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Sample records for apocrine molecular subtype

  1. 15-prostaglandin dehydrogenase expression alone or in combination with ACSM1 defines a subgroup of the apocrine molecular subtype of breast carcinoma

    DEFF Research Database (Denmark)

    Celis, J.E.; Gromov, P.; Cabezon, T.;

    2008-01-01

    is not expressed by other breast cancer types as determined by gel-based proteomics and immunohistochemistry analysis and that antibodies against this protein can identify IACs in an unbiased manner in a large breast cancer tissue microarray making them potentially useful as a diagnostic aid Udgivelsesdato: 2008/10...... and subtype these lesions as well as targets that may lead to the development of novel targeted therapies and chemoprevention strategies. By comparing the protein expression profiles of apocrine macrocysts and non-malignant breast epithelial tissue we have previously reported the identification of a few...... proteins that are specifically expressed by benign apocrine lesions as well as by the few IACs that were available to us at the time. Here we reiterate our strategy to reveal apocrine cell markers and present novel data, based on the analysis of a considerably larger number of samples, establishing...

  2. Molecular pathology of breast apocrine carcinomas

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    Celis, J.E.; Gromova, I.; Gromov, P.;

    2006-01-01

    Breast cancer is a heterogeneous disease that encompasses a wide range of histopathological types including: invasive ductal carcinoma, lobular carcinoma, medullary carcinoma, mucinous carcinoma, tubular carcinoma, and apocrine carcinoma among others. Pure apocrine carcinomas represent about 0...... benign apocrine changes and breast carcinoma is unclear and has been a matter of discussion for many years. Recent proteome expression profiling studies of breast apocrine macrocysts, normal breast tissue, and breast tumours have identified specific apocrine biomarkers [15-hydroxyprostaglandin...... dehydrogenase (15-PGDH) and hydroxymethylglutaryl coenzyme A reductase (HMG-CoA reductase)] present in early and advanced apocrine lesions. These biomarkers in combination with proteins found to be characteristically upregulated in pure apocrine carcinomas (psoriasin, S100A9, and p53) provide a protein...

  3. Molecular characterization of apocrine carcinoma of the breast: validation of an apocrine protein signature in a well-defined cohort

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    Celis, J.E.; Cabezon, T.; Moreira, José;

    2009-01-01

    1), in addition to a set of categorizing markers that are consistently expressed (AR, CD24) or not expressed (ERalpha, PgR, Bcl-2, and GATA-3) by apocrine metaplasia in benign breast lesions and apocrine sweat glands. This panel was used to analyze a well-defined cohort consisting of 14 apocrine...... that IACs correspond to a distinct, even if heterogeneous, molecular subgroup of breast carcinomas that can be readily identified in an unbiased way using a combination of markers that recapitulate the phenotype of apocrine sweat glands (15-PGDH(+), ACSM1(+), AR(+), CD24(+), ERalpha(-), PgR(-), Bcl-2...

  4. Apocrine-eccrine carcinomas: molecular and immunohistochemical analyses.

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    Long P Le

    Full Text Available Apocrine-eccrine carcinomas are rare and associated with poor prognosis. Currently there is no uniform treatment guideline. Chemotherapeutic drugs that selectively target cancer-promoting pathways may complement conventional therapeutic approaches. However, studies on genetic alterations and EGFR and Her2 status of apocrine-eccrine carcinomas are few in number. In addition, hormonal studies have not been comprehensive and performed only on certain subsets of apocrine-eccrine carcinomas. To investigate whether apocrine-eccrine carcinomas express hormonal receptors or possess activation of oncogenic pathways that can be targeted by available chemotherapeutic agent we performed immunohistochemistry for AR, PR, ER, EGFR, and HER2 expression; fluorescence in situ hybridization (FISH for EGFR and ERBB2 gene amplification; and molecular analyses for recurrent mutations in 15 cancer genes including AKT-1, EGFR, PIK3CA, and TP53 on 54 cases of apocrine-eccrine carcinomas. They include 10 apocrine carcinomas, 7 eccrine carcinomas, 9 aggressive digital papillary adenocarcinomas, 10 hidradenocarcinomas, 11 porocarcinomas, 1 adenoid cystic carcinoma, 4 malignant chondroid syringomas, 1 malignant spiradenoma, and 1 malignant cylindroma. AR, ER, PR, EGFR and HER2 expression was seen in 36% (19/53, 27% (14/51, 16% (8/51, 85% (44/52 and 12% (6/52, respectively. Polysomy or trisomy of EGFR was detected by FISH in 30% (14/46. Mutations of AKT-1, PIK3CA, and TP53 were detected in 1, 3, and 7 cases, respectively (11/47, 23%. Additional investigation regarding the potential treatment of rare cases of apocrine-eccrine carcinomas with PI3K/Akt/mTOR pathway inhibitors, currently in clinical testing, may be of clinical interest.

  5. p62 Regulates the Proliferation of Molecular Apocrine Breast Cancer Cells

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    Nozaki, Fumi; Hirotani, Yukari; Nakanishi, Yoko; Yamaguchi, Hiromi; Nishimaki, Haruna; Noda, Hiroko; Tang, Xiaoyan; Yamamoto, Hisae; Suzuki, Atsuko; Seki, Toshimi; Masuda, Shinobu

    2016-01-01

    p62, also called sequestosome 1 (SQSTM1), is a multifunctional signaling molecule that affects cell proliferation. Recently, we found accumulation of p62 in apocrine carcinoma of the breast, however, the biological role of p62 expression in apocrine carcinoma still remains unclear. To investigate whether p62 might contribute to tumor cell proliferation in apocrine carcinomas, we used the MDA-MB-453 (androgen receptor-positive, HER2-type) and MFM223 (androgen receptor-positive, triple-negative type) breast cancer cell lines as models of molecular apocrine carcinoma. Both MDA-MB-453 and MFM223 showed strong and d high p62 protein expression than MCF7 cells (androgen receptor-negative, luminal A type). Knockdown of p62 resulted in significant reduction of the cell proliferative activity in both MDA-MB-453 (P<0.01) and MFM223 (P<0.05). In conclusion, p62 could contribute to cell proliferation and represent a therapeutic target in apocrine carcinoma.

  6. Immunohistochemical and molecular profiling of histologically defined apocrine carcinomas of the breast.

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    Vranic, Semir; Marchiò, Caterina; Castellano, Isabella; Botta, Cristina; Scalzo, Maria Stella; Bender, Ryan P; Payan-Gomez, Cesar; di Cantogno, Ludovica Verdun; Gugliotta, Patrizia; Tondat, Fabrizio; di Celle, Paola Francia; Mariani, Sara; Gatalica, Zoran; Sapino, Anna

    2015-09-01

    Despite the marked improvement in the understanding of molecular mechanisms and classification of apocrine carcinoma, little is known about its specific molecular genetic alterations and potentially targetable biomarkers. In this study, we explored immunohistochemical and molecular genetic characteristics of 37 invasive apocrine carcinomas using immunohistochemistry (IHC), fluorescent in situ hybridization (FISH), multiplex ligation-dependent probe amplification (MLPA), and next-generation sequencing (NGS) assays. IHC revealed frequent E-cadherin expression (89%), moderate (16%) proliferation activity [Ki-67, phosphohistone H3], infrequent (~10%) expression of basal cell markers [CK5/6, CK14, p63, caveolin-1], loss of PTEN (83%), and overexpression of HER2 (32%), EGFR (41%), cyclin D1 (50%), and MUC-1 (88%). MLPA assay revealed gene copy gains of MYC, CCND1, ZNF703, CDH1, and TRAF4 in 50% or greater of the apocrine carcinomas, whereas gene copy losses frequently affected BRCA2 (75%), ADAM9 (54%), and BRCA1 (46%). HER2 gain, detected by MLPA in 38% of the cases, was in excellent concordance with HER2 results obtained by IHC/FISH (κ = 0.915, P carcinomas exhibit complex molecular genetic alterations that are consistent with the "luminal-complex" phenotype. Some of the identified molecular targets are promising biomarkers; however, functional studies are needed to prove these observations.

  7. An androgen receptor mutation in the MDA-MB-453 cell line model of molecular apocrine breast cancer compromises receptor activity.

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    Moore, Nicole L; Buchanan, Grant; Harris, Jonathan M; Selth, Luke A; Bianco-Miotto, Tina; Hanson, Adrienne R; Birrell, Stephen N; Butler, Lisa M; Hickey, Theresa E; Tilley, Wayne D

    2012-08-01

    Recent evidence indicates that the estrogen receptor-α-negative, androgen receptor (AR)-positive molecular apocrine subtype of breast cancer is driven by AR signaling. The MDA-MB-453 cell line is the prototypical model of this breast cancer subtype; its proliferation is stimulated by androgens such as 5α-dihydrotestosterone (DHT) but inhibited by the progestin medroxyprogesterone acetate (MPA) via AR-mediated mechanisms. We report here that the AR gene in MDA-MB-453 cells contains a G-T transversion in exon 7, resulting in a receptor variant with a glutamine to histidine substitution at amino acid 865 (Q865H) in the ligand binding domain. Compared with wild-type AR, the Q865H variant exhibited reduced sensitivity to DHT and MPA in transactivation assays in MDA-MB-453 and PC-3 cells but did not respond to non-androgenic ligands or receptor antagonists. Ligand binding, molecular modeling, mammalian two-hybrid and immunoblot assays revealed effects of the Q865H mutation on ligand dissociation, AR intramolecular interactions, and receptor stability. Microarray expression profiling demonstrated that DHT and MPA regulate distinct transcriptional programs in MDA-MB-453 cells. Gene Set Enrichment Analysis revealed that DHT- but not MPA-regulated genes were associated with estrogen-responsive transcriptomes from MCF-7 cells and the Wnt signaling pathway. These findings suggest that the divergent proliferative responses of MDA-MB-453 cells to DHT and MPA result from the different genetic programs elicited by these two ligands through the AR-Q865H variant. This work highlights the necessity to characterize additional models of molecular apocrine breast cancer to determine the precise role of AR signaling in this breast cancer subtype. PMID:22719059

  8. Transcriptome classification reveals molecular subtypes in psoriasis

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    Ainali Chrysanthi

    2012-09-01

    Full Text Available Abstract Background Psoriasis is an immune-mediated disease characterised by chronically elevated pro-inflammatory cytokine levels, leading to aberrant keratinocyte proliferation and differentiation. Although certain clinical phenotypes, such as plaque psoriasis, are well defined, it is currently unclear whether there are molecular subtypes that might impact on prognosis or treatment outcomes. Results We present a pipeline for patient stratification through a comprehensive analysis of gene expression in paired lesional and non-lesional psoriatic tissue samples, compared with controls, to establish differences in RNA expression patterns across all tissue types. Ensembles of decision tree predictors were employed to cluster psoriatic samples on the basis of gene expression patterns and reveal gene expression signatures that best discriminate molecular disease subtypes. This multi-stage procedure was applied to several published psoriasis studies and a comparison of gene expression patterns across datasets was performed. Conclusion Overall, classification of psoriasis gene expression patterns revealed distinct molecular sub-groups within the clinical phenotype of plaque psoriasis. Enrichment for TGFb and ErbB signaling pathways, noted in one of the two psoriasis subgroups, suggested that this group may be more amenable to therapies targeting these pathways. Our study highlights the potential biological relevance of using ensemble decision tree predictors to determine molecular disease subtypes, in what may initially appear to be a homogenous clinical group. The R code used in this paper is available upon request.

