fertility-preserving options. In order to perform the procedure without delay, we opted to perform luteal phase stimulation prior to oocyte retrieval. We conclude by discussing the current literature on the state of fertility preservation in the treatment of borderline ovarian tumours.

Resolution of vitiligo following excision of halo congenital melanocytic nevus: a rare case report.

Science.gov (United States)

Wang, Kai; Wang, Zhi; Huang, Weiqing

2016-05-01

Halo congenital melanocytic nevus (CMN) associated with vitiligo is rare, especially with regard to CMN excision. Only two reports of excision of halo CMN following repigmentation of vitiligo are found in the literature. We present a case of a girl with halo CMN and periorbital vitiligo. The halo CMN was excised and followed by spontaneous improvement of vitiligo. The result suggests excision of the inciting lesion may be a promising way to control vitiligo. © 2015 Wiley Periodicals, Inc.

Borderline personality disorder and regularly drinking alcohol before sex.

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Thompson, Ronald G; Eaton, Nicholas R; Hu, Mei-Chen; Hasin, Deborah S

2017-07-01

Drinking alcohol before sex increases the likelihood of engaging in unprotected intercourse, having multiple sexual partners and becoming infected with sexually transmitted infections. Borderline personality disorder (BPD), a complex psychiatric disorder characterised by pervasive instability in emotional regulation, self-image, interpersonal relationships and impulse control, is associated with substance use disorders and sexual risk behaviours. However, no study has examined the relationship between BPD and drinking alcohol before sex in the USA. This study examined the association between BPD and regularly drinking before sex in a nationally representative adult sample. Participants were 17 491 sexually active drinkers from Wave 2 of the National Epidemiologic Survey on Alcohol and Related Conditions. Logistic regression models estimated effects of BPD diagnosis, specific borderline diagnostic criteria and BPD criterion count on the likelihood of regularly (mostly or always) drinking alcohol before sex, adjusted for controls. Borderline personality disorder diagnosis doubled the odds of regularly drinking before sex [adjusted odds ratio (AOR) = 2.26; confidence interval (CI) = 1.63, 3.14]. Of nine diagnostic criteria, impulsivity in areas that are self-damaging remained a significant predictor of regularly drinking before sex (AOR = 1.82; CI = 1.42, 2.35). The odds of regularly drinking before sex increased by 20% for each endorsed criterion (AOR = 1.20; CI = 1.14, 1.27) DISCUSSION AND CONCLUSIONS: This is the first study to examine the relationship between BPD and regularly drinking alcohol before sex in the USA. Substance misuse treatment should assess regularly drinking before sex, particularly among patients with BPD, and BPD treatment should assess risk at the intersection of impulsivity, sexual behaviour and substance use. [Thompson Jr RG, Eaton NR, Hu M-C, Hasin DS Borderline personality disorder and regularly drinking alcohol

Borderline Personality Features and Implicit Shame-Prone Self-Concept in Middle Childhood and Early Adolescence

Science.gov (United States)

Hawes, David J.; Helyer, Rebekah; Herlianto, Eugene C.; Willing, Jonah

2013-01-01

This study tested if children and adolescents with high levels of borderline personality features (BPF) exhibit the same shame-prone self-concept previously found to characterize adults with borderline personality disorder (Rusch et al., 2007). Self-concept was indexed using the Implicit Association Test, in a community sample of…

Melanin offers protection against induction of cyclobutane pyrimidine dimers and 6-4 photoproducts by UVB in cultured human melanocytes

NARCIS (Netherlands)

Smit, N.P.M.; Vink, A.A.; Kolb, R.M.; Steenwinkel, M.J.S.T.; Berg, P.T.M. van den; Nieuwpoort, F. van; Roza, L.; Pavel, S.

2001-01-01

The goal of this investigation was to correlate the melanin content in human pigmentary cells with the generation of UVB-induced photoproducts and to examine the relationship between the melanin content and the removal of the photoproducts. Cultured melanocytes from light-skinned individuals

ER, p53 and MIB-1 are significantly associated with malignant phyllodes tumor.

Science.gov (United States)

Munawer, Nurhayati H; Md Zin, Reena; Md Ali, Siti-Aishah; Muhammad, Rohaizak; Ali, Jasmi; Das, Srijit

2012-01-01

Fibroadenomas (FA) are common while phyllodes tumors (PT) are rare and both tumors are composed of epithelial and stromal components. We evaluated the expression status of ER, Bc12, p53, and MIB-1 protein in these tumors. One hundred and ninety-three tumors comprising of 117 FAs and 76 PTs were examined using immunohistochemistry on tissue microarray. The mean age of patients with FA was 28.5 years while the mean ages of patients with benign, borderline and malignant PTs were 41.7, 48.6 and 42.1 years, respectively. Also all types of PTs were large (>Scm). ER showed a strong nuclear staining in the epithelial component of all tumors while ER/3 immunoreactivity was detected in both the epithelial and stromal components ofF A and PT. ER/β (pcomponent were associated with tumor size. p53 expression was significantly associated with both the epithelial and stromal components of malignant PTs (pcomponent (p=0.000). In addition, MIB-1 was also found to be associated with ER and ER/3 in the stromal component (p=0.000). The expression of p53 with tumor size and histological grade in PT may increase the risk for malignancy.

HGF/SF increases number of skin melanocytes but does not alter quality or quantity of follicular melanogenesis.

Directory of Open Access Journals (Sweden)

Agnieszka Wolnicka-Glubisz

Full Text Available Melanins are an important factor determining the vulnerability of mammalian skin to UV radiation and thus to UV-induced skin cancers. Transgenic mice overexpressing hepatocyte growth factor/scatter factor (HGF/SF have extra-follicular dermal melanocytes, notably in the papillary upper dermis, and are susceptible to UV-induced melanoma. Pigmented HGF/SF neonatal mice are more susceptible than albino HGF/SF animals to UVA -induced melanoma, indicating an involvement of melanin in melanoma formation. This raises the question of the effect of transgenic HGF/SF on melanization. We developed a methodology to accurately quantitate both the production of melanin and the efficiency of melanogenesis in normal, and HGF/SF transgenic mice in vivo. Skin and hair shafts of 5 day old and adult (3 week old C57BL/6-HGF/SF and corresponding C57BL/6 wild type mice were investigated by electron paramagnetic resonance spectroscopy (EPR to quantitate melanin, by transmission electron microscopy (TEM for the presence of melanosomes, and by standard histology and by Western blotting and zymography to determine the expression and activity of melanogenesis-related proteins. Eumelanin but no phaeomelanin was detected in transgenic C57BL/6-HGF and C57BL/6 wild type mice. Transgenic HGF/SF overexpression did not change the type of melanin produced in the skin or hair, did not affect the terminal content of melanin production in standard samples of hair and did not influence hair cycle/morphogenesis-related changes in skin thickness. No melanocytes were found in the epidermis and no melanosomes were found in epidermal keratinocytes. HGF/SF transgenic mice thus lack the epidermal melanin UV-protection found in constitutively dark human skin. We conclude that melanocytes in the HGF/SF transgenic mouse, particularly in the papillary dermis, are vulnerable to UVA which interacts with eumelanin but not phaeomelanin to induce melanoma.

Trustworthiness Appraisal in Borderline Personality Disorder

OpenAIRE

Masland, Sara Rose

2016-01-01

Borderline personality (BPD) is a highly impairing illness with marked instability across multiple domains, including affect, interpersonal functioning, identity, and behavior. Within the past 15 years, researchers have sought to understand and characterize deficits in social cognition that might contribute to or arise from affective or interpersonal dysfunction. The purpose of this dissertation is to understand one aspect of impaired social cognition in BPD: biased trust processing. Individu...

Phylloedes tumor of breast: findings at mammography, sonography and color Doppler imaging

International Nuclear Information System (INIS)

Park, Kun Choon; Ahn, Sei Hyun; Kim, Young Hwan; Choi, Hye Yong; Baek, Seung Yon; Yoon, Jeong Hyun

1994-01-01

The phylloides tumor of the breast is rare. the purposes of this study were to find the characteristic findings at mammography, sonography, and color Doppler imaging and to evaluate the usefulness of color Doppler study as an additional modality in the diagnosis of phylloides tumor and differentiation between benign and malignant varieties. Eight cases, who were pathologically proven as pylloides tumors, were retrospectively studied. The findings at histologic examination suggested benign in five, malignantin two, and borderline in one. We analyzed the mammograms of all eight patients and sonogram and color Doppler images of four patients. Phylloides tumors were seen as dense masses with lobulated margins in mammograms. On sonography, they showed relatively well-defined masses with in homogenous internal echo pattern and central echogenic areas. They were characterized by the presence of arterial and venous flows in the center and periphery of the lesion on color Doppler imaging and spectral analysis. We conclude that mammographic, sonographic and even color Doppler findings are not predictive of benign or malignant nature of the phylloides tumor. However, mammography and sonography with color Doppler interrogation are helpful in the diagnosis of phylloides tumor

Echinococcus cysticus of the liver - sonographic pattern suggestive of solid tumor

Energy Technology Data Exchange (ETDEWEB)

Grosser, G.; Hauenstein, K.H.; Henke, W.

