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Sample records for borderline melanocytic tumor

  1. [Molecular diagnosis of melanocytic tumors].

    PubMed

    Bauer, J

    2016-01-01

    Melanoma therapy has undergone a paradigm shift. Classic chemotherapies with poor treatment responses have been replaced by modern immune checkpoint blockades and targeted therapies with excellent responses. The latter require precise diagnosis of mutations in the melanoma genome as molecular targets for the small molecules. The diagnosis of melanomas has also been supplemented by molecular techniques. Differential diagnosis of melanoma and melanoma simulators such as atypical Spitz nevi can be supported by fluorescence in situ hybridization (FISH) and comparative genomic hybridization (CGH). Here we review the indications and methods for molecular diagnosis of melanocytic tumors.

  2. GI tract tumors with melanocytic differentiation.

    PubMed

    Karamchandani, Dipti M; Patil, Deepa T; Goldblum, John R

    2013-11-01

    Gastrointestinal (GI) tract tumors with melanocytic differentiation may present significant diagnostic challenges both for the pathologist and the clinician. This comprehensive review discusses the relatively common as well as rare entities that have melanocytic differentiation in the GI tract. Clinical, histologic, immunohistochemical and molecular features are discussed along with prognosis and differential diagnosis.

  3. Borderline ovarian tumors: a review of treatment.

    PubMed Central

    Chambers, J. T.

    1989-01-01

    Borderline ovarian tumors have an excellent prognosis. In stage I disease, no therapy in addition to surgery is needed, and conservation of ovarian tissue for future childbearing may be appropriate. In advanced stages, the use of adjuvant therapy has not consistently led to cures, and complications have been reported. A randomized study of no adjuvant therapy versus adjuvant treatment with long-term follow-up will be necessary to determine the efficacy of additional treatment. PMID:2556863

  4. The ultrastructure of conjunctival melanocytic tumors.

    PubMed Central

    Jakobiec, F A

    1984-01-01

    The ultrastructure of conjunctival melanocytic lesions in 49 patients was evaluated to find significant differences between benign and malignant cells. The patients studied included 9 with benign epithelial (racial) melanosis, 2 with pigmented squamous cell papillomas, 16 with conjunctival nevi, 18 with primary acquired melanosis, and 11 with invasive nodules of malignant melanoma. In benign epithelial melanosis, dendritic melanocytes were situated along the basement membrane region of the conjunctival epithelium, with one basilar dendritic melanocyte lodged among every five or six basilar keratinocytes. The dendritic melanocytes extended arborizing cellular processes between the basilar and among the suprabasilar keratinocytes, which manifested considerable uptake of melanin granules into their cytoplasm. The benign dendritic melanocytes possessed nuclei with clumped heterochromatin at the nuclear membrane, small, tightly wound nucleoli, and large, elongated, fully melaninized melanin granules. In two patients with benign hyperplasia of the dendritic melanocytes, occasional dendritic melanocytes were located in a suprabasilar position, but were always separated from each other by keratinocytes or their processes. In the two black patients with benign pigmented squamous papillomas, the benign dendritic melanocytes were located hapharzardly at all levels of the acanthotic epithelium and not just along the basement membrane region. Melanin uptake by the proliferating keratinocytes was minimal. In benign melanocytic nevi of the conjunctiva, nevus cells within the intraepithelial junctional nests displayed a more rounded cellular configuration; short villi and broader cellular processes suggestive of abortive dendrites were found. The nuclear chromatin pattern was clumped at the nuclear membrane, but the nucleoli were somewhat larger than those of benign dendritic melanocytes in epithelial melanosis. The melanosomes were smaller and rounder than those in dendritic

  5. Extremely rare borderline phyllodes tumor in the male breast: a case report.

    PubMed

    Kim, Jung Gyu; Kim, Shin Young; Jung, Hae Yoen; Lee, Deuk Young; Lee, Jong Eun

    2015-01-01

    Phyllodes tumor of the male breast is an extremely rare disease, and far fewer cases of borderline phyllodes tumors than benign or malignant tumors in the male breast have been reported. We report a case of borderline phyllodes tumor in the male breast with imaging findings of the tumor and pathologic correlation.

  6. An unusual case of a borderline Brenner tumor associated with bilateral serous cystadenoma and endometrial carcinoma.

    PubMed

    Cruz-Galarza, Daniel; Pérez-Rodríguez, Omar; Laboy-Torres, Joaquín; Gutiérrez-Rivera, Silvia

    2014-01-01

    Brenner tumor accounts for 1.5 to 2.5% of ovarian tumors. Nearly all are benign and 1% malignant. Less than twenty-five cases of borderline Brenner tumor have been reported worldwide. Our case is the first one related to a bilateral ovarian serous cystadenofibroma and endometrioid adenocarcinoma. This unusual case increases the limited data for borderline Brenner tumors.

  7. Incidentally Discovered Extensive Squamous Metaplasia within Borderline Phyllodes Tumor: Presentation of a Rare Tumor.

    PubMed

    Uğraş, Nesrin; Tolunay, Şahsine; Öz Atalay, Fatma; Gökgöz, Şehsuvar

    2016-01-01

    Phyllodes tumors are uncommon biphasic fibroepithelial neoplasms of breast, comprising less than 1% of all breast neoplasms. We therefore aimed to present the case with its microscopic findings. In this article, we report a 59-year-old female admitted to the general surgery department with a rapidly, enlarging, palpable mass in right breast. After histopathological examination, it was diagnosed as borderline phyllodes tumor with extensive squamous metaplasia. Metaplastic changes are infrequent in the stromal and epithelial component of these tumors. Extensive squamous metaplasia within phyllodes tumor is rare and may occur in benign, borderline and malign subtypes.

  8. Mucinous Borderline Ovarian Tumor in Very Old Aged Postmenopausal Woman

    PubMed Central

    Lee, Seung-Hee; Lee, Hae-Hyeog; Lee, Arum; Kim, Yeon-Suk; Jeon, Dong-Su; Kwak, Jeong Ja; Yang, Yo-Sep

    2015-01-01

    Mucinous borderline ovarian tumors (BOTs) occur most often in women between the ages of 20 and 30. Early-stage detection of the condition has a more favorable prognosis. In this case report, the authors present an elderly 93-year old woman who visited our hospital due to severe abdominal pain after being diagnosed with a pelvic mass 2 years ago and not undergoing any treatment since the diagnosis was made. She underwent emergency left salpingo-oophorectomy and was diagnosed with mucinous BOT according to biopsy results. PMID:26793682

  9. Morphological features of melanocytic tumors with depigmented halo: review of the literature and personal results.

    PubMed

    Nedelcu, Roxana Ioana; Zurac, Sabina Andrada; Brînzea, Alice; Cioplea, Mirela Daniela; Turcu, Gabriela; Popescu, Raluca; Popescu, Cătălin Mihai; Ion, Daniela Adriana

    2015-01-01

    Halo (Sutton's) phenomenon has been described as a depigmented halo that is associated most commonly with acquired melanocytic nevi; but it may be associated with various types of melanocytic skin tumors, melanoma being the most concerning. Different authors have been preoccupied with elucidating morphological features of melanocytic tumors associated with a depigmented halo. We reviewed the literature and discussed the main features of melanocytic halo tumors regarding histopathological, immune microenvironment profile and dermatoscopic appearance. We highlighted similarities and differences between Sutton's nevus and halo melanoma, also presenting relevant aspects of our results. Depigmented halo must be regarded as a phenomenon that may be associated with different types of melanocytic tumors and with a broad spectrum of histopathological atypia degree. Certain correlations between the shape, diameter, symmetry observed in clinical examination, histopathological appearance, dermatoscopic aspect of peritumoral halo and central tumor type could not be established due to insufficient data and contrasting results. Further studies are expected to add valuable information regarding the depigmented halo tumors features.

  10. Mucinous borderline ovarian tumor: a case report with diagnostic insights on ultrasound findings

    PubMed Central

    Śniadecki, Marcin; Bianek-Bodzak, Agnieszka; Liro, Marcin; Szurowska, Edyta

    2016-01-01

    Borderline ovarian tumors represent about 10% of all epithelial ovarian cancers, but in contrast to epithelial ovarian cancers, they constitute a group of tumors with a much better prognosis. An assessment of clinical presentation, physical examination, radiological and biochemical findings is necessary to tailor management strategies for patients with ovarian tumors. The article, which is based on a case report, describes different approaches for preoperative diagnosis as well as discusses approaches that might bring some insights on tumor histology. Furthermore, it raises a question about which imaging techniques should be proposed for a reliable diagnosis of borderline ovarian tumors to ensure safe surgery planning. PMID:28138412

  11. The molecular pathology of ovarian serous borderline tumors.

    PubMed

    Malpica, A; Wong, K-K

    2016-04-01

    Molecular studies in ovarian serous borderline tumors (OSBTs) have been used to understand different aspects of this neoplasm. (i) Pathogenesis, Kras and Braf mutations represent very early events in the tumorigenesis of OSBT as both are detected in serous cystadenomas associated with OSBTs. In contrast, serous cystadenomas without OSBTs do not show Kras or Braf mutations. In OSBTs, Kras mutations range from 17% to 39.5%, while Braf mutations range from 23% to 48%. The former is comparable with the range of Kras mutations in ovarian low-grade serous carcinomas (OLGSCa), 19%-54.5%. In contrast, Braf mutations in OLGSCa range from 0% to 33%. Serous cystadenomas appear to progress to OSBT due to a Braf mutation, but this mutation is rarely involved in the progression to OLGSCa. OSBTs with Braf mutation are associated with cellular senescence and up-regulation of tumor suppressor genes. In contrast, OSBTs without a Braf mutation may progress to OLGSCa due to Kras mutation or some other genetic alterations. (ii) The relationship between OSBTs and the extraovarian disease, a monoclonal versus mutifocal origin? This is still matter of debate as studies using different techniques have failed to settle this controversy. (iii) Biological behavior, Braf mutations appear to have a protective role against the progression of OSBT to OLGSCa, while Kras mutations are commonly seen in cases of OSBT that recurred as LGSCa. Nevertheless, LGSCa as a recurrence of an OSBT can originate from OSBTs with or without detectable Kras mutations. Also, it appears to be an association between Kras G12v mutation and a more aggressive phenotype of OSBT that recurred as LGSCa. (iv) Actionable targets, currently there are limited data. It has been reported that cancer cell lines with Kras G12v mutation are more sensitive to selumetinib than cell lines with wild-type Kras.

  12. Isolated subcutaneous implantation of a borderline ovarian tumor: A case report and review of the literature

    PubMed Central

    Banys-Paluchowski, Malgorzata; Yeganeh, Borsu; Luettges, Jutta; Maibach, Achim; Langenberg, Ruediger; Krawczyk, Natalia; Paluchowski, Peter; Maul, Holger; Gebauer, Gerhard

    2016-01-01

    Laparoscopy-related tumor implantations of gynecological malignancies into the subcutaneous tissue are rarely diagnosed. We report an interesting case of a 46-year-old female who presented with an abdominal subcutaneous metastasis of a borderline ovarian tumor. The patient received a laparoscopic unilateral adnexectomy for a solid-cystic tumor of the right ovary. Histopathological workup showed a papillary borderline tumor of mucinous type. Nine days later she underwent a hysterectomy, left adnexectomy, appendectomy and omentectomy. Exploration of the peritoneum revealed no intraperitoneal implants. Further exploration showed a non-invasive implant of a borderline tumor in the subcutaneous tissue above the fascia that had no contact to the peritoneum. It is hypothesized that tumor cells may have been implanted during a previous laparoscopy, the most recent of which had been fourteen years prior to her current presentation. Various risk factors for port-site malignancies have been identified. Tumor manipulation and extraction of tumor tissue without a protective bag may contribute to development of trocar-site metastasis. PMID:27081651

  13. Rare Skin Adnexal and Melanocytic Tumors Arising in Ovarian Mature Cystic Teratomas: A Report of 3 Cases and Review of the Literature.

    PubMed

    Moulla, Alexandra A; Magdy, Nesreen; Francis, Nicholas; Taube, Janis; Ronnett, Brigitte M; El-Bahrawy, Mona

    2016-09-01

    Mature teratoma of the ovary is the most common primary ovarian tumor accounting for 15% (10%-20%) of all ovarian neoplasms. Skin and skin adnexal structures are the most common elements identified in mature teratomas. Benign and malignant skin tumors can arise in ovarian teratomas, the most common being epithelial tumors. Melanocytic and adnexal tumors developing in a teratoma are rare and can be easily overlooked. We report 3 cases and review melanocytic and skin adnexal tumors encountered in ovarian teratomas.

  14. Paraganglioma-like dermal melanocytic tumor: a unique entity distinct from cellular blue nevus, clear cell sarcoma, and cutaneous melanoma.

    PubMed

    Deyrup, Andrea T; Althof, Pamela; Zhou, Ming; Morgan, Michael; Solomon, Alvin R; Bridge, Julia A; Weiss, Sharon W

    2004-12-01

    We are reporting a previously undescribed primary dermal melanocytic tumor identified by reviewing all dermal melanocytic tumors referred in consultation that did not qualify histologically as a previously described entity. From these cases, 8 were remarkably similar. We termed them "paraganglioma-like dermal melanocytic tumor" (PDMT) based on their nested growth pattern. This term is used descriptively and does not imply any histogenetic or biologic similarity to true paraganglioma. PDMT is primarily a tumor of the extremities of adult females (18-53 years, mean 35 years; males 2; females 6) which present as a dermal nodule (range, 0.5-4.2 cm; mean, 1.4 cm) composed of nests of clear to amphophilic oval cells separated by delicate fibrous strands. Nuclear atypia was mild and mitotic activity low (1-4 mitoses/10 HPF). Melanin was not obvious on light microscopy. Tumors expressed S-100 protein (8 of 8), Melan-A (4 of 8), HMB-45 (8 of 8), and microphthalmia transcription factor (8 of 8) and lacked pancytokeratin (8 of 8) and smooth muscle actin (8 of 8). FISH analysis of 5 cases revealed an intact EWS gene locus, supporting absence of the clear cell sarcoma 12;22 translocation. Follow-up information in 8 patients (range, 35-92 months; mean, 54 months) indicated that all were alive without disease. PDMT comprises a clinically and pathologically unique subtype of dermal melanocytic tumors. Our study suggests a benign course, although a lesion of low malignant potential cannot be excluded.

  15. Ovarian serous borderline tumors with noninvasive and invasive peritoneal implants: A case report each.

    PubMed

    Srinivasamurthy, Banushree C; Kulandai Velu, Ambedkar Raj; Krishnan, Nagarajan; Patil, Anand Shankar Rao

    2015-01-01

    Serous borderline tumors (SBT) are defined by the World Health Organization (WHO) as serous neoplasms that show epithelial proliferation greater than that seen in serous cystadenomas, as evidenced by cellular stratification, cytologic atypicality, and epithelial tufting, but which exhibit no evidence of "destructive stromal" invasion and can show extra-ovarian implants. Characterization of invasive peritoneal implants from patients with noninvasive serous ovarian tumors has important prognostic and treatment implications. Peritoneal implants have been classified as either noninvasive or invasive based on their histopathologic appearance. Three criteria were applied for the diagnosis of "invasive" implants: Invasion of underlying normal tissue, micropapillary architecture, and solid epithelial nests surrounded by clefts. We encountered two cases of unilateral ovarian serous borderline tumors with non-invasive peritoneal implants in a 43-year-old female, and invasive peritoneal implants in 76-year-old female.

  16. Endometrioid Paraovarian Borderline Cystic Tumor in an Infant with Proteus Syndrome

    PubMed Central

    Vasquez, Liliana; Tello, Mariela; Maza, Ivan; Oscanoa, Monica; Dueñas, Milagros; Castro, Haydee; Latorre, Alan

    2015-01-01

    Ovarian and paraovarian neoplasms are uncommon in children, mainly originating from germ cell tumors and, least frequently, epithelial tumors. There is an association between genital tract tumors and Proteus syndrome, a rare, sporadic, and progressive entity, characterized by a postnatal overgrowth in several tissues caused by a mosaic mutation in the AKT1 gene. We describe a 20-month-old asymptomatic infant with Proteus syndrome who developed an endometrioid paraovarian borderline cystic tumor. This is the youngest patient so far reported in the literature with this rare syndrome and an adnexal tumor of borderline malignancy. A total of nine patients have been described with female tract tumors and associated Proteus syndrome, which includes bilateral ovarian cystadenomas and other benign masses. A paraovarian neoplasm is extremely rare in children and could be considered a criterion for Proteus syndrome. Standardized staging and treatment of these tumors are not well established; however, most authors conclude that these neoplasms must be treated as their ovarian counterparts. PMID:26558123

  17. Decision making in borderline ovarian tumors: report of a rare case of mesosigma psammocarcinoma.

    PubMed

    Grimaldi, Luciano; Danzi, Michele; Reggio, Stefano; Pannullo, Mario; Danzi, Roberta; Lauria, Rossella

    2013-09-03

    Psammocarcinoma is a rare variant of serous carcinoma arising either from ovary or peritoneum, characterized by massive psammoma body formation, low-grade of cytologic differentiation and invasiveness. Its clinical behavior is similar to the serous borderline tumors, whose prognosis is significantly better compared to invasive forms, with a 5-year survival in stage I greater than 95%. A typical feature of borderline ovary tumors is the presence, in more than 30% of cases, of borderline peritoneal implants similar to primary ovarian cancer or of invasive forms. We report a case of a 44-years-old woman who referred to our clinic for mesosigmoid mass , accidentally discovered by ultrasonography. Sigmoidectomy with fertility sparing surgery was performed in september 2010. The mass was hystologically characterized by many psammoma bodies and low grade cytological features with diagnosis of psammocarcinoma of mesosigma. One year after the primary surgery, the patient showed with left adnexial mass; optimal debulking surgery was performed including omentectomy, total abdominal hysterectomy, bilateral adnexectomy and appendicectomy. The patient did not receive any adjuvant chemotherapy and to date she is alive and with no evidence of disease. The conclusion is that psammocarcinoma is a very rare tumor that behaves less aggressively than typical serous carcinoma, the mainstay of treatment is surgical debulking , with fertility sparing surgery as possible option in young patients with ovaries macroscopically free of disease.

  18. Borderline ovarian tumors: a study of 100 cases from a Tertiary Care Hospital

    PubMed Central

    Mun, Semih; Uysal, Fatma; Öztekin, Murat; Büyüktosun, Cem; Şehirali1, Salim; Başoğul, Ömer; Taner, Cüneyt E.

    2013-01-01

    Aim of the study The purpose of the study was to evaluate patients with borderline ovarian tumors. Material and methods Clinical features, treatment and survival status of 100 patients with borderline ovarian tumors were retrospectively evaluated between 1998 and 2007. Results Patients’ mean age was 37.75 years (range: 15–72); 22 of them were postmenopausal. Histopathological diagnoses were serous, mucinous, endometrioid and clear cell in 54%, 41%, 2% and 3% of the patients, respectively; 70 patients had stage IA disease, 8 were at stage IB, 16 at stage IC, 2 at stage IIIA, 3 at stage IIIB and 1 at stage IIIC. Restaging laparotomies were performed on 19 patients; fertility-sparing surgery was performed on 52 patients; 2 patients received chemotherapy because of advanced-stage disease. All patients are currently alive. The 5-year disease-free survival rate for 71 cases was 100%. Conclusions Borderline ovarian tumors have excellent prognoses, and fertility-conserving surgery can be performed in young patients with early-stage disease. PMID:24596520

  19. CD44 and melanocytic tumors: a possible role for standard CD44 in the epidermotropic spread of melanoma.

    PubMed

    Fernández-Figueras, M T; Ariza, A; Calatrava, A; Puig, L; Fernández-Vasalo, A; Ferrándiz, C

    1996-04-01

    CD44 is a polymorphic family of cell membrane glycoproteins that mediate cell-matrix and cell-cell interactions involved in the mechanisms of tumor invasion and metastasis, and are subject to differential regulation during normal and malignant cell growth. We have investigated immunohistochemically the expression of CD44S and the variant isoforms CD44v3 and CD44v6 in paraffin-embedded tissue from 5 Spitz nevi, 3 compound melanocytic nevi, 2 blue nevi, 6 primary melanomas, 15 cutaneous metastases (three epidermotropic, nine dermal and three ulcerated) and 10 lymph node metastases of melanoma. Melanocytes were extensively positive for CD44S in primary melanomas and benign melanocytic proliferations. Among 15 cases of cutaneous metastases of melanoma, the three epidermotropic metastases, as well as one of the three ulcerated ones were positive for CD44S. CD44S expression was diminished or totally absent in six of the nine dermal metastases, in two of the ulcerated metastases and in seven of the ten lymph node metastases. CD44v3 and CD44v6 melanocytic expression was absent in all the lesions studied. According to our results, selective retention of CD44S expression by melanocytes in epidermotropic metastases of melanoma seems to indicate that preservation of CD44S may contribute to the intraepidermal spread of melanoma.

  20. In vitro evidence for senescent multinucleated melanocytes as a source for tumor-initiating cells

    PubMed Central

    Leikam, C; Hufnagel, A L; Otto, C; Murphy, D J; Mühling, B; Kneitz, S; Nanda, I; Schmid, M; Wagner, T U; Haferkamp, S; Bröcker, E-B; Schartl, M; Meierjohann, S

    2015-01-01

    Oncogenic signaling in melanocytes results in oncogene-induced senescence (OIS), a stable cell-cycle arrest frequently characterized by a bi- or multinuclear phenotype that is considered as a barrier to cancer progression. However, the long-sustained conviction that senescence is a truly irreversible process has recently been challenged. Still, it is not known whether cells driven into OIS can progress to cancer and thereby pose a potential threat. Here, we show that prolonged expression of the melanoma oncogene N-RAS61K in pigment cells overcomes OIS by triggering the emergence of tumor-initiating mononucleated stem-like cells from senescent cells. This progeny is dedifferentiated, highly proliferative, anoikis-resistant and induces fast growing, metastatic tumors. Our data describe that differentiated cells, which are driven into senescence by an oncogene, use this senescence state as trigger for tumor transformation, giving rise to highly aggressive tumor-initiating cells. These observations provide the first experimental in vitro evidence for the evasion of OIS on the cellular level and ensuing transformation. PMID:25837487

  1. Interaction between omega 3 PUFA and UVB radiation: Photoprotective effect in normal and tumoral murine melanocytes?

    PubMed

    Vasconcelos, Renata Ottes; Bustos, Silvina Odete; Gonzalez, Juliana Ramos; Soares, Camila Wink; Barbosa, Makely Daiane; Chammas, Roger; Votto, Ana Paula de Souza; Trindade, Gilma Santos

    2016-11-01

    Omega 3 polyunsaturated fatty acids (omega 3 PUFA) are attracting a growing interest as potential adjuvants for cancer prevention and treatment. There is evidence about photoprotection in normal cells, but few previous studies have evaluated it in tumoral cells. Therefore, this study investigated the effect of α-linolenic acid (ALA) in normal murine melanocytic cells (Melan-a) and in tumoral murine melanocytic cells (B16F10) exposed to UVB radiation. Our results showed that ALA exhibited an antiproliferative effect in B16F10 cells, and had minimal effect in Melan-a cells, as demonstrated by MTT assay. On the other hand, the combination of ALA (7.5μM) and UVB (0.01J/cm(2)) showed a protective effect for both cell lines, Melan-a and B16F10. ALA and UVB combined or UVB alone induced an accumulation of cell lines at the S/G2/M phase. In addition, the combination of ALA and UVB, and UVB alone, both induced cell death in 24h; and in 48h, ALA attenuated this effect in both cells. Further to these findings, it was demonstrated that ALA did not alter ROS levels in both cells exposed to UVB radiation. The effect of an omega 6 PUFA, linoleic acid, under the same conditions of ALA were tested. It was not protective in either cell line. Therefore, our results can be very important since it was shown another role to an omega 3 PUFA as a photoprotective agent in a melanoma cell.

  2. Epidemiologic and molecular characteristics of borderline and malignant epithelial ovarian tumors

    NASA Astrophysics Data System (ADS)

    Bastos, Eugenia Maria Chaves De Moraes

    Data from the Cancer and Steroid Hormone Study, a multicenter, population-based, case-control study were used to identify risk factors for epithelial ovarian cancer according to tumor behavior, histologic types, as well as p53 expression. Cases were women between 20 to 54 years old diagnosed with epithelial ovarian cancer from 1980 to 1982. Controls were women selected by random digit dialing. Tumor samples were analyzed for p53 overexpression using immunohistochemistry. Case-case and case-control conditional logistic regression models matched on age and diagnosing centers were used to calculate odds ratios (OR's) and 95% confidence intervals (CI's) for borderline, malignant, mucinous, and nonmucinous tumors, and p53 positive and p53 negative cases. The OR's for high number of lifetime ovulatory cycles (376-533 compared with less than 234) were 3.1 (95% CI 1.6-6.1) for malignant and 1.4 (95% CI 0.5-3.7) for borderline cases. The high number of ovulatory cycles was also a strong risk factor among nonmucinous cases. OR's for current and recent ex-smokers compared with never smokers were 2.8 (95% CI 1.7-4.8) for mucinous and 0.9 (95% CI 0.7-1.1) for nonmucinous types. Infertility showed a positive association with borderline ovarian cancer. Family history of ovarian or breast cancer was positively associated with malignant and nonmucinous cases. Parity had an inverse association with malignant ovarian cancer cases. When cases were subdivided by p53 results, the OR for tobacco smoking and p53 positive ovarian cancer was elevated for mucinous (OR = 3.9; 95% CI 0.8-18) at localized stage. Alcohol use showed a positive association with p53 positive malignant cases at advanced stage (OR = 2.0; 95% CI 1.2-3.2) and with p53 positive nonmucinous cases at advanced stage (OR = 2.1; 95% CI 1.2-3.4). A positive association between high number of ovulatory cycles and p53 positive malignant cases was observed in cases with localized stage (OR = 6.6; 95% CI 1.0-45) and advanced

  3. Mucinous borderline ovarian tumors: Analysis of 75 patients from a single center

    PubMed Central

    Cömert, Duygu Kavak; Üreyen, Işın; Karalok, Alper; Taşçı, Tolga; Türkmen, Osman; Öcalan, Reyhan; Turan, Taner; Tulunay, Gökhan

    2016-01-01

    Objective To analyze the clinicopathologic features, recurrence and survival rates, reproductive history, and treatment of patients with mucinous borderline ovarian tumors (mBOTs). Material and Methods Patients with a diagnosis of mBOT were evaluated retrospectively. Patients with borderline ovarian tumors other than mucinous type and concomitant invasive cancer were excluded. Results A total of 75 patients were identified. Median age was 38 years. The most common symptom was pain (42.7%). Median CA-125 level was 23.5 IU/mL (range, 1–809 IU/mL). Median tumor size was 200 mm (range, 40–400 mm), and 6.7% of mBOTs were bilateral. Thirty-six (48%) patients underwent staging surgery. Two patients (5.9%) had nodal involvement. One patient received platinum-based adjuvant chemotherapy. One (1.3%) patient had recurrence. None of the patients died because of the ovarian tumor. A total of 43 patients had conservative surgery. Conclusion Prognosis of mBOTs is excellent, and fertility-sparing surgery should be considered in the reproductive age group. Furthermore, the necessity of staging surgery is controversial. PMID:27403076

  4. Intramedullary and retroperitoneal melanocytic tumor associated with congenital blue nevus and nevus flammeus: an uncommon combination of neurocutaneous melanosis and phacomatosis pigmentovascularis--case report.

    PubMed

    Kurokawa, Ryu; Kim, Phyo; Kawamoto, Toshiki; Matsuda, Hadzki; Hayashi, Shujiro; Yamazaki, Soji; Hatamochi, Atsushi; Mori, Shozo; Shimoda, Mitsugi; Kubota, Keiichi

    2013-01-01

    Neurocutaneous melanosis (NCM) is a rare condition characterized by central nervous system melanocytic tumors associated with congenital melanocytic nevi. Phacomatosis pigmentovascularis (PPV) is an association of vascular nevus with pigmentary nevus. Aberrant maturation of neural crest-derived cells is considered to be related to pathogenesis in both conditions. However, association of NCM and PPV has not been reported to the best of our knowledge. Melanocytoma, which usually involves the leptomeninges or spinal cord, is extremely rare in the retroperitoneum. We present here a case of a patient with NCM, PPV, and melanocytic tumors in the spinal cord and retroperitoneum, which were treated surgically. A 40-year-old woman had a 2-year history of dysesthesia and weakness in the left leg. History included congenital giant blue nevus-like lesion in the trunk, a port-wine stain in the sacral area, and Caesarean section performed 8 years before, when diffuse pigmentation in the peritoneum was noted. Magnetic resonance (MR) imaging of the spine revealed an intramedullary tumor at T10 level with paramagnetic signal characteristics. The spinal cord tumor was totally removed, and the histological diagnosis was melanocytoma. Three months later, a left retroperitoneal mass with histological features of melanocytic tumor was removed. Neither tumors recurred and the patient stays ambulatory 4 years after the surgery. Multiple subtypes of melanocytic tumors with distinctive features of NCM and PPV can develop simultaneously, mimicking malignant melanoma. Gross total resection of each tumor, when indicated, is beneficial.

  5. Differentiating intratumoral melanocytes from Langerhans cells in nonmelanocytic pigmented skin tumors in vivo by label-free third-harmonic generation microscopy

    NASA Astrophysics Data System (ADS)

    Weng, Wei-Hung; Liao, Yi-Hua; Tsai, Ming-Rung; Wei, Ming-Liang; Huang, Hsin-Yi; Sun, Chi-Kuang

    2016-07-01

    Morphology and distribution of melanocytes are critical imaging information for the diagnosis of melanocytic lesions. However, how to image intratumoral melanocytes noninvasively in pigmented skin tumors is seldom investigated. Third-harmonic generation (THG) is shown to be enhanced by melanin, whereas high accuracy has been demonstrated using THG microscopy for in vivo differential diagnosis of nonmelanocytic pigmented skin tumors. It is thus desirable to investigate if label-free THG microscopy was capable to in vivo identify intratumoral melanocytes. In this study, histopathological correlations of label-free THG images with the immunohistochemical images stained with human melanoma black (HMB)-45 and cluster of differentiation 1a (CD1a) were made. The correlation results indicated that the intratumoral THG-bright dendritic-cell-like signals were endogenously derived from melanocytes rather than Langerhans cells (LCs). The consistency between THG-bright dendritic-cell-like signals and HMB-45 melanocyte staining showed a kappa coefficient of 0.807, 84.6% sensitivity, and 95% specificity. In contrast, a kappa coefficient of -0.37, 21.7% sensitivity, and 30% specificity were noted between the THG-bright dendritic-cell-like signals and CD1a staining for LCs. Our study indicates the capability of noninvasive label-free THG microscopy to differentiate intratumoral melanocytes from LCs, which is not feasible in previous in vivo label-free clinical-imaging modalities.

  6. Ovarian high-grade serous carcinoma with a noninvasive growth pattern simulating a serous borderline tumor.

    PubMed

    Imamura, Hiroko; Ohishi, Yoshihiro; Aman, Murasaki; Shida, Kaai; Shinozaki, Tomoko; Yasutake, Nobuko; Sonoda, Kenzo; Kato, Kiyoko; Oda, Yoshinao

    2015-10-01

    Ovarian serous borderline tumors (SBTs) being a precursor of low-grade serous carcinomas are morphologically characterized by noninvasive growth and low-grade cytology. On the other hand, many pathologists regard cytologically high-grade, noninvasive (HG-noninv) ovarian serous tumors resembling SBTs in low magnification as conventional high-grade serous carcinomas (HGSCs) by personal experiences. Nonetheless, there are no established molecular characteristic of such tumors. In this study, therefore, we attempted to provide the molecular evidence. We selected 37 ovarian serous tumors that exhibited a cytologically HG-noninv growth pattern, including 36 tumors that coexisted with conventional invasive HGSC components (HG-inv) and a single tumor exclusively composed of pure HG-noninv. Histologically, all HG-noninv showed many mitotic figures, and serous tubal intraepithelial carcinomas were identified in 3 tumors with HG-noninv. Immunohistochemically, most HG-noninv showed aberrant p53 expression, frequent IMP3 positivity, p16 overexpression, a high MIB-1 labeling index, and infrequent PAX2. By molecular analysis, the pure HG-noninv and 13 HGSCs with HG-noninv showed TP53 mutations, but KRAS/BRAF mutations were not detected in any of them. In 1 tumor, we detected an identical TP53 mutation in both HG-noninv and HG-inv components by using laser capture microdissection. These immunohistochemical and molecular features of HG-noninv were similar to those of conventional invasive HGSCs but different from those of SBTs. In conclusion, our results showed that a cytologically HG-noninv growth pattern simulating an SBT is a morphological spectrum of HGSC, but not a true SBT.

  7. Sox10 – A marker for not only Schwannian and melanocytic neoplasms but also myoepithelial cell tumors of soft tissue. A systematic analysis of 5134 tumors

    PubMed Central

    Miettinen, Markku; McCue, Peter A.; Sarlomo-Rikala, Maarit; Biernat, Wojciech; Czapiewski, Piotr; Kopczynski, Janusz; Thompson, Lester D.; Lasota, Jerzy; Wang, Zengfeng; Fetsch, John F.

    2015-01-01

    Sox10 transcription factor is expressed in Schwannian and melanocytic lineages and is important in their development and can be used as a marker for corresponding tumors. Additionally, it has been reported in subsets of myoepithelial/basal cell epithelial neoplasms, but its expression remains incompletely characterized. In this study, we examined Sox10 express-ion in 5134 human neoplasms spanning a wide spectrum of neuroectodermal, mesenchymal, lymphoid, and epithelial tumors. A new rabbit monoclonal antibody (clone EP268) and Leica Bond Max automation were used on multitumor block libraries containing 30–70 cases per slide. Sox10 was consistently expressed in benign Schwann cell tumors of soft tissue and the GI-tract and metastatic melanoma, and was variably present in malignant peripheral nerve sheath tumors. In contrast, Sox10 was absent in many potential mimics of nerve sheath tumors such as cellular neurothekeoma, meningioma, gastrointestinal stromal tumors, PEComa, and a variety of fibroblastic-myofibroblastic tumors. Sox10 was virtually absent in mesenchymal tumors but occasionally seen in alveolar rhabdomyosarcoma. In epithelial tumors of soft tissue, Sox10 was expressed only in myoepitheliomas, although often absent in malignant variants. Carcinomas, other than basal cell type breast cancers, were only rarely positive but included rare squamous carcinomas of head and neck and pulmonary small cell carcinomas. Furthermore, Sox10 was often focally expressed in embryonal carcinoma reflecting a primitive Sox10-positive phenotype or neuroectodermal differentiation. Expression of Sox10 in entrapped non-neoplastic Schwann cells or melanocytes in various neoplasms has to be considered in diagnosing Sox10-positive tumors. The Sox10 antibody belongs in a modern immunohistochemical panel for the diagnosis of soft tissue and epithelial tumors. PMID:25724000

  8. Differential expression of basic fibroblast growth factor (bFGF) in melanocytic lesions demonstrated by in situ hybridization. Implications for tumor progression.

    PubMed Central

    Reed, J. A.; McNutt, N. S.; Albino, A. P.

    1994-01-01

    Basic fibroblast growth factor (bFGF) is an angiogenic and mitogenic polypeptide produced by diverse cell types including cell lines derived from malignant melanomas but not from normal melanocytes. However, there is no consensus concerning in vivo expression of bFGF in melanocytic lesions due in part to the small numbers of cases studied to date. To evaluate further the possible differential expression of bFGF in melanocytic lesions, we examined 110 formalin-fixed, paraffin-embedded metastatic and primary invasive melanomas, melanomas in situ, nevi with architectural disorder and cytological atypia, and ordinary benign melanocyte nevi by nucleic acid in situ hybridization. All metastatic and primary invasive melanomas studied expressed bFGF mRNA, whereas melanomas in situ and benign melanocyte nevi were negative. Melanomas in situ with features of tumor regression and a majority of nevi with architectural disorder and cytological atypia also contained bFGF mrNA. The results suggest that in vivo bFGF expression is not requisite for malignant transformation per se, but appears to correlate more with invasion or fibroblastic reactions adjacent to the melanocyte lesions. Images Figure 1 Figure 2 PMID:8311116

  9. Clinical and molecular comparison between borderline serous ovarian tumors and advanced serous papillary ovarian carcinomas.

    PubMed

    Halperin, R; Zehavi, S; Dar, P; Habler, L; Hadas, E; Bukovsky, I; Schneider, D

    2001-01-01

    The aim of this study was to characterize the clinical and molecular markers of borderline serous ovarian tumors (BSOT), and to study their expression in the progression from benign lesions to advanced serous papillary ovarian carcinomas (SPOC). The clinical records of 20 patients with BSOT and 22 patients with SPOC were reviewed. Specimens from all these cases and from six benign ovarian serous cystadenomas were evaluated for expression of estrogen receptors (ER), progesterone receptors (PR), p53. HER-2/neu and Ki-67 by immunohistochemical techniques. The mean patient age and the age at menarche differed significantly between the compared groups of BSOT and SPOC (p=0.0006 and p=0.0014, respectively). No difference was observed comparing the other clinical parameters. The immunohistochemical analysis demonstrated a significant increase in the expression of ER (100% vs 72.7%), and a significant decrease in the immunoreactivity for p53 (0% vs 45.4%) and Ki-67 (2% vs 26.8%) in cases of BSOT compared with those of SPOC (p=0.007, p=0.0003 and p=0.012, respectively). No significant difference was demonstrated comparing the expression of PR and HER-2/neu. The immunostaining of benign ovarian serous cystadenoma specimens did not differ significantly from immunoreactivity observed in cases of BSOT. According to immunohistochemical analysis, BSOT had much more in common with benign serous tumors than with SPOC. The main difference between BSOT and SPOC was regarding the overexpression of p53 and Ki-67.

  10. A Case of a Giant Borderline Phyllodes Tumor Early in Pregnancy Treated with Mastectomy and Immediate Breast Reconstruction.

    PubMed

    Gentile, Lori F; Gaillard, William Foster; Wallace, Jodi-Ann; Spiguel, Lisa R P; Alizadeh, Layla; Lentz, Ashley; Shaw, Christiana

    2016-11-01

    Breast tumors in pregnancy are often times diagnosed at advanced stages secondary to difficulty distinguishing between pathologic from normal physiologic changes. Often benign, phyllodes tumors are rare fibroepithelial stromal tumors of the breast, most commonly diagnosed in the 4th and 5th decades of life. However, these tumors may be characterized by malignancy with metastases in 10% of cases. In this paper, we report a novel case of a young woman presenting at 8 weeks gestation with a large borderline phyllodes tumor. An exceedingly rare condition, with only nine previously reported cases, phyllodes tumors in pregnancy frequently display more aggressive characteristics with larger median tumor size, more malignant potential, and more rapid growth rate. Here, we describe our experience safely and effectively treating this rare condition in a young gravid women with mastectomy and immediate breast reconstruction in the second trimester.

  11. Neoadjuvant Chemotherapy in Locally Advanced and Borderline Resectable Nonsquamous Sinonasal Tumors (Esthesioneuroblastoma and Sinonasal Tumor with Neuroendocrine Differentiation)

    PubMed Central

    Patil, Vijay M.; Joshi, Amit; Noronha, Vanita; Sharma, Vibhor; Zanwar, Saurabh; Dhumal, Sachin; Kane, Shubhada; Pai, Prathamesh; D'Cruz, Anil; Chaturvedi, Pankaj; Bhattacharjee, Atanu; Prabhash, Kumar

    2016-01-01

    Introduction. Sinonasal tumors are chemotherapy responsive which frequently present in advanced stages making NACT a promising option for improving resection and local control in borderline resectable and locally advanced tumours. Here we reviewed the results of 25 such cases treated with NACT. Materials and Methods. Sinonasal tumor patients treated with NACT were selected for this analysis. These patients received NACT with platinum and etoposide for 2 cycles. Patients who responded and were amenable for gross total resection underwent surgical resection and adjuvant CTRT. Those who responded but were not amenable for resection received radical CTRT. Patients who progressed on NACT received either radical CTRT or palliative radiotherapy. Results. The median age of the cohort was 42 years (IQR 37–47 years). Grades 3-4 toxicity with NACT were seen in 19 patients (76%). The response rate to NACT was 80%. Post-NACT surgery was done in 12 (48%) patients and radical chemoradiation in 9 (36%) patients. The 2-year progression free survival and overall survival were 75% and 78.5%, respectively. Conclusion. NACT in sinonasal tumours has a response rate of 80%. The protocol of NACT followed by local treatment is associated with improvement in outcomes as compared to our historical cohort. PMID:26955484

  12. Histopathologic tumor response after induction chemotherapy and stereotactic body radiation therapy for borderline resectable pancreatic cancer

    PubMed Central

    Chuong, Michael D.; Frakes, Jessica M.; Figura, Nicholas; Hoffe, Sarah E.; Shridhar, Ravi; Mellon, Eric A.; Hodul, Pamela J.; Malafa, Mokenge P.; Springett, Gregory M.

    2016-01-01

    Background While clinical outcomes following induction chemotherapy and stereotactic body radiation therapy (SBRT) have been reported for borderline resectable pancreatic cancer (BRPC) patients, pathologic response has not previously been described. Methods This single-institution retrospective review evaluated BRPC patients who completed induction gemcitabine-based chemotherapy followed by SBRT and surgical resection. Each surgical specimen was assigned two tumor regression grades (TRG), one using the College of American Pathologists (CAP) criteria and one using the MD Anderson Cancer Center (MDACC) criteria. Overall survival (OS) and progression free survival (PFS) were correlated to TRG score. Results We evaluated 36 patients with a median follow-up of 13.8 months (range, 6.1-24.8 months). The most common induction chemotherapy regimen (82%) was GTX (gemcitabine, docetaxel, capecitabine). A median SBRT dose of 35 Gy (range, 30-40 Gy) in 5 fractions was delivered to the region of vascular involvement. The margin-negative resection rate was 97.2%. Improved response according to MDACC grade trended towards superior PFS (P=061), but not OS. Any neoadjuvant treatment effect according to MDACC scoring (IIa-IV vs. I) was associated with improved OS and PFS (both P=0.019). We found no relationship between CAP score and OS or PFS. Conclusions These data suggest that the increased pathologic response after induction chemotherapy and SBRT is correlated with improved survival for BRPC patients. PMID:27034789

  13. DNA Cytometry and Nuclear Morphometry in Ovarian Benign, Borderline and Malignant Tumors

    PubMed Central

    el Din, Amina A. Gamal; Badawi, Manal A.; Aal, Shereen E. Abdel; Ibrahim, Nihad A.; Morsy, Fatma A.; Shaffie, Nermeen M.

    2015-01-01

    BACKDROUND: Ovarian carcinoma is a leading cause of death in gynecological malignancy. Ovarian surface epithelial serous and mucinous tumours are classified as benign, borderline, and malignant. The identification of borderline tumours most likely to act aggressively remains an important clinical issue. AIM: This work aimed to study DNA ploidy and nuclear area in ovarian serous and mucinous; benign, borderline and malignant tumours. MATERIAL AND METHODS: This study included forty ovarian (23 serous and 17 mucinous) tumours. Paraffin blocks were sectioned; stained with haematoxylin and eosin for histopathologic and morphometric studies and with blue feulgen for DNA analysis. RESULTS: All four serous and six out of nine mucinous benign tumours were diploid. All eight serous and five mucinous malignant tumours were aneuploid. Nine of eleven (81.8%) serous and all three mucinous borderline tumours were aneuploid. There were highly significant differences in mean aneuploid cells percentage between serous benign (1.5%), borderline (45.6%) and malignant (74.5%) (p = 0.0001) and between mucinous benign (13.2%) and both borderline (63.7%) and malignant (68.4%) groups (p = 0.0001). There were significant differences in nuclear area between serous benign (26.191%), borderline (45.619%) and malignant (67.634 %) and a significant positive correlation between mean percentage aneuploid value and mean nuclear area in all serous and mucinous groups. CONCLUSION: We suggest that DNA ploidy and nuclear area combined, may be adjuncts to histopathology; in ovarian serous and mucinous benign, borderline and malignant neoplasms; identifying the aggressive borderline tumours. PMID:27275284

  14. Cytoskeleton alterations in melanoma: aberrant expression of cortactin, an actin-binding adapter protein, correlates with melanocytic tumor progression

    PubMed Central

    Xu, Xu-Zhi; Garcia, Marileila Varella; Li, Tian-yu; Khor, Li-Yan; Gajapathy, R Sujatha; Spittle, Cindy; Weed, Scott; Lessin, Stuart R; Wu, Hong

    2010-01-01

    Cortactin is a multidomain actin-binding protein important for the functions of cytoskeleton by regulating cortical actin dynamics. It is involved in a diverse array of basic cellular functions. Tumorigenesis and tumor progression involves alterations in actin cytoskeleton proteins. We sought to study the role of cortactin in melanocytic tumor progression using immunohistochemistry on human tissues. The results reveal quantitative differences between benign and malignant lesions. Significantly higher cortactin expression is found in melanomas than in nevi (P<0.0001), with levels greater in metastatic than in invasive melanomas (P<0.05). Qualitatively, tumor tissues often show aberrant cortactin localization at the cell periphery, corresponding to its colocalization with filamentous actin in cell cortex of cultured melanoma cells. This suggests an additional level of protein dysregulation. Furthermore, in patients with metastatic disease, high-level cortactin expression correlates with poor disease-specific survival. Our data, in conjunction with outcome data on several other types of human cancers and experimental data from melanoma cell lines, supports a potential role of aberrant cortactin expression in melanoma tumor progression and a rational for targeting key elements of actin-signaling pathway for developmental therapeutics in melanomas. PMID:19898426

  15. Genetics of Melanocytic Nevi

    PubMed Central

    Roh, Mi Ryung; Eliades, Philip; Gupta, Sameer; Tsao, Hensin

    2015-01-01

    Melanocytic nevi are a benign clonal proliferation of cells expressing the melanocytic phenotype, with heterogeneous clinical and molecular characteristics. In this review, we discuss the genetics of nevi by salient nevi subtypes: congenital melanocytic nevi, acquired melanocytic nevi, blue nevi, and Spitz nevi. While the molecular etiology of nevi has been less thoroughly studied than melanoma, it is clear that nevi and melanoma share common driver mutations. Acquired melanocytic nevi harbor oncogenic mutations in BRAF, which is the predominant oncogene associated with melanoma. Congenital melanocytic nevi and blue nevi frequently harbor NRAS mutations and GNAQ mutations, respectively, while Spitz and atypical Spitz tumors often exhibit HRAS and kinase rearrangements. These initial “driver” mutations are thought to trigger the establishment of benign nevi. After this initial phase of cell proliferation, a senescence program is executed, causing termination of nevi growth. Only upon the emergence of additional tumorigenic alterations, which may provide an escape from oncogene-induced senescence, can malignant progression occur. Here, we review the current literature on the pathobiology and genetics of nevi in the hope that additional studies of nevi promise to inform our understanding of the transition from benign neoplasm to malignancy. PMID:26300491

  16. Plasminogen activators, their inhibitors, and urokinase receptor emerge in late stages of melanocytic tumor progression.

    PubMed Central

    de Vries, T. J.; Quax, P. H.; Denijn, M.; Verrijp, K. N.; Verheijen, J. H.; Verspaget, H. W.; Weidle, U. H.; Ruiter, D. J.; van Muijen, G. N.

    1994-01-01

    Degradation of the extracellular matrix and other tissue barriers by proteases like plasminogen activators (PAs) is a prerequisite for neoplastic growth and metastasis. Recently, we reported that highly metastatic behavior of human melanoma cells in nude mice correlates with urokinase-type PA (u-PA) expression and activity and with PA inhibitor type 1 and 2 (PAI-1, PAI-2) expression. Here we report on the occurrence of components of the PA system in the various stages of human melanoma tumor progression in situ. We studied the protein distribution on freshly frozen lesions of common nevocellular nevi (n = 25), dysplastic (= atypical) nevi (n = 16), early primary melanomas (n = 8), advanced primary melanomas (n = 11), and melanoma metastases (n = 17). Tissue-type PA was present in endothelial cells in all lesions, whereas in metastases it could be detected in tumor cells in a minority of the lesions. u-PA, its receptor, PAI-1, and PAI-2 could not be detected in benign and in early stages but appeared frequently in advanced primary melanoma and melanoma metastasis lesions. u-PA was detected in stromal cells and in tumor cells at the invasive front, the u-PA receptor and PAI-2 in tumor cells, and PAI-1 in the extracellular matrix surrounding tumor cells. Localization of the corresponding messenger RNAs and enzyme activities revealed a similar distribution. We conclude that plasminogen activation is a late event in melanoma tumor progression. Images Figure 1 Figure 3 Figure 4 Figure 5 PMID:8291613

  17. Five-Year Disease-Free Follow-Up of a Borderline Breast Phyllodes Tumor in a 15-year-old Patient

    PubMed Central

    Güler, Sertaç Ata; Uğurlu, M. Ümit; Güllüoğlu, Bahadır M.

    2015-01-01

    Phyllodes tumors are large breast tumors representing only 1% of breast neoplasms and are rarely seen in young women. Histologically, phyllodes tumors are classified as benign, borderline, or malignant based on the characteristics of the stroma. Although wide local excision is recommended for the treatment modality, the reoccurrence rate after surgical excision varies between 36% and 65%, with recurrence more likely in those with the tumor at the margins of excision. Our aim was to report -a case in a 15-year-old girl with a 115-mm borderline phyllodes tumor in her left breast mimicking a juvenile fibroadenoma. We presented a 5-year disease-free follow-up after wide local excision with negative margins.

  18. HER-2 and cancer antigen 125 evaluation in ovarian borderline tumors by immunohistochemistry and fluorescence in situ hybridization.

    PubMed

    Heinrich, J K R; Böttcher-Luiz, F; Andrade, L L A; Davidson, S; Bonds, L; Stephens, J; Varella-Garcia, M

    2004-01-01

    The study determined the expression of cancer antigen (CA) 125 and HER-2 in 45 borderline ovarian tumors (BOTs) and investigated the correlation of these biologic markers with histologic type, clinical stage, and outcome. The level of CA 125 protein was assessed using DAKO's M-11 clone antibody in immunohistochemistry (IHC) assays (Carpinteria, CA). The HER-2 protein expression was assessed in IHC assays using the HercepTest (DAKO), and the HER-2 gene copy number per cell was investigated through fluorescence in situ hybridization (FISH) assays using VYSIS' PathVysion DNA Probe (Downers Grove, IL). Expression of the CA 125 protein was detected in 49% of the samples (22 out of 45 tumors) and significantly associated with the serous histologic type. However, CA 125 expression did not associate with clinical stage or outcome. Protein overexpression or gene amplification of HER-2 was not found. However, abnormal FISH results were detected in 16% (seven out of 45 patients) of specimens comprising extranumerary copies of HER-2 and/or chromosome 17 per cell. Abnormal FISH results were found to be independent of CA 125 expression and histologic type whereas they positively associate with advanced clinical stage. Our data show that HER-2 is not altered in BOTs, and the presence of aneusomy for chromosome 17 and HER-2 may predict tumor progression.

  19. "Borderline" Children.

    ERIC Educational Resources Information Center

    Gualtieri, C. Thomas C.; And Others

    1983-01-01

    The use of the diagnosis "borderline" was evaluated with 16 children (6 to 13 years old) who were referred for comprehensive evaluation. None met DSM III criteria for borderline personality disorder. The borderline label had a negative impact on some children and was not helpful for treatment planning or disposition. (Author/SEW)

  20. [A case of coexisting borderline phyllodes tumor and non-invasive ductal carcinoma].

    PubMed

    Toyoda, Yasuhiro; Hojo, Shigeyuki; Yoshioka, Setsuko; Kojima, Fumiyoshi; Matsunaga, Hiroki; Fujie, Yujiro; Fukunaga, Hiroki; Ota, Hirofumi; Endo, Wakio; Maeura, Yoshiichi

    2013-11-01

    A 36-year-old woman with benign phyllodes tumor of the left breast had undergone lumpectomy 1 year ago and was admitted to our hospital because of a left breast mass on the operation scar. Ultrasonography showed a 35 mm low-echoic, elliptical mass with a high depth to width( D/W) ratio in the C area and a 10 mm low-echoic, polygonal mass with a high D/W ratio in the E area. Histological examination of an ultrasonography-guided vacuum-assisted biopsy specimen indicated recurrent phyllodes tumor. Since both tumors were assumed to be recurrent phyllodes tumors, quadrantectomy was performed. Finally, the mass in the C area was diagnosed as a recurrent phyllodes tumor and the mass in the E area was diagnosed as a fibroadenoma. A non-invasive ductal carcinoma was incidentally detected between the 2 tumors, and the surgical margin was negative. Radiotherapy was performed on the remnant breast tissue.

  1. A Case of Giant Borderline Phyllodes Tumor of the Breast Associated with Hypoglycemia.

    PubMed

    Saito, Yuki; Suzuki, Yasuhiro; Inomoto, Chie; Kumaki, Nobue; Yokoyama, Kozue; Ogiya, Rin; Oshitanai, Risa; Terao, Mayako; Tsuda, Banri; Morioka, Tooru; Niikura, Naoki; Okamura, Takuho; Masuda, Shinobu; Tokuda, Yutaka

    2016-09-20

    We report a patient with a giant phyllodes tumor of the right breast associated with a hypoglycemic attack. A 48-year-old woman experienced a loss of consciousness and was transferred via ambulance to our hospital emergency department. Upon arrival, her blood glucose level was 26 mg/dl, and a giant tumor (>20 cm in diameter) with skin ulceration was observed on the right breast. Core needle biopsy led to a histological diagnosis of a phyllodes tumor of the breast. Ultrasonography and computed tomography detected neither distant metastasis nor a pancreatic endocrine tumor. Her preoperative serum insulin-like growth factor (IGF)-II and insulin levels were 1,330 ng/ml (normal range, 519-1067 ng/ml) and <1.0 µU/ml, respectively. Following a simple mastectomy, the 24-h postoperative serum IGF-II and insulin levels were 496 ng/ml and 10.0 µU/ml, respectively. The IGF-II levels detected in the phyllodes tumor and normal breast tissue were 10,600 ng/Wg (wet weight in grams) and 855 ng/Wg. We conclude from these findings that the hypoglycemic attack was related to the elevated IGF-II level in the giant phyllodes tumor of the breast.

  2. A Tete – a – tete of benign, borderline and malignant fibrohistiocytic tumor

    PubMed Central

    M.V, Rashmi.; P, Pavithra; G.M, Shivakumarappa

    2016-01-01

    Dermatofibrosarcoma protruberans is a relatively uncommon slow growing, locally aggressive fibrous tumor of the skin. It has a prospensity of progressing to fibrosarcomatous change in 5% of the cases. We present a case of a 56 yr old male with presented to the outpatient department of surgery, Sri Siddhartha Medical College, Tumkur with a chest swelling in 2013. FNAC was inconclusive and the mass was excised. On histopathology, areas of benign fibrohistiocytic tumor, dermatofibrosarcoma protruberans and fibrosarcomatous dermatofibrosarcoma were identified in the same tumor. Immunohistochemistry confirmed the diagnosis of DFSP with fibrosarcomatous change. Although, transformed DFSP is more aggressive, the prognosis is influenced by the extent of excision and with wide excision, there may be little increased risk for recurrence and metastasis over that of conventional DFSP. PMID:27799980

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

    PubMed

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

    2016-07-01

    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.

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

    SciTech Connect

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

    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.

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

    PubMed

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

    2014-03-07

    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.

  6. Endometriosis-associated serous borderline tumor and endometrial stromal sarcoma of the ovary: a report of a rare lesion in an infant.

    PubMed

    Ho, Ronnie S L; Chan, Godfrey C F; Ha, Shau Yin; Ip, Philip P C

    2012-01-01

    Endometriosis in infancy is most unusual, and associated tumors in this age group are exceptionally rare. We report a case of a serous borderline tumor and endometrial stromal sarcoma arising in an ovarian endometriotic cyst. The patient was an infant of 18 months of age who presented with an incidental abdominal mass. The serum sex hormones were at prepubertal levels. There was no evidence of precocious puberty or any obvious genital anomaly. Intraoperative findings included a solitary solid and multicystic right ovarian mass without evidence of any extraovarian disease. On microscopic examination, the tumor was composed of an intimate mixture of florid papillary and stromal cell proliferation in the wall of an endometriotic cyst. The papillae showed hierarchical branching and had hyalinized and edematous cores with scattered psammoma bodies. The epithelial cells were mildly atypical and mitotically inactive. The underlying endometrial stromal cells were arranged in irregular tongues that permeated the thickened fibrous cyst wall. They were mitotically active and immunoreactive for CD10. There was no evidence of any primitive germ cell tumor. The patient received no adjuvant treatment and had an uneventful postoperative follow-up period of 30 months. To the best of our knowledge, endometriosis associated with this most unusual combination of ovarian tumors has never been reported in an infant.

  7. Clinical application of optical coherence tomography for the imaging of non–melanocytic cutaneous tumors: a pilot multi–modal study

    PubMed Central

    Carstea, EM; Ghervase, L; Giurcaneanu, C; Pavelescu, G

    2010-01-01

    Context: Optical coherence tomography (OCT) is an emergent imaging technique, based on the interference of infrared radiation and living tissues, that allows the in vivo visualisation of the skin structures, at high resolution and up to 1.6 mm depth. As such, there is mounting evidence that OCT may be an interesting technique for the diagnossis of skin diseases, including the non–invasive early detection of cutaneous tumors. Objective: We aimed to investigate the utility of OCT for the diagnosis of non–melanocytic, non–pigmented cutaneous tumors. Methods: Preliminary results are presented from an initiated study. Fifteen consecutive patients with clinical suspicion of epithelial cancers and precancers registered over one week in an university dermatologic department were included. As control were selected 7 patients with inflammatory skin diseases (psoriasis, lichen planus, cutaneous lupus erythematosus). In all study and control patients the lesions and samples of normal, perilesional skin were documented by clinical digital photography, contact dermoscopy with digital image capture and OCT with central wavelength of 930 nm. Final diagnosis was certified by histopathological analysis. Results: We could identify morphological features in OCT examination that distinguished between normal and lesional skin, and between neoplastic vs. inflamatory lesions. In the same time, combining OCT and dermatoscopical evaluation of a lesion improved the performance of diagnosis when compared to clinical diagnosis alone and with either OCT or dermoscopy imaging used alone. Conclusions: OCT appears as a promising method of in vivo diagnosis of early neoplastic cutaneous lesions with equivocal clinical and/or dermoscopic aspect. Continuation of our study as well as other larger investigation will be able to contribute with new insights in the role of OCT in the non–invasive diagnosis of skin disease. PMID:21254735

  8. Mucins MUC16 and MUC1 are major carriers of SLe(a) and SLe(x) in borderline and malignant serous ovarian tumors.

    PubMed

    Ricardo, Sara; Marcos-Silva, Lara; Valente, Cristina; Coelho, Ricardo; Gomes, Rosa; David, Leonor

    2016-06-01

    Mucins are heavily glycosylated proteins overexpressed and associated with truncated or sialylated glycans upon malignant transformation. We previously identified a panel of four glyco-mucin profiles (MUC16/Tn, MUC16/STn, MUC1/Tn, and MUC1/STn) with 100 % specificity and 100 % positive predictive value for detection of borderline/malignant serous tumors of the ovary, using proximity ligation assay (PLA). In the present work, using the same method, we studied other mucin glycosylation profiles that might add relevant information for diagnostic purposes. We used PLA probes to MUC16, MUC1, sialyl Lewis(a) (SLe(a)), and sialyl Lewis(x) (SLe(x)) to study a series of 39 ovarian serous tumors (14 adenocarcinomas, 10 borderline ovarian tumors (BOTs), and 15 cystadenomas). Our results demonstrated that, in adenocarcinomas and BOTs, the major carriers of SLe(a) and SLe(x) are MUC16 and/or MUC1 (100 and 92 % for SLe(a) and 64 and 70 % for SLe(x), respectively). In cystadenomas, SLe(a) and SLe(x) are mainly carried by unidentified proteins (85 and 78 %, respectively). Our study identified, for the first time, the major protein carriers of SLe(a) and SLe(x) in ovarian adenocarcinomas and BOTs, MUC1 and MUC16, and also that distinct unidentified carriers are involved in cystadenomas. These results emphasize the relevance of multiple biomarker recognition provided by multiplex assays, such as PLA, to enhance sensitivity and specificity of serum and tissue assays.

  9. Loss of p16 expression and copy number changes of CDKN2A in a spectrum of spitzoid melanocytic lesions.

    PubMed

    Harms, Paul W; Hocker, Thomas L; Zhao, Lili; Chan, May P; Andea, Aleodor A; Wang, Min; Harms, Kelly L; Wang, Michael L; Carskadon, Shannon; Palanisamy, Nallasivam; Fullen, Douglas R

    2016-12-01

    Spitzoid melanocytic lesions, including Spitz nevi (benign), spitzoid melanoma (malignant), and borderline atypical Spitz tumors (ASTs), frequently present challenges for accurate diagnosis and prognosis. Evaluation for loss of the tumor suppressor p16, encoded by CDKN2A gene on chromosome 9p21.3, has been proposed to be useful for evaluation of spitzoid melanocytic lesions. However, reports on the utility of p16 immunohistochemistry for spitzoid lesions have been conflicting, and few studies have directly compared p16 immunohistochemistry with fluorescence in situ hybridization (FISH) for CDKN2A genomic status. We analyzed a spectrum of benign (n=24), borderline (n=27), and malignant (n=19) spitzoid lesions for p16 protein expression by immunohistochemistry and CDKN2A copy number by FISH. Immunohistochemistry was evaluated by 2 scoring methods: H score and 2-tiered score (positive or negative for p16 loss). By immunohistochemistry, loss of p16 expression was not observed in Spitz nevi (0/24) but was seen in ASTs (7/27; 26%) and spitzoid melanomas (3/19; 16%). By H score, p16 expression was significantly higher in Spitz nevi relative to ASTs or spitzoid melanomas. Similarly, copy number aberrations of CDKN2A by FISH were absent in Spitz nevi but were found in 2 (9.5%) of 21 ASTs and 4 (33%) of 12 spitzoid melanomas. Our findings from this large cohort suggest that p16 aberrations are highly specific for borderline and malignant spitzoid neoplasms relative to Spitz nevi. Similar to ASTs, p16 loss in spitzoid melanomas may occur in the presence or absence of genomic CDKN2A loss.

  10. 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.

    PubMed

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

    2017-02-06

    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.

  11. Giant congenital melanocytic nevus*

    PubMed Central

    Viana, Ana Carolina Leite; Gontijo, Bernardo; Bittencourt, Flávia Vasques

    2013-01-01

    Giant congenital melanocytic nevus is usually defined as a melanocytic lesion present at birth that will reach a diameter ≥ 20 cm in adulthood. Its incidence is estimated in <1:20,000 newborns. Despite its rarity, this lesion is important because it may associate with severe complications such as malignant melanoma, affect the central nervous system (neurocutaneous melanosis), and have major psychosocial impact on the patient and his family due to its unsightly appearance. Giant congenital melanocytic nevus generally presents as a brown lesion, with flat or mammilated surface, well-demarcated borders and hypertrichosis. Congenital melanocytic nevus is primarily a clinical diagnosis. However, congenital nevi are histologically distinguished from acquired nevi mainly by their larger size, the spread of the nevus cells to the deep layers of the skin and by their more varied architecture and morphology. Although giant congenital melanocytic nevus is recognized as a risk factor for the development of melanoma, the precise magnitude of this risk is still controversial. The estimated lifetime risk of developing melanoma varies from 5 to 10%. On account of these uncertainties and the size of the lesions, the management of giant congenital melanocytic nevus needs individualization. Treatment may include surgical and non-surgical procedures, psychological intervention and/or clinical follow-up, with special attention to changes in color, texture or on the surface of the lesion. The only absolute indication for surgery in giant congenital melanocytic nevus is the development of a malignant neoplasm on the lesion. PMID:24474093

  12. Giant congenital melanocytic nevus.

    PubMed

    Viana, Ana Carolina Leite; Gontijo, Bernardo; Bittencourt, Flávia Vasques

    2013-01-01

    Giant congenital melanocytic nevus is usually defined as a melanocytic lesion present at birth that will reach a diameter ≥ 20 cm in adulthood. Its incidence is estimated in <1:20,000 newborns. Despite its rarity, this lesion is important because it may associate with severe complications such as malignant melanoma, affect the central nervous system (neurocutaneous melanosis), and have major psychosocial impact on the patient and his family due to its unsightly appearance. Giant congenital melanocytic nevus generally presents as a brown lesion, with flat or mammilated surface, well-demarcated borders and hypertrichosis. Congenital melanocytic nevus is primarily a clinical diagnosis. However, congenital nevi are histologically distinguished from acquired nevi mainly by their larger size, the spread of the nevus cells to the deep layers of the skin and by their more varied architecture and morphology. Although giant congenital melanocytic nevus is recognized as a risk factor for the development of melanoma, the precise magnitude of this risk is still controversial. The estimated lifetime risk of developing melanoma varies from 5 to 10%. On account of these uncertainties and the size of the lesions, the management of giant congenital melanocytic nevus needs individualization. Treatment may include surgical and non-surgical procedures, psychological intervention and/or clinical follow-up, with special attention to changes in color, texture or on the surface of the lesion. The only absolute indication for surgery in giant congenital melanocytic nevus is the development of a malignant neoplasm on the lesion.

  13. Inverse expression of cystein-rich 61 (Cyr61/CCN1) and connective tissue growth factor (CTGF/CCN2) in borderline tumors and carcinomas of the ovary.

    PubMed

    Bartel, Frank; Balschun, Katharina; Gradhand, Elise; Strauss, Hans G; Dittmer, Jürgen; Hauptmann, Steffen

    2012-09-01

    Members of the CCN [cystein-rich 61 (Cyr61)/connective tissue growth factor (CTGF)/nephroblastoma (NOV)] protein family are involved in the regulation of cellular proliferation, apoptosis, and migration and are also assumed to play a role in carcinogenesis. Therefore, we performed a retrospective study to investigate the immunohistochemical expression of both Cyr61 and CTGF in 92 borderline tumors (BOTs) and 107 invasive carcinomas of the ovary (IOCs). To determine their diagnostic and prognostic value, we correlated protein expression with clinicopathologic factors including overall and disease-free survival. Cyr61 and CTGF were found to be inversely expressed in both BOTs and IOCs, with a stronger expression of Cyr61 in IOCs. Moreover, Cyr61 was found to be preferentially expressed in high-grade serous carcinomas, whereas CTGF was found more frequently in low-grade serous carcinomas. Weak Cyr61 levels correlated with both low estrogen receptor and p53 expression (P=0.038, P=0.04, respectively). However, no association was observed between CTGF, estrogen receptor, and p53 expression levels in IOCs. Regarding prognosis, Cyr61 was found to be of no value, but the loss of CTGF was found to be associated with a poor prognosis in multivariate analysis of overall (relative risk 2.8; P=0.050) and disease-free (relative risk 2.3; P=0.031) survival. Cyr61 and CTGF are inversely expressed in BOTs and IOCs, and loss of CTGF independently indicates poor prognosis in IOCs.

  14. Melanocytes: the new Black.

    PubMed

    Goding, Colin R

    2007-01-01

    Melanocytes, pigment-producing cells residing primarily in the hair follicle, epidermis and eye, are responsible for skin hair and eye pigmentation. Pigmentation is achieved by the highly regulated manufacture of the pigment melanin in specialised organelles, melanosomes that are transported along dendritic processes before being transferred to growing hair, or keratinocytes where melanin protects from UV-induced DNA damage. Because loss of melanocytes gives a clear pigmentation phenotype yet is non-lethal, over 130 genes implicated in the development or function of this cell type have been identified to date, and in humans the loss of melanocytes or their ability to produce pigment, or transport or transfer melanosomes is associated with several diseases such as vitiligo, albinism and Hermansky-Pudlak syndrome. Importantly, the effective combination of genetics, cell and molecular biology possible with this cell type is attracting an increasing number of researchers focussed on understanding how cells coordinate survival, proliferation, differentiation and stem cell maintenance.

  15. [Dysplastic melanocytic nevus].

    PubMed

    Bierhoff, E

    2015-02-01

    Dysplastic nevus is still a controversial entity both clinically and histologically. The occurrence of dysplastic nevus especially in the context of dysplastic nevus cell syndrome is associated with an increased risk for melanoma. The following minimal histological criteria should be fulfilled: nests of melanocytes varying in size and shape, bridging and confluent, proliferation of single melanocytes basal and suprabasal, cytoplasmic and nuclear atypia of melanocytes and subepidermal fibroplasia. The biological behavior (common nevus variant or precursor of melanoma?) is difficult to evaluate by presently available methods. The further development of new molecular biology techniques may allow a better prognosis of dysplastic nevi in an objective and reproducible manner. Against this background complete excision followed by clinical surveillance has to be recommended for the routine practice.