  9. The consensus molecular subtypes of colorectal cancer.

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    Guinney, Justin; Dienstmann, Rodrigo; Wang, Xin; de Reyniès, Aurélien; Schlicker, Andreas; Soneson, Charlotte; Marisa, Laetitia; Roepman, Paul; Nyamundanda, Gift; Angelino, Paolo; Bot, Brian M; Morris, Jeffrey S; Simon, Iris M; Gerster, Sarah; Fessler, Evelyn; De Sousa E Melo, Felipe; Missiaglia, Edoardo; Ramay, Hena; Barras, David; Homicsko, Krisztian; Maru, Dipen; Manyam, Ganiraju C; Broom, Bradley; Boige, Valerie; Perez-Villamil, Beatriz; Laderas, Ted; Salazar, Ramon; Gray, Joe W; Hanahan, Douglas; Tabernero, Josep; Bernards, Rene; Friend, Stephen H; Laurent-Puig, Pierre; Medema, Jan Paul; Sadanandam, Anguraj; Wessels, Lodewyk; Delorenzi, Mauro; Kopetz, Scott; Vermeulen, Louis; Tejpar, Sabine

    2015-11-01

    Colorectal cancer (CRC) is a frequently lethal disease with heterogeneous outcomes and drug responses. To resolve inconsistencies among the reported gene expression-based CRC classifications and facilitate clinical translation, we formed an international consortium dedicated to large-scale data sharing and analytics across expert groups. We show marked interconnectivity between six independent classification systems coalescing into four consensus molecular subtypes (CMSs) with distinguishing features: CMS1 (microsatellite instability immune, 14%), hypermutated, microsatellite unstable and strong immune activation; CMS2 (canonical, 37%), epithelial, marked WNT and MYC signaling activation; CMS3 (metabolic, 13%), epithelial and evident metabolic dysregulation; and CMS4 (mesenchymal, 23%), prominent transforming growth factor-β activation, stromal invasion and angiogenesis. Samples with mixed features (13%) possibly represent a transition phenotype or intratumoral heterogeneity. We consider the CMS groups the most robust classification system currently available for CRC-with clear biological interpretability-and the basis for future clinical stratification and subtype-based targeted interventions.

  10. Molecular subtypes and clinicopathological features of breastcancer

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    Irianiwati Irianiwati

    2013-04-01

    Full Text Available Breast cancer is a heterogeneous disease with regard to morphological spectrum, clinical presentation and response to therapy. Based on immunohistochemistry detection of estrogen receptor, progesterone receptor, Her-2 status, proliferation rate and clusters of basal gene expression, breast cancers can be classified into luminal A, luminal B, basal-like/triple negative, and Her-2 positive. It was suggested that there was a close relationship between molecular subtypes and clinicopathological features of breast cancer, as they are very important to predict prognosis and therapeutic implications. Keywords: molecular subtypes - breast cancer- clinicopathological features -heterogeneity –theraputicimplications   Normal 0 false false false EN-US X-NONE X-NONE /* Style Definitions */ table.MsoNormalTable {mso-style-name:"Table Normal"; mso-tstyle-rowband-size:0; mso-tstyle-colband-size:0; mso-style-noshow:yes; mso-style-priority:99; mso-style-qformat:yes; mso-style-parent:""; mso-padding-alt:0in 5.4pt 0in 5.4pt; mso-para-margin:0in; mso-para-margin-bottom:.0001pt; mso-pagination:widow-orphan; font-size:11.0pt; font-family:"Calibri","sans-serif"; mso-ascii-font-family:Calibri; mso-ascii-theme-font:minor-latin; mso-fareast-font-family:"Times New Roman"; mso-fareast-theme-font:minor-fareast; mso-hansi-font-family:Calibri; mso-hansi-theme-font:minor-latin; mso-bidi-font-family:"Times New Roman"; mso-bidi-theme-font:minor-bidi;}

  11. Apocrine adenocarcinoma of the vulva

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    Babita Kajal

    2013-09-01

    Full Text Available Cutaneous vulvar carcinomas are predominantly of squamous cell carcinoma type. Primary vulvar adenocarcinomas are rare with a poorly understood histogenesis. They are classified into extramammary Paget’s disease, sweat gland carcinomas, and breast-like adenocarcinomas of the vulva. Adenocarcinomas, originating from Bartholin glands, can also present as vulvar adenocarcinoma. Rare adenocarcinomas with apocrine features have been described in the literature. The origin of these neoplasms from the native apocrine sweat glands or from anogenital mammary-like glands is still debatable. We report herein a case of a 67 year old female with a rare primary apocrine carcinoma of the vulva.

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

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

    2014-01-01

    with the well-established intrinsic molecular subtypes of breast cancer. METHODS: Global gene expression profiling using Illumina's HT12 Bead Arrays was applied to 59 fresh-frozen serous ovarian malignant, benign and borderline tumors. Nearest centroid classification was performed applying previously published...... to the luminal A breast cancer subtype. These findings remained when analyzed in an independent dataset, supporting links between the molecular subtypes of ovarian cancer and breast cancer beyond those recently acknowledged. CONCLUSIONS: These data link the transcriptional profiles of serous ovarian cancer...... to the intrinsic molecular subtypes of breast cancer, in line with the shared clinical and molecular features between high-grade serous ovarian cancer and basal-like breast cancer, and suggest that biomarkers and targeted therapies may overlap between these tumor subsets. The link between benign and borderline...

  13. Identification of a novel luminal molecular subtype of breast cancer.

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    Anna Dvorkin-Gheva

    Full Text Available The molecular classification of human breast tumors has afforded insights into subtype specific biological processes, patient prognosis and response to therapies. However, using current methods roughly one quarter of breast tumors cannot be classified into one or another molecular subtype. To explore the possibility that the unclassifiable samples might comprise one or more novel subtypes we employed a collection of publically available breast tumor datasets with accompanying clinical information to assemble 1,593 transcript profiles: 25% of these samples could not be assigned to one of the current molecular subtypes of breast cancer. All of the unclassifiable samples could be grouped into a new molecular subtype, which we termed "luminal-like". We also identified the luminal-like subtype in an independent collection of tumor samples (NKI295. We found that patients harboring tumors of the luminal-like subtype have a better prognosis than those with basal-like breast cancer, a similar prognosis to those with ERBB2+, luminal B or claudin-low tumors, but a worse prognosis than patients with luminal A or normal-like breast tumors. Our findings suggest the occurrence of another molecular subtype of breast cancer that accounts for the vast majority of previously unclassifiable breast tumors.

  14. FABP7 and HMGCS2 are novel protein markers for apocrine differentiation categorizing apocrine carcinoma of the breast

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    Gromov, Pavel; Espinoza, Jaime A.; Talman, Maj-Lis;

    2014-01-01

    from other breast lesions, no standard molecular criteria are currently available for their diagnosis. Using gel-based proteomics in combination with mass spectrometry and immunohistochemistry we have identified two novel markers, HMGCS2 and FABP7 that categorize the entire breast apocrine......Apocrine carcinoma of the breast is a distinctive malignancy with unique morphological and molecular features, generally characterized by being negative for estrogen and progesterone receptors, and thus not electable for endocrine therapy. Despite the fact that they are morphologically distinct......1, together they provide a signature that may represent a golden molecular standard for defining the apocrine phenotype in the breast. Moreover, we show that combining HMGCS2 to the steroidal profile (HMGCS2+/Androgen Receptor (AR)+/Estrogen Receptor(ER)-/Progesteron Receptor (PR)- identifies IACs...

  15. Molecular subtyping of serous ovarian tumors reveals multiple connections to intrinsic breast cancer subtypes.

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    Jenny-Maria Jönsson

    Full Text Available OBJECTIVE: Transcriptional profiling of epithelial ovarian cancer has revealed molecular subtypes correlating to biological and clinical features. We aimed to determine gene expression differences between malignant, benign and borderline serous ovarian tumors, and investigate similarities with the well-established intrinsic molecular subtypes of breast cancer. METHODS: Global gene expression profiling using Illumina's HT12 Bead Arrays was applied to 59 fresh-frozen serous ovarian malignant, benign and borderline tumors. Nearest centroid classification was performed applying previously published gene profiles for the ovarian and breast cancer subtypes. Correlations to gene expression modules representing key biological breast cancer features were also sought. Validation was performed using an independent, publicly available dataset. RESULTS: 5,944 genes were significantly differentially expressed between benign and malignant serous ovarian tumors, with cell cycle processes enriched in the malignant subgroup. Borderline tumors were split between the two clusters. Significant correlations between the malignant serous tumors and the highly aggressive ovarian cancer signatures, and the basal-like breast cancer subtype were found. The benign and borderline serous tumors together were significantly correlated to the normal-like breast cancer subtype and the ovarian cancer signature derived from borderline tumors. The borderline tumors in the study dataset, in addition, also correlated significantly to the luminal A breast cancer subtype. These findings remained when analyzed in an independent dataset, supporting links between the molecular subtypes of ovarian cancer and breast cancer beyond those recently acknowledged. CONCLUSIONS: These data link the transcriptional profiles of serous ovarian cancer to the intrinsic molecular subtypes of breast cancer, in line with the shared clinical and molecular features between high-grade serous ovarian cancer and

  16. Molecular based subtyping of feline mammary carcinomas and clinicopathological characterization.

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    Soares, Maria; Madeira, Sara; Correia, Jorge; Peleteiro, Maria; Cardoso, Fátima; Ferreira, Fernando

    2016-06-01

    Molecular classification of feline mammary carcinomas (FMC) from which specific behavioral patterns may be estimated has potential applications in veterinary clinical practice and in comparative oncology. In this perspective, the main goal of this study was to characterize both the clinical and the pathological features of the different molecular phenotypes found in a population of FMC (n = 102), using the broadly accepted IHC-based classification established by St. Gallen International Expert Consensus panel. The luminal B/HER2-negative subtype was the most common (29.4%, 30/102) followed by luminal B/HER2-positive subtype (19.6%, 20/102), triple negative basal-like (16.7%, 17/102), luminal A (14.7%, 15/102), triple negative normal-like (12.7%, 13/102) and finally, HER2-positive subtype (6.9%, 7/102). Luminal A subtype was significantly associated with smaller tumors (p = 0.024) and with well differentiated ones (p molecular subtypes in each carcinoma, revealing that all independent lesions should be analyzed in order to improve the clinical management of animals. Finally, the similarities between the subtypes of feline mammary tumors and human breast cancer, reveal that feline can be a valuable model for comparative studies. PMID:27212699

  17. Apocrine Adenocarcinoma of the Vulva

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    Babita Kajal; Hetal Talati; Dean Daya; Salem Alowami

    2013-01-01

    Cutaneous vulvar carcinomas are predominantly of squamous cell carcinoma type. Primary vulvar adenocarcinomas are rare with a poorly understood histogenesis. They are classified into extramammary Paget’s disease, sweat gland carcinomas, and breast-like adenocarcinomas of the vulva. Adenocarcinomas, originating from Bartholin glands, can also present as vulvar adenocarcinoma. Rare adenocarcinomas with apocrine features have been described in the literature. The origin of these neoplasms from t...

  18. Apocrine carcinoma of the male breast: a case report of an exceptional tumor

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    Sekal, Mohammed; Znati, Kaoutar; Harmouch, Taoufiq; Riffi, Afaf Amarti

    2014-01-01

    Apocrine carcinoma of the male breast is an exceptional malignant tumor. It does not have a particular clinical or radiological appearance, but it's microscopically characterized by the presence of granular cells and foamy cells representing over 90% of tumor cells. These cells express most of the time the GCDFP-15 and the androgen receptors. This tumor is a distinct molecular entity. In this observation, we report the case of a 70 year old man presenting apocrine carcinoma of the left breast...

  19. Clinical implications of the intrinsic molecular subtypes of breast cancer.

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    Prat, Aleix; Pineda, Estela; Adamo, Barbara; Galván, Patricia; Fernández, Aranzazu; Gaba, Lydia; Díez, Marc; Viladot, Margarita; Arance, Ana; Muñoz, Montserrat

    2015-11-01

    Gene-expression profiling has had a considerable impact on our understanding of breast cancer biology. During the last 15 years, 5 intrinsic molecular subtypes of breast cancer (Luminal A, Luminal B, HER2-enriched, Basal-like and Claudin-low) have been identified and intensively studied. In this review, we will focus on the current and future clinical implications of the intrinsic molecular subtypes beyond the current pathological-based classification endorsed by the 2013 St. Gallen Consensus Recommendations. Within hormone receptor-positive and HER2-negative early breast cancer, the Luminal A and B subtypes predict 10-year outcome regardless of systemic treatment administered as well as residual risk of distant recurrence after 5 years of endocrine therapy. Within clinically HER2-positive disease, the 4 main intrinsic subtypes can be identified and dominate the biological and clinical phenotype. From a clinical perspective, patients with HER2+/HER2-enriched disease seem to benefit the most from neoadjuvant trastuzumab, or dual HER2 blockade with trastuzumab/lapatinib, in combination with chemotherapy, and patients with HER2+/Luminal A disease seem to have a relative better outcome compared to the other subtypes. Finally, within triple-negative breast cancer (TNBC), the Basal-like disease predominates (70-80%) and, from a biological perspective, should be considered a cancer-type by itself. Importantly, the distinction between Basal-like versus non-Basal-like within TNBC might predict survival following (neo)adjvuvant multi-agent chemotherapy, bevacizumab benefit in the neoadjuvant setting (CALGB40603), and docetaxel vs. carboplatin benefit in first-line metastatic disease (TNT study). Overall, this data suggests that intrinsic molecular profiling provides clinically relevant information beyond current pathology-based classifications.