1985-09-01

In a patient with Hodgkin's disease, an intrahepatic echodense mass was diagnosed incidentally by ultrasonography. The sonographic pattern suggested a solid tumor. Despite negative or borderline serology, computed tomography establised the diagnosis of echinococcus cysticus by documentation of one ''daughter'' cyst; this diagnosis was confirmed by surgery. The criteria of echinococcus cysticus in modern imaging methods like sonography and computed tomography are summarized and the diagnostic value of various procedures including diagnostic procedure in seronegative cases are discussed.

The Relationship between Childhood Attention Deficit/Hyperactivity Disorder and Adulthood Borderline Personality Disorder

Directory of Open Access Journals (Sweden)

Ali Mashhadi

2013-02-01

Full Text Available Background: Attention Deficit Hyperactivity Disorder (ADHD is a risk factor for Borderline Personality Disorder (BPD during adulthood. Studying the relationship between childhood ADHD disorder symptoms and depression and borderline personality disorder symptoms among students was the main aim of this study. Materials and Methods: A total of 291 students, who were studying in Shiraz and Tabriz universities inThe academic year of 2010-2011, were selected from three groups of Humanities, Basic Sciences, and Technical-Engineering Sciences using simple sampling method. They participated in the study through completing Wender Utah Rating Scale (WURS, Borderline Personality Scale (STB and Beck Depression Inventory (BDI-II. Pearsons correlation coefficient and multiple regression analysis were used to analyze the data. Results: The results showed that there is a significant positive relationship between childhood ADHD and borderline Personality Disorder (BPD in adulthood and childhood ADHD is able to predict BPD in adulthood (p<0.01. Similarly, the relationship between symptoms of childhood ADHD and depression was positive and significant (p<0.01. Conclusion: There is a relationship between symptoms of childhood ADHD, BPD and depression in students. It is recommended to pay due attention to the comorbidity disorders such as BPD and depression in the treatment of ADHD disorder.

Uveal Melanoma Cell Lines: Where do they come from? (An American Ophthalmological Society Thesis).

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Jager, Martine J; Magner, J Antonio Bermudez; Ksander, Bruce R; Dubovy, Sander R

2016-08-01

To determine whether some of the most often used uveal melanoma cell lines resemble their original tumor. Analysis of the literature, patient charts, histopathology, mutations, chromosome status, HLA type, and expression of melanocyte markers on cell lines and their primary tumors. We examined five cell lines and the primary tumors from which they were derived. Four of the five examined primary tumors were unusual: one occupied the orbit, two were recurrences after prior irradiation, and one developed in an eye with a nevus of Ota. One cell line did not contain the GNA11 mutation, but it was present in the primary tumor. Three of the primary tumors had monosomy 3 (two of these lacked BAP1 expression); however, all five cell lines showed disomy 3 and BAP1 expression. All of the cell lines had gain of 8q. Two cell lines lacked expression of melanocyte markers, although these were present in the corresponding primary tumor. All cell lines could be traced back to their original uveal melanoma. Four of the five primary tumors were unusual. Cell lines often differed from their primary tumor in chromosome status and melanocyte markers. However, their specific chromosome aberrations and capacity to continue proliferation characterize them as uveal melanoma cell lines.

The Study of Main and Interactive Effects of Attachment Dimension and Basic Personality Characteristics in Borderline Traits

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Ali Mohammadzadeh

2012-10-01

Full Text Available Background: There are models of the development of personality disorders which include individual differences in attachment relationships as causal factors contributed in explanation of these phenomena. The dimensional view of personality disorders represents these conditions as extreme variants of normal personality continua. This study investigated main and interactional effects of attachment styles and personality traits in relation to borderline characteristics. Materials and Methods: The current study was conducted in expo fact context. Randomly selected 603 participants (134 male  469 female from Tabriz Payam-e-Noor, Tarbait Moallem of Azarbaijan and Sarab Payam-e-Noor university students took part in this research. Participants answered to Borderline Personality Inventory (BPI, Eysenck Personality Questionnaire Revised, Short form (EPQ-RS and Adult Attachment Inventory (AAI. Data were analyzed using two way analysis of variance method.Results: Results indicate main effects of attachment styles and personality traits, so, individual with ambivalent insecure attachment experience more intensity of borderline traits than individual with avoidant insecure and secure attachments. Individual with high psychoticim and neuroticism traits experience more intensity of borderline characteristics than individual with extraversion personality traits. Also, there are no interactional effects of attachment styles and personality traits in relation to borderline characteristics. Conclusion: These findings reiterate contribution of childhood risk factors in developing borderline personality disorder, especially in children with emotionally vulnerability.

Generation of a double binary transgenic zebrafish model to study myeloid gene regulation in response to oncogene activation in melanocytes.

Science.gov (United States)

Kenyon, Amy; Gavriouchkina, Daria; Zorman, Jernej; Chong-Morrison, Vanessa; Napolitani, Giorgio; Cerundolo, Vincenzo; Sauka-Spengler, Tatjana

2018-04-06

A complex network of inflammatory genes is closely linked to somatic cell transformation and malignant disease. Immune cells and their associated molecules are responsible for detecting and eliminating cancer cells as they establish themselves as the precursors of a tumour. By the time a patient has a detectable solid tumour, cancer cells have escaped the initial immune response mechanisms. Here, we describe the development of a double binary zebrafish model that enables regulatory programming of the myeloid cells as they respond to oncogene-activated melanocytes to be explored, focussing on the initial phase when cells become the precursors of cancer. A hormone-inducible binary system allows for temporal control of expression of different Ras oncogenes ( NRas Q61K , HRas G12V and KRas G12V ) in melanocytes, leading to proliferation and changes in morphology of the melanocytes. This model was coupled to binary cell-specific biotagging models allowing in vivo biotinylation and subsequent isolation of macrophage or neutrophil nuclei for regulatory profiling of their active transcriptomes. Nuclear transcriptional profiling of neutrophils, performed as they respond to the earliest precursors of melanoma in vivo , revealed an intricate landscape of regulatory factors that may promote progression to melanoma, including Serpinb1l4, Fgf1, Fgf6, Cathepsin H, Galectin 1 and Galectin 3. The model presented here provides a powerful platform to study the myeloid response to the earliest precursors of melanoma. © 2018. Published by The Company of Biologists Ltd.

Cerebellar Cognitive Affective Syndrome Presented as Severe Borderline Personality Disorder

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Danilo Pesic

2014-01-01

Full Text Available An increasing number of findings confirm the significance of cerebellum in affecting regulation and early learning. Most consistent findings refer to association of congenital vermis anomalies with deficits in nonmotor functions of cerebellum. In this paper we presented a young woman who was treated since sixteen years of age for polysubstance abuse, affective instability, and self-harming who was later diagnosed with borderline personality disorder. Since the neurological and neuropsychological reports pointed to signs of cerebellar dysfunction and dysexecutive syndrome, we performed magnetic resonance imaging of brain which demonstrated partially developed vermis and rhombencephalosynapsis. These findings match the description of cerebellar cognitive affective syndrome and show an overlap with clinical manifestations of borderline personality disorder.

A randomized trial of dialectical behavior therapy versus general psychiatric management for borderline personality disorder.

Science.gov (United States)

McMain, Shelley F; Links, Paul S; Gnam, William H; Guimond, Tim; Cardish, Robert J; Korman, Lorne; Streiner, David L

2009-12-01

The authors sought to evaluate the clinical efficacy of dialectical behavior therapy compared with general psychiatric management, including a combination of psychodynamically informed therapy and symptom-targeted medication management derived from specific recommendations in APA guidelines for borderline personality disorder. This was a single-blind trial in which 180 patients diagnosed with borderline personality disorder who had at least two suicidal or nonsuicidal self-injurious episodes in the past 5 years were randomly assigned to receive 1 year of dialectical behavior therapy or general psychiatric management. The primary outcome measures, assessed at baseline and every 4 months over the treatment period, were frequency and severity of suicidal and nonsuicidal self-harm episodes. Both groups showed improvement on the majority of clinical outcome measures after 1 year of treatment, including significant reductions in the frequency and severity of suicidal and nonsuicidal self-injurious episodes and significant improvements in most secondary clinical outcomes. Both groups had a reduction in general health care utilization, including emergency visits and psychiatric hospital days, as well as significant improvements in borderline personality disorder symptoms, symptom distress, depression, anger, and interpersonal functioning. No significant differences across any outcomes were found between groups. These results suggest that individuals with borderline personality disorder benefited equally from dialectical behavior therapy and a well-specified treatment delivered by psychiatrists with expertise in the treatment of borderline personality disorder.