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

    PubMed

    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.

  17. State of the art, nomenclature, and points of consensus and controversy concerning benign melanocytic lesions: outcome of an international workshop.

    PubMed

    Barnhill, Raymond L; Cerroni, Lorenzo; Cook, Martin; Elder, David E; Kerl, Helmut; LeBoit, Philip E; McCarthy, Stanley W; Mihm, Martin C; Mooi, Wolter J; Piepkorn, Michael W; Prieto, Victor G; Scolyer, Richard A

    2010-03-01

    The following communication summarizes the proceedings of a one-day International Workshop focusing on the histology of benign melanocytic nevi. Areas of controversy identified in 6 focus sessions were the nomenclature and relationships among common nevi including nevi with halo reactions, traumatized nevi, "dysplastic" nevi, and nevi from particular anatomic sites; developmental biology and frequency of malignant transformation associated with congenital nevi; the characterization and biologic nature of atypical spitzoid neoplasms; the basic definition of particular melanocytic cellular phenotypes, and the nomenclature and biologic nature of many candidate blue nevi, combined nevi, and other controversial lesions such as deep penetrating nevus and pigmented epithelioid melanocytoma. Concentrated data collection and follow-up, molecular characterization, and future consensus Workshops may facilitate the resolution of some of these problems. The Group recommended the description of ambiguous or "borderline" lesions as tumors with indeterminate or uncertain biologic/malignant potential. The participants also advised that such lesions at a minimum should be managed by complete excision with clear surgical margins.

  18. A new transgenic mouse line for tetracycline inducible transgene expression in mature melanocytes and the melanocyte stem cells using the Dopachrome tautomerase promoter.

    PubMed

    Woods, Susan L; Bishop, J Michael

    2011-04-01

    We have generated a novel transgenic mouse to direct inducible and reversible transgene expression in the melanocytic compartment. The Dopachrome tautomerase (Dct) control sequences we used are active early in the development of melanocytes and so this system was designed to enable the manipulation of transgene expression during development in utero and in the melanocyte stem cells as well as mature melanocytes. We observed inducible lacZ and GFP reporter transgene activity specifically in melanocytes and melanocyte stem cells in mouse skin. This mouse model will be a useful tool for the pigment cell community to investigate the contribution of candidate genes to normal melanocyte and/or melanoma development in vivo. Deregulated expression of the proto-oncogene MYC has been observed in melanoma, however whether MYC is involved in tumorigenesis in pigment cells has yet to be directly investigated in vivo. We have used our system to over-express MYC in the melanocytic compartment and show for the first time that increased MYC expression can indeed promote melanocytic tumor formation.

  19. MITF accurately highlights epidermal melanocytes in atypical intraepidermal melanocytic proliferations.

    PubMed

    Nybakken, Grant E; Sargen, Michael; Abraham, Ronnie; Zhang, Paul J; Ming, Michael; Xu, Xiaowei

    2013-02-01

    Atypical intraepidermal melanocytic proliferations (AIMP) have random cytologic atypia and other histologic features that are concerning for malignancy and often require immunohistochemistry to differentiate from melanoma in situ. Immunostaining with S100, Melan-A, and microphthalmia-associated transcription factor (MITF) was performed for 49 morphologically well-characterized AIMP lesions. The percentage of cells in the basal layer of the epidermis that were identified as melanocytes by immunohistochemistry was compared with the percentage observed by morphology on hematoxylin and eosin staining, which is the gold standard stain for identifying cytologic atypia within an AIMP. Melan-A estimated the highest percentage of melanocytes and S100 the fewest in 47 of the 49 lesions examined. The estimated percentage of melanocytes was 23.3% (95% confidence interval: 18.6-28.1; P < 0.001) higher for Melan-A compared with hematoxylin and eosin staining. Melanocyte estimates were similar for hematoxylin and eosin and MITF (P = 0.15) although S100 estimated 21.8% (95% confidence interval: -27.2 to -16.4; P < 0.001) fewer melanocytes than hematoxylin and eosin. Melan-A staining produces higher estimates of epidermal melanocytes than S100 and MITF, which may increase the likelihood of diagnosing melanoma in situ. In contrast, melanoma in situ may be underdiagnosed with the use of S100, which results in lower estimates of melanocytes than the other 2 immunostains. Therefore, the best immunohistochemical marker for epidermal melanocytes is MITF.

  20. Pirin Inhibits Cellular Senescence in Melanocytic Cells

    PubMed Central

    Licciulli, Silvia; Luise, Chiara; Scafetta, Gaia; Capra, Maria; Giardina, Giuseppina; Nuciforo, Paolo; Bosari, Silvano; Viale, Giuseppe; Mazzarol, Giovanni; Tonelli, Chiara; Lanfrancone, Luisa; Alcalay, Myriam

    2011-01-01

    Cellular senescence has been widely recognized as a tumor suppressing mechanism that acts as a barrier to cancer development after oncogenic stimuli. A prominent in vivo model of the senescence barrier is represented by nevi, which are composed of melanocytes that, after an initial phase of proliferation induced by activated oncogenes (most commonly BRAF), are blocked in a state of cellular senescence. Transformation to melanoma occurs when genes involved in controlling senescence are mutated or silenced and cells reacquire the capacity to proliferate. Pirin (PIR) is a highly conserved nuclear protein that likely functions as a transcriptional regulator whose expression levels are altered in different types of tumors. We analyzed the expression pattern of PIR in adult human tissues and found that it is expressed in melanocytes and has a complex pattern of regulation in nevi and melanoma: it is rarely detected in mature nevi, but is expressed at high levels in a subset of melanomas. Loss of function and overexpression experiments in normal and transformed melanocytic cells revealed that PIR is involved in the negative control of cellular senescence and that its expression is necessary to overcome the senescence barrier. Our results suggest that PIR may have a relevant role in melanoma progression. PMID:21514450

  1. Melanocytes and Their Diseases

    PubMed Central

    Yamaguchi, Yuji; Hearing, Vincent J.

    2014-01-01

    Human melanocytes are distributed not only in the epidermis and in hair follicles but also in mucosa, cochlea (ear), iris (eye), and mesencephalon (brain) among other tissues. Melanocytes, which are derived from the neural crest, are unique in that they produce eu-/pheo-melanin pigments in unique membrane-bound organelles termed melanosomes, which can be divided into four stages depending on their degree of maturation. Pigmentation production is determined by three distinct elements: enzymes involved in melanin synthesis, proteins required for melanosome structure, and proteins required for their trafficking and distribution. Many genes are involved in regulating pigmentation at various levels, and mutations in many of them cause pigmentary disorders, which can be classified into three types: hyperpigmentation (including melasma), hypopigmentation (including oculocutaneous albinism [OCA]), and mixed hyper-/hypopigmentation (including dyschromatosis symmetrica hereditaria). We briefly review vitiligo as a representative of an acquired hypopigmentation disorder. PMID:24789876

  2. Congenital melanocytic nevus with features of hybrid schwannoma/perineurioma.

    PubMed

    Wang, Lei; Wang, Gang; Gao, Tianwen

    2013-05-01

    Neural differentiation by melanocytic nevi represents a well-recognized phenomenon, and melanocytic nevi with perineurial differentiation have been reported recently. We reported a case of a congenital melanocytic nevus with histopathologic features of hybrid schwannoma/perineurioma. The patient was a 36-year-old male who presented with a black tumor on his arm since birth. Histopathology showed a congenital melanocytic nevus in the superficial dermis, but more strikingly, in continuity with the melanocytic nevus, there was a well-circumscribed but unencapsulated nodule in the deep dermis. The nodule was composed of cellular and myxoid areas with storiform, laminated or whorled growth patterns. The cellular area was mainly composed of proliferation of plump spindle, oval or epithelioid cells. The myxoid area was mainly composed of proliferation of slender spindle cells with mucin deposition. Immunohistochemical stains showed that the cellular area was positive for S100 and CD34, weakly positive for EMA, negative for Glut-1 and collagen IV, the myxoid area was positive for S100, negative for CD34, strongly positive for EMA and focally positive for Glut-1 and collagen IV. Our results show that congenital melanocytic nevi may show neural differentiation with histopathologic features of hybrid schwannoma/perineurioma.

  3. Borderline Space for Voice

    ERIC Educational Resources Information Center

    Batchelor, Denise

    2012-01-01

    Being on the borderline as a student in higher education is not always negative, to do with marginalisation, exclusion and having a voice that is vulnerable. Paradoxically, being on the edge also has positive connections with integration, inclusion and having a voice that is strong. Alternative understandings of the concept of borderline space can…

  4. VITILIGO AND THE MELANOCYTE RESERVOIR

    PubMed Central

    Falabella, Rafael

    2009-01-01

    Repigmentation of vitiligo depends on available melanocytes from three possible sources: from the hair follicle unit which is the main provider of pigment cells, from the border of vitiligo lesions, and from unaffected melanocytes within depigmented areas; pigment cells at these locations originate a perifollicular, border spreading and a diffuse repigmentation pattern. In order for repigmentation to take place under stimulation with diverse therapies, melanocytes should be present in appropriate numbers. Melanocyte tissue stem cells located in the niche at the bulge region of the hair follicle are the most important sources for providing immature pigment cells that undergo terminal differentiation and originate repigmentation, but cytokines, UVR and other molecules acting in melanogenesis with adequate regulation mechanisms contribute to successful recovery in vitiligo. The presence of keratinocyte stem cells in the interfollicular epidermis raises the question on the possibility of melanocyte stem cells in a similar location and the development of future strategies for therapeutic purposes. PMID:20101329

  5. Borderline personality disorder

    MedlinePlus

    American Psychiatric Association. Borderline personality disorder. Diagnostic and Statistical Manual of Mental Disorders . 5th ed. Arlington, VA: American Psychiatric Publishing. 2013:663-666. Blais MA, Smallwood P, Groves ...

  6. Treatment of Borderline Adolescents.

    ERIC Educational Resources Information Center

    Green, Maurice R.

    1983-01-01

    Describes characteristics of borderline adolescents and reviews diagnostic issues. Uses two case studies to illustrate general treatment strategies that could be useful to clinicians in mental health programs and family courts. (JAC)

  7. The biology of melanocyte and melanocyte stem cell.

    PubMed

    Li, Ang

    2014-04-01

    The melanocyte stem cells of the hair follicle provide an attractive system for the study of the stem cells. Successful regeneration of a functional organ relies on the organized and timely orchestration of molecular events among distinct stem/progenitor cell populations. The stem cells are regulated by communication with their specialized microenvironment known as the niche. Despite remarkable progress in understanding stem cell-intrinsic behavior, the molecular nature of the extrinsic factors provided to the stem cells by the niche microenvironment remains poorly understood. In this regard, the bulge niche of the mammalian hair follicle offers an excellent model for study. It holds two resident populations of SCs: epidermal stem cells and melanocyte stem cells. While their behavior is tightly coordinated, very little of the crosstalk involved is known. This review summarized the recent development in trying to understand the regulation of melanocyte and melanocyte stem cells. A better understanding of the normal regulation and behaviors of the melanocytes and the melanocyte stem cells will help to improve the clinical applications in regenerative medicine, cancer therapy, and aging.

  8. Amelanotic Melanoma in the Vicinity of Acquired Melanocytic Nevi and not Arising from Agminated Melanocytic Nevi: Masquerading as Pyogenic Granuloma

    PubMed Central

    Rao, Angoori Gnaneshwar; Babu, V Ashok; Koppada, Divya; Haritha, M; Chandana, P; Swapna; Anoosha

    2016-01-01

    Amelanotic melanoma (AMM) presenting as pyogenic granuloma and occurring in the vicinity of acquired melanocytic nevi is rare. Herein, we report such a manifestation in a 68-year-old male who presented with the painful red nodule and multiple pigmented patches involving the left great toe. Histopathological examination of skin biopsy taken from the nodule with an immunohistochemical study using HMB45 and S-100 confirmed the diagnosis of AMM. Biopsy from the pigmented patch near the nodule showed features of melanocytic nevus. Investigative work up revealed metastatic deposits in the left inguinal lymph node with no evidence of systemic involvement, placing him in malignant melanoma Stage IIIC of American Joint Committee on Cancer (AJCC) tumor node metastasis system. The development of AMM in the vicinity of acquired melanocytic nevi and manifesting as granuloma pyogenicum is unique in this case. PMID:26955141

  9. Signet ring cell melanocytic nevus: report of a case over trichilemmal cyst and review of the literature.

    PubMed

    Sabater Marco, Vicente; Escutia Muñoz, Begoña; Morera Faet, Arturo; Botella Estrada, Rafael

    2012-02-01

    Different melanocytic nevi have been reported as being associated with dermal cysts. Signet ring cell melanocytic nevus is a rare variant of melanocytic nevus characterized by cells with signet ring morphology within a common melanocytic nevus. This article describes an exceptional case of melanocytic nevus composed exclusively of signet ring cells over a trichilemmal cyst. Histologically, above the cyst, there was a small, symmetrical and sharply demarcated lesion showing a compound proliferation of small, round, monomorphous cells with signet ring morphology. Immunohistochemically, signet ring cells were negative for cytokeratin AE1/3, leukocyte common antigen, HMB-45, and CD34. Occasionally, isolated signet ring cells were positive for S-100 and melan A. Melanocytic nevus composed of signet ring cells should raise the differential diagnosis with other cutaneous tumors exhibiting signet ring cells. Previous cases of this entity reported in the literature are also reviewed.

  10. Pathology of eyelid tumors

    PubMed Central

    Pe’er, Jacob

    2016-01-01

    The eyelids are composed of four layers: skin and subcutaneous tissue including its adnexa, striated muscle, tarsus with the meibomian glands, and the palpebral conjunctiva. Benign and malignant tumors can arise from each of the eyelid layers. Most eyelid tumors are of cutaneous origin, mostly epidermal, which can be divided into epithelial and melanocytic tumors. Benign epithelial lesions, cystic lesions, and benign melanocytic lesions are very common. The most common malignant eyelid tumors are basal cell carcinoma in Caucasians and sebaceous gland carcinoma in Asians. Adnexal and stromal tumors are less frequent. The present review describes the more important eyelid tumors according to the following groups: Benign and malignant epithelial tumors, benign and malignant melanocytic tumors, benign and malignant adnexal tumors, stromal eyelid tumors, lymphoproliferative and metastatic tumors, other rare eyelid tumors, and inflammatory and infections lesions that simulate neoplasms. PMID:27146927

  11. Genetics Home Reference: giant congenital melanocytic nevus

    MedlinePlus

    ... noncancerous skin patch (nevus) that is composed of pigment-producing cells called melanocytes . It is present from ... called neurocutaneous melanosis, which is the presence of pigment-producing skin cells (melanocytes) in the tissue that ...

  12. Immobilized alpha-melanocyte stimulating hormone 10-13 (GKPV) inhibits tumor necrosis factor-alpha stimulated NF-kappaB activity.

    PubMed

    Kelly, J M; Moir, A J G; Carlson, K; Yang, Y; MacNeil, S; Haycock, J W

    2006-02-01

    alpha-MSH is an anti-inflammatory peptide which signals by binding to the melanocortin-1 receptor (MC1R) and elevating cyclic AMP in several different cells and tissues. The carboxyl terminal peptides of alpha-MSH (KPV/GKPV) are the smallest minimal sequences that prevent inflammation, but it is not known if they operate via MC1R or cyclic AMP. The aim of this study was to examine the intracellular signaling potential of the GKPV peptide sequence when immobilized to polystyrene beads via a polyethylene glycol moiety. Beads containing an immobilized GKPV peptide were investigated for their ability to inhibit proinflammatory tumor necrosis factor-alpha (TNF-alpha) stimulated activation of NF-kappaB in HBL cells stably transfected with an NF-kappaB-luciferase reporter construct. Peptide functionalized beads were compared with the ability of soluble peptide alone (alpha-MSH or GKPV) or non-functionalized beads to inhibit TNF-alpha stimulated activation of NF-kappaB. GKPV peptide functionalized beads significantly inhibited NF-kappaB-luciferase activity in comparison to beads containing no peptide moiety in one of two growths conditions investigated. Soluble alpha-MSH and GKPV peptides were also confirmed to inhibit NF-kappaB-luciferase. The present study suggests that the carboxyl terminal MSH peptide acts via a cell receptor-based mechanism and furthermore may support the potential use of such immobilized ligands for anti-inflammatory therapeutic use.

  13. [Borderline personality disorder].

    PubMed

    Sipos, V; Schweiger, U

    2006-02-23

    Characteristics of a borderline personality disorder include emotional instability and a self-threatening lack of impulsive control. As a result, interpersonal relationships are rendered difficult. The central elements of treatment are psychoeducation, self-management, improved stress tolerance and awareness, emotion managment and training in social competence.

  14. Cutaneous photobiology. The melanocyte vs. the sun: who will win the final round?

    PubMed

    Kadekaro, Ana Luisa; Kavanagh, Renny J; Wakamatsu, Kazumasa; Ito, Shosuke; Pipitone, Michelle A; Abdel-Malek, Zalfa A

    2003-10-01

    Solar ultraviolet radiation (UV) is a major environmental factor that dramatically alters the homeostasis of the skin as an organ by affecting the survival, proliferation and differentiation of various cutaneous cell types. The effects of UV on the skin include direct damage to DNA, apoptosis, growth arrest, and stimulation of melanogenesis. Long-term effects of UV include photoaging and photocarcinogenesis. Epidermal melanocytes synthesize two main types of melanin: eumelanin and pheomelanin. Melanin, particularly eumelanin, represents the major photoprotective mechanism in the skin. Melanin limits the extent of UV penetration through the epidermal layers, and scavenges reactive oxygen radicals that may lead to oxidative DNA damage. The extent of UV-induced DNA damage and the incidence of skin cancer are inversely correlated with total melanin content of the skin. Given the importance of the melanocyte in guarding against the adverse effects of UV and the fact that the melanocyte has a low self-renewal capacity, it is critical to maintain its survival and genomic integrity in order to prevent malignant transformation to melanoma, the most fatal form of skin cancer. Melanocyte transformation to melanoma involves the activation of certain oncogenes and the inactivation of specific tumor suppressor genes. This review summarizes the current state of knowledge about the role of melanin and the melanocyte in photoprotection, the responses of melanocytes to UV, the signaling pathways that mediate the biological effects of UV on melanocytes, and the most common genetic alterations that lead to melanoma.

  15. Neuroendocrine activity of the melanocyte

    PubMed Central

    Slominski, Andrzej

    2009-01-01

    More than 15 years ago, we have proposed that melanocytes are sensory and regulatory cells with computing capability, which transform external and/or internal signals/energy into organized regulatory network(s) for the maintenance of the cutaneous homeostasis. This concept is substantiated by accumulating evidence that melanocytes produce classical stress neurotransmitters, neuropeptides and hormones, express corresponding receptors and these processes are modified and/or regulated by ultraviolet radiation, biological factors or stress. Examples of the above are catecholamines, serotonin, N-acetyl-serotonin, melatonin, proopiomelanocortin-derived adrenocorticotropic hormone, β-endorphin or melanocyte-stimulating hormone peptides, corticotropin releasing factor, related urocortins and corticosteroids including cortisol and corticosterone as well as their precursors. Furthermore, their production is not random, but hierarchical and follows the structures of classical neuroendocrine organizations such as hypothalamic-pituitary-adrenal axis, serotoninergic, melatoninergic and catecholaminergic systems. An example of an intrinsic but overlooked neuroendocrine activity is production and secretion of melanogenesis intermediates including L-DOPA or its derivatives that could enter circulation and act on distant sites. Such capabilities have defined melanocytes as neuroendocrine cells that not only coordinate cutaneous but also can affect a global homeostasis. PMID:19558501

  16. Pigment-Synthesizing Melanocytic Neoplasm With Protein Kinase C Alpha (PRKCA) Fusion

    PubMed Central

    Bahrami, Armita; Lee, Seungjae; Wu, Gang; Kerstetter, Justin; Rahvar, Maral; Li, Xinmin; Easton, John; Zhang, Jinghui; Barnhill, Raymond L.

    2016-01-01

    IMPORTANCE Melanocytic neoplasms with prominent pigment synthesis mimicking equine melanoma represent a rare variant of biologically indeterminate or low-grade malignant melanocytic tumors in which the molecular profile and exact histologic classification are not established. Tumors with these characteristics rarely occur as congenital lesions. We performed genomic analysis of a congenital pigment synthesizing melanocytic neoplasm with indeterminate biological potential. OBSERVATIONS The patient was a 5-month-old girl presenting with a 6-cm protuberant scalp mass, which had doubled in size since birth. Histologic examination showed heavily pigmented intradermal proliferation of large, epithelioid melanocytes with mild cytologic atypia, low mitotic activity, focal necrosis, and ulceration. RNA sequencing identified a novel ATPase, Ca2+ transporting, plasma membrane 4 (ATP2B4)–protein kinase C-alpha (PRKCA) fusion transcript. The fusion resulted in an in-frame linkage of the PRKCA catalytic domain with the N-terminal of ATP2B4 and high expression of the PRKCA kinase domain. Break-apart fluorescence in situ hybridization showed PRKCA rearrangement, and reverse transcriptase–polymerase chain reaction confirmed the presence of the fusion transcript. The patient was alive and well, with no evidence of recurrence, at the 1-year follow-up. CONCLUSIONS AND RELEVANCE To our knowledge, this is the first report of PRKCA fusions in melanocytic neoplasms. Future studies need to determine the frequency of PRKCA fusions in pigment-synthesizing melanocytic neoplasms. PMID:26676968

  17. Melanocytes Affect Nodal Expression and Signaling in Melanoma Cells: A Lesson from Pediatric Large Congenital Melanocytic Nevi.

    PubMed

    Margaryan, Naira V; Gilgur, Alina; Seftor, Elisabeth A; Purnell, Chad; Arva, Nicoleta C; Gosain, Arun K; Hendrix, Mary J C; Strizzi, Luigi

    2016-03-22

    Expression of Nodal, a Transforming Growth Factor-beta (TGF-β) related growth factor, is associated with aggressive melanoma. Nodal expression in adult dysplastic nevi may predict the development of aggressive melanoma in some patients. A subset of pediatric patients diagnosed with giant or large congenital melanocytic nevi (LCMN) has shown increased risk for development of melanoma. Here, we investigate whether Nodal expression can help identify the rare cases of LCMN that develop melanoma and shed light on why the majority of these patients do not. Immunohistochemistry (IHC) staining results show varying degree of Nodal expression in pediatric dysplastic nevi and LCMN. Moreover, median scores from Nodal IHC expression analysis were not significantly different between these two groups. Additionally, none of the LCMN patients in this study developed melanoma, regardless of Nodal IHC levels. Co-culture experiments revealed reduced tumor growth and lower levels of Nodal and its signaling molecules P-SMAD2 and P-ERK1/2 when melanoma cells were grown in vivo or in vitro with normal melanocytes. The same was observed in melanoma cells cultured with melanocyte conditioned media containing pigmented melanocyte derived melanosomes (MDM). Since MDM contain molecules capable of inactivating radical oxygen species, to investigate potential anti-oxidant effect of MDM on Nodal expression and signaling in melanoma, melanoma cells were treated with either N-acetyl-l-cysteine (NAC), a component of the anti-oxidant glutathione or synthetic melanin, which in addition to providing pigmentation can also exert free radical scavenging activity. Melanoma cells treated with NAC or synthetic melanin showed reduced levels of Nodal, P-SMAD2 and P-ERK1/2 compared to untreated melanoma cells. Thus, the potential role for Nodal in melanoma development in LCMN is less evident than in adult dysplastic nevi possibly due to melanocyte cross-talk in LCMN capable of offsetting or delaying the pro

  18. [Whose borderline is it? Hypothesized etiologies of borderline personality].

    PubMed

    Gil, Tsvi E

    2008-11-01

    Borderline personality is a well known concept in psychiatric literature, however, not fully understood as to its very nature. This article presents a short review of hypothesized etiologies of the borderline personality, starting with so called traditional theories, namely, borderline personality as a consolidated personality organization, in which the patient pathologically deals with his or her inner aggression, or with an enduring developmental failure. More modern hypotheses focus on possible childhood sexual abuse as the origin of the borderline, viewing the adult personality as a chronic, unresolved, post-traumatic disorder. Additionally, a neuro-epigenetic view hypothesized that a unique congenital neurological structure interacts with consequential events in early childhood to create the borderline personality.

  19. Sox proteins in melanocyte development and melanoma

    PubMed Central

    Harris, Melissa L.; Baxter, Laura L.; Loftus, Stacie K.; Pavan, William J.

    2010-01-01

    Over ten years has passed since the first Sox gene was implicated in melanocyte development. Since then, we have discovered that SOX5, SOX9, SOX10 and SOX18 all participate as transcription factors that affect key melanocytic genes in both regulatory and modulatory fashions. Both SOX9 and SOX10 play major roles in the establishment and normal function of the melanocyte; SOX10 has been shown to heavily influence melanocyte development and SOX9 has been implicated in melanogenesis in the adult. Despite these advances, the precise cellular and molecular details of how these SOX proteins are regulated and interact during all stages of the melanocyte life cycle remain unknown. Improper regulation of SOX9 or SOX10 is also associated with cancerous transformation, and thus understanding the normal function of SOX proteins in the melanocyte will be key to revealing how these proteins contribute to melanoma. PMID:20444197

  20. The melanocyte lineage in development and disease

    PubMed Central

    Mort, Richard L.; Jackson, Ian J.; Patton, E. Elizabeth

    2015-01-01

    Melanocyte development provides an excellent model for studying more complex developmental processes. Melanocytes have an apparently simple aetiology, differentiating from the neural crest and migrating through the developing embryo to specific locations within the skin and hair follicles, and to other sites in the body. The study of pigmentation mutations in the mouse provided the initial key to identifying the genes and proteins involved in melanocyte development. In addition, work on chicken has provided important embryological and molecular insights, whereas studies in zebrafish have allowed live imaging as well as genetic and transgenic approaches. This cross-species approach is powerful and, as we review here, has resulted in a detailed understanding of melanocyte development and differentiation, melanocyte stem cells and the role of the melanocyte lineage in diseases such as melanoma. PMID:25670789

  1. Melanocyte expression of Survivin promotes development and metastasis of UV-induced melanoma in HGF-transgenic mice

    PubMed Central

    Thomas, Joshua; Liu, Tong; Cotter, Murray A.; Florell, Scott R.; Robinette, Kyle; Hanks, Adrianne N.; Grossman, Douglas

    2008-01-01

    We previously found the apoptosis inhibitor Survivin to be expressed in melanocytic nevi and melanoma, but not in normal melanocytes. To investigate the role of Survivin in melanoma development and progression, we examined the consequences of forced Survivin expression in melanocytes in vivo. Transgenic (Tg) mouse lines (Dct-Survivin) were generated with melanocyte-specific expression of Survivin, and melanocytes grown from Dct-Survivin mice expressed Survivin. Dct-Survivin melanocytes exhibited decreased susceptibility to UV-induced apoptosis but no difference in proliferative capacity compared to melanocytes derived from non-Tg littermates. Induction of nevi in Dct-Survivin and non-Tg mice by topical application of DMBA did not reveal significant differences in lesion onset (median 10 wks) or density (4 lesions/mouse after 15 wks). Dct-Survivin mice were bred with melanoma-prone MH19/HGF-B6 Tg mice and all progeny expressing either individual, neither, or both (Survivin/HGF) transgenes were UV-treated as neonates and then monitored for 43 wks. Melanocytes in neonatal Survivin+/HGF+ mouse skin were less susceptible to UV-induced apoptosis than those from Survivin−/HGF+ mice. Onset of melanocytic tumors was earlier (median 18 vs. 24 wks, p = .01, log-rank test) and overall tumor density was greater (7.7 vs. 5.2 tumors/mouse, p = .04) in Survivin+/HGF+ compared to Survivin−/HGF+ mice. Strikingly, melanomas arising in Survivin+/HGF+ mice demonstrated a greater tendency for lymph node (35% vs. 0%, p = .04) and lung (53% vs. 22%) metastasis, and lower rates of spontaneous apoptosis, than those in Survivin−/HGF+ mice. These studies demonstrate a role for Survivin in promoting both early and late events of UV-induced melanoma development in vivo. PMID:17545596

  2. Repression of genes involved in melanocyte differentiation in uveal melanoma

    PubMed Central

    Bergeron, Marjorie-Allison; Champagne, Sophie; Gaudreault, Manon; Deschambeault, Alexandre

    2012-01-01

    Purpose Uveal melanoma (UM) has been the subject of intense interest due to its distinctive metastatic pattern, which involves hematogenous dissemination of cancerous cells toward the liver in 50% of patients. To search for new UM prognostic markers, the Suppressive Subtractive Hybridization (SSH) technique was used to isolate genes that are differentially expressed between UM primary tumors and normal uveal melanocytes (UVM). Methods A subtracted cDNA library was prepared using cDNA from uncultured UM primary tumors and UVM. The expression level of selected genes was further validated by cDNA microarray, semi-quantitative reverse transcription polymerase chain reaction (RT-PCR), and immunofluorescence analyses. Results One hundred-fifteen genes were identified using the SSH technique. Microarray analyses comparing the gene expression profiles of UM primary tumors to UVM validated a significant differential expression for 48% of these genes. The expression pattern of selected genes was then analyzed by semi-quantitative RT–PCR and was found to be consistent with the SSH and cDNA microarray findings. A down-regulation of genes associated with melanocyte differentiation was confirmed in UM primary tumors. Presence of undifferentiated cells in the UM was demonstrated by the expression of stem cell markers ATP-binding cassette sub-family G member 2 (ABCG2) and octamer-binding protein 4 (OCT4). Conclusions We demonstrated that the SSH technique is efficient to detect differentially expressed genes between UM and UVM. The genes identified in this study represent valuable candidates for further functional analysis in UM and should be informative in studying the biology of this tumor. In addition, deregulation of the melanocyte differentiation pathway revealed the presence of UM cells exhibiting a stem cell-like phenotype. PMID:22815634

  3. Ocular surface tumors

    PubMed Central

    Othman, Ihab Saad

    2009-01-01

    Tumors of the conjunctiva and cornea comprise a large and varied spectrum of conditions. These tumors are grouped into two major categories of congenital and acquired lesions. The acquired lesions are further subdivided based on origin of the mass into surface epithelial, mucoepidermoid, melanocytic, vascular, fibrous, neural, histiocytic, myxoid, myogenic, lipomatous, lymphoid, leukemic, metastatic and secondary tumors. Ocular surface tumors include a variety of neoplasms originating from squamous epithelium, melanocytic tumors and lymphocytic resident cells of the conjunctival stroma. In this review, we highlight clinical features of these lesions, important diagnostic and investigative tools and standard care of management. PMID:21234217

  4. Risk factors for growth and metastasis of small choroidal melanocytic lesions.

    PubMed Central

    Shields, C L; Shields, J A; Kiratli, H; De Potter, P; Cater, J R

    1995-01-01

    PURPOSE: To investigate the clinical features that predict growth and metastasis of an unselected group of small melanocytic choroidal tumors. METHODS: A retrospective review was performed on 1329 patients with small melanocytic choroidal tumors measuring 3 mm in thickness or less. Clinical parameters of the patient and tumor were extracted and analyzed for their relationship to eventual tumor growth and metastasis using a Cox proportional hazards regression model. RESULTS: Tumor growth was documented in 18% of patients. The factors predictive of tumor growth (multivariate analysis) included greater tumor thickness, posterior tumor margin touching optic disc, symptoms of flashes, floaters, and blurred vision, orange pigment on the tumor surface, and the presence of subretinal fluid. The relative risk (rr) was greatest for initial tumor thickness > 2.0 mm (rr 5.2) and posterior margin touching the optic disc (rr 2.6). After adjusting for significant tumor variables, the effect of interventional tumor treatment showed a decreasing risk for tumor growth as compared to continued observation without treatment. Of 1329 patients, 35 (3%) developed metastases. The factors predictive of metastases (multivariate analysis) included: posterior tumor margin touching the optic disc, documented growth, and greater tumor thickness. The relative risk for metastases was greatest for tumor thickness 1.1-3.0 mm (rr 8.8) and growth (rr 3.2). CONCLUSION: Of small choroidal melanocytic tumors measuring 3 mm or less in thickness at the time of initial examination, 18% demonstrate growth and 3% metastasize during the period of followup. Based on this analysis, the clinical features of these tumors can be used to estimate the risk for tumor growth and metastases and assist the clinician with patient management. PMID:8719682

  5. Prescribing and borderline personality disorder

    PubMed Central

    Chanen, Andrew M; Thompson, Katherine N

    2016-01-01

    Summary Accurate diagnosis is fundamental to effective management of borderline personality disorder, but many patients remain undetected. The first-line management for borderline personality disorder is psychosocial treatment, not drugs. There are major prescribing hazards including polypharmacy, overdose and misuse. Drug treatment might be warranted for patients who have a co-occurring mental disorder such as major depression. If a drug is prescribed for borderline personality disorder, it should only be as an adjunct to psychosocial treatment. There should be clear and collaborative goals that are regularly reviewed with the patient. Use single drugs prescribed in limited quantities for a limited time. Stop drugs that are ineffective. PMID:27340322

  6. Biological characteristics of mouse skin melanocytes.

    PubMed

    Shi, Zhanquan; Ji, Kaiyuan; Yang, Shanshan; Zhang, Junzhen; Yao, Jianbo; Dong, Changsheng; Fan, Ruiwen

    2016-04-01

    The objective of this research was to evaluate the optimal passage number according to the biological characteristics of mouse skin melanocytes from different passages. Skin punch biopsies harvested from the dorsal region of 2-day old mice were used to establish melanocyte cultures. The cells from passage 4, 7, 10 and 13 were collected and evaluated for their melanogenic activity. Histochemical staining for tyrosinase (TYR) activity and immunostaining for the melanocyte specific markers including S-100 antigen, TYR, tyrosinase related protein 1 (TYRP1), tyrosinase related protein 2 (TYRP2) and micropthalmia associated transcription factor (MITF) confirmed purity and melanogenic capacity of melanocytes from different passages, with better melanogenic activity of passage 10 and 13 cells being observed. Treatment of passage 13 melanocytes with α-melanocyte stimulating hormone (α-MSH) showed increased expression of MITF, TYR and TYRP2 mRNA. However, considering the TYR mRNA dramatically high expression which is the characteristics of melanoma cells, melanocytes from passage 10 was the optimal passage number for the further research. Our results demonstrate culture of pure populations of mouse melanocytes to at least 10 passages and illustrate the potential utility of passage 10 cells for studies of intrinsic and extrinsic regulation of genes controlling pigmentation and coat color in mouse.

  7. 4-Tertiary butyl phenol exposure sensitizes human melanocytes to dendritic cell-mediated killing: relevance to vitiligo.

    PubMed

    Kroll, Tara M; Bommiasamy, Hemamalini; Boissy, Raymond E; Hernandez, Claudia; Nickoloff, Brian J; Mestril, Ruben; Caroline Le Poole, I

    2005-04-01

    The trigger initiating an autoimmune response against melanocytes in vitiligo remains unclear. Patients frequently experience stress to the skin prior to depigmentation. 4-tertiary butyl phenol (4-TBP) was used as a model compound to study the effects of stress on melanocytes. Heat shock protein (HSP)70 generated and secreted in response to 4-TBP was quantified. The protective potential of stress proteins generated following 4-TBP exposure was examined. It was studied whether HSP70 favors dendritic cell (DC) effector functions as well. Melanocytes were more sensitive to 4-TBP than fibroblasts, and HSP70 generated in response to 4-TBP exposure was partially released into the medium by immortalized vitiligo melanocyte cell line PIG3V. Stress protein HSP70 in turn induced membrane tumor necrosis factor-related apoptosis-inducing ligand (TRAIL) expression and activation of DC effector functions towards stressed melanocytes. Melanocytes exposed to 4-TBP demonstrated elevated TRAIL death receptor expression. DC effector functions were partially inhibited by blocking antibodies to TRAIL. TRAIL expression and infiltration by CD11c+ cells was abundant in perilesional vitiligo skin. Stressed melanocytes may mediate DC activation through release of HSP70, and DC effector functions appear to play a previously unappreciated role in progressive vitiligo.

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

    PubMed Central

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

    2011-01-01

    Semaphorins are secreted and membrane bound proteins involved in neural pathfinding, organogenesis, and tumor progression, through Plexin and neuropilins receptors. We recently reported that Plexin B1, the Semaphorin 4D receptor, is a tumor suppressor protein for melanoma, 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 ultraviolet irradiation, that it stimulates proliferation, and regulates the activity of the c-Met receptor. c-Met receptor signaling stimulates melanocyte migration, in part through down-regulation 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 Semaphorin 4D 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 down-regulated by UVB in melanocytes, loss of Plexin B1 may accentuate HGF dependent effects on melanocytes, including melanocyte migration. PMID:22189792

  9. Isolation, culture, and transfection of melanocytes.

    PubMed

    Godwin, Lauren S; Castle, Joanna T; Kohli, Jaskaren S; Goff, Philip S; Cairney, Claire J; Keith, W Nicol; Sviderskaya, Elena V; Bennett, Dorothy C

    2014-06-03

    Located in the basal epidermis and hair follicles, melanocytes of the integument are responsible for its coloration through production of melanin pigments. Melanin is produced in lysosomal-like organelles called melanosomes. In humans, this skin pigmentation acts as an ultraviolet radiation filter. Abnormalities in the division of melanocytes are quite common, with potentially oncogenic growth usually followed by cell senescence producing benign naevi (moles), or occasionally melanoma. Therefore, melanocytes are a useful model for studying melanoma, as well as pigmentation and organelle transport and the diseases affecting these mechanisms. This chapter focuses on the isolation, culture, and transfection of human and murine melanocytes. The first basic protocol describes the primary culture of melanocytes from human skin and the maintenance of growing cultures. The second basic protocol details the subculture and preparation of mouse keratinocyte feeder cells. The primary culture of melanocytes from mouse skin is described in the third basic protocol, and, lastly, the fourth basic protocol outlines a technique for transfecting melanocytes and melanoma cells.

  10. Borderline Personality Disorder

    PubMed Central

    Brüne, Martin

    2016-01-01

    The term ‘Borderline Personality Disorder’ (BPD) refers to a psychiatric syndrome that is characterized by emotion dysregulation, impulsivity, risk-taking behavior, irritability, feelings of emptiness, self-injury and fear of abandonment, as well as unstable interpersonal relationships. BPD is not only common in psychiatric populations but also more prevalent in the general community than previously thought, and thus represents an important public health issue. In contrast to most psychiatric disorders, some symptoms associated with BPD may improve over time, even without therapy, though impaired social functioning and interpersonal disturbances in close relationships often persist. Another counterintuitive and insufficiently resolved question is why depressive symptoms and risk-taking behaviors can occur simultaneously in the same individual. Moreover, there is an ongoing debate about the nosological position of BPD, which impacts on research regarding sex differences in clinical presentation and patterns of comorbidity. In this review, it is argued that many features of BPD may be conceptualized within an evolutionary framework, namely behavioral ecology. According to Life History Theory, BPD reflects a pathological extreme or distortion of a behavioral ‘strategy’ which unconsciously aims at immediate exploitation of resources, both interpersonal and material, based on predictions shaped by early developmental experiences. Such a view is consistent with standard medical conceptualizations of BPD, but goes beyond classic ‘deficit’-oriented models, which may have profound implications for therapeutic approaches. PMID:26929090

  11. Pigmentation PAX-ways: The role of Pax3 in melanogenesis, melanocyte stem cell maintenance, and disease

    PubMed Central

    Kubic, Jennifer D.; Young, Kacey P.; Plummer, Rebecca S.; Ludvik, Anton E.; Lang, Deborah

    2010-01-01

    Transcription factors initiate a program of gene expression and are catalysts in downstream molecular cascades that modulate a variety of cellular processes. Pax3 is a transcription factor that is important in the melanocyte and influences melanocytic proliferation, resistance to apoptosis, migration, lineage specificity and differentiation. In this review, we focus on Pax3 and the molecular pathways that Pax3 is a part of during melanogenesis and in the melanocyte stem cell. These roles of Pax3 are emphasized during the development of diseases and syndromes resulting from either too much or too little Pax3 function. Due to its key task in melanocyte stem cells and tumors, the Pax3 pathway may provide an ideal target for either stem cell or cancer therapies. PMID:18983540

  12. [Whose borderline is it? Reconsidering diagnosing borderline personality].

    PubMed

    Gil, Tsvi E

    2008-11-01

    The present article critically discusses diagnosing borderline personality, demonstrating ideas raised with a treated case. In contrast to routine diagnoses made by psychiatrists according to common diagnosing systems (such as the American DSM or the WHO's ICD), we wonder whether this diagnosis reflects a medico-social construct, which is associated to the female status in masculine (or even patriarch) society, and probably associated even to the context of a woman diagnosed by a psychiatric system. In the context of critically viewing aetiological hypotheses to borderline personality (presented in our former article as a personality constellated around complex and prolonged trauma) in this article we suggest viewing borderline behaviours and symptoms as manifestations of coping and survival of a woman-victim in abusing surroundings.

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

    PubMed

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

    2017-01-01

    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 (κw) or kappa (κ) analysis (original cytology vs cytology review κw = 0.24; original cytology vs original histopathology κw = 0.007; original cytology vs histopathology review κw = 0.23; cytology review vs original histopathology κw = 0.008; cytology review vs histopathology review κw = 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.

  14. The Long Noncoding RNA SPRIGHTLY Regulates Cell Proliferation in Primary Human Melanocytes.

    PubMed

    Zhao, Wei; Mazar, Joseph; Lee, Bongyong; Sawada, Junko; Li, Jian-Liang; Shelley, John; Govindarajan, Subramaniam; Towler, Dwight; Mattick, John S; Komatsu, Masanobu; Dinger, Marcel E; Perera, Ranjan J

    2016-04-01

    The long noncoding RNA SPRIGHTLY (formerly SPRY4-IT1), which lies within the intronic region of the SPRY4 gene, is up-regulated in human melanoma cells compared to melanocytes. SPRIGHTLY regulates a number of cancer hallmarks, including proliferation, motility, and apoptosis. To better understand its oncogenic role, SPRIGHTLY was stably transfected into human melanocytes, which resulted in increased cellular proliferation, colony formation, invasion, and development of a multinucleated dendritic-like phenotype. RNA sequencing and mass spectrometric analysis of SPRIGHTLY-expressing cells revealed changes in the expression of genes involved in cell proliferation, apoptosis, chromosome organization, regulation of DNA damage responses, and cell cycle. The proliferation marker Ki67, minichromosome maintenance genes 2-5, antiapoptotic gene X-linked inhibitor of apoptosis, and baculoviral IAP repeat-containing 7 were all up-regulated in SPRIGHTLY-expressing melanocytes, whereas the proapoptotic tumor suppressor gene DPPIV/CD26 was down-regulated, followed by an increase in extracellular signal-regulated kinase 1/2 phosphorylation, suggesting an increase in mitogen-activated protein kinase activity. Because down-regulation of DPPIV is known to be associated with malignant transformation in melanocytes, SPRIGHTLY-mediated DPPIV down-regulation may play an important role in melanoma pathobiology. Together, these findings provide important insights into how SPRIGHTLY regulates cell proliferation and anchorage-independent colony formation in primary human melanocytes.

  15. Porcine melanotic cutaneous lesions and lymph nodes: immunohistochemical differentiation of melanocytes and melanophages.

    PubMed

    Grossi, A B; Hyttel, P; Jensen, H E; Leifsson, P S

    2015-01-01

    Porcine melanomas have proven interesting in a wider biological perspective due to a common phenomenon of spontaneous regression, which is characterized by infiltration of macrophages, among others. Separation of neoplastic melanocytes from pigment-laden macrophages may, however, be challenging as the morphology of melanocytes varies considerably and sometimes resembles macrophages. The aim of this study was correspondingly to characterize and differentiate the cells in 20 porcine melanocytomas and regional lymph nodes by histologic examination and immunohistochemistry for melan A, PNL2, S100, lysozyme, alpha-1-antitrypsin, and ionized calcium binding adaptor molecule 1 (Iba1). Grossly, the melanocytomas were divided into 2 distinct types: pigmented maculae (n = 7) and raised tumors (n = 13). In the maculae, the pigmented cells were mainly melanocytes reactive for melan A, PNL2 and S100. In contrast, the majority of the cells in the raised tumors were melanophages, which expressed Iba1, alpha-1-antitrypsin, and lysozyme. Yet, cells histomorphologically indistinguishable from the melanophages expressed melan A and PNL2. These cells were Iba1 and S100 negative, and ultrastructurally, they were devoid of lysosomal bodies and filled with stage III and IV melanosomes. In the regional lymph nodes, melanocytes were present in the trabecular sinuses. In focally or diffusely black lymph nodes, pigmentation was, however, mainly due to aggregates of melanophages, which were confined to the trabeculae, deep cortex, and peripheral lymphoreticular tissue. Normal and neoplastic porcine melanocytes express melan A and PNL2, and immunohistochemical staining for melan A, PNL2, and Iba1 was found useful to identify and distinguish melanocytes and melanophages in porcine melanotic lesions.

  16. "Melanocytic Nests Arising in Lichenoid Inflammation": Reappraisal of the Terminology "Melanocytic Pseudonests".

    PubMed

    Chung, Hye Jin; Simkin, A David; Bhawan, Jag; Wolpowitz, Deon

    2015-12-01

    Pseudonests or pseudomelanocytic nests represent aggregates of cells and cell fragments, including keratinocytes, macrophages, lymphocytes, and occasional melanocytes. Pseudomelanocytic nests in the setting of lichenoid inflammation can mimic atypical melanocytic proliferations. Several reports documented nonspecific staining of pseudonests with melanoma antigen recognized by T cells-1/Melan-A, which can be detected in the cytoplasm of nonmelanocytic cells. In contrast, nuclear stains, such as MITF and SOX10, avoid this nonmelanocyte cytoplasmic staining. The authors have previously proposed the term melanocytic pseudonests to describe junctional nests with numerous (>2) true melanoma antigen recognized by T cells-1/Melan-A, SOX10, and MITF in a nonmelanocytic lesion with lichenoid inflammation (unilateral lichen planus pigmentosus/erythema dyschromicum perstans). In this study, the authors report another case of this phenomenon arising in a different lichenoid inflammatory dermatitis (lichen planus). The immunophenotype and number of clustered true melanocytes indicate that these dermoepidermal aggregates represent true melanocytic nests and not pseudonests of any type. Therefore, the authors propose the revised terminology of "melanocytic nests arising in lichenoid inflammation" to describe this novel pattern of benign melanocytic reorganization or proliferation in a subset of lichenoid dermatitides. Because this phenomenon can mimic atypical melanocytic proliferations, clinicopathologic correlation is essential for the correct diagnosis.

  17. Melanocytic Nests Arising in Lichenoid Inflammation”: Reappraisal of the Terminology “Melanocytic Pseudonests”

    PubMed Central

    Chung, Hye Jin; Simkin, A. David; Bhawan, Jag

    2015-01-01

    Abstract: Pseudonests or pseudomelanocytic nests represent aggregates of cells and cell fragments, including keratinocytes, macrophages, lymphocytes, and occasional melanocytes. Pseudomelanocytic nests in the setting of lichenoid inflammation can mimic atypical melanocytic proliferations. Several reports documented nonspecific staining of pseudonests with melanoma antigen recognized by T cells-1/Melan-A, which can be detected in the cytoplasm of nonmelanocytic cells. In contrast, nuclear stains, such as MITF and SOX10, avoid this nonmelanocyte cytoplasmic staining. The authors have previously proposed the term melanocytic pseudonests to describe junctional nests with numerous (>2) true melanoma antigen recognized by T cells-1/Melan-A, SOX10, and MITF in a nonmelanocytic lesion with lichenoid inflammation (unilateral lichen planus pigmentosus/erythema dyschromicum perstans). In this study, the authors report another case of this phenomenon arising in a different lichenoid inflammatory dermatitis (lichen planus). The immunophenotype and number of clustered true melanocytes indicate that these dermoepidermal aggregates represent true melanocytic nests and not pseudonests of any type. Therefore, the authors propose the revised terminology of “melanocytic nests arising in lichenoid inflammation” to describe this novel pattern of benign melanocytic reorganization or proliferation in a subset of lichenoid dermatitides. Because this phenomenon can mimic atypical melanocytic proliferations, clinicopathologic correlation is essential for the correct diagnosis. PMID:26588340

  18. Links between Schwann cells and melanocytes in development and disease.

    PubMed

    Van Raamsdonk, Catherine D; Deo, Mugdha

    2013-09-01

    Melanocytes are pigment-producing cells that reside in the skin, eyes, ears, heart, and central nervous system meninges of mammals. Schwann cells are glial cells, which closely associate with peripheral nerves, myelinating, and sheathing them. Melanocytes and Schwann cells both arise from the neural crest during development, and some melanocytes arise directly from Schwann cell precursors lining developing spinal nerves. In this review, we explore the connections between melanocytes and Schwann cells in development and transformation.

  19. UV light phototransduction depolarizes human melanocytes.

    PubMed

    Bellono, Nicholas W; Oancea, Elena

    2013-01-01

    Exposure of human skin to low doses of solar UV radiation (UVR) causes increased pigmentation, while chronic exposure is a powerful risk factor for skin cancers. The mechanisms mediating UVR detection in skin, however, remain poorly understood. Our recent studies revealed that UVR activates a retinal-dependent G protein-coupled signaling pathway in melanocytes. This phototransduction pathway leads to the activation of transient receptor potential A1 (TRPA1) ion channels, elevation of intracellular calcium (Ca( 2+)) and rapid increase in cellular melanin content. Here we report that physiological doses of solar-like UVR elicit a retinal-dependent membrane depolarization in human epidermal melanocytes. This transient depolarization correlates with delayed inactivation time of the UVR-evoked photocurrent and with sustained Ca( 2+) responses required for early melanin synthesis. Thus, the cellular depolarization induced by UVR phototransduction in melanocytes is likely to be a critical signaling mechanism necessary for the protective response represented by increased melanin content.

  20. Congenital Melanocytic Nevus Syndrome: A Case Series.

    PubMed

    Recio, A; Sánchez-Moya, A I; Félix, V; Campos, Y

    2017-01-19

    Congenital melanocytic nevus syndrome (CMNS) is the result of an abnormal proliferation of melanocytes in the skin and central nervous system caused by progenitor-cell mutations during embryonic development. Mutations in the NRAS gene have been detected in many of these cells. We present 5 cases of giant congenital melanocytic nevus, 3 of them associated with CMNS; NRAS gene mutation was studied in these 3 patients. Until a few years ago, surgery was the treatment of choice, but the results have proved unsatisfactory because aggressive interventions do not improve cosmetic appearance and only minimally reduce the risk of malignant change. In 2013, trametinib was approved for use in advanced melanoma associated with NRAS mutations. This drug, which acts on the intracellular RAS/RAF/MEK/pERK/MAPK cascade, could be useful in pediatric patients with CMNS. A better understanding of this disease will facilitate the development of new strategies.

  1. The Relationship of Psoriasis and Melanocytic Nevi

    PubMed Central

    Cengiz, Fatma Pelin; Emiroglu, Nazan; Bahali, Anil Gulsel; Ozkaya, Dilek Biyik; Su, Ozlem; Onsun, Nahide

    2016-01-01

    Background: There is limited data about the relationship between psoriasis and melanocytic lesions and melanoma. Immunologic pathways which were implicated in psoriasis induce a reduction in the number of melanocytic nevi. Aims and Objectives: To investigate the number of melanocytic nevi in psoriatic patients compared with controls and its relationship with disease severity and type of treatment. Methods: We performed a prospective study in 100 psoriatic patients and 100 controls. Clinical data were recorded for all participants. Results: As compared with controls, patients had overall fewer nevi congenital nevi. Among psoriatic patients, biologic agents and disease severity did not correlate with the number of nevi. Conclusions: Psoriatic patients have fewer nevi than controls. Frequency of nevi in psoriatic patients is not related to treatment and disease severity. PMID:27904187

  2. Congenital agminated melanocytic nevus - case report*

    PubMed Central

    da Rocha, Camila Roos Mariano; Grazziotin, Thaís Corsetti; Rey, Maria Carolina Widholzer; Luzzatto, Laura; Bonamigo, Renan Rangel

    2013-01-01

    Agminated nevus is a cluster group of melanocytic nevi confined to a localized area of the body. There are many pigmented lesions described in the literature as agminated, such as blue nevi, multiple lentigines and Spitz nevi, but only a few cases of congenital agminated melanocytic nevi have been described. We report a case of a male child who presented with congenital agminated nevi, emphasizing the importance of physical examination, dermoscopy, histopathological evaluation, differential diagnosis and follow up to rule out the possibility of dysplastic or malignant changes. PMID:24346910

  3. THE MOLECULAR PATHOLOGY OF MELANOMA: AN INTEGRATED TAXONOMY OF MELANOCYTIC NEOPLASIA

    PubMed Central

    Bastian, Boris C.

    2016-01-01

    Melanomas are comprised of multiple biologically distinct categories, which differ in cell of origin, age of onset, clinical and histologic presentation, pattern of metastasis, ethnic distribution, causative role of UV radiation, predisposing germ line alterations, mutational processes, and patterns of somatic mutations. Neoplasms are initiated by gain of function mutations in one of several primary oncogenes, typically leading to benign melanocytic nevi with characteristic histologic features. The progression of nevi is restrained by multiple tumor suppressive mechanisms. Secondary genetic alterations override these barriers and promote intermediate or overtly malignant tumors along distinct progression trajectories. The current knowledge about pathogenesis, clinical, histological and genetic features of primary melanocytic neoplasms is reviewed and integrated into a taxonomic framework. PMID:24460190

  4. Eating disorder symptoms and borderline personality symptomatology.

    PubMed

    Sansone, R A; Chu, J W; Wiederman, M W; Lam, C

    2011-06-01

    According to the empirical literature, there are high rates of borderline personality disorder (BPD) among individuals with formal diagnoses of eating disorders, and high rates of eating disorders among individuals with BPD. In this study, we examined relationships between three eating disorder symptoms (i.e., binge eating, starving oneself, abusing laxatives) and borderline personality symptomatology according to two self-report measures (the borderline personality scale of the Personality Diagnostic Questionnaire-4 and the Self- Harm Inventory) in a sample of psychiatric inpatients (N=126) and in a sample of internal medicine outpatients (N=419). Each individual eating disorder item, as well as a composite score of all three items, demonstrated statistically significant correlations with both measures of borderline personality symptomatology in both samples. In addition, endorsement of all three symptoms was invariably associated with borderline personality symptomatology on both measures. Specific eating disorder symptoms, alone, may predict for borderline personality symptomatology.

  5. Metastatic melanoma in association with a giant congenital melanocytic nevus in an adult: controversial CGH findings.

    PubMed

    Machan, Salma; Molina-Ruiz, Ana M; Fernández-Aceñero, Maria J; Encabo, Beatriz; LeBoit, Philip; Bastian, Boris C; Requena, Luis

    2015-06-01

    Giant congenital melanocytic nevi (GCMNs) represent a distress to patients for 2 reasons: one is disfigurement, and the other is the increased risk of developing secondary melanocytic tumors, such as benign proliferative nodules (BPNs) and malignant melanoma (MM). BPN present as a rapid growth nodule arising within a congenital melanocytic nevus (CMN) that often ulcerates, occurs in children younger than 2 years of age. BPNs arising within a CMN are exceedingly rare after childhood, and very few cases have been described in adults. Despite the worrisome clinical and histologic findings of BPN, most laboratory investigations seem to support their benignity. The distinction between MM and BPN is extremely important, but the histopathology of BPN of GCMN can be a challenge to differentiate from MM. In the recent years, molecular tests that investigate DNA copy number alterations such as fluorescence in situ hybridization and comparative genomic hybridization have shown promise to help guide the diagnosis of ambiguous melanocytic proliferations arising within CMNs. We report the case of a 22-year-old woman with a nodule arising in a GCMN and with an axillary mass suggesting a nodal metastasis of melanoma, and discuss the unusual clinical, histopathologic, and molecular findings that make this case particularly interesting.

  6. Recollections of family experience in borderline patients.

    PubMed

    Frank, H; Paris, J

    1981-09-01

    To test psychodynamic hypotheses about the etiology of the borderline syndrome, female borderline patients were asked whether they remembered their mothers and fathers as having responded with approval, disinterest, or criticism to dependent and independent behaviors. Comparisons were made with a group of normal controls and with a group of neurotics and patients with personality disorders. The main finding was that borderline patients remembered their fathers as neglectful. The recollections did not support an overprotection hypothesis.

  7. [A psychoanalytical approach of the borderline personality].

    PubMed

    Slucki, Daniel; Wikinski, Mariana

    A bibliographic review of the last year's psychoanalytic literature on borderline personality is presented. We expose diagnostic considerations, with special emphasis on those which refer to the boundaries between borderline personality, neurosis and psychosis on one hand, and those which distinguish between borderline personality and narcissistic disorders on the other. Vicissitudes of these patient's object relationships, their bond with other significant persons, their main psychic mechanisms, clinical traits and technical difficulties in the treatment are also described.

  8. Emotional Hypochondriasis, Hyperbole, and the Borderline Patient

    PubMed Central

    ZANARINI, MARY C.; FRANKENBURG, FRANCES R.

    1994-01-01

    The authors define a new defense mechanism, emotional hypochondriasis, that is hypothesized to be central to borderline psychopathology. The behavioral manifestation of this defense—the hyperbolic stance of the borderline patient—is also defined and related to the complex phenomenology of borderline personality disorder. Borderline patients are seen as making an active attempt to maintain a tolerable, if tenuous, adaptation in the face of tremendous subjective emotional pain that has been shaped in large measure by traumatic childhood events that have never been validated. Twelve treatment implications and three expectable, if overlapping, stages of treatment stemming from the use of this defense and its behavioral sequelae are detailed. PMID:22700171

  9. Clear-cell melanocytic lesions with balloon-cell and sebocyte-like melanocytes: a unifying concept.

    PubMed

    Kazlouskaya, Viktoryia; Guo, Ying; Maia-Cohen, Sandra; Mones, Joan

    2014-05-01

    Melanocytes may assume unique shapes and sizes but rarely have clear cytoplasm. We studied 28 melanocytic lesions that contained clear-cell melanocytes of the balloon-cell and sebocyte-like types. Clear-cell melanocytes were found more commonly in females (64%) than in males (36%), with predominance in females younger than 50 years (79%) and predominance in males older than 50 years (67%). They were distributed evenly throughout the body but were not found on acral sites. Clear-cell melanocytes were most prevalent in congenital nevi (18 or 72%) but were also found in 5 Clark nevi, 2 Meischer nevi, 1 Unna nevus, 1 atypical intra-epidermal proliferation, and 1 melanoma. The clear cells were distributed diffusely in 86% of the lesions and focally in 14%. The overall percentage of clear-cell melanocytes was 56%. The percentage of balloon cells was 57% and sebocyte-like melanocytes 32%. Clear cells with morphologic features of both balloon cells and sebocyte-like melanocytes, that is, intermediate cells, were present in all lesions with an overall percentage of 12%. The presence of melanocytes of both the balloon-cell and sebocyte-like types and the finding of clear-cell melanocytes with intermediate features in all lesions lends support to the theory that balloon-cell and sebocyte-like melanocytes may represent morphologic expressions of the same alteration in melanogenesis.

  10. Tissue Inhibitor of Metalloproteinase 1 Expression Associated with Gene Demethylation Confers Anoikis Resistance in Early Phases of Melanocyte Malignant Transformation1

    PubMed Central

    Ricca, Tatiana I; Liang, Gangning; Suenaga, Ana Paula M; Han, Sang W; Jones, Peter A; Jasiulionis, Miriam G

    2009-01-01

    Although anoikis resistance has been considered a hallmark of malignant phenotype, the causal relation between neoplastic transformation and anchorage-independent growth remains undefined. We developed an experimental model of murine melanocyte malignant transformation, where a melanocyte lineage (melan-a) was submitted to sequential cycles of anchorage blockade, resulting in progressive morphologic alterations, and malignant transformation. Throughout this process, cells corresponding to premalignant melanocytes and melanoma cell lines were established and show progressive anoikis resistance and increased expression of Timp1. In melan-a melanocytes, Timp1 expression is suppressed by DNA methylation as indicated by its reexpression after 5-aza-2′-deoxycytidine treatment. Methylation-sensitive single-nucleotide primer extension analysis showed increased demethylation in Timp1 in parallel with its expression along malignant transformation. Interestingly, TIMP1 expression has already been related with negative prognosis in some human cancers. Although described as a MMP inhibitor, this protein has been associated with apoptosis resistance in different cell types. Melan-a cells overexpressing Timp1 showed increased survival in suspension but were unable to form tumors in vivo, whereas Timp1-overexpressing melanoma cells showed reduced latency time for tumor appearance and increased metastatic potential. Here, we demonstrated for the first time an increment in Timp1 expression since the early phases of melanocyte malignant transformation, associated to a progressive gene demethylation, which confers anoikis resistance. In this way, Timp1 might be considered as a valued marker for melanocyte malignant transformation. PMID:19956395

  11. The usefulness of c-Kit in the immunohistochemical assessment of melanocytic lesions

    PubMed Central

    Pilloni, L.; Bianco, P.; Difelice, E.; Cabras, S.; Castellanos, M.E.; Atzori, L.; Ferreli, C.; Mulas, P.; Nemolato, S.; Faa, G.

    2011-01-01

    C-Kit (CD117), the receptor for the stem cell factor, a growth factor for melanocyte migration and proliferation, has shown differential immunostaining in various benign and malignant melanocytic lesions. The purpose of this study is to compare c-Kit immunostaining in benign nevi and in primary and metastatic malignant melanomas, to determine whether c-Kit can aid in the differential diagnosis of these lesions. c-Kit immunostaining was performed in 60 cases of pigmented lesions, including 39 benign nevi (5 blue nevi, 5 intra-dermal nevi, 3 junctional nevi, 15 cases of primary compound nevus, 11 cases of Spitz nevus), 18 cases of primary malignant melanoma and 3 cases of metastatic melanoma. The vast majority of nevi and melanomas examined in this study were positive for c-Kit, with minimal differences between benign and malignant lesions. C-Kit cytoplasmatic immunoreactivity in the intraepidermal proliferating nevus cells, was detected in benign pigmented lesions as well as in malignant melanoma, increasing with the age of patients (P=0.007) in both groups. The patient’s age at presentation appeared to be the variable able to cluster benign and malignant pigmented lesions. The percentage of c-Kit positive intraepidermal nevus cells was better associated with age despite other variables (P=0.014). The intensity and percentage of c-Kit positivity in the proliferating nevus cells in the dermis was significantly increased in malignant melanocytic lesions (P=0.015 and P=0.008) compared to benign lesions (compound melanocytic nevi, Spitz nevi, intradermal nevi, blue nevi). Immunostaning for c-Kit in metastatic melanomas was negative. Interestingly in two cases of melanoma occurring on a pre-existent nevus, the melanoma tumor cells showed strong cytoplasmatic and membranous positivity for c-kit, in contrast with the absence of any immunoreactivity in pre-existent intradermal nevus cells. C-Kit does not appear to be a strong immunohistochemical marker for distinguishing

  12. Borderline Clients: Practice Implications of Recent Research.

    ERIC Educational Resources Information Center

    Johnson, Harriette C.

    1991-01-01

    Reviews current research on treatment of borderline clients with medication, individual counseling, and family interventions. Notes that recent studies indicate that borderline personality is heterogeneous condition in which different underlying disorders (affective, schizotypal, and neurological) may be present. Reviews effectiveness of various…

  13. The Borderline Personality--An Adlerian Overview.

    ERIC Educational Resources Information Center

    Rattner, Leo

    The person with a borderline personality is considered to be neither neurotic nor psychotic, but to exist somewhere in between these two diagnostic categories. Psychoanalytic theorists who have researched the phenomenon of the borderline personality have shifted their emphasis away from Freud's instinct psychology and toward an ego psychology…

  14. Immunohistochemical study of melanocyte-melanocyte stem cell lineage in vitiligo; a clue to interfollicular melanocyte stem cell reservoir.

    PubMed

    Seleit, Iman; Bakry, Ola Ahmed; Abdou, Asmaa Gaber; Dawoud, Noha Mohammed

    2014-05-01

    There has been a long lasting controversy over whether melanocytes (MCs) in vitiligo are actually lost or still present but functionally inactive. We aimed to evaluate the MC cell lineage in follicular and interfollicular vitiliginous epidermis through immunohistochemical localization of Human Melanoma Black-45 (HMB-45) and Tyrosinase Related Protein 2 (TRP2) and to correlate it with clinicopathologic parameters. Using immunohistochemical techniques, skin biopsies from 50 vitiligo patients and 20 age- and gender-matched healthy subjects were examined. Differentiated active MCs were detected in 44% of interfollicular epidermis (IFE) and 46.7% of follicular epidermis (FE) in lesional skin. Melanocyte precursors/stem cells were detected in 54% of IFE and 63.3% of FE in lesional skin. Melanocyte precursors/stem cells of IFE were significantly associated with residual melanin pigment (p = 0.007) and with absence of angiogenesis (p = 0.05). HMB-45 percentage of expression in IFE was positively correlated with MC precursors/stem cells percentage in FE (r = +0.65, p < 0.001) and IFE (r = +0.33, p = 0.01). Melanocyte precursors/stem cells positivity (p < 0.001) was progressively decreasing with advanced histopathologic grading. There was no significant association between interfollicular or follicular expression of HMB-45, TRP2 or MC precursors/stem cells and the clinical type of vitiligo or its duration. In conclusion, functioning MCs may exist in vitiligo. The presence of MC precursors/stem cells in IFE may provide an additional reservoir needed for repigmentation.

  15. Apoptosis of melanocytes in vitiligo results from antibody penetration.

    PubMed

    Ruiz-Argüelles, Alejandro; Brito, Gustavo Jiménez; Reyes-Izquierdo, Paola; Pérez-Romano, Beatriz; Sánchez-Sosa, Sergio

    2007-12-01

    Vitiligo is a rather common disease characterized by depigmentation of skin and mucosae due to the loss of melanocytes, most likely as a result of autoimmune phenomena. In this study we demonstrated apoptotic markers in residual melanocytes in skin biopsies of patients with vitiligo, as well as the presence of serum antibodies to melanocyte-specific antigens in the vast majority of patients. Moreover, we were able to prove that serum IgG antibodies from vitiligo patients, but not from healthy controls, were capable to penetrate into cultured melanocytes in vitro, and trigger them to engage in apoptosis. Our results are consonant with the theory that melanocyte-specific antibodies are responsible for the deletion of melanocytes through antibody penetration and apoptosis.

  16. The inflammatory infiltrate of melanocytic nevus.

    PubMed

    Fernandez-Flores, Angel; Saeb-Lima, Marcela

    2014-01-01

    Melanocytic nevi are frequently accompanied by inflammatory cells of different types, in varied amounts and distributed in different patterns. In the current report, we review the knowledge on inflammation seen in different types of melanocytic nevi. As an additional contribution, we studied the lymphocytic inflammatory component of Duperrat nevus, as well as the cytotoxic component of Sutton nevus, two contributions that we have not found in the literature. We conclude that: (a) Duperrat nevus has a mixed inflammatory reaction that includes histiocytes, foreign-body multinucleated giant cells, polymorphonuclears, lymphocytes (predominantly CD4+) and plasma cells (commonly abundant); (b) common melanocytic nevi with reactive inflammatory infiltrate usually show a CD4+ predominant population; (c) Meyerson nevus commonly shows an inflammatory infiltrate mainly made up of CD4+ T-cells; (d) Sutton nevus with halo phenomenon is accompanied by a dense inflammatory infiltrate with lymphocytes in a CD4:CD8 ratio varying from 1:1 to 1:3 and in which most of the CD8+ T-cells do not express cytotoxic markers; (e) Wiesner nevus commonly shows a spare lymphocytic infiltrate but the nature of the infiltrate has not yet been investigated.

  17. Growth of melanocytes in human epidermal cell cultures

    SciTech Connect

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

    1990-08-01

    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.