  20. Breast cancer molecular subtypes: from TNBC to QNBC

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    Hon, Jane Date C; Singh, Baljit; Sahin, Aysegul; Du, Gang; Wang, Jinhua; Wang, Vincent Y; Deng, Fang-Ming; Zhang, David Y; Monaco, Marie E; Lee, Peng

    2016-01-01

    Treatment protocols for breast cancer depend predominantly on receptor status with respect to estrogen (estrogen receptor alpha), progesterone (progesterone receptor) and human epidermal growth factor [human epidermal growth factor receptor 2 (HER2)]. The presence of one or more of these receptors suggests that a treatment targeting these pathways might be effective, while the absence of, or in the case of HER2, lack of overexpression of, all of these receptors, termed triple negative breast cancer (TNBC), indicates a need for the more toxic chemotherapy. In an effort to develop targeted therapies for TNBC, it will be necessary to differentiate among specific TNBC subtypes. The subset of TNBC that expresses androgen receptor (AR) has been determined to express genes consistent with a luminal subtype and therefore may be amenable to therapies targeting either AR, itself, or other pathways typical of a luminal subtype. Recent investigations of the AR signal pathway within breast cancer lead to AR as a significant target for breast cancer therapy with several clinical trials currently in progress. The subclass of TNBC that lacks AR, which we have termed quadruple negative breast cancer (QNBC) currently lacks a defined targetable pathway. Unlike AR-positive TNBC, QNBC predominantly exhibits a basal-like molecular subtype. Several subtypes and related pathway proteins are preferentially expressed in QNBC that may serve as effective targets for treatment, such as ACSL4, SKP2 and EGFR. ACSL4 expression has been demonstrated to be inversely correlated with expression of hormone/growth factor receptors and may thus serve as a biomarker for QNBC as well as a target for therapy. In the following review we summarize some of the current efforts to develop alternatives to chemotherapy for TNBC and QNBC.

  1. Molecular subtyping of breast cancer: opportunities for new therapeutic approaches.

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    Mullan, P B; Millikan, R C

    2007-12-01

    Evidence is accumulating that breast cancer is not one disease but many separate diseases. DNA microarray-based gene expression profiling has demonstrated subtypes with distinct phenotypic features and clinical responses. Prominent among the new subtypes is 'basal-like' breast cancer, one of the 'intrinsic' subtypes defined by negativity for the estrogen, progesterone, and HER2/neu receptors and positivity for cytokeratins-5/6. Focusing on basal-like breast cancer, we discuss how molecular technologies provide new chemotherapy targets, optimising treatment whilst sparing patients from unnecessary toxicity. Clinical trials are needed that incorporate long-term follow-up of patients with well-characterised tumour markers. Whilst the absence of an obvious dominant oncogene driving basal-like breast cancer and the lack of specific therapeutic agents are serious stumbling blocks, this review will highlight several promising therapeutic candidates currently under evaluation. Thus, new molecular technologies should provide a fundamental foundation for better understanding breast and other cancers which may be exploited to save lives. (Part of a Multi-author Review). PMID:17957336

  2. Molecular epidemiology of salmonid alphavirus (SAV subtype 3 in Norway

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    Jansen Mona D

    2010-08-01

    by other researchers. Larger scale, full length sequence analyses should be instigated to allow further phylogenetic and molecular epidemiology investigations of SAV subtype 3.

  3. Genomics Study of Gastric Cancer and Its Molecular Subtypes.

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    Yuen, Siu Tsan; Leung, Suet Yi

    2016-01-01

    Gastric cancer is a heterogeneous disease encompassing diverse morphological (intestinal versus diffuse) and molecular subtypes (MSI, EBV, TP53 mutation). Recent advances in genomic technology have led to an improved understanding of the driver gene mutational profile, gene expression, and epigenetic alterations that underlie each of the subgroups, with therapeutic implications in some of these alterations. There have been attempts to classify gastric cancers based on these genomic features, with an aim to improve prognostication and predict responsiveness to specific drug therapy. The eventual aims of these genomic studies are to develop deep biological insights into the carcinogenic pathway in each of these subtypes. Future large-scale drug screening strategies may then be able to link these genomic features to drug responsiveness, eventually leading to genome-guided personalized medicine with improved cure rates. PMID:27573784

  4. Pure Apocrine Carcinomas Represent a Clinicopathologically Distinct Androgen Receptor-Positive Subset of Triple-Negative Breast Cancers.

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    Mills, Anne M; E Gottlieb, Chelsea; M Wendroth, Scott; M Brenin, Christiana; Atkins, Kristen A

    2016-08-01

    Apocrine carcinomas comprise ∼1% of all breast cancers and are characterized by large cells bearing abundant eosinophilic granular cytoplasm, round nuclei, and prominent nucleoli. They are typically estrogen receptor/progesterone receptor/HER2 negative, making them unresponsive to typical hormonal or HER2-based chemotherapy. However, this subtype of triple-negative breast cancers expresses androgen receptor (AR), a feature not shared by most nonapocrine triple-negative cancers (NA-TNCs). AR therefore represents a potential diagnostic tool and therapeutic target for apocrine breast carcinoma. All pure apocrine carcinomas diagnosed during a 10-year period were reviewed, and clinicopathologic characteristics were compared with a control group of 26 NA-TNC cases. Twenty apocrine carcinomas were identified (∼0.8% of all breast cancers). The mean age at diagnosis was 69.3 years for apocrine carcinomas and 56.7 years for NA-TNC. All apocrine carcinomas and no NA-TNC were AR positive. The proportions of apocrine carcinoma grades varied, with G1 being seen in 15% of patients, G2 in 55%, and G3 in 30%. In contrast, 100% of NA-TNC cases were G3. The majority of apocrine carcinomas presented at low T stage (T1: 70%; T2: 20%; T3: 10%; T4: 0%), whereas NA-TNC cases more often presented at T2 or higher (T1: 46.2%; T2: 30.8%; T3: 11.5%; T4: 11.5%). Thirty percent of apocrine carcinomas and 30.8% of NA-TNCs had nodal metastases at presentation. Apocrine carcinomas had a favorable clinical prognosis, with 80% of patients showing no evidence of disease-related morbidity or mortality (mean follow-up: 45.2 mo). Pure apocrine carcinomas represent a clinicopathologically distinct subgroup of triple-negative breast cancer characterized by AR positivity. When compared with NA-TNC, apocrine carcinomas more often present in older women with lower grade and T stage, a group in which a more conservative treatment regimen is often desired. PMID:27259012

  5. Breast Conservation Therapy: The Influence of Molecular Subtype and Margins

    International Nuclear Information System (INIS)

    Purpose: To evaluate treatment results and prognostic factors, especially margin status and molecular subtype, in early-stage breast cancer patients treated with breast conservation therapy (BCT). Methods and Materials: The records of 1,058 Stage I or II breast cancer patients treated with BCT (surgical excision plus radiotherapy) at Duke University Medical Center, Durham, North Carolina, from 1985–2005 were retrospectively reviewed. Conventional receptor analyses were used as surrogate markers for molecular subtype classification (luminal A, luminal B, Her2 positive, and basal like). Actuarial estimates of overall survival (OS), cause-specific survival (CSS), failure-free survival, and locoregional control (LRC) were computed by use of Kaplan-Meier plots. We analyzed prognostic variables for significance using Cox proportional hazards univariate and multivariate analysis. The study was approved by the Duke University Medical Center Institutional Review Board. Results: The median age of the patients was 56 years (range, 18–89 years). Of the patients, 80% had T1 disease and 66% N0 disease pathologically. With a median follow-up of 9.8 years, an in-breast recurrence developed in 53 patients and 10 patients had nodal failure. For all patients, the 10-year CSS rate was 94%; LRC rate, 94%; and failure-free survival rate, 88%. Luminal A patients had a CSS rate of 95% and LRC rate of 99%. Basal-type patients appeared to do worse, with regard to both CSS rate (74%) and LRC rate (76%), but the numbers were small and the difference was not statistically significant. LRC rates of patients with negative margins (widely negative, close, and extent of margin not known) were virtually identical (93%, 96%, and 94%, respectively). Those with positive margins appeared to fare slightly worse based on LRC rate (88%), but again, the numbers were small and the difference was not statistically significant. Conclusions: BCT remains the treatment of choice for early-stage breast cancer

  6. Breast Conservation Therapy: The Influence of Molecular Subtype and Margins

    Energy Technology Data Exchange (ETDEWEB)

    Demirci, Senem, E-mail: senem.demirci@ege.edu.tr [Department of Radiation Oncology, Duke University Medical Center, Durham, NC (United States); Department of Radiation Oncology, Ege University Faculty of Medicine, Izmir (Turkey); Broadwater, Gloria [Department of Biostatistics and Bioinformatics, Duke Cancer Institute, Durham, NC (United States); Cancer and Leukemia Group B Statistical Center, Duke Cancer Institute, Durham, NC (United States); Marks, Lawrence B. [Department of Radiation Oncology, University of North Carolina School of Medicine, Chapel Hill, NC (United States); Clough, Robert; Prosnitz, Leonard R. [Department of Radiation Oncology, Duke University Medical Center, Durham, NC (United States)

    2012-07-01

    Purpose: To evaluate treatment results and prognostic factors, especially margin status and molecular subtype, in early-stage breast cancer patients treated with breast conservation therapy (BCT). Methods and Materials: The records of 1,058 Stage I or II breast cancer patients treated with BCT (surgical excision plus radiotherapy) at Duke University Medical Center, Durham, North Carolina, from 1985-2005 were retrospectively reviewed. Conventional receptor analyses were used as surrogate markers for molecular subtype classification (luminal A, luminal B, Her2 positive, and basal like). Actuarial estimates of overall survival (OS), cause-specific survival (CSS), failure-free survival, and locoregional control (LRC) were computed by use of Kaplan-Meier plots. We analyzed prognostic variables for significance using Cox proportional hazards univariate and multivariate analysis. The study was approved by the Duke University Medical Center Institutional Review Board. Results: The median age of the patients was 56 years (range, 18-89 years). Of the patients, 80% had T1 disease and 66% N0 disease pathologically. With a median follow-up of 9.8 years, an in-breast recurrence developed in 53 patients and 10 patients had nodal failure. For all patients, the 10-year CSS rate was 94%; LRC rate, 94%; and failure-free survival rate, 88%. Luminal A patients had a CSS rate of 95% and LRC rate of 99%. Basal-type patients appeared to do worse, with regard to both CSS rate (74%) and LRC rate (76%), but the numbers were small and the difference was not statistically significant. LRC rates of patients with negative margins (widely negative, close, and extent of margin not known) were virtually identical (93%, 96%, and 94%, respectively). Those with positive margins appeared to fare slightly worse based on LRC rate (88%), but again, the numbers were small and the difference was not statistically significant. Conclusions: BCT remains the treatment of choice for early-stage breast cancer

  7. Advances in Molecular Serotyping and Subtyping of Escherichia coli

    Directory of Open Access Journals (Sweden)

    Pina M. Fratamico

    2016-05-01

    Full Text Available E. coli plays an important role as a member of the gut microbiota; however, pathogenic strains also exist, including various diarrheagenic E. coli pathotypes and extraintestinal pathogenic E. coli that cause illness outside of the GI-tract. E. coli have traditionally been serotyped using antisera against the ca. 186 O-antigens and 53 H-flagellar antigens. Phenotypic methods, including bacteriophage typing and O- and H- serotyping for differentiating and characterizing E. coli have been used for many years; however, these methods are generally time consuming and not always accurate. Advances in next generation sequencing technologies have made it possible to develop genetic-based subtyping and molecular serotyping methods for E. coli, which are more discriminatory compared to phenotypic typing methods. Furthermore, whole genome sequencing (WGS of E. coli is replacing established subtyping methods such as pulsed-field gel electrophoresis (PFGE, providing a major advancement in the ability to investigate food-borne disease outbreaks and for trace-back to sources. A variety of sequence analysis tools and bioinformatic pipelines are being developed to analyze the vast amount of data generated by WGS and to obtain specific information such as O- and H-group determination and the presence of virulence genes and other genetic markers.