Self-image and perception of mother and father in psychotic and borderline patients.

Science.gov (United States)

Armelius, K; Granberg

2000-02-01

Psychotic and borderline patients rated their self-image and their perception of their mother and father using the Structural Analysis of Social Behavior model (SASB). The borderline patients had more negative images of themselves and their parents, especially their fathers, than did the psychotic patients and the normal subjects, while the psychotic patients' ratings did not differ much from those of the normal subjects. The self-image was related to the images of both parents for borderline patients and normal subjects, while for the psychotic patients only the image of the mother was important for the self-image. In addition, the psychotic patients did not differentiate between the poles of control and autonomy in the introjected self-image. It was concluded that borderline patients are characterized by negative attachment, while psychotic patients are characterized by poor separation from the mother and poor differentiation between autonomy and control. The paper also discusses how this may influence the patients' relations to others. Psychotische und Borderline Patienten beurteilten ihr Selbstbild und ihre Wahrnehmung von Mutter und Vater mit Hilfe der strukturalen Analyse sozialen Verhaltens (SASB). Die Borderline Patienten hattten negativere Selbstbilder und Elternbilder (speziell Vaterbilder) als die psychotischen Patienten und gesunde Personen. Die Beurteilungen der psychotischen Patienten unterschieden sich dagegen nicht besonders von jenen Gesunder. Das Selbstbild stand in Beziehung zu beiden Elternbildern bei den Borderline Patienten und den Gesunden, während bei den psychotischen Patienten nur das Mutterbild für das Selbstbild bedeutsam war. Außerdem konnte bei den psychotischen Patienten nicht zwischen den Polen der Kontrolle und Autonomie bzgl. der introjizierten Selbstbilder differenziert werden. Aus den Ergebnissen wird gefolgert, dass Borderline Patienten durch eine negative Bindung charackterisiert sind, psychotische Patienten dagegen durch

Recurrent suicide attempts in patients with depressive and anxiety disorders: The role of borderline personality traits

NARCIS (Netherlands)

C. Licht; M. Eikelenboom; prof Berno van Meijel; A.T. Beekman; dr Barbara Stringer; B. Koekkoek; A.J. Kerkhof; B.W. Penninx

2013-01-01

Background The presence of a comorbid borderline personality disorder (BPD) may be associated with an increase of suicidal behaviors in patients with depressive and anxiety disorders. The aim of this study is to examine the role of borderline personality traits on recurrent suicide

M42. Metacognitive Deficits in Schizophrenia; Comparisons With Borderline Personality Disorder and Substance Use Disorder

Science.gov (United States)

Buck, Kelly; Leonhardt, Bethany; George, Sunita; James, Alison; Vohs, Jenifer; Lysaker, Paul

2017-01-01

Abstract Background: Metacognition is a psychological function that includes a spectrum of mental activities. These activities involve thinking about thinking and range from more discrete acts, in which people recognize specific thoughts and feelings, to more synthetic acts in which an array of intentions, thoughts, feelings, and connections between events are integrated into larger complex representations. Recently, interest has arisen in the important role that metacognitive deficits may play in schizophrenia spectrum disorders. Research has found that many with schizophrenia experience compromised metacognitive capacity and the degree of impairment in metacognition has been linked to negative and disorganized symptoms, decrement in social functioning, and lower levels of subjective indicators of recovery. While metacognitive deficits have been broadly explored in schizophrenia, less is known about whether these deficits are similar or different than those found in other forms of serious mental illness. Methods: To explore this issue, we administered assessments of metacognition using the Metacognition Assessment Scale-Abbreviated, Alexithymia using the Toronto Alexithymia Scale and Social Cognition using the Bell Lysaker Emotion Recognition Scale to 65 adults with Schizophrenia, 34 adults with Borderline Personality Disorder (PD) and 32 adults with a Substance Use Disorder. We chose Borderline PD as our primary comparison because this group has also been found to have profound alterations in the ability to recognize and think about one’s own and others’ mental activities. We chose substance use disorder as a third psychiatric condition given that this is a common comorbidity of Borderline PD and Schizophrenia and because it has also been linked with deficits in the ability to reflect about mental states. Results: ANCOVA controlling for age revealed the Schizophrenia group had significant poorer overall metacognition compared to the other 2 groups while the

Sonographic evaluation of borderline hips in the newborn

International Nuclear Information System (INIS)

Rabassini, A.; Piovesan, L.; Rupeni, L.; Donadi, M.; Bacarini, L.; Gerardi, A.; Ortolani, M.

1991-01-01

Infant hips are classified, according to Graf, in 4 US types on the basis of the morphologic changes in both the cartilaginous and the bony roofs (type I, II, III, IV). Out of 6,000 examined hips, 170 (2.8%) were considered, which could be classified neither as type I (mature) nor as type II (delayed/immature ossification). These hips were called borderline hips. They exhibited some charecteristic US features: good bone modeling, rounded cotyle, and α angle 60 grades ±2. They were always observed during the first month of the patients' life. Anamnestic data were not specific (27.5% breech delivery, and 13% oligohydramnios); clinics sometimes overestimated tha actual anatomic development (64/170 cases with positivity of Ortolani's sign and/or restricted abduction; 25% of patients presented with no suspicious signs) Dynamic hip examination showed only physiological cranial deflection of the cartilaginous roof. Finally, borderline hips developed into type I hips in 99% of cases, within the third month of the patients' life

[Brownish coloration of the left nipple in a 60-year-old woman].

Science.gov (United States)

Blum, A; Hartmann, K W; Rütten, A

2010-01-01

Pigmented Paget disease of the nipple is a rare disease. We report on a 60-year-old woman in whom this diagnosis was made based on clinical findings, dermoscopy, histology and immunohistology. Circumscribed pigmentation of the nipple includes a wide spectrum of benign and malignant differential diagnostic considerations. Dermoscopy can enhance the clinical diagnosis. Biopsies should always be performed on unclear pigmentation of the nipple in both women and men. On histology, rare melanocytic tumors must be differentiated from pigmented Paget disease and pigmented Bowen disease. Pagetoid intraepithelial cells of a melanocytic tumor are positive for S100, HMB45 or melan A, but not for cytokeratins. Intraepithelial tumor cells of Paget disease are positive for cytokeratin 7. The clear cells in Bowen diseases are usually not positive for cytokeratin 7 and are also negative for all melanocytic markers.

Recurrent suicide attempts in patients with depressive and anxiety disorders : The role of borderline personality traits

NARCIS (Netherlands)

Stringer, Barbara; van Meijel, Berno; Eikelenboom, Merijn; Koekkoek, Bauke; Licht, Carmilla M. M.; Kerkhof, Ad J. F. M.; Penninx, Brenda W. J. H.; Beekman, Aartjan T. F.

2013-01-01

Background: The presence of a comorbid borderline personality disorder (BPD) may be associated with an increase of suicidal behaviors in patients with depressive and anxiety disorders. The aim of this study is to examine the role of borderline personality traits on recurrent suicide attempts.

The Melanocyte Fate in Neural Crest is Triggered by Myb Proteins through Activation of c-kit

Czech Academy of Sciences Publication Activity Database

Karafiát, Vít; Dvořáková, Marta; Pajer, Petr; Čermák, Vladimír; Dvořák, Michal

2007-01-01

Roč. 64, č. 21 (2007), s. 2975-2984 ISSN 1420-682X R&D Projects: GA MŠk(CZ) LC06061; GA ČR GA204/06/1728 Institutional research plan: CEZ:AV0Z50520514 Keywords : c-myb proto-oncogene * v-mybAMV oncogene * neural crest * cell fate determination * melanocytes * c-kit signal Subject RIV: EB - Genetics ; Molecular Biology Impact factor: 5.239, year: 2007

The experience of borderline phenomena through cinema: Guentin Tarantino's Reservoir dogs, true romance, and pulp fiction.

Science.gov (United States)

Ross, Donald R; Favero, Marcus

2002-01-01

The experience of many patients with borderline personality is intense and kaleidoscopic. These qualities may be represented in film in ways that reflect and convey their essential features that are less readily captured in words. Quentin Tarantino has produced a trilogy of films that bring to light and to life the borderline experience. We use these movies to illustrate and discuss five key borderline themes: the fluid nature of drive derivatives, the discontinuous experience of time and space, the coniflicted search for an idealized parent, antisocial distortions of the superego, and the organizing and stabilizing function of a central romantic fantasy.