  18. A novel BAP1 mutation is associated with melanocytic neoplasms and thyroid cancer.

    PubMed

    McDonnell, Kevin J; Gallanis, Gregory T; Heller, Kathleen A; Melas, Marilena; Idos, Gregory E; Culver, Julie O; Martin, Sue-Ellen; Peng, David H; Gruber, Stephen B

    2016-03-01

    Germline mutations in the tumor suppressor gene, BRCA-1 associated protein (BAP1), underlie a tumor predisposition syndrome characterized by increased risk for numerous cancers including uveal melanoma, melanocytic tumors and mesothelioma, among others. In the present study we report the identification of a novel germline BAP1 mutation, c.1777C>T, which produces a truncated BAP1 protein product and segregates with cancer. Family members with this mutation demonstrated a primary clinical phenotype of autosomal dominant, early-onset melanocytic neoplasms with immunohistochemistry (IHC) of these tumors demonstrating lack of BAP1 protein expression. In addition, family members harboring the BAP1 c.1777C>T germline mutation developed other neoplastic disease including thyroid cancer. IHC analysis of the thyroid cancer, as well, demonstrated loss of BAP1 protein expression. Our investigation identifies a new BAP1 mutation, further highlights the relevance of BAP1 as a clinically important tumor suppressor gene, and broadens the range of cancers associated with BAP1 inactivation. Further study will be required to understand the full scope of BAP1-associated neoplastic disease.

  19. Borderline personality disorder: toward integration.

    PubMed

    Stein, Dan J

    2009-07-01

    Several psychiatric disorders, including borderline personality disorder (BPD), are characterized by emotional dysregulation and impulse dyscontrol. More specifically, symptoms in patients with BPD often occur within the context of disruptions in attachment and related distortions in cognitive-affective processing of the self and others. From a neurocircuitry perspective, findings include prefrontal hypoactivity, amygdala hyperreactivity, and alterations in prefrontal-limbic interaction. Molecular pathways relevant to these circuits include the serotonergic, noradrenergic, and dopaminergic systems, and there is some evidence that pharmacotherapy with agents that act on these systems may be useful. Given the disruptions in attachment and schemas of the self and others in BPD, establishing a therapeutic alliance is crucial while psychotherapy remains the cornerstone of an integrated approach to management.

  20. Patient With Borderline Personality Disorder

    PubMed Central

    Griffiths, Dorothy E.

    1989-01-01

    Every family practice includes people who are difficult to manage. Persons with a borderline personality disorder can be the most difficult of all. They will trust no one, and consequently few, if any, others will be able to tolerate their profoundly difficult interpersonal communication style. These patients will present to their family physician more and more often with a variety of somatic and emotional symptoms. They will demand, either verbally or silently, that these symptoms be relieved immediately. This increasing demand for immediate response may eventually cause the physician to reject the patient. An understanding of this condition and how it develops in infancy may enable the physician to help the patient. A family physician who can set appropriate limits to the patient's demands may slowly convince the patient that he can trust and not be hurt. PMID:21248944

  1. Tumor

    MedlinePlus

    ... plants (aflatoxins) Excessive sunlight exposure Genetic problems Obesity Radiation exposure Viruses Types of tumors known to be caused by or linked with viruses are: Cervical cancer (human papillomavirus) Most anal cancers (human papillomavirus) Some throat ...

  2. Cancer of the melanocytic system

    SciTech Connect

    Setlow, R.B.

    1994-12-31

    Within reasonably homogenous populations, skin cancer increases toward low latitudes, but this association does not indicate the wavelength regions involved in cancer induction. At present, the only animal model suitable for determining the wavelengths effective in melanoma induction are certain inter- and intraspecies hybrids of the small fish, Xiphophorus. Genetic evidence indicates that the hybrids contain only one tumor suppressor gene and, therefore, are very sensitive to cancer induction by single exposures to light. 5-Day old fish were exposed in spectrophotometer cuvettes, to different monochromatic wavelengths and fluences. The fish were kept for two months in tanks shielded with yellow plastic, so as to minimize the possibility of photoreactivation, and were scored at four months. The melanoma prevalence increased with exposure to a maximum of {approximately} 0.5. The fluence-response curves were fitted to surviving fraction = a+b(l-e{sup {minus}kE}), where a is the background prevalence with no exposure, b is the maximum induced prevalence, k is the sensitivity parameter (the cross section for melanoma induction), and E is the incident fluence. The value of k at 302 nm was 0.05 m{sup 2}/J giving a mean melanoma inducing exposure, for swimming fish, of 200 J/m{sup 2}, corresponding to 3.5 cyclobutane pyrimidine dimers per Mbp of DNA in irradiated fish skin.

  3. A murine model for the development of melanocytic nevi and their progression to melanoma

    PubMed Central

    Nasti, Tahseen H.; Cochran, J. Barry; Tsuruta, Yuko; Yusuf, Nabiha; McKay, Kristopher M.; Athar, Mohammad; Elmets, Craig A.

    2015-01-01

    Acquired melanocytic nevi are commonly found in sun exposed and unexposed human skin, but the potential for their transformation into invasive melanoma is not clear. Therefore, a mouse model of nevus initiation and progression was developed in C3H/HeN mice using a modified chemical carcinogenesis protocol. Nevi develop due to DNA damage initiated by dimethylbenz(a) anthracene (DMBA) followed by chronic promotion with 12‐O‐tetradecanoyl‐phorbol‐13‐acetate (TPA). Dysplastic pigmented skin lesions appeared in 7–9 wk with 100% penetrance. Nests of melanocytic cells appeared in a subset of skin draining lymph nodes (dLN) by 25 wk, but not in age matched controls. Immunohistochemistry, real‐time PCR, and flow cytometric analyses confirmed their melanocytic origin. Transformed cells were present in a subset of nevi and dLNs, which exhibited anchorage‐independent growth, tumor development, and metastasis in nude mice. Approximately 50% of the cell lines contained H‐Ras mutations and lost tumor suppressor p16Ink4a expression. While most studies of melanoma focus on tumor progression in transgenic mouse models where the mutations are present from birth, our model permits investigation of acquired mutations at the earliest stages of nevus initiation and promotion of nevus cell transformation. This robust nevus/melanoma model may prove useful for identifying genetic loci associated with nevus formation, novel oncogenic pathways, tumor targets for immune‐prevention, screening therapeutics, and elucidating mechanisms of immune surveillance and immune evasion. © 2015 The Authors. Molecular Carcinogenesis, published by Wiley Periodicals, Inc. PMID:25788145

  4. Defense Mechanisms Associated with Borderline Personality Disorder

    PubMed Central

    Zanarini, Mary C.; Weingeroff, Jolie L.; Frankenburg, Frances R.

    2011-01-01

    This study assessed the defensive functioning of 290 criteria-defined borderline patients and compared it to that of 72 patients with other forms of axis II psychopathology. The Defense Style Questionnaire, a self-report measure with demonstrated criterion validity and internal consistency, was administered to 362 axis II inpatients diagnosed using semistructured interviews of proven reliability. Borderline patients had significantly higher scores than axis II comparison subjects on three of the four defense styles assessed by the DSQ: self-sacrificing, maladaptive action, and image-distorting defenses. They also had significantly higher scores than axis II comparison subjects on eight of the 19 defense mechanisms studied. More specifically, borderline patients had significantly higher scores on one neurotic-level defense (undoing), four immature defenses (acting out, emotional hypochondriasis, passive aggression, and projection), and two image- distorting/borderline defenses (projective identification and splitting). In contrast, axis II comparison subjects had a significantly higher score than borderline patients on one mature defense (suppression). When all significant defenses were considered together, three were found to be significant predictors of a borderline diagnosis: acting out, emotional hypochondriasis, and undoing. This model has both good sensitivity (.95) and positive predictive power (.86). Taken together, the results of this study suggest that the defensive profile of borderline patients is distinct from that of patients with other forms of axis II pathology. They also suggest that the defensive triad of acting out, emotional hypochondriasis, and undoing may serve as a useful clinical marker for the borderline diagnosis, particularly in settings where the base rate of the disorder is high. PMID:19379090

  5. In vitro dedifferentiation of melanocytes from adult epidermis.

    PubMed

    Kormos, Bernadett; Belso, Nóra; Bebes, Attila; Szabad, Gábor; Bacsa, Sarolta; Széll, Márta; Kemény, Lajos; Bata-Csörgo, Zsuzsanna

    2011-02-23

    In previous work we described a novel culture technique using a cholera toxin and PMA-free medium (Mel-mix) for obtaining pure melanocyte cultures from human adult epidermis. In Mel-mix medium the cultured melanocytes are bipolar, unpigmented and highly proliferative. Further characterization of the cultured melanocytes revealed the disappearance of c-Kit and TRP-1 and induction of nestin expression, indicating that melanocytes dedifferentiated in this in vitro culture. Cholera toxin and PMA were able to induce c-Kit and TRP-1 protein expressions in the cells, reversing dedifferentiation. TRP-1 mRNA expression was induced in dedifferentiated melanocytes by UV-B irradiated keratinocyte supernatants, however direct UV-B irradiation of the cells resulted in further decrease of TRP-1 mRNA expression. These dedifferentiated, easily accessible cultured melanocytes provide a good model for studying melanocyte differentiation and possibly transdifferentiation. Because melanocytes in Mel-mix medium can be cultured with human serum as the only supplement, this culture system is also suitable for autologous cell transplantation.

  6. [Concepts of the borderline personality disorders].

    PubMed

    Ogłodek, Ewa; Araszkiewicz, Aleksander

    2011-08-01

    For many years, the borderline personality disorders have mainly been researched in terms of psychoanalytical theories, such as theories on relations with the object. Nowadays, there are three kinds of concepts that are distinguishable. The first ones are those which are group models, serving attempts to made characteristic sets of qualities, represented by individuals suffering from the borderline personality disorders, more precise. The remaining concepts are models of conflict and deficit, which explain complicated mechanisms of interactions of social, psychological and biological factors, and therefore, contribute to better understanding of the genesis of the symptoms of this disorder. Upon the basis of the attempts made so far in the field of describing the borderline personality disorders, one may indicate certain criteria, representative for the entire group of individuals with this diagnosis, regardless of the assumptions applicable to the genesis of the disorder and its symptoms, even though the population of the infirm suffering from the borderline personality disorders is not internally homogenous. The interest of psychologists, attempting to describe the borderline personality disorders, is focused upon certain sets of qualities, presented as the examples of descriptive models. Among the researchers, working on the issues of the borderline personality disorders in this manner, there are: Gunderson, Kernberg, Kohut, Winnicot, Guntrip, Fairbaim, Adler and Buie.

  7. Neurochemical alterations associated with borderline personality disorder.

    PubMed

    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.

  8. Meningeal Melanocytes in the Mouse: Distribution and Dependence on Mitf

    PubMed Central

    Gudjohnsen, Stefán A. H.; Atacho, Diahann A. M.; Gesbert, Franck; Raposo, Graca; Hurbain, Ilse; Larue, Lionel; Steingrimsson, Eirikur; Petersen, Petur Henry

    2015-01-01

    Summary: Melanocytes are pigment producing cells derived from the neural crest. They are primarily found in the skin and hair follicles, but can also be found in other tissues including the eye, ear and heart. Here, we describe the distribution of pigmented cells in C57BL/6J mouse meninges, the membranes that envelope the brain. These cells contain melanosomes of all four stages of development and they depend on Microphthalmia associated transcription factor (MITF), the master regulator of melanocyte development, suggesting that they are bona-fide melanocytes. The location of these pigmented cells is consistent with the location of meningeal melanomas in humans and animal models. Significance: Here, we document and define pigmented cells in the meninges of the mouse brain and confirm that they are melanocytes. This is important for understanding the role of this cell type and for understanding primary meningeal melanoma, a rare disease that likely arises from normal meningeal melanocytes. PMID:26635543

  9. Exosomes released by keratinocytes modulate melanocyte pigmentation

    PubMed Central

    Cicero, Alessandra Lo; Delevoye, Cédric; Gilles-Marsens, Floriane; Loew, Damarys; Dingli, Florent; Guéré, Christelle; André, Nathalie; Vié, Katell; van Niel, Guillaume; Raposo, Graça

    2015-01-01

    Cells secrete extracellular vesicles (EVs), exosomes and microvesicles, which transfer proteins, lipids and RNAs to regulate recipient cell functions. Skin pigmentation relies on a tight dialogue between keratinocytes and melanocytes in the epidermis. Here we report that exosomes secreted by keratinocytes enhance melanin synthesis by increasing both the expression and activity of melanosomal proteins. Furthermore, we show that the function of keratinocyte-derived exosomes is phototype-dependent and is modulated by ultraviolet B. In sum, this study uncovers an important physiological function for exosomes in human pigmentation and opens new avenues in our understanding of how pigmentation is regulated by intercellular communication in both healthy and diseased states. PMID:26103923

  10. Exosomes released by keratinocytes modulate melanocyte pigmentation.

    PubMed

    Lo Cicero, Alessandra; Delevoye, Cédric; Gilles-Marsens, Floriane; Loew, Damarys; Dingli, Florent; Guéré, Christelle; André, Nathalie; Vié, Katell; van Niel, Guillaume; Raposo, Graça

    2015-06-24

    Cells secrete extracellular vesicles (EVs), exosomes and microvesicles, which transfer proteins, lipids and RNAs to regulate recipient cell functions. Skin pigmentation relies on a tight dialogue between keratinocytes and melanocytes in the epidermis. Here we report that exosomes secreted by keratinocytes enhance melanin synthesis by increasing both the expression and activity of melanosomal proteins. Furthermore, we show that the function of keratinocyte-derived exosomes is phototype-dependent and is modulated by ultraviolet B. In sum, this study uncovers an important physiological function for exosomes in human pigmentation and opens new avenues in our understanding of how pigmentation is regulated by intercellular communication in both healthy and diseased states.

  11. Effects of hydroxybenzyl alcohols on melanogenesis in melanocyte-keratinocyte co-culture and monolayer culture of melanocytes.

    PubMed

    Liu, Szu-Hsiu; Chu, I-Ming; Pan, I-Horng

    2008-08-01

    In mammalian skin, melanocyte proliferation and melanogenesis can be stimulated by keratinocytes, fibroblasts and other regulatory factors. To determine whether hydroxybenzyl alcohols (HBAs) show more inhibitory in melanocytes cultured alone or in melanocytes co-cultured with keratinocytes, we developed a murine melanocyte-keratinocyte co-culture model to investigate the pigmentation regulators in company with other melanogenic inhibitors and stimulators. It was found that the effects of HBAs and melanogenic factors were more evident in melanocytes co-cultured with keratinocytes. Keratinocytes may play a synergistic role in melanocyte melanogenesis and influence the pigment production. The tests in the co-culture model also imply that the inhibitory effects of HBAs on melanogenesis are due to the direct inhibition of melanosomal tyrosinase activity. HBAs showed a low cytotoxicity. The eventual results proved that HBAs are promising and safe agents for skin whitening in melanocyte alone and in co-culture systems. The co-culture model provides a more physiologically realistic condition to study the interaction between melanocytes and keratinocytes, which enables a reliable screening system for depigmenting compounds.

  12. Attachment and borderline personality disorder.

    PubMed

    Fonagy, P

    2000-01-01

    The author outlines his concept of reflective function or mentalization, which is defined as the capacity to think about mental states in oneself and in others. He presents evidence to suggest that the capacity for reflective awareness in a child's caregiver increases the likelihood of the child's secure attachment, which in turn facilitates the development of mentalization in the child. He proposes that a secure attachment relationship offers the child a chance to explore the mind of the caregiver, and in this way to learn about minds; he formulates this model of the birth of the psychological self as a variation on the Cartesian cogito: "My caregiver thinks of me as thinking and therefore I exist as a thinker." This model is then applied to provide insight into some personality-disordered individuals who were victims of childhood abuse. The author proposes (1) that individuals who experience early trauma may defensively inhibit their capacity to mentalize to avoid having to think about their caregiver's wish to harm them; and (2) that some characteristics of severe borderline personality disorder may be rooted in developmental pathology associated with this inhibition. He offers evidence for and some qualifications of this model, and argues that the therapeutic effect of psychoanalysis depends on its capacity to activate patients' ability to evolve an awareness of mental states and thus find meaning in their own and other people's behavior.

  13. Malevolence, splitting, and parental ratings by borderlines.

    PubMed

    Baker, L; Silk, K R; Westen, D; Nigg, J T; Lohr, N E

    1992-04-01

    Malevolent object relations as well as splitting have long been considered by psychodynamic theorists as central features of borderline personality disorder. We tested the hypotheses that borderlines would a) perceive their parents more negatively than both nonborderline major depressive patients and nonpatient normal controls, and b) split their representations of their parents into opposites more than the comparison subjects. Borderlines (N = 31), who were identified by the Diagnostic Interview for Borderlines, Research Diagnostic Criteria major depressives (N = 15), and nonpatient controls (N = 14) were asked to rate each parent on the Adjective Check List (ACL; Gough and Heilbrun, 1983). Seven ACL scales were studied: Favorable, Unfavorable, Critical Parent, Nurturing Parent, Nurturance, Aggression, and Dominance. Correlations were performed between scores for mother and father on the various scales for each of the three cohorts. Analysis of variance and one-way t-tests with Bonferroni correction were used to test group differences. Borderlines rated their parents, especially their fathers, not only as more unfavorable on negative scales than depressives or normals, but as less favorable on positive scales than the comparison groups. Analysis of covariance revealed that a significant portion of the variance in father scores, but not in mother scores, was related to age of respondent and history of sexual abuse. While borderlines did not appear to split their parents into one good and one bad parent, they did show significantly less correlation between parents on the Favorable scale when compared with either depressives or normal subjects. The results imply that borderlines have a greater tendency to view the world in negative, malevolent ways than to split their object representations.

  14. Non psammomatous melanocytic schwannoma presenting as a subcutaneous nodule: A rare presentation of a rare lesion

    PubMed Central

    Gulati, Harveen Kaur; Joshi, Avinash R.; Anand, Mani; Deshmukh, S. D.

    2016-01-01

    Melanocytic schwannoma (MS) is an extremely rare soft tissue tumor accounting for less than 1% of all primitive nerve sheath tumors, with a predilection for spinal nerve involvement. To date, only 20 cases of cutaneous/subcutaneous MS have been described in literature. Here, we describe a case of MS presenting as a subcutaneous nodule in a 22-year-old male in right thigh. On examination, the nodule measured 2.5 × 2.0 × 1.5 cm with overlying skin showing a bluish hue and an ulcer. With a preoperative diagnosis of hemangioma, the patient was taken up for wide local excision and was diagnosed as a case of non psammomatous melanocytic schwannoma based on clinical, histological, and immunohistochemical studies. Immunohistochemistry revealed positivity with S-100, HMB-45, and Melan A with pericellular Laminin positivity. Carney's syndrome was ruled out. MS needs to be differentiated from other pigmented lesions like pigmented neurofibroma, Bednar tumor, cellular blue neavus, and especially malignant melanoma, which has an obvious ominous prognosis. Since MS can show unpredictable behavior especially in absence of overt malignant features, a long term follow up with or without radiotherapy is recommended. PMID:27366278

  15. Positive and negative elements regulate a melanocyte-specific promoter.

    PubMed Central

    Lowings, P; Yavuzer, U; Goding, C R

    1992-01-01

    Melanocytes are specialized cells residing in the hair follicles, the eye, and the basal layer of the human epidermis whose primary function is the production of the pigment melanin, giving rise to skin, hair, and eye color. Melanogenesis, a process unique to melanocytes that involves the processing of tyrosine by a number of melanocyte-specific enzymes, including tyrosinase and tyrosinase-related protein 1 (TRP-1), occurs only after differentiation from the melanocyte precursor, the melanoblast. In humans, melanogenesis is inducible by UV irradiation, with melanin being transferred from the melanocyte in the epidermis to the surrounding keratinocytes as protection from UV-induced damage. Excessive exposure to UV, however, is the primary cause of malignant melanoma, an increasingly common and highly aggressive disease. As an initial approach to understanding the regulation of melanocyte differentiation and melanocyte-specific transcription, we have isolated the gene encoding TRP-1 and examined the cis- and trans-acting factors required for cell-type-specific expression. We find that the TRP-1 promoter comprises both positive and negative regulatory elements which confer efficient expression in a TRP-1-expressing, pigmented melanoma cell line but not in NIH 3T3 or JEG3 cells and that a minimal promoter extending between -44 and +107 is sufficient for cell-type-specific expression. Assays for DNA-protein interactions coupled with extensive mutagenesis identified three factors, whose binding correlated with the function of two positive and one negative regulatory element. One of these factors, termed M-box-binding factor 1, binds to an 11-bp motif, the M box, which acts as a positive regulatory element both in TRP-1-expressing and -nonexpressing cell lines, despite being entirely conserved between the melanocyte-specific tyrosinase and TRP-1 promoters. The possible mechanisms underlying melanocyte-specific gene expression are discussed. Images PMID:1321344

  16. Giant melanocytic nevi with neurocutaneous melanosis masquerading as neurofibromas

    PubMed Central

    Gowda, Vykuntaraju K.; Basude, Anita; Srinivas, Sahana M.; Bhat, Maya

    2016-01-01

    Neurocutaneous melanosis is congenital melanocytic nevus with neurological manifestations. We report a 4-year-old female child presenting with hyperpigmented and nodular skin lesion associated with developmental delay and convulsions. The child had multiple brownish-black nevi on the face and chest and giant melanocytic nevi on thoraco-abdomen, back, and gluteal region. Computed tomography scan of the brain showed calcification in the pons, right cerebellar hemisphere, and left medial temporal lobe. Skin biopsy done from nodular hyperpigmented site was suggestive of melanocytic nevi. Electroencephalogram showed multifocal epileptiform discharges. PMID:27857802

  17. Multiple roles of NF1 in the melanocyte lineage.

    PubMed

    Larribère, Lionel; Utikal, Jochen

    2016-07-01

    NF1 is a tumour suppressor gene, germline mutations of which lead to neurofibromatosis type 1 syndrome. Patients develop benign tumours from several types of cells including neural crest-derived cells. NF1 somatic mutations also occur in 15% of sporadic melanoma, a cancer originating from melanocytes. Evidence now suggests the involvement of NF1 mutations in melanoma resistance to targeted therapies. Although NF1 is ubiquitously expressed, genetic links between NF1 and genes involved in melanocyte biology have been described, implying the lineage-specific mechanisms. In this review, we summarize and discuss the latest advances related to the roles of NF1 in melanocyte biology and in cutaneous melanoma.

  18. Comparative Study of Efficacy of Epidermal Melanocyte Transfer Versus Hair Follicular Melanocyte Transfer in Stable Vitiligo

    PubMed Central

    Donaparthi, Navya; Chopra, Ajay

    2016-01-01

    Background: Vitiligo surgery has come up a long way from punch skin grafts to epidermal cell suspension and latest to the extracted hair follicle outer root sheath cell suspension (EHFORSCS) transplantation. The progressive development from one technique to the other is always on a quest for the best. In the latest development, EHFORSCS, which is an enriched source of follicular inactive melanocyte (melanocyte stem cells), seems to be a good addition to the prevailing cell-based therapies for vitiligo. However, it needs to be explored further in larger, clinical trials. Methodology: A total of 11 patients with sixty stable vitiligo sites attending dermatology outpatient department were included for the open-labeled, prospective, comparative study. The sites were sequentially distributed into two groups of thirty each. Sites of one group were subjected to epidermal melanocyte transfer (EMT) and the others to hair follicular melanocyte transfer (HFMT). Response to treatment was evaluated on the basis of degree of repigmentation; final evaluation of area of involvement was done after completion of 6 months. Results: At the end of 6 months, repigmentation >90% was observed in 83.33% patches of EMT group and 43.33% in HFMT group. Repigmentation >75% was observed in 90% of patches in Group A and 43.34% of patches in Group B, respectively. There was statistically significant difference in the overall pigmentation between these two groups. Conclusion: Both noncultured autologous epidermal cell suspension transfer and noncultured EHFORSCS transfer are safe and effective surgical modalities in the management of stable vitiligo though EMT has shown a better response in the present study. Outer root sheath cell suspension transfer is a novel, minimally invasive technique in its nascent stage in the surgical management of vitiligo which requires further larger clinical trials for evaluation of its efficacy. PMID:27904182

  19. A quantum probability perspective on borderline vagueness.

    PubMed

    Blutner, Reinhard; Pothos, Emmanuel M; Bruza, Peter

    2013-10-01

    The term "vagueness" describes a property of natural concepts, which normally have fuzzy boundaries, admit borderline cases, and are susceptible to Zeno's sorites paradox. We will discuss the psychology of vagueness, especially experiments investigating the judgment of borderline cases and contradictions. In the theoretical part, we will propose a probabilistic model that describes the quantitative characteristics of the experimental finding and extends Alxatib's and Pelletier's () theoretical analysis. The model is based on a Hopfield network for predicting truth values. Powerful as this classical perspective is, we show that it falls short of providing an adequate coverage of the relevant empirical results. In the final part, we will argue that a substantial modification of the analysis put forward by Alxatib and Pelletier and its probabilistic pendant is needed. The proposed modification replaces the standard notion of probabilities by quantum probabilities. The crucial phenomenon of borderline contradictions can be explained then as a quantum interference phenomenon.

  20. Accurately Diagnosing and Treating Borderline Personality Disorder

    PubMed Central

    Gentile, Julie P.; Correll, Terry L.

    2010-01-01

    The high prevalence of comorbid bipolar and borderline personality disorders and some diagnostic criteria similar to both conditions present both diagnostic and therapeutic challenges. This article delineates certain symptoms which, by careful history taking, may be attributed more closely to one of these two disorders. Making the correct primary diagnosis along with comorbid psychiatric conditions and choosing the appropriate type of psychotherapy and pharmacotherapy are critical steps to a patient's recovery. In this article, we will use a case example to illustrate some of the challenges the psychiatrist may face in diagnosing and treating borderline personality disorder. In addition, we will explore treatment strategies, including various types of therapy modalities and medication classes, which may prove effective in stabilizing or reducing a broad range of symptomotology associated with borderline personality disorder. PMID:20508805

  1. Unblending Borderline Personality and Bipolar Disorders.

    PubMed

    di Giacomo, Ester; Aspesi, Flora; Fotiadou, Maria; Arntz, Arnoud; Aguglia, Eugenio; Barone, Lavinia; Bellino, Silvio; Carpiniello, Bernardo; Colmegna, Fabrizia; Lazzari, Marina; Lorettu, Liliana; Pinna, Federica; Sicaro, Aldo; Signorelli, Maria Salvina; Clerici, Massimo

    2017-03-07

    Borderline Personality (BPD) and Bipolar (BP) disorders stimulate an academic debate between their distinction and the inclusion of Borderline in the Bipolar spectrum. Opponents to this inclusion attribute the important differences and possible diagnostic incomprehension to overlapping symptoms. We tested 248 Borderline and 113 Bipolar patients, consecutively admitted to the Psychiatric Unit, through DSM-IV Axis I and II Disorders (SCID-I/II), Hamilton Depression Rating Scale (HAM-D), Hamilton Anxiety Rating Scale (HAM-A), Young Mania Rating Scale (YMRS) and Borderline Personality Disorder Severity Index-IV (BPDSI-IV). All the tests statistically discriminated the disorders (p < 0.0001). Overlapping symptoms resulted significantly different (impulsivity = 5.32 in BPD vs 1.55 in BP, p < 0.0001; emotional instability = 7.11 in BPD vs 0.55 in BP, p < 0.0001) and the range of their scores gives the opportunity for an even more precise discrimination. Distinctive traits (e.g. irritability or sexual arousal) are also discussed in order to try to qualify the core of these disorders to a higher degree. Comorbidity proves to be extremely small (3.6%). However, Borderline patients with manic features offer a privileged point of view for a deeper analysis. This allows for the possibility of a more precise examination of the nature and load of each symptom. Borderline Personality and Bipolar Disorders can be distinguished with high precision using common and time-sparing tests. The importance of discriminating these clinical features may benefit from this evidence.

  2. An Overview of Countertransference With Borderline Patients

    PubMed Central

    GABBARD, GLEN O.

    1993-01-01

    Successful management of countertransference is critical to the psychotherapy of borderline patients. The author discusses the most common countertransference reactions encountered in such treatments. A theoretical framework is also proposed that conceptualizes countertransference as a joint creation between therapist and patient. It follows from this conceptual framework that therapists must constantly monitor their own contributions from past relationships as well as the aspects of countertransference evoked by the patient’s behavior. Countertransference in the psychotherapy of borderline patients must be viewed as a source of valuable diagnostic and therapeutic information and not simply as interference with the therapeutic process. PMID:22700123

  3. Radioimmunoassay for. gamma. -melanocyte stimulating hormone

    SciTech Connect

    Shibasaki, T.; Ling, N.; Guillemin, R.

    1980-05-26

    A specific radioimmunoassay for ..gamma..-melanocyte stimulating hormone-like peptides was developed. An antiserum raised in rabbit to synthetic bovine ..gamma../sub 3/-MSH, one of the possible ..gamma..-MSH peptides, specifically recognizes the portion between His/sup 5/ and Arg/sup 14/ of ..gamma../sub 3/-MSH without significant cross-reaction with other synthetic ..gamma..-MSH-like peptides, ..cap alpha..-, ..beta..-MSH, adrenocorticotropin, and ..beta..-endorphin. The usable range of this RIA is 10 pg to 600 pg of synthetic ..gamma../sub 3/-MSH. Three immunoreactive ..gamma..-MSH peaks were thus found in gel permeation chromatography of the whole bovine pituitary extract.

  4. Congenital melanocytic nevus: two clinicopathological forms.

    PubMed

    Magaña, Mario; Sánchez-Romero, Elizabeth; Magaña, Pablo; Beck-Magaña, Andrés; Magaña-Lozano, Mario

    2015-01-01

    Congenital melanocytic nevus (CMN) is a hamartomatous disease for which many attempts at classification have been proposed. This disease is relevant not only because of its functional and esthetic implications but also because it is a well-documented precursor to malignant melanoma. We performed a clinical and pathological prospective study of 200 cases of CMN and were able to identify 2 different forms of CMN, each one with biological, clinical, and histopathological features and criteria that are consistent and repeatable. We propose to name them types I and II. Type I CMN is the most common, usually, if not always, a single lesion, it consists of a plaque that involves only 1 anatomic region and does not go beyond it; type I CNM grows in proportion to the growth of the child, melanoma rarely develops from it, and when it does it usually arises at the dermoepidermal junction. Its histopathology shows cords, strands, nests, and single units of melanocytes spreading between collagen bundles only in the dermis and frequently the epidermis too, but without trespassing to the hypodermis, that is, it is superficial. Type II CMN is always made up of many lesions, one of them being very large and surrounded by many lesions; histopathologically, it involves not only the skin but also deeper structures, sometimes bone and central nervous system; therefore, it is deep; when melanoma develops, it does in the dermal component and usually from the largest plaque. This type of CMN is the one that develops neurocutaneous melanocytosis. This system is not only easy and logical but it also has biologic advantages and the clinical-pathological correlation and criteria are repeatable by clinicians and pathologists.

  5. Monitoring human melanocytic cell responses to piperine using multispectral imaging

    NASA Astrophysics Data System (ADS)

    Samatham, Ravikant; Phillips, Kevin G.; Sonka, Julia; Yelma, Aznegashe; Reddy, Neha; Vanka, Meenakshi; Thuillier, Philippe; Soumyanath, Amala; Jacques, Steven

    2011-03-01

    Vitiligo is a depigmentary disease characterized by melanocyte loss attributed most commonly to autoimmune mechanisms. Currently vitiligo has a high incidence (1% worldwide) but a poor set of treatment options. Piperine, a compound found in black pepper, is a potential treatment for the depigmentary skin disease vitiligo, due to its ability to stimulate mouse epidermal melanocyte proliferation in vitro and in vivo. The present study investigates the use of multispectral imaging and an image processing technique based on local contrast to quantify the stimulatory effects of piperine on human melanocyte proliferation in reconstructed epidermis. We demonstrate the ability of the imaging method to quantify increased pigmentation in response to piperine treatment. The quantization of melanocyte stimulation by the proposed imaging technique illustrates the potential use of this technology to quickly assess therapeutic responses of vitiligo tissue culture models to treatment non-invasively.

  6. Immunohistochemical diagnosis of canine oral amelanotic melanocytic neoplasms.

    PubMed

    Smedley, R C; Lamoureux, J; Sledge, D G; Kiupel, M

    2011-01-01

    Definitive diagnosis of canine oral melanocytic neoplasms is often difficult because of variability in pigmentation and cellular pleomorphism. These neoplasms can resemble carcinomas, sarcomas, and round cell neoplasms, which differ in prognosis and treatment. A variety of immunohistochemical antibodies have been used for diagnosis of melanocytic neoplasms in humans and dogs; however, sensitivity and specificity of many markers have not been determined in amelanotic melanocytic neoplasms in dogs. The authors investigated a comprehensive panel of immunohistochemical markers in 49 canine oral amelanotic melanocytic neoplasms--namely, Melan-A, PNL2, HMB-45, microphthalmia transcription factor (MiTF), S-100, tyrosine hydroxylase, tyrosinase, tyrosinase-related proteins 1 and 2 (TRP-1 and TRP-2), and CD34. Ten well-differentiated cutaneous soft tissue spindle cell sarcomas were negative controls. Melan-A, PNL2, TRP-1, and TRP-2 were highly sensitive and 100% specific for the diagnosis of canine oral amelanotic melanocytic neoplasms. S-100 and MiTF showed high sensitivity but were less specific; that is, they also labeled a proportion of the soft tissue spindle cell sarcomas. HMB-45, tyrosinase, and tyrosine hydroxylase were 100% specific but had low sensitivities. CD34 did not label any of the melanocytic neoplasms but did label 80% of the soft tissue spindle cell sarcomas. A cost-effective and efficient immunodiagnostic cocktail containing antibodies against PNL2, Melan-A, TRP-1, and TRP-2 was created that had 100% specificity and 93.9% sensitivity in identifying canine oral amelanotic melanocytic neoplasms. The spindloid variant was the variant with the lowest sensitivity to the cocktail. The likelihood of correctly diagnosing canine oral amelanotic melanocytic neoplasms was dramatically higher when biopsy samples contained ample overlying and adjacent epithelium.

  7. Distinctive molecular responses to ultraviolet radiation between keratinocytes and melanocytes

    PubMed Central

    Sun, Xiaoyun; Kim, Arianna; Nakatani, Masashi; Shen, Yao; Liu, Liang

    2017-01-01

    Solar ultraviolet radiation (UVR) is the major risk factor for skin carcinogenesis. To gain new insights into the molecular pathways mediating UVR effects in the skin, we performed comprehensive transcriptomic analyses to identify shared and distinctive molecular responses to UVR between human keratinocytes and melanocytes. Keratinocytes and melanocytes were irradiated with varying doses of UVB (10, 20 and 30 mJ/cm2) then analysed by RNA-Seq at different time points post-UVB radiation (4, 24 and 72 h). Under basal conditions, keratinocytes and melanocytes expressed similar number of genes, although they each expressed a distinctive subset of genes pertaining to their specific cellular identity. Upon UVB radiation, keratinocytes displayed a clear pattern of time- and dose-dependent changes in gene expression that was different from melanocytes. The early UVB-responsive gene set (4 h post-UVR) differed significantly from delayed UVB-responsive gene sets (24 and 72 h). We also identified multiple novel UVB signature genes including PRSS23, SERPINH1, LCE3D and CNFN, which were conserved between melanocyte and keratinocyte lines from different individuals. Taken together, our findings elucidated both common and distinctive molecular features between melanocytes and keratinocytes and uncovered novel UVB signature genes that might be utilized to predict UVB photobiological effects on the skin. PMID:27119462

  8. The borderline diagnosis in adolescents: symptoms and developmental history.

    PubMed

    Ludolph, P S; Westen, D; Misle, B; Jackson, A; Wixom, J; Wiss, F C

    1990-04-01

    Adult criteria for borderline personality disorder distinguished a group of 27 inpatient adolescent girls from 23 nonborderline inpatient female comparison subjects. The two groups were compared on retrospectively assessed variables measuring psychological, familial, and constitutional factors. Variables most likely to predict borderline personality disorder included history of disrupted attachments, maternal neglect, maternal rejection, grossly inappropriate parental behavior, number of mother and father surrogates, physical abuse, and sexual abuse. Families of borderline adolescents were chronically disrupted, particularly during the patients' early childhoods. The traumatic childhood experiences of the borderline adolescents were similar to those of adults with borderline personality disorder in recent studies.

  9. Borderline Intellectual Functioning: A Systematic Literature Review

    ERIC Educational Resources Information Center

    Peltopuro, Minna; Ahonen, Timo; Kaartinen, Jukka; Seppälä, Heikki; Närhi, Vesa

    2014-01-01

    The literature related to people with borderline intellectual functioning (BIF) was systematically reviewed in order to summarize the present knowledge. Database searches yielded 1,726 citations, and 49 studies were included in the review. People with BIF face a variety of hardships in life, including neurocognitive, social, and mental health…

  10. The Relationship Between Borderline Personality and Obesity

    PubMed Central

    Sansone, Lori A.

    2013-01-01

    Obesity is a significant health problem in the United States. Therefore, it is extremely important to understand potential clinical associations with obesity, including personality pathology. From studies of personality disorders in other types of eating pathology, it appears that restrictive personality disorders (e.g., obsessive-compulsive disorder) are associated with restrictive eating pathology (e.g., anorexia nervosa, restricting type) whereas impulsive personality disorders (e.g., borderline personality disorder) are associated with impulsive eating pathology (e.g., anorexia nervosa, binge-eating/purging type; bulimia nervosa, binge eating disorder). Because binge eating disorder is oftentimes associated with an obese status, it seems likely that borderline personality disorder may also be associated with obesity. At the present time, there appear to be nine accessible studies in this area, comprising 639 obese individuals. While rates of borderline personality disorder in these studies vary from 2.2 to 94.1 percent, 10 of 19 measures detected this disorder at rates of 25 percent or higher, and the average of all percentages is 26.9 percent. Findings appear to support the association between impulsive personality pathology and impulsive eating pathology, and underscore that a significant minority of obese individuals may suffer from borderline personality disorder. PMID:23696958

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

    PubMed

    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.

  12. Nanostructural change of human melanocytes stimulated with α-melanocyte stimulating hormone observed by atomic force microscopy.

    PubMed

    Shin, Min Kyung; Lim, Hee Kyeong; Kang, Boo Kyoung; Lee, Gi-Ja; Uhm, Yun-Kyung; Lee, Mu-Hyoung

    2014-01-01

    It is well known that α-melanocyte stimulating hormone (α-MSH) induces melanization, but structural changes of melanocytes after α-MSH exposure are not well known. This study investigated the serial morphologic changes of human cultured melanocytes after stimulation with α-MSH using atomic force microscopy (AFM). Cultured human melanocytes were treated with α-MSH for 7 days. Contact mode AFM images were obtained using a NANOstation II and fixed melanocytes were scanned in PBS solution at a resolution of 512 × 512 pixels, at a scan speed of 0.4 line/s. The surface roughness and pore-like structures of the melanocytes were measured from topographic images using the Scanning Probe Imaging Processor. The surface roughness of cell body did not change significantly over time. All three roughness parameters (Sa, Sq, Sz) inside the pore-like structures on the dendrites increased significantly. The number of pore-like structures increased and the length and the breadth of pore-like structures also increased gradually. Pore-like structures changed statistically significantly in response to α-MSH stimulation. Further study will be needed to clarify whether the nature of pore-like structures is related to movement of melanosomes.

  13. TFAP2 paralogs regulate melanocyte differentiation in parallel with MITF

    PubMed Central

    Loftus, Stacie K.; Liu, Huan; Sompallae, Ramakrishna; Gildea, Derek E.; Santana, Juan F.; Manak, J. Robert; Pavan, William J.; Williams, Trevor; Cornell, Robert A.

    2017-01-01

    Mutations in the gene encoding transcription factor TFAP2A result in pigmentation anomalies in model organisms and premature hair graying in humans. However, the pleiotropic functions of TFAP2A and its redundantly-acting paralogs have made the precise contribution of TFAP2-type activity to melanocyte differentiation unclear. Defining this contribution may help to explain why TFAP2A expression is reduced in advanced-stage melanoma compared to benign nevi. To identify genes with TFAP2A-dependent expression in melanocytes, we profile zebrafish tissue and mouse melanocytes deficient in Tfap2a, and find that expression of a small subset of genes underlying pigmentation phenotypes is TFAP2A-dependent, including Dct, Mc1r, Mlph, and Pmel. We then conduct TFAP2A ChIP-seq in mouse and human melanocytes and find that a much larger subset of pigmentation genes is associated with active regulatory elements bound by TFAP2A. These elements are also frequently bound by MITF, which is considered the “master regulator” of melanocyte development. For example, the promoter of TRPM1 is bound by both TFAP2A and MITF, and we show that the activity of a minimal TRPM1 promoter is lost upon deletion of the TFAP2A binding sites. However, the expression of Trpm1 is not TFAP2A-dependent, implying that additional TFAP2 paralogs function redundantly to drive melanocyte differentiation, which is consistent with previous results from zebrafish. Paralogs Tfap2a and Tfap2b are both expressed in mouse melanocytes, and we show that mouse embryos with Wnt1-Cre-mediated deletion of Tfap2a and Tfap2b in the neural crest almost completely lack melanocytes but retain neural crest-derived sensory ganglia. These results suggest that TFAP2 paralogs, like MITF, are also necessary for induction of the melanocyte lineage. Finally, we observe a genetic interaction between tfap2a and mitfa in zebrafish, but find that artificially elevating expression of tfap2a does not increase levels of melanin in mitfa

  14. Muse Cells Derived from Dermal Tissues Can Differentiate into Melanocytes.

    PubMed

    Tian, Ting; Zhang, Ru-Zhi; Yang, Yu-Hua; Liu, Qi; Li, Di; Pan, Xiao-Ru

    2017-02-07

    The objective of the authors has been to obtain multilineage-differentiating stress-enduring cells (Muse cells) from primary cultures of dermal fibroblasts, identify their pluripotency, and detect their ability to differentiate into melanocytes. The distribution of SSEA-3-positive cells in human scalp skin was assessed by immunohistochemistry, and the distribution of Oct4, Sox2, Nanog, and SSEA-3-positive cells was determined by immunofluorescence staining. The expression levels of Sox2, Oct4, hKlf4, and Nanog mRNAs and proteins in Muse cells were determined by reverse transcription polymerase chain reaction (RT-PCR) analyses and Western blots, respectively. These Muse cells differentiated into melanocytes in differentiation medium. The SSEA-3-positive cells were scattered in the basement membrane zone and the dermis, with comparatively more in the sebaceous glands, vascular and sweat glands, as well as the outer root sheath of hair follicles, the dermal papillae, and the hair bulbs. Muse cells, which have the ability to self-renew, were obtained from scalp dermal fibroblasts by flow cytometry sorting with an anti-SSEA-3 antibody. The results of RT-PCR, Western blot, and immunofluorescence staining showed that the expression levels of Oct4, Nanog, Sox2, and Klf4 mRNAs and proteins in Muse cells were significantly different from their parental dermal fibroblasts. Muse cells differentiated into melanocytes when cultured in melanocyte differentiation medium, and the Muse cell-derived melanocytes expressed the melanocyte-specific marker HMB45. Muse cells could be obtained by flow cytometry from primary cultures of scalp dermal fibroblasts, which possessed the ability of pluripotency and self-renewal, and could differentiate into melanocytes in vitro.

  15. Wnt inhibitory factor (WIF)-1 promotes melanogenesis in normal human melanocytes.

    PubMed

    Park, Tae Jun; Kim, Misun; Kim, Hyeran; Park, Sun Yi; Park, Kyoung-Chan; Ortonne, Jean-Paul; Kang, Hee Young

    2014-01-01

    Wnt signaling plays a role in the differentiation as well as the development of melanocytes. Using a microarray analysis, hyperpigmentary skin of melasma expressed high levels of Wnt inhibitory factor-1 (WIF-1) compared with perilesional normal skin. In this study, the expression and functional roles of WIF-1 on melanocytes were investigated. WIF-1 was expressed both in the melanocytes of normal human skin and in cultured melanocytes. The upregulation of WIF-1 on cultured normal human melanocytes significantly induced expressions of MITF and tyrosinase, which were associated with increased melanin content and tyrosinase activity. Consistent with the stimulatory effect of WIF-1, WIF-1 siRNA reduced melanogenesis in the cells. Moreover, WIF-1 increases pigmentation in melanocytes co-cultured with WIF-1-overexpressed fibroblasts and of organ-cultured human skin. These findings suggest that melanocytes express WIF-1 constitutively in vivo and in vitro and that WIF-1 promotes melanogenesis in normal human melanocytes.

  16. Alpha-melanocyte-stimulating hormone suppresses oxidative stress through a p53-mediated signaling pathway in human melanocytes.

    PubMed

    Kadekaro, Ana Luisa; Chen, Juping; Yang, Jennifer; Chen, Shuna; Jameson, Joshua; Swope, Viki B; Cheng, Tan; Kadakia, Madhavi; Abdel-Malek, Zalfa

    2012-06-01

    Epidermal melanocytes are skin cells specialized in melanin production. Activation of the melanocortin 1 receptor (MC1R) on melanocytes by α-melanocyte-stimulating hormone (α-MSH) induces synthesis of the brown/black pigment eumelanin that confers photoprotection from solar UV radiation (UVR). Contrary to keratinocytes, melanocytes are slow proliferating cells that persist in the skin for decades, in an environment with high levels of UVR-induced reactive oxygen species (ROS). We previously reported that in addition to its role in pigmentation, α-MSH also reduces oxidative stress and enhances the repair of DNA photoproducts in melanocytes, independent of melanin synthesis. Given the significance of ROS in carcinogenesis, here we investigated the mechanisms by which α-MSH exerts antioxidant effects in melanocytes. We show that activation of the MC1R by α-MSH contributes to phosphorylation of p53 on serine 15, a known requirement for stabilization and activation of p53, a major sensor of DNA damage. This effect is mediated by the cAMP/PKA pathway and by the activation of phosphoinositide 3-kinase (PI3K) ATR and DNA protein kinase (DNA-PK). α-MSH increases the levels of 8-oxoguanine DNA glycosylase (OGG1) and apurinic apyrimidinic endonuclease 1 (APE-1/Ref-1), enzymes essential for base excision repair. Nutlin-3, an HDM2 inhibitor, mimicked the effects of α-MSH resulting in reduced phosphorylation of H2AX (γ-H2AX), a marker of DNA damage. Conversely, the p53 inhibitor pifithrin-α or silencing of p53 abolished the effects of α-MSH and augmented oxidative stress. These results show that p53 is an important target of the downstream MC1R signaling that reduces oxidative stress and possibly malignant transformation of melanocytes.

  17. Pigmented odontogenic tumors: Adding color to diagnosis?

    PubMed Central

    Bhanu, Udhay; Kulkarni, Rasika; Boaz, Karen; Srikant, N

    2014-01-01

    Melanocytes are neural crest derivatives that exhibit a ubiquitous presence in the epidermis. They determine the complexion of an individual and most importantly, provide a barrier against ultraviolet radiations from the sun. Their presence in the oral cavity is a consistent finding, especially in the gingiva and buccal mucosa of the dark complexioned. Melanocytes occasionally form a part of the histology of a variety of odontogenic cysts and tumors. How these cells make their way into the lesional tissue and the diagnostic relevance of their presence remains elusive. This write up attempts to trace the path melanocytes take to find themselves within odontogenic tumors and also offer possible explanations for the same. PMID:25948995

  18. Transplantation of cultured autologous melanocytes: hope or danger?

    PubMed

    Czajkowski, Rafal; Pokrywczynska, Marta; Placek, Waldemar; Zegarska, Barbara; Tadrowski, Tadeusz; Drewa, Tomasz

    2010-01-01

    Cultured human melanocytes are increasingly being used in the treatment of vitiligo. The growth media contain various types of mitogenic factors, both recombinant human (e.g., rhbFGF and rhSCF) and synthetic (e.g., TPA). High concentrations of mitogenic factors accelerate the cell cycle, and consequently may increase the risk of carcinogenesis of transplanted cells. Mutations of genes of the RAS/RAF/MEK/ERK signaling pathway are very often found in the early stages of the development of melanoma. TPA is considered to be an oncogenic factor, but so far there is no evidence to show that it is responsible for damage to the genetic material of cultured melanocytes. The aim of our study was to assess the risk of the development of mutations in selected genes of the RAS/RAF/MEK/ERK signaling pathway during the culturing of melanocytes in various growth media. Based on the results obtained, it can be concluded that TPA and high concentrations of other growth factors intensify the proliferation of melanocytes, without the risk of damage to the HRAS (exon 1 and 2), KRAS (exon 1 and 2), NRAS (exon 1 and 2), and BRAF (exon 11 and 15) genes. In order to assess the total safety of the transplantation of cultured melanocytes, it is necessary to carry out further studies on other signaling pathways as well as carry out biological tests on an animal model.

  19. Effect of streptomycin on melanogenesis and antioxidant status in melanocytes.

    PubMed

    Wrześniok, Dorota; Beberok, Artur; Otręba, Michał; Buszman, Ewa

    2013-11-01

    Streptomycin is an aminoglycoside antibiotic with an antituberculosis activity commonly used in clinical practice due to its good antimicrobial characteristics. A well-known undesirable side effect of this drug is ototoxicity, which may be caused by overproduction of reactive oxygen species and loss of melanocytes in the inner ear. The aim of this study was to examine the effect of streptomycin on melanogenesis and antioxidant defense system in cultured normal human melanocytes (HEMa-LP). Streptomycin induced concentration-dependent loss in melanocytes viability. The value of EC50 was determined to be ~5.0 mM. It has been shown that streptomycin causes inhibition of tyrosinase activity and reduces melanin content in human melanocytes in a concentration-dependent manner. Significant changes in the activity of cellular antioxidant enzymes: superoxide dismutase, catalase, and glutathione peroxidase were also stated. The results obtained in vitro may explain a potential role of melanocytes and melanin in the causative mechanisms of aminoglycosides ototoxic effects in vivo.

  20. Hesperetin induces melanin production in adult human epidermal melanocytes.

    PubMed

    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 < 0.01) and 1.1-fold (p < 0.01), respectively, and the corresponding increases in the case of 50 µM HSP were 1.9-fold (p < 0.001) and 1.3-fold (p < 0.001). Therefore, HSP could be considered a valuable photoprotective substance if its capacity to increase melanin production in human melanocyte cultures could be reproduced on human skin.

  1. Melanin: the biophysiology of oral melanocytes and physiological oral pigmentation.

    PubMed

    Feller, Liviu; Masilana, Aubrey; Khammissa, Razia A G; Altini, Mario; Jadwat, Yusuf; Lemmer, Johan

    2014-03-24

    The presence of melanocytes in the oral epithelium is a well-established fact, but their physiological functions are not well defined. Melanin provides protection from environmental stressors such as ultraviolet radiation and reactive oxygen species; and melanocytes function as stress-sensors having the capacity both to react to and to produce a variety of microenvironmental cytokines and growth factors, modulating immune, inflammatory and antibacterial responses. Melanocytes also act as neuroendocrine cells producing local neurotransmitters including acetylcholine, catecholamines and opioids, and hormones of the melanocortin system such as proopiomelanocortin, adrenocorticotropic hormone and α-melanocyte stimulating hormone, that participate in intracellular and in intercellular signalling pathways, thus contributing to tissue homeostasis.There is a wide range of normal variation in melanin pigmentation of the oral mucosa. In general, darker skinned persons more frequently have oral melanin pigmentation than light-skinned persons. Variations in oral physiological pigmentation are genetically determined unless associated with some underlying disease.In this article, we discuss some aspects of the biophysiology of oral melanocytes, of the functions of melanin, and of physiological oral pigmentation.

  2. Treatment of Borderline Personality Disorder in Youth

    PubMed Central

    Biskin, Robert S.

    2013-01-01

    Objectives: Borderline personality disorder (BPD) is frequently encountered in both adult and youth populations. There is a robust literature supporting psychotherapy for adults with BPD, but the literature supporting its use for BPD in youth is more limited. Methods: A literature review was conducted using the keywords “borderline personality disorders” and “adolescence.” Relevant articles were reviewed for inclusion. Results: Several specialized treatments have been studied with mixed results. Dialectical behaviour therapy has no randomized controlled trials in adolescents, emotion regulation training has not demonstrated superiority of treatment as usual, and cognitive analytic therapy has demonstrated more rapid recovery but little difference at follow-up. Mentalization-based treatment has one study supporting its use in self-harming adolescents. Pharmacotherapy has no evidence supporting its use in this population. Conclusions: Structured therapy may be the most important therapeutic component in this population. PMID:23970912

  3. Maturation in patients with borderline personality disorder.

    PubMed

    Levallius, Johanna; Rydén, Göran; Norring, Claes

    2015-08-30

    Patients with borderline personality disorder have a characteristic and extreme personality associated with psychopathology. The aim was to investigate personality change in relation to suicidality following treatment. 21 patients were assessed before and after psychotherapy on personality (NEO PI-R) and suicidality (SUAS). At follow-up, Neuroticism and Conscientiousness normalized along with six lower-order facets; Depression, Impulsiveness, Competence, Achievement Striving, Self-Discipline and Deliberation. Thirteen patients showed a positive personality development paralleled by a lesser degree of suicidality.

  4. [Borderline personality disorders in somatic illness].

    PubMed

    Vender, Simone; Callegari, Camilla; Poloni, Nicola

    2004-06-01

    The borderline personality disorders are very frequent in modern society because of cultural and social reasons. The authors analyze the disturbed mental processes (impulsiveness and memory) because they represent risk factors for the treatment of diseases. On the base of experience of consultation-liaison psychiatry, the authors show some guidelines in the medical practice (primary care and general hospital) in order to overcome the troubles of the treatment.

  5. N-acetylcysteine protects melanocytes against oxidative stress/damage and delays onset of UV-induced melanoma in mice

    PubMed Central

    Cotter, Murray A.; Thomas, Joshua; Cassidy, Pamela; Robinette, Kyle; Jenkins, Noah; Scott, R. Florell; Leachman, Sancy; Samlowski, Wolfram E.; Grossman, Douglas

    2008-01-01

    UV radiation is the major environmental risk factor for melanoma and a potent inducer of oxidative stress, which is implicated in the pathogenesis of several malignancies. We evaluated whether the thiol antioxidant N-acetylcysteine (NAC) could protect melanocytes from UV-induced oxidative stress/damage in vitro and from UV-induced melanoma in vivo. In melan-a cells, a mouse melanocyte line, NAC (1–10 mM) conferred protection from several UV-induced oxidative sequelae including production of intracellular peroxide, formation of the signature oxidative DNA lesion 8-oxoguanine (8-OG), and depletion of free reduced thiols (primarily glutathione). Mice transgenic for hepatocyte growth factor and Survivin, previously shown to develop melanoma following a single neonatal dose of UV irradiation, were administered NAC (7 mg/ml, mother’s drinking water) transplacentally and through nursing until two weeks after birth. Delivery of NAC in this manner reduced thiol depletion and blocked formation of 8-OG in skin following neonatal UV treatment. Mean onset of UV-induced melanocytic tumors was significantly delayed in NAC-treated compared to control mice (21 vs. 14 weeks, p=0.0003). Our data highlight the potential importance of oxidative stress in the pathogenesis of melanoma, and suggest that NAC may be useful as a chemopreventive agent. PMID:17908992

  6. Presence of cytoadhesins (IIb-IIIa-like glycoproteins) on human metastatic melanomas but not on benign melanocytes.

    PubMed

    McGregor, B C; McGregor, J L; Weiss, L M; Wood, G S; Hu, C H; Boukerche, H; Warnke, R A

    1989-10-01

    Glycoproteins IIb and IIIa, a heterodimer complex, play a vital role in blood platelet aggregation and are members of a wide family of membrane receptors known as integrins or cytoadhesins. Cellular interaction to extracellular matrix (ECM) adhesive proteins is mediated by integrins. Certain tumor cells are known to interact with ECM and blood platelets in the process of metastasis. However, it is not known if tumor cells, compared with their normal counterparts, acquire IIb-IIIa-like receptors to help them in their metastatic spread. In this study, monoclonal antibodies directed against the IIb-IIIa platelet glycoprotein complex were used on frozen biopsies of normal and various tumor tissues to detect the presence of these integrins. These studies demonstrate the presence of IIb-IIIa-like glycoproteins on the cells of metastatic malignant melanoma but not on benign melanocytes and rarely on other tumors. The presence of integrins on melanomas may help explain their propensity for frequent metastasis.

  7. INTEGRATIVE BORDERLINE ADOLESCENT FAMILY THERAPY: MEETING THE CHALLENGES OF TREATING ADOLESCENTS WITH BORDERLINE PERSONALITY DISORDER

    PubMed Central

    SANTISTEBAN, DANIEL A.; MUIR, JOAN A.; MENA, MAITE P.; MITRANI, VICTORIA B.

    2014-01-01

    With the growing acceptance of the borderline personality disorder diagnosis for adolescents has come a need for specialized treatments for this challenging population. Further, because of the prominence of the family system during early and later adolescence, family treatments are particularly needed. The purpose of this article is to present the integrative borderline adolescent family therapy (I-BAFT) model that emerged from a National Institute on Drug Abuse–funded (Stage 1) treatment development and enhancement effort. I-BAFT integrates (a) key interventions from the family treatment of adolescent drug abuse (D. A. Santisteban et al., 2003; J. Szapocznik & W. Kurtines, 1989), (b) skills training shown effective with adults with borderline personality disorder (M. Linehan, 1993a) and adapted for adolescents, and (c) individual treatment interventions that promote motivation for treatment and enhance the integration of the 3 treatment components. PMID:25663719

  8. Induction of nerve growth factor receptors on cultured human melanocytes

    SciTech Connect

    Peacocke, M.; Yaar, M.; Mansur, C.P.; Chao, M.V.; Gilchrest, B.A. )

    1988-07-01

    Normal differentiation and malignant transformation of human melanocytes involve a complex series of interactions during which both genetic and environmental factors play roles. At present, the regulation of these processes is poorly understood. The authors have induced the expression of nerve growth factor (NGF) receptors on cultured human melanocytes with phorbol 12-tetradecanoate 13-acetate and have correlated this event with the appearance of a more differentiated, dendritic morphology. Criteria for NGF receptor expression included protein accumulation and cell-surface immunofluorescent staining with a monoclonal antibody directed against the human receptor and induction of the messenger RNA species as determined by blot-hybridization studies. The presence of the receptor could also be induced by UV irradiation or growth factor deprivation. The NGF receptor is inducible in cultured human melanocytes, and they suggest that NGF may modulate the behavior of this neural crest-derived cell in the skin.

  9. Metaplastic breast carcinoma; melanocytic variant, a very rare tumour

    PubMed Central

    Nzegwu, Martin A.; Sule, Emmanuel; Uzoigwe, Joseph; Achi, Franklyn

    2015-01-01

    Metaplastic breast carcinoma (MBC) is a rare heterogeneous malignancy, accounting for <1% of all invasive breast carcinomas, in which adenocarcinoma is found to coexist with an admixture of spindle, squamous, chondroid or bone-forming neoplastic cells. Melanocytic variant was first described by Ruffolo et al. in 1997. We report a case of MBC, melanocytic variant, in a 57-year-old Nigerian female who presented with a left breast mass 8 cm in diameter in the upper outer quadrant, hard and gradually increase in size to become painful. Breast examination showed gross asymmetry. Left breast was oedematous and shiny with extensive peau d'orange. No palpable axillary nodes were seen. Chest X-ray and abdominal ultrasound scan showed no involvement. Breast biopsy revealed an invasive metaplastic ductal carcinoma with melanocytic differentiation. PMID:25666364

  10. Management considerations for giant congenital melanocytic nevi in adults.

    PubMed

    Green, Margaret C; Mitchum, Marsha D; Marquart, Jason D; Bingham, Jonathan L

    2014-04-01

    Giant congenital melanocytic nevi (GCMN) are a rare type of melanocytic nevus that covers a large body surface, often with satellite nevi scattered on the rest of the skin. There are several complications associated with GCMN, including malignant melanoma and neurocutaneous melanosis. The management of GCMN is very complex because of the cosmetic appearance and the associated psychological distress, the risk of severe complications, and the need for long-term follow-up. We report a case of a 43-year-old active-duty female with a GCMN reporting new and symptomatic satellite lesions with atypical features on dermoscopy.

  11. The risk of cutaneous melanoma in melanocytic nevi*

    PubMed Central

    Fernandes, Nurimar Conceição

    2013-01-01

    The data on melanoma associaed with melanocytic nevus are controversial. A longitudinal prospective study of 107 cases of cutaneous melanoma revealed that 9 (8.4%) cases were presumed to be linked to a precursor lesion, but only in 1 (0.9%) out of these cases the histopathological examination showed an associated melanocytic nevus. The vague information of a preexisting lesion of cutaneous melanoma is not sufficient to consider it a tumour precursor and it requires histopathological evidence to confirm the diagnosis. PMID:23739702

  12. Collecting Tumor Samples From Patients With Gynecological Tumors

    ClinicalTrials.gov

    2016-10-26

    Borderline Ovarian Clear Cell Tumor; Borderline Ovarian Serous Tumor; Cervical Adenocarcinoma; Cervical Adenosquamous Carcinoma; Cervical Small Cell Carcinoma; Cervical Squamous Cell Carcinoma, Not Otherwise Specified; Childhood Embryonal Rhabdomyosarcoma; Childhood Malignant Ovarian Germ Cell Tumor; Endometrioid Stromal Sarcoma; Gestational Trophoblastic Tumor; Malignant Mesothelioma; Malignant Ovarian Epithelial Tumor; Melanoma; Neoplasm of Uncertain Malignant Potential; Ovarian Brenner Tumor; Ovarian Clear Cell Cystadenocarcinoma; Ovarian Serous Cystadenocarcinoma; Paget Disease of the Vulva; Recurrent Cervical Carcinoma; Recurrent Fallopian Tube Carcinoma; Recurrent Ovarian Carcinoma; Recurrent Ovarian Germ Cell Tumor; Recurrent Primary Peritoneal Carcinoma; Recurrent Uterine Corpus Carcinoma; Recurrent Vaginal Carcinoma; Recurrent Vulvar Carcinoma; Stage I Ovarian Cancer; Stage I Uterine Corpus Cancer; Stage I Vaginal Cancer; Stage I Vulvar Cancer; Stage IA Cervical Cancer; Stage IA Fallopian Tube Cancer; Stage IA Ovarian Cancer; Stage IA Ovarian Germ Cell Tumor; Stage IB Cervical Cancer; Stage IB Fallopian Tube Cancer; Stage IB Ovarian Cancer; Stage IB Ovarian Germ Cell Tumor; Stage IC Fallopian Tube Cancer; Stage IC Ovarian Cancer; Stage IC Ovarian Germ Cell Tumor; Stage II Ovarian Cancer; Stage II Uterine Corpus Cancer; Stage II Vaginal Cancer; Stage II Vulvar Cancer; Stage IIA Cervical Cancer; Stage IIA Fallopian Tube Cancer; Stage IIA Ovarian Cancer; Stage IIA Ovarian Germ Cell Tumor; Stage IIB Cervical Cancer; Stage IIB Fallopian Tube Cancer; Stage IIB Ovarian Cancer; Stage IIB Ovarian Germ Cell Tumor; Stage IIC Fallopian Tube Cancer; Stage IIC Ovarian Cancer; Stage IIC Ovarian Germ Cell Tumor; Stage III Borderline Ovarian Surface Epithelial-Stromal Tumor; Stage III Cervical Cancer; Stage III Uterine Corpus Cancer; Stage III Vaginal Cancer; Stage III Vulvar Cancer; Stage IIIA Fallopian Tube Cancer; Stage IIIA Ovarian Cancer; Stage IIIA Ovarian Germ Cell

  13. Differential effects of selenite and selenate on human melanocytes, keratinocytes, and melanoma cells.

    PubMed

    Bandura, Laura; Drukala, Justyna; Wolnicka-Glubisz, Agnieszka; Björnstedt, Mikael; Korohoda, Wlodzimierz

    2005-04-01

    Among the substances that attracted the attention of oncologists in recent years are selenium-containing compounds, both inorganic and organic. Several epidemiological studies have shown an inverse correlation between selenium intake and cancer incidence. In the experiments reported here, we compared the effects of 2 inorganic selenium-containing salts that differed in the level of selenium oxidation, selenite IV and selenate VI. We tested the effects of these 2 compounds on cell survival and growth, cell cycle processing, cell morphology, cytoskeleton, and lipid peroxidation in 3 human skin cell types: normal keratinocytes, melanocytes, and human melanoma cell line HTB140. The different effects of selenite and selenate on the viability, growth, and morphology of normal cells and tumor cells are reported and provide a base for future research and treatment of some neoplastic diseases. The attention is paid to cell apoptosis induced by selenite and not by selenate, and the effects of tested substances on thioredoxin reductase system are postulated.

  14. Traumatic iridial extrusion mimicking a conjunctival melanocytic neoplasm

    PubMed Central

    Zoroquiain, Pablo; Ganimi, Maria SB; Alghamdi, Sarah; Burnier, Julia V; Aldrees, Sultan S; Burnier, Miguel N

    2016-01-01

    Conjunctival melanoma is a rare malignant tumour of the eye. Its diagnosis represents a challenge for general pathologists due to low exposure to ocular biopsies and a broad differential diagnosis. In addition, conjunctival samples are often small and are associated with a high frequency of artefacts due to their processing. Here, we present the first case to date of a traumatic iridial extrusion masquerading as a conjunctival melanocytic neoplasm. An 83-year-old Asian man presented with a conjunctival-pigmented nodule surrounded by an area of diffuse pigmentation. Histopathology revealed in the nodule a well-demarcated lesion composed of spindle shaped melanocytes with thick-walled blood vessels. At higher magnification, the blood vessels were composed of thick walls with collagen fibres in an onion-skin-like arrangement. The histological findings were consistent with extruded iridial tissue. The map biopsies of the flat, pigmented lesion showed melanocytic cell proliferation with dendritic processes restricted to the lamina propria without any epithelial involvement, consistent with ocular melanocytosis. The diagnosis of conjunctival melanocytic lesions is challenging, and non-neoplastic conditions should always be included in the differential diagnosis. Pathologists should correlate clinicopathological findings and be familiar with the normal histology in order to achieve the correct diagnosis. PMID:26913071

  15. Molecular biology of normal melanocytes and melanoma cells.

    PubMed

    Bandarchi, Bizhan; Jabbari, Cyrus Aleksandre; Vedadi, Ali; Navab, Roya

    2013-08-01

    Malignant melanoma is one of the most aggressive malignancies in humans and is responsible for 60-80% of deaths from skin cancers. The 5-year survival of patients with metastatic malignant melanoma is about 14%. Its incidence has been increasing in the white population over the past two decades. The mechanisms leading to malignant transformation of melanocytes and melanocytic lesions are poorly understood. In developing malignant melanoma, there is a complex interaction of environmental and endogenous (genetic) factors, including: dysregulation of cell proliferation, programmed cell death (apoptosis) and cell-to-cell interactions. The understanding of genetic alterations in signalling pathways of primary and metastatic malignant melanoma and their interactions may lead to therapeutics modalities, including targeted therapies, particularly in advanced melanomas that have high mortality rates and are often resistant to chemotherapy and radiotherapy. Our knowledge regarding the molecular biology of malignant melanoma has been expanding. Even though several genes involved in melanocyte development may also be associated with melanoma cell development, it is still unclear how a normal melanocyte becomes a melanoma cell. This article reviews the molecular events and recent findings associated with malignant melanoma.