  8. Genomic analyses identify molecular subtypes of pancreatic cancer.

    Science.gov (United States)

    Bailey, Peter; Chang, David K; Nones, Katia; Johns, Amber L; Patch, Ann-Marie; Gingras, Marie-Claude; Miller, David K; Christ, Angelika N; Bruxner, Tim J C; Quinn, Michael C; Nourse, Craig; Murtaugh, L Charles; Harliwong, Ivon; Idrisoglu, Senel; Manning, Suzanne; Nourbakhsh, Ehsan; Wani, Shivangi; Fink, Lynn; Holmes, Oliver; Chin, Venessa; Anderson, Matthew J; Kazakoff, Stephen; Leonard, Conrad; Newell, Felicity; Waddell, Nick; Wood, Scott; Xu, Qinying; Wilson, Peter J; Cloonan, Nicole; Kassahn, Karin S; Taylor, Darrin; Quek, Kelly; Robertson, Alan; Pantano, Lorena; Mincarelli, Laura; Sanchez, Luis N; Evers, Lisa; Wu, Jianmin; Pinese, Mark; Cowley, Mark J; Jones, Marc D; Colvin, Emily K; Nagrial, Adnan M; Humphrey, Emily S; Chantrill, Lorraine A; Mawson, Amanda; Humphris, Jeremy; Chou, Angela; Pajic, Marina; Scarlett, Christopher J; Pinho, Andreia V; Giry-Laterriere, Marc; Rooman, Ilse; Samra, Jaswinder S; Kench, James G; Lovell, Jessica A; Merrett, Neil D; Toon, Christopher W; Epari, Krishna; Nguyen, Nam Q; Barbour, Andrew; Zeps, Nikolajs; Moran-Jones, Kim; Jamieson, Nigel B; Graham, Janet S; Duthie, Fraser; Oien, Karin; Hair, Jane; Grützmann, Robert; Maitra, Anirban; Iacobuzio-Donahue, Christine A; Wolfgang, Christopher L; Morgan, Richard A; Lawlor, Rita T; Corbo, Vincenzo; Bassi, Claudio; Rusev, Borislav; Capelli, Paola; Salvia, Roberto; Tortora, Giampaolo; Mukhopadhyay, Debabrata; Petersen, Gloria M; Munzy, Donna M; Fisher, William E; Karim, Saadia A; Eshleman, James R; Hruban, Ralph H; Pilarsky, Christian; Morton, Jennifer P; Sansom, Owen J; Scarpa, Aldo; Musgrove, Elizabeth A; Bailey, Ulla-Maja Hagbo; Hofmann, Oliver; Sutherland, Robert L; Wheeler, David A; Gill, Anthony J; Gibbs, Richard A; Pearson, John V; Waddell, Nicola; Biankin, Andrew V; Grimmond, Sean M

    2016-03-01

    Integrated genomic analysis of 456 pancreatic ductal adenocarcinomas identified 32 recurrently mutated genes that aggregate into 10 pathways: KRAS, TGF-β, WNT, NOTCH, ROBO/SLIT signalling, G1/S transition, SWI-SNF, chromatin modification, DNA repair and RNA processing. Expression analysis defined 4 subtypes: (1) squamous; (2) pancreatic progenitor; (3) immunogenic; and (4) aberrantly differentiated endocrine exocrine (ADEX) that correlate with histopathological characteristics. Squamous tumours are enriched for TP53 and KDM6A mutations, upregulation of the TP63∆N transcriptional network, hypermethylation of pancreatic endodermal cell-fate determining genes and have a poor prognosis. Pancreatic progenitor tumours preferentially express genes involved in early pancreatic development (FOXA2/3, PDX1 and MNX1). ADEX tumours displayed upregulation of genes that regulate networks involved in KRAS activation, exocrine (NR5A2 and RBPJL), and endocrine differentiation (NEUROD1 and NKX2-2). Immunogenic tumours contained upregulated immune networks including pathways involved in acquired immune suppression. These data infer differences in the molecular evolution of pancreatic cancer subtypes and identify opportunities for therapeutic development.

  9. Correlation of microarray-based breast cancer molecular subtypes and clinical outcomes: implications for treatment optimization

    International Nuclear Information System (INIS)

    Optimizing treatment through microarray-based molecular subtyping is a promising method to address the problem of heterogeneity in breast cancer; however, current application is restricted to prediction of distant recurrence risk. This study investigated whether breast cancer molecular subtyping according to its global intrinsic biology could be used for treatment customization. Gene expression profiling was conducted on fresh frozen breast cancer tissue collected from 327 patients in conjunction with thoroughly documented clinical data. A method of molecular subtyping based on 783 probe-sets was established and validated. Statistical analysis was performed to correlate molecular subtypes with survival outcome and adjuvant chemotherapy regimens. Heterogeneity of molecular subtypes within groups sharing the same distant recurrence risk predicted by genes of the Oncotype and MammaPrint predictors was studied. We identified six molecular subtypes of breast cancer demonstrating distinctive molecular and clinical characteristics. These six subtypes showed similarities and significant differences from the Perou-Sørlie intrinsic types. Subtype I breast cancer was in concordance with chemosensitive basal-like intrinsic type. Adjuvant chemotherapy of lower intensity with CMF yielded survival outcome similar to those of CAF in this subtype. Subtype IV breast cancer was positive for ER with a full-range expression of HER2, responding poorly to CMF; however, this subtype showed excellent survival when treated with CAF. Reduced expression of a gene associated with methotrexate sensitivity in subtype IV was the likely reason for poor response to methotrexate. All subtype V breast cancer was positive for ER and had excellent long-term survival with hormonal therapy alone following surgery and/or radiation therapy. Adjuvant chemotherapy did not provide any survival benefit in early stages of subtype V patients. Subtype V was consistent with a unique subset of luminal A intrinsic

  10. Discovery of new molecular subtypes in oesophageal adenocarcinoma.

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    Daniela Berg

    Full Text Available A large number of patients suffering from oesophageal adenocarcinomas do not respond to conventional chemotherapy; therefore, it is necessary to identify new predictive biomarkers and patient signatures to improve patient outcomes and therapy selections. We analysed 87 formalin-fixed and paraffin-embedded (FFPE oesophageal adenocarcinoma tissue samples with a reverse phase protein array (RPPA to examine the expression of 17 cancer-related signalling molecules. Protein expression levels were analysed by unsupervised hierarchical clustering and correlated with clinicopathological parameters and overall patient survival. Proteomic analyses revealed a new, very promising molecular subtype of oesophageal adenocarcinoma patients characterised by low levels of the HSP27 family proteins and high expression of those of the HER family with positive lymph nodes, distant metastases and short overall survival. After confirmation in other independent studies, our results could be the foundation for the development of a Her2-targeted treatment option for this new patient subgroup of oesophageal adenocarcinoma.

  11. Discovery of new molecular subtypes in oesophageal adenocarcinoma.

    Science.gov (United States)

    Berg, Daniela; Wolff, Claudia; Langer, Rupert; Schuster, Tibor; Feith, Marcus; Slotta-Huspenina, Julia; Malinowsky, Katharina; Becker, Karl-Friedrich

    2011-01-01

    A large number of patients suffering from oesophageal adenocarcinomas do not respond to conventional chemotherapy; therefore, it is necessary to identify new predictive biomarkers and patient signatures to improve patient outcomes and therapy selections. We analysed 87 formalin-fixed and paraffin-embedded (FFPE) oesophageal adenocarcinoma tissue samples with a reverse phase protein array (RPPA) to examine the expression of 17 cancer-related signalling molecules. Protein expression levels were analysed by unsupervised hierarchical clustering and correlated with clinicopathological parameters and overall patient survival. Proteomic analyses revealed a new, very promising molecular subtype of oesophageal adenocarcinoma patients characterised by low levels of the HSP27 family proteins and high expression of those of the HER family with positive lymph nodes, distant metastases and short overall survival. After confirmation in other independent studies, our results could be the foundation for the development of a Her2-targeted treatment option for this new patient subgroup of oesophageal adenocarcinoma.

  12. Apoptotic machinery diversity in Multiple Myeloma molecular subtypes.

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    Patricia eGomez-Bougie

    2013-12-01

    Full Text Available Multiple myeloma (MM is a plasma cell malignancy that is heterogeneous in its clinical presentation and prognosis. Monoclonal gammopathy of undetermined significance (MGUS consistently preceded development of MM. The presence of primary IgH translocations and the universal over-expression of cyclin D genes led to a molecular classification of MM patients into different disease subtypes. Since Bcl-2 family proteins determine cell fate, we analyzed a publicly available Affymetrix gene expression of 44 MGUS and 414 newly diagnosed MM patients to investigate (1 the global change of Bcl-2 family members in MM versus MGUS (2 whether the four major subtypes defined as hyperdiploid, CCND1, MAF and MMSET, display specific apoptotic machineries.We showed that among the main anti-apoptotic members (Bcl-2, Bcl-xL and Mcl-1, Mcl-1 up-regulation discriminated MM from MGUS, in agreement with the prominent role of Mcl-1 in plasma cell differentiation. Surprisingly, the expression of multi-domain pro-apoptotic Bak and Bax were increased during the progression of MGUS to MM. The combined profile of Bcl-2, Bcl-xL and Mcl-1 was sufficient to distinguish MM molecular groups. While specific pro-apoptotic members expression was observed for each MM subtypes, CCDN1 subgroup, was identified as a particular entity characterized by a low expression of both BH3-only (Puma, Bik and Bad and multi-domain pro-apoptotic members (Bax and Bak. Our analysis supports the notion that MM heterogeneity is extended to the differential expression of the Bcl-2 family content in each MM subgroup. The influence of Bcl-2 family profile in the survival of the different patient groups will be further discussed to establish the potential consequences for therapeutic interventions. Finally, the use of distinct pro-survival members in the different steps of immune responses to antigen rise also the question of whether the different Bcl-2 anti-apoptotic profile could reflect a different origin of

  13. Distinct molecular features of different macroscopic subtypes of colorectal neoplasms.

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    Kenichi Konda

    Full Text Available BACKGROUND: Colorectal adenoma develops into cancer with the accumulation of genetic and epigenetic changes. We studied the underlying molecular and clinicopathological features to better understand the heterogeneity of colorectal neoplasms (CRNs. METHODS: We evaluated both genetic (mutations of KRAS, BRAF, TP53, and PIK3CA, and microsatellite instability [MSI] and epigenetic (methylation status of nine genes or sequences, including the CpG island methylator phenotype [CIMP] markers alterations in 158 CRNs including 56 polypoid neoplasms (PNs, 25 granular type laterally spreading tumors (LST-Gs, 48 non-granular type LSTs (LST-NGs, 19 depressed neoplasms (DNs and 10 small flat-elevated neoplasms (S-FNs on the basis of macroscopic appearance. RESULTS: S-FNs showed few molecular changes except SFRP1 methylation. Significant differences in the frequency of KRAS mutations were observed among subtypes (68% for LST-Gs, 36% for PNs, 16% for DNs and 6% for LST-NGs (P<0.001. By contrast, the frequency of TP53 mutation was higher in DNs than PNs or LST-Gs (32% vs. 5% or 0%, respectively (P<0.007. We also observed significant differences in the frequency of CIMP between LST-Gs and LST-NGs or PNs (32% vs. 6% or 5%, respectively (P<0.005. Moreover, the methylation level of LINE-1 was significantly lower in DNs or LST-Gs than in PNs (58.3% or 60.5% vs. 63.2%, P<0.05. PIK3CA mutations were detected only in LSTs. Finally, multivariate analyses showed that macroscopic morphologies were significantly associated with an increased risk of molecular changes (PN or LST-G for KRAS mutation, odds ratio [OR] 9.11; LST-NG or DN for TP53 mutation, OR 5.30; LST-G for PIK3CA mutation, OR 26.53; LST-G or DN for LINE-1 hypomethylation, OR 3.41. CONCLUSION: We demonstrated that CRNs could be classified into five macroscopic subtypes according to clinicopathological and molecular differences, suggesting that different mechanisms are involved in the pathogenesis of colorectal

  14. Molecular Mechanisms and Genome-Wide Aspects of PPAR Subtype Specific Transactivation

    DEFF Research Database (Denmark)

    Bugge, Anne Skovsø; Mandrup, Susanne

    2010-01-01

    The peroxisome proliferator-activated receptors (PPARs) are central regulators of fat metabolism, energy homeostasis, proliferation, and inflammation. The three PPAR subtypes, PPARα, β/δ, and γ activate overlapping but also very different target gene programs. This review summarizes the insights...... into PPAR subtype-specific transactivation provided by genome-wide studies and discusses the recent advances in the understanding of the molecular mechanisms underlying PPAR subtype specificity with special focus on the regulatory role of AF-1....