Advance statements for borderline personality disorder: a qualitative study of future crisis treatment preferences.

Science.gov (United States)

Borschmann, Rohan; Trevillion, Kylee; Henderson, R Claire; Rose, Diana; Szmukler, George; Moran, Paul

2014-06-01

Little is known about the crisis treatment preferences of people with borderline personality disorder. Clinicians may also question service users' ability to make considered decisions about their treatment when in crisis. Therefore, this qualitative study aimed to investigate crisis treatment preferences of a sample of community-dwelling adults with borderline personality disorder. Participants were 41 adults with borderline personality disorder who had created joint crisis plans during a randomized controlled trial. Data from all 41 joint crisis plans were analyzed iteratively via a thematic analysis framework. Participants gave clear statements in their crisis plans relating to the desire to recover from the crisis and to improve their social functioning. Key themes included the desire to be treated with dignity and respect and to receive emotional and practical support from clinicians. Many participants spoke of the importance of connecting with others during periods of crisis, but several reported a clear desire to be left alone during a future crisis. Other themes concerned preferences for specific treatment refusals during crises, including particular types of psychotropic medication and involuntary treatment. The variation of participants' preferences underscores the importance of developing individually tailored crisis plans for people with borderline personality disorder. The need to be treated with dignity and respect and to be given autonomy in decision making--also identified in global surveys of people with severe mental illness--is important to people with borderline personality disorder. Key messages for clinicians, service users, and policy makers, in addition to staff training issues, are discussed.

Inflammatory myofibroblastic tumor of the larynx-a case report.

Science.gov (United States)

Do, Bao Anh; Varshney, Rickul; Zawawi, Faisal; Levental, Mark; Caglar, Derin; Young, Jonathan

2014-03-01

Inflammatory myofibroblastic tumor (IMT) is a borderline neoplasm with uncertain malignant potential. It is a rare disease also referred to as an inflammatory pseudotumor, a plasma cell granuloma, and an inflammatory fibrosarcoma. IMT rarely also involves the head and neck region with only 50 cases of laryngeal IMT reported in the literature, and this is the first case with reported magnetic resonance imaging (MRI) findings. A 37-year-old man with a 1-year history of hoarseness, dysphagia, and fatigue presented with a right vocal fold submucosal mass and was treated conservatively. The MRI of the neck revealed a mildly spontaneously hyperintense right true vocal fold on GRE images and relative hyperintensity on fat-saturation T2-weighted images. A biopsy of the right-sided submucosal laryngeal mass was performed and the pathologic examination revealed a lesion consistent with an IMT. IMT is a borderline neoplasm with uncertain malignant potential. There are many variants of IMT and its etiology is not truly understood. In general, IMT of the larynx has a benign clinical course with low rates of recurrence. Copyright © 2014 The Voice Foundation. Published by Mosby, Inc. All rights reserved.

Sleep EEG findings in ICD-10 borderline personality disorder in Egypt.

Science.gov (United States)

Asaad, Tarek; Okasha, Tarek; Okasha, Ahmed

2002-09-01

Previous work has demonstrated that patients with borderline personality disorder show some similarities to patients with major depression, especially regarding their sleep profile. This study aimed at investigating such a hypothesis in an Egyptian sample, considering the possible influence of cultural differences. All night polysomnographic assessments were made for 20 ICD-10 diagnosed borderline patients (without co-morbid depression), in addition to 20 patients with major depression and 20 healthy matched controls. The two patient groups differed significantly from controls in their sleep profile, especially regarding sleep continuity measures, decreased SWS and REM sleep abnormalities. High similarity was found in EEG sleep profile of the two patient groups, though the changes were more robust in patients with depression. The small number of subjects precluded finer analyses of sleep microstructure by depressive symptoms. The great similarity in EEG sleep profile between borderline personality disorder patients and patients with major depression suggests a common biological origin for both conditions, with the difference being 'quantitative' rather than 'qualitative'. Our data are all the more compelling in that the presumed personality disturbance in the Egyptian culture manifests neurophysiologically as in the Western world.

Primary intraosseous smooth muscle tumor of uncertain malignant potential: original report and molecular characterization

Directory of Open Access Journals (Sweden)

Lauren Kropp

2016-11-01

Full Text Available We report the first case of primary intraosseous smooth muscle tumor of uncertain malignant potential (STUMP which is analogous to borderline malignant uterine smooth muscle tumors so designated. The tumor presented in the femur of an otherwise healthy 30-year-old woman. Over a 3-year period, the patient underwent 11 biopsies or resections and 2 cytologic procedures. Multiple pathologists reviewed the histologic material including musculoskeletal pathologists but could not reach a definitive diagnosis. However, metastases eventually developed and were rapidly progressive and responsive to gemcitabine and docetaxel. Molecular characterization and ultrastructural analysis was consistent with smooth muscle origin, and amplification of unmutated chromosome 12p and 12q segments appears to be the major genomic driver of this tumor. Primary intraosseous STUMP is thought to be genetically related to leiomyosarcoma of bone, but likely representing an earlier stage of carcinogenesis. Wide excision and aggressive followup is warranted for this potentially life-threatening neoplasm.

Primary Intraosseous Smooth Muscle Tumor of Uncertain Malignant Potential: Original Report and Molecular Characterization.

Science.gov (United States)

Kropp, Lauren; Siegal, Gene P; Frampton, Garrett M; Rodriguez, Michael G; McKee, Svetlana; Conry, Robert M

2016-11-17

We report the first case of primary intraosseous smooth muscle tumor of uncertain malignant potential (STUMP) which is analogous to borderline malignant uterine smooth muscle tumors so designated. The tumor presented in the femur of an otherwise healthy 30-year-old woman. Over a 3-year period, the patient underwent 11 biopsies or resections and 2 cytologic procedures. Multiple pathologists reviewed the histologic material including musculoskeletal pathologists but could not reach a definitive diagnosis. However, metastases eventually developed and were rapidly progressive and responsive to gemcitabine and docetaxel. Molecular characterization and ultrastructural analysis was consistent with smooth muscle origin, and amplification of unmutated chromosome 12p and 12q segments appears to be the major genomic driver of this tumor. Primary intraosseous STUMP is thought to be genetically related to leiomyosarcoma of bone, but likely representing an earlier stage of carcinogenesis. Wide excision and aggressive follow-up is warranted for this potentially life-threatening neoplasm.

Modelling borderline and mild dysplasia associated with HPV 6 and 11 infection.

Science.gov (United States)

Chapman, Ruth; Soldan, Kate; Jit, Mark

2011-04-05

Low risk HPV types 6/11 are responsible for some low-grade cytological abnormalities. Most economic analyses of HPV vaccination have estimated the additional benefit of HPV 6/11 protection by the quadrivalent vaccine, over the bivalent, based on reduction of genital warts but have not included reduction in repeat smears and colposcopies due to low-grade abnormalities. We investigate the contribution of HPV types 6/11 to abnormal smears and associated costs in England. The risk of borderline or mild dysplasia due to HPV 6/11 infection was estimated from a study of type-specific HPV DNA in cervical screening specimens collected throughout England. A Markov model representing 10 million women with HPV 6/11 or with no HPV infection from 24 to 64 years was developed to estimate the number of abnormal smears, subsequent repeat smears and colposcopies due to HPV 6/11 associated with borderline or mild dysplasia. Fitting was achieved by varying the force of infection, probability of borderline or mild dysplasia if HPV-uninfected or infected with HPV 6/11 and the duration of infection. The relative risks of borderline or mild dysplasia when infected with HPV 6/11 compared to not being HPV infected were 6.32 (95% credible interval 1.56-25.6) and 17.5 (1.02-300) respectively. Using best fitting parameters we find the costs incurred are between £170 and £195 per abnormal smear due to infection with HPV 6/11. In England, the impact of cytological abnormalities due to HPV 6/11 is relatively small, but not negligible. A vaccine that protects against HPV 6/11 infections could reduce costs associated with borderline and mild dysplasia, and associated colposcopies. These benefits should be considered when formulating immunisation policy, if possible. Smears and colposcopies in those uninfected with HPV far outnumber those in women infected with HPV 6/11. Copyright © 2011 Elsevier Ltd. All rights reserved.

A New Perspective on the Pathophysiology of Borderline Personality Disorder: A Model of the Role of Oxytocin.