  16. Genome-wide transcriptome analysis of human epidermal melanocytes

    PubMed Central

    Haltaufderhyde, Kirk D.; Oancea, Elena

    2015-01-01

    Because human epidermal melanocytes (HEMs) provide critical protection against skin cancer, sunburn, and photoaging, a genome-wide perspective of gene expression in these cells is vital to understanding human skin physiology. In this study we performed high throughput sequencing of HEMs to obtain a complete data set of transcript sizes, abundances, and splicing. As expected, we found that melanocyte specific genes that function in pigmentation were among the highest expressed genes. We analyzed receptor, ion channel and transcription factor gene families to get a better understanding of the cell signalling pathways used by melanocytes. We also performed a comparative transcriptomic analysis of lightly versus darkly pigmented HEMs and found 16 genes differentially expressed in the two pigmentation phenotypes; of those, only one putative melanosomal transporter (SLC45A2) has known function in pigmentation. In addition, we found 166 genes with splice isoforms expressed exclusively in one pigmentation phenotype, 17 of which are genes involved in signal transduction. Our melanocyte transcriptome study provides a comprehensive view and may help identify novel pigmentation genes and potential pharmacological targets. PMID:25451175

  17. Adipose-Derived Stem Cells Improve Efficacy of Melanocyte Transplantation in Animal Skin

    PubMed Central

    Lim, Won-Suk; Kim, Chang-Hyun; Kim, Ji-Young; Do, Byung-Rok; Kim, Eo Jin; Lee, Ai-Young

    2014-01-01

    Vitiligo is a pigmentary disorder induced by a loss of melanocytes. In addition to replacement of pure melanocytes, cocultures of melanocytes with keratinocytes have been used to improve the repigmentation outcome in vitiligo treatment. We previously identified by in vitro studies, that adipose-derived stem cells (ADSCs) could be a potential substitute for keratinocytes in cocultures with melanocytes. In this study, the efficacy of pigmentation including durability of grafted melanocytes and short-term safety was examined in the nude mouse and Sprague-Dawley rat after grafting of primary cultured human melanocytes, with or without different ratios of primary cultured human ADSCs. Simultaneous grafting of melanocytes and ADSCs, which were separately cultured and mixed on grafting at the ratios of 1:1, 1:2, or 1:3, showed better efficacy than that of pure melanocytes. Grafting of melanocytes cocultured with ADSCs resulted in a similar outcome as the grafting of cell mixtures. Skin pigmentation by melanocytes : ADSCs at the ratios of 1:1 and 1:2 was better than at 1:3. No significant difference was observed between the 1-week and 2-week durations in coculturing. Time-course microscopic examination showed that the grafted melanocytes remained a little longer than 6-week post-grafting. No inflammatory cell infiltration was observed in the grafted skin and no melanocytes were detectable in other organs. Collectively, grafting of melanocytes and ADSCs was equally safe and more effective than grafting of melanocytes alone. Despite the absence of significant differences in efficacy between the group of 1:1 and that of 1:2 ratio, 1:2 ratio for 1-week coculturing may be better for clinical use from the cost-benefit viewpoint. PMID:25143812

  18. Mental capacity and borderline personality disorder

    PubMed Central

    Ayre, Karyn; Owen, Gareth S.; Moran, Paul

    2017-01-01

    The use of the Mental Capacity Act 2005 in assessing decision-making capacity in patients with borderline personality disorder (BPD) is inconsistent. We believe this may stem from persisting confusion regarding the nosological status of personality disorder and also a failure to recognise the fact that emotional dysregulation and characteristic psychodynamic abnormalities may cause substantial difficulties in using and weighing information. Clearer consensus on these issues is required in order to provide consistent patient care and reduce uncertainty for clinicians in what are often emergency and high-stakes clinical scenarios. PMID:28184315

  19. The Lifetime Course of Borderline Personality Disorder

    PubMed Central

    Biskin, Robert S

    2015-01-01

    Borderline personality disorder (BPD) has historically been seen as a lifelong, highly disabling disorder. Research during the past 2 decades has challenged this assumption. This paper reviews the course of BPD throughout life, including childhood, adolescence, and adulthood. BPD can be accurately identified in adolescence, and the course of the disorder, in adolescence and adulthood, is generally similar, with reductions in symptoms over time. Functional recovery is less consistent, and further research on factors or treatments that may improve the long-term functional outcome of patients with BPD is warranted. PMID:26175388

  20. Therapeutic Self-Disclosure With Borderline Patients

    PubMed Central

    WILKINSON, SALLYE M.; GABBARD, GLEN O.

    1993-01-01

    The therapeutic use of countertransference disclosure as a means of highlighting the borderline patient’s intrapsychic and interpersonal use of the therapist is discussed. Countertransference disclosure is narrowly defined as a form of clinical honesty that focuses on the therapist’s experience of the patient in the here-and-now moment of the session. The effects of disclosure on transference exploration, neutrality, and patient revelations are explored through examination of detailed process notes of therapy sessions. Technical issues such as indirect versus direct disclosure and responses to direct questions are also addressed. PMID:22700154

  1. Treating Obesity: Clinical Implications of Comorbid Borderline Personality Disorder.

    ERIC Educational Resources Information Center

    Sansone, Randy A.; Wiederman, Michael W.; Sansone, Lori A.

    1999-01-01

    Reviews possible links between obesity and borderline-personality disorder and discusses treatment approaches for those individuals demonstrating such comorbidity. Approaches include modification of current techniques for obesity treatment and incorporation of psychodynamic counseling specific to borderline-personality disorder. (Author/GCP)

  2. Principles in the Psychotherapy of Self-Destructive Borderline Patients

    PubMed Central

    PLAKUN, ERIC M.

    1994-01-01

    Patients with borderline personality disorder often exhibit lethal or nonlethal self-destructive behavior. The author offers seven principles for establishing and maintaining a therapeutic alliance in the insight-oriented psychodynamic psychotherapy of borderline personality disorder patients with self-destructive behavior serious enough to threaten the continuity of the therapy. PMID:22700187

  3. Relationship between schizotypal and borderline traits in college students.

    PubMed

    Fonseca-Pedrero, Eduardo; Lemos-Giráldez, Serafín; Paino, Mercedes; Sierra-Baigrie, Susana; Muñiz, José

    2012-03-01

    The main objective of the present investigation was to analyze the relationship between self-reported schizotypal and borderline personality traits in a sample of 759 college students (M = 19.63 years; SD = 2.03). For this purpose, the Schizotypal Personality Questionnaire-Brief (SPQ-B; Raine and Benishay, 1995) and Borderline Personality Questionnaire (BPQ; Poreh et al., 2006) were administered. The results showed that schizotypal and borderline features are partially related at subclinical level. The exploratory factor analysis conducted on the subscales revealed a three-factor solution comprised of the following factors: Identity/Interpersonal, Lack of Control and Schizotypal. The canonical correlation analysis showed that schizotypal features and borderline personality traits shared 34.8% of the variance. The data highlight the overlap between schizotypal and borderline personality traits in nonclinical young adults. Future studies should continue to examine the relationship and the degree of overlap between these traits in community samples.

  4. Altered E-Cadherin Levels and Distribution in Melanocytes Precede Clinical Manifestations of Vitiligo.

    PubMed

    Wagner, Roselyne Y; Luciani, Flavie; Cario-André, Muriel; Rubod, Alain; Petit, Valérie; Benzekri, Laila; Ezzedine, Khaled; Lepreux, Sébastien; Steingrimsson, Eirikur; Taieb, A; Gauthier, Yvon; Larue, Lionel; Delmas, Véronique

    2015-07-01

    Vitiligo is the most common depigmenting disorder resulting from the loss of melanocytes from the basal epidermal layer. The pathogenesis of the disease is likely multifactorial and involves autoimmune causes, as well as oxidative and mechanical stress. It is important to identify early events in vitiligo to clarify pathogenesis, improve diagnosis, and inform therapy. Here, we show that E-cadherin (Ecad), which mediates the adhesion between melanocytes and keratinocytes in the epidermis, is absent from or discontinuously distributed across melanocyte membranes of vitiligo patients long before clinical lesions appear. This abnormality is associated with the detachment of the melanocytes from the basal to the suprabasal layers in the epidermis. Using human epidermal reconstructed skin and mouse models with normal or defective Ecad expression in melanocytes, we demonstrated that Ecad is required for melanocyte adhesiveness to the basal layer under oxidative and mechanical stress, establishing a link between silent/preclinical, cell-autonomous defects in vitiligo melanocytes and known environmental stressors accelerating disease expression. Our results implicate a primary predisposing skin defect affecting melanocyte adhesiveness that, under stress conditions, leads to disappearance of melanocytes and clinical vitiligo. Melanocyte adhesiveness is thus a potential target for therapy aiming at disease stabilization.

  5. The "Umbrella Sign": A Useful Clue in the Diagnosis of Melanocytic Lesions in Sun Damaged Skin.

    PubMed

    Wood, Benjamin A; Harvey, Nathan T

    2016-07-01

    As ultraviolet radiation is an important aetiological agent in melanoma development, the presence of solar elastosis is an important factor in the assessment of any melanocytic lesion. However, melanocytic naevi are also seen in chronically sun damaged skin, particularly in regions with high levels of ultraviolet exposure and fair skinned populations. It has previously been noted that the relationship of a melanocytic proliferation to elastic fibers in the dermis can be of discriminatory value in the separation of melanoma from melanocytic naevus, in particular, it has been proposed that naevi act as a "sunscreen," which may result in a histological clue that the authors colloquially refer to in practice as "the umbrella sign." The aim of this study was to evaluate the patterns of solar elastosis within and beneath melanocytic proliferations developing in sun damaged skin and to determine the utility of the "umbrella sign" in diagnostic practice. We assessed 81 melanocytic proliferations in sun damaged skin for the presence of an umbrella sign, that was present in 49/53 melanocytic naevi (92%) compared with only 2/28 melanomas (7%, P < 0.05). In addition, entrapped elastotic fibers displaying distinct purple discolouration were identified in 16 melanocytic naevi. This finding was not identified in any of the melanomas. The umbrella sign appears to be a useful clue in the distinction of melanoma from melanocytic naevus in sun damaged skin, although as with all histological features in melanocytic pathology, it requires interpretation within a multifactorial assessment cognizant of potential diagnostic pitfalls.

  6. Endothelin-1 increases melanin synthesis in an established sheep skin melanocyte culture.

    PubMed

    Pang, Yamiao; Geng, Jianjun; Qin, Yilong; Wang, Haidong; Fan, Ruiwen; Zhang, Ying; Li, Hongquan; Jiang, Shan; Dong, Changsheng

    2016-08-01

    The aims of the study were to establish a culture system for sheep skin melanocytes and uncover the effects of endothelin-1 on melanin synthesis in cultured melanocytes in order to provide an optimal cell system and a theoretical basis for studying the regulatory mechanism of coat color in sheep. In this study, skin punch biopsies were harvested from the dorsal region of 1-3-yr-old sheep, and skin melanocytes were then obtained by the two-step digestion using dispase II and trypsin/ethylene diamine tetraacetic acid (EDTA). The primary cultures of the melanocytes were established and characterized by dopa-staining, immunocytochemical localization of melanocyte markers, and RT-polymerase chain reaction (PCR) analysis of coat color genes. To determine the effect of endothelin-1 on proliferation and melanin synthesis of melanocytes, the cultured cells were treated with different doses of endothelin-1 (10(-7), 10(-8), 10(-9), 10(-10), and 0 mol/L), and the growth rate of melanocytes, production of melanin, expression of related genes, and location of related protein in cultured cells were examined by 3-(4,5-dimethylthiazol-2-yl)-2,5-diphenyltetrazolium bromide (MTT), ultraviolet spectrophotometry, qRT-PCR, and immunocytochemical localization, respectively. The results showed that the established melanocyte culture functions properly. Endothelin-1 treatment increased markedly the number of melanocytes and melanin content. In responding to this treatment, expressions of microphthalmia-associated transcription factor (MITF), melanocortin 1 receptor (MC1R), tyrosinase (TYR), and endothelin receptor B (EDNRB) in the melanocytes were significantly up regulated (P < 0.05). Immunocytochemical localization revealed that TYR was mainly localized in the cytoplasm. Positive staining of TYR in the melanocytes was significant. The findings demonstrated that the culture system of sheep skin melanocytes was established successfully in vitro, and endothelin-1 promotes the

  7. Borderline personality features in depressed or anxious patients.

    PubMed

    Distel, Marijn A; Smit, Johannes H; Spinhoven, Philip; Penninx, Brenda W J H

    2016-07-30

    Anxiety and depression frequently co-occur with borderline personality disorder. Relatively little research examined the presence of borderline personality features and its main domains (affective instability, identity problems, negative relationships and self-harm) in individuals with remitted and current anxiety and depression. Participants with current (n=597) or remitted (n=1115) anxiety and/or depression and healthy controls (n=431) were selected from the Netherlands Study of Depression and Anxiety. Assessments included the Personality Assessment Inventory - Borderline Features Scale and several clinical characteristics of anxiety and depression. Borderline personality features were more common in depression than in anxiety. Current comorbid anxiety and depression was associated with most borderline personality features. Anxiety and depression status explained 29.7% of the variance in borderline personality features and 3.8% (self-harm) to 31% (identity problems) of the variance in the four domains. A large part of the variance was shared between anxiety and depression but both disorders also explained a significant amount of unique variance. The severity of anxiety and depression and the level of daily dysfunctioning was positively associated with borderline personality features. Individuals with a longer duration of anxiety and depression showed more affective instability and identity problems. These findings suggest that patients with anxiety and depression may benefit from an assessment of personality pathology as it may have implications for psychological and pharmacological treatment.

  8. Dracula. Disorders of the self and borderline personality organization.

    PubMed

    Raines, J M; Raines, L C; Singer, M

    1994-12-01

    It has been proposed that Bram Stoker's novel Dracula can best be understood as a dramatic, hyperbolic, and fantastic expression of themes consistent with contemporary psychoanalytic conceptions of borderline personality disorder organization. Such an understanding may, in turn, shed further light on the nature of the intrapsychic world and experiences of borderline patients. Excerpts from the novel can be used to support the conceptualization of recent contributions to object relations theory and the understanding of borderline personality organization. It is uncanny how consistent Dracula's characteristics are to the generally seen complaints of patients suffering from this disorder.

  9. Cellular origin and developmental mechanisms during the formation of skin melanocytes

    SciTech Connect

    Ernfors, Patrik

    2010-05-01

    Melanocytes are derived from the neural crest (NC), which are transient multipotent cells arising by delamination from the developing dorsal neural tube. During recent years, signaling systems and molecular mechanisms of melanocyte development have been studied in detail, but the exact diversification of the NC into melanocytes and how they migrate, expand and disperse in the skin have not been fully understood. The recent finding that Schwann cell precursors (SCPs) of the growing nerve represents a stem cell niche from which various cell types, including Schwann cells, endoneural fibroblasts and melanocytes arise has exposed new knowledge on the cellular basis for melanocyte development. This opens for the identification of new factors and reinterpretation of old data on cell fate instructive, proliferative, survival and cell homing factors participating in melanocyte development.

  10. Paracrine Secreted Frizzled-Related Protein 4 Inhibits Melanocytes Differentiation in Hair Follicle

    PubMed Central

    Guo, Haiying; Lei, Mingxing; Li, Yuhong; Liu, Yingxin; Tang, Yinhong; Xing, Yizhan; Deng, Fang

    2017-01-01

    Wnt signaling plays crucial role in regulating melanocyte stem cells/melanocyte differentiation in the hair follicle. However, how the Wnt signaling is balanced to be overactivated to control follicular melanocytes behavior remains unknown. Here, by using immunofluorescence staining, we showed that secreted frizzled-related protein 4 (sFRP4) is preferentially expressed in the skin epidermal cells rather than in melanocytes. By overexpression of sFRP4 in skin cells in vivo and in vitro, we found that sFRP4 attenuates activation of Wnt signaling, resulting in decrease of melanocytes differentiation in the regenerating hair follicle. Our findings unveiled a new regulator that involves modulating melanocytes differentiation through a paracrine mechanism in hair follicle, supplying a hope for potential therapeutic application to treat skin pigmentation disorders. PMID:28337220

  11. Use of New Techniques in Addition to IHC Applied to the Diagnosis of Melanocytic Lesions, With Emphasis on CGH, FISH, and Mass Spectrometry.

    PubMed

    Nagarajan, P; Tetzlaff, M T; Curry, J L; Prieto, V G

    Melanoma remains one of the most aggressive forms of cutaneous malignancies. While its diagnosis based on histologic parameters is usually straight forward in most cases, distinguishing a melanoma from a melanocytic nevus can be challenging in some instances, especially when there are overlapping clinical and histopathologic features. Occasionally, melanomas can histologically mimic other tumors and even demonstration of melanocytic origin can be challenging. Thus, several ancillary tests may be employed to arrive at the correct diagnosis. The objective of this review is to summarize these tests, including the well-established and commonly used ones such as immunohistochemistry, with specific emphasis on emerging techniques such as comparative genomic hybridization, fluorescence in situ hybridization and imaging mass spectrometry.

  12. Spontaneous Involution of Congenital Melanocytic Nevus With Halo Phenomenon.

    PubMed

    Lee, Noo Ri; Chung, Hee-Chul; Hong, Hannah; Lee, Jin Wook; Ahn, Sung Ku

    2015-12-01

    Congenital melanocytic nevus (CMN) is a neural crest-derived hamartoma, which appear at or soon after birth. CMN has a dynamic course and may show variable changes over time, including spontaneous involution. Spontaneous involution of CMN is a rare phenomenon and is often reported in association with halo phenomenon or vitiligo. The mechanism of halo phenomenon is yet to be investigated but is suggested to be a destruction of melanocytes by immune responses of cytotoxic T cells or IgM autoantibodies. Here, the authors report an interesting case of spontaneously regressed medium-sized CMN with halo phenomenon and without vitiligo, which provides evidence that cytotoxic T cells account for the halo formation and pigmentary regression of CMN.

  13. Molecular pathogenesis of cutaneous melanocytic neoplasms.

    PubMed

    Ibrahim, Nageatte; Haluska, Frank G

    2009-01-01

    Melanoma is the deadliest form of skin cancer without an effective treatment. An understanding of the genetic basis of melanoma has recently shed light on some of the mechanisms of melanomagenesis. This review explores the major genes involved in familial and sporadic cutaneous melanoma with an emphasis on CDKN2A, CDK4, MC1R, and MAPK pathway targets (e.g., RAS and BRAF), apoptosis regulators (e.g., BCL-2, AKT, and APAF-1), and the tumor-suppressor genes TP53 and PTEN. New directions for therapeutics based on our current knowledge of the genes implicated in melanoma are also discussed.

  14. [Discriminative features of borderline personality disorder].

    PubMed

    Kazuko, Tamura; Inoue, Kako

    2009-02-01

    This study investigated some discriminative features of Borderline Personality Disorder (BPD) with both clinical and normal samples using a self-report questionnaire. This questionnaire was administered to 116 clinical outpatients (diagnoses: thirty two BPD; twenty four schizophrenia; twenty six depression; twenty nine neurosis; and five other mental disorders) and to 216 college students as a normal sample. Factor analysis produced six factors: emptiness; hallucination and egorrhea; distortional body image and acts of self-inflicted injury; impulsive acting-out; loss of emotional control; and grandiose omnipotence. Distortional body image and acts of self-inflicted injury discriminated BPD the most from the other samples. No significant differences were seen between the BPD and Schizophrenia samples in terms of the hallucination or egorrhea subscales. An intense loss of emotional control, particularly control of negative emotions such as rage, was apparent in the clinical samples, which was not evident in the normal sample.

  15. Borderline personality disorder and emotional intelligence.

    PubMed

    Peter, Mathell; Schuurmans, Hanneke; Vingerhoets, Ad J J M; Smeets, Guus; Verkoeijen, Peter; Arntz, Arnoud

    2013-02-01

    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 emotions and impairments in the ability to regulate emotions. EI was assessed with the Mayer-Salovey-Caruso Emotional Intelligence Test (Mayer, Salovey, and Caruso [New York: MHS, 2002]). As compared with the PD group and the nonpatient group, the patients with BPD displayed the anticipated deficits in their ability to understand, whereas no differences emerged with respect to their ability to perceive, use, and regulate emotions. In addition, a negative relationship was found between the severity of BPD and total EI score. However, this relationship disappeared when intelligence quotient was partialled out. These results suggest that BPD is associated with emotion understanding deficits, whereas temporary severity of BPD is associated with emotion regulation deficits.

  16. Attachment, borderline personality, and romantic relationship dysfunction.

    PubMed

    Hill, Jonathan; Stepp, Stephanie D; Wan, Ming Wai; Hope, Holly; Morse, Jennifer Q; Steele, Miriam; Steele, Howard; Pilkonis, Paul A

    2011-12-01

    Previous studies have implicated attachment and disturbances in romantic relationships as important indicators for Borderline Personality Disorder (BPD). The current research extends our current knowledge by examining the specific associations among attachment, romantic relationship dysfunction, and BPD, above and beyond the contribution of emotional distress and nonromantic interpersonal functioning in two distinct samples. Study 1 comprised a community sample of women (N = 58) aged 25-36. Study 2 consisted of a psychiatric sample (N = 138) aged 21-60. Results from both Study 1 and Study 2 demonstrated that (1) attachment was specifically related to BPD symptoms and romantic dysfunction, (2) BPD symptoms were specifically associated with romantic dysfunction, and (3) the association between attachment and romantic dysfunction was statistically mediated by BPD symptoms. The findings support specific associations among attachment, BPD symptoms, and romantic dysfunction.

  17. Borderline personality and substance use in women.

    PubMed

    Feske, Ulrike; Tarter, Ralph E; Kirisci, Levent; Pilkonis, Paul A

    2006-01-01

    The association between borderline personality disorder (BPD) and substance use disorder (SUD) was examined in a predominantly psychiatric (77.6%) sample of 232 women. BPD proved to be a significant predictor of a lifetime diagnosis of SUD across four different categories: any SUD (including alcohol); alcohol use; drug use; and heroin, cocaine, or poly-substance use. BPD continued to be a predictor of SUD even when the effects of other cluster B and all cluster C PDs were controlled statistically. Antisocial personality disorder generally yielded larger odds ratios than BPD and emerged as a partial mediator of the relation between BPD and SUD. Histrionic PD was the only other PD that showed meaningful relations with SUD.

  18. Emotional Granularity and Borderline Personality Disorder

    PubMed Central

    Suvak, Michael K.; Litz, Brett T.; Sloan, Denise M.; Zanarini, Mary C.; Barrett, Lisa Feldman; Hofmann, Stefan G.

    2011-01-01

    This study examined the affective dysregulation component of borderline personality disorder (BPD) from an emotional granularity perspective, which refers to the specificity in which one represents emotions. Forty-six female participants meeting criteria for BPD and 51 female control participants without BPD and Axis I pathology completed tasks that assessed the degree to which participants incorporated information about valence (pleasant–unpleasant) and arousal (calm–activated) in their semantic/conceptual representations of emotions and in using labels to represent emotional reactions. As hypothesized, participants with BPD emphasized valence more and arousal less than control participants did when using emotion terms to label their emotional reactions. Implications and future research directions are discussed. PMID:21171723

  19. Psychopharmacologic treatment of borderline personality disorder.

    PubMed

    Ripoll, Luis H

    2013-06-01

    The best available evidence for psychopharmacologic treatment of borderline personality disorder (BPD) is outlined here. BPD is defined by disturbances in identity and interpersonal functioning, and patients report potential medication treatment targets such as impulsivity, aggression, transient psychotic and dissociative symptoms, and refractory affective instability Few randomized controlled trials of psychopharmacological treatments for BPD have been published recently, although multiple reviews have converged on the effectiveness of specific anticonvulsants, atypical antipsychotic agents, and omega-3 fatty acid supplementation. Stronger evidence exists for medication providing significant improvements in impulsive aggression than in affective or other interpersonal symptoms. Future research strategies will focus on the potential role of neuropeptide agents and medications with greater specificity for 2A serotonin receptors, as well as optimizing concomitant implementation of evidence-based psychotherapy and psychopharmacology, in order to improve BPD patients' overall functioning.

  20. Molecular pharmacognosy: a new borderline discipline.

    PubMed

    Huang, Lu-Qi; Yuan, Yuan; Cui, Guang-Hong; Dai, Zhu-Bo; Xiao, Pei-Gen

    2009-11-01

    Pharmacognosy has developed rapidly in recent years and now represents a highly interdisciplinary science. At the boundary between pharmacognosy and molecular biology, molecular pharmacognosy has developed as a new borderline discipline. Using the method and technology of molecular biology, molecular pharmacognosy focuses on resolving a wide range of challenging problems, such as distinguishing herbal and animal drug populations by molecular marker assay, conserving and utilizing wild resources on the basis of knowledge of genetic diversity, investigating the mechanism of active compound accumulation and obtaining new resources with higher quality through genetic engineering. Recent research results show that molecular pharmacognosy has extended the scope of pharmacognostical science and plays an important role in the safe and efficient usage of crude drugs.

  1. Developmental trajectories to male borderline personality disorder.

    PubMed

    Goodman, Marianne; Patel, Uday; Oakes, Allison; Matho, Andrea; Triebwasser, Joseph

    2013-12-01

    Due to the higher diagnostic prevalence of borderline personality disorder (BPD) in females, there exists a dearth of literature on the manifestations of BPD in men and minimal information on male developmental trajectories to the disorder. To identify precursors of BPD in males, surveys were administered to parents about their BPD male offspring and non-BPD male siblings. Questions covered aspects of probands' lives from infancy to late adolescence. BPD offspring were identified through self-reported clinical diagnoses and standardized diagnostic criteria embedded within the survey. A total of 263 male offspring (97 meeting strict criteria for BPD and 166 non-BPD siblings) were studied. The authors found that parents describe the early emergence of a constellation of symptoms in their BPD sons that include separation anxiety starting in infancy, body image concerns in childhood, and impulsivity, emptiness, and odd thinking in adolescence. This trajectory differs from the developmental course found in females diagnosed with BPD.

  2. Ultraviolet radiation directly induces pigment production by cultured human melanocytes

    SciTech Connect

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

    1987-10-01

    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 /sup 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.

  3. Clues to the diagnosis of atypical melanocytic lesions.

    PubMed

    McKee, Phillip H

    2010-01-01

    This review, based on a lecture given at the 2009 Update in Dermatopathology meeting held at the Institute of Dermatology (London, UK), discusses the problem of misdiagnosing atypical benign melanocytic lesions as melanoma and the alternative problem of interpreting naevoid melanoma as a banal naevus. Consequences are considered. Brief consideration of a range of other melanoma variants that may be a source of diagnostic difficulty is also included.

  4. Expression profiling of human melanocytes in response to UV-B irradiation

    PubMed Central

    López, Saioa; Smith-Zubiaga, Isabel; Alonso, Santos

    2015-01-01

    A comprehensive gene expression analysis of human melanocytes was performed assessing the transcriptional profile of dark melanocytes (DM) and light melanocytes (LM) at basal conditions and after UV-B irradiation at different time points (6, 12 and 24 h), and in culture with different keratinocyte-conditioned media (KCM + and KCM −). The data, previously published in [1], have been deposited in NCBI's Gene Expression Omnibus (GEO accession number: GSE70280). PMID:26697372

  5. The optical properties and spectral features of malignant skin melanocytes in the terahertz frequency range

    NASA Astrophysics Data System (ADS)

    Goryachuk, A. A.; Begaeva, V. A.; Khodzitsky, M. K.; Truloff, A. S.

    2016-08-01

    The samples of cells of mice's melanocytes have been investigated. Their optical properties and spectral features were investigated by terahertz time-domain spectroscopy (TDS) in transmission mode. It was found that the optical properties of oncological melanocytes and normal cells are different and oncological cells have spectral features of absorption coefficient so it can be concluded that it is easy to discriminate mice's oncological skin melanocytes by using THz TDS.

  6. UVA phototransduction drives early melanin synthesis in human melanocytes.

    PubMed

    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.

  7. Automatic Classification of Specific Melanocytic Lesions Using Artificial Intelligence

    PubMed Central

    Jaworek-Korjakowska, Joanna; Kłeczek, Paweł

    2016-01-01

    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. PMID:26885520

  8. Diagnostic utility of 5-hydroxymethylcytosine immunohistochemistry in melanocytic proliferations

    PubMed Central

    Rodić, Nemanja; Zampella, John; Sharma, Reema; Burns, Kathleen H.; Taube, Janis M.

    2015-01-01

    Decreased hydroxymethylated cytosine (5-hydroxymethycytosine, 5-hmC) is reported to correlate with melanocyte dysplasia. The purpose of this study was to assess the diagnostic utility of this observation. 5-hmC immunohistochemistry was performed on tissue microarrays containing 171-melanocytic lesions from two different institutions. An immunohistochemical staining score representing the percentage and intensity of nuclear staining was assigned. The performance characteristics of 5-hmC immunohistochemistry for discriminating between a nevus and melanoma were determined. Additional cases of melanoma arising in a nevus (n = 8), nodal nevi (n = 5) and melanoma micrometastases to a lymph node (n = 6) were also assessed. Pronounced 5-hmC loss was observed in melanomas when compared with nevi (mean ± standard deviation = 6.71 ± 11.78 and 55.19 ± 23.66, respectively, p < 0.0001). While the mean immunohistochemical staining score values for melanocytic nevi and melanoma were distinct, there was considerable variability in immunohistochemical staining score within a single diagnostic category. The sensitivity and specificity of this assay for nevus vs. melanoma is 92.74 and 97.78%, respectively. Distinct biphasic staining patterns were observed in cases of melanoma arising in association with a nevus. Relative changes of 5-hmC expression within a single lesion may be more informative than absolute values when using 5-hmC as a diagnostic adjunct. PMID:26239102

  9. Ultrastructural changes in the melanocytes of aging human choroid.

    PubMed

    Nag, Tapas Chandra

    2015-12-01

    Retinal pigment epithelial cells as well as choroidal melanocytes (CM) possess melanin granules. The former show clear, age-related changes (formation of lipofuscin granules with a concomitant decrease in melanin content); however, data on changes in the CM with aging are fairly limited. We examined CM in human macular and mid-peripheral areas by light- and transmission electron microscopy in 50-94 year-old donor eyes (N=12). Unlike in the choroid of lower ages, the melanocytes from aging choroid (>75 years) showed partial fusion of about 8-15 melanosomes, forming rosettes-like structures. Besides, there was evidence of emptiness in cytoplasm caused by the loss of melanosomes in aged CM, as was confirmed by quantification in macular part of choroid. In advanced aged eyes (85-94-year-old), the CM possessed many lipid droplets as well as irregular lipofuscin granules, the latter had a tendency to fuse with melanosomes, as happens in aged retinal pigment epithelium. Macrophages in their cytoplasm contained abundant irregular as well as clumped melanosomes of variable size, suggesting that damaged granules/melanocytes are cleared by these phagocytes. These obvious changes in the CM are likely to make the choroid prone to damage by visible light.

  10. Epithelioid melanocytic nevus with tubule and pseudoacini formation.

    PubMed

    Uhlenhake, Elizabeth E; Smoller, Bruce R; Gardner, Jerad M; Shalin, Sara C

    2015-03-01

    A 26-year-old female presented with a 7 mm irritated pink-red papule on the left posterior shoulder. A shave biopsy revealed a dermal proliferation of epithelioid cells arranged in small nests with central lumen-like structures resembling glands set in a densely sclerotic stroma. S100 and Melanoma antigen recognized by T cells 1 (MART-1) immunohistochemical positivity confirmed a dermal melanocytic neoplasm. Pan-cytokeratin and cytokeratin 7 were negative within the nests ruling out an adnexal neoplasm or metastatic adenocarcinoma. A Spitz nevus variant characterized by the presence of focal tubular structures (tubular epithelioid cell nevus) has rarely been described in the literature and is of uncertain biological significance. Similar structures have also been observed in Clark/dysplastic nevi and melanoma. Glandular differentiation is seen in a wide variety of benign and malignant epithelial neoplasms; however, melanocytes are not known to be capable of forming true glands. The exact mechanism and significance of this phenomenon are currently unknown. Certain postulations include central melanocyte apoptosis, autocrine or paracrine factor secretion or retraction artifact caused by tissue fixation. This distinctive finding is important to recognize in order to avoid misdiagnosis as a glandular neoplasm.

  11. Boron uptake in normal melanocytes and melanoma cells and boron biodistribution study in mice bearing B16F10 melanoma for boron neutron capture therapy.

    PubMed

    Faião-Flores, Fernanda; Coelho, Paulo Rogério Pinto; Arruda-Neto, João Dias Toledo; Camillo, Maria Aparecida Pires; Maria-Engler, Silvya Stuchi; Rici, Rose Eli Grassi; Sarkis, Jorge Eduardo Souza; Maria, Durvanei Augusto

    2012-08-01

    Information on (10)B distribution in normal tissues is crucial to any further development of boron neutron capture therapy (BNCT). The goal of this study was to investigate the in vitro and in vivo boron biodistribution in B16F10 murine melanoma and normal tissues as a model for human melanoma treatment by a simple and rapid colorimetric method, which was validated by HR-ICP-MS. The B16F10 melanoma cell line showed higher melanin content than human melanocytes, demonstrating a greater potential for boronophenylalanine uptake. The melanocytes showed a moderate viability decrease in the first few minutes after BNCT application, stabilizing after 75 min, whereas the B16F10 melanoma showed the greatest intracellular boron concentration at 150 min after application, indicating a different boron uptake of melanoma cells compared to normal melanocytes. Moreover, at this time, the increase in boron uptake in melanoma cells was approximately 1.6 times higher than that in normal melanocytes. The (10)B concentration in the blood of mice bearing B16F10 melanoma increased until 90 min after BNCT application and then decreased after 120 min, and remained low until the 240th minute. On the other hand, the (10)B concentration in tumors was increased from 90 min and maximal at 150 min after application, thus confirming the in vitro results. Therefore, the present in vitro and in vivo study of (10)B uptake in normal and tumor cells revealed important data that could enable BNCT to be possibly used as a treatment for melanoma, a chemoresistant cancer associated with high mortality.

  12. Pharmacological inhibitors of c-KIT block mutant c-KIT mediated migration of melanocytes and melanoma cells in vitro and in vivo.

    PubMed

    Posch, Christian; Moslehi, Homayoun; Sanlorenzo, Martina; Green, Gary; Vujic, Igor; Panzer-Grümayer, Renate; Rappersberger, Klemens; Ortiz-Urda, Susana

    2016-07-19

    Mutations in the receptor tyrosine kinase c-KIT (KIT) are frequent oncogenic alterations in melanoma and are predominantly detected in tumors of acral, mucosal, and chronically sun-damaged skin. Research indicates that melanocytes with aberrant KIT signaling can be found in the distant periphery of the primary tumor; However, it is hitherto unknown whether KIT might confer a migratory advantage, thereby enabling genetically abnormal cells to populate a distal area. In this study, we investigated the role of mutant KIT in melanocyte- and melanoma cell migration using KIT mutant lines as well as genetically manipulated murine and primary human melanocytes. Our results revealed that melanocytes, stably transduced with mutant KIT closed a gap inflicted on cell monolayers faster than wild-type controls. Similarly, KIT mutant human melanoma lines were able to populate a larger area in a 3D in vitro skin model compared to KIT wild type and BRAF mutant lines. Genomic profiling revealed that genes associated with increased cell-dispersal of KIT mutant variants were linked to a statistically significant up-regulation of 60 migratory genes (z-score 1.334; p=0.0001). In addition, in vivo experiments harnessing a mouse xenograft model of early melanoma development demonstrated rapid lateral migration of KIT mutant cells compared to respective controls. The specific kinase inhibitors imatinib and nilotinib, could abrogate this migratory advantage in vitro and in vivo. Our work suggests that KIT inhibition might help to target migratory active, KIT mutant melanoma cells, thus representing a potential strategy to reduce spread and local recurrence.

  13. Pharmacological inhibitors of c-KIT block mutant c-KIT mediated migration of melanocytes and melanoma cells in vitro and in vivo

    PubMed Central

    Posch, Christian; Moslehi, Homayoun; Sanlorenzo, Martina; Green, Gary; Vujic, Igor; Panzer-Grümayer, Renate; Rappersberger, Klemens; Ortiz-Urda, Susana

    2016-01-01

    Mutations in the receptor tyrosine kinase c-KIT (KIT) are frequent oncogenic alterations in melanoma and are predominantly detected in tumors of acral, mucosal, and chronically sun-damaged skin. Research indicates that melanocytes with aberrant KIT signaling can be found in the distant periphery of the primary tumor; However, it is hitherto unknown whether KIT might confer a migratory advantage, thereby enabling genetically abnormal cells to populate a distal area. In this study, we investigated the role of mutant KIT in melanocyte- and melanoma cell migration using KIT mutant lines as well as genetically manipulated murine and primary human melanocytes. Our results revealed that melanocytes, stably transduced with mutant KIT closed a gap inflicted on cell monolayers faster than wild-type controls. Similarly, KIT mutant human melanoma lines were able to populate a larger area in a 3D in vitro skin model compared to KIT wild type and BRAF mutant lines. Genomic profiling revealed that genes associated with increased cell-dispersal of KIT mutant variants were linked to a statistically significant up-regulation of 60 migratory genes (z-score 1.334; p=0.0001). In addition, in vivo experiments harnessing a mouse xenograft model of early melanoma development demonstrated rapid lateral migration of KIT mutant cells compared to respective controls. The specific kinase inhibitors imatinib and nilotinib, could abrogate this migratory advantage in vitro and in vivo. Our work suggests that KIT inhibition might help to target migratory active, KIT mutant melanoma cells, thus representing a potential strategy to reduce spread and local recurrence. PMID:27322141

  14. Intelligent bioengineering in vitiligo treatment: transdermal protein transduction of melanocyte-lineage-specific genes.

    PubMed

    Mou, Yi; Jiang, Xian; Du, Yu; Xue, Li

    2012-12-01

    Vitiligo is a common, incurable skin disease with a prevalence of about 1%. Although many vitiligo therapies are available in clinics, there is almost no one method that causes significant improvement in all vitiligo patients. Some have hypothesized that melanocyte dysfunction or deficiency underlies the loss of skin pigmentation observed in vitiligo. The autoimmune-mediated apoptosis of melanocytes might be an important part of the etiology of vitiligo, which prevents the formation of melanocytes in the skin. Here we propose a novel hypothesis for vitiligo treatment using in situ melanocyte regeneration induced by melanocyte-lineage-specific genes (MLSGs). This may serve as an intelligent bioengineering prototype. The hypothesis is based on the fact that MLSGs regulate melanocyte differentiation through epigenetic reprogramming, which includes microphthalmia-associated transcription factor (MITF), paired box 3 (PAX3), and Notch signaling. MITF directs the terminal differentiation of melanocytes, and PAX3 helps to establish the properties of the melanocyte stem cells. Notch signaling promotes adult stem cell proliferation and self-renewal. This process could be mimicked by Notch intracellular domain (NICD). MLSGs could also stimulate anti-apoptotic gene expression. Recent improvements in relevant biotechniques allow the transdermal delivery of MLSG proteins into the patient, where they enter cells through protein transduction. This process may promote melanocyte regeneration in situ with little impact on the hair follicular cycle or on carcinogenesis. This simple and efficient treatment may have significant impact on the treatment of vitiligo patients.

  15. Differential PAX3 functions in normal skin melanocytes and melanoma cells

    SciTech Connect

    Medic, Sandra; Rizos, Helen; Ziman, Mel

    2011-08-12

    Highlights: {yields} PAX3 retains embryonic roles in adult melanocytes and melanoma cells. {yields} Promotes 'stem' cell-like phenotype via NES and SOX9 in both cells types. {yields} Regulates melanoma and melanocyte migration through MCAM and CSPG4. {yields} PAX3 regulates melanoma but not melanocyte proliferation via TPD52. {yields} Regulates melanoma cell (but not melanocyte) survival via BCL2L1 and PTEN. -- Abstract: The PAX3 transcription factor is the key regulator of melanocyte development during embryogenesis and is also frequently found in melanoma cells. While PAX3 is known to regulate melanocyte differentiation, survival, proliferation and migration during development, it is not clear if its function is maintained in adult melanocytes and melanoma cells. To clarify this we have assessed which genes are targeted by PAX3 in these cells. We show here that similar to its roles in development, PAX3 regulates complex differentiation networks in both melanoma cells and melanocytes, in order to maintain cells as 'stem' cell-like (via NES and SOX9). We show also that mediators of migration (MCAM and CSPG4) are common to both cell types but more so in melanoma cells. By contrast, PAX3-mediated regulation of melanoma cell proliferation (through TPD52) and survival (via BCL2L1 and PTEN) differs from that in melanocytes. These results suggest that by controlling cell proliferation, survival and migration as well as maintaining a less differentiated 'stem' cell like phenotype, PAX3 may contribute to melanoma development and progression.

  16. Melanocytes in the Skin – Comparative Whole Transcriptome Analysis of Main Skin Cell Types

    PubMed Central

    Reemann, Paula; Reimann, Ene; Ilmjärv, Sten; Porosaar, Orm; Silm, Helgi; Jaks, Viljar; Vasar, Eero; Kingo, Külli; Kõks, Sulev

    2014-01-01

    Melanocytes possess several functions besides a role in pigment synthesis, but detailed characteristics of the cells are still unclear. We used whole transcriptome sequencing (RNA-Seq) to assess differential gene expression of cultivated normal human melanocytes with respect to keratinocytes, fibroblasts and whole skin. The present results reveal cultivated melanocytes as highly proliferative cells with possible stem cell-like properties. The enhanced readiness to regenerate makes melanocytes the most vulnerable cells in the skin and explains their high risk of developing into malignant melanoma. PMID:25545474

  17. Melanocytes in the skin--comparative whole transcriptome analysis of main skin cell types.

    PubMed

    Reemann, Paula; Reimann, Ene; Ilmjärv, Sten; Porosaar, Orm; Silm, Helgi; Jaks, Viljar; Vasar, Eero; Kingo, Külli; Kõks, Sulev

    2014-01-01

    Melanocytes possess several functions besides a role in pigment synthesis, but detailed characteristics of the cells are still unclear. We used whole transcriptome sequencing (RNA-Seq) to assess differential gene expression of cultivated normal human melanocytes with respect to keratinocytes, fibroblasts and whole skin. The present results reveal cultivated melanocytes as highly proliferative cells with possible stem cell-like properties. The enhanced readiness to regenerate makes melanocytes the most vulnerable cells in the skin and explains their high risk of developing into malignant melanoma.

  18. Dysregulated autophagy increased melanocyte sensitivity to H2O2-induced oxidative stress in vitiligo

    PubMed Central

    He, Yuanmin; Li, Shuli; Zhang, Weigang; Dai, Wei; Cui, Tingting; Wang, Gang; Gao, Tianwen; Li, Chunying

    2017-01-01

    In vitiligo, melanocytes are particularly vulnerable to oxidative stress owing to the pro-oxidant state generated during melanin synthesis and to the genetic antioxidant defects. Autophagy is a controlled self-digestion process which can protect cells against oxidative damage. However, the exact role of autophagy in vitiligo melanocytes in response to oxidative stress and the mechanism involved are still not clear. To determine the implications of autophagy for melanocyte survival in response to oxidative stress, we first detected the autophagic flux in normal melanocytes exposure to H2O2, and found that autophagy was significantly enhanced in normal melanocytes, for protecting cells against H2O2-induced oxidative damage. Nevertheless, vitiligo melanocytes exhibited dysregulated autophagy and hypersensitivity to H2O2-induced oxidative injury. In addition, we confirmed that the impairment of Nrf2-p62 pathway is responsible for the defects of autophagy in vitiligo melanocytes. Noteworthily, upregulation of the Nrf2-p62 pathway or p62 reduced H2O2-induced oxidative damage of vitiligo melanocytes. Therefore, our data demonstrated that dysregulated autophagy owing to the impairment of Nrf2-p62 pathway increase the sensitivity of vitiligo melanocytes to oxidative stress, thus promote the development of vitiligo. Upregulation of p62-dependent autophagy may be applied to vitiligo treatment in the future. PMID:28186139

  19. Sex Bias in Classifying Borderline and Narcissistic Personality Disorder.

    PubMed

    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.

  20. Food consumption as affect modulation in borderline personality.

    PubMed

    Ambwani, Suman; Morey, Leslie C

    2015-04-01

    The present study examined relationships among negative affect, borderline personality features, and eating behavior through the experimental manipulation of mood. Undergraduate women (N = 307) completed a baseline mood assessment, viewed a 39-minute sad film either with or without concurrent food presentation, then completed a second mood assessment and questionnaires assessing personality and eating attitudes/behaviors. Women reporting more borderline personality features exhibited greater negative affect across time and were more reactive to the sad film. Food presentation appeared to have a small ameliorative effect on sadness and general negative affect. However, quantity of food consumption was associated with improvements in mood only for women reporting higher levels of borderline personality features. These data suggest that women with borderline personality characteristics may be at elevated risk for developing problems with binge eating, because consuming larger quantities of food appeared to have a tempering effect on their negative mood and feelings of sadness.

  1. Parental qualities as perceived by borderline personality disorders.

    PubMed

    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.

  2. Four factors of impulsivity differentiate antisocial and borderline personality disorders.

    PubMed

    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.

  3. Narrow Band Ultraviolet B Treatment for Human Vitiligo Is Associated with Proliferation, Migration, and Differentiation of Melanocyte Precursors.

    PubMed

    Goldstein, Nathaniel B; Koster, Maranke I; Hoaglin, Laura G; Spoelstra, Nicole S; Kechris, Katerina J; Robinson, Steven E; Robinson, William A; Roop, Dennis R; Norris, David A; Birlea, Stanca A

    2015-08-01

    In vitiligo, the autoimmune destruction of epidermal melanocytes produces white spots that can be repigmented by melanocyte precursors from the hair follicles, following stimulation with UV light. We examined by immunofluorescence the distribution of melanocyte markers (C-KIT, DCT, PAX3, and TYR) coupled with markers of proliferation (KI-67) and migration (MCAM) in precursors and mature melanocytes from the hair follicle and the epidermis of untreated and narrow band UVB (NBUVB)-treated human vitiligo skin. NBUVB was associated with a significant increase in the number of melanocytes in the infundibulum and with restoration of the normal melanocyte population in the epidermis, which was lacking in the untreated vitiligo. We identified several precursor populations (melanocyte stem cells, melanoblasts, and other immature phenotypes), and progressively differentiating melanocytes, some with putative migratory and/or proliferative abilities. The primary melanocyte germ was present in the untreated and treated hair follicle bulge, whereas a possible secondary melanocyte germ composed of C-KIT+ melanocytes was found in the infundibulum and interfollicular epidermis of UV-treated vitiligo. This is an exceptional model for studying the mobilization of melanocyte stem cells in human skin. Improved understanding of this process is essential for designing better treatments for vitiligo, ultimately based on melanocyte stem cell activation and mobilization.

  4. Ultraviolet B, melanin and mitochondrial DNA: Photo-damage in human epidermal keratinocytes and melanocytes modulated by alpha-melanocyte-stimulating hormone

    PubMed Central

    Böhm, Markus; Hill, Helene Z.

    2016-01-01

    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. PMID:27303631

  5. New melanogenesis and photobiological processes in activation and proliferation of precursor melanocytes after UV-exposure: ultrastructural differentiation of precursor melanocytes from Langerhans cells

    SciTech Connect

    Jimbow, K.; Uesugi, T.

    1982-02-01

    Photobiological processes involving new melanogenesis after exposure to ultraviolet (UV) light were experimentally studied in C57 black adult mice by histochemistry, cytochemistry, and autoradiography. The trunk and the plantar region of the foot, where no functioning melanocytes were present before exposure, were exposed to UV-A for 14 consecutive days. Both regions revealed a basically similar pattern for new melanogenesis which involved an activation of precursor melanocytes. Essentially all of ''indeterminate'' cells appeared to be precursor melanocytes, the fine structure of which could be differentiated even from poorly developed Langerhans cells. New melanogenesis was manifested by 4 stages of cellular and subcellular reactions of these cells as indicated by histochemistry of dihydroxyphenylalanine (dopa) and autoradiography of thymidine incorporation: (a) an initial lag in the activation of precursor melanocytes with development of Golgi cisternae and rough endoplasmic reticulum followed by formation of unmelanized melanosomes (day 0 to 2); (b) synthesis of active tyrosinase accumulated in Golgi cisternae and vesicles with subsequent formation of melanized melanosomes in these cells (day 3 to 5); (c) mitotic proliferation of many of these activated cells, followed by an exponential increase of new melanocytes (day 6 to 7); and (d) melanosome transfer with differentiation of 10 nm filaments and arborization of dendrites, but without any significant change in the melanocyte population (day 8 to 14). The melanosome transfer was, however, not obvious until after 7 days of exposure. The size of newly synthesized melanosomes was similar to that of tail skin where native melanocytes were present before exposure.

  6. [Anorexia and borderline personality disorder : bonds pathology].

    PubMed

    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.

  7. Adverse perinatal outcomes in borderline amniotic fluid index

    PubMed Central

    Jamal, Ashraf; Kazemi, Maryam; Marsoosi, Vajiheh; Eslamian, Laleh

    2016-01-01

    Background: Normal amniotic fluid predicts normal placental function, fetal growth and fetal well-being. Objective: To determine adverse pregnancy outcomes in borderline amniotic fluid index (AFI). Materials and Methods: Pregnant women (37-40 wks) with diagnosis of borderline AFI between December 2012 and August 2014 were identified. Antepartum, intrapartum and neonatal data were collected and compared with those of pregnant women with normal AFI. An AFI less than 8 and more than 5 cm was defined for borderline AFI. Pregnancy outcomes included Cesarean section for non-reassuring fetal heart rate, meconium stained amniotic fluid, 5-min Apgar score <7, low birth weight, umbilical cord blood pH at term and NICU admission. Results: Gestational age at delivery in pregnancies with borderline AFI was significantly lower than normal AFI. Cesarean section rate for non-reassuring fetal heart rate in women of borderline AFI was significantly higher and there was an increased incidence of birth weight less than 10th percentile for gestation age in borderline AFI group. Incidence of low Apgar score and low umbilical artery pH in pregnancies with borderline AFI was significantly higher than women with normal AFI. There were no significant difference in the rate of NICU admission and meconium staining in both groups. Conclusion: There are significant differences for adverse pregnancy outcomes , such as Cesarean section due to non-reassuring fetal heart rate, birth weight less than 10th percentile for gestation age, low 5 min Apgar score and low umbilical artery pH between pregnancies with borderline and normal AFI. PMID:27981256

  8. Vitamin A metabolism in benign and malignant melanocytic skin cells: importance of lecithin/retinol acyltransferase and RPE65.

    PubMed

    Amann, Philipp M; Luo, Chonglin; Owen, Robert W; Hofmann, Claudia; Freudenberger, Muriel; Schadendorf, Dirk; Eichmüller, Stefan B; Bazhin, Alexandr V

    2012-02-01

    Disturbance in vitamin A metabolism seems to be an important attribute of cancer cells. Retinoids, particularly retinoic acid, have critical regulatory functions and appear to modulate tumor development and progression. The key step of vitamin A metabolism is the esterification of all-trans retinol, catalyzed by lecithin/retinol acyltransferase (LRAT). In this work, we show that malignant melanoma cells are able to esterify all-trans retinol and subsequently isomerize all-trans retinyl esters (RE) into 11-cis retinol, whereas their benign counterparts-melanocytes are not able to catalyze these reactions. Besides, melanoma cell lines express lecithin/retinol acyltranseferase both at the mRNA and protein levels. In contrast, melanocytes do not express this enzyme at the protein level, but mRNA of lecithin/retinol acyltransefrase could still be present at mRNA level. RPE65 is expressed in both melanocytic counterparts, and could be involved in the subsequent isomerization of RE produced by lecithin/retinol acyltransefrase to 11-cis retinol. Cellular retinol-binding protein 2 does not appear to be involved in the regulation of all-trans retinol esterification in these cells. Expression of LRAT and RPE65 can be modulated by retinoids. We propose that the post-transcriptional regulation of lecithin/retinol acyltransefrase could be involved in the differential expression of this enzyme. Besides, activities of LRAT and RPE65 may be important for removal of all-trans retinal which is the substrate for retinoic acid production in skin cells. Consequently, the decreasing cellular amount of retinoic acid and its precursor molecules could result in a change of gene regulation.

  9. Principles of Treatment for Borderline, Micropapillary Serous, and Low-Grade Ovarian Cancer.

    PubMed

    Hacker, Kari E; Uppal, Shitanshu; Johnston, Carolyn

    2016-09-01

    Borderline ovarian tumors (BOTs) are less common than epithelial ovarian cancers (EOCs). Low-grade EOCs (LG-EOCs) occur even less frequently than BOTs. After primary therapy, recurrence rates of BOTs and LG-EOCs are significantly lower and the stage-adjusted survival is higher than for high-grade EOCs. Thus, determining the best management in terms of traditional ovarian cancer staging and debulking procedures is more challenging and has been recently brought to question. This article reviews the particulars of BOTs and LG-EOCs, their similarities and differences, and how they are best managed and treated, and emphasizes the major role of surgery and the controversial role of chemotherapy. Because these tumors disproportionately affect younger women, this review addresses ovarian preservation in circumstances when fertility or hormonal preservation is desired.

  10. Detection of auto antibodies and transplantation of cultured autologous melanocytes for the treatment of vitiligo

    PubMed Central

    Zhu, Mei-Cai; Ma, Hong-Yu; Zhan, Zhi; Liu, Cheng-Gang; Luo, Wei; Zhao, Guang

    2017-01-01

    The aim of the present study was to establish an immunofluorescence method of antibody detection to identify melanocytes in the serum of vitiligo patients. Furthermore, we aimed to establish a method for the culture and proliferation of autologous pure melanocytes and to observe the effect of their transplantation for the treatment of vitiligo. Suspension of epidermal cells with melanocytes was performed using trypsin digestion of normal epiderm from eyelid operation and melanocytes were selectively cultured and proliferated in serum-free M2 medium. FITC-labeled rabbit anti-human antibody was used to detect the relative fluorescence intensity of the melanocytes. After identification with immunological and biological examinations, the melanocytes were transplanted to depigmented areas of vitiligo. Repigmentation was observed continuously. The results indicated that melanocytes could be selectively proliferated in the medium. Subsequently, pure melanocytes without contamination of fibroblast and keratinocyte were harvested. A total of 34 patients suffering vitiligo for between 3 months and 20 years with depigmented area (between 4 cm2 and 70% of body surface) were divided into 19 cases of developing stage and 15 cases of stable stage, according to the change of depigmentation. A total of 15 developing cases were positive for the antibody against melanocytes, with the positive rate of 79%. The titers of serum was >1:50 in 10 patients at the developing stage, and 5 developing patients were 1:10. Among the 15 stable cases, four were positive, with a positive rate of 27%. Fluorescence of antibody was localized in the cytoplasm of the melanocytes. Autologous melanocytes of vitiligo patients could be selectively proliferated in the medium. Next, pure melanocytes without contamination with fibroblasts and keratinocytes were harvested. A total of 16 vitiligo patients with 28 depigmented areas (2–200 cm2) were treated with transplantation of melanocytes. Repigmentation of

  11. Plexin B1 inhibits MET through direct association and regulates Shp2 expression in melanocytes.

    PubMed

    Soong, Joanne; Scott, Glynis

    2013-01-15

    Plexin B1, the receptor for Semaphorin 4D (Sema4D), is expressed by melanocytes in the skin. We recently showed that Sema4D suppresses activation of the hepatocyte growth factor receptor, MET, in melanocytes, and that knockdown of Plexin B1 results in activation of MET. MET signaling mediates proliferation, survival and migration in melanocytes, and its activation is associated with transformation of melanocytes to melanoma. In this report we investigated the mechanism by which Plexin B1 inhibits MET activation. Our results show that Plexin B1 and MET exist as an oligomeric receptor-receptor complex in melanocytes, and that receptor association is increased by Sema4D. MET and Plexin B1 receptor complexes were identified along the cell body of melanocytes, and Sema4D increased receptor association on dendrites, suggesting that Sema4D regulates MET-dependent processes at precise locations on the melanocyte. Despite activation of MET, Plexin B1 knockdowns proliferated slowly and showed increased apoptosis compared with controls. Shp2, a non-receptor protein tyrosine phosphatase, translates growth and survival signals from MET and other receptor tyrosine kinases. Plexin B1 knockdowns had markedly lower levels of Shp2 compared with controls, and Sema4D upregulated Shp2 expression at the protein and message level in normal melanocytes. Functional studies showed that blockade of Shp2 activity abrogated MET-dependent activation of Erk1/Erk2 and Akt in melanocytes. These results suggest a complex role for Sema4D and Plexin B1 in orchestrating signaling from the MET receptor in melanocytes. Because Shp2 is a downstream adaptor protein for multiple receptors, Sema4D may control the effects of several growth factors on melanocytes through regulation of Shp2.

  12. Isolating RNA from precursor and mature melanocytes from human vitiligo and normal skin using laser capture microdissection

    PubMed Central

    Goldstein, Nathaniel B.; Koster, Maranke I.; Hoaglin, Laura G.; Wright, Michael J.; Robinson, Steven E.; Robinson, William A.; Roop, Dennis R.; Norris, David A.; Birlea, Stanca A.

    2017-01-01

    To characterize the gene expression profile of regenerated melanocytes in the narrow band UVB (NBUVB)-treated vitiligo epidermis and their precursors in the hair follicle, we present here a strategy of RNA isolation from in situ melanocytes using human frozen skin. We developed a rapid immunostaining protocol using the NKI-beteb antibody, which labels differentiated and precursor melanocytes, followed by fluorescent laser capture microdissection. This technique enabled the direct isolation, from melanocyte and adjacent keratinocyte populations, of satisfactory quality RNA that was successfully amplified and analysed by qRT-PCR. The melanocyte-specific gene transcripts TYR, DCT, TYRP1 and PMEL were significantly upregulated in our NBUVB-treated melanocyte samples as compared with the keratinocyte samples, while keratinocyte-specific genes (KRT5 and KRT14) were expressed significantly higher in the keratinocyte samples as compared with the melanocyte samples. Furthermore, in both NBUVB-treated vitiligo skin and normal skin, when bulge melanocytes were compared with epidermal melanocytes, we found significantly lower expression of melanocyte-specific genes and significantly higher expression of three melanocytic stem cell genes (SOX9, WIF1 and SFRP1), while ALCAM and ALDH1A1 transcripts did not show significant variation. We found significantly higher expression of melanocyte-specific genes in the epidermis of NBUVB-treated vitiligo, as compared to the normal skin. When comparing bulge melanocyte samples from untreated vitiligo, NBUVB-treated vitiligo and normal skin, we did not find significant differences in the expression of melanocyte-specific genes or melanocytic stem cell genes. These techniques offer valuable opportunities to study melanocytes and their precursors in vitiligo and other pigmentation disorders. PMID:27193292

  13. Borderline personality disorder in suicidal adolescents.

    PubMed

    Yen, Shirley; Gagnon, Kerry; Spirito, Anthony

    2013-05-01

    The diagnosis of borderline personality disorder (BPD) in adolescents has been controversial. Thus, few studies have examined BPD in suicidal adolescents, even though it is strongly associated with suicidal behaviours in adults. This study examines differences between suicidal adolescents with (n = 47) and without (n = 72) BPD on history and characteristics of suicidal behaviour, Axis I co-morbidity, affect regulation and aggression. Assessments were completed with both adolescents and parents, and consensus ratings based on best available data were analysed. BPD participants were more likely to have a history of suicide attempts and to have been admitted because of a suicide attempt (vs. suicidal ideation). There were no significant differences in self-injurious behaviours or degree of suicidal ideation. BPD participants also had more psychiatric co-morbidity and higher aggression scores but no significant differences in affective dysregulation compared with suicidal adolescents without BPD. Diagnostic stability over 6 months was modest. Our results demonstrate that, compared with other acutely suicidal adolescents, the clinical profile of BPD participants is unique and suggests an increased risk for suicidal behaviours. This extends upon other studies that support the construct validity of BPD during adolescence and suggests that BPD should be considered in suicide risk assessment for adolescents.

  14. Dissociation in schizophrenia and borderline personality disorder

    PubMed Central

    Pec, Ondrej; Bob, Petr; Raboch, Jiri

    2014-01-01

    Background Dissociation likely plays a key role in schizophrenia and borderline personality disorder (BPD), although empirical studies that compare specific manifestations of these symptoms in schizophrenia and BPD are rare. In this context, the purpose of this study was to compare the occurrence of dissociative and other psychopathological symptoms in these disorders, and to assess the possible influence of antipsychotic medication on the dissociative symptoms. Methods We assessed 31 patients with schizophrenia and 36 patients with BPD. Dissociative symptoms were measured by the Dissociative Experiences Scale (DES), symptoms related to stress and traumatic experiences were assessed using the Trauma Symptom Checklist-40 (TSC-40), and other psychopathological symptoms were measured with the Health of the Nation Outcome Scales (HoNOS). We also assessed actual daily doses of antipsychotic medication in chlorpromazine equivalents in all participants. Results The results show that symptoms of traumatic stress measured by the TSC-40 had significantly higher scores in the BPD group. The data also show that dissociative symptoms (DES) were significantly correlated with symptoms of traumatic stress (TSC-40) and with symptoms assessed by the HoNOS. Remarkably significant correlations were found between levels of antipsychotic medication and the DES and between antipsychotic medication and the depersonalization/derealization component of the DES in BPD patients. Conclusion The results support an important role of dissociative processes in schizophrenia and BPD and suggest a significant relationship between manifestations of dissociative symptoms in BPD and antipsychotic medication. PMID:24672239

  15. Splitting in Schizophrenia and Borderline Personality Disorder

    PubMed Central

    Pec, Ondrej; Bob, Petr; Raboch, Jiri

    2014-01-01

    Background Splitting describes fragmentation of conscious experience that may occur in various psychiatric disorders. A purpose of this study is to examine relationships between psychological process of splitting and disturbed cognitive and affective functions in schizophrenia and borderline personality disorder (BPD). Methods In the clinical study, we have assessed 30 patients with schizophrenia and 35 patients with BPD. The symptoms of splitting were measured using self-reported Splitting Index (SI). As a measure of semantic memory disorganization we have used verbal fluency test. Other psychopathological symptoms were assessed using Health of the Nation Outcome Scale (HoNOS). Results Main results show that SI is significantly higher in BPD group than in schizophrenia, and on the other hand, verbal fluency is significantly lower in schizophrenia group. Psychopathological symptoms measured by HoNOS are significantly higher in the BPD group than in schizophrenia. Significant relationship was found between verbal fluency and the SI “factor of others” (Spearman r = −0.52, p<0.01) in schizophrenia patients. Conclusions Processes of splitting are different in schizophrenia and BPD. In BPD patients splitting results to mental instability, whereas in schizophrenia the mental fragmentation leads to splitting of associations observed as lower scores of verbal fluency, which in principle is in agreement with Bleuler’s historical concept of splitting in schizophrenia. PMID:24603990

  16. Compulsive buying and borderline personality symptomatology.

    PubMed

    Sansone, Randy A; Chang, Joy; Jewell, Bryan; Sellbom, Martin; Bidwell, Mark

    2013-04-01

    In this study, the authors investigated the relationship between compulsive buying and borderline personality disorder (BPD) symptomatology--two disorders possibly linked through impulsivity. Using a survey methodology in a cross-sectional consecutive sample of nonemergent female outpatients from an obstetrics/gynecology clinic, the authors assessed compulsive buying with the compulsive buying scale (CBS) and BPD symptomatology through the BPD scale of the personality diagnostic questionnaire-4 (PDQ-4) and the self-harm Inventory (SHI). In this sample, 8% of Caucasian women and 9% of African-American women scored positively for compulsive buying. The correlations between scores on the CBS and the PDQ-4 and SHI were 0.43 and 0.41, respectively-both statistically significant at the p < .001 level. Compared to Caucasian women, African-American women demonstrated statistical associations between the BPD measures and the CBS scale scores that were significantly larger. Findings suggest relationships between compulsive buying and BPD, particularly among African-American women.

  17. Metarepresentative functions in borderline personality disorder.

    PubMed

    Semerari, Antonio; Carcione, Antonino; Dimaggio, Giancarlo; Nicoló, Giuseppe; Pedone, Roberto; Procacci, Michele

    2005-12-01

    Many authors consider that patients suffering from Borderline Personality Disorder (BPD) are hampered in their ability to metarepresent, which is the correct ascribing of states of mind to oneself and to others and the reflecting thereon. Although the ability to mentalize is generally described as being uniform, various authors pinpoint problems which appear to be of a diverse psychological nature. Some describe difficulties in identifying emotions or a shortfall in their regulation, others identify a lack of integration between representations of self and those of others, and yet others focus on the failure to distinguish between fantasy and reality. In the present research all sessions during the first year of therapy of four patients suffering from BPD were tape-recorded and transcribed, and then analyzed using the Metacognition Assessment Scale (MAS), which is designed for the evaluation of the ability to metarepresent in clinical reports. The results support the hypothesis that there is a metarepresentation impairment in BPD but that it is more selective than was thought until now. In particular, such patients maintain their ability to identify internal states, whereas they are impaired in the integration of representations of self and others and in the differentiation between fantasy and reality.

  18. Relationships between melanocytes, mechanical properties and extracellular matrix composition in mouse heart valves.

    PubMed

    Carneiro, Flavia; Kruithof, Boudewijn Pt; Balani, Kanthesh; Agarwal, Arvind; Gaussin, Vinciane; Kos, Lidia

    2015-01-01

    Heart valves are complex structures composed of organized layers of extracellular matrix, and interstitial and overlying endothelial cells. In this article, we present the specific localization of a population of melanocytes within the murine heart valves at ages important for their post-natal development. In all stages analyzed in our study, melanocytes were found in high numbers populating the atrial aspect of the tricuspid and mitral leaflets. The pulmonary valve did not present melanocytes. To characterize a putative role for the valve melanocytes, the dynamic nanomechanical properties of tricuspid leaftets containing large numbers or no melanocytes were measured. The stiffness coefficient of hyperpigmented leaflets was higher (11.5 GPa) than the ones from wild-type (7.5 GPa) and hypopigmented (5.5 GPa) leaflets. These results suggest that melanocytes may contribute to the mechanical properties of the heart valves. The arrangement of extracellular matrix molecules such as Collagen I and Versican B is responsible for the mechanical characteristics of the leaflets. Melanocytes were found to reside primarily in areas of Versican B expression. The patterns of expression of Collagen I and Versican B were not, however, disrupted in hyper or hypopigmented leaflets. Melanocytes may affect other extracellular matrix molecules to alter the valves' microenvironment.

  19. In vitro modeling of hyperpigmentation associated to neurofibromatosis type 1 using melanocytes derived from human embryonic stem cells

    PubMed Central

    Allouche, Jennifer; Bellon, Nathalia; Saidani, Manoubia; Stanchina-Chatrousse, Laure; Masson, Yolande; Patwardhan, Anand; Gilles-Marsens, Floriane; Delevoye, Cédric; Domingues, Sophie; Nissan, Xavier; Martinat, Cécile; Lemaitre, Gilles; Peschanski, Marc; Baldeschi, Christine

    2015-01-01

    “Café-au-lait” macules (CALMs) and overall skin hyperpigmentation are early hallmarks of neurofibromatosis type 1 (NF1). One of the most frequent monogenic diseases, NF1 has subsequently been characterized with numerous benign Schwann cell-derived tumors. It is well established that neurofibromin, the NF1 gene product, is an antioncogene that down-regulates the RAS oncogene. In contrast, the molecular mechanisms associated with alteration of skin pigmentation have remained elusive. We have reassessed this issue by differentiating human embryonic stem cells into melanocytes. In the present study, we demonstrate that NF1 melanocytes reproduce the hyperpigmentation phenotype in vitro, and further characterize the link between loss of heterozygosity and the typical CALMs that appear over the general hyperpigmentation. Molecular mechanisms associated with these pathological phenotypes correlate with an increased activity of cAMP-mediated PKA and ERK1/2 signaling pathways, leading to overexpression of the transcription factor MITF and of the melanogenic enzymes tyrosinase and dopachrome tautomerase, all major players in melanogenesis. Finally, the hyperpigmentation phenotype can be rescued using specific inhibitors of these signaling pathways. These results open avenues for deciphering the pathological mechanisms involved in pigmentation diseases, and provide a robust assay for the development of new strategies for treating these diseases. PMID:26150484

  20. In vitro modeling of hyperpigmentation associated to neurofibromatosis type 1 using melanocytes derived from human embryonic stem cells.

    PubMed

    Allouche, Jennifer; Bellon, Nathalia; Saidani, Manoubia; Stanchina-Chatrousse, Laure; Masson, Yolande; Patwardhan, Anand; Gilles-Marsens, Floriane; Delevoye, Cédric; Domingues, Sophie; Nissan, Xavier; Martinat, Cécile; Lemaitre, Gilles; Peschanski, Marc; Baldeschi, Christine

    2015-07-21

    "Café-au-lait" macules (CALMs) and overall skin hyperpigmentation are early hallmarks of neurofibromatosis type 1 (NF1). One of the most frequent monogenic diseases, NF1 has subsequently been characterized with numerous benign Schwann cell-derived tumors. It is well established that neurofibromin, the NF1 gene product, is an antioncogene that down-regulates the RAS oncogene. In contrast, the molecular mechanisms associated with alteration of skin pigmentation have remained elusive. We have reassessed this issue by differentiating human embryonic stem cells into melanocytes. In the present study, we demonstrate that NF1 melanocytes reproduce the hyperpigmentation phenotype in vitro, and further characterize the link between loss of heterozygosity and the typical CALMs that appear over the general hyperpigmentation. Molecular mechanisms associated with these pathological phenotypes correlate with an increased activity of cAMP-mediated PKA and ERK1/2 signaling pathways, leading to overexpression of the transcription factor MITF and of the melanogenic enzymes tyrosinase and dopachrome tautomerase, all major players in melanogenesis. Finally, the hyperpigmentation phenotype can be rescued using specific inhibitors of these signaling pathways. These results open avenues for deciphering the pathological mechanisms involved in pigmentation diseases, and provide a robust assay for the development of new strategies for treating these diseases.

  1. Keratinocytes and fibroblasts in a human skin equivalent model enhance melanocyte survival and melanin synthesis after ultraviolet irradiation.