  15. Cancer Hallmarks, Biomarkers and Breast Cancer Molecular Subtypes.

    Science.gov (United States)

    Dai, Xiaofeng; Xiang, Liangjian; Li, Ting; Bai, Zhonghu

    2016-01-01

    Breast cancer is a complex disease encompassing multiple tumor entities, each characterized by distinct morphology, behavior and clinical implications. Besides estrogen receptor, progesterone receptor and human epidermal growth factor receptor 2, novel biomarkers have shown their prognostic and predictive values, complicating our understanding towards to the heterogeneity of such cancers. Ten cancer hallmarks have been proposed by Weinberg to characterize cancer and its carcinogenesis. By reviewing biomarkers and breast cancer molecular subtypes, we propose that the divergent outcome observed from patients stratified by hormone status are driven by different cancer hallmarks. 'Sustaining proliferative signaling' further differentiates cancers with positive hormone receptors. 'Activating invasion and metastasis' and 'evading immune destruction' drive the differentiation of triple negative breast cancers. 'Resisting cell death', 'genome instability and mutation' and 'deregulating cellular energetics' refine breast cancer classification with their predictive values. 'Evading growth suppressors', 'enabling replicative immortality', 'inducing angiogenesis' and 'tumor-promoting inflammation' have not been involved in breast cancer classification which need more focus in the future biomarker-related research. This review novels in its global view on breast cancer heterogeneity, which clarifies many confusions in this field and contributes to precision medicine. PMID:27390604

  16. Modern Molecular Genetic Technologies in the Supervision over HIV-1 Subtypes Circulation

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    N.N. Zaitseva

    2016-03-01

    Full Text Available The aim of the investigation was to assess the capabilities of modern technologies in the monitoring of genetic HIV-1 subtypes circulating within some administrative territories (by the example of Privolzhsky Federal District (PFD during the period of 2008–2014. Materials and Methods. We carried out molecular genetic analysis of 647 blood plasma samples of HIV-1 infected patients from 13 regions of PFD (Russia. Genotyping was carried out using a test kit ViroSeqТМ HIV-1 and Genotyping System Software v.2.8 (Celera Diagnostic, USA. Subtyping was performed online using COMET HIV-1/2 and REGA HIV-1 Subtyping Tool, and Phylogenic analysis including reference nucleotide sequences from GenBank of European countries, America, Australia, CIS and Russian regions, was carried out using MEGA 5.2, Maximum Likelihood analysis and Kimura (bootstrap level 1000. Results. The study of HIV-1 subtypes in PFD revealed the tendency for subtype A dominating, both in the period of 2008–2010 (91.3%, and in 2011–2014 (95.6%. Subtype B appeared to be the second most frequent HIV-1 subtype (8.7 and 2%, respectively. We found the increase of subtype diversity of genetic HIV-1 variants in the samples dated 2011–2014, mainly, due to recombinant variants (AB, AG, CRF06_cpx, CRF01_AE and subtype C strain. There was revealed phylogenic affinity and proved molecular epidemiological relationships between nucleotide sequences of viruses isolated in HIV positive patients in PFD, and the sequences taken as reference from international base GenBank. Conclusion. Modern molecular genetic techniques used in epidemiological surveillance over HIV infection, and when studying subtype structure of HIV, can serve as the prime tools to monitor a current situation, as well as for epidemic prognosis. The methods are able to assess, study the subtypes in order to make decisions for developing preventive and anti-epidemic measures to stabilize HIV infection epidemic.

  17. Pattern of distant recurrence according to the molecular subtypes in Korean women with breast cancer

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    Park Hyung Seok

    2012-01-01

    Full Text Available Abstract Background Distant recurrence is one of the most important risk factors in overall survival, and distant recurrence is related to a complex biologic interaction of seed and soil factors. The aim of the study was to investigate the association between the molecular subtypes and patterns of distant recurrence in patients with breast cancer. Methods In an investigation of 313 women with breast cancer who underwent surgery from 1994 and 2000, the expressions of estrogen and progestrone receptor (ER/PR, and human epithelial receptor-2 (HER2 were evaluated. The subtypes were defined as luminal-A, luminal-HER2, HER2-enriched, and triple negative breast cancer (TNBC according to ER, PR, and HER2 status. Results Bone was the most common site of distant recurrence. The incidence of first distant recurrence site was significantly different among the subtypes. Brain metastasis was more frequent in the luminal-HER2 and TNBC subtypes. In subgroup analysis, overall survival in patients with distant recurrence after 24 months after surgery was significantly different among the subtypes. Conclusions Organ-specific metastasis may depend on the molecular subtype of breast cancer. Tailored strategies against distant metastasis concerning the molecular subtypes in breast cancer may be considered.

  18. Molecular subtype analysis determines the association of advanced breast cancer in Egypt with favorable biology

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    DuQuette Rachelle A

    2011-09-01

    Full Text Available Abstract Background Prognostic markers and molecular breast cancer subtypes reflect underlying biological tumor behavior and are important for patient management. Compared to Western countries, women in North Africa are less likely to be prognosticated and treated based on well-characterized markers such as the estrogen receptor (ER, progesterone receptor (PR and Her2. We conducted this study to determine the prevalence of breast cancer molecular subtypes in the North African country of Egypt as a measure of underlying biological characteristics driving tumor manifestations. Methods To determine molecular subtypes we characterized over 200 tumor specimens obtained from Egypt by performing ER, PR, Her2, CK5/6, EGFR and Ki67 immunohistochemistry. Results Our study demonstrated that the Luminal A subtype, associated with favorable prognosis, was found in nearly 45% of cases examined. However, the basal-like subtype, associated with poor prognosis, was found in 11% of cases. These findings are in sharp contrast to other parts of Africa in which the basal-like subtype is over-represented. Conclusions Egyptians appear to have favorable underlying biology, albeit having advanced disease at diagnosis. These data suggest that Egyptians would largely profit from early detection of their disease. Intervention at the public health level, including education on the benefits of early detection is necessary and would likely have tremendous impact on breast cancer outcome in Egypt.

  19. Efficient molecular subtype classification of high-grade serous ovarian cancer.

    Science.gov (United States)

    Leong, Huei San; Galletta, Laura; Etemadmoghadam, Dariush; George, Joshy; Köbel, Martin; Ramus, Susan J; Bowtell, David

    2015-07-01

    High-grade serous carcinomas (HGSCs) account for approximately 70% of all epithelial ovarian cancers diagnosed. Using microarray gene expression profiling, we previously identified four molecular subtypes of HGSC: C1 (mesenchymal), C2 (immunoreactive), C4 (differentiated), and C5 (proliferative), which correlate with patient survival and have distinct biological features. Here, we describe molecular classification of HGSC based on a limited number of genes to allow cost-effective and high-throughput subtype analysis. We determined a minimal signature for accurate classification, including 39 differentially expressed and nine control genes from microarray experiments. Taqman-based (low-density arrays and Fluidigm), fluorescent oligonucleotides (Nanostring), and targeted RNA sequencing (Illumina) assays were then compared for their ability to correctly classify fresh and formalin-fixed, paraffin-embedded samples. All platforms achieved > 90% classification accuracy with RNA from fresh frozen samples. The Illumina and Nanostring assays were superior with fixed material. We found that the C1, C2, and C4 molecular subtypes were largely consistent across multiple surgical deposits from individual chemo-naive patients. In contrast, we observed substantial subtype heterogeneity in patients whose primary ovarian sample was classified as C5. The development of an efficient molecular classifier of HGSC should enable further biological characterization of molecular subtypes and the development of targeted clinical trials. PMID:25810134

  20. Prediction consistency and clinical presentations of breast cancer molecular subtypes for Han Chinese population

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    Huang Chi-Cheng

    2012-09-01

    Full Text Available Abstract Background Breast cancer is a heterogeneous disease in terms of transcriptional aberrations; moreover, microarray gene expression profiles had defined 5 molecular subtypes based on certain intrinsic genes. This study aimed to evaluate the prediction consistency of breast cancer molecular subtypes from 3 distinct intrinsic gene sets (Sørlie 500, Hu 306 and PAM50 as well as clinical presentations of each molecualr subtype in Han Chinese population. Methods In all, 169 breast cancer samples (44 from Taiwan and 125 from China of Han Chinese population were gathered, and the gene expression features corresponding to 3 distinct intrinsic gene sets (Sørlie 500, Hu 306 and PAM50 were retrieved for molecular subtype prediction. Results For Sørlie 500 and Hu 306 intrinsic gene set, mean-centring of genes and distance-weighted discrimination (DWD remarkably reduced the number of unclassified cases. Regarding pairwise agreement, the highest predictive consistency was found between Hu 306 and PAM50. In all, 150 and 126 samples were assigned into identical subtypes by both Hu 306 and PAM50 genes, under mean-centring and DWD. Luminal B tended to show a higher nuclear grade and have more HER2 over-expression status than luminal A did. No basal-like breast tumours were ER positive, and most HER2-enriched breast tumours showed HER2 over-expression, whereas, only two-thirds of ER negativity/HER2 over-expression tumros were predicted as HER2-enriched molecular subtype. For 44 Taiwanese breast cancers with survival data, a better prognosis of luminal A than luminal B subtype in ER-postive breast cancers and a better prognosis of basal-like than HER2-enriched subtype in ER-negative breast cancers was observed. Conclusions We suggest that the intrinsic signature Hu 306 or PAM50 be used for breast cancers in the Han Chinese population during molecular subtyping. For the prognostic value and decision making based on intrinsic subtypes, further prospective

  1. Molecular dating of HIV-1 subtype C from Bangladesh.

    Science.gov (United States)

    Bontell, Irene; Sarker, Md Safiullah; Rahman, Mustafizur; Afrad, Mokibul Hassan; Sönnerborg, Anders; Azim, Tasnim

    2013-01-01

    Bangladesh has an overall low HIV prevalence of Bangladesh and related strains from other countries, and thereby clarify when and from where subtype C was introduced in the country and how it subsequently spread within Bangladesh. The phylogenetic analysis included 118 Bangladeshi gag sequences and 128 sequences from other countries and was performed using the BEAST package. Our analysis revealed that the vast majority of Bangladeshi sequences (97/118, 82%) fall into a large regional cluster of samples from Bangladesh, India, China and Myanmar, which dates back to the early 1960's. Following its establishment in the region, this strain has entered Bangladesh multiple times from around 1975 and onwards, but extensive in-country transmission could only be detected among drug users and not through sexual transmission. In addition, there have been multiple (at least ten) introductions of subtype C to Bangladesh from outside this region, but no extensive spread could be detected for any of these. Since many HIV-infections remain undetected while asymptomatic, the true extent of the transmission of each strain remains unknown, especially among hard to reach groups such as clients of sex workers and returning migrants with families.

  2. Recurrent Glioblastomas Reveal Molecular Subtypes Associated with Mechanistic Implications of Drug-Resistance.

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    So Mee Kwon

    Full Text Available Previously, transcriptomic profiling studies have shown distinct molecular subtypes of glioblastomas. It has also been suggested that the recurrence of glioblastomas could be achieved by transcriptomic reprograming of tumors, however, their characteristics are not yet fully understood. Here, to gain the mechanistic insights on the molecular phenotypes of recurrent glioblastomas, gene expression profiling was performed on the 43 cases of glioblastomas including 15 paired primary and recurrent cases. Unsupervised clustering analyses revealed two subtypes of G1 and G2, which were characterized by proliferation and neuron-like gene expression traits, respectively. While the primary tumors were classified as G1 subtype, the recurrent glioblastomas showed two distinct expression types. Compared to paired primary tumors, the recurrent tumors in G1 subtype did not show expression alteration. By contrast, the recurrent tumors in G2 subtype showed expression changes from proliferation type to neuron-like one. We also observed the expression of stemness-related genes in G1 recurrent tumors and the altered expression of DNA-repair genes (i.e., AURK, HOX, MGMT, and MSH6 in the G2 recurrent tumors, which might be responsible for the acquisition of drug resistance mechanism during tumor recurrence in a subtype-specific manner. We suggest that recurrent glioblastomas may choose two different strategies for transcriptomic reprograming to escape the chemotherapeutic treatment during tumor recurrence. Our results might be helpful to determine personalized therapeutic strategy against heterogeneous glioma recurrence.