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Herpertz, Sabine C; Bertsch, Katja

2015-09-01

Borderline personality disorder is characterized by three domains of dysfunction: affect dysregulation, behavioral dyscontrol, and interpersonal hypersensitivity. Interpersonal hypersensitivity is associated with a (pre)attentive bias toward negative social information and, on the level of the brain, enhanced bottom-up emotion generation, while affect dysregulation results from abnormal top-down processes. Additionally, the problems of patients with borderline personality disorder in interpersonal functioning appear to be related to alterations in the (social) reward and empathy networks. There is increasing evidence that the oxytocinergic system may be involved in these domains of dysfunction and may thus contribute to borderline psychopathology and even open new avenues for targeted pharmacotherapeutic approaches. From studies in healthy and clinical subjects (including first studies with borderline personality disorder patients), the authors provide a conceptual framework for future research in borderline personality disorder that is based on oxytocinergic modulation of the following biobehavioral mechanisms: 1) the brain salience network favoring adaptive social approach behavior, 2) the affect regulation circuit normalizing top-down processes, 3) the mesolimbic circuit improving social reward experiences, and 4) modulating brain regions involved in cognitive and emotional empathy. In addition, preliminary data point to interactions between the oxytocin and cannabinoid system, with implications for pain processing. These mechanisms, which the authors believe to be modulated by oxytocin, may not be specific for borderline personality disorder but rather may be common to a host of psychiatric disorders in which disturbed parent-infant attachment is a major etiological factor.

Diagnostic difficulties in the differentiation of neurogenic tumors of the parapharyngeal space in helical CT evaluations: A case report

International Nuclear Information System (INIS)

Czerniewicz-Kaminska, A.; Nowicki, J.; Jazwiec, P.; Kedzierski, B.; Janeczek, T.; Wilczynski, K.; Prudlak, E.

2005-01-01

Computerized tomography (CT) with contrast infusion and magnetic resonance imaging (MRI) play important roles in establishing the place of origin of neurogenic tumors. In this article we do not compare these two methods, but focus on the crucial role of CT imaging in the estimation and differential diagnosis of these tumors. We present the case of a 50-year-old man with clinical symptoms of peritonsillar abscess, which appeared to be a neurogenic tumor. The images obtained were deemed ambiguous. The possibility of a parotid gland tumor or a tumor of neurogenic origin was assumed. In this case we observed atypical clinical and radiological symptoms. The final diagnosis was based on a combination of radiological, clinical, and microbiological features of the tumor. Thanks to the cooperation of many professionals, we managed to establish the diagnosis of neuroangiofibroma, which exemplifies a tumor of the borderline, including elements of the neurogenic sheath and connective and chromaffin tissue. (author)

Evaluation of the relationship between cognitive functioning in patients with borderline personality disorder and their general functioning.

Science.gov (United States)

Mosiołek, Anna; Gierus, Jacek; Koweszko, Tytus; Szulc, Agata

2018-02-28

The purpose of the study was to examine the relation between cognitive functioning in people with borderline personality disorder and their overall functioning level, as well as psychopathology intensification specific for this type of disorders. 64 patients aged 18-55 (M = 30.09) with borderline personality disorder (emotionally unstable personality - borderline type in the ICD-10) were examined. The study used: demographic-descriptive questionnaire, SCID II, Borderline Symptom Checlist-23, and Global Assessment of Functioning (GAF). For cognitive assessment, The Rey Auditory Verbal Learning Test, The Rey-Osterrieth Complex Figure test, TMTA, TMTB, verbal fluency test, Stroop test and Frontal Assessment Battery (FAB) were used. The average GAF score in the sample was M =43.65. Significant differences between the comorbidity group and non-comorbidity group were observed with respect to the GAF scores (Mann-Whitney U = 300.500, p = 0.008) as well as a number of significant (p borderline personality disorder. The obtained data seem to suggest that the cognitive functions affect the overall functioning only in patients with psychiatric co-morbidity. In people without psychiatric co-morbidity there is a relationship of cognitive functions only with certain aspects of psychopathology specific to BPD.

[The problems in dealing with the incest experiences of borderline patients].

Science.gov (United States)

Dulz, B; Schreyer, D

1997-11-01

Sexual and/or physical abuse can be found in large numbers in the history of severely disturbed borderline patients. The treatment of experiences of incest can induce new symptoms as well as reinforce still existing symptoms. Thus the free-floating anxiety, which is connected with the anxiety of impending doom in early childhood, can be reduced. During in-patient treatment the extent of free-floating anxiety of borderline patients can be reduced by the holding function of the therapeutic team. Reduction of the other symptoms can take place only subsequent to this. A therapy geared to the reduction of singular symptoms might be less successful.

Different aspects of emotional intelligence of borderline personality disorder

NARCIS (Netherlands)

Peter, Mathell; Arntz, Arnoud R; Klimstra, T.A.; Vingerhoets, A.J.J.M.

2018-01-01

Objectives: The present study investigated deficiencies in different components of emotional intelligence in borderline personality disorder (BPD). Method: The Mayer-Salovey-Caruso Emotional Intelligence Test (MSCEIT) and the Emotional Quotient Inventory (EQ-i) were used to assess EI dimensions. BPD

77 FR 18831 - Government-Owned Inventions; Availability for Licensing

Science.gov (United States)

2012-03-28

... Technology: Inflammatory processes associated with the over-production of tumor necrosis-alpha (TNF-[alpha... treat insulin resistance. Insulin resistance is associated with reduced gene expression and production... and at low levels in normal melanocytes. MART-1 is a melanocyte differentiation antigen found on the...

Schema therapy for borderline personality disorder : A comprehensive review of its empirical foundations, effectiveness and implementation possibilities

NARCIS (Netherlands)

Sempertegui Vallejo, G.A.; Karreman, A.; Arntz, A.; Bekker, M.H.J.

2013-01-01

Borderline personality disorder is a serious psychiatric disorder for which the effectiveness of the current pharmacotherapeutical and psychotherapeutic approaches has shown to be limited. In the last decades, schema therapy has increased in popularity as a treatment of borderline personality

Contrasting metacognitive, social cognitive and alexithymia profiles in adults with borderline personality disorder, schizophrenia and substance use disorder.

Science.gov (United States)

Lysaker, Paul H; George, Sunita; Chaudoin-Patzoldt, Kelly A; Pec, Ondrej; Bob, Petr; Leonhardt, Bethany L; Vohs, Jenifer L; James, Alison V; Wickett, Amanda; Buck, Kelly D; Dimaggio, Giancarlo

2017-11-01

Deficits in the ability to recognize and think about mental states are broadly understood to be a root cause of dysfunction in Borderline Personality Disorder (PD). This study compared the magnitude of those deficits relative to other forms of serious mental illness or psychiatric conditions. Assessments were performed using the metacognition assessment scale-abbreviated (MAS-A), emotion recognition using the Bell Lysaker Emotion Recognition Test and alexithymia using the Toronto Alexithymia Scale among adults with schizophrenia (n = 65), Borderline PD (n = 34) and Substance Use disorder without psychosis or significant Borderline traits (n = 32). ANCOVA controlling for age revealed the Borderline PD group had significantly greater levels of metacognitive capacity on the MAS-A than the schizophrenia group and significantly lower levels of metacognitive capacity than the Substance Use group. Multiple comparisons revealed the Borderline PD group had significantly higher self-reflectivity and awareness of the other's mind than the schizophrenia group but lesser mastery and decentration on the MAS-A than substance use group, after controlling for self-report of psychopathology and overall number of PD traits. The Borderline PD and Schizophrenia group had significantly higher levels of alexithymia than the substance use group. No differences were found for emotion recognition. Results suggest metacognitive functioning is differentially affected in different mental disorders. Published by Elsevier B.V.

Phorbol 12-myristate 13-acetate enhances nm23 gene expression in murine melanocytes but not in syngeneic B16-BL6 melanoma variants.

Science.gov (United States)

Huijzer, J C; McFarland, M; Niles, R M; Meadows, G G

1996-03-01

The nm23 gene has been described as a potential metastasis suppressor gene in certain rodent and human tumors. We previously demonstrated that tyrosine and phenylalanine restriction suppresses metastatic heterogeneity of B16-BL6 murine melanoma and selects for tumor variants with decreased metastatic potential. In this study, we investigated nm23 expression in the highly metastatic B16-BL6 (ND) melanoma, its nutritionally derived poorly metastatic (LT) variant, and the syngeneic non-tumorigenic Mel-ab melanocytes. No differences in nm23 expression were observed between ND and LT cells, and nm23 expression varied between different isolates. Previously, we showed that metastatic potential of 1-ND cells decreases and is not altered in 1-LT cells after prolonged in vitro cell passage; however, nm23 expression is equivalently increased by 2-fold. In 2-ND and 2-LT cells, expression of nm23 is not different at higher in vitro cell passage. Expression of nm23 decreased about 2-fold when phorbol 12-myristate 13-acetate (PMA) was removed from Mel-ab cells, which induces these cells to become quiescent. Although membrane-associated protein kinase C (PKC) activity decreased after prolonged PMA treatment in all cells, neither nm23 expression nor proliferation of ND and LT cells was affected by PMA. These data indicate that nm23 expression is related to proliferative activity rather than to the suppression of metastatic potential.