    PubMed

    Archambault, M; Yaar, M; Gilchrest, B A

    1995-05-01

    To investigate paracrine effects of fibroblasts and keratinocytes on melanocyte behavior after ultraviolet (UV) irradiation, we compared an in vitro skin equivalent model with melanocyte cultures. Human melanocytes were maintained alone in monolayer cultures or on dermal equivalents with or without keratinocytes and were irradiated daily with solar-simulated light. After seven daily UV irradiations, monolayer melanocytes displayed dose-dependent increases in cellular damage. In contrast, melanocytes on dermal equivalents survived strikingly better. Moreover, UV-irradiated skin equivalent melanocytes became highly dendritic as compared with sham-irradiated cells, closely mimicking their morphology in UV-irradiated skin. In addition, in skin equivalents melanocytes migrated from the center to the periphery of the keratinocyte layer after UV irradiation. Melanin production per culture, as measured by 14C-dihydroxyphenylalanine incorporation, was consistently higher in skin equivalent melanocytes than in monolayer melanocytes from the same donor, and it was highest in melanocytes from skin equivalents containing both keratinocytes and fibroblasts. Our data strongly suggest that fibroblasts and keratinocytes modulate melanocyte function in skin. The skin equivalent is a valuable model for investigating paracrine effects on melanocytes after UV irradiation.

  2. The important role of interdisciplinary collaboration in the management of a melanocytic skin lesion

    PubMed Central

    Balato, Anna; Raimondo, Annunziata; Cantelli, Mariateresa; Siano, Maria; Lembo, Serena; Scalvenzi, Massimiliano; Balato, Nicola

    2011-01-01

    One of the most confounding characteristics, commonly seen in malignant, but even in benign melanocytic nevi, is represented by the regression phenomenon. The identification of regression, through dermoscopical observation, can be predictive of a tricky histopathological examination. Therefore, this feature should be an alert to a meticulous clinical, dermoscopical and histopathological correlation for correct analysis of melanocytic skin lesions. A 26-year-old man was referred to our department for a pigmented skin lesion localized on his trunk. It was clinically and dermoscopically diagnosed as atypical melanocytic nevus with central regression. After 1 year the lesion underwent considerable changes, leading to a nearly complete regression. The lesion was excised and, on the basis of clinical, dermoscopical and histopathological correlation, was interpreted as a junctional melanocytic nevus with regression. In our case the association of clinical, dermoscopical and histopathological experience, resulted an important and useful method, in order to proper interpret and correctly diagnose an atypical melanocytic skin lesion. PMID:25386254

  3. Nicotinamide enhances repair of ultraviolet radiation-induced DNA damage in primary melanocytes.

    PubMed

    Thompson, Benjamin C; Surjana, Devita; Halliday, Gary M; Damian, Diona L

    2014-07-01

    Cutaneous melanoma is a significant cause of morbidity and mortality. Nicotinamide is a safe, widely available vitamin that reduces the immune suppressive effects of UV, enhances DNA repair in keratinocytes and has shown promise in the chemoprevention of non-melanoma skin cancer. Here, we report the effect of nicotinamide on DNA damage and repair in primary human melanocytes. Nicotinamide significantly enhanced the repair of oxidative DNA damage (8-oxo-7,8-dihydro-2'-deoxyguanosine) and cyclobutane pyrimidine dimers induced by UV exposure. It also enhanced the repair of 8-oxo-7,8-dihydro-2'-deoxyguanosine induced by the culture conditions in unirradiated melanocytes. A significant increase in the percentage of melanocytes undergoing unscheduled but not scheduled DNA synthesis was observed, confirming that nicotinamide enhances DNA repair in human melanocytes. In summary, nicotinamide, by enhancing DNA repair in melanocytes, is a potential agent for the chemoprevention of cutaneous melanoma.

  4. Oral Congenital Melanocytic Nevus: A Rare Case Report and Review of the Literature.

    PubMed

    Marangon Júnior, Helvécio; Souza, Paulo Eduardo Alencar; Soares, Rodrigo Villamarim; de Andrade, Bruno Augusto Benevenuto; de Almeida, Oslei Paes; Horta, Martinho Campolina Rebello

    2015-12-01

    Melanocytic nevi are congenital or acquired benign proliferations of cells of melanocytic origin. Oral congenital melanocytic nevi are rare, and only a few cases have been reported in the literature. The purpose of this study is to present the clinical, histological and immunohistochemical features of an oral congenital melanocytic nevus in a 16-year-old female with an 11-year follow-up and to review the pertinent literature. The reported case is the fifth well-documented case report of oral congenital melanocytic nevus in the English literature and the first with a long period of follow-up, thereby making it an important contribution to the knowledge regarding this uncommon oral mucosa lesion.

  5. The most common mistakes on dermatoscopy of melanocytic lesions.

    PubMed

    Kamińska-Winciorek, Grażyna; Placek, Waldemar

    2015-02-01

    Dermatoscopy is a method of in vivo evaluation of the structures within the epidermis and dermis. Currently, it may be the most precise pre-surgical method of diagnosing melanocytic lesions. Diagnostic errors may result in unnecessary removal of benign lesions or what is even worse, they can cause early and very early melanomas to be overlooked. Errors in assessment of dermatoscopy can be divided into those arising from failure to maintain proper test procedures (procedural and technical errors) and knowledge based mistakes related to the lack of sufficient familiarity and experience in dermatoscopy. The article discusses the most common mistakes made by beginner or inexperienced dermatoscopists.

  6. Ocular Albinism Type 1 Regulates Melanogenesis in Mouse Melanocytes.

    PubMed

    Chen, Tianzhi; Wang, Haidong; Liu, Yu; Zhao, Bingling; Zhao, Yuanyuan; Fan, Ruiwen; Wang, Pengchao; Dong, Changsheng

    2016-09-27

    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 participate in the

  7. The most common mistakes on dermatoscopy of melanocytic lesions

    PubMed Central

    Kamińska-Winciorek, Grażyna

    2015-01-01

    Dermatoscopy is a method of in vivo evaluation of the structures within the epidermis and dermis. Currently, it may be the most precise pre-surgical method of diagnosing melanocytic lesions. Diagnostic errors may result in unnecessary removal of benign lesions or what is even worse, they can cause early and very early melanomas to be overlooked. Errors in assessment of dermatoscopy can be divided into those arising from failure to maintain proper test procedures (procedural and technical errors) and knowledge based mistakes related to the lack of sufficient familiarity and experience in dermatoscopy. The article discusses the most common mistakes made by beginner or inexperienced dermatoscopists. PMID:25821425

  8. The E3 ligase APC/C(Cdh1) promotes ubiquitylation-mediated proteolysis of PAX3 to suppress melanocyte proliferation and melanoma growth.

    PubMed

    Cao, Juxiang; Dai, Xiangpeng; Wan, Lixin; Wang, Hongshen; Zhang, Jinfang; Goff, Philip S; Sviderskaya, Elena V; Xuan, Zhenyu; Xu, Zhixiang; Xu, Xiaowei; Hinds, Philip; Flaherty, Keith T; Faller, Douglas V; Goding, Colin R; Wang, Yongjun; Wei, Wenyi; Cui, Rutao

    2015-09-01

    The anaphase-promoting complex or cyclosome with the subunit Cdh1 (APC/C(Cdh1)) is an E3 ubiquitin ligase involved in the control of the cell cycle. Here, we identified sporadic mutations occurring in the genes encoding APC components, including Cdh1, in human melanoma samples and found that loss of APC/C(Cdh1) may promote melanoma development and progression, but not by affecting cell cycle regulatory targets of APC/C. Most of the mutations we found in CDH1 were those associated with ultraviolet light (UV)-induced melanomagenesis. Compared with normal human skin tissue and human or mouse melanocytes, the abundance of Cdh1 was decreased and that of the transcription factor PAX3 was increased in human melanoma tissue and human or mouse melanoma cell lines, respectively; Cdh1 abundance was further decreased with advanced stages of human melanoma. PAX3 was a substrate of APC/C(Cdh1) in melanocytes, and APC/C(Cdh1)-mediated ubiquitylation marked PAX3 for proteolytic degradation in a manner dependent on the D-box motif in PAX3. Either mutating the D-box in PAX3 or knocking down Cdh1 prevented the ubiquitylation and degradation of PAX3 and increased proliferation and melanin production in melanocytes. Knocking down Cdh1 in melanoma cells in culture or before implantation in mice promoted doxorubicin resistance, whereas reexpressing wild-type Cdh1, but not E3 ligase-deficient Cdh1 or a mutant that could not interact with PAX3, restored doxorubicin sensitivity in melanoma cells both in culture and in xenografts. Thus, our findings suggest a tumor suppressor role for APC/C(Cdh1) in melanocytes and that targeting PAX3 may be a strategy for treating melanoma.

  9. Neuroendocrine functions of melanocytes: beyond the skin-deep melanin maker.

    PubMed

    Takeda, Kazuhisa; Takahashi, Na-Ho; Shibahara, Shigeki

    2007-03-01

    The skin is armored with "dead cells", the stratum corneum, and is continuously exposed to external stressful environments, such as atmospheric oxygen, solar radiations, and thermal and chemical insults. Melanocytes of neural crest origin are located in the skin, eye, inner ear, and leptomeninges. Melanin pigment in the skin is produced by melanocytes under the influence of various endogenous factors, derived from neighboring keratinocytes and underlying fibroblasts. The differentiation and functions of melanocytes are regulated at multiple processes, including transcription, RNA editing, melanin synthesis, and the transport of melanosomes to keratinocytes. Impairment at each step causes the pigmentary disorders in humans, with the historical example of oculocutaneous albinism. Moreover, heterozygous mutations in the gene coding for microphthalmia-associated transcription factor, a key regulator for melanocyte development, are associated with Waardenburg syndrome type 2, an auditory-pigmentary disorder. Sun tanning, melasma, aging spots (lentigo senilis), hair graying, and melanoma are well-known melanocyte-related pathologies. Melanocytes therefore have attracted much attention of many ladies, makeup artists and molecular biologists. More recently, we have shown that lipocalin-type prostaglandin D synthase (L-PGDS) is expressed in melanocytes but not in other skin cell types. L-PGDS generates prostaglandin D2 and also functions as an inter-cellular carrier protein for lipophilic ligands, such as bilirubin and thyroid hormones. Thus, melanocytes may exert hitherto unknown functions through L-PGDS and prostaglandin D2. Here we update the neuroendocrine functions of melanocytes and discuss the possible involvement of melanocytes in the control of the central chemosensor that generates respiratory rhythm.

  10. Increased endogenous DNA oxidation correlates to increased iron levels in melanocytes relative to keratinocytes.

    PubMed

    Pelle, Edward; Huang, Xi; Zhang, Qi; Pernodet, Nadine; Yarosh, Daniel B; Frenkel, Krystyna

    2014-01-01

    The endogenous oxidative state of normal human epidermal melanocytes was investigated and compared to normal human epidermal keratinocytes (NHEKs) in order to gain new insight into melanocyte biology. Previously, we showed that NHEKs contain higher levels of hydrogen peroxide (H2O2) than melanocytes and that it can migrate from NHEKs to melanocytes by passive permeation. Nevertheless, despite lower concentrations of H2O2, we now report higher levels of oxidative DNA in melanocytes as indicated by increased levels of 8-oxo-2'-deoxyguanosine (8-oxo-dG): 4.49 (±0.55 SEM) 8-oxo-dG/10(6) dG compared to 1.49 (±0.11 SEM) 8-oxo-dG/10(6) dG for NHEKs. An antioxidant biomarker, glutathione (GSH), was also lower in melanocytes (3.14 nmoles (±0.15 SEM)/cell) in comparison to NHEKs (5.98 nmoles (±0.33 SEM)/cell). Intriguingly, cellular bioavailable iron as measured in ferritin was found to be nearly fourfold higher in melanocytes than in NHEKs. Further, ferritin levels in melanocytes were also higher than in hepatocarcinoma cells, an iron-rich cell, and it indicates that higher relative iron levels may be characteristic of melanocytes. To account for the increased oxidative DNA and lower GSH and H2O2 levels that we observe, we propose that iron may contribute to higher levels of oxidation by reacting with H2O2 through a Fenton reaction leading to the generation of DNA-reactive hydroxyl radicals. In conclusion, our data support the concept of elevated oxidation and high iron levels as normal parameters of melanocytic activity. We present new evidence that may contribute to our understanding of the melanogenic process and lead to the development of new skin care products.

  11. S100B as a potential biomarker for the detection of cytotoxicity of melanocytes.

    PubMed

    Cheong, Kyung Ah; Noh, Minsoo; Kim, Chang-Hyun; Lee, Ai-Young

    2014-03-01

    Skin irritation is one of the most common adverse reactions in hydroquinone (HQ) and retinoic acid (RA). Although melanocytes have rarely been considered to be involved in skin irritation, RA and particularly HQ could induce melanocyte toxicity, resulting in depigmentation. We chose S100B as a candidate gene for melanocytotoxicity from a genome-wide transcriptional profiling analysis after applying irritant doses of HQ, RA and sodium lauryl sulphate (SLS) to cultures of keratinocytes and/or melanocytes. In this study, the role of S100B on melanocyte viability and cytotoxicity was examined. S100B was detected in melanocytes, but not in keratinocytes or fibroblasts. Melanocytes after treatment with increasing concentrations of HQ, RA, SLS and urushiol showed significant increases in intracellular and extracellular S100B expression with reduced viable cell number and increased release of lactate dehydrogenase. No RAGE expression and no significant function of CD166/ALCAM in melanocyte survival and cytotoxicity favoured the role of intracellular S100B in chemically irritated melanocytes. S100B knock-down increased apoptosis through inhibition of PI3K/AKT, NF-κB and ERK activation, suggesting the increased intracellular S100B expression by chemical irritation as a compensatory reaction to reduce cytotoxicity. The numerical decrease in S100B/c-kit-double-positive melanocytes was also examined in human skin epidermis irritated by HQ or RA with stronger staining intensities of S100B. Collectively, the decrease in viable cell number by reduced intracellular S100B levels in vitro and by chemical irritation in vivo suggests that S100B could be a potential biomarker for melanocytes cytotoxicity.

  12. PGE2 is a UVR-inducible autocrine factor for human melanocytes that stimulates tyrosinase activation

    PubMed Central

    Starner, Renny J.; McClelland, Lindy; Abdel-Malek, Zalfa; Fricke, Alex; Scott, Glynis

    2013-01-01

    Melanocyte proliferation, dendrite formation, and pigmentation are controlled by paracrine factors, particularly following exposure to ultraviolet radiation (UVR). Little is known about autocrine factors for melanocytes. Prostaglandins activate signaling pathways involved in growth, differentiation and apoptosis. Prostaglandin E2 (PGE2) is the most abundant prostaglandin released by keratinocytes following UVR, and stimulates the formation of dendrites in melanocytes. Synthesis of PGE2 is controlled by cPLA2, which releases arachidonic acid from membranes, and COX-2 and prostaglandin E2 synthases (PGES), which convert arachidonic acid to PGH2 and PGH2 to PGE2, respectively. In this report we show that multiple irradiations of human melanocytes with UVR stimulates tyrosinase activity, independent of expression of a functional melanocortin 1 receptor, suggesting the presence of a non-melanocortin autocrine factor. Irradiation of melanocytes activated cPLA2, the rate-limiting step in eicosanoid synthesis, and stimulated PGE2 secretion. PGE2 increased cAMP production, tyrosinase activity and proliferation in melanocytes. PGE2 binds to four distinct G-protein coupled receptors (EP1–4). We show that EP4 receptor signaling stimulates cAMP production in melanocytes. Conversely, stimulation of the EP3 receptor lowered basal cAMP levels. These data suggest that relative levels or activity of these receptors controls effects of PGE2 on cAMP in melanocytes. The data are the first to identify PGE2 as an UVR-inducible autocrine factor for melanocytes that stimulates tyrosinase activity and proliferation, and to show that EP3 and EP4 receptor signaling have opposing effects on cAMP production, a critical signaling pathway that regulates proliferation and melanogenesis in melanocytes. PMID:20500768

  13. Betrayal trauma and dimensions of borderline personality organization.

    PubMed

    Yalch, Matthew M; Levendosky, Alytia A

    2014-01-01

    Borderline personality pathology can be conceptualized as one of many conditions within a broader spectrum of borderline personality organization (BPO). This spectrum is composed of several specific dimensions of psychological functioning (primitive psychological defenses, identity diffusion, and reality testing). Although several theories associate trauma with borderline pathology, betrayal trauma theory specifies that trauma with a high degree of betrayal has an especially pernicious influence on borderline pathology. In addition, betrayal trauma theorists propose that constructs related to each BPO dimension are influenced by traumatic betrayal, but this has not yet been tested within the context of borderline pathology specifically. In this article, we examine the relation between trauma with varying levels of betrayal and the specific dimensions of BPO using a Bayesian approach to multiple regression. Results indicated that trauma with a high degree of betrayal was associated with each dimension of BPO, that medium betrayal trauma was associated with problems in reality testing, and that low betrayal trauma was associated with primitive psychological defenses. These effects differed by gender. Limitations of the study and directions for future research are also discussed.

  14. Perceptions of childhood caretakers and borderline personality symptomatology.

    PubMed

    Sansone, Randy A; Farukhi, Shahzad; Wiederman, Michael W

    2013-11-01

    Previous studies indicate that individuals with borderline personality disorder come from families marked by high levels of psychopathology as well as dysfunctional parenting styles-themes that tend to engender negative attitudes toward parents. However, we are not aware of any studies that have examined perceptions of parenting quality and borderline personality symptoms in a clinical but non-psychiatric population-the purpose of the present study. Using a cross-sectional self-report survey methodology in a sample of internal medicine outpatients, we examined participants' perceptions of the quality of parental caretaking using a one-item assessment, and examined borderline personality symptomatology using two measures. Ratings of the quality of parental care were statistically significantly inversely correlated with scores on both measures of borderline personality symptomatology. After controlling for the number of caretakers during childhood, the observed statistical relationships remained statistically significant. In this primary care sample, participants with borderline personality symptomatology perceived parents more negatively than those without such symptomatology.

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

    PubMed

    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.

  16. Targeted Melanoma Imaging and Therapy with Radiolabeled Alpha-Melanocyte Stimulating Hormone Peptide Analogues

    PubMed Central

    Quinn, Thomas; Zhang, Xiuli; Miao, Yubin

    2010-01-01

    Radiolabeled alpha-melanocyte stimulating hormone (α-MSH) analogues have been used to define the expression, affinity and function of the melanocortin-1 receptor (MC1-R). The MC1-R is one of a family of five G-protein linker receptors, which is primarily involved in regulation of skin pigmentation. Over-expression of the MC1-R on melanoma tumor cells has made it an attractive target for the development of α-MSH peptide based imaging and therapeutic agents. Initially, the native α-MSH peptide was radiolabeled directly, but it suffered from low specific activity and poor stability. The addition of non-natural amino acids yielded α-MSH analogues with greater MC-1R affinity and stability. Furthermore, peptide cyclization via disulfide and lactam bond formation as well as site-specific metal coordination resulted in additional gains in receptor affinity and peptide stability in vitro and in vivo. Radiochemical stability of the α-MSH analogues was improved through the conjugation of metal chelators to the peptide’s N-terminus or lysine residues for radionuclide coordination. In vitro cell binding studies demonstrated that the radiolabeled α-MSH analogues had low to subnanomolar affinities for the MC1-R. Biodistribution and imaging studies in the B16 mouse melanoma modeled showed rapid tumor uptake of the radiolabeled peptides, with the cyclic peptides demonstrating prolonged tumor retention. Cyclic α-MSH analogues labeled with beta and alpha emitting radionuclides demonstrated melanoma therapeutic efficacy in the B16 melanoma mouse model. Strong pre-clinical imaging and therapy data highlight the clinical potential use of radiolabeled α-MSH peptides for melanoma imaging and treatment of disseminated disease. PMID:20467398

  17. ADHD in adolescents with borderline personality disorder

    PubMed Central

    2011-01-01

    Background The aims of this study were to assess the prevalence of a comorbid Attention Deficit Hyperactivity Disorder (ADHD) diagnosis in Borderline Personality Disorder (BPD), and its impact on the clinical presentation of BPD in adolescents, and to determine which type of impulsivity specifically characterizes adolescents with BPD-ADHD. Methods ADHD diagnoses were sought in a sample of 85 DSM-IV BPD adolescents drawn from the EURNET BPD. Axis-I and -II disorders were determined with the K-SADS-PL and the SIDP-IV, respectively. Impulsivity was assessed with the BIS-11. Results 11% (N = 9) of BPD participants had a current ADHD diagnosis. BPD-ADHD adolescents showed higher prevalence of Disruptive disorders (Chi2 = 9.09, p = 0.01) and a non-significant trend for a higher prevalence of other cluster B personality disorders (Chi2 = 2.70, p = 0.08). Regression analyses revealed a significant association between Attentional/Cognitive impulsivity scores and ADHD (Wald Z = 6.69; p = 0.01; Exp(B) = 2.02, CI 95% 1.19-3.45). Conclusions Comorbid ADHD influences the clinical presentation of adolescents with BPD and is associated with higher rates of disruptive disorders, with a trend towards a greater likelihood of cluster B personality disorders and with higher levels of impulsivity, especially of the attentional/cognitive type. A subgroup of BPD patients may exhibit developmentally driven impairments of the inhibitory system persisting since childhood. Specific interventions should be recommended for this subsample of BPD adolescents. PMID:21961882

  18. The actions of melanin and melanocyte stimulating hormone (MSH).

    PubMed

    Rasmussen, Natalie; Nelson, Francine; Govitrapong, Piyarat; Ebadi, Manuchair

    1999-01-01

    The skin, the largest organ of the body, plays an important role in the total metabolism of several hormones. Melanin, the major product of the melanocyte, is largely responsible for the coloring of skin. Melanin is a complex of insoluble, polyquinone, brown or red pigment and protein, formed by the oxidation of tyrosine and 3,4-dihydroxyphenylalanine in the presence of tyrosinase. There exists two main groups of melanin: the black to dark-brown insoluble eumelanins and the yellow to reddish brown, alkali-soluble pheomelanins. MSH, ACTH and beta-lipoprotein are able to influence skin pigmentation. The functions attributed to melanins are acting as a barrier against ionizing radiation; participating in developmental processes, serving as a cosmetic entity, and scavenging cytotoxic radicals and intermediates. Melanocytes express numerous receptors that allow interaction with other cells in their microenvironment, including keratinocytes and the immune component of the skin Langerhans cells. Albinism represents a group of inherited abnormalities that present with congenital hypopigmentation that can involve the skin, hair, and eyes (oculocutaneous albinism) or be limited primarily to the eyes (ocular albinism). The inherited disorders of keratin include epidermolysis bullosu simplex causing cell degeneration within the basal layer. Sunlight and ultraviolet radiation from artificial light sources could be tonic or toxic to human skin. The harmful effects of solar radiation are skin cancer, photosensitivity diseases, sunburn, photoallergy, photoimmunologic alterations, cataracts, mutations, skin aging and phototoxicity. Sunscreen chemicals protect the skin against ultraviolet radiation.

  19. [Borderline personality disorder. Kingdom of women, land without men].

    PubMed

    Ruiz, Martín; Vairo, María Carolina

    2008-01-01

    In the last decade, literature concerning gender and borderline personality disorder has aroused much controversy and little lightness. Recently, borderline personality disorder has been characterized as the "bad girl" of the psychiatric terms; this implies a bigger use of this diagnose in women and a biased gender in the identification of this disorder. The Diagnostic and Statistical Manual of Mental Disorders states that borderline personality disorder is mostly diagnosed in women (75%). The essential question to discuss is whether the larger prevalence in women is due to a biased sample or a biased diagnoses or it reflects a sociocultural and biological difference between men and women. The aim of this paper is to analyze some issues about the difference 3:1 women and men in this disorder.

  20. Family history of alcoholism in borderline personality disorder.

    PubMed

    Loranger, A W; Tulis, E H

    1985-02-01

    The lifetime expectancy (morbid risk) of alcoholism was determined in the parents and siblings of 83 women with DSM-III borderline personality disorder and compared with that in the parents and siblings of 100 women with DSM-III schizophrenia and 100 women with DSM-III bipolar disorder. The relatives of the borderline probands had two to three times more alcoholism than the relatives of the bipolar and schizophrenic probands. The condition was most common in the fathers of the borderline probands, almost one third of whom were either alcoholics or heavy drinkers. When the three groups of probands were subdivided according to whether they, themselves, had occasionally abused alcohol, there were no longer any significant differences in alcoholism among their relatives.

  1. Emotional Hyper-Reactivity in Borderline Personality Disorder

    PubMed Central

    Sansone, Lori A.

    2010-01-01

    According to clinical experience, the Diagnostic and Statistical Manual of Mental Disorders, and authorities in the field, patients with borderline personality disorder tend to be hyper-reactive to environmental stimuli. In addition to the preceding clinical impressions and experiences, the majority of empirical studies in this area have concluded that patients with borderline personality disorder are indeed hyper-responsive to experimental environmental stimuli, whether the stimuli are negative, positive, or even neutral or ambiguous. While two empirical studies did not find hyper-responsiveness, both were undertaken in inpatients with borderline personality disorder, and the potential for emotional blunting from psychotropic medications may have been a potential confound. These findings have several clinical implications in both mental health and primary care settings. PMID:20941347

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

    SciTech Connect

    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

  3. Endothelin-1 is a transcriptional target of p53 in epidermal keratinocytes and regulates UV induced melanocyte homeostasis

    PubMed Central

    Hyter, Stephen; Coleman, Daniel J.; Ganguli-Indra, Gitali; Merrill, Gary F.; Ma, Steven; Yanagisawa, Masashi; Indra, Arup K.

    2013-01-01

    Summary Keratinocytes contribute to melanocyte activity by influencing their microenvironment, in part, through secretion of paracrine factors. Here we discovered that p53 directly regulates Edn1 expression in epidermal keratinocytes and controls UV-induced melanocyte homeostasis. Selective ablation of EDN1 in murine epidermis (EDN1ep−/−) does not alter melanocyte homeostasis in newborn skin but decreases dermal melanocytes in adult skin. Results showed that keratinocytic EDN1 in a non-cell autonomous manner controls melanocyte proliferation, migration, DNA damage and apoptosis after UVB irradiation. Expression of other keratinocyte derived paracrine factors did not compensate for the loss of EDN1. Topical treatment with EDN1 receptor (EDNRB) antagonist BQ788 abrogated UV induced melanocyte activation and recapitulated the phenotype seen in EDN1ep−/− mice. Altogether, present studies establish an essential role of EDN1 in epidermal keratinocytes to mediate UV induced melanocyte homeostasis in vivo. PMID:23279852

  4. Autonomic mechanisms underpinning the stress response in borderline hypertensive rats

    PubMed Central

    Šarenac, Olivera; Lozić, Maja; Drakulić, Srdja; Bajić, Dragana; Paton, Julian F; Murphy, David; Japundžić-Žigon, Nina

    2011-01-01

    This study investigates blood pressure (BP) and heart rate (HR) short-term variability and spontaneous baroreflex functioning in adult borderline hypertensive rats and normotensive control animals kept on normal-salt diet. Arterial pulse pressure was recorded by radio telemetry. Systolic BP, diastolic BP and HR variabilities and baroreflex were assessed by spectral analysis and the sequence method, respectively. In all experimental conditions (baseline and stress), borderline hypertensive rats exhibited higher BP, increased baroreflex sensitivity and resetting, relative to control animals. Acute shaker stress (single exposure to 200 cycles min-1 shaking platform) increased BP in both strains, while chronic shaker stress (3-day exposure to shaking platform) increased systolic BP in borderline hypertensive rats alone. Low- and high-frequency HR variability increased only in control animals in response to acute and chronic shaker (single exposure to restrainer) stress. Acute restraint stress increased BP, HR, low- and high-frequency variability of BP and HR in both strains to a greater extent than acute shaker stress. Only normotensive rats exhibited a reduced ratio of low- to high-frequency HR variability, pointing to domination of vagal cardiac control. In borderline hypertensive rats, but not in control animals, chronic restraint stress (9-day exposure to restrainer) increased low- and high-frequency BP and HR variability and their ratio, indicating a shift towards sympathetic cardiovascular control. It is concluded that maintenance of BP in borderline hypertensive rats in basal conditions and during stress is associated with enhanced baroreflex sensitivity and resetting. Imbalance in sympathovagal control was evident only during exposure of borderline hypertensive rats to stressors. PMID:21421701

  5. Autonomic mechanisms underpinning the stress response in borderline hypertensive rats.

    PubMed

    Šarenac, Olivera; Lozić, Maja; Drakulić, Srdja; Bajić, Dragana; Paton, Julian F; Murphy, David; Japundžić-Žigon, Nina

    2011-06-01

    This study investigates blood pressure (BP) and heart rate (HR) short-term variability and spontaneous baroreflex functioning in adult borderline hypertensive rats and normotensive control animals kept on normal-salt diet. Arterial pulse pressure was recorded by radio telemetry. Systolic BP, diastolic BP and HR variabilities and baroreflex were assessed by spectral analysis and the sequence method, respectively. In all experimental conditions (baseline and stress), borderline hypertensive rats exhibited higher BP, increased baroreflex sensitivity and resetting, relative to control animals. Acute shaker stress (single exposure to 200 cycles min-1 shaking platform) increased BP in both strains, while chronic shaker stress (3-day exposure to shaking platform) increased systolic BP in borderline hypertensive rats alone. Low- and high-frequency HR variability increased only in control animals in response to acute and chronic shaker (single exposure to restrainer) stress. Acute restraint stress increased BP, HR, low- and high-frequency variability of BP and HR in both strains to a greater extent than acute shaker stress. Only normotensive rats exhibited a reduced ratio of low- to high-frequency HR variability, pointing to domination of vagal cardiac control. In borderline hypertensive rats, but not in control animals, chronic restraint stress (9-day exposure to restrainer) increased low- and high-frequency BP and HR variability and their ratio, indicating a shift towards sympathetic cardiovascular control. It is concluded that maintenance of BP in borderline hypertensive rats in basal conditions and during stress is associated with enhanced baroreflex sensitivity and resetting. Imbalance in sympathovagal control was evident only during exposure of borderline hypertensive rats to stressors.

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

    ERIC Educational Resources Information Center

    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…

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

    ERIC Educational Resources Information Center

    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…

  8. Race Does Not Predict Melanocyte Heterogeneous Responses to Dermal Fibroblast-Derived Mediators

    PubMed Central

    Sirimahachaiyakul, Pornthep; Sood, Ravi F.; Muffley, Lara A.; Seaton, Max; Lin, Cheng-Ta; Qiao, Liang; Armaly, Jeffrey S.; Hocking, Anne M.; Gibran, Nicole S.

    2015-01-01

    Introduction Abnormal pigmentation following cutaneous injury causes significant patient distress and represents a barrier to recovery. Wound depth and patient characteristics influence scar pigmentation. However, we know little about the pathophysiology leading to hyperpigmentation in healed shallow wounds and hypopigmentation in deep dermal wound scars. We sought to determine whether dermal fibroblast signaling influences melanocyte responses. Methods and Materials Epidermal melanocytes from three Caucasians and three African-Americans were genotyped for single nucleotide polymorphisms (SNPs) across the entire genome. Melanocyte genetic profiles were determined using principal component analysis. We assessed melanocyte phenotype and gene expression in response to dermal fibroblast-conditioned medium and determined potential mesenchymal mediators by proteome profiling the fibroblast-conditioned medium. Results Six melanocyte samples demonstrated significant variability in phenotype and gene expression at baseline and in response to fibroblast-conditioned medium. Genetic profiling for SNPs in receptors for 13 identified soluble fibroblast-secreted mediators demonstrated considerable heterogeneity, potentially explaining the variable melanocyte responses to fibroblast-conditioned medium. Discussion Our data suggest that melanocytes respond to dermal fibroblast-derived mediators independent of keratinocytes and raise the possibility that mesenchymal-epidermal interactions influence skin pigmentation during cutaneous scarring. PMID:26418010

  9. Preferential secretion of inducible HSP70 by vitiligo melanocytes under stress.

    PubMed

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

    2014-03-01

    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.

  10. RICTOR involvement in the PI3K/AKT pathway regulation in melanocytes and melanoma.

    PubMed

    Laugier, Florence; Finet-Benyair, Adeline; André, Jocelyne; Rachakonda, P Sivaramakrishna; Kumar, Rajiv; Bensussan, Armand; Dumaz, Nicolas

    2015-09-29

    Several studies have highlighted the importance of the PI3K pathway in melanocytes and its frequent over-activation in melanoma. However, little is known about regulation of the PI3K pathway in melanocytic cells. We showed that normal human melanocytes are less sensitive to selective PI3K or mTOR inhibitors than to dual PI3K/mTOR inhibitors. The resistance to PI3K inhibitor was due to a rapid AKT reactivation limiting the inhibitor effect on proliferation. Reactivation of AKT was linked to a feedback mechanism involving the mTORC2 complex and in particular its scaffold protein RICTOR. RICTOR overexpression in melanocytes disrupted the negative feedback, activated the AKT pathway and stimulated clonogenicity highlighting the importance of this feedback to restrict melanocyte proliferation. We found that the RICTOR locus is frequently amplified and overexpressed in melanoma and that RICTOR over-expression in NRAS-transformed melanocytes stimulates their clonogenicity, demonstrating that RICTOR amplification can cooperate with NRAS mutation to stimulate melanoma proliferation. These results show that RICTOR plays a central role in PI3K pathway negative feedback in melanocytes and that its deregulation could be involved in melanoma development.

  11. Human melanocytes mitigate keratinocyte-dependent contraction in an in vitro collagen contraction assay.

    PubMed

    Rakar, Jonathan; Krammer, Markus P; Kratz, Gunnar

    2015-08-01

    Scarring is an extensive problem in burn care, and treatment can be especially complicated in cases of hypertrophic scarring. Contraction is an important factor in scarring but the contribution of different cell types remains unclear. We have investigated the contractile behavior of keratinocytes, melanocytes and fibroblasts by using an in vitro collagen gel assay aimed at identifying a modulating role of melanocytes in keratinocyte-mediated contraction. Cells were seeded on a collagen type I gel substrate and the change in gel dimensions were measured over time. Hematoxylin & Eosin-staining and immunohistochemistry against pan-cytokeratin and microphthalmia-associated transcription factor showed that melanocytes integrated between keratinocytes and remained there throughout the experiments. Keratinocyte- and fibroblast-seeded gels contracted significantly over time, whereas melanocyte-seeded gels did not. Co-culture assays showed that melanocytes mitigate the keratinocyte-dependent contraction (significantly slower and 18-32% less). Fibroblasts augmented the contraction in most assays (approximately 6% more). Non-contact co-cultures showed some influence on the keratinocyte-dependent contraction. Results show that mechanisms attributable to melanocytes, but not fibroblasts, can mitigate keratinocyte contractile behavior. Contact-dependent mechanisms are stronger modulators than non-contact dependent mechanisms, but both modes carry significance to the contraction modulation of keratinocytes. Further investigations are required to determine the mechanisms involved and to determine the utility of melanocytes beyond hypopigmentation in improved clinical regimes of burn wounds and wound healing.

  12. Borderline personality disorder in the primary care setting.

    PubMed

    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.

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

    SciTech Connect

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

    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.

  14. In ovo gene manipulation of melanocytes and their adjacent keratinocytes during skin pigmentation of chicken embryos.

    PubMed

    Murai, Hidetaka; Tadokoro, Ryosuke; Sakai, Ken-Ichiro; Takahashi, Yoshiko

    2015-04-01

    During skin pigmentation in avians and mammalians, melanin is synthesized in the melanocytes, and subsequently transferred to adjacently located keratinocytes, leading to a wide coverage of the body surface by melanin-containing cells. The behavior of melanocytes is influenced by keratinocytes shown mostly by in vitro studies. However, it has poorly been investigated how such intercellular cross-talk is regulated in vivo because of a lack of suitable experimental models. Using chicken embryos, we developed a method that enables in vivo gene manipulations of melanocytes and keratinocytes, where these cells are separately labeled by different genes. Two types of gene transfer techniques were combined: one was a retrovirus-mediated gene infection into the skin/keratinocytes, and the other was the in ovo DNA electroporation into neural crest cells, the origin of melanocytes. Since the Replication-Competent Avian sarcoma-leukosis virus long terminal repeat with Splice acceptor (RCAS) infection was available only for the White leghorn strain showing little pigmentation, melanocytes prepared from the Hypeco nera (pigmented) were back-transplanted into embryos of White leghorn. Prior to the transplantation, enhanced green fluorescent protein (EGFP)(+) Neo(r+) -electroporated melanocytes from Hypeco nera were selectively grown in G418-supplemented medium. In the skin of recipient White leghorn embryos infected with RCAS-mOrange, mOrange(+) keratinocytes and transplanted EGFP(+) melanocytes were frequently juxtaposed each other. High-resolution confocal microscopy also revealed that transplanted melanocytes exhibited normal behaviors regarding distribution patterns of melanocytes, dendrite morphology, and melanosome transfer. The method described in this study will serve as a useful tool to understand the mechanisms underlying intercellular regulations during skin pigmentation in vivo.

  15. Dual roles of lineage restricted transcription factors: the case of MITF in melanocytes.

    PubMed

    Levy, Carmit; Fisher, David E

    2011-01-01

    Microphthalmia-associated Transcription Factor, MITF, is a master regulator of melanocyte development, differentiation, migration, and survival.(1) A broad collection of studies have indicated that MITF directly regulates the transcription of genes involved in pigmentation, which are selective to the melanocyte lineage. In addition, MITF controls expression of genes which are expressed in multiple cell lineages, and may also play differential roles in activating vs. maintaining gene expression patterns. In this Point of View article, we discuss lineage restricted transcription factor activation of both tissue-specific and ubiquitously expressed genes using melanocytes and MITF as a model system that may eventually provide insights into such processes in multiple cell lineages.

  16. Melanocytic aggregation in the skin: diagnostic clues from lentigines to melanoma.

    PubMed

    de Giorgi, Vincenzo; Sestini, Serena; Massi, Daniela; Lotti, Torello

    2007-07-01

    Pigmented skin lesions are among the most common skin lesions. Among them, melanocytic proliferations are morphologically diverse and their behavior may be difficult to discern with certainty. Researchers must be able to distinguish melanocytic from nonmelanocytic pigmented skin lesions and, in particular, benign from malignant lesions. The majority of these lesions can be diagnosed with ease; however, a minority of cases is difficult and have potential for error. The authors have systematically analyzed the clinical and dermoscopic features of melanocytic skin lesions, so as to increase in vivo diagnostic accuracy.

  17. Ocular Albinism Type 1 Regulates Melanogenesis in Mouse Melanocytes

    PubMed Central

    Chen, Tianzhi; Wang, Haidong; Liu, Yu; Zhao, Bingling; Zhao, Yuanyuan; Fan, Ruiwen; Wang, Pengchao; Dong, Changsheng

    2016-01-01

    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 participate in the

  18. Preclinical Melanoma Imaging with 68Ga-Labeled α-Melanocyte-Stimulating Hormone Derivatives Using PET

    PubMed Central

    Zhang, Chengcheng; Zhang, Zhengxing; Lin, Kuo-Shyan; Pan, Jinhe; Dude, Iulia; Hundal-Jabal, Navjit; Colpo, Nadine; Bénard, François

    2017-01-01

    It is estimated that melanoma accounted for 76,380 new cases and 10,130 deaths in the United States in 2016. The melanocortin 1 receptor (MC1R) is highly expressed in the vast majority of melanomas, which makes it an attractive target for molecular imaging and radionuclide therapy. Lactam bridge-cyclized α-melanocyte-stimulating hormone (Ac-Nle4-cyclo[Asp5-His-D-Phe7-Arg-Trp-Lys10]-NH2, or Nle-CycMSHhex) analogues have been successfully developed and studied for MC1R-targeted imaging, predominantly with single-photon emission computed tomography (SPECT). The goal of this study was to design and evaluate novel peptides for melanoma imaging with positron emission tomography (PET). We designed and synthesized three peptides, DOTA-PEG2-Nle-CycMSHhex (CCZ01047), DOTA-4-amino-(1-carboxymethyl) piperidine (Pip)-Nle-CycMSHhex (CCZ01048), and DOTA-Pip-Pip-Nle-CycMSHhex (CCZ01056). All three peptides exhibited high binding affinity to MC1R with sub-nanomolar Ki values, rapid internalization into B16F10 melanoma cells and high in vivo stability with more than 93% remaining intact at 15 min post-injection (p.i.) in blood plasma. All three 68Ga-labeled tracers produced high contrast PET images in C57BL/6J mice bearing B16F10 tumors, and their respective tumor uptakes were 8.0 ± 3.0, 12.3 ± 3.3, and 6.5 ± 1.4 %ID/g at 1 h p.i. Minimal normal organ activity was observed at 1 h p.i., except for kidneys (5.1 ± 1.4, 4.7 ± 0.5, and 6.2 ± 2.0 %ID/g, respectively), and thyroid (4.1 ± 0.6 %ID/g for CCZ01047 and 2.4 ± 0.6 %ID/g for CCZ01048). Due to high accumulation at tumor sites and rapid background clearance of 68Ga-CCZ01048, we further evaluated it at 2 h p.i., and a tumor uptake of 21.9 ± 4.6 %ID/g was observed, with background activity further decreased. Exceptional image contrast was also achieved, i.e. tumor-to-blood, tumor-to-muscle, tumor-to-bone and tumor-to-kidney ratios were 96.4 ± 13.9, 210.9 ± 20.9, 39.6 ± 11.9 and 4.0 ± 0.9, respectively. A blocking study

  19. [Brenner tumor: one case report and bibliographic review].

    PubMed

    Guerrero-Martínez, Elly; Mateos-Vizcayno, Julio; Huerta-Hentschel, José Manuel

    2014-06-01

    Brenner tumor is a rare tumor that represents approximately 1.5% of the tumors of ovary. It is defined as a tumor of transitional cells composed by urothelial cells arranged in solid or cystic groups absorbed in a fibrous stroma. It classifies in benign Brenner tumor (95%), borderline (3-4%) and malignant (1%). Let's sense beforehand the clinical case of a 46-year-old patient who underwent surgery having an adnexal mass of which the pathological intraoperative report brought a benign Brenner tumor.

  20. Cutaneous melanocytic lesions: do not miss the invisible gorilla.

    PubMed

    Prieto, Victor G

    2012-07-01

    Of all pathology fields, the analysis of melanocytic lesions has one of the highest rates of review for legal reasons, particularly regarding the distinction between nevus and melanoma. Among the most frequently involved are desmoplastic melanoma, nevoid melanoma, and Spitz nevus versus spitzoid melanoma. Therefore, it follows that pathologists and dermatopathologists should pay special attention when dealing with such type of lesions. This review article will emphasize a number of clinical, histologic, and immunohistochemical features we believe are essential when evaluating lesions whose differential diagnosis includes melanoma/nevus. Furthermore, we want to stress the importance of examining the entire slide within the context of all available information in order to not miss the invisible gorilla in the slide. Regarding this apparently bizarre choice to illustrate these problems (to not miss an invisible gorilla), we request the reader to continue reading this article to find out why.

  1. CEACAM1: Expression and Role in Melanocyte Transformation

    PubMed Central

    Turcu, Gabriela; Ion, Daniela Adriana; Brînzea, Alice; Cioplea, Mirela Daniela; Jilaveanu, Lucia Beatrice

    2016-01-01

    Metastases represent the main cause of death in melanoma patients. Despite the current optimized targeted therapy or immune checkpoint inhibitors the treatment of metastatic melanoma is unsatisfactory. Because of the poor prognosis of advanced melanoma there is an urgent need to identify new biomarkers to differentiate melanoma cells from normal melanocytes, to stratify patients according to their risk, and to identify subgroups of patients that require close follow-up or more aggressive therapy. Furthermore, melanoma progression has been associated with the dysregulation of cell adhesion molecules. We have reviewed the literature and have discussed the important role of the expression of the carcinoembryonic antigen cell adhesion molecule 1 (CEACAM1) in the development of melanoma. Thus, novel insights into CEACAM1 may lead to promising strategies in melanoma treatment, in monitoring melanoma patients, in assessing the response to immunotherapy, and in completing the standard immunohistochemical panel used in melanoma examination. PMID:27642217

  2. Assessing at the Borderline: Judging a Vocationally Related Portfolio Holistically

    ERIC Educational Resources Information Center

    Johnson, Martin

    2008-01-01

    This study investigated the cognitive strategies that underpin assessors' holistic judgments of a school-based vocationally-related portfolio performance. Using a portfolio already identified as containing borderline qualities, quantitative data were gathered about features that six assessors attended to as they holistically evaluated the…

  3. Investigation of Borderline Personality Disorder among Nonpsychotic, Involuntarily Hospitalized Clients.

    ERIC Educational Resources Information Center

    Sansone, Randy A.; Gage, Mark D.; Wiederman, Michael W.

    1998-01-01

    Clients (N=32) who were involuntarily hospitalized in a psychiatric facility were assessed for borderline personality disorder (BPD) using an interview and two self-report questionnaires. The majority (53.1%) met criteria for BPD on all three measures, 18.8% on two measures, and 18.8% on only one measure. Implications of these findings are…

  4. Borderline Personality in Adolescence: An Overview for Counselors.

    ERIC Educational Resources Information Center

    Craig, Stephen E.; Fall, Kevin A.

    1998-01-01

    Borderline-personality disorder in adolescence is thought to develop through environmental sources, and object-relations theory posits a developmental arrest in the separation-individuation phase of development. This article discusses gender and race considerations, issues related to counseling, general treatment strategies such as coping-skills…

  5. Borderline Personality Disorder and the Misdiagnosis of Bipolar Disorder

    PubMed Central

    Ruggero, Camilo J.; Zimmerman, Mark; Chelminski, Iwona; Young, Diane

    2009-01-01

    Recent reports suggest bipolar disorder is not only under-diagnosed but may at times be over-diagnosed. Little is known about factors that increase the odds of such mistakes. The present work explores whether symptoms of borderline personality disorder increase the odds of a bipolar misdiagnosis. Psychiatric outpatients (N = 610) presenting for treatment were administered the Structured Clinical Interview for DSM-IV (SCID) and the Structured Interview for DSM-IV Personality for DSM-IV axis II disorders (SIDP-IV), as well as a questionnaire asking if they had ever been diagnosed with bipolar disorder by a mental health care professional. Eighty-two patients who reported having been previously diagnosed with bipolar disorder but who did not have it according to the SCID were compared to 528 patients who had never been diagnosed with bipolar disorder. Patients with borderline personality disorder had significantly greater odds of a previous bipolar misdiagnosis, but no specific borderline criteria was unique in predicting this outcome. Patients with borderline personality disorder, regardless of how they meet criteria, may be at increased risk of being misdiagnosed with bipolar disorder. PMID:19889426

  6. The Borderline Personality Diagnosis in Adolescents: Gender Differences and Subtypes

    ERIC Educational Resources Information Center

    Bradley, Rebekah; Zittel Conklin, Carolyn; Westen, Drew

    2005-01-01

    Background: This study aimed to identify personality features characterizing adolescent girls and boys with borderline personality disorder (BPD) and to see whether meaningful patterns of heterogeneity exist among adolescents diagnosed with the disorder. Methods: Two hundred and ninety-four randomly selected doctoral-level clinicians described…

  7. Borderline Personality Disorder: A Dysregulation of the Endogenous Opioid System?

    ERIC Educational Resources Information Center

    Bandelow, Borwin; Schmahl, Christian; Falkai, Peter; Wedekind, Dirk

    2010-01-01

    The neurobiology of borderline personality disorder (BPD) remains unclear. Dysfunctions of several neurobiological systems, including serotoninergic, dopaminergic, and other neurotransmitter systems, have been discussed. Here we present a theory that alterations in the sensitivity of opioid receptors or the availability of endogenous opioids…

  8. Interpersonal Precipitants and Suicide Attempts in Borderline Personality Disorder

    ERIC Educational Resources Information Center

    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…

  9. Borderline Personality Disorder and Posttraumatic Stress Disorder: Time for Integration?

    ERIC Educational Resources Information Center

    Hodges, Shannon

    2003-01-01

    An increasing prevalence of borderline personality disorder (BPD) and posttraumatic stress disorder (PTSD) diagnoses among women illustrates problems and limitations of the medical model system. Article explores overlapping relationship between BPD and PTSD and critiques how both are viewed within the mental health community. Previous research is…

  10. Development and Validation of the Minnesota Borderline Personality Disorder Scale

    ERIC Educational Resources Information Center

    Bornovalova, Marina A.; Hicks, Brian M.; Patrick, Christopher J.; Iacono, William G.; McGue, Matt

    2011-01-01

    Although large epidemiological data sets can inform research on the etiology and development of borderline personality disorder (BPD), they rarely include BPD measures. In some cases, however, proxy measures can be constructed using instruments already in these data sets. In this study, the authors developed and validated a self-report measure of…

  11. Autonomic Impairment in Borderline Personality Disorder: A Laboratory Investigation

    ERIC Educational Resources Information Center

    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…

  12. Treatment of Borderline Adolescents in Family Court Services.

    ERIC Educational Resources Information Center

    Green, Maurice R.

    A recent revision of the proposed DSM III description of the borderline category is presented with reference to the work of Masterson and Grinker. The contributions of Roger Shapiro and his group to a psychoanalytic formulation of the developmental and familial dynamics are summarized with reference to genetic factors and the lack of validation,…

  13. Improving the management of women with borderline personality disorder.

    PubMed

    Bhebhe, Siziwe; Fuller, Mark

    An inpatient service for women with borderline personality disorder adapted a therapeutic approach developed for use with outpatients. Mentalisation-based therapy helps clients to understand the meaning of their own behaviour and that of others, and allows positive risk-taking. It has led to real improvements in clients' progress towards more independent life.

  14. The Objective Borderline Method: A Probabilistic Method for Standard Setting

    ERIC Educational Resources Information Center

    Shulruf, Boaz; Poole, Phillippa; Jones, Philip; Wilkinson, Tim

    2015-01-01

    A new probability-based standard setting technique, the Objective Borderline Method (OBM), was introduced recently. This was based on a mathematical model of how test scores relate to student ability. The present study refined the model and tested it using 2500 simulated data-sets. The OBM was feasible to use. On average, the OBM performed well…

  15. Comorbid bipolar disorder and borderline personality disorder and history of suicide attempts.

    PubMed

    Zimmerman, Mark; Martinez, Jennifer; Young, Diane; Chelminski, Iwona; Morgan, Theresa A; Dalrymple, Kristy

    2014-06-01

    Both bipolar disorder and borderline personality disorder are associated with elevated rates of attempted suicide; however, no studies have examined whether there is an independent, additive risk for suicide attempts in patients diagnosed with both disorders. In the present study from the Rhode Island Methods to Improve Diagnostic Assessment and Services (MIDAS) project, 3,465 psychiatric outpatients were interviewed with semistructured interviews. Compared to the bipolar patients without borderline personality disorder, the patients diagnosed with both bipolar and borderline personality disorder were significantly more likely to have made a prior suicide attempt. The patients with borderline personality disorder and bipolar disorder were nonsignificantly more likely than the borderline patients without bipolar disorder to have made a prior suicide attempt. Bipolar disorder and borderline personality disorder were each associated with an increased rate of suicide attempts. The co-occurrence of these disorders conferred an additive risk, although the influence of borderline personality disorder was greater than that of bipolar disorder.

  16. Pleiotrophin inhibits melanogenesis via Erk1/2-MITF signaling in normal human melanocytes.

    PubMed

    Choi, Woo Jong; Kim, Misun; Park, Ji-Youn; Park, Tae Jun; Kang, Hee Young

    2015-01-01

    Pleiotrophin (PTN) is a secreted heparin-binding protein that is involved in various biological functions of cell growth and differentiation. Little is known about the effects of PTN on the melanocyte function and skin pigmentation. In this study, we investigated whether PTN would affect melanogenesis. PTN was expressed in melanocytes and fibroblasts of human skin. Transfection studies revealed that PTN decreased melanogenesis, probably through MITF degradation via Erk1/2 activation in melanocytes. The inhibitory action of PTN in pigmentation was further confirmed in ex vivo cultured skin and in the melanocytes cocultured with fibroblasts. These findings suggest that PTN is a crucial factor for the regulation of melanogenesis in the skin.

  17. Serum Antibodies to Melanocytes in Patients With Vitiligo Are Predictors of Disease Progression.

    PubMed

    Jimenez-Brito, Gustavo; Garza-de-La-Peña, Eduardo; Pérez-Romano, Beatriz; Ruiz-Argüelles, Alejandro

    2016-01-01

    The aim of this study was to investigate whether the amount of serum antibodies to melanocyte antigens could predict clinical activity or disease progression in patients with vitiligo. A solid-phase enzyme immunoassay was developed to semiquantitate serum antibodies to a human melanocyte extract and was used in 127 patients, 93 of whom showed clinical progression of the disease, while the remaining 34 were quiescent. Results showed different values for clinical sensitivity and specificity depending on the cutoff level for decision, but the overall performance of the test was adequate and supported statistical significance to predict clinical activity/progression or quietness of the disease process. The test might prove useful in deciding the indication and aggressiveness of immunosuppressive therapy in patients with vitiligo. Previous findings suggest that melanocyte-specific antibodies might play a pathogenetic role in the depletion of melanocytes, which characterizes this disorder, and that this depletion might be due to apoptosis following antibody internalization.

  18. EdnrB governs regenerative response of melanocyte stem cells by crosstalk with Wnt signaling

    PubMed Central

    Takeo, Makoto; Lee, Wendy; Rabbani, Piul; Sun, Qi; Hu, Hai; Lim, Chae Ho; Manga, Prashiela; Ito, Mayumi

    2017-01-01

    Delineating the crosstalk between distinct signaling pathways is key to understanding the diverse and dynamic responses of adult stem cells during tissue regeneration. Here we demonstrate that the Edn/EdnrB signaling pathway can interact with other signaling pathways to elicit distinct stem cell functions during tissue regeneration. EdnrB signaling promotes proliferation and differentiation of melanocyte stem cells (McSCs), dramatically enhancing the regeneration of hair and epidermal melanocytes. This effect is dependent upon active Wnt signaling that is initiated by Wnt ligand secretion from the hair follicle epithelial niche. Further, this Wnt-dependent EdnrB signaling can rescue the defects in melanocyte regeneration caused by Mc1R loss. This suggests that targeting Edn/EdnrB signaling in McSCs can be a therapeutic approach to promote photoprotective-melanocyte regeneration, which may be useful for those with increased risk of skin cancers due to Mc1R variants. PMID:27134165

  19. ARP101 inhibits α-MSH-stimulated melanogenesis by regulation of autophagy in melanocytes.

    PubMed

    Kim, Eun Sung; Jo, Yoon Kyung; Park, So Jung; Chang, Huikyoung; Shin, Ji Hyun; Choi, Eun Sun; Kim, Jun Bum; Seok, Su Hyeon; Kim, Jae-Sung; Oh, Jeong Su; Kim, Myoung-Hwan; Lee, Eunjoo H; Cho, Dong-Hyung

    2013-12-11

    Autophagy is a cooperative process between autophagosomes and lysosomes that degrades cellular organelles. Although autophagy regulates the turnover of cellular components, its role in melanogenesis is not clearly established. Previously, we reported that ARP101 induces autophagy in various cancer cells. Here, we show that ARP101 inhibits melanogenesis by regulation of autophagy. ARP101 inhibited α-MSH-stimulated melanin synthesis and suppressed the expression of tyrosinase and TRP1 in immortalized mouse melanocytes. ARP101 also induced autophagy in melanocytes. Knockdown of ATG5 reduced both anti-melanogenic activity and autophagy mediated by ARP101 in α-MSH treated melanocytes. Electron microscopy analysis further revealed that autophagosomes engulf melanin or melanosome in α-MSH and ARP101-treated cells. Collectively, our results suggest that ARP101 inhibits α-MSH-stimulated melanogenesis through the activation of autophagy in melanocytes.

  20. Modulation of Melanogenesis and Antioxidant Status of Melanocytes in Response to Phototoxic Action of Doxycycline.

    PubMed

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

    2015-11-01

    Doxycycline is a commonly used tetracycline antibiotic showing the broad spectrum of antibacterial action. However, the use of this antibiotic is often connected with the risk of phototoxic reactions that lead to various skin disorders. One of the factors influencing the photosensitivity reactions is the melanin content in melanocytes. In this study, the impact of doxycycline and UVA irradiation on cell viability, melanogenesis and antioxidant defense system in cultured normal human epidermal melanocytes (HEMn-DP) was examined. The exposure of cells to doxycycline and UVA radiation resulted in concentration-dependent loss in melanocytes viability and induced melanin biosynthesis. Significant changes were stated in cellular antioxidant enzymes activity: SOD, CAT and GPx, which indicates alterations of antioxidant defense system. The results obtained in vitro may explain the mechanisms of phototoxic reactions that occur in normal human epidermal melanocytes in vivo after exposure of skin to doxycycline and UVA radiation.

  1. Molecular mechanisms of gravity-dependent signaling in human melanocytic cells involve cyclic GMP

    NASA Astrophysics Data System (ADS)

    Ivanova, Krassimira; Lambers, Britta; Block, Ingrid; Bromeis, Birgit; Das, Pranab K.; Gerzer, Rupert

    2005-08-01

    Gravity alteration (micro- and hypergravity) is known to influence cell functions. As guanosine 3',5'-cyclic monophosphate (cGMP) is an important messenger in melanocyte signaling we have compared the regulation of cGMP levels in human melanocytes and melanoma cells with different metastatic potential under hypergravity conditions. We were able to demonstrate that long-term exposure to hypergravity stimulates cGMP efflux in cultured human melanocytes and non- metastatic melanoma cells, whereas highly metastatic melanoma cells appear to be insensitive to hypergravity, most probably, due to an up-regulated cGMP efflux at 1g. Here we report that these effects are associated with the expression of the multidrug resistance proteins 4 and 5 known to act as selective export pumps for amphiphilic anions like cGMP. Thus, an altered gravity vector may induce cGMP-dependent signaling events in melanocytic cells that could be important for malignant transformation.

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

    PubMed

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

    2014-10-01

    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 EC50 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.

  3. NF1 loss induces senescence during human melanocyte differentiation in an iPSC-based model.

    PubMed

    Larribere, Lionel; Wu, Huizi; Novak, Daniel; Galach, Marta; Bernhardt, Mathias; Orouji, Elias; Weina, Kasia; Knappe, Nathalie; Sachpekidis, Christos; Umansky, Ludmila; Beckhove, Philipp; Umansky, Viktor; De Schepper, Sofie; Kaufmann, Dieter; Ballotti, Robert; Bertolotto, Corine; Utikal, Jochen

    2015-07-01

    Neurofibromatosis type 1 (NF1) is a frequent genetic disease leading to the development of Schwann cell-derived neurofibromas or melanocytic lesions called café-au-lait macules (CALMs). The molecular mechanisms involved in CALMs formation remain largely unknown. In this report, we show for the first time pathophysiological mechanisms of abnormal melanocyte differentiation in a human NF1(+/-) -induced pluripotent stem cell (iPSC)-based model. We demonstrate that NF1 patient-derived fibroblasts can be successfully reprogrammed in NF1(+/-) iPSCs with active RAS signaling and that NF1 loss induces senescence during melanocyte differentiation as well as in patient's-derived CALMs, revealing a new role for NF1 in the melanocyte lineage.

  4. Atypical histopathologic features in a melanocytic nevus after cryotherapy and pregnancy.

    PubMed

    Wilford, Casey E; Brantley, Julie S; Diwan, A Hafeez

    2014-10-01

    Melanocytic nevi can undergo clinical and histopathologic changes during pregnancy, as well as after various forms of surgical and nonsurgical trauma. We report the case of a 9-month postpartum 29-year-old female who presented to her dermatologist with a clinically worrisome nevus. This nevus had been treated with liquid nitrogen by her primary care physician 6 months prior to presentation. Histopathologic evaluation revealed a crowded proliferation of atypical melanocytes at the dermal-epidermal junction overlying a scar. The dermal component contained scattered mitotic figures. A combined MART-1, tyrosinase and Ki-67 immunohistochemical study showed foci of increased melanocytic proliferation. These atypical features were interpreted as associated with both the prior cryotherapy, as well as her recent pregnancy. Knowledge of the clinical context in evaluating difficult melanocytic lesions is essential.

  5. Pharmacological interventions for borderline personality disorder

    PubMed Central

    Stoffers, Jutta; Völlm, Birgit A; Rücker, Gerta; Timmer, Antje; Huband, Nick; Lieb, Klaus

    2014-01-01

    Background Drugs are widely used in borderline personality disorder (BPD) treatment, chosen because of properties known from other psychiatric disorders (“off-label use”), mostly targeting affective or impulsive symptom clusters. Objectives To assess the effects of drug treatment in BPD patients. Search methods We searched bibliographic databases according to the Cochrane Developmental, Psychosocial and Learning Problems Group strategy up to September 2009, reference lists of articles, and contacted researchers in the field. Selection criteria Randomised studies comparing drug versus placebo, or drug versus drug(s) in BPD patients. Outcomes included total BPD severity, distinct BPD symptom facets according to DSM-IV criteria, associated psychopathology not specific to BPD, attrition and adverse effects. Data collection and analysis Two authors selected trials, assessed quality and extracted data, independently. Main results Twenty-eight trials involving a total of 1742 trial participants were included. First-generation antipsychotics (flupenthixol decanoate, haloperidol, thiothixene); second-generation antipsychotics (aripirazole, olanzapine, ziprasidone), mood stabilisers (carbamazepine, valproate semisodium, lamotrigine, topiramate), antidepressants (amitriptyline, fluoxetine, fluvoxamine, phenelzine sulfate, mianserin), and dietary supplementation (omega-3 fatty acid) were tested. First-generation antipsychotics were subject to older trials, whereas recent studies focussed on second-generation antipsychotics and mood stabilisers. Data were sparse for individual comparisons, indicating marginal effects for first-generation antipsychotics and antidepressants. The findings were suggestive in supporting the use of second-generation antipsychotics, mood stabilisers, and omega-3 fatty acids, but require replication, since most effect estimates were based on single studies. The long-term use of these drugs has not been assessed. Adverse event data were scarce

  6. [Affective mentalizing in Addictive Borderline Personality: A literature review].

    PubMed

    Lecointe, P; Bernoussi, A; Masson, J; Schauder, S

    2016-10-01

    This literature review concerns affective mentalizing in borderline addictive personality. This concept postulates the group between addictions and borderline personalities may correspond to Personality Disorders (PDs). First, we will present conceptualizations and evaluations of affective mentalizing. The latter refers to one dimension of mentalization, a process by which an individual interprets his/her mental states and those of others. Lecours and Bouchard proposed a hierarchic model: the Élaboration verbale de l'affect (EVA). They also developed an empiric methodology: the Grille de l'élaboration verbale de l'affect (GEVA). The methodological approach of Lecours fulfils the requirements made by Cho-Kain, Gunderson and Luyten, involving a narrower operationalization of the mentalization concept through the evaluation of its dimensions. Conceptualizations and evaluations enabled focus on mentalization psychopathology. Fonagy and Bateman studied this latter in the subjects with PDs, particularly in Borderline Personality Disorders (BPD). We describe mentalization failure, its etiology and consequences in the BPD. Several forms of mentalization psychopathology are identified. Its etiology is largely environmental. Fonagy and Bateman developed the optimum developmental model of mentalization and referred to it to explain etiology of mentalization failure in BPD. Consequences of mentalization failure explicate its functioning. Mentalization may be considered as essential in their comprehension and their care. Research about mentalization of PDs does not integrate addiction as one comorbidity factor. However, Allen, Fonagy and Bateman describe a bidirectional interaction between mentalization failure and addiction. We propose to examine the mentalization of Borderline Addictive Personality. This concept groups addictions and borderline personalities in just one clinical entity other than their links of co-morbidities.

  7. Prostaglandin E{sub 2} regulates melanocyte dendrite formation through activation of PKC{zeta}

    SciTech Connect

    Scott, Glynis Fricke, Alex; Fender, Anne; McClelland, Lindy; Jacobs, Stacey

    2007-11-01

    Prostaglandins are lipid signaling intermediates released by keratinocytes in response to ultraviolet irradiation (UVR) in the skin. The main prostaglandin released following UVR is PGE{sub 2}, a ligand for 4 related G-protein-coupled receptors (EP{sub 1}, EP{sub 2}, EP{sub 3} and EP{sub 4}). Our previous work established that PGE{sub 2} stimulates melanocyte dendrite formation through activation of the EP{sub 1} and EP{sub 3} receptors. The purpose of the present report is to define the signaling intermediates involved in EP{sub 1}- and EP{sub 3}-dependent dendrite formation in human melanocytes. We recently showed that activation of the atypical PKC{zeta} isoform stimulates melanocyte dendricity in response to treatment with lysophosphatidylcholine. We therefore examined the potential contribution of PKC{zeta} activation on EP{sub 1}- and EP{sub 3}-dependent dendrite formation in melanocytes. Stimulation of the EP{sub 1} and EP{sub 3} receptors by selective agonists activated PKC{zeta}, and inhibition of PKC{zeta} activation abrogated EP{sub 1}- and EP{sub 3}-receptor-mediated melanocyte dendricity. Because of the importance of Rho-GTP binding proteins in the regulation of melanocyte dendricity, we also examined the effect of EP{sub 1} and EP{sub 3} receptor activation on Rac and Rho activity. Neither Rac nor Rho was activated upon treatment with EP{sub 1,3}-receptor agonists. We show that melanocytes express only the EP{sub 3A1} isoform, but not the EP{sub 3B} receptor isoform, previously associated with Rho activation, consistent with a lack of Rho stimulation by EP{sub 3} agonists. Our data suggest that PKC{zeta} activation plays a predominant role in regulation of PGE{sub 2}-dependent melanocyte dendricity.

  8. Sensitivity of mouse Skh:HR-2 to ultraviolet radiation: melanocyte inactivation

    SciTech Connect

    Warren, R.; Gardner, P.A.; Reed, J.C.

    1987-03-01

    The hairless mouse, Skh:HR-2, was exposed to doses of ultraviolet (UV) radiation known to induce skin pigmentation. Three parameters associated with perturbations in skin pigmentation were monitored following UV exposure. These include spectroscopy (skin darkness), histology (melanocyte density), and biochemistry (melanin). Within 90 min of UV exposure, the skin became lighter. This was associated with a reduction of quantifiable melanin and the inactivation of epidermal melanocytes.

  9. Regulatory effects of heat on normal human melanocyte growth and melanogenesis: comparative study with UVB.

    PubMed

    Nakazawa, K; Sahuc, F; Damour, O; Collombel, C; Nakazawa, H

    1998-06-01

    Although energy-rich ultraviolet B (UVB) is considered to be primarily responsible for most of the effects associated with solar radiation, small energy recorded as heat appears to contribute to the biologic effects of solar radiation on the skin. We compared the effects of heat and UVB on normal human melanocyte functions. In monolayer culture the following was found. (i) Heat-treated melanocytes showed an increased dendricity and exhibited a larger cell body compared with nontreated melanocytes. (ii) After multiple treatments with UVB (20 mJ per cm2, 312 nm) or heat (42 degrees C for 1 h) for 3 d, melanocytes had a lower survival than nontreated melanocytes, but they resumed proliferation within 6 d in the same manner as seen in control. (iii) The expression levels of cell cycle regulators, p53 and p21 proteins, were increased after multiple treatments with UVB or heat. (iv) The tyrosinase (dopa-oxidase) activity per cell was increased after the multiple treatments with UVB or heat. (v) The number of dopa-positive melanocytes in coculture with keratinocytes in epithelial sheets was greatly increased by UVB or heat treatments. (vi) Similarly, the increased number of tyrosinase-related protein 1 positive melanocytes was seen in skin equivalents after UVB (100 mJ per cm2) or heat (42 degrees C for 1 h) treatments for 7 d. These results suggest that heat shares significant biologic activities with UVB in melanocyte functions. These results could be considered as one of the protective or adaptive responses of the skin pigmentary system to the environment.

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

    PubMed Central

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

    2015-01-01

    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.—Adini, I., Adini, A., Bazinet, L., Watnick, R. S., Bielenberg, D. R., and D’Amato, R. J. Melanocyte pigmentation inversely correlates with MCP-1 production and angiogenesis-inducing potential. PMID:25406462

  11. A new, rapid, microwave-stimulated method of staining melanocytic lesions.

    PubMed

    Leong, A S; Gilham, P

    1989-03-01

    A new and sensitive method of staining melanocytic lesions is described. Tissue sections covered by a solution of colloidal silver nitrate are exposed to microwaves for 45 sec in a domestic oven to produce clean, crisp staining of melanocytes and melanoma cells, often showing long delicate dendritic cell processes. The staining technique does not stain other pigments or argyrophilic tissues and is shown to be more sensitive than the standard Masson-Fontana procedure.