  3. Gene expression classification of colon cancer into molecular subtypes: characterization, validation, and prognostic value.

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    Laetitia Marisa

    Full Text Available BACKGROUND: Colon cancer (CC pathological staging fails to accurately predict recurrence, and to date, no gene expression signature has proven reliable for prognosis stratification in clinical practice, perhaps because CC is a heterogeneous disease. The aim of this study was to establish a comprehensive molecular classification of CC based on mRNA expression profile analyses. METHODS AND FINDINGS: Fresh-frozen primary tumor samples from a large multicenter cohort of 750 patients with stage I to IV CC who underwent surgery between 1987 and 2007 in seven centers were characterized for common DNA alterations, including BRAF, KRAS, and TP53 mutations, CpG island methylator phenotype, mismatch repair status, and chromosomal instability status, and were screened with whole genome and transcriptome arrays. 566 samples fulfilled RNA quality requirements. Unsupervised consensus hierarchical clustering applied to gene expression data from a discovery subset of 443 CC samples identified six molecular subtypes. These subtypes were associated with distinct clinicopathological characteristics, molecular alterations, specific enrichments of supervised gene expression signatures (stem cell phenotype-like, normal-like, serrated CC phenotype-like, and deregulated signaling pathways. Based on their main biological characteristics, we distinguished a deficient mismatch repair subtype, a KRAS mutant subtype, a cancer stem cell subtype, and three chromosomal instability subtypes, including one associated with down-regulated immune pathways, one with up-regulation of the Wnt pathway, and one displaying a normal-like gene expression profile. The classification was validated in the remaining 123 samples plus an independent set of 1,058 CC samples, including eight public datasets. Furthermore, prognosis was analyzed in the subset of stage II-III CC samples. The subtypes C4 and C6, but not the subtypes C1, C2, C3, and C5, were independently associated with shorter relapse

  4. Molecular epidemiology of HIV-1 subtypes in India: origin and evolutionary history of the predominant subtype C.

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    Ujjwal Neogi

    Full Text Available BACKGROUND: India has the third largest HIV-1 epidemic with 2.4 million infected individuals. Molecular epidemiological analysis has identified the predominance of HIV-1 subtype C (HIV-1C. However, the previous reports have been limited by sample size, and uneven geographical distribution. The introduction of HIV-1C in India remains uncertain due to this lack of structured studies. To fill the gap, we characterised the distribution pattern of HIV-1 subtypes in India based on data collection from nationwide clinical cohorts between 2007 and 2011. We also reconstructed the time to the most recent common ancestor (tMRCA of the predominant HIV-1C strains. METHODOLOGY/PRINCIPAL FINDINGS: Blood samples were collected from 168 HIV-1 seropositive subjects from 7 different states. HIV-1 subtypes were determined using two or three genes, gag, pol, and env using several methods. Bayesian coalescent-based approach was used to reconstruct the time of introduction and population growth patterns of the Indian HIV-1C. For the first time, a high prevalence (10% of unique recombinant forms (BC and A1C was observed when two or three genes were used instead of one gene (p<0.01; p = 0.02, respectively. The tMRCA of Indian HIV-1C was estimated using the three viral genes, ranged from 1967 (gag to 1974 (env. Pol-gene analysis was considered to provide the most reliable estimate [1971, (95% CI: 1965-1976]. The population growth pattern revealed an initial slow growth phase in the mid-1970s, an exponential phase through the 1980s, and a stationary phase since the early 1990s. CONCLUSIONS/SIGNIFICANCE: The Indian HIV-1C epidemic originated around 40 years ago from a single or few genetically related African lineages, and since then largely evolved independently. The effective population size in the country has been broadly stable since the 1990s. The evolving viral epidemic, as indicated by the increase of recombinant strains, warrants a need for continued molecular

  5. High-resolution molecular epidemiology and evolutionary history of HIV-1 subtypes in Albania.

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    Marco Salemi

    Full Text Available BACKGROUND: HIV-1 epidemic in Western Europe is largely due to subtype B. Little is known about the HIV-1 in Eastern Europe, but a few studies have shown that non-B subtypes are quite common. In Albania, where a recent study estimated a ten-fold increase of AIDS incidence during the last six years, subtype A and B account for 90% of the know infections. METHODOLOGY/PRINCIPAL FINDINGS: We investigated the demographic history of HIV-1 subtype A and B in Albania by using a statistical framework based on coalescent theory and phylogeography. High-resolution phylogenetic and molecular clock analysis showed a limited introduction to the Balkan country of subtype A during the late 1980s followed by an epidemic outburst in the early 1990 s. In contrast, subtype B was apparently introduced multiple times between the mid-1970s and mid-1980s. Both subtypes are growing exponentially, although the HIV-1A epidemic displays a faster growth rate, and a significantly higher basic reproductive number R(0. HIV-1A gene flow occurs primarily from the capital Tirane, in the center of the country, to the periphery, while HIV-1B flow is characterized by a balanced exchange between center and periphery. Finally, we calculated that the actual number of infections in Albania is at least two orders of magnitude higher than previously thought. CONCLUSIONS/SIGNIFICANCE: Our analysis demonstrates the power of recently developed computational tools to investigate molecular epidemiology of pathogens, and emphasize the complex factors involved in the establishment of HIV-1 epidemics. We suggest that a significant correlation exists between HIV-1 exponential spread and the socio-political changes occurred during the Balkan wars. The fast growth of a relatively new non-B epidemic in the Balkans may have significant consequences for the evolution of HIV-1 epidemiology in neighboring countries in Eastern and Western Europe.

  6. TCGA divides gastric cancer into four molecular subtypes:implications for individualized therapeutics

    Institute of Scientific and Technical Information of China (English)

    Wei Zhang

    2014-01-01

    Gastric cancer is a leading cause of cancer deaths in the world. The treatment of gastric cancer is chalenging because of its highly heterogeneous etiology and clinical characteristics. Recent genomic and molecular characterization of gastric cancer, especialy the findings reported by the Cancer Genome Atlas (TCGA), have shed light on the heterogeneity and potential targeted therapeutics for four different subtypes of gastric cancer.

  7. Association between {sup 18}F-FDG uptake and molecular subtype of breast cancer

    Energy Technology Data Exchange (ETDEWEB)

    Kitajima, Kazuhiro; Fukushima, Kazuhito; Igarashi, Yoko; Katsuura, Takayuki; Maruyama, Kaoru [Hyogo College of Medicine, Department of Nuclear Medicine and PET center, Nishinomiya, Hyogo (Japan); Miyoshi, Yasuo; Nishimukai, Arisa [Hyogo College of Medicine, Department of Breast and Endocrine Surgery, Nishinomiya, Hyogo (Japan); Hirota, Seiichi [Hyogo College of Medicine, Department of Surgical Pathology, Nishinomiya, Hyogo (Japan); Hirota, Shozo [Hyogo College of Medicine, Department of Radiology, Nishinomiya, Hyogo (Japan)

    2015-08-15

    To determine whether {sup 18}F-FDG uptake in breast cancer correlates with immunohistochemically defined subtype and is able to predict molecular subtypes. This retrospective study involved 306 patients with 308 mass-type invasive breast cancers (mean size 2.65 cm, range 1.0-15.0 cm) who underwent {sup 18}F-FDG PET/CT before therapy. The correlations between primary tumour {sup 18}F-FDG uptake on PET/CT, expressed as SUVmax, and clinicopathological findings and molecular subtype, i.e. luminal A, luminal B (HER2-negative), luminal B (HER2-positive), HER2-positive and triple-negative, were analysed. The predictors of these subtypes were investigated. The mean SUVmax of the 308 tumours was 5.33 ± 3.63 (range 1.15-19.01). Among the subtypes of the 308 tumours, 87 (28.2 %) were luminal A, 111 (36.0 %) were luminal B (HER2-negative), 31 (10.1 %) were luminal B (HER2-positive), 26 (8.4 %) were HER2-positive and 53 (17.2 %) were triple-negative, and the corresponding mean SUVmax were 3.41 ± 2.07 (range 1.18-14.30), 5.17 ± 3.52 (range 1.35-19.01), 6.57 ± 3.84 (range 1.42-15.58), 7.55 ± 3.63 (range 2.30-13.60) and 6.97 ± 4.17 (range 1.15-16.06), respectively. A cut-off value of 3.60 yielded 70.1 % sensitivity and 66.1 % specificity with an area under the receiver operating characteristics curve (AUC) of 0.734 for predicting that a tumour was of the luminal A subtype. A cut-off value of 6.75 yielded 65.4 % sensitivity and 75.2 % specificity with an AUC of 0.704 for predicting a HER2-positive subtype. SUVmax, a metabolic semiquantitative parameter, shows a significant correlation with the molecular subtype of breast cancer, and is useful for predicting the luminal A or HER2-positive subtype. (orig.)

  8. Characterization of molecular subtypes of Korean breast cancer: An ethnically and clinically distinct population

    OpenAIRE

    Han, Wonshik; Nicolau, Monica; Noh, Dong-Young; Jeffrey, Stefanie S.

    2010-01-01

    We aimed to investigate the molecular characteristics of Korean breast cancer. A cDNA microarray study (>42k clones) was performed on 69 breast cancers and three normal breast tissues. The subjects had a high percentage of HER-2 expression, hormone receptor negativity, and young onset. Molecular subtypes according to gene expression profiles were determined and their correlations to the clinicopathologic characteristics and patients outcome were analyzed. The tumors were subdivided into lumin...

  9. The molecular subtype classification is a determinant of sentinel node positivity in early breast carcinoma.

    Directory of Open Access Journals (Sweden)

    Fabien Reyal

    Full Text Available INTRODUCTION: Several authors have underscored a strong relation between the molecular subtypes and the axillary status of breast cancer patients. The aim of our work was to decipher the interaction between this classification and the probability of a positive sentinel node biopsy. MATERIALS AND METHODS: Our dataset consisted of a total number of 2654 early-stage breast cancer patients. Patients treated at first by conservative breast surgery plus sentinel node biopsies were selected. A multivariate logistic regression model was trained and validated. Interaction covariate between ER and HER2 markers was a forced input of this model. The performance of the multivariate model in the training and the two validation sets was analyzed in terms of discrimination and calibration. Probability of axillary metastasis was detailed for each molecular subtype. RESULTS: The interaction covariate between ER and HER2 status was a stronger predictor (p = 0.0031 of positive sentinel node biopsy than the ER status by itself (p = 0.016. A multivariate model to determine the probability of sentinel node positivity was defined with the following variables; tumour size, lympho-vascular invasion, molecular subtypes and age at diagnosis. This model showed similar results in terms of discrimination (AUC = 0.72/0.73/0.72 and calibration (HL p = 0.28/0.05/0.11 in the training and validation sets. The interaction between molecular subtypes, tumour size and sentinel nodes status was approximated. DISCUSSION: We showed that biologically-driven analyses are able to build new models with higher performance in terms of breast cancer axillary status prediction. The molecular subtype classification strongly interacts with the axillary and distant metastasis process.

  10. Metastatic apocrine sweat gland adenocarcinoma in a terrier dog

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    Akhtardanesh Baharak

    2012-08-01

    Full Text Available This report describes the clinical and pathological aspects of an apocrine sweat gland carcinoma with distant metastasis in an aged dog. A 7-year-old male terrier dog was referred to small animal hospital of Shahid Bahonar University of Kerman with a 5.5×3.5 centimeter pedunculated mass on its head near left auricular region which had been progressively growing since three months ago. The radiography showed no local and distant metastasis. Surgical excision and histological evaluation was done. Histologically, the mass was composed of epithelial cells arranged in glandular and solid patterns. The morphologic findings suggested either a primary or metastatic apocrine-gland carcinoma. Immunohistochemically, the tumor cells were intensely positive for cytokeratin 7 and 20 and negative for S100 protein. On the basis of histopathological and clinical findings, the tumor was diagnosed as a malignant apocrine gland tumor, arising from apocrine sweat glands of the skin. Local tumor recurrence with anorexia and weight loss was reported by the owner nine month later. Severe submandibular and prescapular lymphadenomegaly was noted in clinical examination. Several large pulmonary nodules were noted in chest radiographs resembling mediastinal lymph node metastasis. Second surgery and chemotherapy was rejected by the owner due to grave prognosis of the patient. The animal was died 45 days later due to respiratory complications. Tumors of apocrine sweat glands are relatively uncommon in dogs whereas apocrine gland adenocarcinoma with distant metastasis is extremely rare.