Ultrasonic elastography features of phyllodes tumors of the breast: a clinical research.

Directory of Open Access Journals (Sweden)

Lu-Jing Li

Full Text Available The purpose of this study was to analyze the ultrasonic elastography features of phyllodes tumors of the breast comparing with fibroadenomas. A retrospective database was queried for the patients diagnosed as phyllodes tumors and fibroadenomas at Sun Yat-sen Memorial Hospital from January 2008 to August 2012. Three hundred and fifty lesions from 323 consecutive patients were included in the study. All the cases were examined by conventional ultrasonography and ultrasound elastography. Ultrasound elastography was used to calculate strain ratio of the lesions with bilateral breast tissue at the same depth as reference. There were 36 phyllodes tumors (27 benign, 8 borderline, 1 malignant and 314 fibroadenomas (158 the pericanalicular type, 103 the intracanalicular type, 53 other special types. The strain ratio for phyllodes tumors (3.19 ± 2.33 was significantly higher than for fibroadenomas (1.69 ± 0.88 (p<0.05. The Spearman(.s correlation coefficient between strain ratio of ultrasound elastography and pathological groups was significant, with a value of 0.17 (p<0.05. Ultrasound elastography could provide additional information to differentiate phyllodes tumors from fibroadenoma in breast.

MRI features in differentiation borderline from benign mucinous ovarian cystadenoma

International Nuclear Information System (INIS)

Zhao Shuhui; Qiang Jinwei; Zhang Guofu; Qiu Haiying; Wang Xuezhen; Wang Li

2012-01-01

Objective: To investigate MRI features for differentiating borderline from benign mucinous cystadenoma (MC) of the ovary. Methods: Twenty three patients with 23 benign MCs and 19 patients with 20 borderline mucinous cystadenomas (BMC)proven by surgery and pathology underwent MRI, with 23 benign MCs and 20 BMC. MRI features of tumor were evaluated and compared between two groups including location, shape, size, loculation, signal intensity of the fluid, thickness of septa and wall, and vegetations. The findings were correlated with those of pathology. The loculation, the signal intensity of the intracystic content, the thickness of the septation and the wall, and the vegetations between the benign MCs and the BMCs were compared using the Chi-square test.Results Homogenous low signal on T 1 WI and homogenous high signal on T 2 WI were the main signal patterns of benign MC seen more commonly in benign MC (18/23 and 17/23, respectively) than in BMC (5/20 and 8/20, respectively) (χ 2 =12.1979, 5.0553; P<0.05). The honeycomb loculi, high signal on T 1 WI, low signal on T 2 WI, thickened septa or wall (≥5 mm), and vegetations (≥5 mm) were significantly more common in BMC (10/20, 9/20, 8/20, 10/20 and 14/20, respectively) than in benign MC(4/23, 3/23, 1/23, 1/23 and 1/23, respectively) (χ 2 =5.1804, 5.4300, 8.2163, 11.7113 and 20.2990, P<0.05), with the sensitivity and specificity for characterizing BMC of 50.0% and 82.6%, 45.0% and 87.0%, 40.0% and 95.7%, 50.0% and 95.7%, and 70.0% and 95.7%, respectively. When one of honeycomb loculi with low signal on T 2 WI, thickened septa or wall (≥5 mm), and vegetations (≥5 mm) were found, the sensitivity, specificity and accuracy for characterizing BMC were 90.0%, 91.3% and 90.7% respectively. Conclusion: MRI is accurate for demonstrating morphological features of ovarian MC which well correlated to pathological characteristics, and for differentiating BMC from benign MC, thus helpful for making surgery strategy. (authors)

Parenting of children with borderline to mild intellectual disability

NARCIS (Netherlands)

Kleefman, Marijke

2015-01-01

Raising children with borderline to mild intellectual disability (BMID) may cause parenting stress, especially when the child with BMID has psychosocial problems. To improve support, it is important to have a better understanding of the effectiveness of interventions to reduce problems in raising

Aspirin reduces serum anti-melanocyte antibodies and soluble interleukin-2 receptors in vitiligo patients

International Nuclear Information System (INIS)

Zailaie, Mohamad Z.

2005-01-01

Increased serum levels of certain immunologic markers including immunoglobulin G (IgG) anti-melanocyte/ vitiligo antibodies (V-IgG) and soluble interleukin-2 receptors (sIL-2R) are associated with augmented humoral and cellular immunity involved in melanocyte cytotoxicity during the active phase of non-segmental vitiligo. Recent reports have shown that, aspirin possesses a wide range of immunomodulatory and antioxidant properties. Therefore, the aim of the present study is to investigate the effect of long-term treatment of vitiligo patients with low-dose oral aspirin on serum V-IgG activity and sIL-2R concentration. The present study was carried out at the Vitiligo Unit, King Abdul-Aziz University Medical Center, Jeddah, Kingdom of Saudi Arabia between March and October 2003. Eighteen female and 14 male patients with a recent onset of non-segmental vitiligo were divided into 2 equal groups. One group received a daily single dose of oral aspirin (300 mg) and the second group received only placebo for a period of 12 weeks. Serum V-IgG activity and sIL-2R concentration were determined before and at the end of treatment period. The V-IgG activity was measured using cellular enzyme-linked immunosorbent assay (ELISA) following incubation of IgG antibodies with an adult cultured melanocytes. Serum sIL-2R concentration was measured using the highly sensitive quantitative sandwich ELISA utilizing a commercially available kit. As expected, the serum V-IgG activity and sIL-2R concentration of the active vitiligo patients (0.81 +/- 0.23 optical density (O.D.), 1428 +/- 510 pg/ml) were significantly increased compared with that of controls (0.27 +/- 0.1 O.D., 846 +/- 312 pg/ml; p<0.05, p<0.01). Aspirin-treated vitiligo patients showed significant decrease in serum V-IgG activity and sIL-2R concentration (0.32 +/- 0.08 O.D., 756 +/- 216 pg/ml) compared with that of placebo-treated patients (0.83 +/- 0.19 O.D., 1327 +/- 392 pg/ml; p<0.01). Low-dose oral aspirin treatment of

Recent Updates in Melanocyte Function: The Use of Promising Bioactive Compounds for the Treatment of Hypopigmentary Disorders.

Science.gov (United States)

Ali, Sharique A; Naaz, Ishrat; Zaidi, Kamal Uddin; Ali, Ayesha S

2017-01-01

Skin pigmentation is a broadly appearing phenomenon in nature which plays an important task of determining the appearance and biology of all vertebrates including human beings. Skin color is a crucial attribute, determined by the synthesis of melanin pigment within melanocytes by the process of melanogenesis and is regulated by many extrinsic as well as intrinsic factors. Tyrosinase catalyzes the key step of melanogenesis, dysfunction of tyrosinase leads to reduce melanin production which results in severe clinical and aesthetical problems of hypopigmentation. Therefore, the regulation of melanin production is an important strategy in the treatment of abnormal skin pigmentation for cosmetic and medicinal purpose. The present review covers the various aspects of mammalian melanocyte biology which will help in the identification of key regulators of melanogenesis from pharmaceutical and pharmacological point of view. Further sections of the review focus on the dysfunctions of melanogenic pathways, which result in severe clinical and aesthetical problems of hypopigmentation. We have also attempted to highlight the ability of available scientifically validated plant extracts to naturally enhance melanin synthesis in order to cure hypopigmentation. Copyright© Bentham Science Publishers; For any queries, please email at epub@benthamscience.org.

Comparing the experience of voices in borderline personality disorder with the experience of voices in a psychotic disorder: A systematic review.