  12. NFIB is a governor of epithelial-melanocyte stem cell behaviour in a shared niche.

    PubMed

    Chang, Chiung-Ying; Pasolli, H Amalia; Giannopoulou, Eugenia G; Guasch, Géraldine; Gronostajski, Richard M; Elemento, Olivier; Fuchs, Elaine

    2013-03-07

    Adult stem cells reside in specialized niches where they receive environmental cues to maintain tissue homeostasis. In mammals, the stem cell niche within hair follicles is home to epithelial hair follicle stem cells and melanocyte stem cells, which sustain cyclical bouts of hair regeneration and pigmentation. To generate pigmented hairs, synchrony is achieved such that upon initiation of a new hair cycle, stem cells of each type activate lineage commitment. Dissecting the inter-stem-cell crosstalk governing this intricate coordination has been difficult, because mutations affecting one lineage often affect the other. Here we identify transcription factor NFIB as an unanticipated coordinator of stem cell behaviour. Hair follicle stem-cell-specific conditional targeting of Nfib in mice uncouples stem cell synchrony. Remarkably, this happens not by perturbing hair cycle and follicle architecture, but rather by promoting melanocyte stem cell proliferation and differentiation. The early production of melanin is restricted to melanocyte stem cells at the niche base. Melanocyte stem cells more distant from the dermal papilla are unscathed, thereby preventing hair greying typical of melanocyte stem cell differentiation mutants. Furthermore, we pinpoint KIT-ligand as a dermal papilla signal promoting melanocyte stem cell differentiation. Additionally, through chromatin-immunoprecipitation with high-throughput-sequencing and transcriptional profiling, we identify endothelin 2 (Edn2) as an NFIB target aberrantly activated in NFIB-deficient hair follicle stem cells. Ectopically induced Edn2 recapitulates NFIB-deficient phenotypes in wild-type mice. Conversely, endothelin receptor antagonists and/or KIT blocking antibodies prevent precocious melanocyte stem cell differentiation in the NFIB-deficient niche. Our findings reveal how melanocyte and hair follicle stem cell behaviours maintain reliance upon cooperative factors within the niche, and how this can be uncoupled in

  13. Complete regression of a melanocytic nevus after epilation with diode laser therapy

    PubMed Central

    Boleira, Manuela; de Almeida Balassiano, Laila Klotz; Jeunon3, Thiago

    2015-01-01

    The use of lasers and intense pulsed light (IPL) technology has become an established practice in dermatology and aesthetic medicine. The use of laser therapy and IPL in the treatment of pigmented melanocytic lesions is a controversial issue. We report clinical, dermoscopic and histological changes of a completely regressed pigmented melanocytic nevus after hair removal treatment with the LightSheer™ Diode Laser (Lumenis Ltd, Yokneam, Israel). PMID:26114064

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

    NASA Astrophysics Data System (ADS)

    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.

  15. Cooperative response of keratinocytes and melanocytes to UV radiation during PUVA therapy

    NASA Astrophysics Data System (ADS)

    Stolnitz, Mikhail M.; Baskakov, Pavel V.; Peshkova, Anna Y.

    1999-03-01

    The mathematical model of processes in UV-irradiated furocoumarin-sensitized epidermis is presented taking into account the mutual influence of keratinocytes and melanocytes populations. The model describes epidermis as a hierarchical structure on tissue (keratinocytes-melanocytes cooperation, melanin screen formation), cellular (proliferation and differentiation, transitions between subpopulations), subcellular (cell movement on mitotic cycle, generation, maturing and migration of melanosomes), and molecular (melanin synthesis, processes of DNA damage and repair, molecular signal transduction) levels.

  16. NFIB is a governor of epithelial–melanocyte stem cell behaviour in a shared niche

    PubMed Central

    Chang, Chiung-Ying; Pasolli, H. Amalia; Giannopoulou, Eugenia G.; Guasch, Géraldine; Gronostajski, Richard M.; Elemento, Olivier; Fuchs, Elaine

    2013-01-01

    Adult stem cells reside in specialized niches where they receive environmental cues to maintain tissue homeostasis. In mammals, the stem cell niche within hair follicles is home to epithelial hair follicle stem cells and melanocyte stem cells, which sustain cyclical bouts of hair regeneration and pigmentation1–4. To generate pigmented hairs, synchrony is achieved such that upon initiation of a new hair cycle, stem cells of each type activate lineage commitment2,5. Dissecting the inter-stem-cell crosstalk governing this intricate coordination has been difficult, because mutations affecting one lineage often affect the other. Here we identify transcription factor NFIB as an unanticipated coordinator of stem cell behaviour. Hair follicle stem-cell-specific conditional targeting of Nfib in mice uncouples stem cell synchrony. Remarkably, this happens not by perturbing hair cycle and follicle architecture, but rather by promoting melanocyte stem cell proliferation and differentiation. The early production of melanin is restricted to melanocyte stem cells at the niche base. Melanocyte stem cells more distant from the dermal papilla are unscathed, thereby preventing hair greying typical of melanocyte stem cell differentiation mutants. Furthermore, we pinpoint KIT-ligand as a dermal papilla signal promoting melanocyte stem cell differentiation. Additionally, through chromatin-immunoprecipitation with high-throughput-sequencing and transcriptional profiling, we identify endothelin 2 (Edn2) as an NFIB target aberrantly activated in NFIB-deficient hair follicle stem cells. Ectopically induced Edn2 recapitulates NFIB-deficient phenotypes in wild-type mice. Conversely, endothelin receptor antagonists and/or KIT blocking antibodies prevent precocious melanocyte stem cell differentiation in the NFIB-deficient niche. Our findings reveal how melanocyte and hair follicle stem cell behaviours maintain reliance upon cooperative factors within the niche, and how this can be uncoupled

  17. Nitric oxide enhances the sensitivity of alpaca melanocytes to respond to {alpha}-melanocyte-stimulating hormone by up-regulating melanocortin-1 receptor

    SciTech Connect

    Dong, Yanjun; Cao, Jing; Wang, Haidong; Zhang, Jie; Zhu, Zhiwei; Bai, Rui; Hao, HuanQing; He, Xiaoyan; Fan, Ruiwen; Dong, Changsheng

    2010-06-11

    Nitric oxide (NO) and {alpha}-melanocyte-stimulating hormone ({alpha}-MSH) have been correlated with the synthesis of melanin. The NO-dependent signaling of cellular response to activate the hypothalamopituitary proopiomelanocortin system, thereby enhances the hypophysial secretion of {alpha}-MSH to stimulate {alpha}-MSH-receptor responsive cells. In this study we investigated whether an NO-induced pathway can enhance the ability of the melanocyte to respond to {alpha}-MSH on melanogenesis in alpaca skin melanocytes in vitro. It is important for us to know how to enhance the coat color of alpaca. We set up three groups for experiments using the third passage number of alpaca melanocytes: the control cultures were allowed a total of 5 days growth; the UV group cultures like the control group but the melanocytes were then irradiated everyday (once) with 312 mJ/cm{sup 2} of UVB; the UV + L-NAME group is the same as group UV but has the addition of 300 {mu}M L-NAME (every 6 h). To determine the inhibited effect of NO produce, NO produces were measured. To determine the effect of the NO to the key protein and gene of {alpha}-MSH pathway on melanogenesis, the key gene and protein of the {alpha}-MSH pathway were measured by quantitative real-time PCR and Western immunoblotting. The results provide exciting new evidence that NO can enhance {alpha}-MSH pathway in alpaca skin melanocytes by elevated MC1R. And we suggest that the NO pathway may more rapidly cause the synthesis of melanin in alpaca skin under UV, which at that time elevates the expression of MC1R and stimulates the keratinocytes to secrete {alpha}-MSH to enhance the {alpha}-MSH pathway on melanogenesis. This process will be of considerable interest in future studies.

  18. Nitric oxide enhances the sensitivity of alpaca melanocytes to respond to alpha-melanocyte-stimulating hormone by up-regulating melanocortin-1 receptor.

    PubMed

    Dong, Yanjun; Cao, Jing; Wang, Haidong; Zhang, Jie; Zhu, Zhiwei; Bai, Rui; Hao, HuanQing; He, Xiaoyan; Fan, Ruiwen; Dong, Changsheng

    2010-06-11

    Nitric oxide (NO) and alpha-melanocyte-stimulating hormone (alpha-MSH) have been correlated with the synthesis of melanin. The NO-dependent signaling of cellular response to activate the hypothalamopituitary proopiomelanocortin system, thereby enhances the hypophysial secretion of alpha-MSH to stimulate alpha-MSH-receptor responsive cells. In this study we investigated whether an NO-induced pathway can enhance the ability of the melanocyte to respond to alpha-MSH on melanogenesis in alpaca skin melanocytes in vitro. It is important for us to know how to enhance the coat color of alpaca. We set up three groups for experiments using the third passage number of alpaca melanocytes: the control cultures were allowed a total of 5 days growth; the UV group cultures like the control group but the melanocytes were then irradiated everyday (once) with 312 mJ/cm(2) of UVB; the UV+L-NAME group is the same as group UV but has the addition of 300 microM L-NAME (every 6h). To determine the inhibited effect of NO produce, NO produces were measured. To determine the effect of the NO to the key protein and gene of alpha-MSH pathway on melanogenesis, the key gene and protein of the alpha-MSH pathway were measured by quantitative real-time PCR and Western immunoblotting. The results provide exciting new evidence that NO can enhance alpha-MSH pathway in alpaca skin melanocytes by elevated MC1R. And we suggest that the NO pathway may more rapidly cause the synthesis of melanin in alpaca skin under UV, which at that time elevates the expression of MC1R and stimulates the keratinocytes to secrete alpha-MSH to enhance the alpha-MSH pathway on melanogenesis. This process will be of considerable interest in future studies.

  19. Phosphoproteomic Analyses of NRAS(G12) and NRAS(Q61) Mutant Melanocytes Reveal Increased CK2α Kinase Levels in NRAS(Q61) Mutant Cells.

    PubMed

    Posch, Christian; Sanlorenzo, Martina; Vujic, Igor; Oses-Prieto, Juan A; Cholewa, Brian D; Kim, Sarasa T; Ma, Jeffrey; Lai, Kevin; Zekhtser, Mitchell; Esteve-Puig, Rosaura; Green, Gary; Chand, Shreya; Burlingame, Alma L; Panzer-Grümayer, Renate; Rappersberger, Klemens; Ortiz-Urda, Susana

    2016-10-01

    In melanoma, mutant and thereby constantly active neuroblastoma rat sarcoma (NRAS) affects 15-20% of tumors, contributing to tumor initiation, growth, invasion, and metastasis. Recent therapeutic approaches aim to mimic RAS extinction by interfering with critical signaling pathways downstream of the mutant protein. This study investigates the phosphoproteome of primary human melanocytes bearing mutations in the two hot spots of NRAS, NRAS(G12) and NRAS(Q61). Stable isotope labeling by amino acids in cell culture followed by mass spectrometry identified 14,155 spectra of 3,371 unique phosphopeptides mapping to 1,159 proteins (false discovery rate < 2%). Data revealed pronounced PI3K/AKT signaling in NRAS(G12V) mutant cells and pronounced mitogen-activated protein kinase (MAPK) signaling in NRAS(Q61L) variants. Computer-based prediction models for kinases involved, revealed that CK2α is significantly overrepresented in primary human melanocytes bearing NRAS(Q61L) mutations. Similar differences were found in human NRAS(Q61) mutant melanoma cell lines that were also more sensitive to pharmacologic CK2α inhibition compared with NRAS(G12) mutant cells. Furthermore, CK2α levels were pronounced in patient samples of NRAS(Q61) mutant melanoma at the mRNA and protein level. The preclinical findings of this study reveal that codon 12 and 61 mutant NRAS cells have distinct signaling characteristics that could allow for the development of more effective, mutation-specific treatment modalities.

  20. Alpha-melanocyte stimulating hormone inhibits monocytes adhesion to vascular endothelium

    PubMed Central

    Yang, Yang; Zhang, Weihua; Meng, Lin; Yu, Haitao; Lu, Na; Fu, Gang

    2015-01-01

    Inflammation and its subsequent endothelial dysfunction have been reported to play a pivotal role in the initiation and progression of chronic vascular diseases. Inhibiting the attachment of monocytes to endothelium is a potential therapeutic strategy for vascular diseases treatment. α-Melanocyte stimulating hormone is generated from a precursor hormone called proopiomelanocortin by post-translational processing. However, whether α-melanocyte stimulating hormone plays a role in regulating endothelial inflammation is still unknown. In this study, the effects of α-melanocyte stimulating hormone on endothelial inflammation in human umbilical vein endothelial cell lines were investigated. And the result indicated that α-melanocyte stimulating hormone inhibits the expression of endothelial adhesion molecules, including vascular adhesion molecule-1 and E-selectin, thereby attenuating the adhesion of THP-1 cells to the surface of endothelial cells. Mechanistically, α-melanocyte stimulating hormone was found to inhibit NF-κB transcriptional activity. Finally, we found that the effect of α-melanocyte stimulating hormone on endothelial inflammation is dependent on its receptor melanocortin receptor 1. PMID:25898835

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

    SciTech Connect

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

    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.

  2. Recombinant Adeno-Associated Virus Serotype 6 Efficiently Transduces Primary Human Melanocytes

    PubMed Central

    Verdon, Daniel; Chen, Jennifer; Taylor, John A.; Dunbar, P. Rod

    2013-01-01

    The study of melanocyte biology is important to understand their role in health and disease. However, current methods of gene transfer into melanocytes are limited by safety or efficacy. Recombinant adeno-associated virus (rAAV) has been extensively investigated as a gene therapy vector, is safe and is associated with persistent transgene expression without genome integration. There are twelve serotypes and many capsid variants of rAAV. However, a comparative study to determine which rAAV is most efficient at transducing primary human melanocytes has not been conducted. We therefore sought to determine the optimum rAAV variant for use in the in vitro transduction of primary human melanocytes, which could also be informative to future in vivo studies. We have screened eight variants of rAAV for their ability to transduce primary human melanocytes and identified rAAV6 as the optimal serotype, transducing 7–78% of cells. No increase in transduction was seen with rAAV6 tyrosine capsid mutants. The number of cells expressing the transgene peaked at 6–12 days post-infection, and transduced cells were still detectable at day 28. Therefore rAAV6 should be considered as a non-integrating vector for the transduction of primary human melanocytes. PMID:23646140

  3. Pax3 and regulation of the melanocyte-specific tyrosinase-related protein-1 promoter.

    PubMed

    Galibert, M D; Yavuzer, U; Dexter, T J; Goding, C R

    1999-09-17

    Previous work has established that the melanocyte-specific tyrosinase-related protein-1 (TRP-1) promoter is regulated positively by the microphthalmia-associated transcription factor Mitf, acting through the conserved M box and negatively by the T-box factor Tbx2, which can bind two "melanocyte-specific elements" termed the MSEu and MSEi. Both the MSEu and MSEi, which share a 6-base pair GTGTGA consensus, are also recognized by a previously unidentified melanocyte-specific factor, MSF. Here we show using a combination of DNA binding assays, proteolytic clipping, and anti-Pax3 antibodies that MSF is indistinguishable from Pax3, a paired homeodomain transcription factor implicated genetically in melanocyte development and the regulation of the Mitf promoter. Consistent with Pax3 being able to bind the TRP-1 promoter, Pax3 is expressed in melanocytes and melanomas, and TRP-1 promoter activity is up-regulated by Pax3. The results identify a novel role for Pax3 in the expression of TRP-1, and the potential role of Pax3 in the melanocyte lineage is discussed.

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

    PubMed

    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.

  5. MELANOCYTIC GALECTIN-3 IS ASSOCIATED WITH TYROSINASE RELATED PROTEIN-1 AND PIGMENT BIOSYNTHESIS

    PubMed Central

    Chalupa, Allison; Koshoffer, Amy; Galan, Emily; Yu, Lan; Liu, Fu-Tong; Boissy, Raymond E.

    2014-01-01

    Galectin-3 is a family member of the carbohydrate binding proteins widely expressed by many cell types and exhibits multiple cellular functions. We demonstrate that melanocytes express galectin-3, which is predominantly localized to the cell body peripherally along the Golgi zone. Downregulation of galectin-3 in human melanocytes using shRNA technology resulted in reduction of both melanin synthesis and expression/activity of Tyrp-1. In the cell body, galectin-3 co-localizes with melanosome destined cargo, specifically tyrosinase and tyrosinase-related protein-1. We studied melanocytes cultured from patients with forms of Hermansky-Pudlak syndrome containing defects in trafficking steps governed by BLOC-2 (HPS5), BLOC-3 (HPS1) and adaptin-3 (HPS2). We found galectin-3 expression mimicked the defective expression of the tyrosinase cargo in dendrites of HPS-5 melanocytes, but was not altered in HPS1 or HPS2 melanocytes. In addition, galectin-3 co-localized predominantly with the HPS-5 component of BLOC-2 in normal human melanocytes. These data indicate that galectin-3 is a regulatory component in melanin synthesis affecting the expression of Tyrp-1. PMID:25054620

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

    PubMed

    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.

  7. Melanocytes--a novel tool to study mitochondrial dysfunction in Duchenne muscular dystrophy.

    PubMed

    Pellegrini, Camilla; Zulian, Alessandra; Gualandi, Francesca; Manzati, Elisa; Merlini, Luciano; Michelini, Maria E; Benassi, Luisa; Marmiroli, Sandra; Ferlini, Alessandra; Sabatelli, Patrizia; Bernardi, Paolo; Maraldi, Nadir M

    2013-06-01

    Dystrophin is a subsarcolemmal protein that, by linking the actin cytoskeleton to the extracellular matrix via dystroglycans, is critical for the integrity of muscle fibers. Here, we report that epidermal melanocytes, obtained from conventional skin biopsy, express dystrophin with a restricted localization to the plasma membrane facing the dermal-epidermal junction. In addition the full-length muscle isoform mDp427 was clearly detectable in melanocyte cultures as assessed by immunohistochemistry, RNA, and Western blot analysis. Melanocytes of Duchenne muscular dystrophy (DMD) patients did not express dystrophin, and the ultrastructural analysis revealed typical mitochondrial alterations similar to those occurring in myoblasts from the same patients. Mitochondria of melanocytes from DMD patients readily accumulated tetramethylrhodamine methyl ester, indicating that they are energized irrespective of the presence of dystrophin but, at variance from mitochondria of control donors, depolarized upon the addition of oligomycin, suggesting that they are affected by a latent dysfunction unmasked by inhibition of the ATP synthase. Pure melanocyte cultures can be readily obtained by conventional skin biopsies and may be a feasible and reliable tool alternative to muscle biopsy for functional studies in dystrophinopathies. The mitochondrial dysfunction occurring in DMD melanocytes could represent a promising cellular biomarker for monitoring dystrophinopathies also in response to pharmacological treatments.

  8. Understanding Melanocyte Stem Cells for Disease Modeling and Regenerative Medicine Applications.

    PubMed

    Mull, Amber N; Zolekar, Ashwini; Wang, Yu-Chieh

    2015-12-21

    Melanocytes in the skin play an indispensable role in the pigmentation of skin and its appendages. It is well known that the embryonic origin of melanocytes is neural crest cells. In adult skin, functional melanocytes are continuously repopulated by the differentiation of melanocyte stem cells (McSCs) residing in the epidermis of the skin. Many preceding studies have led to significant discoveries regarding the cellular and molecular characteristics of this unique stem cell population. The alteration of McSCs has been also implicated in several skin abnormalities and disease conditions. To date, our knowledge of McSCs largely comes from studying the stem cell niche of mouse hair follicles. Suggested by several anatomical differences between mouse and human skin, there could be distinct features associated with mouse and human McSCs as well as their niches in the skin. Recent advances in human pluripotent stem cell (hPSC) research have provided us with useful tools to potentially acquire a substantial amount of human McSCs and functional melanocytes for research and regenerative medicine applications. This review highlights recent studies and progress involved in understanding the development of cutaneous melanocytes and the regulation of McSCs.

  9. Melanocytic galectin-3 is associated with tyrosinase-related protein-1 and pigment biosynthesis.

    PubMed

    Chalupa, Allison; Koshoffer, Amy; Galan, Emily; Yu, Lan; Liu, Fu-Tong; Boissy, Raymond E

    2015-01-01

    Galectin-3 is a family member of the carbohydrate-binding proteins widely expressed by many cell types and exhibits multiple cellular functions. We demonstrate that melanocytes express galectin-3, which is predominantly localized to the cell body peripherally along the Golgi zone. Downregulation of galectin-3 in human melanocytes using short hairpin RNA technology resulted in the reduction of both melanin synthesis and expression/activity of tyrosinase-related protein-1 (Tyrp-1). In the cell body, galectin-3 colocalizes with melanosome-destined cargo, specifically tyrosinase and Tyrp-1. We studied melanocytes cultured from patients with forms of Hermansky-Pudlak syndrome (HPS) containing defects in trafficking steps governed by biogenesis of lysosome-related organelle complex-2 (BLOC-2) (HPS-5), BLOC-3 (HPS-1), and adaptin-3 (HPS-2). We found that galectin-3 expression mimicked the defective expression of the tyrosinase cargo in dendrites of HPS-5 melanocytes, but it was not altered in HPS-1 or HPS-2 melanocytes. In addition, galectin-3 colocalized predominantly with the HPS-5 component of BLOC-2 in normal human melanocytes. These data indicate that galectin-3 is a regulatory component in melanin synthesis affecting the expression of Tyrp-1.

  10. The effects of IGF1 on the melanogenesis in alpaca melanocytes in vitro.

    PubMed

    Hu, Shuaipeng; Liu, Yu; Yang, Shanshan; Ji, Kaiyuan; Liu, Xuexian; Zhang, Junzhen; Fan, Ruiwen; Dong, Changsheng

    2016-09-01

    In order to investigate the effects of the insulin-like growth factor 1(IGF-1) on alpaca melanocyte in vitro, different dosees of IGF1 (0, 10, 20, 40 ng/ml) were added in the medium of alpaca melanocyte. The RTCA machine was used to monitor the proliferation, quantitative real-time PCR, and western blot to test the relative gene expression, ELISA to test cAMP production, and spectrum method to test the melanin production. The results showed that compared to the normal melanocyte, the proliferation of melanocytes was increased within 60 h following adding IGF1. It also showed that cAMP content produced by melanocytes was increased, microphthalmia-associtated transcription factor (MITF), tyrosinase (TYR) and tyrosinase-related protein 2 (TYRP2) expression was increased, and melanin production with most obvious change in 10 ng/ml supplementary group, when compared with the control group. The results suggested that IGF1 with the dose of 10 ng/ml had the important effects on the melanogenesis in alpaca melanocyte by the cAMP pathway.

  11. Diagnosis problems in a case of ovarian tumor - case presentation.

    PubMed

    Albu, Dinu Florin; Albu, Cristina CrenguŢa; Văduva, Constantin Cristian; Niculescu, Mihaela; Edu, Antoine

    2016-01-01

    Ovarian epithelial tumors are the most common ovarian neoplasms, standing for more than half of all ovarian tumors. Borderline ovarian tumors represent a distinct group recognized by the World Health Organization (WHO), histologically distinct low ovarian carcinomas. They are tumors with low grade of malignancy with good progress and prognosis. The authors present a case of an ovarian tumor with diagnosis problems. It was the case of a 38-year-old patient with no genital pathological history, presenting hypogastric pain, dysmenorrhea, abdominal distension. The imaging performed examinations suggested an ovarian tumor with potential malignancy. The symptoms were nonspecific and the treatment was surgical. The piece was processed by paraffin inclusion and microscopically examined. Although the imaging examinations may be suggestive for potentially malignant lesions, the histopathological relation with the immunohistochemical one is the one that establishes the diagnosis. Following these examinations, there was established an ovarian borderline tumor. This is included in the lesions with low malignancy, the further evolution of the patient being a good one. The purpose of this presentation was the warning of the importance of histopathological examination linked with the immunohistochemical one, although the imaging may present lesions with malignancy criteria. Also, it was performed a literature review of borderline tumors in young women in terms of diagnosis and therapeutic conduct.

  12. The correlation of TRPM1 (Melastatin) mRNA expression with microphthalmia-associated transcription factor (MITF) and other melanogenesis-related proteins in normal and pathological skin, hair follicles and melanocytic nevi

    PubMed Central

    Lu, Song; Slominski, Andrzej; Yang, Sung-Eun; Sheehan, Christine; Ross, Jeffrey; Carlson, J. Andrew

    2010-01-01

    Background Melastatin (TRPM1), a.k.a. transient receptor potential cation channel, subfamily M, member 1 (TRPM-1) regulates melanocyte differentiation and proliferation. TRPM1 is transcriptionally regulated by the essential melanocyte transcription factor MITF (microphthalmia-associated transcription factor). For the most part, MITF expression is preserved during melanoma progression, while TRPM1 mRNA expression decreases or is completely lost. The loss of TRPM1 is associated with melanomas that are more aggressive. Objective To assess the relationship between TRPM1 mRNA expression and the expression of MITF and nine other markers of melanocytes and melanin-related proteins by immunohistochemistry in normal skin, scars, hair follicles and ordinary melanocytic nevi. Methods Samples of normal skin (n = 102; from tumor excisions and plastic procedures), scars (n = 5; from re-excision specimens) and compound melanocytic nevi (n = 4) were evaluated for the presence of TRPM1 mRNA transcripts as detected by chromogenic in situ hybridization (CISH). Immunohistochemical techniques were used to detect melanin-related proteins including: MITF, S100 protein, Mart-1, tyrosinase, Mel5, HMB45, tyrosinase-related protein-1 (TRP1), TRP2 and α-melanocyte stimulating hormone (αMSH). The labeling index (LI) was defined as the number of intraepidermal cells expressing mRNA or protein per one hundred basal keratinocytes. Results A wide range of LI was found for all markers (0–33 positive cells/100 keratinocytes). When these LI were compared, no significant differences in the expression of MITF, S100, Mart1, tyrosinase proteins and TRPM1 mRNA were identified. The LI for TRPM1 mRNA expression ranged from 74% of that for MITF to 86% for tyrosinase. The LI for TRP-1, TRP-2 and Mel5 was similar to that of TRPM1, while HMB-45 had a significantly lower LI than all other markers. TRPM1 mRNA correlated most tightly with MITF and tyrosinase expression (r = 0.81 and 0.68, respectively, both p

  13. Assessment of Borderline Personality Features in Population Samples: Is the Personality Assessment Inventory-Borderline Features Scale Measurement Invariant across Sex and Age?

    ERIC Educational Resources Information Center

    De Moor, Marleen H. M.; Distel, Marijn A.; Trull, Timothy J.; Boomsma, Dorret I.

    2009-01-01

    Borderline personality disorder (BPD) is more often diagnosed in women than in men, and symptoms tend to decline with age. Using a large community sample, the authors investigated whether sex and age differences in four main features of BPD, measured with the "Personality Assessment Inventory-Borderline Features" scale (PAI-BOR; Morey,…

  14. Functional melanocytes are readily reprogrammable from multilineage-differentiating stress-enduring (muse) cells, distinct stem cells in human fibroblasts.

    PubMed

    Tsuchiyama, Kenichiro; Wakao, Shohei; Kuroda, Yasumasa; Ogura, Fumitaka; Nojima, Makoto; Sawaya, Natsue; Yamasaki, Kenshi; Aiba, Setsuya; Dezawa, Mari

    2013-10-01

    The induction of melanocytes from easily accessible stem cells has attracted attention for the treatment of melanocyte dysfunctions. We found that multilineage-differentiating stress-enduring (Muse) cells, a distinct stem cell type among human dermal fibroblasts, can be readily reprogrammed into functional melanocytes, whereas the remainder of the fibroblasts do not contribute to melanocyte differentiation. Muse cells can be isolated as cells positive for stage-specific embryonic antigen-3, a marker for undifferentiated human embryonic stem cells, and differentiate into cells representative of all three germ layers from a single cell, while also being nontumorigenic. The use of certain combinations of factors induces Muse cells to express melanocyte markers such as tyrosinase and microphthalmia-associated transcription factor and to show positivity for the 3,4-dihydroxy-L-phenylalanine reaction. When Muse cell-derived melanocytes were incorporated into three-dimensional (3D) cultured skin models, they localized themselves in the basal layer of the epidermis and produced melanin in the same manner as authentic melanocytes. They also maintained their melanin production even after the 3D cultured skin was transplanted to immunodeficient mice. This technique may be applicable to the efficient production of melanocytes from accessible human fibroblasts by using Muse cells, thereby contributing to autologous transplantation for melanocyte dysfunctions, such as vitiligo.

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

    PubMed Central

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

    2016-01-01

    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. Implications for Practice: 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. PMID:26834159

  16. The beneficial effect on family life in treating borderline personality.

    PubMed

    Gerull, Friederike; Meares, Russell; Stevenson, Janine; Korner, Anthony; Newman, Louise

    2008-01-01

    The harmful effect of borderline patients on their families is an important but relatively neglected aspect of outcome studies. This study concerns changes in perceived quality of relationships with partners and children of 24 patients suffering Borderline Personality Disorder (BPD) after 12 months of treatment with the Conversational Model (CM). They were compared to 21 parents with BPD receiving "Treatment as Usual" (TAU) from their referring clinicians for the same period. Both groups developed naturalistically giving the study a quasi-experimental design. The Social Adjustment Scale (SAS-SR) was administered on intake and again after 12 months. The subscales dealing with relationships with children, with partners and with the family unit were scored and compared between groups. It was found that the perceived relationships with children and partners improved significantly for the CM group but not for the TAU group.

  17. Cerebellar cognitive affective syndrome presented as severe borderline personality disorder.

    PubMed

    Pesic, Danilo; Peljto, Amir; Lukic, Biljana; Milovanovic, Maja; Svetozarevic, Snezana; Lecic Tosevski, Dusica

    2014-01-01

    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.

  18. Attachment and its vicissitudes in borderline personality disorder.

    PubMed

    Levy, Kenneth N; Beeney, Joseph E; Temes, Christina M

    2011-02-01

    This article reviews the recent literature on attachment and attachment-related constructs in borderline personality disorder, with attention given to how recent findings in this area may inform understanding of the mechanisms underlying the etiology, maintenance, and treatment of the disorder. Most findings on this topic have stemmed from three major areas of research, each of which is reviewed in this article: 1) developmental psychopathology studies; 2) experimental psychopathology studies, particularly those using a neuroscience approach; and 3) treatment studies that have examined variables relevant to attachment. Overall, these findings suggest that attachment and related constructs may factor greatly into the underlying psychopathology of borderline personality disorder and may significantly impact the process and outcome of psychotherapy for the disorder. These findings are discussed as they relate to existing theories and ongoing debates in the field, and the implications for future research and clinical practice are highlighted.

  19. Dysfunctional beliefs and psychopathology in Borderline Personality Disorder.

    PubMed

    Bhar, Sunil S; Brown, Gregory K; Beck, Aaron T

    2008-04-01

    This study examined the factor structure of the Borderline Personality Disorder subscale of the Personality Beliefs Questionnaire (PBQ-BPD; Butler, Brown, Beck, & Grisham, 2002), and the relationships between the emergent factors and psychopathology. The sample comprised 184 patients diagnosed with borderline personality disorder (BPD). Exploratory factor analysis yielded three factors relating respectively to dependency, distrust, and the belief that one should act preemptively to avoid threat. Although the three factors were significantly associated with depression, only dependency and distrust significantly correlated with hopelessness. Distrust was the sole factor that correlated significantly with suicide ideation. These findings support the dimensional structure of the PBQ-BPD. Given its multidimensional structure, the scale can be used as a measure of belief profiles associated with BPD and as an aid to conceptualizing beliefs underlying a range of psychopathology associated with patients with BPD.

  20. The Transcription Factors Ets1 and Sox10 Interact During Murine Melanocyte Development

    PubMed Central

    Saldana-Caboverde, Amy; Perera, Erasmo M.; Watkins-Chow, Dawn; Hansen, Nancy F.; Vemulapalli, Meghana; Mullikin, James C; Pavan, William J.; Kos, Lidia

    2015-01-01

    Melanocytes, the pigment-producing cells, arise from multipotent neural crest (NC) cells during embryogenesis. Many genes required for melanocyte development were identified using mouse pigmentation mutants. The variable spotting mouse pigmentation mutant arose spontaneously at the Jackson Laboratory. We identified a G-to-A nucleotide transition in exon 3 of the Ets1 gene in variable spotting, which results in a missense G102E mutation. Homozygous variable spotting mice exhibit sporadic white spotting. Similarly, mice carrying a targeted deletion of Ets1 exhibit hypopigmentation; nevertheless, the function of Ets1 in melanocyte development is unknown. The transcription factor Ets1 is widely expressed in developing organs and tissues, including the NC. In the chick, Ets1 is required for the expression of Sox10, a transcription factor critical for the development of various NC derivatives, including melanocytes. We show that Ets1 is required early for murine NC cell and melanocyte precursor survival in vivo. Given the importance of Ets1 for Sox10 expression in the chick, we investigated a potential genetic interaction between these genes by comparing the hypopigmentation phenotypes of single and double heterozygous mice. The incidence of hypopigmentation in double heterozygotes was significantly greater than in single heterozygotes. The area of hypopigmentation in double heterozygotes was significantly larger than would be expected from the addition of the areas of hypopigmentation of single heterozygotes, suggesting that Ets1 and Sox10 interact synergistically in melanocyte development. Since Sox10 is also essential for enteric ganglia development, we examined the distal colons of Ets1 null mutants and found a significant decrease in enteric innervation, which was exacerbated by Sox10 heterozygosity. At the molecular level, Ets1 was found to activate an enhancer critical for Sox10 expression in NC-derived structures. Furthermore, enhancer activation was

  1. Melanocytic lesions of the genital area with attention given to atypical genital nevi.

    PubMed

    Ribé, Adriana

    2008-11-01

    Melanocytic lesions of the genital area are rare. They arise mainly in the vulva, although they can also occur less frequently in the perineum, mons pubis and male genitalia and represent 10-12% of pigmented lesions of White women. These pigmented lesions include melanocytic nevi, lentigines, melanocytic nevi with architectural disorder and atypia of melanocytes (dysplastic nevi) and melanomas with microscopic features similar to those seen elsewhere on the body. There is a small subset of benign nevi named atypical melanocytic nevi of the genital type (AMNGT) that occur in young women, with distinctive histologic features in some cases overlapping morphologically with those of melanoma. Thus, it is important to distinguish AMNGT from melanomas in terms of prognosis and treatment. We retrieved 58 cases of genital pigmented lesions diagnosed at our hospital from 1986 to 2008 to evaluate their clinicopathologic features with especial consideration to those cases with atypical features. Thirty-two cases (55%) were common nevi, 10 (17%) lentigines, 6 (10%) melanomas, 3 (5%) dysplastic nevi and 1 blue nevus. Six cases (10%) corresponded to AMNGT and were taken from women with a median age of 21 years. All cases showed symmetry, and the melanocytic proliferation was well demarcated at the lateral margins. The junctional component was very prominent and formed by round or fusiform nests with common retraction artifact and/or cellular dyshesion or as a single cell proliferation with mild (33%) to moderate (67%) cytologic atypia, focal pagetoid spread (17%) and a benign-appearing dermal component (83%) with maturation and dense eosinophilic fibrosis in the superficial dermis. Neither nuclear atypia of melanocytes in the superficial dermis nor dermal mitoses were observed. AMNGT were excised, and no recurrences were recorded in the follow up (median 10.5 years). Therefore, it seems that there is no evidence that AMNGT are precursors of dysplastic nevi or melanomas.

  2. Cytosolic dsDNA triggers apoptosis and pro-inflammatory cytokine production in normal human melanocytes.

    PubMed

    Wang, Suiquan; Liu, Dongyin; Ning, Weixuan; Xu, Aie

    2015-04-01

    Considerable evidence implicates that viral infection might be a participant factor in the pathogenesis of vitiligo. However, it is still unclear how viral infection leads to the melanocyte destruction. To elucidate the effects of viral dsDNA on the viability and cytokine synthesis of normal human melanocytes and to explore the underlying mechanisms, primary cultured normal human melanocytes were transfected with poly(dA:dT). The results demonstrated that poly(dA:dT) triggered apoptosis instead of pyroptosis in melanocytes. Knocking down AIM2 or RIG-I by RNA interference partially reduced the poly(dA:dT)-induced LDH release, suggesting the involvement of both nucleic acid sensors in the process of melanocyte death. Poly(dA:dT) induced the expression of pro-inflammatory cytokine genes including IFN-β, TNF-α, IL-6 and IL-8 as well, whereas the pro-inflammatory cytokine production was suppressed by RIG-I siRNA, but not by AIM2 siRNA. Poly(dA:dT) treatment increased the phosphorylation of p38 and JNK and NFκB. Accordingly, NFκB inhibitor Bay 11-7082 and JNK inhibitor SP600125 blocked the induction of the cytokine genes except IFN-β. The production of IL6 and IL8 was also suppressed by p38 inhibitor SB203580. On the contrary, the Poly(dA:dT)-induced melanocyte death was only decreased by SP600125. This study provides the possible mechanism of melanocyte destruction and immuno-stimulation in vitiligo by innate immune response following viral infection.

  3. Differentiating the stem cell pool of human hair follicle outer root sheath into functional melanocytes.

    PubMed

    Schneider, Marie; Dieckmann, Christina; Rabe, Katrin; Simon, Jan-Christoph; Savkovic, Vuk

    2014-01-01

    Bench-to-Bedside concepts for regenerative therapy place significant weight on noninvasive approaches, with harvesting of the starting material as a header. This is particularly important in autologous treatments, which use one's bodily constituents for therapy. Precisely the stretch between obtaining therapeutic elements invasively and noninvasively places non-intrusive "sampling" rather than "biopsy" in the center of the road map of developing an autologous regenerative therapy. We focus on such a noninvasively available source of adult stem cells that we carry with us throughout our life, available at our fingertips-or shall we say hair roots, by a simple plucking of hair: the human hair follicle. This chapter describes an explant procedure for cultivating melanocytes differentiated from the stem cell pool of the hair follicle Outer Root Sheath (ORS). In vivo, the most abundant derivatives of the heterogeneous ORS stem cell pool are epidermal cells-melanocytes and keratinocytes which complete their differentiation-either spontaneously or upon picking up regenerative cues from damaged skin-and migrate from the ORS towards the adjacent regenerating area of the epidermis. We have taken advantage of the ORS developmental potential by optimizing explant primary culture, expansion and melanogenic differentiation of resident ORS stem cells towards end-stage melanocytes in order to obtain functional melanocytes noninvasively for the purposes of transplantation and use them for the treatment of depigmentation disorders. Our protocol specifies sampling of hair with their ORS, follicle medium-air interface primary culture, stimulation of cell outgrowth, adherent culture and differentiation of ORS stem cells and precursors towards fully functional melanocytes. Along with cultivation, we describe selection techniques for establishing and maintaining a pure melanocyte population and methods suitable for determining melanocyte identity.

  4. Differential responses of choroidal melanocytes and uveal melanoma cells to low oxygen conditions

    PubMed Central

    Weidmann, Cindy; Pomerleau, Jade; Trudel-Vandal, Laurence

    2017-01-01

    Purpose Tissue culture is traditionally performed at atmospheric oxygen concentration (21%), which induces hyperoxic stress, as endogenous physiologic oxygen tension found in tissues varies between 2% and 9%. This discrepancy may lead to misinterpretation of results and may explain why effects observed in vitro cannot always be reproduced in vivo and vice versa. Only a few studies have been conducted in low physiologic oxygen conditions to understand the development and differentiation of cells from the eye. Methods The aim of this study was to investigate the growth and gene expression profile of melanocytes from the choroid permanently exposed to 21% (hyperoxic) or 3% (physiologic) oxygen with proliferation assays and DNA microarray. The cellular behavior of the melanocytes was then compared to that of cancer cells. Results The gross morphology and melanin content of choroidal melanocytes changed slightly when they were exposed to 3% O2, and the doubling time was statistically significantly faster. There was an increase in the percentage of choroidal melanocytes in the active phases of the cell cycle as observed by using the proliferation marker Ki67. The caveolin-1 senescence marker was not increased in choroidal melanocytes or uveal melanoma cells grown in hyperoxia. In comparison, the morphology of the uveal melanoma cells was similar between the two oxygen levels, and the doubling time was slower at 3% O2. Surprisingly, gene expression profiling of the choroidal melanocytes did not reveal a large list of transcripts considerably dysregulated between the two oxygen concentrations; only the lactate transporter monocarboxylate transporter (MCT4) was statistically significantly upregulated at 3% O2. Conclusions This study showed that the oxygen concentration must be tightly controlled in experimental settings, because it influences the subsequent cellular behavior of human choroidal melanocytes. PMID:28356703

  5. A retrospective chart review: adolescents with borderline personality disorder, borderline personality traits, and controls.

    PubMed

    Jopling, Ellen N; Khalid-Khan, Sarosh; Chandrakumar, Shivani F; Segal, Shira C

    2016-07-21

    With an estimated lifetime prevalence as high as 5.9% in the general population, borderline personality disorder (BPD) is a psychiatric disorder characterized by marked impulsivity as well as difficulties in interpersonal relationships, self-image, and affects. The burden on the health care system is immense with BPD patients accounting for 10%-20% of the patients in mental health outpatient facilities and 15%-40% in mental health inpatient facilities. Further, while 75%-80% of BPD patients attempt to commit suicide, 10% succeed; this mortality rate exceeds even that of anorexia nervosa which, with a weighted mortality rate of 5.1%, has often been considered to have the highest mortality rate of any mental disorder. In order to provide treatment and to implement preventative measures, a risk profile as well as clinical features must be identified within the adolescent population. This is presently crucial, as the current criteria for BPD are not developmentally focused, and as a result, criteria initially developed for the adult population are being applied in diagnoses of adolescents. A population of adolescents (n=80) between 16 and 19 years of age meeting the Diagnostic and Statistical Manual of Mental Disorders (DSM-V) criteria either for BPD traits (n=46) or for BPD (n=36) were included in a retrospective chart review; a control group consisting of n=30 mood and anxiety control subjects were included to allow for further comparisons. Complex significant differences were discovered between the three groups in the following areas: history of sexual abuse, suicidal ideation, internalizing/externalizing symptoms, interpersonal difficulties, impulsivity, pre-perinatal stress, bullying, substance abuse, anxiety disorders, disruptive disorders, and finally, learning disorders.

  6. Epistemic injustice and responsibility in borderline personality disorder.

    PubMed

    Kyratsous, Michalis; Sanati, Abdi

    2016-08-04

    Miranda Fricker's concept of epistemic injustice has been quite a novel idea in epistemology. It brings something new to the fields of epistemology and ethics. Fricker draws our attention to a distinctive species of injustice, the epistemic injustice, in which someone is specifically wronged in his capacity as a knower. There has been a significant amount of work done in epistemic injustice, both in race and gender studies. The application of the concept in the context of mental health is less explored. Here, we aim to apply the concept of epistemic injustice in attributing responsibility to patients with borderline personality disorder. Attributing responsibility involves holding someone accountable for his presumed wrongdoings, making judgments on whether the agent has control on his action, on whether is aware of its consequences. It is generally agreed that in order to be morally responsible for an action the person should be worthy of praise or blame for it. Following Aristotle, we focus on epistemic condition in attribution of responsibility. We will discuss the role of epistemic injustice in assessment of epistemic condition of responsibility. We will show that we can misinterpret the agent's intentions because of the presence of systematic prejudices. We will focus on patients suffering from borderline personality disorder. We provide a case vignette to show a tendency in the professionals in holding these patients responsible for their action when it can be argued otherwise. We argue that prejudice against the patient with borderline personality disorder where the person is seen as manipulative plays a significant role in the process of epistemic injustice. The suggested manipulative nature of patients with borderline personality disorder leads to professionals to ascribe agency and knowledge where it is not due.

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

    PubMed

    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.

  8. Sunscreen use and melanocytic nevi in children: a systematic review.

    PubMed

    de Maleissye, Marie-Florence; Beauchet, Alain; Saiag, Phillippe; Corrêa, Marcelo; Godin-Beeckmann, Sophie; Haeffelin, Martial; Mahé, Emmanuel

    2013-01-01

    We conducted a systematic review of the association between melanocytic nevi (MN) in childhood and sunscreen use. A bibliographic search was conducted between November 2008 and January 2009 using the following key words on MEDLINE and EMBASE: child*, in combination with naevi, nevi, naevus, nevus and sunscreen, sun protection. We also used Medical Subject Headings [sunscreening agents], or [radiation protection] with [nevus, pigmented]. A first screening was done on title and abstract reading. Randomized trials and cohort and cross-sectional studies analyzing the relationship between the use of sunscreen and MN in children were selected. Three reviewers abstracted data from each article. The three sets of results were compared for concordance and rereviewed if necessary. Fifteen articles were included (20,743 children). The studies were not consistent in terms of the ages of the children, MN count methods, or sunscreen use assessment. Owing to this heterogeneity, we were unable to pool the studies and conduct a meta-analysis. Twelve studies did not report that the use of sunscreen had a protective effect against MN development. Three studies reported a lower MN count when sunscreen was applied. This systematic review underlines the methodologic differences between studies. Eight of 15 studies reported a positive association between sunscreen application and MN count. Differences in MN counts, overexposure to sun, and inadequate sunscreen application on fair-skinned children could explain the disparity in the results. There is still no evidence of a protective effect of sunscreen against MN development in children.

  9. Lack of prognostic significance of angiogenesis in canine melanocytic tumours.

    PubMed

    Cuitiño, M C; Massone, A R; Idiart, J R

    2012-01-01

    The prognostic significance of angiogenesis in some canine tumours has been investigated, but little is known about its relevance in canine melanocytic tumours (MTs). The aim of this study was to evaluate the prognostic significance of angiogenesis in canine MTs. A total of 36 cutaneous melanocytomas (benign MTs), 40 cutaneous melanomas (malignant MTs) and 43 oral melanomas were studied. Survival data were available for a subset of 59 cases. Microvessel density (MVD) and endothelial area (EA) were determined by immunolabelling using an antibody specific for von Willebrand factor (vWF). Mean MVD (expressed as the number of microvessels per mm(2)) was 129 ± 14 in melanocytomas, 191 ± 16 in cutaneous melanomas and 208 ± 16 in oral melanomas. Mean EA (expressed as the percentage of the total area) was 1.5 ± 0.14 in melanocytomas, 2.6 ± 0.2 in cutaneous melanomas and 2.4 ± 0.3 in oral melanomas. The differences in MVD and EA between melanocytomas and melanomas were significant (P = 0.001 and P = 0.003, respectively). MVD and EA were significantly correlated between cutaneous and oral MTs (r = 0.54; P <0.001 and r = 0.63; P <0.001, respectively). MVD and EA were not related to survival in cutaneous and oral MTs. In conclusion, tumour vascularization was higher in melanomas than in melanocytomas, but it seemed to have no prognostic significance in these tumours.

  10. Central nervous system imaging and congenital melanocytic naevi

    PubMed Central

    Kinsler, V; Aylett, S; Coley, S; Chong, W; Atherton, D

    2001-01-01

    AIM—To establish the prevalence of central nervous system (CNS) abnormalities on magnetic resonance imaging (MRI) in a population of children with congenital melanocytic naevi (CMN) over the head and/or spine, and to compare this with clinical findings.
METHODS—Forty three patients identified from outpatient clinics underwent MRI of the brain and/or spine. These were reported by a paediatric radiologist and findings compared with the clinical picture.
RESULTS—Nine patients had abnormal clinical neurology, seven had abnormal findings on MRI, and six had both abnormal clinical and radiological findings. Only three of the abnormal MRIs showed features of intracranial melanosis. Three others showed structural brain abnormalities: one choroid plexus papilloma, one cerebellar astrocytoma, and one posterior fossa arachnoid cyst; the first two of these have not previously been described in association with CMN. The last abnormal MRI showed equivocal changes requiring reimaging.
CONCLUSIONS—The prevalence of radiological CNS abnormality in this group of children was 7/43. Six of these developed abnormal clinical neurological signs within the first 18 months of life, but two did not do so until after the MRI. Two of the CNS lesions were operable; for this reason we support the routine use of early MRI in this group.

 PMID:11159293

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

    PubMed

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

    2016-03-01

    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.

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

    PubMed

    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.

  13. Hyperoside protects human primary melanocytes against H2O2-induced oxidative damage

    PubMed Central

    YANG, BIN; YANG, QIN; YANG, XIN; YAN, HONG-BO; LU, QI-PING

    2016-01-01

    Cuscutae semen has been shown to have beneficial effects in the treatment of vitiligo, recorded in the Chinese Pharmacopoeia, whereas the effects of its constituent compounds remains to be elucidated. Using a tetrazolium bromide assay, the present study found that hyperoside (0.5–200 µg/ml) significantly increased the viability of human melanocytes in a time- and dose-dependent manner. The present study used a cell model of hydrogen peroxide (H2O2)-induced oxidative damage to examine the effect of hyperoside on human primary melanocytes. The results demonstrated that hyperoside pretreatment for 2 h decreased cell apoptosis from 54.03±9.11 to 17.46±3.10% in the H2O2-injured melanocytes. The levels of oxidative stress in the mitochondrial membrane potential of the melanocytes increased following hyperoside pretreatment. The mRNA and protein levels of B-cell lymphoma-2/Bcl-2-associated X protein and caspase 3 were regulated by hyperoside, and phosphoinositide 3-kinase/AKT and mitogen-activated protein kinase signaling were also mediated by hyperoside. In conclusion, the results of the present study demonstrated that hyperoside protected the human primary melanocytes against oxidative damage. PMID:27082158

  14. UV light phototransduction activates transient receptor potential A1 ion channels in human melanocytes.

    PubMed

    Bellono, Nicholas W; Kammel, Laura G; Zimmerman, Anita L; Oancea, Elena

    2013-02-05

    Human skin is constantly exposed to solar ultraviolet radiation (UVR), the most prevalent environmental carcinogen. Humans have the unique ability among mammals to respond to UVR by increasing their skin pigmentation, a protective process driven by melanin synthesis in epidermal melanocytes. The molecular mechanisms used by melanocytes to detect and respond to long-wavelength UVR (UVA) are not well understood. We recently identified a UVA phototransduction pathway in melanocytes that is mediated by G protein-coupled receptors and leads to rapid calcium mobilization. Here we report that in human epidermal melanocytes physiological doses of UVR activate a retinal-dependent current mediated by transient receptor potential A1 (TRPA1) ion channels. The TRPA1 photocurrent is UVA-specific and requires G protein and phospholipase C signaling, thus contributing to UVA-induced calcium responses to mediate downstream cellular effects and providing evidence for TRPA1 function in mammalian phototransduction. Remarkably, TRPA1 activation is required for the UVR-induced and retinal-dependent early increase in cellular melanin. Our results show that TRPA1 is essential for a unique extraocular phototransduction pathway in human melanocytes that is activated by physiological doses of UVR and results in early melanin synthesis.

  15. Melanocyte-like cells in the heart and pulmonary veins contribute to atrial arrhythmia triggers

    PubMed Central

    Levin, Mark D.; Lu, Min Min; Petrenko, Nataliya B.; Hawkins, Brian J.; Gupta, Tara H.; Lang, Deborah; Buckley, Peter T.; Jochems, Jeanine; Liu, Fang; Spurney, Christopher F.; Yuan, Li J.; Jacobson, Jason T.; Brown, Christopher B.; Huang, Li; Beermann, Friedrich; Margulies, Kenneth B.; Madesh, Muniswamy; Eberwine, James H.; Epstein, Jonathan A.; Patel, Vickas V.

    2009-01-01

    Atrial fibrillation is the most common clinical cardiac arrhythmia. It is often initiated by ectopic beats arising from the pulmonary veins and atrium, but the source and mechanism of these beats remains unclear. The melanin synthesis enzyme dopachrome tautomerase (DCT) is involved in intracellular calcium and reactive species regulation in melanocytes. Given that dysregulation of intracellular calcium and reactive species has been described in patients with atrial fibrillation, we investigated the role of DCT in this process. Here, we characterize a unique DCT-expressing cell population within murine and human hearts that populated the pulmonary veins, atria, and atrioventricular canal. Expression profiling demonstrated that this population expressed adrenergic and muscarinic receptors and displayed transcriptional profiles distinct from dermal melanocytes. Adult mice lacking DCT displayed normal cardiac development but an increased susceptibility to atrial arrhythmias. Cultured primary cardiac melanocyte-like cells were excitable, and those lacking DCT displayed prolonged repolarization with early afterdepolarizations. Furthermore, mice with mutations in the tyrosine kinase receptor Kit lacked cardiac melanocyte-like cells and did not develop atrial arrhythmias in the absence of DCT. These data suggest that dysfunction of melanocyte-like cells in the atrium and pulmonary veins may contribute to atrial arrhythmias. PMID:19855129

  16. Amides from Piper nigrum L. with dissimilar effects on melanocyte proliferation in-vitro.

    PubMed

    Lin, Zhixiu; Liao, Yonghong; Venkatasamy, Radhakrishnan; Hider, Robert C; Soumyanath, Amala

    2007-04-01

    Melanocyte proliferation stimulants are of interest as potential treatments for the depigmentary skin disorder, vitiligo. Piper nigrum L. (Piperaceae) fruit (black pepper) water extract and its main alkaloid, piperine (1), promote melanocyte proliferation in-vitro. A crude chloroform extract of P. nigrum containing piperine was more stimulatory than an equivalent concentration of the pure compound, suggesting the presence of other active components. Piperine (1), guineensine (2), pipericide (3), N-feruloyltyramine (4) and N-isobutyl-2E, 4E-dodecadienamide (5) were isolated from the chloroform extract. Their activity was compared with piperine and with commercial piperlongumine (6) and safrole (7), and synthetically prepared piperettine (8), piperlonguminine (9) and 1-(3, 4-methylenedioxyphenyl)-decane (10). Compounds 6-10 either occur in P. nigrum or are structurally related. Compounds 1, 2, 3, 8 and 9 stimulated melanocyte proliferation, whereas 4, 5, 6, 7 and 10 did not. Comparison of structures suggests that the methylenedioxyphenyl function is essential for melanocyte stimulatory activity. Only those compounds also possessing an amide group were active, although the amino component of the amide group and chain linking it to the methylenedioxyphenyl group can vary. P. nigrum, therefore, contains several amides with the ability to stimulate melanocyte proliferation. This finding supports the traditional use of P. nigrum extracts in vitiligo and provides new lead compounds for drug development for this disease.

  17. Differential PAX3 functions in normal skin melanocytes and melanoma cells.

    PubMed

    Medic, Sandra; Rizos, Helen; Ziman, Mel

    2011-08-12

    The PAX3 transcription factor is the key regulator of melanocyte development during embryogenesis and is also frequently found in melanoma cells. While PAX3 is known to regulate melanocyte differentiation, survival, proliferation and migration during development, it is not clear if its function is maintained in adult melanocytes and melanoma cells. To clarify this we have assessed which genes are targeted by PAX3 in these cells. We show here that similar to its roles in development, PAX3 regulates complex differentiation networks in both melanoma cells and melanocytes, in order to maintain cells as "stem" cell-like (via NES and SOX9). We show also that mediators of migration (MCAM and CSPG4) are common to both cell types but more so in melanoma cells. By contrast, PAX3-mediated regulation of melanoma cell proliferation (through TPD52) and survival (via BCL2L1 and PTEN) differs from that in melanocytes. These results suggest that by controlling cell proliferation, survival and migration as well as maintaining a less differentiated "stem" cell like phenotype, PAX3 may contribute to melanoma development and progression.

  18. UVB represses melanocyte cell migration and acts through β-catenin.

    PubMed

    Bertrand, Juliette U; Petit, Valérie; Hacker, Elke; Berlin, Irina; Hayward, Nicholas K; Pouteaux, Marie; Sage, Evelyne; Whiteman, David C; Larue, Lionel

    2017-02-13

    The exposure of skin to ultraviolet (UV) radiation can have both beneficial and deleterious effects: it can lead, for instance, to increased pigmentation and vitamin D synthesis but also to inflammation and skin cancer. UVB may induce genetic and epigenetic alterations, and have reversible effects associated with post-translational and gene regulation modifications. β-catenin is a main driver in melanocyte development; although infrequently mutated in melanoma, its cellular localization and activity is frequently altered. Here, we evaluate the consequence of UVB on β-catenin in the melanocyte lineage. We report that in vivo, UVB induces cytoplasmic/nuclear relocalization of β-catenin in melanocytes of newborn mice and adult human skin. In mouse melanocyte and human melanoma cell lines in vitro, UVB increases β-catenin stability, accumulation in the nucleus, and co-transcriptional activity, leading to the repression of cell motility and velocity. The activation of the β-catenin signaling pathway and its effect on migration by UVB are increased by an inhibitor of GSK3β, and decreased by an inhibitor of β-catenin. In conclusion, UVB represses melanocyte migration and does so by acting through the GSK3-β-catenin axis. This article is protected by copyright. All rights reserved.

  19. Hypergravity modulates cyclic GMP efflux in nitric oxide-stimulated human melanocytic cells

    NASA Astrophysics Data System (ADS)

    Stieber, Christiane; Ivannova, Krassimira; Block, Ingrid; Gerzer, Rupert

    2005-08-01

    Gravity alteration is known to influence cell functions. We recently found that hypergravity may stimulate cGMP efflux in human melanocytic cells when cGMP hydrolysis is inhibited. Here we examined whether hypergravity modulates cGMP efflux in nitric oxide (NO)-stimulated melanocytes and melanoma cells (MCs) using NONOates as direct NO donors. In the presence of 0.1 mM DETA-NO and long-term application of hypergravity (up to 5g for 24 h) an elevated cGMP efflux in cultured melanocytes and non-metastatic MCs compared to 1g was observed, whereas short-term exposure was not effective. The hypergravity-stimulated cGMP efflux was inhibited by 1 μM trequinsin, a selective inhibitor of the multidrug resistance proteins 4 and 5 (MRP4/5). The results of the present study indicate that hypergravity may stimulate cGMP efflux in NO- stimulated human melanocytes and non-metastatic MCs most probably by an enhanced expression of MRP4/5. Thus, an altered acceleration vector may induce signaling events in human melanocytic cells.

  20. Nicotine impact on melanogenesis and antioxidant defense system in HEMn-DP melanocytes.

    PubMed

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

    2014-10-01

    Nicotine is a compound of tobacco plants and is responsible for addictive properties of tobacco which is used by about one billion of smokers all over the world. Recently, nicotine has drawn even more attention due to its presumed neuroprotective and antioxidant features as far as common use in various forms of smoking cessation therapies. It is suggested that nicotine may be accumulated in human tissues containing melanin. This may in turn influence biochemical processes in human cells producing melanin. The aim of this study was to examine the impact of nicotine on melanogenesis and antioxidant defense system in cultured normal human melanocytes (HEMn-DP). Nicotine induced concentration-dependent loss in melanocytes viability. The value of EC50 was determined to be 2.52 mM. Nicotine modulated melanin biosynthesis in normal human melanocytes. Significant changes in hydrogen peroxide content and cellular antioxidant enzymes: SOD, CAT, and GPx activities were stated in melanocytes exposed to nicotine, which indicates alterations of antioxidant defense system. The results obtained in vitro may explain a potential influence of nicotine on biochemical processes in melanocytes in vivo during long-term exposition to nicotine.

  1. Melanocytes and keratinocytes have distinct and shared responses to ultraviolet radiation and arsenic.

    PubMed

    Cooper, K L; Yager, J W; Hudson, L G

    2014-01-30

    The rise of melanoma incidence in the United States is a growing public health concern. A limited number of epidemiology studies suggest an association between arsenic levels and melanoma risk. Arsenic acts as a co-carcinogen with ultraviolet radiation (UVR) for the development of squamous cell carcinoma and proposed mechanisms include generation of oxidative stress by arsenic and UVR and inhibition of UVR-induced DNA repair by arsenic. In this study, we investigate similarities and differences in response to arsenic and UVR in keratinocytes and melanocytes. Normal melanocytes are markedly more resistant to UVR-induced cytotoxicity than normal keratinocytes, but both cell types are equally sensitive to arsenite. Melanocytes were more resistant to arsenite and UVR stimulation of superoxide production than keratinocytes, but the concentration of arsenite necessary to inhibit the activity of the DNA repair protein poly(ADP-ribose)polymerase and enhance retention of UVR-induced DNA damage was essentially equivalent in both cell types. These findings suggest that although melanocytes are less sensitive than keratinocytes to initial UVR-mediated DNA damage, both of these important target cells in the skin share a mechanism related to arsenic inhibition of DNA repair. These findings suggest that concurrent chronic arsenic exposure could promote retention of unrepaired DNA damage in melanocytes and act as a co-carcinogen in melanoma.

  2. Impact of kanamycin on melanogenesis and antioxidant enzymes activity in melanocytes--an in vitro study.

    PubMed

    Wrześniok, Dorota; Otręba, Michał; Beberok, Artur; Buszman, Ewa

    2013-12-01

    Aminoglycosides, broad spectrum aminoglycoside antibiotics, are used in various infections therapy due to their good antimicrobial characteristics. However, their adverse effects such as nephrotoxicity and auditory ototoxicity, as well as some toxic effects directed to pigmented tissues, complicate the use of these agents. This study was undertaken to investigate the effect of aminoglycoside antibiotic-kanamycin on viability, melanogenesis and antioxidant enzymes activity in cultured human normal melanocytes (HEMa-LP). It has been demonstrated that kanamycin induces concentration-dependent loss in melanocytes viability. The value of EC50 was found to be ~6.0 mM. Kanamycin suppressed melanin biosynthesis: antibiotic was shown to inhibit cellular tyrosinase activity and to reduce melanin content in normal human melanocytes. Significant changes in the cellular antioxidant enzymes: SOD, CAT and GPx were stated in melanocytes exposed to kanamycin. Moreover, it was observed that kanamycin caused depletion of antioxidant defense sytem. It is concluded that the inhibitory effect of kanamycin on melanogenesis and not sufficient antioxidant defense mechanism in melanocytes in vitro may explain the potential mechanisms of undesirable side effects of this drug directed to pigmented tissues in vivo.

  3. Manassantin B inhibits melanosome transport in melanocytes by disrupting the melanophilin-myosin Va interaction.

    PubMed

    Chang, Huikyoung; Choi, Hyunjung; Joo, Kyung-Mi; Kim, Daegun; Lee, Tae Ryong

    2012-11-01

    Human skin hyperpigmentation disorders occur when the synthesis and/or distribution of melanin increases. The distribution of melanin in the skin is achieved by melanosome transport and transfer. The transport of melanosomes, the organelles where melanin is made, in a melanocyte precedes the transfer of the melanosomes to a keratinocyte. Therefore, hyperpigmentation can be regulated by decreasing melanosome transport. In this study, we found that an extract of Saururus chinensis Baill (ESCB) and one of its components, manassantin B, inhibited melanosome transport in Melan-a melanocytes and normal human melanocytes (NHMs). Manassantin B disturbed melanosome transport by disrupting the interaction between melanophilin and myosin Va. Manassantin B is neither a direct nor an indirect inhibitor of tyrosinase. The total melanin content was not reduced when melanosome transport was inhibited in a Melan-a melanocyte monoculture by manassantin B. Manassantin B decreased melanin content only when Melan-a melanocytes were co-cultured with SP-1 keratinocytes or stimulated by α-MSH. Therefore, we propose that specific inhibitors of melanosome transport, such as manassantin B, are potential candidate or lead compounds for the development of agents to treat undesirable hyperpigmentation of the skin.

  4. Interventions for the treatment of borderline ovarian tumours

    PubMed Central

    Faluyi, Olusola; Mackean, Melanie; Gourley, Charlie; Bryant, Andrew; Dickinson, Heather O

    2014-01-01

    Background The safety of conservative surgery and the benefit of additional interventions after surgery for borderline ovarian tumours are unknown. Objectives To evaluate the benefits and harm of different treatment modalities offered for borderline ovarian tumours. Search methods We searched the Cochrane Gynaecological Cancer Group Trials Register to 2009, Cochrane Central Register of Controlled Trials (CENTRAL) (The Cochrane Library 2008, Issue 4), MEDLINE and EMBASE to 2009. We also searched registers of clinical trials, abstracts of scientific meetings, reference lists of included studies. Selection criteria Randomised controlled trials (RCTs) that compared different interventions in adult women diagnosed with borderline ovarian tumours of any histological variant. Data collection and analysis Two review authors independently abstracted data and assessed risk of bias. Main results We identified seven RCTs that enrolled 372 women. We could not pool results of trials as the treatment comparisons differed. Six RCTs (n = 340) conducted over 15 years ago, evaluated adjuvant therapy (chemotherapy, pelvic external irradiation or intraperitoneal radioactive isotope therapy) after radical surgery; over 87% of participants had Stage I tumours. Most participants were followed up for over 10 years. Overall and recurrence-free survival were similar between both arms of these trials, except that one trial (n = 66) showed a significantly lower survival (P = 0.03) in women who received chemotherapy (thio-TEPA). Adverse effects of treatment were incompletely reported and all six trials were at high risk of bias. One further trial (n = 32) that recruited participants with bilateral serous tumours who were wishing fertility preservation, revealed a significantly increased chance of pregnancy (hazard ratio (HR) = 3.3, 95% CI 1.4 to 8.0) but non-significantly earlier disease recurrence (HR = 1.5, 95% CI 0.6 to 3.8) in the women who had ultra-conservative surgery (bilateral

  5. Treatment of a giant congenital melanocytic nevus in the adult: review of the current management of giant congenital melanocytic nevus.

    PubMed

    Su, Jeannie J; Chang, Daniel K; Mailey, Brian; Gosman, Amanda

    2015-05-01

    Giant congenital melanocytic nevi (GCMNs) create cosmetic disfigurements and pose risk for malignant transformation. Adult GCMN cases are uncommon because most families opt for surgical treatment during childhood. We review the current literature on GCMN and present an interesting case of an adult with a GCMN encompassing the entire back with painful nodules exhibiting gross involvement of his back musculature, without pathologic evidence of malignancy. Surgical management was deferred in childhood because of parental desires to allow the patient to make his own decision, and treatment in adulthood was pursued on the basis of the significant impairment of the patient's quality of life and self-esteem due to the massive size and deforming nature of the nevus. The treatment strategy used for this young adult male patient involved a massive en bloc excision of the GCMN with partial resection of the latissimus dorsi, followed by a 5-week staged reconstructive process using dermal regenerative matrices and split-thickness skin grafting. Because of the shift in GCMN management from early surgical management to more conservative management, we may see an increase in adult cases of GCMN. Thus, it is critical to better understand the controversy surrounding early versus delayed management of GCMN.

  6. Paired box gene 2 is associated with estrogen receptor α in ovarian serous tumors: Potential theory basis for targeted therapy.

    PubMed

    Wang, Min; Ma, Haifen

    2016-08-01

    It has been suggested that Paired box gene (PAX)2 is activated by estradiol via estrogen receptor (ER)α in breast and endometrial cancer. The expression of PAX2 was restricted to ovarian serous tumors and only one case was positive in borderline mucinous tumor in our previous study. In the present study, immunohistochemistry was performed to assess the expression of ERα in 58 cases of ovarian serous tumors, including 30 serous cystadenomas, 16 borderline serous cystadenomas, 12 serous carcinomas and 67 cases of ovarian mucinous tumors, including 29 mucinous cystadenoma, 23 borderline mucinous cystadenoma and 15 mucinous carcinoma, which were the same specimens with detection of PAX2 expression. The results demonstrated that ERα was expressed in 10% (3/30) of serous cystadenomas, 62.5% (10/16) borderline serous cystadenomas and 66.7% (8/12) serous carcinomas. The expression of ERα in borderline serous cystadenomas and serous carcinomas were significantly higher compared with that in serous cystadenomas (P<0.01). ERα was detected in 3.4% (1/29) mucinous cystadenoma, 26.1% (6/23) borderline mucinous cystadenoma and only 6.7% (1/15) mucinous carcinoma. Furthermore, a scatter plot of the expression of PAX2 and ERα revealed a linear correlation between them in ovarian serous tumors (P<0.0001). With few positive results, no correlation was determined in ovarian mucinous tumors. It was demonstrated that PAX2 is associated with ERα in ovarian serous tumors, and this may become a potential theory basis for targeted therapy for ovarian serous tumors. Further research is required to determine how PAX2 and ERα work together, and the role of targeted therapy in ovarian serous tumors.

  7. Melanocyte migration is influenced by E-cadherin-dependent adhesion of keratinocytes in both two- and three-dimensional in vitro wound models.