  11. Metastatic apocrine sweat gland adenocarcinoma in a terrier dog

    Institute of Scientific and Technical Information of China (English)

    Akhtardanesh Baharak; Kheirandish Reza; Dabiri Shahriar; Azari Omid; Vosoogh Daruoosh; Askari Nasrin

    2012-01-01

    This report describes the clinical and pathological aspects of an apocrine sweat gland carcinoma with distant metastasis in an aged dog. A 7-year-old male terrier dog was referred to small animal hospital of Shahid Bahonar University of Kerman with a 5.5×3.5 centimeter pedunculated mass on its head near left auricular region which had been progressively growing since three months ago. The radiography showed no local and distant metastasis. Surgical excision and histological evaluation was done. Histologically, the mass was composed of epithelial cells arranged in glandular and solid patterns. The morphologic findings suggested either a primary or metastatic apocrine-gland carcinoma. Immunohistochemically, the tumor cells were intensely positive for cytokeratin 7 and 20 and negative for S100 protein. On the basis of histopathological and clinical findings, the tumor was diagnosed as a malignant apocrine gland tumor, arising from apocrine sweat glands of the skin. Local tumor recurrence with anorexia and weight loss was reported by the owner nine month later. Severe submandibular and prescapular lymphadenomegaly was noted in clinical examination. Several large pulmonary nodules were noted in chest radiographs resembling mediastinal lymph node metastasis. Second surgery and chemotherapy was rejected by the owner due to grave prognosis of the patient. The animal was died 45 days later due to respiratory complications. Tumors of apocrine sweat glands are relatively uncommon in dogs whereas apocrine gland adenocarcinoma with distant metastasis is extremely rare.

  12. DNA Repair Gene Patterns as Prognostic and Predictive Factors in Molecular Breast Cancer Subtypes

    OpenAIRE

    Santarpia, Libero; Iwamoto, Takayuki; Di Leo, Angelo; Hayashi, Naoki; Bottai, Giulia; Stampfer, Martha; André, Fabrice; Turner, Nicholas C.; Symmans, W Fraser; Hortobágyi, Gabriel N.; Pusztai, Lajos; Bianchini, Giampaolo

    2013-01-01

    DNA repair pathways can enable tumor cells to survive DNA damage induced by chemotherapy and thus provide prognostic and/or predictive value. In this study, the authors sought to assess the differential expression, bimodal distribution, and prognostic and predictive role of DNA repair genes in individual breast cancer molecular subtypes including estrogen receptor-positive/ HER2-negative, estrogen receptor-negative/HER2-negative, and HER2-positive cancers. The predictive value of DNA repair g...

  13. Distinct molecular mechanisms underlying clinically relevant subtypes of breast cancer: gene expression analyses across three different platforms

    Directory of Open Access Journals (Sweden)

    Naume Bjørn

    2006-05-01

    Full Text Available Abstract Background Gene expression profiling has been used to define molecular phenotypes of complex diseases such as breast cancer. The luminal A and basal-like subtypes have been repeatedly identified and validated as the two main subtypes out of a total of five molecular subtypes of breast cancer. These two are associated with distinctly different gene expression patterns and more importantly, a significant difference in clinical outcome. To further validate and more thoroughly characterize these two subtypes at the molecular level in tumors at an early stage, we report a gene expression profiling study using three different DNA microarray platforms. Results Expression data from 20 tumor biopsies of early stage breast carcinomas were generated on three different DNA microarray platforms; Applied Biosystems Human Genome Survey Microarrays, Stanford cDNA Microarrays and Agilent's Whole Human Genome Oligo Microarrays, and the resulting gene expression patterns were analyzed. Both unsupervised and supervised analyses identified the different clinically relevant subtypes of breast tumours, and the results were consistent across all three platforms. Gene classification and biological pathway analyses of the genes differentially expressed between the two main subtypes revealed different molecular mechanisms descriptive of the two expression-based subtypes: Signature genes of the luminal A subtype were over-represented by genes involved in fatty acid metabolism and steroid hormone-mediated signaling pathways, in particular estrogen receptor signaling, while signature genes of the basal-like subtype were over-represented by genes involved in cell proliferation and differentiation, p21-mediated pathway, and G1-S checkpoint of cell cycle-signaling pathways. A minimal set of 54 genes that best discriminated the two subtypes was identified using the combined data sets generated from the three different array platforms. These predictor genes were further

  14. Molecular evolution of the porcine type I interferon family: subtype-specific expression and antiviral activity.

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    Yongming Sang

    Full Text Available Type I interferons (IFNs, key antiviral cytokines, evolve to adapt with ever-changing viral threats during vertebrate speciation. Due to novel pathogenic pressure associated with Suidae speciation and domestication, porcine IFNs evolutionarily engender both molecular and functional diversification, which have not been well addressed in pigs, an important livestock species and animal model for biomedical sciences. Annotation of current swine genome assembly Sscrofa10.2 reveals 57 functional genes and 16 pseudogenes of type I IFNs. Subfamilies of multiple IFNA, IFNW and porcine-specific IFND genes are separated into four clusters with ∼ 60 kb intervals within the IFNB/IFNE bordered region in SSC1, and each cluster contains mingled subtypes of IFNA, IFNW and IFND. Further curation of the 57 functional IFN genes indicates that they include 18 potential artifactual duplicates. We performed phylogenetic construction as well as analyses of gene duplication/conversion and natural selection and showed that porcine type I IFN genes have been undergoing active diversification through both gene duplication and conversion. Extensive analyses of the non-coding sequences proximal to all IFN coding regions identified several genomic repetitive elements significantly associated with different IFN subtypes. Family-wide studies further revealed their molecular diversity with respect to differential expression and restrictive activity on the resurgence of a porcine endogenous retrovirus. Based on predicted 3-D structures of representative animal IFNs and inferred activity, we categorized the general functional propensity underlying the structure-activity relationship. Evidence indicates gene expansion of porcine type I IFNs. Genomic repetitive elements that associated with IFN subtypes may serve as molecular signatures of respective IFN subtypes and genomic mechanisms to mediate IFN gene evolution and expression. In summary, the porcine type I IFN profile has

  15. Epstein-Barr virus-positive gastric cancer: a distinct molecular subtype of the disease?

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    Alexandre Andrade dos Anjos Jácome

    2016-04-01

    Full Text Available Abstract: Approximately 90% of the world population is infected by Epstein-Barr virus (EBV. Usually, it infects B lymphocytes, predisposing them to malignant transformation. Infection of epithelial cells occurs rarely, and it is estimated that about to 10% of gastric cancer patients harbor EBV in their malignant cells. Given that gastric cancer is the third leading cause of cancer-related mortality worldwide, with a global annual incidence of over 950,000 cases, EBV-positive gastric cancer is the largest group of EBV-associated malignancies. Based on gene expression profile studies, gastric cancer was recently categorized into four subtypes; EBV-positive, microsatellite unstable, genomically stable and chromosomal instability. Together with previous studies, this report provided a more detailed molecular characterization of gastric cancer, demonstrating that EBV-positive gastric cancer is a distinct molecular subtype of the disease, with unique genetic and epigenetic abnormalities, reflected in a specific phenotype. The recognition of characteristic molecular alterations in gastric cancer allows the identification of molecular pathways involved in cell proliferation and survival, with the potential to identify therapeutic targets. These findings highlight the enormous heterogeneity of gastric cancer, and the complex interplay between genetic and epigenetic alterations in the disease, and provide a roadmap to implementation of genome-guided personalized therapy in gastric cancer. The present review discusses the initial studies describing EBV-positive gastric cancer as a distinct clinical entity, presents recently described genetic and epigenetic alterations, and considers potential therapeutic insights derived from the recognition of this new molecular subtype of gastric adenocarcinoma.

  16. GliomaPredict: a clinically useful tool for assigning glioma patients to specific molecular subtypes

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    Fine Howard A

    2010-07-01

    Full Text Available Abstract Background Advances in generating genome-wide gene expression data have accelerated the development of molecular-based tumor classification systems. Tools that allow the translation of such molecular classification schemas from research into clinical applications are still missing in the emerging era of personalized medicine. Results We developed GliomaPredict as a computational tool that allows the fast and reliable classification of glioma patients into one of six previously published stratified subtypes based on sets of extensively validated classifiers derived from hundreds of glioma transcriptomic profiles. Our tool utilizes a principle component analysis (PCA-based approach to generate a visual representation of the analyses, quantifies the confidence of the underlying subtype assessment and presents results as a printable PDF file. GliomaPredict tool is implemented as a plugin application for the widely-used GenePattern framework. Conclusions GliomaPredict provides a user-friendly, clinically applicable novel platform for instantly assigning gene expression-based subtype in patients with gliomas thereby aiding in clinical trial design and therapeutic decision-making. Implemented as a user-friendly diagnostic tool, we expect that in time GliomaPredict, and tools like it, will become routinely used in translational/clinical research and in the clinical care of patients with gliomas.

  17. Molecular-based tumour subtypes of canine mammary carcinomas assessed by immunohistochemistry

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    Sarli Giuseppe

    2010-01-01

    Full Text Available Abstract Background Human breast cancer is classified by gene expression profile into subtypes consisting of two hormone (oestrogen and/or progesterone receptor-positive types (luminal-like A and luminal-like B and three hormone receptor-negative types [human epidermal growth factor receptor 2-expressing, basal-like, and unclassified ("normal-like"]. Immunohistochemical surrogate panels are also proposed to potentially identify the molecular-based groups. The present study aimed to apply an immunohistochemical panel (anti-ER, -PR, -ERB-B2, -CK 5/6 and -CK14 in a series of canine malignant mammary tumours to verify the molecular-based classification, its correlation with invasion and grade, and its use as a prognostic aid in veterinary practice. Results Thirty-five tumours with luminal pattern (ER+ and PR+ were subgrouped into 13 A type and 22 B type, if ERB-B2 positive or negative. Most luminal-like A and basal-like tumours were grade 1 carcinomas, while the percentage of luminal B tumours was higher in grades 2 and 3 (Pearson Chi-square P = 0.009. No difference in the percentage of molecular subtypes was found between simple and complex/mixed carcinomas (Pearson Chi-square P = 0.47. No significant results were obtained by survival analysis, even if basal-like tumours had a more favourable prognosis than luminal-like lesions. Conclusion The panel of antibodies identified only three tumour groups (luminal-like A and B, and basal-like in the dog. Even though canine mammary tumours may be a model of human breast cancer, the existence of the same carcinoma molecular subtypes in women awaits confirmation. Canine mammary carcinomas show high molecular heterogeneity, which would benefit from a classification based on molecular differences. Stage and grade showed independent associations with survival in the multivariate regression, while molecular subtype grouping and histological type did not show associations. This suggests that caution should be

  18. Characterization of breast precancerous lesions and myoepithelial hyperplasia in sclerosing adenosis with apocrine metaplasia

    DEFF Research Database (Denmark)

    Celis, J.E.; Gromova, I.; Cabezón, T.;

    2007-01-01

    . First, we identify specific protein biomarkers for benign apocrine metaplasia and thereafter we search for biomarkers that are highly overexpressed by pure invasive apocrine carcinomas. Here we present studies in which we have used antibodies against components of a benign apocrine signature...... the three markers associated with pure invasive apocrine carcinomas. These studies also revealed p53 positive, non-apocrine putative precancerous lesions as well as novel phenotypes for ME and some luminal cells characterized by the expression of cytokeratin 15. © 2007 Federation of European Biochemical...

  19. Molecular Evolution of Antibody Cross-Reactivity for Two Subtypes of Type a Botulinum Neurotoxin

    Energy Technology Data Exchange (ETDEWEB)

    Garcia-Rodriguez, C.; Levy, R.; Arndt, J.W.; Forsyth, C.M.; Razai, A.; Lou, J.; Geren, I.; Stevens, R.C.; Marks, J.D.; /UC, San Francisco /Scripps Res. Inst.