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Merrett, Zalie; Rossell, Susan L; Castle, David J

2016-07-01

In clinical settings, there is substantial evidence both clinically and empirically to suggest that approximately 50% of individuals with borderline personality disorder experience auditory verbal hallucinations. However, there is limited research investigating the phenomenology of these voices. The aim of this study was to review and compare our current understanding of auditory verbal hallucinations in borderline personality disorder with auditory verbal hallucinations in patients with a psychotic disorder, to critically analyse existing studies investigating auditory verbal hallucinations in borderline personality disorder and to identify gaps in current knowledge, which will help direct future research. The literature was searched using the electronic database Scopus, PubMed and MEDLINE. Relevant studies were included if they were written in English, were empirical studies specifically addressing auditory verbal hallucinations and borderline personality disorder, were peer reviewed, used only adult humans and sample comprising borderline personality disorder as the primary diagnosis, and included a comparison group with a primary psychotic disorder such as schizophrenia. Our search strategy revealed a total of 16 articles investigating the phenomenology of auditory verbal hallucinations in borderline personality disorder. Some studies provided evidence to suggest that the voice experiences in borderline personality disorder are similar to those experienced by people with schizophrenia, for example, occur inside the head, and often involved persecutory voices. Other studies revealed some differences between schizophrenia and borderline personality disorder voice experiences, with the borderline personality disorder voices sounding more derogatory and self-critical in nature and the voice-hearers' response to the voices were more emotionally resistive. Furthermore, in one study, the schizophrenia group's voices resulted in more disruption in daily functioning

Multidirectional Vector Excision Leads to Better Outcomes than Traditional Elliptical Excision of Facial Congenital Melanocytic Nevus

Directory of Open Access Journals (Sweden)

Seung Il Oh

2013-09-01

Full Text Available Background The elliptical excision is the standard method of removing benign skin lesions,such as congenital melanocytic nevi. This technique allows for primary closure, with little to nodog-ear deformity, but may sacrifice normal tissue adjacent to the lesion, resulting in scarswhich are unnecessarily long. This study was designed to compare the predicted results ofelliptical excision with those resulting from our excision technique.Methods Eighty-two patients with congenital melanocytic nevus on the face were prospectivelystudied. Each lesion was examined and an optimal ellipse was designed and marked onthe skin. After an incision on one side of the nevus margin, subcutaneous undermining wasperformed in the appropriate direction. The skin flap was pulled up and approximated alongseveral vectors to minimize the occurrence of dog-ear deformity.Results Overall, the final wound length was 21.1% shorter than that achieved by ellipticalexcision. Only 8.5% of the patients required dog-ear repair. There was no significant distortionof critical facial structures. All of the scars were deemed aesthetically acceptable based ontheir Patient and Observer Scar Assessment Scale scores.Conclusions When compared to elliptical excision, our technique appears to minimize dogeardeformity and decrease the final wound length. This technique should be considered analternative method for excision of facial nevi.

Borderline Personality Disorder in an Intermediate Psychological Therapies Service

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Ryan, Seamus; Danquah, Adam N.; Berry, Katherine; Hopper, Mary

2017-01-01

The intermediate psychological therapies service is provided for individuals referred with common mental health problems within the primary care psychological therapies service, but whose difficulties are longstanding and/or complex. The prevalence of borderline personality disorder (BPD) in intermediate psychological therapy services has not been…

Facilitation of self-empowerment of women living with borderline ...

African Journals Online (AJOL)

Background: Borderline personality disorder is characterised by a pattern of instability in interpersonal relationships, self-image, affects and marked impulsivity. Objective: The objective is to define the central concept of “facilitation of self- empowerment”. Method: Analysis and synthesis reasoning methods as indicated by ...

Autonomic Impairment in Borderline Personality Disorder: A Laboratory Investigation

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Weinberg, Anna; Klonsky, E. David; Hajcak, Greg

2009-01-01

Recent research suggests that emotional dysfunction in psychiatric disorders can be reflected in autonomic abnormalities. The present study examines sympathetic and parasympathetic autonomic nervous system activity in individuals with Borderline Personality Disorder (BPD) before, during, and following a social stressor task. Data were obtained…

Use of dialectical behavior therapy in inpatient treatment of borderline personality disorder: a systematic review.

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Bloom, Jill Myerow; Woodward, Eva N; Susmaras, Teresa; Pantalone, David W

2012-09-01

Dialectical behavior therapy (DBT) is an empirically supported treatment for outpatients with borderline personality disorder. However, the utility of DBT strategies for inpatients with the disorder is unclear. This review summarizes and synthesizes findings from trials of DBT in inpatient settings. Multiple research databases were searched for articles published through June 2011 that reported on any implementation of DBT in an inpatient setting to address symptoms related to borderline personality disorder, including suicidal and self-injurious behavior. Eleven studies that reported pre- and posttreatment symptoms related to borderline personality disorder were evaluated. Studies indicated that many variations of standard DBT have been used in inpatient settings, including approaches that do not include phone consultation, that include group therapy only, and that vary in treatment duration (from two weeks to three months). Most studies reported reductions in suicidal ideation, self-injurious behaviors, and symptoms of depression and anxiety, whereas results for reducing anger and violent behaviors were mixed. Follow-up data indicated that symptom reduction was often maintained between one and 21 months posttreatment. On the basis of the evidence, the authors identify essential components of an inpatient DBT package and discuss its potential function as an "intensive orientation" to outpatient DBT services. There is considerable variation in the configuration and duration of DBT implementation for inpatients with borderline personality disorder. However, findings suggest that DBT may be effective in reducing symptoms related to borderline personality disorder in inpatient settings. Future research should standardize and systematically test inpatient DBT. (Psychiatric Services 63:881-888, 2012; doi: 10.1176/appi.ps.201100311).

Immunohistochemical Expression of FXR1 in Canine Normal Tissues and Melanomas.

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Nordio, Laura; Marques, Andreia T; Lecchi, Cristina; Luciano, Alberto M; Stefanello, Damiano; Giudice, Chiara

2018-04-01

Fragile X mental retardation-related protein 1 (FXR1) is a cytoplasmic RNA-binding protein highly conserved among vertebrates. It has been studied for its role in muscle development, inflammation, and tumorigenesis, being related, for example, to metastasizing behavior in human and canine uveal melanoma. Anti-FXR1 antibodies have never been validated in the canine species. To investigate FXR1 expression in canine melanocytic tumors, the present study tested two commercially available polyclonal anti-human FXR1 antibodies, raised in goat and rabbit, respectively. The cross-reactivity of the anti-FXR1 antibodies was assessed by Western blot analysis, and the protein was localized by IHC in a set of normal canine tissues and in canine melanocytic tumors (10 uveal and 10 oral). Western blot results demonstrated that the antibody raised in rabbit specifically recognized the canine FXR1, while the antibody raised in goat did not cross-react with this canine protein. FXR1 protein was immunodetected using rabbit anti-FXR1 antibody, in canine normal tissues with different levels of intensity and distribution. It was also detected in 10/10 uveal and 9/10 oral melanocytic tumors. The present study validated for the first time the use of anti-FXR1 antibody in dogs and highlighted different FXR1 protein expression in canine melanocytic tumors, the significance of which is undergoing further investigations.

Exploring the Moderating Role of Problematic Substance Use in the Relations Between Borderline and Antisocial Personality Features and Intimate Partner Violence.

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Armenti, Nicholas A; Snead, Alexandra L; Babcock, Julia C

2018-02-01

Borderline and antisocial personality features relate to multiple externalizing behaviors, including intimate partner violence (IPV). However, not all individuals with borderline and antisocial traits perpetrate IPV. The strength of the personality-IPV link may be related to problematic substance use. We examined borderline and antisocial personality features, problematic substance use, and IPV in a community sample of couples. Positive relations between both borderline and antisocial features and IPV were stronger in conditions of high problematic alcohol use relative to low problematic alcohol use. Alcohol misuse may be an important factor to consider for IPV reduction in men with these personality features.

Stereological estimation of nuclear volume in benign and malignant melanocytic lesions of the skin. Inter- and intraobserver variability of malignancy grading

DEFF Research Database (Denmark)

Sørensen, Flemming Brandt; Ottosen, P D

1991-01-01

The volume-weighted, mean nuclear volume (nuclear vv) may be estimated without any assumptions regarding nuclear shape using modern stereological techniques. As a part of an investigation concerning the prospects of nuclear vv for classification and malignancy grading of cutaneous melanocytic tum...

Interpersonal Precipitants and Suicide Attempts in Borderline Personality Disorder

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Brodsky, Beth S.; Groves, Shelly A.; Oquendo, Maria A.; Mann, J. John; Stanley, Barbara

2006-01-01

Borderline personality disorder (BPD) is often characterized by multiple low lethality suicide attempts triggered by seemingly minor incidents, and less commonly by high lethality attempts that are attributed to impulsiveness or comorbid major depression. The relationships among life events, impulsiveness, and type of suicidal behavior has hardly…

Sex bias in classifying borderline and narcissistic personality disorder

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Braamhorst, W.; Lobbestael, J.; Emons, W.H.M.; Arntz, A.; Witteman, C.L.M.; Bekker, M.H.J.