    PubMed

    Keswell, Dheshnie; Kidson, Susan H; Davids, Lester M

    2015-02-01

    During wound healing, melanocytes are required to migrate into the wounded area that is still in the process of re-construction. The role and behaviour of melanocytes during this process is poorly understood, that is, whether melanocyte migration into the wound is keratinocyte-dependent or not. This paper attempts, through the use of both two- and three-dimensional in vitro models, to understand the role and behaviour of melanocytes during the process of wound healing. In addition, it sheds light on whether keratinocytes influence/contribute toward melanocyte migration and ultimately wound healing. Scratch assays were performed to analyse migration and Western blot analyses measured cellular E-cadherin expression. Immunohistochemistry was used to analyse the in vivo 3D wound healing effect. Scratch assays performed on co-cultures of melanocytes and keratinocytes demonstrated that melanocytes actively migrated, with the use of their dendrites, into the scratch ahead of the proliferating keratinocyte sheet. Migration of the melanocyte into the wound bed was accompanied by loss of attachment to keratinocytes at the wound front with concomitant downregulation of E-cadherin expression as observed through immunocytochemistry. This result suggests that, in vitro, melanocyte migration occurs independently of keratinocytes but that the migration is influenced by keratinocyte E-cadherin expression. We now demonstrate that melanocyte migration during re-pigmentation is an active process, and suggest that targeting of mechanisms involved in active melanocyte migration (e.g. the melanocyte dendrite) may enhance the re-pigmentation process.

  8. The master role of microphthalmia-associated transcription factor in melanocyte and melanoma biology.

    PubMed

    Kawakami, Akinori; Fisher, David E

    2017-03-06

    Certain transcription factors have vital roles in lineage development, including specification of cell types and control of differentiation. Microphthalmia-associated transcription factor (MITF) is a key transcription factor for melanocyte development and differentiation. MITF regulates expression of numerous pigmentation genes to promote melanocyte differentiation, as well as fundamental genes for maintaining cell homeostasis, including genes encoding proteins involved in apoptosis (eg, BCL2) and the cell cycle (eg, CDK2). Loss-of-function mutations of MITF cause Waardenburg syndrome type IIA, whose phenotypes include depigmentation due to melanocyte loss, whereas amplification or specific mutation of MITF can be an oncogenic event that is seen in a subset of familial or sporadic melanomas. In this article, we review basic features of MITF biological function and highlight key unresolved questions regarding this remarkable transcription factor.Laboratory Investigation advance online publication, 6 March 2017; doi:10.1038/labinvest.2017.9.

  9. Topology of feather melanocyte progenitor niche allows complex pigment patterns to emerge.

    PubMed

    Lin, S J; Foley, J; Jiang, T X; Yeh, C Y; Wu, P; Foley, A; Yen, C M; Huang, Y C; Cheng, H C; Chen, C F; Reeder, B; Jee, S H; Widelitz, R B; Chuong, C M

    2013-06-21

    Color patterns of bird plumage affect animal behavior and speciation. Diverse patterns are present in different species and within the individual. Here, we study the cellular and molecular basis of feather pigment pattern formation. Melanocyte progenitors are distributed as a horizontal ring in the proximal follicle, sending melanocytes vertically up into the epithelial cylinder, which gradually emerges as feathers grow. Different pigment patterns form by modulating the presence, arrangement, or differentiation of melanocytes. A layer of peripheral pulp further regulates pigmentation via patterned agouti expression. Lifetime feather cyclic regeneration resets pigment patterns for physiological needs. Thus, the evolution of stem cell niche topology allows complex pigment patterning through combinatorial co-option of simple regulatory mechanisms.

  10. Parents' attitudes related to melanocytic nevus count in children.

    PubMed

    de Maleissye, Marie-Florence; Beauchet, Alain; Aegerter, Philippe; Saiag, Philippe; Mahé, Emmanuel

    2010-11-01

    Sun exposure, fair phototype, and a high common melanocytic nevus (MN) count have been identified as the most important risk factors for melanoma. MN are mainly acquired during childhood, and their relationship to sun exposure, sunburn, and light skin complexion is well documented. The purpose of this study was to investigate how the sun protection attitudes of parents and their offspring affect MN development in children. We designed a cross-sectional study in 828 9-year-old school children. Trained nurses counted the MN on each child's back and arms, depending on their size. Questionnaires filled by children and parents provided information about sun exposure, attitude towards the sun, and sun-protection behaviors. Multivariate analysis showed that the childhood MN count was linked to fair phenotype--fair skin: rate ratio (RR)=3.80, 95% confidence interval (CI)=2.25-6.41; blue/green eyes: RR=1.2, 95% CI=1.11-1.34; blond hair: RR=1.25, 95% CI=1.10-1.41; history of sunburn: RR=1.13, 95% CI=1.03-1.23, seaside sun exposure--RR=1.14, 95% CI=1.01-1.28, and to their parents' behaviors during exposure to the sun--increase in the number of MN when parents used sunscreen: RR=1.23, 95% CI=1.08-1.40; decrease in MN count when parents wore a tee-shirt: RR=0.86, 95% CI=0.79-0.93. In conclusion, fair phenotype and sun exposure are known major risk factors for MN. Parents' behaviors influence their children and appeared in our analysis as another determinant predictor of MN count, being protective against (wearing a tee-shirt when exposed to sun) or increasing the risk (sunscreen use, reflecting higher sun exposure) for childhood MN development.

  11. Tumoral melanosis in an adolescent after trauma: a clinicopathological dilemma.

    PubMed

    Dogruk Kacar, Seval; Ozuguz, Pinar; Karaca, Semsettin; Aktepe, Fatma

    2014-01-01

    Tumoral melanosis (TM) is a histologic term used to indicate a nodular accumulation of melanophages in the dermis clinically presenting as a pigmented lesion. It is usually associated with regression of melanoma and nonmelanoma melanocytic pigmented lesions. We present the case of a 16-year-old girl with a suspicious pigmented macule on her right knee that appeared after trauma. The lesion was completely excised and diagnosed as TM.

  12. siRNA-mediated knock-down of COX-2 in melanocytes suppresses melanogenesis.

    PubMed

    Kim, Ji Y; Shin, Jae Y; Kim, Miri R; Hann, Seung-Kyung; Oh, Sang H

    2012-06-01

    Cyclooxygenase-2 (COX-2) is an enzyme induced in response to multiple mitogenic and inflammatory stimuli, including UV light. UV-induced COX-2 expression induces production of prostaglandin E2 (PGE2) in keratinocytes, which mediates inflammation and cell proliferation. Until recently, studies regarding COX-2 and PGE2 in the skin have focused on keratinocytes and skin cancer and the effect of PGs produced by keratinocytes on melanocytes. However, the effects of COX-2 itself or COX-2 inhibitors on melanogenesis are not well known. Therefore, to establish the role of COX-2 in melanogenesis, we investigated the effects of knock-down of COX-2 in melanocytes on melanin production and the expression of melanogenic molecules through silencing of COX-2 expression with COX-2 short interfering RNA (siRNA). COX-2 knock-down in melanocytes decreased the expressions of tyrosinase, TRP-1, TRP-2, gp100 and MITF and also reduced tyrosinase enzyme activity. Furthermore, COX-2 siRNA-transfected melanocytes showed markedly reduced alpha-melanocyte stimulating hormone (α-MSH)-induced melanin production. In addition, α-MSH-induced COX-2 expression in both scrambled siRNA-transfected and COX-2 siRNA-transfected melanocytes was greater than α-MSH-untreated cells. Our results suggest that COX-2 might be a candidate target for the development of anti-melanogenic agents and α-MSH-induced pigmentation could be closely associated with COX-2 expression. COX-2 inhibitors might therefore be of particular use in whitening cosmetics for hyperpigmentation disorders such as melasma, postinflammatory hyperpigmentation and solar lentigo.

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

    PubMed

    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.

  14. Differential responses of normal human melanocytes to intra- and extracellular dsRNA.

    PubMed

    Wang, Suiquan; Liu, Dongyin; Jin, Rong; Zhu, Yiping; Xu, Aie

    2015-06-01

    Viral factor has been implicated in the etiopathogenesis of vitiligo. To elucidate the effects of viral double-stranded RNA (dsRNA) on melanocytes and to explore the underlying mechanisms, primary cultured normal human melanocytes were treated with synthetic viral dsRNA analog poly(I:C). The results demonstrated that poly(I:C)-triggered apoptosis when transfected into melanocytes, while extracellular poly(I:C) did not have that effect. Intracellular poly(I:C)-induced melanocyte death was decreased by RIG-I or MDA5 siRNA, but not by TLR3 siRNA. Both intracellular and extracellular poly(I:C) induced the expression of IFNB, TNF, IL6, and IL8. However, extracellular poly(I:C) demonstrated a much weaker induction capacity of cytokine genes than intracellular poly(I:C). Further analysis revealed that phosphorylation of TBK1, IRF3, IRF7, and TAK1 was differentially induced by intra- or extracellular poly(I:C). NFκB inhibitor Bay 11-7082 decreased the induction of all the cytokines by poly(I:C), suggesting the ubiquitous role of NFκB in the process. Poly(I:C) treatment also induced the phosphorylation of p38 and JNK in melanocytes. Both JNK and p38 inhibitors showed suppression on the cytokine induction by intra- or extracellular poly(I:C). However, only the JNK inhibitor decreased the intracellular poly(I:C)-induced melanocyte death. Taken together, this study provides the possible mechanism of viral factor in the pathogenesis of vitiligo.

  15. Phyllodes tumor: diagnostic imaging and histopathology findings.

    PubMed

    Venter, Alina Cristiana; Roşca, Elena; Daina, Lucia Georgeta; Muţiu, Gabriela; Pirte, Adriana Nicoleta; Rahotă, Daniela

    2015-01-01

    Phyllodes tumors are rare breast tumors, accounting for less than 1% of all primary tumors of the breast. Histologically, phyllodes tumors can be divided into benign (60%), borderline (20%) and malignant (20%). The mammography examination was performed by means of a digital mammography system Giotto 3D Images; the ultrasound examination was performed through a GE Logiq P6 device and histological confirmation was possible after surgery or following the histological biopsy. We grouped the nine patients who presented clinically palpable nodules into two groups, namely: the six patients presenting histological benign results into Group I, and Group II where we included those with borderline and malignant histological results. Mammography performed in 77.7% revealed a well-circumscribed round or oval opacity or with contour lobules. Ultrasound examination was performed in all patients. Mammography and ultrasound have limitation in differentiating between benign lesion and phyllodes tumor. In the nine analyzed cases, mammographic and ultrasound examinations did not allow the differentiation into the three groups of phyllodes tumor. Histopathological examination is considered the golden standard for their diagnosis. Correlations between mammographic and microscopic aspects were inconclusive for determining the degree of differentiation, ultrasound changes could be correlated with the histopathological aspects.

  16. Mechanisms contributing to differential regulation of PAX3 downstream target genes in normal human epidermal melanocytes versus melanoma cells.

    PubMed

    Bartlett, Danielle; Boyle, Glen M; Ziman, Mel; Medic, Sandra

    2015-01-01

    Melanoma is a highly aggressive and drug resistant form of skin cancer. It arises from melanocytes, the pigment producing cells of the skin. The formation of these melanocytes is driven by the transcription factor PAX3 early during embryonic development. As a result of alternative splicing, the PAX3 gene gives rise to eight different transcripts which encode isoforms that have different structures and activate different downstream target genes involved in pathways of cell proliferation, migration, differentiation and survival. Furthermore, post-translational modifications have also been shown to alter the functions of PAX3. We previously identified PAX3 downstream target genes in melanocytes and melanoma cells. Here we assessed the effects of PAX3 down-regulation on this panel of target genes in primary melanocytes versus melanoma cells. We show that PAX3 differentially regulates various downstream target genes involved in cell proliferation in melanoma cells compared to melanocytes. To determine mechanisms behind this differential downstream target gene regulation, we performed immunoprecipitation to assess post-translational modifications of the PAX3 protein as well as RNAseq to determine PAX3 transcript expression profiles in melanocytes compared to melanoma cells. Although PAX3 was found to be post-translationally modified, there was no qualitative difference in phosphorylation and ubiquitination between melanocytes and melanoma cells, while acetylation of PAX3 was reduced in melanoma cells. Additionally, there were differences in PAX3 transcript expression profiles between melanocytes and melanoma cells. In particular the PAX3E transcript, responsible for reducing melanocyte proliferation and increasing apoptosis, was found to be down-regulated in melanoma cells compared to melanocytes. These results suggest that alternate transcript expression profiles activate different downstream target genes leading to the melanoma phenotype.

  17. Dissociation and borderline personality disorder: an update for clinicians.

    PubMed

    Korzekwa, Marilyn I; Dell, Paul F; Pain, Clare

    2009-02-01

    Dissociation occurs in about two thirds of people with borderline personality disorder (BPD) but is still not well understood by clinicians. In the past decade, however, research has used new measures of dissociation that provide some of the detail that clinicians need to understand and treat the dissociative symptoms of patients with BPD. In particular, this review examines BPD's comorbidity with the dissociative disorders, the neurobiology of dissociation in BPD, the role of trauma and disorganized attachment in the etiology of dissociation in BPD, and the clinical assessment and treatment of dissociation in BPD.

  18. Alchemy, homeopathy and the treatment of borderline cases.

    PubMed

    Whitmont, E C

    1996-07-01

    Homeopathy is presented as a modality of potential usefulness in the treatment of borderline patients refractory to psychoanalytic work. In these instances a minimally adequate centre of consciousness did not solidify from the identity with the psychoid stratum. In the view of Alchemy, this failure of the mind to separate from the unio naturalis or massa confusa could be remedied by a medicamentum spagyricum, an archtypal essence acting according to the simile principle, which was to be extracted from various substances. Homeopathy is described as a modern, clinically effective modification of the alchemistic method. Two cases example are given for illustration.

  19. [Impulse control disorders in borderline and antisocial personality disorder].

    PubMed

    Herpertz, S

    2007-01-18

    A borderline personality disorder is associated with highly impulsive acts that cannot be controlled by cognitive inhibition. In a psychopathic/antisocial personality disorder emotional inhibition of hostile acts is lacking. The patient has a high proclivity for risk-seeking, and is incapable of responding appropriately to punishment. In both disorders, the result is (auto)aggressive behavior. The family doctor must refer such patients to a specialist, when there is an acute danger of self-harm or when a grave functional limitation in the areas of work or interpersonal relationship has persisted over a long period of time.

  20. Family relationships of adults with borderline personality disorder.

    PubMed

    Allen, D M; Farmer, R G

    1996-01-01

    Current, ongoing interactions between adults exhibiting borderline personality disorder (BPD) traits and their families of origin may influence and maintain self-destructive behavior. Family interactions in such patients are often characterized by coexisting extremes of overinvolvement and underinvolvement by parental figures. Such parental behavior may trigger preexisting role relationship schemata in vulnerable individuals. Negative family reactions to new behavior patterns may make change difficult. A model for how present-day interpersonal patterns lead to self-destructive behavior, based on clinical observations, is proposed and case examples are presented.

  1. A Case of Oncocytic Adrenocortical Neoplasm of Borderline (Uncertain) Malignant Potential

    PubMed Central

    Brown, Linda G; Denning, Krista L; Pacioles, Toni

    2016-01-01

    Oncocytic neoplasms are tumors composed predominantly or exclusively of oncocytes (large polygonal cells with granular eosinophilic cytoplasm due to abnormal mitochondrial accumulation). These tumors are frequently reported in the thyroid, kidneys, and salivary glands. However, they are distinctly rare in the adrenal cortex. Oncocytic adrenocortical neoplasms (OAN) are classified regarding their biological behavior by their histological features according to the Lin-Weiss-Bisceglia system (LWB). Here, we report a case of OAN of borderline or uncertain malignant potential (BMP) with subsequently identified papillary thyroid carcinoma (PTC). A 34-year-old female with a nine-month history of fatigue presented with chest pain. A right adrenal mass was incidentally found while ruling out pulmonary embolism. A CT-guided adrenal biopsy, although not routinely indicated, was performed and interpreted as malignant with no definitive origin. Hormonal workup was unremarkable. PET-scan showed hypermetabolic adrenal mass with peak standardized uptake value of 15, suspicious of malignancy. A hypermetabolic thyroid nodule was also identified, but there was no evidence of metastatic disease. The patient underwent adrenalectomy, and the initial pathology report was interpreted as atypical pink cell tumor. A second pathology report from another laboratory favored OAN based on the morphology and immunohistochemical staining. While the histologic criteria of malignancy were not met, the large tumor size makes it compatible with BMP according to LWB criteria. A follow-up thyroid ultrasound revealed a complex thyroid nodule. A total thyroidectomy was performed, and pathology was consistent with PTC. Of interest, PTC frequently shows an increase in mitochondrial content, which is characteristic of oncocytic tumors. This case illustrates that OAN, although rare, should be considered in the differential diagnosis of adrenal masses. When OAN is identified, it should be classified

  2. A Case of Oncocytic Adrenocortical Neoplasm of Borderline (Uncertain) Malignant Potential.

    PubMed

    Shenouda, Mina; Brown, Linda G; Denning, Krista L; Pacioles, Toni

    2016-06-13

    Oncocytic neoplasms are tumors composed predominantly or exclusively of oncocytes (large polygonal cells with granular eosinophilic cytoplasm due to abnormal mitochondrial accumulation). These tumors are frequently reported in the thyroid, kidneys, and salivary glands. However, they are distinctly rare in the adrenal cortex. Oncocytic adrenocortical neoplasms (OAN) are classified regarding their biological behavior by their histological features according to the Lin-Weiss-Bisceglia system (LWB). Here, we report a case of OAN of borderline or uncertain malignant potential (BMP) with subsequently identified papillary thyroid carcinoma (PTC). A 34-year-old female with a nine-month history of fatigue presented with chest pain. A right adrenal mass was incidentally found while ruling out pulmonary embolism. A CT-guided adrenal biopsy, although not routinely indicated, was performed and interpreted as malignant with no definitive origin. Hormonal workup was unremarkable. PET-scan showed hypermetabolic adrenal mass with peak standardized uptake value of 15, suspicious of malignancy. A hypermetabolic thyroid nodule was also identified, but there was no evidence of metastatic disease. The patient underwent adrenalectomy, and the initial pathology report was interpreted as atypical pink cell tumor. A second pathology report from another laboratory favored OAN based on the morphology and immunohistochemical staining. While the histologic criteria of malignancy were not met, the large tumor size makes it compatible with BMP according to LWB criteria. A follow-up thyroid ultrasound revealed a complex thyroid nodule. A total thyroidectomy was performed, and pathology was consistent with PTC. Of interest, PTC frequently shows an increase in mitochondrial content, which is characteristic of oncocytic tumors. This case illustrates that OAN, although rare, should be considered in the differential diagnosis of adrenal masses. When OAN is identified, it should be classified

  3. Use of Dialectical Behavior Therapy in Borderline Personality Disorder: A View from Residency

    ERIC Educational Resources Information Center

    Sharma, Binali; Dunlop, Boadie W.; Ninan, Philip T.; Bradley, Rebekah

    2007-01-01

    Objective: The authors describe the use of dialectical behavior therapy (DBT) in treating borderline personality disorder during psychiatry residency, and assess the status of DBT education within psychiatry residencies in the United States. Method: The authors present a patient with borderline personality disorder treated by a resident using DBT,…

  4. Adolescent Borderline Symptoms in the Community: Prognosis for Functioning over 20 Years

    ERIC Educational Resources Information Center

    Winograd, Greta; Cohen, Patricia; Chen, Henian

    2008-01-01

    Background: The long-term prognosis associated with adolescent symptoms of borderline personality disorder (BPD) in the general population is virtually unknown. In this study, the relationship of early borderline symptoms to subsequent psychosocial functioning and attainment was investigated based on data from the Children in the Community cohort.…

  5. Emotion Regulation Training for Adolescents with Borderline Personality Disorder Traits: A Randomized Controlled Trial

    ERIC Educational Resources Information Center

    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.…

  6. Using Student Ability and Item Difficulty for Making Defensible Pass/Fail Decisions for Borderline Grades

    ERIC Educational Resources Information Center

    Shulruf, Boaz; Jones, Phil; Turner, Rolf

    2015-01-01

    The determination of Pass/Fail decisions over Borderline grades, (i.e., grades which do not clearly distinguish between the competent and incompetent examinees) has been an ongoing challenge for academic institutions. This study utilises the Objective Borderline Method (OBM) to determine examinee ability and item difficulty, and from that…

  7. Cutaneous perivascular epithelioid cell tumors: A review on an infrequent neoplasm

    PubMed Central

    Llamas-Velasco, Mar; Requena, Luis; Mentzel, Thomas

    2016-01-01

    “Perivascular epithelioid cutaneous” cell tumors (PEComa) are a family of mesenchymal tumors with shared microscopic and immunohistochemical properties: They exhibit both smooth muscle cell and melanocytic differentiation. Non-neoplastic counterpart of PEComa’s cells are unknown, as well as the relationship between extracutaneous PEComa and primary cutaneous ones. We will review the clinical setting, histopathologic features, chromosomal abnormalities, differential diagnosis and treatment options for cutaneous PEComa. PMID:27019799

  8. Reducing renal uptake of 90Y- and 177Lu-labeled alpha-melanocyte stimulating hormone peptide analogues

    SciTech Connect

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

    2006-06-15

    The purpose of this study was to improve the tumor-to-kidney uptake ratios of 90Y- and 177Lu-[1,2,7,10-tetraazacyclododecane-1,4,7,10-tetraacetic acid-Re-Cys,D-Phe,Arg]alpha-melanocyte stimulating hormone (DOTA-RE(Arg)CCMSH), through coupling a negatively charged glutamic acid (Glu) to the peptide sequence. A new peptide of DOTA-Re(Glu,Arg)CCMSH was designed, synthesized and labeled with 90Y and 177Lu. Pharmacokinetics of 90Y- and 177Lu-DOTA-RE(Glu,Arg)CCNSH were determined in B16/F1 murine melanoma-bearing C57 mice. Both exhibited significantly less renal uptake than 90Y- and 177Lu-DOTA-Re(Arg)CCMSH at 30 min and at 2, 3, and 24 h after dose administration. The renal uptake values of 90Y- and 177Lu-DOTA-Re(Glu,Arg)CCMSH were 28.16% and 28.81% of those of 90Y- and 177Lu-DOTA-RE(Arg)CCMSH, respectively, at 4 hr post-injection. We also showed higher tumor-to-kidney uptake ratios 2.28 and 1.69 times that of 90Y- and 177Lu-DOTA-Re(Arg)CCMSH, respectively, at 4 h post-injection. The90Y- and 177Lu-DOTA-Re(Glu,Arg)CCMSH activity accumulation was low in normal organs except for kidneys. 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 90Y- and 177Lu-DOTA-Re(Glu,Arg)CCMSH, facilitating their potential applications as radiopharmaceuticals for targeted radionuclide therapy of melanoma.

  9. Borderline Personality Characteristics and Treatment Outcome in Cognitive-Behavioral Treatments for PTSD in Female Rape Victims

    ERIC Educational Resources Information Center

    Clarke, Stephanie B.; Rizvi, Shireen L.; Resick, Patricia A.

    2008-01-01

    Many studies report that comorbid borderline personality pathology is associated with poorer outcomes in the treatment of Axis I disorders. Given the high rates of comorbidity between borderline personality pathology and posttraumatic stress disorder (PTSD), it is essential to determine whether borderline symptomatology affects PTSD treatment…

  10. Association between schizotypal and borderline personality disorder traits, and cannabis use in young adults.

    PubMed

    Raynal, Patrick; Chabrol, Henri

    2016-09-01

    The aim of the study was to examine the association of schizotypal and borderline personality traits to cannabis use. Participants were 476 college students (95 males; 381 females; mean age of males=21; mean age of females=20.7) who completed self-report questionnaires assessing cannabis use, schizotypal and borderline personality traits. Problematic cannabis use, depressive symptoms, borderline and schizotypal traits were significantly inter-correlated. A logistic regression analysis showed that only borderline traits contributed significantly to cannabis use in the total sample. A multiple regression analysis showed that only schizotypal traits were positively and uniquely associated to problematic cannabis use symptoms among users. These results may imply that schizotypal traits are not a risk factor for initiating use, but may facilitate the development of problematic use symptoms among users. This study showed the necessity of taking into account schizotypal traits when exploring the relationships between depressive symptoms, borderline traits and cannabis use.

  11. The influence of borderline personality features on inpatient adolescent suicide risk.

    PubMed

    Yalch, Matthew M; Hopwood, Christopher J; Fehon, Dwain C; Grilo, Carlos M

    2014-01-01

    Suicide is a leading cause of death among adolescents and suicidal behavior is one of the primary risk factors for youth psychiatric hospitalizations. A number of studies indicate that depression and substance abuse are associated with suicide risk in this population, but less is known about the role of borderline personality features or their incremental influence over other known risk factors in indicating suicidal behavior among adolescents. This study examined whether borderline features were associated with suicide risk when controlling for symptoms of depression and substance abuse in a sample of adolescents hospitalized in an inpatient psychiatric facility. Self-report data from 477 adolescent psychiatric inpatients were used to test hypotheses about the association of borderline features with suicide risk after controlling for other common risk factors. Borderline features were significantly related to suicide risk even after accounting for symptoms of depression and substance abuse. These findings underscore the clinical value of routinely assessing borderline features among adolescents.

  12. Borderline personality features in childhood: the role of subtype, developmental timing, and chronicity of child maltreatment.

    PubMed

    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.

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

    PubMed

    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.

  14. An unusual association of malignant gastrointestinal neuroectodermal tumor (clear cell sarcoma-like) and Ewing sarcoma.

    PubMed

    Insabato, Luigi; Guadagno, Elia; Natella, Valentina; Somma, Anna; Bihl, Michel; Pizzolorusso, Antonio; Mainenti, Pier Paolo; Apice, Gaetano; Tornillo, Luigi

    2015-09-01

    Very recently a new designation of "Malignant Neuroectodermal Gastrointestinal Tumor" has been proposed for an aggressive form of neuroectodermal tumor with features similar to that of Clear Cell Sarcoma of Soft Tissue, however without a melanocytic differentiation. Also known as "clear cell sarcoma-like tumors of the gastrointestinal tract", these tumors show some features strongly suggesting an origin from a gastrointestinal neuroectodermal precursor cell unable to differentiate along the melanocytic lineage. They occur mainly in young and middle-aged adults, and have a poor prognosis with a high rate of liver and lymphnode metastases. Histologically they are composed of epithelioid or oval-to spindle cells with a sheet-like or nested pattern of growth, strongly positive for neural markers (S-100, SOX10, and vimentin) and negative for the melanocytic ones. EWSR1 gene rearrangements including EWSR1-ATF1 or EWSR1-CREB1 GENE fusions are typically assessed in these tumors. Here we report a case of malignant neuroectodermal gastrointestinal tumor which immunophenotypically unusually expressed FLI-1, occurring in a 29-year-old man with a previous medical history of Ewing sarcoma. We finally suggest that this case might be a further evidence of a link between these two entities.

  15. Selective proliferation of normal human melanocytes in vitro in the presence of phorbol ester and cholera toxin by Eisinger and Marko.

    PubMed

    Scott, Glynis

    2014-01-01

    Melanocytes are pigment producing cells that arise from the neural crest and migrate to the skin early in fetal development. The pigment that melanocytes synthesize, melanin, plays a critical role in protecting the skin from mutagenic ultraviolet irradiation. Melanocytes are also precursor cells for melanoma, a deadly form of skin cancer. Because melanocytes make up a minority population of cells in the epidermis they have been difficult to propagate in culture. The landmark paper by Eisinger and Marko, described below, was the first successful report of large scale propagation of pure cultures of melanocytes. This paper set the stage for an explosive growth in knowledge in the biology of human melanocytes and allowed scientists to begin dissecting the different oncogenic events involved in the transition of melanocytes to melanoma.

  16. Dissociation in borderline personality disorder: a detailed look.

    PubMed

    Korzekwa, Marilyn I; Dell, Paul F; Links, Paul S; Thabane, Lehana; Fougere, Philip

    2009-01-01

    The objective of the present study was to assess in detail the whole spectrum of normal and pathological dissociative experiences and dissociative disorder (DD) diagnoses in borderline personality disorder (BPD) as diagnosed with the Revised Diagnostic Interview for Borderlines. Dissociation was measured comprehensively in 21 BPD outpatients using the Structured Clinical Interview for DSM-IV Dissociative Disorders-Revised, the Multidimensional Inventory of Dissociation (MID), the Dissociative Experiences Scale pathological taxon analysis, and the Somatoform Dissociation Questionnaire. The frequencies of DDs in this BPD sample were as follows: 24% no DD, 29% mild DD (dissociative amnesia and depersonalization disorder), 24% DD Not Otherwise Specified (DDNOS), and 24% dissociative identity disorder. With regard to the dissociative experiences endorsed, almost all patients reported identity confusion, unexplained mood changes, and depersonalization. Even those BPD patients with mild DD reported derealization, depersonalization, and dissociative amnesia. BPD patients with DDNOS reported frequent depersonalization, frequent amnesia, and notable experiences of identity alteration. BPD patients with dissociative identity disorder endorsed severe dissociative symptoms in all categories. Analysis of the MID pathological dissociation items revealed that 32% of the items were endorsed at a clinically significant level of frequency by more than 50% of our BPD patients. In conclusion, the frequencies of Diagnostic and Statistical Manual of Mental Disorders (4th ed.) DDs in these patients with BPD were surprisingly high. Likewise, the "average" BPD patient endorsed a wide variety of recurrent pathological dissociative symptoms.

  17. Effects of PGF{sub 2{alpha}} on human melanocytes and regulation of the FP receptor by ultraviolet radiation

    SciTech Connect

    Scott, Glynis . E-mail: Glynis_Scott@urmc.rochester.edu; Jacobs, Stacey; Leopardi, Sonya; Anthony, Frank A.; Learn, Doug; Malaviya, Rama; Pentland, Alice

    2005-04-01

    Prostaglandins are potent lipid hormones that activate multiple signaling pathways resulting in regulation of cellular growth, differentiation, and apoptosis. In the skin, prostaglandins are rapidly released by keratinocytes following ultraviolet radiation and are chronically present in inflammatory skin lesions. We have shown previously that melanocytes, which provide photoprotection to keratinocytes through the production of melanin, express several receptors for prostaglandins, including the PGE{sub 2} receptors EP{sub 1} and EP{sub 3} and the PGF{sub 2{alpha}} receptor FP, and that PGF{sub 2{alpha}} stimulates melanocyte dendricity. We now show that PGF{sub 2{alpha}} stimulates the activity and expression of tyrosinase, the rate-limiting enzyme in melanin synthesis. Analysis of FP receptor regulation showed that the FP receptor is regulated by ultraviolet radiation in melanocytes in vitro and in human skin in vivo. We also show that ultraviolet irradiation stimulates production of PGF{sub 2{alpha}} by melanocytes. These results show that PGF{sub 2{alpha}} binding to the FP receptor activates signals that stimulate a differentiated phenotype (dendricity and pigmentation) in melanocytes. The regulation of the FP receptor and the stimulation of production of PGF{sub 2{alpha}} in melanocytes in response to ultraviolet radiation suggest that PGF{sub 2{alpha}} could act as an autocrine factor for melanocyte differentiation.

  18. Meyerson phenomenon in children: observation in five cases of congenital melanocytic nevi.

    PubMed

    Rolland, Sébastien; Kokta, Victor; Marcoux, Danielle

    2009-01-01

    To describe the characteristics of five pediatric patients with the Meyerson phenomenon associated with congenital melanocytic nevi, five cases were reviewed to retrieve information relating to clinical presentation, treatment and evolution of the eczematous phenomenon and of the nevi. Three of five patients were male. Mean age at presentation of the Meyerson phenomenon was 23 months (range: 4 mos-4 yrs). Three patients presented with only one halo eczematous lesion, while two patients presented with more then one halo eczematous lesions. The halo eczematous lesions were located on the leg, arm, and trunk in four, two, and two patients, respectively. All were associated with congenital melanocytic nevi with overlying hypertrichosis. Four were treated with topical corticosteroids, and five developed some degree of hypopigmentation within the nevic lesion. In children with Meyerson phenomenon associated with congenital hairy melanocytic nevi, neither trigger to the eczematous eruption nor preferential gender or anatomical site location was identified. The Meyerson phenomenon evolved towards hypopigmentation of the congenital melanocytic nevic lesions in all patients but no other cutaneous changes were observed on follow-up.

  19. Discrimination of Dysplastic Nevi from Common Melanocytic Nevi by Cellular and Molecular Criteria.

    PubMed

    Mitsui, Hiroshi; Kiecker, Felix; Shemer, Avner; Cannizzaro, Maria Vittoria; Wang, Claire Q F; Gulati, Nicholas; Ohmatsu, Hanako; Shah, Kejal R; Gilleaudeau, Patricia; Sullivan-Whalen, Mary; Cueto, Inna; McNutt, Neil Scott; Suárez-Fariñas, Mayte; Krueger, James G

    2016-10-01

    Dysplastic nevi (DNs), also known as Clark's nevi or atypical moles, are distinguished from common melanocytic nevi by variegation in pigmentation and clinical appearance, as well as differences in tissue patterning. However, cellular and molecular differences between DNs and common melanocytic nevi are not completely understood. Using cDNA microarray, quantitative RT-PCR, and immunohistochemistry, we molecularly characterized DNs and analyzed the difference between DNs and common melanocytic nevi. A total of 111 probesets (91 annotated genes, fold change > 2.0 and false discovery rate < 0.25) were differentially expressed between the two lesions. An unexpected finding in DNs was altered differentiation and activation of epidermal keratinocytes with increased expression of hair follicle-related molecules (keratin 25, trichohyalin, ribonuclease, RNase A family, 7) and inflammation-related molecules (S100A7, S100A8) at both genomic and protein levels. The immune microenvironment of DNs was characterized by an increase of T helper type 1 (IFNγ) and T helper type 2 (IL13) cytokines as well as an upregulation of oncostatin M and CXCL1. DUSP3, which regulates cellular senescence, was identified as one of the disease discriminative genes between DNs and common melanocytic nevi by three independent statistical approaches and its altered expression was confirmed by immunohistochemistry. The molecular and cellular changes in which the epidermal-melanin unit undergoes follicular differentiation as well as upregulation of defined cytokines could drive complex immune, epidermal, and pigmentary alterations.

  20. Enhanced bleaching treatment: opportunities for immune-assisted melanocyte suicide in vitiligo.

    PubMed

    Webb, Kirsten C; Eby, Jonathan M; Hariharan, Vidhya; Hernandez, Claudia; Luiten, Rosalie M; Le Poole, I Caroline

    2014-08-01

    Depigmentation in vitiligo occurs by progressive loss of melanocytes from the basal layer of the skin, and can be psychologically devastating to patients. T cell-mediated autoimmunity explains the progressive nature of this disease. Rather than being confronted with periods of rapid depigmentation and bouts of repigmentation, patients with long-standing, treatment-resistant vitiligo can undergo depigmentation treatment. The objective is to remove residual pigmentation to achieve a cosmetically acceptable result--that of skin with a uniform appearance. In the United States, only the use of mono-benzyl ether of hydroquinone (MBEH) is approved for this purpose. However, satisfactory results can take time to appear, and there is a risk of repigmentation. MBEH induces necrotic melanocyte death followed by a cytotoxic T-cell response to remaining, distant melanocytes. As cytotoxic T-cell responses are instrumental to depigmentation, we propose that combining MBEH with immune adjuvant therapies will accelerate immune-mediated melanocyte destruction to achieve faster, more definitive depigmentation than with MBEH alone. As Toll-like Receptor (TLR) agonists--imiquimod, CpG, and Heat Shock Protein 70 (HSP 70)--all support powerful Th1 responses, we propose that using MBEH in combination with these agents can achieve superior depigmentation results for vitiligo patients.

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

    PubMed

    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.

  2. Investigation by in vivo reflectance confocal microscopy: melanocytes at the edges of solar lentigines.

    PubMed

    Nakajima, Akiko; Funasaka, Yoko; Kawana, Seiji

    2012-07-01

    In vivo reflectance confocal microscopy (RCM) provides high-resolution, real-time optical sections of the skin in a non-invasive manner, allowing visualization of the skin in its native state. Highly reflective skin components including melanin, collagen and keratin appear bright (white) in RCM images. RCM examination of solar lentigines is known to show features that correlate well with histologic findings such as supranuclear melanin caps, but there are a limited number of reports on melanocyte dendrites. In this study, we utilized RCM to investigate the melanocyte dendricity and distribution within solar lentigines. Seventeen healthy Japanese females who had fairly large solar lentigines on their faces were recruited to join our clinical study, and we examined them by using RCM on their non-lesional areas, and the inside and the outer rim of the lesional areas. As a result, we discovered that dendritic melanocytes were rarely seen in the center of a solar lentigo (SL), but were seen at a very high frequency in the outer rim of a SL. The results suggest that the melanocytes are more active at the edge of a SL, produce more melanin, and often spread their dendrites widely in a horizontal direction. The findings in this report might shed light on the dynamic pathomechanisms of solar lentigines in vivo.

  3. Disruption of melanosome transport in melanocytes treated with theophylline causes their degradation by autophagy.

    PubMed

    Katsuyama, Yushi; Taira, Norihisa; Yoshioka, Masato; Okano, Yuri; Masaki, Hitoshi

    2017-02-07

    Melanosomes containing melanin are transported from the perinuclear area to the tips of dendrites in epidermal melanocytes, and are then transferred to keratinocytes. Thus, skin color is determined by the amount of melanin synthesized in melanocytes and the subsequent dispersion of melanosomes in the epidermis. Therefore, disrupting intracellular melanosome transport in melanocytes is considered an effective approach to regulate skin color. However, the fate of melanosomes that accumulate in melanocytes due to disrupted intracellular transport is unclear. In this study, we disrupted melanosome transport by knockdown of the motor protein MyosinVa. Knock-down of MyosinVa (M-KD) in cells treated with theophylline significantly down-regulated the mRNA and protein expression levels of tyrosinase. Interestingly, intracellular melanin contents in M-KD cells were decreased. Furthermore, M-KD cells showed activation of autophagy through increased expression of Microtubule-associated protein 1 light chain 3 (LC3) -II and decreased expression of p62. The sum of these results indicate that disruption of melanosome transport causes their degradation by autophagy.

  4. The human melanocyte as a particular target for UVA radiation and an endpoint for photoprotection assessment.

    PubMed

    Marrot, L; Belaidi, J P; Meunier, J R; Perez, P; Agapakis-Causse, C

    1999-06-01

    The induction of DNA breaks by UVA (320-400 nm) in the nucleus of normal human melanocytes in culture was investigated using single cell gel electrophoresis, also called the comet assay. Endogenous pigment and/or melanin-related molecules were found to enhance DNA breakage: comets were more intense in melanocytes than in fibroblasts, in cells with high melanin content or after stimulation of melanogenesis by supplying tyrosine in the culture medium. After UVA doses where strong comets were observed, neither cytotoxicity nor stimulation of tyrosinase activity were detected. However, the accumulation of p53 protein suggested that cells reacted to genotoxic stress under these experimental conditions. The same approach was used to compare two sunscreens with identical sun protection factors but different UVA protection factors. The results presented in this paper suggest that human melanocytes may be used as a target cell to evidence broadspectrum photoprotection. Moreover, these data appear to be helpful in getting a better understanding of the role of sunlight in the initiating steps of melanocyte transformation.

  5. Tissue expansion in the treatment of giant congenital melanocytic nevi of the upper extremity

    PubMed Central

    Ma, Tengxiao; Fan, Ke; Li, Lei; Xie, Feng; Li, Hao; Chou, Haiyan; Zhang, Zhengwen

    2017-01-01

    Abstract The aim of our study was to use tissue expansion for the treatment of giant congenital melanocytic nevi of the upper extremity and examine potential advantages over traditional techniques. There were 3 stages in the treatment of giant congenital melanocytic nevi of the upper extremities using tissue expansion: first, the expander was inserted into the subcutaneous pocket; second, the expander was removed, lesions were excised, and the wound of the upper extremity was placed into the pocket to delay healing; third, the residual lesion was excised and the pedicle was removed. The pedicle flap was then unfolded to resurface the wound. During the period between June 2007 and December 2015, there were 11 patients with giant congenital melanocytic nevi of the upper extremities who underwent reconstruction at our department with skin expansion. Few complications were noted in each stage of treatment. The functional and aesthetic results were observed and discussed in this study. Optimal aesthetic and functional results were obtained using tissue expansion to reconstruct the upper extremities due to the giant congenital melanocytic nevi. PMID:28353563

  6. Ultraviolet radiation acts as an independent mitogen for normal human melanocytes in culture

    SciTech Connect

    Libow, L.F.; Scheide, S.; DeLeo, V.A.

    1988-01-01

    Identification of growth factors for normal human melanocytes has been significantly aided by the recent development of in vitro culture systems for this cell. Utilizing such a system, we studied the effect of ultraviolet radiation (UVR) on both melanocyte growth and melanization by incorporation of 3H-thymidine and 3H-L-dihydroxyphenylalanine (3H-DOPA), respectively. 3H-thymidine incorporation was found to be significantly stimulated during the first 24 h following a single irradiation. 3H-DOPA incorporation was stimulated after a delay of 2 days postirradiation. Whereas UVR has long been known to induce melanocyte proliferation in vivo, these studies show that UVR can act as a mitogenic stimulus for this cell independent of the cutaneous environment. UVR can thus be added to a growing list of growth factors for epidermal pigment cells and is the only physical agent conclusively shown to act as a mitogen. Included in this list are substances that act via stimulation of the CAMP-kinase or protein kinase systems such as cholera toxin and phorbol esters. UVR is postulated to induce melanocyte proliferation by modulation of these second messenger pathways. With recent evidence linking growth factors, oncogenes and malignant transformation, this study supports the association between UVR exposure and the development of malignant melanoma, and suggests mechanisms whereby UVR may contribute to malignant transformation of this cell.

  7. CRH stimulation of corticosteroids production in melanocytes is mediated by ACTH.

    PubMed

    Slominski, Andrzej; Zbytek, Blazej; Szczesniewski, Andrzej; Semak, Igor; Kaminski, Jan; Sweatman, Trevor; Wortsman, Jacobo

    2005-04-01

    The response to systemic stress is organized along the hypothalamic-pituitary-adrenal axis (HPA), whereas the response to a peripheral stress (solar radiation) is mediated by epidermal melanocytes (cells of neural crest origin) responsible for the pigmentary reaction. Melanocytes express proopiomelanocortin (POMC), corticotropin-releasing hormone (CRH), and CRH receptor-1 (CRH-R1) and can produce corticosterone. In the present study, incubation of normal epidermal melanocytes with CRH was found to trigger a functional cascade structured hierarchically and arranged along the same algorithm as in the HPA axis: CRH activation of CRH-R1 stimulated cAMP accumulation and increased POMC gene expression and production of ACTH. CRH and ACTH also enhanced production of cortisol and corticosterone, and cortisol production was also stimulated by progesterone. The chemical identity of the cortisol was confirmed by liquid chromatography-mass spectrometry (LC/MS2) with [corrected] mass spectrometry-mass spectrometry analyses. POMC gene silencing abolished the stimulatory effect of CRH on corticosteroid synthesis, indicating that this is indirect and mediated via production of ACTH. Thus the melanocyte response to CRH is highly organized along the same functional hierarchy as the HPA axis. This pattern demonstrates the fractal nature of the response to stress with similar activation sequence at the single-cell and whole body levels.

  8. Proliferation, DNA ploidy, p53 overexpression and nuclear DNA fragmentation in six equine melanocytic tumours.

    PubMed

    Roels, S; Tilmant, K; Van Daele, A; Van Marck, E; Ducatelle, R

    2000-09-01

    Melanocytic tumours are a well-known clinical and pathological entity in horses, but further phenotypic characterization of these tumours is lacking. Six melanocytic tumours from five horses (two metastatic and four benign) were examined by Ki67, PCNA and p53 immunostaining, DNA nick end labelling (Tunel) and Feulgen staining. The stainings were evaluated using quantitative image analysis. The resulting parameters of growth fraction (Ki67), S-phase index (PCNA), p53 index, apoptotic index, DNA index, nuclear diameter, ploidy balance, proliferation index (Feulgen) and hyperploidy were analysed. The metastatic melanomas showed overexpression of p53 in a large portion of the cells. Apoptosis was also found in the metastatic melanomas. No differences were found in growth fraction, S-phase index (PCNA) nor in DNA configuration between the metastatic and the benign tumours. No immunohistochemical evidence of mutant p53 could be found in the tumours. In conclusion, melanocytic tumours in horses seem to have different phenotypic characteristics in comparison with melanocytic tumours in dogs, cats and humans, especially with respect to proliferative activity of the benign tumours. Therefore, markers put forward in these other species for predicting the clinical behaviour of the melanomas seem to be of no value in the horse. Moreover, quantitative DNA changes or p53 mutations do not seem to be involved in tumourogenesis in these cases.

  9. Postnatal lineage mapping of follicular melanocytes with the Tyr::CreER(T) (2) transgene.

    PubMed

    Harris, Melissa L; Pavan, William J

    2013-03-01

    One of the main advantages of using inducible and conditional transgenes to study pigment cell biology is that they allow for genetic manipulation within melanocytes after roles in general neural crest or melanoblast development have been fulfilled. Specifically, we focus here on the ability of the Tyr::CreER(T) (2) transgenic line to alter genes within follicular melanocytes postnatally. Using the Gt(ROSA)26Sor(tm1sor) reporter allele, we present in detail the expression and activity of Tyr::CreER(T) (2) when induced during hair morphogenesis and adult hair cycling. We find that despite similarities in expression pattern to endogenous TYR, Tyr::CreER(T) (2) is effective at targeting both undifferentiated and differentiated melanocytes within the hair follicle. We also find that Tyr::CreER(T) (2) provides the highest levels of recombination when induced during the early phases of hair growth. In conclusion, the descriptions provided here will guide future analyses of gene function within the melanocyte system of the hair follicle when using this Tyr::CreER(T) (2) transgene.

  10. TRPM1 Forms Ion Channels Associated with Melanin Content in Melanocytes

    PubMed Central

    Oancea, Elena; Vriens, Joris; Brauchi, Sebastian; Jun, Janice; Splawski, Igor; Clapham, David E.

    2014-01-01

    TRPM1(melastatin), which encodes the founding member of the TRPM family of transient receptor potential (TRP) ion channels, was first identified by its reduced expression in a highly metastatic mouse melanoma cell line. Clinically, TRPM1 is used as a predictor of melanoma progression in humans because of its reduced abundance in more aggressive forms of melanoma. Although TRPM1 is found primarily in melanin-producing cells and has the molecular architecture of an ion channel, its function is unknown. Here we describe an endogenous current in primary human neonatal epidermal melanocytes and mouse melanoma cells that was abrogated by expression of microRNA directed against TRPM1. Messenger RNA analysis showed that at least five human ion channel–forming isoforms of TRPM1 could be present in melanocytes, melanoma, brain, and retina. Two of these isoforms are encoded by highly conserved splice variants that are generated by previously uncharacterized exons. Expression of these two splice variants in human melanoma cells generated an ionic current similar to endogenous TRPM1 current. In melanoma cells, TRPM1 is prevalent in highly dynamic intracellular vesicular structures. Plasma membrane TRPM1 currents are small, raising the possibility that their primary function is intracellular, or restricted to specific regions of the plasma membrane. In neonatal human epidermal melanocytes, TRPM1 expression correlates with melanin content. We propose that TRPM1 is an ion channel whose function is critical to normal melanocyte pigmentation and is thus a potential target for pigmentation disorders. PMID:19436059

  11. The immunology and inflammatory responses of human melanocytes in infectious diseases.

    PubMed

    Gasque, Philippe; Jaffar-Bandjee, Marie Christine

    2015-10-01

    Melanin is a canonical and major defense molecule in invertebrates but its role in mammalian immunity remains unexplored. In contrast, several recent studies have highlighted the emerging innate immune activities of human melanin-producing cells which can sense and respond to bacterial and viral infections. Indeed, the skin is a major portal of entry for pathogens such as arboviruses (Chikungunya, Dengue) and bacteria (mycobacterium leprae, Leptospira spirochetes). Melanocytes of the epidermis could contribute to the phagocytosis of these invading pathogens and to present antigens to competent immune cells. Melanocytes are known to produce key cytokines such as IL-1β, IL6 and TNF-α as well as chemokines. These molecules will subsequently alert macrophages, neutrophils, fibroblasts and keratinocytes through unique crosstalk mechanisms. The infection and the inflammatory responses will control melanocyte's immune and metabolic functions and could contribute to skin manifestations (rash, hyper or de-pigmentation, epidermolysis and psoriasis-like lesions). This review will address the potential role of melanocytes in immunity, inflammation and infection of the skin in health and diseases.

  12. Nanomedicine as a potent strategy in melanoma tumor microenvironment.

    PubMed

    Pautu, Vincent; Leonetti, Daniela; Lepeltier, Elise; Clere, Nicolas; Passirani, Catherine

    2017-02-20

    Melanoma originated from melanocytes is the most aggressive type of skin cancer. Despite considerable progresses in clinical treatment with the discovery of BRAF or MEK inhibitors and monoclonal antibodies, the durability of response to treatment is often limited to the development of acquired resistance and systemic toxicity. The limited success of conventional treatment highlights the importance of understanding the role of melanoma tumor microenvironment in tumor developement and drug resistance. Nanoparticles represent a promising strategy for the development of new cancer treatments able to improve the bioavailability of drugs and increase their penetration by targeting specifically tumors cells and/or tumor environment. In this review, we will discuss the main influence of tumor microenvironment in melanoma growth and treatment outcome. Furthermore, third generation loaded nanotechnologies represent an exciting tool for detection, treatment, and escape from possible mechanism of resistance mediated by tumor microenvironment, and will be highlighted in this review.

  13. Bone tumor

    MedlinePlus

    Tumor - bone; Bone cancer; Primary bone tumor; Secondary bone tumor; Bone tumor - benign ... The cause of bone tumors is unknown. They often occur in areas of the bone that grow rapidly. Possible causes include: Genetic defects ...

  14. Helium-neon laser irradiation stimulates migration and proliferation in melanocytes and induces repigmentation in segmental-type vitiligo.

    PubMed

    Yu, Hsin-Su; Wu, Chieh-Shan; Yu, Chia-Li; Kao, Ying-Hsien; Chiou, Min-Hsi

    2003-01-01

    Low-energy helium-neon lasers (632.8 nm) have been employed in a variety of clinical treatments including vitiligo management. Light-mediated reaction to low-energy laser irradiation is referred to as biostimulation rather than a thermal effect. This study sought to determine the theoretical basis and clinical evidence for the effectiveness of helium-neon lasers in treating vitiligo. Cultured keratinocytes and fibroblasts were irradiated with 0.5-1.5 J per cm2 helium-neon laser radiation. The effects of the helium-neon laser on melanocyte growth and proliferation were investigated. The results of this in vitro study revealed a significant increase in basic fibroblast growth factor release from both keratinocytes and fibroblasts and a significant increase in nerve growth factor release from keratinocytes. Medium from helium-neon laser irradiated keratinocytes stimulated [3H]thymidine uptake and proliferation of cultured melanocytes. Furthermore, melanocyte migration was enhanced either directly by helium-neon laser irradiation or indirectly by the medium derived from helium-neon laser treated keratinocytes. Thirty patients with segmental-type vitiligo on the head and/or neck were enrolled in this study. Helium-neon laser light was administered locally at 3.0 J per cm2 with point stimulation once or twice weekly. The percentage of repigmented area was used for clinical evaluation of effectiveness. After an average of 16 treatment sessions, initial repigmentation was noticed. Marked repigmentation (>50%) was observed in 60% of patients with successive treatments. Basic fibroblast growth factor is a putative melanocyte growth factor, whereas nerve growth factor is a paracrine factor for melanocyte survival in the skin. Both nerve growth factor and basic fibroblast growth factor stimulate melanocyte migration. It is reasonable to propose that helium-neon laser irradiation clearly stimulates melanocyte migration and proliferation and mitogen release for melanocyte growth

  15. Pattern of HER-2 Gene Amplification and Protein Expression in Benign, Borderline, and Malignant Ovarian Serous and Mucinous Neoplasms.

    PubMed

    Mohammed, Rabab A A; Makboul, Rania; Elsers, Dalia A H; Elsaba, Tarek M A M; Thalab, Abeer M A B; Shaaban, Omar M

    2016-06-15

    Amplification of HER-2 gene and overexpression of HER-2 receptor play a significant role in the progression of a number of malignancies such as breast cancer. Trastuzumab (anti-HER-2 therapeutic agent) has been used successfully in treatment of breast cancer. The aim of this study was to assess the pattern of HER-2 gene amplification and of HER-2 receptor expression in a spectrum of serous and mucinous ovarian tumors to determine whether HER-2 is altered in these neoplasms similar to that occurring in breast cancer. Formalin-fixed paraffin-embedded microarray tissue sections from 212 specimens were stained with HER-2 antibody using immunohistochemistry and with anti-HER-2 DNA probe using chromogenic in situ hybridization. Specimens consisted of 65 benign tumors (50 serous and 15 mucinous), 26 borderline (13 serous and 13 mucinous), 73 malignant (53 serous carcinoma and 20 mucinous carcinoma), 18 metastatic deposits (13 serous and 5 mucinous), in addition to 30 normal tissues (16 ovarian surface and 14 normal fallopian tube). HER-2 protein-positive expression was not detected in the normal or the benign tissues. Borderline neoplasms showed positive staining, but no overexpression. HER-2 overexpression was seen only in 4 carcinoma specimens: 1/53 (1.8%) primary serous carcinomas and 3/20 (15%) primary mucinous carcinomas. HER-2 gene amplification was seen in 4 specimens: 2 primary mucinous carcinomas and 2 malignant deposits of these 2 mucinous carcinomas. In conclusion, alteration of HER-2 was not detected in ovarian serous neoplasms; however, in mucinous carcinoma, HER-2 amplification and overexpression occur more frequently.

  16. Genomic landscapes of breast fibroepithelial tumors.

    PubMed

    Tan, Jing; Ong, Choon Kiat; Lim, Weng Khong; Ng, Cedric Chuan Young; Thike, Aye Aye; Ng, Ley Moy; Rajasegaran, Vikneswari; Myint, Swe Swe; Nagarajan, Sanjanaa; Thangaraju, Saranya; Dey, Sucharita; Nasir, Nur Diyana Md; Wijaya, Giovani Claresta; Lim, Jing Quan; Huang, Dachuan; Li, Zhimei; Wong, Bernice Huimin; Chan, Jason Yong Sheng; McPherson, John R; Cutcutache, Ioana; Poore, Gregory; Tay, Su Ting; Tan, Wai Jin; Putti, Thomas Choudary; Ahmad, Buhari Shaik; Iau, Philip; Chan, Ching Wan; Tang, Anthony P H; Yong, Wei Sean; Madhukumar, Preetha; Ho, Gay Hui; Tan, Veronique Kiak Mien; Wong, Chow Yin; Hartman, Mikael; Ong, Kong Wee; Tan, Benita K T; Rozen, Steven G; Tan, Patrick; Tan, Puay Hoon; Teh, Bin Tean

    2015-11-01

    Breast fibroepithelial tumors comprise a heterogeneous spectrum of pathological entities, from benign fibroadenomas to malignant phyllodes tumors. Although MED12 mutations have been frequently found in fibroadenomas and phyllodes tumors, the landscapes of genetic alterations across the fibroepithelial tumor spectrum remain unclear. Here, by performing exome sequencing of 22 phyllodes tumors followed by targeted sequencing of 100 breast fibroepithelial tumors, we observed three distinct somatic mutation patterns. First, we frequently observed MED12 and RARA mutations in both fibroadenomas and phyllodes tumors, emphasizing the importance of these mutations in fibroepithelial tumorigenesis. Second, phyllodes tumors exhibited mutations in FLNA, SETD2 and KMT2D, suggesting a role in driving phyllodes tumor development. Third, borderline and malignant phyllodes tumors harbored additional mutations in cancer-associated genes. RARA mutations exhibited clustering in the portion of the gene encoding the ligand-binding domain, functionally suppressed RARA-mediated transcriptional activation and enhanced RARA interactions with transcriptional co-repressors. This study provides insights into the molecular pathogenesis of breast fibroepithelial tumors, with potential clinical implications.

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

    NASA Astrophysics Data System (ADS)

    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.

  18. Biological characterization of human fibroblast-derived mitogenic factors for human melanocytes.

    PubMed Central

    Imokawa, G; Yada, Y; Morisaki, N; Kimura, M

    1998-01-01

    To clarify the paracrine linkage between human fibroblasts and melanocytes in cutaneous pigmentation, we studied the effects of human fibroblast-derived factors on the proliferation of human melanocytes. In medium conditioned for 4 days with human fibroblast culture, factors were produced that markedly stimulated DNA synthesis of human melanocytes. The stimulatory effect was higher in medium conditioned with fibroblasts from aged skin than in medium conditioned with fibroblasts from young skin, and was interrupted by inhibitors of tyrosine kinase, such as tyrphostin, genistein and herbimycin, but not by inhibitors of protein kinases C and A, such as H-7 and phloretin. The conditioned medium was also capable of activating mitogen-activated protein kinase of human melanocytes, with old fibroblasts being more effective than young ones. Analysis of factors released into the conditioned medium revealed that levels of hepatocyte growth factor (HGF) and stem cell factor (SCF) were increased in old-fibroblast-conditioned medium compared with young-fibroblast-conditioned medium. In contrast, levels of basic fibroblast growth factor (bFGF) were similar in both media. When the conditioned medium was treated with HGF antibody with or without SCF antibody, the increase in DNA synthesis by human melanocytes was decreased to 20% of the elevated level, whereas antibodies to bFGF had no effect. Analysis of the medium conditioned for 4 days after cytokine application demonstrated that, of the cytokines tested, interleukin 1alpha and tumour necrosis factor alpha are highly effective in stimulating HGF secretion by old fibroblasts. HGF and SCF, but not bFGF, were markedly increased in culture medium in the presence of IL-1alpha, and this stimulatory effect was confined to young human fibroblasts. These findings suggest that SCF and HGF derived from human fibroblasts may play a part in regulating cutaneous pigmentation during inflammation and aging. PMID:9494091

  19. Impression Cytology in a Series of Clinically Diagnosed Ocular Surface Melanocytic Lesions

    PubMed Central

    Kanavi, Mozhgan Rezaei; Hosseini, Seyed Bagher; Aliakbar-Navahi, Roshanak; Aghaei, Hossein

    2017-01-01

    Purpose: To report impression cytology (IC) results of clinically diagnosed ocular surface melanocytic lesions. Methods: Ten patients with a clinical diagnosis of an ocular surface melanocytic lesion underwent IC using cellulose acetate strips and Periodic acid Schiff-Papanicolaou staining. Excisional biopsy of lesions was performed in case of observing atypical cells on IC or at the patient's request, and excised specimens were subjected to histopathological analysis. Agreement between clinical diagnoses and IC results and between IC results and histopathology were evaluated. Results: Clinical diagnoses were nevi in 6, primary acquired melanosis (PAM) with atypia/melanoma in 2, and atypical nevus versus pigmented conjunctival intraepithelial neoplasia (CIN) in 2 cases. IC results were suggestive of a benign nevus in 7, PAM with atypia/melanoma in 2 and CIN versus an atypical epithelioid type melanocytic lesion in 1 case. IC results were consistent with the clinical diagnoses in 9 cases (Cohen's kappa index of 0.83) and excluded CIN in 1. Histopathology in 6 cases disclosed benign melanonevus in 3, malignant melanoma in the context of PAM with atypia in 2, and CIN in 1 case. Histologic results were well correlated with the IC features (Cohen's kappa index of 0.74). Conclusion: By demonstrating typical cytomorphological features of ocular superficial layers IC diagnosed the true nature of melanocytic ocular surface lesions in the majority of cases. Although IC does not substitute histopathology, given the high correlation between IC results and histopathology, it can be of great assistance in diagnosis and management of ocular surface melanocytic lesions. PMID:28299002

  20. Effects of hypergravity on the expression of multidrug resistance proteins in human melanocytic cells

    NASA Astrophysics Data System (ADS)

    Lambers, B.; Stieber, C.; Grigorieva, O.; Block, I.; Bromeis, B.; Buravkova, L.; Gerzer, R.; Ivanova, K.

    In humans the skin serves as a barrier against potentially harmful effects of the environment Human melanocytes constitute the principal cells for skin pigmentation by synthesizing the pigment melanin Melanin acts as a scavenger for free radicals that may arise during metabolic stress The melanocytes are also able to secrete a wide range of signal molecules In previous studies we found that normal human melanocytes NHMs and non-metastatic melanoma cells respond to long-time exposure to hypergravity up to 5 g for 24 h with elevated efflux of guanosine 3 5 -cyclic monophosphate cGMP in the presence of phosphodiesterase PDE inhibitors e g 3-isobutyl-1-methylxanthine Cyclic GMP is known to play a signaling role in human melanocyte physiology It controls the signaling activities of nitric oxide NO in relation to melanogenesis as well as in melanocyte-extracellular matrix interactions that may be important for some pathological processes including metastasis The present study investigated the effects of hypergravity on the expression of the multidrug resistance proteins MRP 4 and 5 as highly selective cGMP exporters in non-stimulated and NO-stimulated NHMs and melanoma cells MCs on mRNA levels using semi-quantitative RT-PCR analysis Hypergravity up to 5 g for 24 h was produced by horizontal centrifugal acceleration The NONOate DETA-NO 0 1 mM was used as a direct NO donor for cell stimulation For 5-g experiments the mRNA levels for the highly specific cGMP transporter MRP5 appeared to be

  1. Preoperative Modified FOLFIRINOX Treatment Followed by Capecitabine-Based Chemoradiation for Borderline Resectable Pancreatic Cancer

    PubMed Central

    Katz, Matthew H. G.; Shi, Qian; Ahmad, Syed A.; Herman, Joseph M.; Marsh, Robert de W.; Collisson, Eric; Schwartz, Lawrence; Frankel, Wendy; Martin, Robert; Conway, William; Truty, Mark; Kindler, Hedy; Lowy, Andrew M.; Bekaii-Saab, Tanios; Philip, Philip; Talamonti, Mark; Cardin, Dana; LoConte, Noelle; Shen, Perry; Hoffman, John P.; Venook, Alan P.

    2016-01-01

    IMPORTANCE Although consensus statements support the preoperative treatment of borderline resectable pancreatic cancer, no prospective, quality-controlled, multicenter studies of this strategy have been conducted. Existing studies are retrospective and confounded by heterogeneity in patients studied, therapeutic algorithms used, and outcomes reported. OBJECTIVE To determine the feasibility of conducting studies of multimodality therapy for borderline resectable pancreatic cancer in the cooperative group setting. DESIGN, SETTING, AND PARTICIPANTS A prospective, multicenter, single-arm trial of a multimodality treatment regimen administered within a study framework using centralized quality control with the cooperation of 14 member institutions of the National Clinical Trials Network. Twenty-nine patients with biopsy-confirmed pancreatic cancer preregistered, and 23 patients with tumors who met centrally reviewed radiographic criteria registered. Twenty-two patients initiated therapy (median age, 64 years [range, 50–76 years]; 55% female). Patients registered between May 29, 2013, and February 7,2014. INTERVENTIONS Patients received modified FOLFIRINOX treatment (85 mg/m2 of oxaliplatin, 180 mg/m2 of irinotecan hydrochloride, 400 mg/m2 of leucovorin calcium, and then 2400 mg/m2 of 5-fluorouracil for 4 cycles) followed by 5.5 weeks of external-beam radiation (50.4 Gy delivered in 28 daily fractions) with capecitabine (825 mg/m2 orally twice daily) prior to pancreatectomy. MAIN OUTCOMES AND MEASURES Feasibility, defined by the accrual rate, the safety of the preoperative regimen, and the pancreatectomy rate. RESULTS The accrual rate of 2.6 patients per month was superior to the anticipated rate. Although 14 of the 22 patients (64% [95% CI, 41%–83%]) had grade 3 or higher adverse events, 15 of the 22 patients (68% [95% CI, 49%–88%]) underwent pancreatectomy. Of these 15 patients, 12 (80%) required vascular resection, 14 (93%) had microscopically negative margins

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

    PubMed

    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.

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

    PubMed Central

    BELSKY, DANIEL W.; CASPI, AVSHALOM; ARSENEAULT, LOUISE; BLEIDORN, WIEBKE; FONAGY, PETER; GOODMAN, MARIANNE; HOUTS, RENATE; MOFFITT, TERRIE E.

    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 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. PMID:22293008

  4. The pericyte antigen RGS5 in perivascular soft tissue tumors.

    PubMed

    Shen, Jia; Shrestha, Swati; Yen, Yu-Hsin; Scott, Michelle A; Soo, Chia; Ting, Kang; Peault, Bruno; Dry, Sarah M; James, Aaron W

    2016-01-01

    Perivascular soft tissue tumors are relatively uncommon neoplasms of unclear lineage of differentiation, although most are presumed to originate from or differentiate to pericytes or a modified perivascular cell. Among these, glomus tumor, myopericytoma, and angioleiomyoma share a spectrum of histologic findings and a perivascular growth pattern. In contrast, solitary fibrous tumor was once hypothesized to have pericytic differentiation--although little bona fide evidence of pericytic differentiation exists. Likewise the perivascular epithelioid cell tumor (PEComa) family shares a perivascular growth pattern, but with distinctive dual myoid-melanocytic differentiation. RGS5, regulator of G-protein signaling 5, is a novel pericyte antigen with increasing use in animal models. Here, we describe the immunohistochemical expression patterns of RGS5 across perivascular soft tissue tumors, including glomus tumor (n = 6), malignant glomus tumor (n = 4), myopericytoma (n = 3), angioleiomyoma (n = 9), myofibroma (n = 4), solitary fibrous tumor (n = 10), and PEComa (n = 19). Immunohistochemical staining and semi-quantification was performed, and compared to αSMA (smooth muscle actin) expression. Results showed that glomus tumor (including malignant glomus tumor), myopericytoma, and angioleiomyoma shared a similar diffuse immunoreactivity for RGS5 and αSMA across all tumors examined. In contrast, myofibroma, solitary fibrous tumor and PEComa showed predominantly focal to absent RGS5 immunoreactivity. These findings further support a common pericytic lineage of differentiation in glomus tumors, myopericytoma and angioleiomyoma. The pericyte marker RGS5 may be of future clinical utility for the evaluation of pericytic differentiation in soft tissue tumors.

  5. Borderline personality disorder: bipolarity, mood stabilizers and atypical antipsychotics in treatment.

    PubMed

    Belli, Hasan; Ural, Cenk; Akbudak, Mahir

    2012-10-01

    In this article, it is aimed to review the efficacies of mood stabilizers and atypical antipsychotics, which are used commonly in psychopharmacological treatments of bipolar and borderline personality disorders. In this context, common phenomenology between borderline personality and bipolar disorders and differential features of clinical diagnosis will be reviewed in line with the literature. Both disorders can demonstrate common features in the diagnostic aspect, and can overlap phenomenologically. Concomitance rate of both disorders is quite high. In order to differentiate these two disorders from each other, quality of mood fluctuations, impulsivity types and linear progression of disorders should be carefully considered. There are various studies in mood stabilizer use, like lithium, carbamazepine, oxcarbazepine, sodium valproate and lamotrigine, in the treatment of borderline personality disorder. Moreover, there are also studies, which have revealed efficacies of risperidone, olanzapine and quetiapine as atypical antipsychotics. It is not easy to differentiate borderline personality disorder from the bipolar disorders. An intensively careful evaluation should be performed. This differentiation may be helpful also for the treatment. There are many studies about efficacy of valproate and lamotrigine in treatment of borderline personality disorder. However, findings related to other mood stabilizers are inadequate. Olanzapine and quetiapine are reported to be more effective among atypical antipsychotics. No drug is approved for the treatment of borderline personality disorder by the entitled authorities, yet. Psychotherapeutic approaches have preserved their significant places in treatment of borderline personality disorder. Moreover, symptom based approach is recommended in use of mood stabilizers and atypical antipsychotics.

  6. Alpha-Melanocyte Stimulating Hormone Protects against Cytokine-Induced Barrier Damage in Caco-2 Intestinal Epithelial Monolayers

    PubMed Central

    Váradi, Judit; Harazin, András; Fenyvesi, Ferenc; Réti-Nagy, Katalin; Gogolák, Péter; Vámosi, György; Bácskay, Ildikó; Fehér, Pálma; Ujhelyi, Zoltán; Vasvári, Gábor; Róka, Eszter; Haines, David; Deli, Mária A.; Vecsernyés, Miklós

    2017-01-01

    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. PMID:28103316

  7. Etiology of Ascites and Pleural Effusion Associated with Ovarian Tumors: Literature Review and Case Reports of Three Ovarian Tumors Presenting with Massive Ascites, but without Peritoneal Dissemination

    PubMed Central

    Miyoshi, Ai; Miyatake, Takashi; Hara, Takeya; Tanaka, Asuka; Komura, Naoko; Komiya, Shinnosuke; Kanao, Serika; Takeda, Masumi; Mimura, Mayuko; Nagamatsu, Masaaki; Yokoi, Takeshi

    2015-01-01

    Borderline ovarian tumors are benign but relatively large tumors that are often initially mistaken as ovarian cancers. We report three cases of stage I borderline ovarian tumors having massive ascites that we (preoperatively) suspected of being advanced ovarian cancer. The three patients (35, 47, and 73 years old) reported feeling fullness of the abdomen before consulting their gynecologist. By CT scan, they were diagnosed with a pelvic tumor accompanied by massive ascites, the diameters of which were 11, 20, and 11 cm, respectively. Postsurgical pathology showed all were stage I borderline ovarian tumors without dissemination; two were mucinous and one was serous. The amount of ascites was 6,300, 2,600, and 3,600 mL, respectively, and was serous in all. Cytodiagnosis of the ascites found that one was positive for tumor cells and two were negative. After resection of the mass, the ascites disappeared in all three cases. No pleural effusion was present at any time. The literature is reviewed concerning ascites and pleural effusions linked to ovarian tumors, and a supposition is forwarded of why pleural effusion presents sporadically in these cases. PMID:26858849

  8. The buffer role of meaning in life in hopelessness in women with borderline personality disorders.

    PubMed

    Marco, José H; Guillén, Veronica; Botella, Cristina

    2017-01-01

    Meaning in life has been found to be a protective factor against suicidal ideation. The aim of this study was to investigate whether meaning in life can moderate and buffer the association between suicide risk factors and hopelessness in women with borderline personality disorders. One hundred twenty-four women diagnosed with borderline personality disorder completed self-report measures of suicide risk factors, hopelessness, and meaning in life. The main result from this study was that meaning in life moderated the association between suicide risk factors and hopelessness. Meaning in life is an important variable in the prevention and treatment of risk of suicide in women with borderline personality disorder.

  9. The experience of borderline phenomena through cinema: Guentin Tarantino's Reservoir dogs, true romance, and pulp fiction.

    PubMed

    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.

  10. Role of nitric oxide and cyclic GMP signaling in melanocyte response to hypergravity

    NASA Astrophysics Data System (ADS)

    Ivanova, Krassimira; Lambers, Britta; Tsiockas, Wasiliki; Block, Ingrid; Gerzer, Rupert

    Nitric oxide (NO) has a prominent role in many (patho)physiological processes in the skin including erythema, inflammation, and cancerogenesis. The soluble guanylyl cyclase (sGC), a key transducer in NO signaling, catalyzes the formation of the second messenger guanosine 3´,5´-cyclic monophosphate (cyclic cGMP or cGMP). For human melanocytes, which are responsible for skin pigmentation by synthesizing the pigment melanin, it has been reported that the NO/sGC/cGMP pathway is involved in UVB-induced melanogenesis. Melanin acts as a scavenger for free radicals that may arise during metabolic stress. It may also act as a photosensitizer that generates active oxygen species upon UV irradiation, which may initiate hypopigmentary disorders (e.g., vitiligo) as well as UV-induced oncogene cell transformation. In addition, melanoma, a deadly skin cancer, which arises from transformed melanocytes, is characterized by a resistance to chemotherapy. In our studies we have shown that NO can induce perturbation of melanocyte-extracellular matrix component interactions, which may contribute to loss of melanocytes or melanoma metastasis. Such NO effects appear to be modulated partly via cGMP. Moreover, we found that different guanylyl cyclase isoforms are responsible for cGMP synthesis in melanocytic cells. Normal human melanocytes and nonmetastatic melanoma cells predominantly express sGC, which appears to be associated with melanogenesis, whereas absence of NO-sensitive GC, but up-regulated activities of the natriuretic peptide-sensitive membrane guanylyl cyclase isoforms were found in highly metastatic phenotypes. Due to the growing interest in the regulation of signaling activities in normal and transformed cells under altered gravity conditions, we have further investigated whether the NO/cGMP signaling is involved in melanocyte response to gravitational stress. We found that normal human melanocytes and non-metastatic melanoma cell lines, but not highly metastatic cells

  11. Hepatic perivascular epithelioid cell tumor

    PubMed Central

    Tang, Da; Wang, Jianmin; Tian, Yuepeng; Li, Qiuguo; Yan, Haixiong; Wang, Biao; Xiong, Li; Li, Qinglong

    2016-01-01

    Abstract Rational: Perivascular epithelioid cell tumor (PEComa) is a rare mesenchymal neoplasm which expresses both myogenic and melanocytic markers. PEComas are found in a variety locations in the body, but up to now only approximately 30 cases about hepatic perivascular epithelioid cell tumor are reported in English language worldwide. Patient concerns: A 32-year-old woman was admitted in our hospital with intermittent right upper quadrant pain for 1 month and recent (1 day) progressive deterioration. Diagnoses: Based on the results of the laboratory examinations and the findings of the computed tomography, the diagnosis of hepatic hamartoma or the hepatocecullar carcinoma with hemorrhage was made. Interventions: The patient underwent a segmentectomy of the liver, and the finally diagnosis of hepatic PEComa was made with immunohistochemical confirmation with HMB-45 and SMA. Outcomes: There is no clinical or radiographic evidence of recurrence 9 months after surgery. Lessons: This kind of tumor is extremely rare and the natural history of PEComa is uncertain, as the treatment protocol for hepatic PEComa has not reached a consensus. But the main treatment of the disease may be surgical resection. Only after long term follow-up can we know whether the tumor is benign or malignant. It appears that longer clinical follow-up is necessary in all patients with hepatic PEComas. PMID:28002331

  12. NMDA neurotransmission as a critical mediator of borderline personality disorder

    PubMed Central

    Grosjean, Bernadette; Tsai, Guochuan E.

    2007-01-01

    Studies of the neurobehavioural components of borderline personality disorder (BPD) have shown that symptoms and behaviours of BPD are partly associated with disruptions in basic neurocognitive processes, in particular, in the executive neurocognition and memory systems. A growing body of data indicates that the glutamatergic system, in particular, the N-methyl-D-aspartate (NMDA) subtype receptor, plays a major role in neuronal plasticity, cognition and memory and may underlie the pathophysiology of multiple psychiatric disorders. In this paper, we review the literature regarding BPD and its cognitive deficits and the current data on glutamatergic and NMDA neurotransmission. We propose that multiple cognitive dysfunctions and symptoms presented by BPD patients, like dissociation, psychosis and impaired nociception, may result from the dysregulation of the NMDA neurotransmission. This impairment may be the result of a combination of biological vulnerability and environmental influences mediated by the NMDA neurotransmission. PMID:17353939

  13. Maternal borderline personality disorder symptoms and adolescent psychosocial functioning.

    PubMed

    Herr, Nathaniel R; Hammen, Constance; Brennan, Patricia A

    2008-10-01

    Borderline personality disorder (BPD) is characterized by severe disruption of interpersonal relationships, yet very little research has examined the relationship between maternal BPD and offspring psychosocial functioning. The present study examined 815 mothers and their 15-year-old children from a community-based sample to determine (1) if there is an association between mothers' BPD symptoms and the interpersonal functioning, attachment cognitions, and depressive symptoms of their offspring, and (2) if the association of maternal BPD and youth outcomes is independent of maternal and youth depression. Measures of youth psychosocial functioning included self, mother, interviewer rated, and teacher reports. Results indicated that there was a significant association between maternal BPD symptoms and youth outcomes, and that this association remained even after controlling for maternal lifetime history of major depression, maternal history of dysthymic disorder, and youth depressive symptoms. This study provides some of the first empirical evidence for a link between mother's BPD symptoms and youth psychosocial outcomes.

  14. Risk factors for borderline personality in male outpatients.

    PubMed

    Paris, J; Zweig-Frank, H; Guzder, J

    1994-07-01

    The purpose of the study was to examine the role of several psychological risk factors--childhood sexual abuse (CSA) and its parameters, childhood physical abuse and its parameters, early separation or loss, and abnormal parental bonding--in male patients with borderline personality disorder (BPD). Subjects with personality disorders were divided into BPD (N = 61) and non-BPD (N = 60) groups. The risk factors were measured by a developmental interview and the Parental Bonding Index. The BPD group had a higher frequency of CSA, more severe CSA, a longer duration of physical abuse, increased rates of early separation or loss, and a higher paternal control score on the Parental Bonding Index. CSA and separation or loss were significant in the multivariate analysis. The risk factors suggest that trauma and loss, as well as problems with fathers, are important for the development of BPD in males.

  15. The neurobiology of empathy in borderline personality disorder.

    PubMed

    Ripoll, Luis H; Snyder, Rebekah; Steele, Howard; Siever, Larry J

    2013-03-01

    We present a neurobiological model of empathic dysfunction in borderline personality disorder (BPD) to guide future empirical research. Empathy is a necessary component of interpersonal functioning, involving two distinct, parallel neural networks. One form of empathic processing relies on shared representations (SR) of others' mental states, while the other is associated with explicit mental state attribution (MSA). SR processing is visceral and automatic, contributing to attunement, but also emotional contagion. MSA processing contributes to deliberate, perspectival forms of empathic understanding. Empathic dysfunction in BPD may involve hyper-reactivity of SR networks and impairment of MSA networks. Nevertheless, this empathic dysfunction is subtle, but contributes to interpersonal difficulties. Interaction between genetic factors and traumatic attachment stressors may contribute to development of BPD, with painful attachment insecurity and disorganization affecting SR and MSA network functioning. Future avenues for BPD research will include developmental assessment of attachment and neurobiological functioning under varying conditions.

  16. Transference interpretation in the treatment of borderline personality disorder patients.

    PubMed

    Higa, Justin K; Gedo, Paul M

    2012-01-01

    Transference is seen as an important change mechanism in psychotherapeutic technique, although questions remain about its therapeutic use, especially with borderline personality disorder (BPD) patients. This article illustrates the lively debate about transference interpretation through the perspective of two psychotherapeutic techniques under empirical scrutiny--transference-focused psychotherapy (TFP) and mentalization-based treatment (MBT). Each technique offers a similar understanding and appreciation of transference, but they differ in their technical use of this change mechanism. The article presents a brief case study of a BPD patient. The treatment highlights the utility of each psychotherapeutic technique in understanding the developmental progress made by the patient in therapy. The authors argue that each technique may be useful in a long-term dynamic therapy, and that one can use an epigenetic framework to understand this observation.

  17. Attachment and Reflective Functioning in Women With Borderline Personality Disorder.

    PubMed

    Badoud, Deborah; Prada, Paco; Nicastro, Rosetta; Germond, Charlotte; Luyten, Patrick; Perroud, Nader; Debbané, Martin

    2017-03-06

    Insecure attachment and impairments in reflective functioning (RF) are thought to play a critical role in borderline personality disorder (BPD). In particular, the mentalization-based model argues that insecure attachment indirectly accounts for increased BPD features, notably via disruption of RF capacities. Although the mediation relationship between attachment, RF, and BPD is supported by previous evidence, it remains to be directly tested in adults with BPD. In the current study, a sample of 55 female adult BPD patients and 105 female healthy controls completed a battery of self-report measures to investigate the interplay between attachment, RF capacities, and BPD clinical status. Overall, the results showed that BPD patients predominantly reported insecure attachment, characterized by negative internal working models of the self as unlovable and unimportant to others, and decreased RF abilities. Our findings further indicated that actual RF capacities mediated the relationships between adult insecure attachment and BPD clinical status.

  18. Disorganized attachment and borderline personality disorder: a clinical perspective.

    PubMed

    Holmes, Jeremy

    2004-06-01

    The aim of this paper is to explore the links between the attachment-theory derived concept of disorganized attachment, and the psychiatric diagnosis of Borderline Personality Disorder (BPD). Disorganized attachment can be understood in terms of an approach-avoidance dilemma for infants for whom stressed or traumatized/traumatizing caregivers are simultaneously a source of threat and a secure base. Interpersonal relationships in BPD including those with care givers is similarly seen in terms of approach-avoidance dilemmas, which manifests themselves in disturbed transference/countertransference interactions between therapists and BPD sufferers. Possible ways of handling these phenomena are suggested, based on notion of 'meta-cognitive monitoring', in the hope of re-instating meaning and more stable self-structures, in these patients' lives.

  19. Adult attachment to transitional objects and borderline personality disorder.

    PubMed

    Hooley, Jill M; Wilson-Murphy, Molly

    2012-04-01

    Borderline personality disorder (BPD) is characterized by tumultuous, unstable personal relationships, difficulty being alone, and an inability to self-soothe. This may explain why patients with BPD tend to develop strong attachments to transitional objects such as stuffed animals. Research in hospital settings has linked the use of transitional objects to the presence of BPD. Using a nonclinical community sample (N = 80) we explored the link between attachments to transitional objects and various aspects of personality pathology, as well as to childhood trauma, and parental rearing styles. People who reported intense current attachments to transitional objects were significantly more likely to meet criteria for a BPD diagnosis than those who did not; they also reported more childhood trauma, rated their early caregivers as less supportive, and had more attachment problems as adults. Heavy emotional reliance on transitional objects in adulthood may be an indicator of underlying pathology, particularly BPD.

  20. Adult attachment in the clinical management of borderline personality disorder.

    PubMed

    Fossati, Andrea

    2012-05-01

    Borderline personality disorder (BPD) is a common psychiatric disorder associated with severe functional impairment, high rates of suicide and comorbid psychiatric illness, intensive use of treatment, and high costs to society. The etiology and pathogenesis of BPD are still uncertain, although an interaction between biological and psychosocial factors has been proposed to explain how the condition develops. Attachment disturbances represent one of the developmental risk factors that have been most consistently found to be associated with BPD, with a number of studies reporting a significant strong association between insecure attachment and BPD, notwithstanding the variety of measures and attachment types employed in these studies. In this article, the author first reviews clinical descriptions and research findings concerning the association between attachment disturbances and BPD and then discusses how attachment theory may help clinicians who work with patients with BPD better understand the psychopathology of the illness and plan treatment.

  1. [A cognitive approach of the borderline personality disorder].

    PubMed

    Keegan, Eduardo

    The development of cognitive models and treatments for borderline personality disorder over the last two decades has been remarkable. This article presents the main ideas of the models developed by Aaron T. Beck and Arthur Freeman, Jeffrey Young and Marsha Linehan. These theories have generated psychotherapies that have proven their efficacy in controlled empirical studies in a difficult to treat population. The models of Beck Freeman and Young are based on the concept of schema. Linehan's dialectical behavior therapy is based on a biosocial transactional conception of the disorder. All these models emphasize the importance of negative experiences in early development. The article presents the structure of these treatments and describes their specific interventions.

  2. Impact of Diagnosis Disclosure on Adolescents with Borderline Personality Disorder

    PubMed Central

    Courtney, Darren B.; Makinen, Judy

    2016-01-01

    Objective Establishing a diagnosis of Borderline Personality Disorder (BPD) in adolescents is often met with controversy, in part, due to potential stigmatizing effects. We wished to explore the adolescent patient experience of being diagnosed with BPD. Method The Impact of Diagnosis Scale (IODS) is a self-report measure we developed with questions targeting patients’ subjective experience of receiving a diagnosis of BPD. The IODS was administered to 23 adolescents approximately one month after a diagnosis of BPD had been disclosed to them. Results Twenty-one participants had analyzable data. The internal consistency of the measure demonstrated Cronbach’s alpha of 0.66. We found wide variability in responses. Patients tended to view the diagnosis as an accurate representation of their symptoms. Conclusion The IODS represents a novel means by which clinicians might better appreciate how disclosing the diagnosis of BPD may impact a patient’s understanding of one’s difficulties. PMID:27924148

  3. Use of Clozapine for Borderline Personality Disorder: A Case Report

    PubMed Central

    Amamou, Badii; Salah, Walid Bel Hadj; Mhalla, Ahmed; Benzarti, Nejla; Elloumi, Hend; Zaafrane, Ferid; Gaha, Lotfi

    2016-01-01

    Patients with borderline personality disorder (BPD) show significant impairment in functioning, particularly in the interpersonal and social domains. Prior reports suggest that clozapine may be effective in the management of BPD. We present the case of a patient with BPD who experienced persistent suicidal ideation and was treated with clozapine at a state psychiatric hospital. After treatment failure with other psychotropic medications, clozapine medication was initiated; not only did suicidal ideation cease, but social and professional functioning also greatly improved to the point of no longer requiring intensive levels of observation or restrictive procedures. Clozapine appears to be efficacious in the management of suicide attempts and self-injurious behavior. Moreover, it appears to be promising as a therapeutic measure for ameliorating the global functioning of patients with severe BPD. Larger, randomized, blinded, and controlled prospective studies are needed to confirm these findings and to determine optimal dosage. PMID:27121437

  4. Patient-reported outcomes in borderline personality disorder.

    PubMed

    Hasler, Gregor; Hopwood, Christopher J; Jacob, Gitta A; Brändle, Laura S; Schulte-Vels, Thomas

    2014-06-01

    Patient-reported outcome (PRO) refers to measures that emphasize the subjective view of patients about their health-related conditions and behaviors. Typically, PROs include self-report questionnaires and clinical interviews. Defining PROs for borderline personality disorder (BPD) is particularly challenging given the disorder's high symptomatic heterogeneity, high comorbidity with other psychiatric conditions, highly fluctuating symptoms, weak correlations between symptoms and functional outcomes, and lack of valid and reliable experimental measures to complement self-report data. Here, we provide an overview of currently used BPD outcome measures and discuss them from clinical, psychometric, experimental, and patient perspectives. In addition, we review the most promising leads to improve BPD PROs, including the DSM-5 Section III, the Recovery Approach, Ecological Momentary Assessments, and novel experimental measures of social functioning that are associated with functional and social outcomes.

  5. Attention deficit hyperactivity disorder and borderline personality disorder.

    PubMed

    Davids, Eugen; Gastpar, Markus

    2005-07-01

    To evaluate the association between attention deficit hyperactivity disorder (ADHD) and the diagnosis of borderline personality disorder (BPD) in adulthood, a systematic review of published follow-up data, mainly from observational studies was done. Electronic databases Medline, PsychInfo and PSYNDEXplus were searched from their earliest entries. All studies suggested significant relationships between ADHD and BPD. From a phenomenological point of view there seem to exist some similarities between these two disorders: deficits in affect regulation and impulse control, substance abuse, low self esteem and disturbed interpersonal relationship are common in both conditions. From a neuropsychological point of view dissociation in BPD might be regarded as a special form of behavioral inhibition and sustained attention comparable to ADHD. Possible therapeutic strategies of comorbid ADHD and BPD are discussed.

  6. Borderline personality disorder and the ethics of risk management.

    PubMed

    Warrender, Dan

    2017-01-01

    Patients with borderline personality disorder are frequent users of inpatient mental health units, with inpatient crisis intervention often used based on the risk of suicide. However, this can present an ethical dilemma for nursing and medical staff, with these clinician responses shifting between the moral principles of beneficence and non-maleficence, dependent on the outcomes of the actions of containing or tolerating risk. This article examines the use of crisis intervention through moral duties, intentions and consequences, culminating in an action/consequence model of risk management, used to explore potential outcomes. This model may be useful in measuring adherence and violation of the principles of beneficence and non-maleficence and therefore an aid to clinical decision making.

  7. Emotion-focused principles for working with borderline personality disorder.

    PubMed

    Warwar, Serine H; Links, Paul S; Greenberg, Leslie; Bergmans, Yvonne

    2008-03-01

    This paper discusses the function of emotion, its importance in the treatment of individuals with borderline personality disorder (BPD), and the integration of emotion-focused therapy (EFT) principles in the psychotherapeutic management of patients with BPD. EFT principles involve emotional assessment; a strong therapeutic alliance as a necessary context for treatment; the therapeutic relationship as a bond that regulates affect through empathy, emotional validation, and interpersonal soothing; emotion-regulation; psychoeducation about emotional processes; the therapist as an emotional coach; and transforming emotion schemes as primary mechanisms of change. The authors discuss how EFT principles can be viewed as primary intervention strategies in the treatment of patients with BPD and how they can be incorporated into various psychotherapy approaches. Based on our experience, the integration of EFT principles into the therapy of patients with BPD shows promise as it has been helpful in targeting BPD symptoms, and is feasible and acceptable to patients.

  8. Identifying Trajectories of Borderline Personality Features in Adolescence

    PubMed Central

    Haltigan, John D.

    2016-01-01

    Objective: To examine trajectories of adolescent borderline personality (BP) features in a normative-risk cohort (n = 566) of Canadian children assessed at ages 13, 14, 15, and 16 and childhood predictors of trajectory group membership assessed at ages 8, 10, 11, and 12. Method: Data were drawn from the McMaster Teen Study, an on-going study examining relations among bullying, mental health, and academic achievement. Participants and their parents completed a battery of mental health and peer relations questionnaires at each wave of the study. Academic competence was assessed at age 8 (Grade 3). Latent class growth analysis, analysis of variance, and logistic regression were used to analyze the data. Results: Three distinct BP features trajectory groups were identified: elevated or rising, intermediate or stable, and low or stable. Parent- and child-reported mental health symptoms, peer relations risk factors, and intra-individual risk factors were significant predictors of elevated or rising and intermediate or stable trajectory groups. Child-reported attention-deficit hyperactivity disorder (ADHD) and somatization symptoms uniquely predicted elevated or rising trajectory group membership, whereas parent-reported anxiety and child-reported ADHD symptoms uniquely predicted intermediate or stable trajectory group membership. Child-reported somatization symptoms was the only predictor to differentiate the intermediate or stable and elevated or rising trajectory groups (OR 1.15, 95% CI 1.04 to 1.28). Associations between child-reported reactive temperament and elevated BP features trajectory group membership were 10.23 times higher among children who were bullied, supporting a diathesis–stress pathway in the development of BP features for these youth. Conclusions: Findings demonstrate the heterogeneous course of BP features in early adolescence and shed light on the potential prodromal course of later borderline personality disorder. PMID:27254092

  9. Toward a genetically-informed model of borderline personality disorder.

    PubMed

    Livesley, John

    2008-02-01

    This article describes a conceptual framework for describing borderline personality disorder (BPD) based on empirical studies of the phenotypic structure and genetic architecture of personality. The proposed phenotype has 2 components: (1) a description of core self and interpersonal pathology-the defining features of personality disorder-as these features are expressed in the disorder; and (2) a set of traits based on the anxious-dependent or emotional dysregulation factor of the four-factor model of PD. Four kinds of traits are described: emotional (anxiousness, emotional reactivity, emotional intensity, and pessimistic-anhedonia), interpersonal (submissiveness, insecure attachment, social apprehensiveness, and need for approval), cognitive (cognitive dysregulation), and self-harm (behaviors and ideas). Formulation of the phenotype was guided by the conceptualization of personality as a system of interrelated sub-systems. The psychopathology associated with BPD involves most components of the system. The trait structure of the disorder is assumed to reflect the genetic architecture of personality and individual traits are assumed to be based on adaptive mechanisms. It is suggested that borderline traits are organized around the trait of anxiousness and that an important feature of BPD is dysregulation of the threat management system leading to pervasive fearfulness and unstable emotions. The interpersonal traits are assumed to be heritable characteristics that evolved to deal with interpersonal threats that arose as a result of social living. The potential for unstable and conflicted interpersonal relationships that is inherent to the disorder is assumed to result from the interplay between the adaptive structure of personality and psychosocial adversity. The etiology of the disorder is discussed in terms of biological and environmental factors associated with each component of the phenotype.

  10. Association of giant congenital melanocytic nevus, halo nevus and vitiligo in a 75-year-old patient.

    PubMed

    Silveira, Marina Leite da; Ferreira, Flávia Regina; Alvarenga, Marcia Lanzoni; Mandelbaum, Samuel Henrique

    2012-01-01

    A giant congenital melanocytic nevus represents a rare condition. The halo phenomenon may be seen in congenital or acquired melanocytic nevi. In the literature, association of halo nevus and giant congenital melanocytic nevus is rare and the association of both with vitiligo even more rare. A 75-yearold woman at first consultation complained of a hyperchromic bluish-brown hairy macula on the lower back, buttocks and thighs present since birth and an achromic halo of onset three years ago. The histological features were consistent with congenital melanocytic nevus and halo nevus, respectively. After two years the patient developed achromic areas in normal skin, histologically consistent with vitiligo. The authors emphasize the rarity of this triple combination, the patient's age and the absence of malignant degeneration to date.

  11. Dysfunction of Autophagy: A Possible Mechanism Involved in the Pathogenesis of Vitiligo by Breaking the Redox Balance of Melanocytes

    PubMed Central

    Qiao, Zhuhui; Wang, Xiuxiu; Xiang, Leihong

    2016-01-01

    Vitiligo is a common chronic acquired pigmentation disorder characterized by loss of functional melanocytes from the epidermis and follicular reservoir. Among multiple hypotheses which have been proposed in the pathogenesis of vitiligo, autoimmunity and oxidative stress-mediated toxicity in melanocytes remain most widely accepted. Macroautophagy is a lysosome-dependent degradation pathway which widely exists in eukaryotic cells. Autophagy participates in the oxidative stress response in many cells, which plays a protective role in preventing damage caused by oxidative stress. Recent studies have enrolled autophagy as an important regulator in limiting damage caused by UV light and lipid oxidation, keeping oxidative stress in a steady state in epidermal keratinocytes and maintaining normal proliferation and aging of melanocytes. Impairment of autophagy might disrupt the antioxidant defense system which renders melanocytes to oxidative insults. These findings provide supportive evidence to explore new ideas of the pathogenesis of vitiligo and other pigmentation disorders. PMID:28018522

  12. Dysfunction of Autophagy: A Possible Mechanism Involved in the Pathogenesis of Vitiligo by Breaking the Redox Balance of Melanocytes.

    PubMed

    Qiao, Zhuhui; Wang, Xiuxiu; Xiang, Leihong; Zhang, Chengfeng

    2016-01-01

    Vitiligo is a common chronic acquired pigmentation disorder characterized by loss of functional melanocytes from the epidermis and follicular reservoir. Among multiple hypotheses which have been proposed in the pathogenesis of vitiligo, autoimmunity and oxidative stress-mediated toxicity in melanocytes remain most widely accepted. Macroautophagy is a lysosome-dependent degradation pathway which widely exists in eukaryotic cells. Autophagy participates in the oxidative stress response in many cells, which plays a protective role in preventing damage caused by oxidative stress. Recent studies have enrolled autophagy as an important regulator in limiting damage caused by UV light and lipid oxidation, keeping oxidative stress in a steady state in epidermal keratinocytes and maintaining normal proliferation and aging of melanocytes. Impairment of autophagy might disrupt the antioxidant defense system which renders melanocytes to oxidative insults. These findings provide supportive evidence to explore new ideas of the pathogenesis of vitiligo and other pigmentation disorders.

  13. Suprabasal spread of melanocytes in dysplastic nevi and melanoma in situ: Ki-67-labeling rate of junctional melanocytes and suprabasal cells may be a helpful clue to the diagnosis.

    PubMed

    Hall, Brian J; LeBoit, Philip E

    2014-08-01

    Multiple criteria on routinely stained sections allow one to make a diagnosis of a dysplastic or "Clark" nevus (CN) versus melanoma in situ (MIS), and one of these is suprabasal spread of melanocytes. The extent of suprabasal spread of melanocytes in otherwise conventional CN and the combination of a sensitive marker of melanocytes combined with Ki-67 to assess the differences between the proliferation of melanocytes at the junction and those above it have not yet been studied. Fifty classic examples of CN and 27 cases of MIS were culled from the files of a university-based dermatopathology practice. All cases were stained with a 2-color method (MART-1/tyrosinase red, Ki-67 brown) to evaluate morphologic and immunohistochemical differences in these lesions. Fifteen of 50 cases of benign CN demonstrated suprabasal spread compared with 27 of 27 cases of MIS. The majority of CNs with suprabasal spread (13 of 15) showed a 0% Ki-67-labeling rate among the suprabasal melanocytes, and the majority of MISs (23 of 27) showed a 20% or greater Ki-67-labeling rate in suprabasal cells. Suprabasal melanocytes can be seen by immunostaining in otherwise unremarkable CN, wherein they are not notable in routinely stained sections, but their proliferation rate is much less than in MIS.

  14. Reversal of developmental restrictions in neural crest lineages: Transition from Schwann cells to glial-melanocytic precursors in vitro

    PubMed Central

    Dupin, Elisabeth; Real, Carla; Glavieux-Pardanaud, Corinne; Vaigot, Pierre; Le Douarin, Nicole M.

    2003-01-01

    In vertebrate embryos, diversification of the lineages arising from the neural crest (NC) is controlled to a large extent by environmental factors. In previous work, we showed that endothelin 3 (ET3) peptide favors the development of glial and melanocytic NC precursors in vitro. This factor is also capable of inducing proliferation of cultured epidermal pigment cells and their conversion to glia. ET3 therefore strongly promotes the emergence of melanocytic and glial phenotypes from precursors and acts on the maintenance of these phenotypes. In the present work, we explored the capacity of ET3 to reprogram glial cells into melanocytes. Schwann cells expressing glial-specific markers [such as the Schwann cell myelin protein (SMP)] were isolated from sciatic nerves of quail embryos and cultured in vitro. We found that ET3 promotes cell growth and sequential expression of melanocyte differentiation markers in cultures of purified SMP-expressing cells, whereas it had no significant effect on SMP-negative cells from the same nerves. Moreover, we provide evidence for the transition of differentiated Schwann cells to melanocytes in clonal cultures. This transition involves the production of a mixed progeny of melanoblasts/melanocytes, glia, and cells bearing differentiation markers of both phenotypes. Therefore, Schwann cells exposed to ET3 transdifferentiate to melanocytes through reversion to the stage of bipotent glial-melanocytic NC precursors. These findings show that NC-derived pigment and glial cells are phenotypically unstable in vitro and may undergo reversal of precursor hierarchy to function as bipotent stem cells. PMID:12702775

  15. Phyllodes tumor of the breast

    PubMed Central

    Herazo, Fernando; Gil, Monica; Echeverri, Carolina; Ángel, Gonzalo; Borrero, Mauricio; Madrid, Jorge; Jaramillo, Ricardo

    2015-01-01

    Introduction: Breast Phyllodes tumors are rare breast tumors present in less than 1% of new cases of breast cancer, usually occurring among middle-aged women (40-50 yrs). Objective: This study shows diagnostic experience, surgical management and follows up of patients with this disease during a period of ten years in a oncology referral center. Methods: Retrospectively, breast cancer registries at the institution were reviewed, identifying 77 patients with Phyllodes tumors between 2002 and 2012, who had been operated on at the Instituto de Cancerología - Clínica Las Américas, in Medellín (Colombia). Clinical and histopathological data belonging to these cases was captured and analyzed and descriptive statistics were used. Results: The follow up median was 22.5 months (IQR: 10.5-60.0), average age was 47.2 yrs (SD: 12.4), mean tumor size was 3.6 cm (SD: 4.6), 88.3% of the patients (68 cases) presented negative margins and none of them received adjuvant chemotherapy. Of the patients with Phyllodes tumors; 33.8% had benign, 31.2% had borderline and 35.0% had malignant tumor. Disease-free survival was 85.8% and overall survival was 94.5%. Discussion: Reported data in this article is in accordance with what has been reported in worldwide literature. In our cohort even the high mean size of the tumors, the risk of local relapse and metastatic disease is low than previously reported in literature. Trials with longer follow up and molecular trials in Phyllodes tumors are necessary to understand the behavior of these tumors in Hispanics population. PMID:26600624

  16. Pigmented Pindborg tumor of the maxilla: A case report

    PubMed Central

    Priya, Subashchandrabose; Madanagopaal, Lakshmikanth Ramiah; Sarada, Venkaterwaran

    2016-01-01

    The calcifying epithelial odontogenic tumor (CEOT), also known as the Pindborg tumor, is a benign locally invasive neoplasm. Common variants of CEOT include noncalcifying, Langerhans cell, bone and cementum forming and clear cell, which have a prognostic significance. Pigmented variants are known to occur in other odontogenic tumors. However, a definitive pigmented variant of CEOT has not been reported in literature so far. Here, we report the first case of pigmented Pindborg tumor arising from the maxilla in a young female. The pigment was demonstrated as melanin by staining and confirmed by immunohistochemistry. The pigmented variant of CEOT did not recur within 18 months postsurgery. Our report indicates that it is essential to recognize the pigmented variant. We discuss the common variants of CEOT and potential histogenesis of the pigmented variant. Further studies are required to reveal the histogenesis of melanocytes and their pathological significance in the odontogenic tumors. PMID:27721633

  17. Association between Melanocytic Nevi and Risk of Breast Diseases: The French E3N Prospective Cohort

    PubMed Central

    Kvaskoff, Marina; Bijon, Anne; Mesrine, Sylvie; Vilier, Alice; Baglietto, Laura; Fournier, Agnès; Clavel-Chapelon, Françoise; Dossus, Laure; Boutron-Ruault, Marie-Christine

    2014-01-01

    Background While melanocytic nevi have been associated with genetic factors and childhood sun exposure, several observations also suggest a potential hormonal influence on nevi. To test the hypothesis that nevi are associated with breast tumor risk, we explored the relationships between number of nevi and benign and malignant breast disease risk. Methods and Findings We prospectively analyzed data from E3N, a cohort of French women aged 40–65 y at inclusion in 1990. Number of nevi was collected at inclusion. Hazard ratios (HRs) for breast cancer and 95% confidence intervals (CIs) were calculated using Cox proportional hazards regression models. Associations of number of nevi with personal history of benign breast disease (BBD) and family history of breast cancer were estimated using logistic regression. Over the period 15 June 1990–15 June 2008, 5,956 incident breast cancer cases (including 5,245 invasive tumors) were ascertained among 89,902 women. In models adjusted for age, education, and known breast cancer risk factors, women with “very many” nevi had a significantly higher breast cancer risk (HR = 1.13, 95% CI = 1.01–1.27 versus “none”; ptrend = 0.04), although significance was lost after adjustment for personal history of BBD or family history of breast cancer. The 10-y absolute risk of invasive breast cancer increased from 3,749 per 100,000 women without nevi to 4,124 (95% CI = 3,674–4,649) per 100,000 women with “very many” nevi. The association was restricted to premenopausal women (HR = 1.40, ptrend = 0.01), even after full adjustment (HR = 1.34, ptrend = 0.03; phomogeneity = 0.04), but did not differ according to breast cancer type or hormone receptor status. In addition, we observed significantly positive dose–response relationships between number of nevi and history of biopsy-confirmed BBD (n = 5,169; ptrend<0.0001) and family history of breast cancer in first-degree relatives (n = 7

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

    PubMed Central

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

    2012-01-01

    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 (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. PMID:25049660

  19. Nests with numerous SOX10 and MiTF-positive cells in lichenoid inflammation: pseudomelanocytic nests or authentic melanocytic proliferation?

    PubMed

    Silva, Claudine Yap; Goldberg, Lynne J; Mahalingam, Meera; Bhawan, Jag; Wolpowitz, Deon

    2011-10-01

    Pseudomelanocytic nests in the setting of lichenoid inflammation can mimic atypical melanocytic proliferations. Both melanocytic and cytokeratin immunohistochemical stains may be utilized to differentiate these entities. Unlike true melanocytic nests, pseudomelanocytic nests contain Melanoma Antigen Recognized by T-cells 1 (MART-1)/ Melan-A-positive cells and cells positive for pan-cytokeratins, CD3 and/or CD68. Recently, rare (1-2 cells/nest) microphthalmia- associated transcription factor (MiTF)-positive cells were also reported in pseudomelanocytic nests. We present a 48-year-old man with a 2 × 3 cm violaceous to hyperpigmented, non-blanching, polygonal patch on the neck. Histopathology showed focal epidermal atrophy, irregularly distributed junctional nests and a lichenoid infiltrate with colloid bodies. Immunoperoxidase studies revealed occasional pan-cytokeratin and MART-1/Melan-A-positive staining in nests as well as focal S-100 protein-positive cells. Importantly, the majority of nests showed numerous cells positive for MiTF and SOX10 (>2 cells/nest and some the majority of cells). This combined staining pattern confounds the above-described immunohistochemical distinction between pseudo and true melanocytic nests. Clinically felt to represent unilateral lichen planus pigmentosus/erythema dyschromicum perstans and not malignant melanoma in situ, this lesion highlights the importance of clinicopathologic correlation and suggests either a new melanocytic entity or a novel pattern of benign melanocytic reorganization in a subset of lichenoid dermatitides.

  20. Metabotropic glutamate receptor 6 signaling enhances TRPM1 calcium channel function and increases melanin content in human melanocytes.

    PubMed

    Devi, Sulochana; Markandeya, Yogananda; Maddodi, Nityanand; Dhingra, Anuradha; Vardi, Noga; Balijepalli, Ravi C; Setaluri, Vijayasaradhi

    2013-05-01

    Mutations in TRPM1, a calcium channel expressed in retinal bipolar cells and epidermal melanocytes, cause complete congenital stationary night blindness with no discernible skin phenotype. In the retina, TRPM1 activity is negatively coupled to metabotropic glutamate receptor 6 (mGluR6) signaling through Gαo and TRPM1 mutations result in the loss of responsiveness of TRPM1 to mGluR6 signaling. Here, we show that human melanocytes express mGluR6, and treatment of melanocytes with L-AP4, a type III mGluR-selective agonist, enhances Ca(2+) uptake. Knockdown of TRPM1 or mGluR6 by shRNA abolished L-AP4-induced Ca(2+) influx and TRPM1 currents, showing that TRPM1 activity in melanocytes is positively coupled to mGluR6 signaling. Gαo protein is absent in melanocytes. However, forced expression of Gαo restored negative coupling of TRPM1 to mGluR6 signaling, but treatment with pertussis toxin, an inhibitor of Gi /Go proteins, did not affect basal or mGluR6-induced Ca(2+) uptake. Additionally, chronic stimulation of mGluR6 altered melanocyte morphology and increased melanin content. These data suggest differences in coupling of TRPM1 function to mGluR6 signaling explain different cellular responses to glutamate in the retina and the skin.

  1. Metabotropic glutamate receptor 6 signaling enhances TRPM1 calcium channel function and increases melanin content in human melanocytes

    PubMed Central

    Devi, Sulochana; Markandeya, Yogananda; Maddodi, Nityanand; Dhingra, Anuradha; Vardi, Noga; Balijepalli, Ravi C; Setaluri, Vijayasaradhi

    2013-01-01

    SUMMARY Mutations in TRPM1, a calcium channel expressed in retinal bipolar cells and epidermal melanocytes, cause complete congenital stationary night blindness with no discernible skin phenotype. In the retina, TRPM1 activity is negatively coupled to metabotropic glutamate receptor 6 (mGluR6) signaling through Gαo and TRPM1 mutations result in the loss of responsiveness of TRPM1 to mGluR6 signaling. Here, we show that human melanocytes express mGluR6 and treatment of melanocytes with L-AP4, a type III mGluR-selective agonist, enhances Ca2+ uptake. Knockdown of TRPM1 or mGluR6 by shRNA abolished L-AP4-induced Ca2+ influx and TRPM1 currents showing that TRPM1 activity in melanocytes is positively coupled to mGluR6 signaling. Gαo protein is absent in melanocytes. However, forced expression of Gαo restored negative coupling of TRPM1 to mGluR6 signaling, but treatment with and pertussis toxin, an inhibitor of Gi/Go proteins, did not affect basal or mGluR6-induced Ca2+ uptake. Additionally, chronic stimulation of mGluR6 altered melanocyte morphology and increased melanin content. These data suggest differences in coupling of TRPM1 function to mGluR6 signaling explain different cellular responses to glutamate in the retina and the skin. PMID:23452348

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

    PubMed

    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.

  3. Differentiating risk for mania and borderline personality disorder: The nature of goal regulation and impulsivity.

    PubMed

    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.

  4. A Computer-Aided Distinction Method of Borderline Grades of Oral Cancer

    NASA Astrophysics Data System (ADS)

    Sami, Mustafa M.; Saito, Masahisa; Muramatsu, Shogo; Kikuchi, Hisakazu; Saku, Takashi

    We have developed a new computer-aided diagnostic system for differentiating oral borderline malignancies in hematoxylin-eosin stained microscopic images. Epithelial dysplasia and carcinoma in-situ (CIS) of oral mucosa are two different borderline grades similar to each other, and it is difficult to distinguish between them. A new image processing and analysis method has been applied to a variety of histopathological features and shows the possibility for differentiating the oral cancer borderline grades automatically. The method is based on comparing the drop-shape similarity level in a particular manually selected pair of neighboring rete ridges. It was found that the considered similarity level in dysplasia was higher than those in epithelial CIS, of which pathological diagnoses were conventionally made by pathologists. The developed image processing method showed a good promise for the computer-aided pathological assessment of oral borderline malignancy differentiation in clinical practice.

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

    PubMed Central

    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. PMID:26351624

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

    PubMed

    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.

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

    PubMed

    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.

  8. Installation of a network for patients with congenital melanocytic nevi in German-speaking countries.

    PubMed

    Krengel, Sven; Breuninger, Helmut; Hauschild, Axel; Höger, Peter; Merl, Volker; Hamm, Henning

    2008-03-01

    In 2005, an Internet-based network for the support of patients with congenital melanocytic nevi in German-speaking countries was started (http://www.naevus-netzwerk.de). Along with detailed information for patients and parents, the home-page includes a nevus registry which is based on an electronic questionnaire and which aims at providing data on the long-term course of nevi estimated to reach > 10 cm in largest diameter. In the past, congenital melanocytic nevi have been subject to various mythological interpretations ("Tierfellnävus", lit."animal coat nevus";"Muttermal"). Today an increasing body of reliable scientific data allows a differentiated reflection of the risk of malignant transformation and has led to progress in the diagnostic and therapeutic management. Recent findings from the literature and considerations from scientific meetings are reviewed.

  9. "Sky Full of Stars" Pattern: Dermoscopic Findings in a Desmoplastic Giant Congenital Melanocytic Nevus.

    PubMed

    Martín-Carrasco, Pablo; Bernabeu-Wittel, José; Dominguez-Cruz, Javier; Zulueta Dorado, Teresa; Conejo-Mir Sanchez, Julian

    2017-02-27

    Desmoplastic giant congenital melanocytic nevus (DGCN) is an uncommon variant of congenital nevus, presenting as a progressive induration and hypopigmentation of the lesion that occasionally causes hair loss and even total or partial disappearance of the nevus. A 6-month-old girl with a giant congenital melanocytic nevus that involved the entire posterior side of the right thigh was seen in our department. Nine months later, the peripheral area of the nevus presented as a marked induration with hypopigmentation. Dermoscopy demonstrated a reticular pattern exclusively located in the perifollicular areas, with a radial distribution from the follicular ostium that mimicked a "sky full of stars." We report a case of DGCN, including a dermoscopic description of the findings noted in the indurated and hypopigmented areas that appear as a "sky full of stars" image.

  10. Melanocyte response to gravitational stress: an overview with a focus on the role of cyclic nucleotides

    NASA Astrophysics Data System (ADS)

    Ivanova, Krassimira; Tsiockas, Wasiliki; Eiermann, Peter; Hauslage, Jens; Hemmersbach, Ruth; Block, Ingrid; Gerzer, Rupert

    Human melanocytes are responsible for skin pigmentation by synthesizing the pigment melanin. A well known modulator of melanogenesis is the second messenger adenosine 3',5'-cyclic monophos-phate (cAMP). It has also been reported that the nitric oxide (NO)/soluble guanylyl cyclase (sGC)/guanosine 3',5'-cyclic monophosphate (cGMP) pathway is involved in UVB-induced melanogenesis. Melanin acts as a scavenger for free radicals during oxidative stress, but it may additionally act as a photosensitizer that generates active oxygen species upon UV radiation, which may initiate hypopigmentary disorders (e.g., vitiligo) as well as UV-induced oncogene cell transformation. Melanoma, a deadly skin cancer which arises from transformed melanocytes, is characterized by a resistance to chemotherapy. In our studies we were able to show that hu-man melanocytic cells differentially respond to gravitational stress. Hypergravity (up to 5 g for 24 h) stimulated cGMP efflux in cultured human melanocytes and non-metastatic melanoma cells, but not in metastatic phenotypes under the conditions of limited degradation [e.g., in the presence of phosphodiesterase (PDE) inhibitors] or stimulated synthesis of cGMP [e.g., by NO donors, but not natriuretic peptides], whereas cellular proliferation and morphology were not altered. Interestingly, long-term exposure to hypergravity stimulated an increase in both intra-cellular as well as extracellular cAMP levels as well as melanogenesis in pigmented melanocytes and non-metastatic melanoma cells. As some cAMP-PDEs are regulated by cGMP, it seems that the hypergravity-induced alteration of melanocyte pigmentation could be a result of a cross-talk between these two cyclic nucleotides. Hypergravity induced further an increase in the mRNA and protein levels of the selective cGMP and cAMP exporters, the multidrug resistance proteins (MRP) 4 and 5 -but not 8 -, whereas simulated microgravity (up to 1.21x10-2 g for 24 h) -provided by a fast-rotating clinostat

  11. [CONGENITAL MELANOCYTIC NEVUS OF THE SHOULDER WITH RAPID GROWTH PROGRESSION DURING PREGNANCY. SUCCESSFUL SURGICAL APPROACH].

    PubMed

    Trayanov, I; Trayanova, E; Chokoeva, A; Tchernev, G

    2015-01-01

    Congenital melanocytic nevi are common subject of scientific debates nowadays, because of their possibility for transformation in malignant melanoma, although relatively rare. The diagnosis is difficult, due to their non-specific clinical and histological presentation, while the therapeutic methods are varied, depending on their size and localization. Surgical excision, however, is the most secure among them, because a complete removal of the lesion could be achieved, which, firstly provides a prevention of a possible malignant transformation, as well as this approach provides material for histological examination. We present a case of a 23-year-old female patient with congenital melanocytic nevus, located on the upper back, which increased significantly its size during her pregnancy, successfully treated by single surgical excision, with excellent aesthetic results.

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

    PubMed Central

    Johnson, Eric D.; Gulbahce, Evin; McNally, Joseph; Buys, Saundra S.

    2016-01-01

    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. PMID:28203179

  13. Responses of mental health clinicians to patients with borderline personality disorder.

    PubMed

    Sansone, Randy A; Sansone, Lori A

    2013-05-01

    Borderline personality disorder is a complex psychiatric syndrome that is characterized by a number of pathological interpersonal and behavioral symptoms. Because of these symptoms, individuals with borderline personality disorder tend to have difficulties in their relationships with others, including mental health clinicians. Through a literature review, we examined the perceptions and reactions of mental health clinicians toward patients with borderline personality disorder. Our findings indicate that psychiatric nurses are the most studied group of mental health clinicians in this regard, followed by samples of mixed mental health clinicians, and then psychologists. Interestingly, there is no study of psychiatrists only. While sample sizes have been generally small and methodologies have varied, the overwhelming majority of these studies indicate negative perceptions of and emotional responses toward patients with borderline personality disorder. Some researchers have interpreted such findings to suggest that mental health clinicians are more judgmental or prejudicial toward patients with borderline personality disorder, in contrast to other types of mental health patients. However, patients with borderline personality disorder have very complex interpersonal behaviors that tend to illicit negative responses from those around them. Perhaps these data simply reflect a very human reaction to the complex and pathological behaviors of these patients-a conclusion that is relevant to clinicians practicing in either mental health or primary care settings.

  14. Parenting, relational aggression, and borderline personality features: associations over time in a Russian longitudinal sample.

    PubMed

    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.

  15. Quantification of the borderline range and implications for evaluating non-animal testing methods' precision.

    PubMed

    Leontaridou, Maria; Urbisch, Daniel; Kolle, Susanne N; Ott, Katharina; Mulliner, Denis S; Gabbert, Silke; Landsiedel, Robert

    2017-02-23

    Testing methods to assess the skin sensitisation potential of a substance usually use threshold criteria to dichotomise continuous experimental read-outs into yes/no conclusions. The threshold criteria are prescribed in the respective OECD test guidelines and the conclusion is used for regulatory hazard assessment, i.e. classification and labelling of the substance. We can identify a borderline range (BR) around the classification threshold within which test results are non-conclusive due to a testing method's biological and technical variability. We quantify BRs in the prediction models of the non-animal testing methods DPRA, LuSens and h-CLAT, and of the animal test LLNA, respectively. Depending on the size of the BR we find that between 6% and 28% of the substances in the sets tested with these methods were considered borderline. If the results of individual non-animal test methods are combined into integrated testing strategies (ITS), borderline test results of individual tests can also affect the overall assessment of the skin sensitisation potential of the testing strategy. This was analysed for the '2-out-of-3' ITS: Four out of 40 substances (10%) were considered borderline. Based on our findings we propose expanding the standard binary classification of substances into 'positive'/'negative' or 'hazardous'/'non-hazardous' by adding a 'borderline' or 'non-conclusive' alert for cases where test results fall within the borderline range.

  16. [The borderline personality (development) disorder during adolescence. Psychological assessment, treatment prerequisites, framework design, treatment phases].

    PubMed

    Streeck-Fischer, Annette

    2008-01-01

    Following a critical discussion on the term Borderline Personality Disorder during adolescence, assessment criteria are compiled that illustrate this disorder. In an overview of the psychodynamic literature it is clearly stated that already in the 1960s Borderline Disorders were described in childhood and adolescence without any development of valid criteria for these since then. Except for numerous case studies of these Borderline Disorders, there has been no research undertaken within psychodynamic psychotherapy on this disorder during childhood and adolescence to date. Specific disorder-related therapy approaches, whose effectiveness have been confirmed in therapy studies on Borderline Disorders in adults, have so far not been adapted to treating children and adolescents that have Borderline Disorders. These are portrayed as well as the treatment prerequisites and framework conditions that allow for a disorder-specific development oriented interactional psychotherapy of adolescents with Borderline Disorders. The interactional psychotherapy in its adolescence-adapted form is only gone into on the side. In conclusion there is an overview given of the various phases of the treatment.

  17. Resolution of vitiligo following excision of halo congenital melanocytic nevus: a rare case report.

    PubMed

    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.

  18. Uncovering the Role of BMP Signaling in Melanocyte Development and Melanoma Tumorigenesis

    DTIC Science & Technology

    2014-07-01

    Signaling in Melanocyte Development and Melanoma Tumorigenesis PRINCIPAL INVESTIGATOR: Craig J. Ceol, Ph.D. CONTRACTING ORGANIZATION...Development 5a. CONTRACT NUMBER And Melanoma Tumorigenesis 5b. GRANT NUMBER W81XWH-13-1-0107 5c. PROGRAM ELEMENT NUMBER 6. AUTHOR(S) Dr. Craig...AVAILABILITY STATEMENT Approved for Public Release; Distribution Unlimited 13. SUPPLEMENTARY NOTES 14. ABSTRACT Melanoma is the most

  19. Characterization and expression of soluble guanylate cyclase in skins and melanocytes of sheep.

    PubMed

    Yang, Shanshan; Zhang, Junzhen; Ji, Kaiyuan; Jiao, Dingxing; Fan, Ruiwen; Dong, Changsheng

    2016-04-01

    The study reported the characterization of soluble guanylate cyclase (sGC) with the size of CDS of 1860bp, encoding a protein of 620 amino acids and containing several conserved functional domains including HNOB, HNOBA, and CHD. Quantitative real time PCR analysis of sGC showed that the expression of sGC mRNA is higher (∼5 fold) in white sheep skin relative to black sheep skin with significant difference (P<0.01). Using a rabbit polyclonal anti-sGC antibody, an immune reactive band corresponding to sheep sGC protein was detected in the skin samples by Western blotting analysis, and the expression of sGC protein was significantly higher in white sheep skin compared to black sheep skin (P<0.01). Immunohistochemical analysis revealed that sGC protein was localized in cytoplasm and intercellular substance of upper hair papilla in hair follicles of white sheep skin, but the protein was localized in cytoplasm and intercellular substance of lower hair bulb and outer root sheath cells in hair follicles of black sheep skin. The immunocytochemical analysis revealed that sGC was expressed in melanocytes in vitro of sheep skin. Over expression of sGC in melanocytes resulted in decreased expression of key melanogenic genes including microphthalmia transcription factor (MITF), tyrosinase (TYR), tyrosinase related protein 1(TYRTP1), and tyrosinase related protein 2(TYRP2) both at mRNA and protein level. Moreover, the melanocytes was capable of producing cGMP and cAMP. The observed differential expression and localization of sGC in sheep skins and melanocytes and the capability of producing cGMP and cAMP, which suggested a potential role for this gene in hair color regulation.

  20. Limbal melanocytes support limbal epithelial stem cells in 2D and 3D microenvironments.

    PubMed

    Dziasko, Marc A; Tuft, Stephen J; Daniels, Julie T

    2015-09-01

    Human limbal epithelial stem cells (LESCs) are essential for the maintenance of the corneal epithelium of the ocular surface. LESCs are located within limbal crypts between the palisades of Vogt in the limbus; the interface between the peripheral cornea and conjunctiva. The limbal crypts have been proposed as a LESC niche owing to their support of epithelial cells, which can form holoclone colonies in vitro. Closely associated with the limbal crypts is a concentrated population of melanocytes. The anatomical location and close proximity to putative LESC suggests that melanocytes might play a role in maintenance of these stem cells in the niche. The aim of this study was to assess the ability of human limbal melanocytes (hLM) to support the expansion of human limbal epithelial cells (LECs) in vitro as an indicator of functional cell-cell interaction. After observing that hLM co-localize with clusters of compact epithelial cells in the native limbal crypts, hLM were isolated from crypt-rich cadaveric limbal biopsies and used as feeders for the culture of LECs. Interestingly, LECs grown on mitotically active hLM were able to generate large epithelial colonies that contained small and compact cells with morphological stem cell characteristics. Immunocytochemistry revealed that LECs expanded on hLM were positive for the expression of the putative stem cell markers CK15, Bmi-1 and p63α and negative for the marker of terminal cell differentiation CK3. LECs and hLM were finally co-cultured on RAFT (real architecture for 3D tissue) collagen tissue equivalents. In 3D co-cultures, hLM promoted multi-layering of the epithelial sheet in which basal cells were maintained in an undifferentiated state. Taken together, these observations suggest melanocytes could play an important role in the maintenance of LESCs in the native human limbal stem cell niche.

  1. Detection of serum anti-melanocyte antibodies and identification of related antigens in patients with vitiligo.

    PubMed

    Zhu, M C; Liu, C G; Wang, D X; Zhan, Z

    2015-12-07

    We detected autoantibodies against melanocytes in serum samples obtained from 50 patients, including 4 with HBV, with vitiligo and identified the associated membrane antigens. Heat shock protein 70 (HSP70) and anti-tyrosinase-related protein 1 (TRP-1) antibody levels were analyzed. The associated antigens in normal human melanocyte were identified by immunofluorescence. Autoantibodies against melanocyte membrane and cytoplasmic proteins were detected by western blot. Membrane antigens with higher frequencies were identified by protein mass spectrometry. The HSP70 and anti-TRP-1 antibody levels (N = 70; 10 with HBV) were detected by ELISA. The specific antigens were detected in melanocyte cytoplasm and membrane (40/50; 80% incidence; western blot). The autoantibodies reacted with several membrane antigens with approximate molecular weights (Mr) of 86,000, 75,000, 60,000, 52,000, and 44,000 (strip positive rates: 36, 58, 22, 2, and 2%, respectively). Thirty percent of the patients showed the presence of cytoplasmic antigens (Mr: 110,000, 90,000, 75,000, 50,000, and 400,000; strip positive rates: 12, 4, 12, 10, and 2%, respectively). Fifteen and 5% of the healthy subjects showed positive expression of membrane and cytoplasmic antigens, respectively. Protein mass spectrometry predicted membrane proteins with Mr of 86,000 and 75,000 and 60,000 to be Lamin A /C and Vimentin X1, respective. High titers of anti-TRP-1 antibody were detected and showed positive correlation with HSP70 (r = 0. 927, P < 0. 01). This study identified a novel membrane antigen associated with vitiligo, which might assist future investigations into autoimmune pathogenesis of vitiligo and formation of autoantibodies. HBV infection was correlated to vitiligo.

  2. Uncovering the Role of BMP Signaling in Melanocyte Development and Melanoma Tumorigenesis

    DTIC Science & Technology

    2015-06-01

    involved. Using genomic studies and cross-species comparisons, we identified the BMP factor GDF6 as a gene that may cooperate with mutant BRAF to...promote melanoma. The aims of this grant are to determine if GDF6 does in fact cooperate with mutant BRAF and uncover the mechanisms by which GDF6 acts...in melanomas and normal melanocytes. Toward these aims, we have used our zebrafish model to demonstrate cooperativity between GDF6 and mutant BRAF

  3. Reelin and its receptors, VLDLR and ApoER2, in melanocytic nevi

    PubMed Central

    Mihail, A; Coman, G; Staniceanu, F; Coman, L; Zurac, S; Coman, OA

    2017-01-01

    Reelin is an extracellular signaling protein synthesized by Cajal-Retius cells in utero and early after birth, its presence being signaled in adult life too. Reelin acts on its receptors, VLDLR and ApoER2, acting on cytoskeleton, controlling migration and subsequently positioning and stabilizing the cortical neurons. We investigated the reelin presence and its receptors, VLDLR and ApoER2, in melanocytic nevi considering the neural crest origin of the nevus cells and their migration into skin during embrionary period. Melanocytic nevi present a strict cellular architecture and an increased malignant transforming capacity. We investigated reelin presence in 32 melanocytic nevi (5 junctional, 27 compound or 14 dysplastic nevi and 18 non dysplastic nevi). The assessment of reelin presence was performed by histological semiquantitative criteria. Results showed the presence of reelin in 29 cases (29/ 32). The presence of reelin was elevated in junctional areas as in dysplastic nevi. VLDLR presented positive values in 16 cases (16/ 32) and ApoER2 was weak positive in 7 cases. Reelin or its receptors was peritumorally absent. Our study showed the presence of reelin in nevus cells from cutaneous melanocytic nevi and, in these cells, only the VLDLR receptor was present in half of the cases. The significance of the reelin presence in cutaneous nevus cells may be hypothetically considered correlated with the position maintenance of the nevus cells or migration of these cells in malignant transforming situation. Abbreviations: ApoER2 = apolipoprotein receptor 2, VLDLR = very low density lipoprotein receptor, DAB-1 = DIABLO protein, HMB45 = gene HMB45 PMID:28255385

  4. Squamomelanocytic tumor: a new case of a unique biphenotypic neoplasm of uncertain biological potential.

    PubMed

    Rongioletti, Franco; Baldari, Manuela; Carli, Carla; Fiocca, Roberto

    2009-04-01

    Squamomelanocytic tumor is an uncommon cutaneous neoplasm composed of an admixture of melanocytic and squamous cellular phenotypes. We describe a case of this tumor in a 94-year-old man who presented with a nodule on the back. Histologically, a well-demarcated expansive dermal nodule was composed of anastomosing epithelial strands with focal formation of squamous pearls and ductal structures commixed with elongated spindle cells with clear cytoplasm grouped in nests. The two cell types were diffusely admixed or clustered in groups within the nodule. Immunohistochemical studies showed that the spindle cells grouped in nests expressed S-100 and HMB-45 antigens, and the squamoid cells expressed cytokeratins and carcinoembrionic antigen (CEA) protein only in the inner layer of the ducts and the cystic space. Atypical features and high mitotic activity was observed in the melanocytic cells but slight atypia, mild dyskeratosis and mitotic figures were observed also in the squamoid component. This tumor represents a proliferation of two phenotypic cells that are distinctive for their intimate admixture and singular immunohistochemical profile. The authors discuss the histogenesis of this tumor, suggesting that it could represent an atypical solid-cystic hidradenoma colonized by a melanocytic malignant component. The biological behavior of this neoplasm remains currently uncertain.

  5. The epidermal melanocyte population in the skin of ultraviolet-irradiated crested newt

    SciTech Connect

    Losa, M.; Zavanella, T.; Milani, S.

    1982-02-01

    The response of the epidermal melanocyte population to repeated ultraviolet (UV) exposure (wavelength spectrum 275-350 nm) has been investigated in the crested newt, Triturus cristatus carnifex. The effects of different doses of UV light were studied. The animals were killed 7 months after the first UV exposure. Only a slight decrease in the number of pigment cells was found after 85 sequential irradiations with a total dose of 1.3 x 10(5) J/m2, whereas striking decreases were observed when the same total dose was fractionated into 14 exposures or when a double dose was given in 57 exposures. The relationship between the square roots of the epidermal melanocyte densities and single doses appeared to be roughly linear, at least over the range of doses administered. The main factor in melanocyte damage seemed to be the single dose of irradiation rather than the cumulative dose administered. Decreased melanin content of the keratinocytes was observed in most irradiated animals.

  6. Rhododendrol, a depigmentation-inducing phenolic compound, exerts melanocyte cytotoxicity via a tyrosinase-dependent mechanism.

    PubMed

    Sasaki, Minoru; Kondo, Masatoshi; Sato, Kohji; Umeda, Mai; Kawabata, Keigo; Takahashi, Yoshito; Suzuki, Tamio; Matsunaga, Kayoko; Inoue, Shintaro

    2014-09-01

    Rhododendrol, an inhibitor of melanin synthesis developed for lightening/whitening cosmetics, was recently reported to induce a depigmentary disorder principally at the sites of repeated chemical contact. Rhododendrol competitively inhibited mushroom tyrosinase and served as a good substrate, while it also showed cytotoxicity against cultured human melanocytes at high concentrations sufficient for inhibiting tyrosinase. The cytotoxicity was abolished by phenylthiourea, a chelator of the copper ions at the active site, and by specific knockdown of tyrosinase with siRNA. Hence, the cytotoxicity appeared to be triggered by the enzymatic conversion of rhododendrol to active product(s). No reactive oxygen species were detected in the treated melanocytes, but up-regulation of the CCAAT-enhancer-binding protein homologous protein gene responsible for apoptosis and/or autophagy and caspase-3 activation were found to be tyrosinase dependent. These results suggest that a tyrosinase-dependent accumulation of ER stress and/or activation of the apoptotic pathway may contribute to the melanocyte cytotoxicity.

  7. Increased melanocytic nevi in patients with inherited ichthyoses: report of a previously undescribed association.

    PubMed

    Fernandes, Juliana Dumêt; Machado, Maria Cecilia Rivitti; Oliveira, Zilda Najjar P

    2010-01-01

    Ichthyosis is a heterogeneous cornification disorder. Melanocytic lesions have not been previously described in association with ichthyosis. Their clinical importance lies in the fact that they may simulate melanoma clinically and dermoscopically, as seen in epidermolysis bullosa. The objective of this study was to evaluate the clinical, dermoscopic, and histopathologic features of nevi and lentigines in 16 patients with autosomal recessive congenital ichthyosis-lamellar ichthyosis and nonbullous ichthyosiform congenital erythroderma. Patients underwent general clinical examination dermoscopy. The more suspicious lesions were excised and to histopathologic examination. Most patients (n = 13) reported no personal or familial history of melanoma or atypical nevi. All of the patients had at least five atypical melanocytic lesions. Ten of the 16 patients had at least one atypical nevus or lentigo. This study suggests that increased atypical melanocytic nevi may be a feature of long-standing congenital ichthyoses. Whether this finding is disease-related or a coincidental observation is difficult to ascertain. As an unequivocal discrimination from malignant melanoma in vivo is not always possible, regular clinical follow-up of patients with ichthyosis and increased or unusual nevi is recommended.

  8. An independent validation of a gene expression signature to differentiate malignant melanoma from benign melanocytic nevi

    PubMed Central

    Flake, Darl D.; Busam, Klaus; Cockerell, Clay; Helm, Klaus; McNiff, Jennifer; Reed, Jon; Tschen, Jaime; Kim, Jinah; Barnhill, Raymond; Elenitsas, Rosalie; Prieto, Victor G.; Nelson, Jonathan; Kimbrell, Hillary; Kolquist, Kathryn A.; Brown, Krystal L.; Warf, M. Bryan; Roa, Benjamin B.; Wenstrup, Richard J.

    2016-01-01

    BACKGROUND Recently, a 23‐gene signature was developed to produce a melanoma diagnostic score capable of differentiating malignant and benign melanocytic lesions. The primary objective of this study was to independently assess the ability of the gene signature to differentiate melanoma from benign nevi in clinically relevant lesions. METHODS A set of 1400 melanocytic lesions was selected from samples prospectively submitted for gene expression testing at a clinical laboratory. Each sample was tested and subjected to an independent histopathologic evaluation by 3 experienced dermatopathologists. A primary diagnosis (benign or malignant) was assigned to each sample, and diagnostic concordance among the 3 dermatopathologists was required for inclusion in analyses. The sensitivity and specificity of the score in differentiating benign and malignant melanocytic lesions were calculated to assess the association between the score and the pathologic diagnosis. RESULTS The gene expression signature differentiated benign nevi from malignant melanoma with a sensitivity of 91.5% and a specificity of 92.5%. CONCLUSIONS These results reflect the performance of the gene signature in a diverse array of samples encountered in routine clinical practice. Cancer 2017;123:617–628. © 2016 American Cancer Society. PMID:27768230

  9. A melanocyte--melanoma precursor niche in sweat glands of volar skin.

    PubMed

    Okamoto, Natsuko; Aoto, Takahiro; Uhara, Hisashi; Yamazaki, Satoshi; Akutsu, Hidenori; Umezawa, Akihiro; Nakauchi, Hiromitsu; Miyachi, Yoshiki; Saida, Toshiaki; Nishimura, Emi K

    2014-11-01

    Determination of the niche for early-stage cancer remains a challenging issue. Melanoma is an aggressive cancer of the melanocyte lineage. Early melanoma cells are often found in the epidermis around sweat ducts of human volar skin, and the skin pigmentation pattern is an early diagnostic sign of acral melanoma. However, the niche for melanoma precursors has not been determined yet. Here, we report that the secretory portion (SP) of eccrine sweat glands provide an anatomical niche for melanocyte-melanoma precursor cells. Using lineage-tagged H2B-GFP reporter mice, we found that melanoblasts that colonize sweat glands during development are maintained in an immature, slow-cycling state but renew themselves in response to genomic stress and provide their differentiating progeny to the epidermis. FISH analysis of human acral melanoma expanding in the epidermis revealed that unpigmented melanoblasts with significant cyclin D1 gene amplification reside deep in the SP of particular sweat gland(s). These findings indicate that sweat glands maintain melanocyte-melanoma precursors in an immature state in the niche and explain the preferential distribution of early melanoma cells around sweat glands in human volar skin.

  10. α-MSH regulates intergenic splicing of MC1R and TUBB3 in human melanocytes

    PubMed Central

    Dalziel, Martin; Kolesnichenko, Marina; das Neves, Ricardo Pires; Iborra, Francisco; Goding, Colin; Furger, André

    2011-01-01

    Alternative splicing enables higher eukaryotes to increase their repertoire of proteins derived from a restricted number of genes. However, the possibility that functional diversity may also be augmented by splicing between adjacent genes has been largely neglected. Here, we show that the human melanocortin 1 receptor (MC1R) gene, a critical component of the facultative skin pigmentation system, has a highly complex and inefficient poly(A) site which is instrumental in allowing intergenic splicing between this locus and its immediate downstream neighbour tubulin-β-III (TUBB3). These transcripts, which produce two distinct protein isoforms localizing to the plasma membrane and the endoplasmic reticulum, seem to be restricted to humans as no detectable chimeric mRNA could be found in MC1R expressing mouse melanocytes. Significantly, treatment with the MC1R agonist α-MSH or activation of the stress response kinase p38-MAPK, both key molecules associated with ultraviolet radiation dermal insult and subsequent skin tanning, result in a shift in expression from MC1R in favour of chimeric MC1R-TUBB3 isoforms in cultured melanocytes. We propose that these chimeric proteins serve to equip melanocytes with novel cellular phenotypes required as part of the pigmentation response. PMID:21071418

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

    PubMed Central

    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. PMID:27941997

  12. Discovering novel phenotypes with automatically inferred dynamic models: a partial melanocyte conversion in Xenopus

    NASA Astrophysics Data System (ADS)

    Lobo, Daniel; Lobikin, Maria; Levin, Michael

    2017-01-01

    Progress in regenerative medicine requires reverse-engineering cellular control networks to infer perturbations with desired systems-level outcomes. Such dynamic models allow phenotypic predictions for novel perturbations to be rapidly assessed in silico. Here, we analyzed a Xenopus model of conversion of melanocytes to a metastatic-like phenotype only previously observed in an all-or-none manner. Prior in vivo genetic and pharmacological experiments showed that individual animals either fully convert or remain normal, at some characteristic frequency after a given perturbation. W