2015-01-01

This study investigated sex bias in the classification of borderline and narcissistic personality disorders. A sample of psychologists in training for a post-master degree (N = 180) read brief case histories (male or female version) and made DSM classification. To differentiate sex bias due to sex

Bullied by Peers in Childhood and Borderline Personality Symptoms at 11-Years of Age: A Prospective Study

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Wolke, Dieter; Schreier, Andrea; Zanarini, Mary C.; Winsper, Catherine

2012-01-01

Background: Abuse by adults has been reported as a potent predictor of borderline personality disorder (BPD). Unclear is whether victimisation by peers increases the risk of borderline personality symptoms. Method: The Avon Longitudinal Study of Parents and Children (ALSPAC) prospective, longitudinal observation study of 6050 mothers and their…

Diagnosing Borderline Personality Disorder: Examination of How Clinical Indicators Are Used by Professionals in the Health Setting

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Treloar, Amanda Jane Commons; Lewis, Andrew J.

2009-01-01

This paper reviews the history of the recognition of borderline personality disorder as a clinical disorder, followed by a review of the contemporary practice of diagnosing borderline personality disorder in psychiatric settings. Many researchers have cautioned against the conflation of difficult patients with the diagnostic category of borderline…

[Differential diagnosis between borderline personality disorder and bipolar disorder].

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Herbst, Luis

2010-01-01

The relationship between bipolar disorder and borderline personality disorder remains controversial since in both conditions there are overlapping and similar symptomatic dimensions. Symptomatic dimensions suitable to subserve differential diagnosis are: mood, mood variability mode, and personal and family history. Characteristics of psychotic symptoms may also be useful in the differentiation. On the other hand, anxiety symptoms, neuropsychological profiles, neuro-imaging procedures and biomarkers seem not to contribute to differentiate between both diseases. The presentation of nonsuicidal self mutilation behavior can offer some differences between bipolar and borderline personality disorders, but both can coexist in clinical comorbid forms and do not significantly contribute to the differential diagnosis. Differential diagnosis is complicated by the fact that a low percentage of patients can experience comorbidity of both conditions. In this work we review all these issues, and particularly emphasize the importance of sitematically take into account the patient background, the course that follows his or her disorder, together with the outcome in response to medical decisions.

Parent-child interaction over time in families of young children with borderline intellectual functioning.

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Fenning, Rachel M; Baker, Jason K; Baker, Bruce L; Crnic, Keith A

2014-06-01

A previous study suggested that mothers of 5-year-old children with borderline intellectual functioning displayed lower positive engagement with their children as compared with both mothers of typically developing children and mothers of children with significant developmental delays (Fenning, Baker, Baker, & Crnic, 2007). The current study integrated father data and followed these families over the subsequent 1-year period. Parent and child behavior were coded from naturalistic home observations at both waves. Results revealed that mothers of children with borderline intellectual functioning displayed a greater increase in negative-controlling parenting from child age 5 to 6 than did other mothers; fathers displayed more negative-controlling behavior in comparison to fathers of typically developing children. In addition, children with borderline intellectual functioning themselves exhibited a more significant escalation in difficult behavior than did typically developing children. Cross-lagged analyses for the sample as a whole indicated that maternal negative-controlling behavior predicted subsequent child difficulties, whereas negative paternal behavior was predicted by earlier child behavior. In conjunction with evidence from Fenning et al. (2007), these findings suggest a complex, dynamic, and systemic developmental pattern in the emotional behavior of families of children with borderline intellectual functioning. Implications and areas in need of additional research are discussed. PsycINFO Database Record (c) 2014 APA, all rights reserved.

Association of Multiple Melanocytic Naevi with Education, Sex and Skin Type. A Northern Finland Birth Cohort 1966 Study with 46 Years Follow-up.

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Sinikumpu, Suvi-Päivikki; Huilaja, Laura; Jokelainen, Jari; Auvinen, Juha; Timonen, Markku; Tasanen, Kaisa

2017-02-08

Having multiple melanocytic naevi (sex, socioeconomic status (education) in childhood and adulthood, skin type and sunbathing habits. The prevalence of multiple melanocytic naevi was 11.6% (223/1,930). Higher education (odds ratio (OR) 2.11, 95% confidence interval (95% CI) 1.51-2.96), male sex (OR 1.48, 95% CI 1.07-2.06), sun-sensitive skin type (OR 2.09, 95% CI 1.34-3.27) and regular use of sunscreen (OR 2.03, 95% CI 1.23-3.37) were associated with increased risk of multiple naevi. Inflammatory skin diseases decreased (OR 0.49, 95 CI% 0.33-0.72) the risk of multiple naevi. In conclusion, several risk factors were found for multiple naevi among adults living in high latitudes, in Northern Finland.

Dysfunctional Affect Regulation : in borderline personality disorder and somatoform disorder

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van Dijke, A.

2011-01-01

The aim of this dissertation was to provide a systematic exploration of the nature and distribution of dysfunctional affect regulation, its associated phenomena, and retrospectively reported potentially traumatizing events in 475 patients diagnosed with borderline personality disorder (BPD),

Exploring the Association between Emotional Abuse and Childhood Borderline Personality Features: The Moderating Role of Personality Traits

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Gratz, Kim L.; Latzman, Robert D.; Tull, Matthew T.; Reynolds, Elizabeth K.; Lejuez, C. W.

2011-01-01

Most of the extant literature on borderline personality disorder has focused on the course, consequences, and correlates of this disorder among adults. However, little is known about childhood borderline personality (BP) features, or the factors associated with the emergence of BP pathology in childhood. A greater understanding of childhood BP…

Study of relation of cognitive emotion regulation styles with impulsivity and borderline personality disorder among university students

Directory of Open Access Journals (Sweden)

mozafar Ghaffari

2014-01-01

Full Text Available Background : Cognitive emotion regulation plays an immense role to control mental disorders. The aim of this research was to study the relationship between cognitive emotion regulation styles and impulsivity and students, borderline personality disorders.   Materials and Methods: Statistical samples of this study included 200 students of Pyam-e-Noor university. Cognitive Emotion Regulation Questionnaire (CERQ, Barrat Impulsivity Scale (BIS and Borderline Personality Scale (STB have been used for data collection. The data was analyzed using Pearson correlation coefficient and multiple regression analysis.   Results: Between variable of borderline personality disorder, and styles self-blame, rumination, catastrophizing and blaming others there was a positive correlation, but a negative relationship with acceptance, positive refocusing and positive reappraisal styles was observed (p>0.05. There was a positive relationship between variable of impulsivity with styles of self-blame, rumination, catastrophizing and blaming others, but had a negative relationship with acceptance, positive refocusing and positive reappraisal styles (p>0.05. The results of multi-variable correlation coefficient with Enter method indicated that cognitive emotion regulation styles play a role in explaining borderline personality disorder (R2= 0.646 and impulsivity (R2= 0.645.  Conclusion: Training the effective strategies of cognitive emotion regulation should be considered as a part of the intervention in the treatment of impulsivity and borderline personality disorder.

Podoplanin-positive Cancer-associated Stromal Fibroblasts in Primary Tumor and Synchronous Lymph Node Metastases of HER2-overexpressing Breast Carcinomas.

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Niemiec, Joanna; Adamczyk, Agnieszka; Harazin-Lechowska, Agnieszka; Ambicka, Aleksandra; Grela-Wojewoda, Aleksandra; Majchrzyk, Kaja; Kruczak, Anna; Sas-Korczyńska, Beata; Ryś, Janusz

2018-04-01

We compared the status of stromal podoplanin-positive cancer-associated fibroblasts (ppCAFs) between primary tumors and paired synchronous lymph node metastases (LNMs) and analyzed the prognostic significance of tumoral ppCAFs in 203 patients with human epidermal growth factor receptor 2-positive breast carcinoma. ppCAFs were found in 167/203 and in 35/87 tumors and LNM, respectively. ppCAFs were most frequently found in tumors and corresponding LNM (n=52, 59.8%; p=0.001). However, for all LNMs (n=12) without ppCAFs, their paired tumors also lacked ppCAFs. In both tumors and LNMs, ppCAFs were α-smooth muscle actin-positive and cluster of differentiation 21 protein-negative, suggesting them not to be resident lymph node cells. Moreover, in our series, the presence of ppCAFs in tumors was borderline related to poor disease-free survival (p=0.058). These results speak in favor of a hypothesis suggesting ppCAFs accompany metastatic cancer cells migrating from tumor to LNMs. Copyright© 2018, International Institute of Anticancer Research (Dr. George J. Delinasios), All rights reserved.

Mild neurological impairment may indicate a psychomotor endophenotype in patients with borderline personality disorder.