    2007-07-09

    Broadening antibody specificity without compromising affinity should facilitate detection and neutralization of toxin and viral subtypes. We used yeast display and a co-selection strategy to increase cross-reactivity of a single chain (sc) Fv antibody to botulinum neurotoxin type A (BoNT/A). Starting with a scFv that binds the BoNT/A1 subtype with high affinity (136 pM) and the BoNT/A2 subtype with low affinity (109 nM), we increased its affinity for BoNT/A2 1,250-fold, to 87 pM, while maintaining high-affinity binding to BoNT/A1 (115 pM). To find the molecular basis for improved cross-reactivity, we determined the X-ray co-crystal structures of wild-type and cross-reactive antibodies complexed to BoNT/A1 at resolutions up to 2.6 A, and measured the thermodynamic contribution of BoNT/A1 and A2 amino acids to wild-type and cross-reactive antibody binding. The results show how an antibody can be engineered to bind two different antigens despite structural differences in the antigen-antibody interface and may provide a general strategy for tuning antibody specificity and cross-reactivity.

  20. Breast Cancer Genetic and Molecular Subtype Impacts Response to Omega-3 Fatty Acid Ethyl Esters.

    Science.gov (United States)

    Chen, Ching Hui; Fabian, Carol; Hursting, Stephen; deGraffenried, Linda A

    2016-01-01

    Epidemiological studies have correlated frequent omega-3 (n-3) fatty acid consumption with a lower risk for breast cancer; however, recent prospective studies have been less conclusive. Efforts in the preventive setting have focused on the use of n-3 fatty acids, and the pharmaceutical ethyl esters (EE) of these natural compounds, for high-risk patient populations. Limited understanding of specific mechanisms by which these agents function has hampered identification of the cancer subtype(s) that would gain the greatest therapeutic benefit. In this study, we investigated the in vitro effects of n-3 EEs in four distinct breast cancer subtypes and explored how they affect not only breast cancer cell survival but also modulate the nuclear factor kappa-light-chain enhancer of activated B cells (NF-κB) and peroxisome proliferator-activated receptor gamma signaling pathways. Similar to the high variance in response observed in human studies, we found that the effectiveness of n-3 EEs depends on the molecular characteristics of the MCF-7, CAMA-1, MDA-MB-231, and SKBR3 breast cancer cell lines and is closely associated with the suppression of NF-κB. These data strongly suggest that the use of n-3 fatty acids and their pharmaceutical ether esters in the prevention and therapeutic setting should be guided by specific tumor characteristics. PMID:27367296

  1. Breast cancer molecular subtypes and survival in a hospital-based sample in Puerto Rico

    International Nuclear Information System (INIS)

    Information on the impact of hormone receptor status subtypes in breast cancer (BC) prognosis is still limited for Hispanics. We aimed to evaluate the association of BC molecular subtypes and other clinical factors with survival in a hospital-based female population of BC cases in Puerto Rico. We analyzed 663 cases of invasive BC diagnosed between 2002 and 2005. Information on HER-2/neu (HER-2) overexpression, estrogen (ER), and progesterone (PR) receptor status and clinical characteristics were retrieved from hospitals cancer registries and record review. Survival probabilities by covariates of interest were described using the Kaplan–Meier estimators. Cox proportional hazards models were employed to assess factors associated with risk of BC death. Overall, 17.3% of BC cases were triple-negative (TN), 61.8% were Luminal-A, 13.3% were Luminal-B, and 7.5% were HER-2 overexpressed. In the multivariate Cox model, among patients with localized stage, women with TN BC had higher risk of death (adjusted hazard ratio [HR]: 2.57, 95% confidence interval [CI]: 1.29–5.12) as compared to those with Luminal-A status, after adjusting for age at diagnosis. In addition, among women with regional/distant stage at diagnosis, those with TN BC (HR: 5.48, 95% CI: 2.63–11.47) and those HER-2+, including HER-2 overexpressed and Luminal-B, (HR: 2.73, 95% CI:1.30–5.75) had a higher mortality. This is the most comprehensive epidemiological study to date on the impact of hormone receptor expression subtypes in BC survival in Puerto Rico. Consistent to results in other populations, the TN subtype and HER-2+ tumors were associated with decreased survival

  2. Radiogenomic analysis of breast cancer: dynamic contrast enhanced - magnetic resonance imaging based features are associated with molecular subtypes

    Science.gov (United States)

    Wang, Shijian; Fan, Ming; Zhang, Juan; Zheng, Bin; Wang, Xiaojia; Li, Lihua

    2016-03-01

    Breast cancer is one of the most common malignant tumor with upgrading incidence in females. The key to decrease the mortality is early diagnosis and reasonable treatment. Molecular classification could provide better insights into patient-directed therapy and prognosis prediction of breast cancer. It is known that different molecular subtypes have different characteristics in magnetic resonance imaging (MRI) examination. Therefore, we assumed that imaging features can reflect molecular information in breast cancer. In this study, we investigated associations between dynamic contrasts enhanced MRI (DCE-MRI) features and molecular subtypes in breast cancer. Sixty patients with breast cancer were enrolled and the MR images were pre-processed for noise reduction, registration and segmentation. Sixty-five dimensional imaging features including statistical characteristics, morphology, texture and dynamic enhancement in breast lesion and background regions were semiautomatically extracted. The associations between imaging features and molecular subtypes were assessed by using statistical analyses, including univariate logistic regression and multivariate logistic regression. The results of multivariate regression showed that imaging features are significantly associated with molecular subtypes of Luminal A (p=0.00473), HER2-enriched (p=0.00277) and Basal like (p=0.0117), respectively. The results indicated that three molecular subtypes are correlated with DCE-MRI features in breast cancer. Specifically, patients with a higher level of compactness or lower level of skewness in breast lesion are more likely to be Luminal A subtype. Besides, the higher value of the dynamic enhancement at T1 time in normal side reflect higher possibility of HER2-enriched subtype in breast cancer.

  3. Colon cancer molecular subtypes identified by expression profiling and associated to stroma, mucinous type and different clinical behavior

    International Nuclear Information System (INIS)

    Colon cancer patients with the same stage show diverse clinical behavior due to tumor heterogeneity. We aimed to discover distinct classes of tumors based on microarray expression patterns, to analyze whether the molecular classification correlated with the histopathological stages or other clinical parameters and to study differences in the survival. Hierarchical clustering was performed for class discovery in 88 colon tumors (stages I to IV). Pathways analysis and correlations between clinical parameters and our classification were analyzed. Tumor subtypes were validated using an external set of 78 patients. A 167 gene signature associated to the main subtype was generated using the 3-Nearest-Neighbor method. Coincidences with other prognostic predictors were assesed. Hierarchical clustering identified four robust tumor subtypes with biologically and clinically distinct behavior. Stromal components (p < 0.001), nuclear β-catenin (p = 0.021), mucinous histology (p = 0.001), microsatellite-instability (p = 0.039) and BRAF mutations (p < 0.001) were associated to this classification but it was independent of Dukes stages (p = 0.646). Molecular subtypes were established from stage I. High-stroma-subtype showed increased levels of genes and altered pathways distinctive of tumour-associated-stroma and components of the extracellular matrix in contrast to Low-stroma-subtype. Mucinous-subtype was reflected by the increased expression of trefoil factors and mucins as well as by a higher proportion of MSI and BRAF mutations. Tumor subtypes were validated using an external set of 78 patients. A 167 gene signature associated to the Low-stroma-subtype distinguished low risk patients from high risk patients in the external cohort (Dukes B and C:HR = 8.56(2.53-29.01); Dukes B,C and D:HR = 1.87(1.07-3.25)). Eight different reported survival gene signatures segregated our tumors into two groups the Low-stroma-subtype and the other tumor subtypes. We have identified novel

  4. Distinct distribution and prognostic significance of molecular subtypes of breast cancer in Chinese women: a population-based cohort study

    Directory of Open Access Journals (Sweden)

    Cai Qiuyin

    2011-07-01

    Full Text Available Abstract Background Molecular classification of breast cancer is an important prognostic factor. The distribution of molecular subtypes of breast cancer and their prognostic value has not been well documented in Asians. Methods A total of 2,791 breast cancer patients recruited for a population-based cohort study were evaluated for molecular subtypes of breast cancer by immunohistochemical assays. Data on clinicopathological characteristics were confirmed by centralized pathology review. The average follow-up of the patients was 53.4 months. Overall and disease-free survival by molecular subtypes of breast cancer were evaluated. Results The prevalence of the luminal A, luminal B, human epidermal growth factor receptor 2 (HER2, and triple-negative subtypes were 48.6%, 16.7%, 13.7%, and 12.9%, respectively. The luminal A subtype was more likely to be diagnosed in older women (P = 0.03 and had a stronger correlation with favorable clinicopathological factors (smaller tumor size, lower histologic grade, and earlier TNM stage than the triple-negative or HER2 subtypes. Women with triple-negative breast cancer had a higher frequency of family history of breast cancer than women with other subtypes (P = 0.048. The 5-year overall/disease-free survival percentages for the luminal A, luminal B, HER2, and triple-negative subtypes were 92.9%/88.6%, 88.6%/85.1%, 83.2%/79.1%, and 80.7%/76.0%, respectively. A similar pattern was observed in multivariate analyses. Immunotherapy was associated with improved overall and disease-free survival for luminal A breast cancer, but reduced disease-free survival (HR = 2.21, 95% CI, 1.09-4.48 for the HER2 subtype of breast cancer. Conclusions The triple-negative and HER2 subtypes were associated with poorer outcomes compared with the luminal A subtype among these Chinese women. The HER2 subtype was more prevalent in this Chinese population compared with Western populations, suggesting the importance of standardized HER2

  5. Treatment outcome in patients with triple negative early stage breast cancers compared with other molecular subtypes

    Energy Technology Data Exchange (ETDEWEB)

    Kim, Ja Young; Chang, Sei Kyung; Lee, Bo Mi; Shin, Hyun Soo [Dept. of Radiation Oncology, CHA Bundang Medical Center, CHA University, Seongnam (Korea, Republic of); Park, Heily [Dept. of Radiation Oncology, Presbyterian Hospital, Jeonju (Korea, Republic of)

    2012-09-15

    To determine whether triple negative (TN) early stage breast cancers have poorer survival rates compared with other molecular types. Between August 2000 and July 2006, patients diagnosed with stage I, II early stage breast cancers, in whom all three markers (estrogen receptor, progesterone receptor, and human epidermal growth factor receptor [HER]-2) were available and treated with modified radical mastectomy or breast conserving surgery followed by radiotherapy, were retrospectively reviewed. Of 446 patients, 94 (21.1%) were classified as TN, 57 (12.8%) as HER-2 type, and 295 (66.1%) as luminal. TN was more frequently associated with young patients younger than 35 years old (p = 0.002), higher histologic grade (p < 0.0001), and nuclear (p < 0.0001). The median follow-up period was 78 months (range, 4 to 130 months). There were 9 local relapses (2.0%), 15 nodal (3.4%), 40 distant metastases (9.0%), and 33 deaths (7.4%) for all patients. The rates of 5-year OS, DFS, LFS, and DMFS for all patients were 95.5%, 89.9%, 95.4%, and 91.7%, respectively. There were no significant differences in OS, DFS, LFS, and DMFS between triple negative and other subtypes (p > 0.05). We found that patients with TN early stage breast cancers had no difference in survival rates compared with other molecular subtypes. Prospective study in homogeneous treatment group will need for a prognosis of TN early stage breast cancer.

  6. Molecular epidemiology of HIV-1 in Panama: origin of non-B subtypes in samples collected from 2007 to 2013.

    Directory of Open Access Journals (Sweden)

    Yaxelis Mendoza

    Full Text Available Phylogenetic studies have suggested that the HIV-1 epidemic in the Americas is mainly dominated by HIV subtype B. However, countries of South America and the Caribbean have recently reported changes in their circulating HIV-1 genetic profiles. The aim of this study was to characterize the molecular profile of the HIV-1 epidemic in Panama by the analysis of 655 polymerase gene (pol sequences that were obtained from HIV-infected Panamanians diagnosed between 1987 and 2013. Blood samples were collected from recently infected, antiretroviral drug-naïve and treatment-experienced subjects since mid-2007 to 2013. Viral RNA from plasma was extracted and sequences of HIV protease and reverse transcriptase genes were obtained. Bootscanning and phylogenetic methods were used for HIV subtyping and to trace the putative origin of non-B subtype strains. Our results showed that HIV-1 infections in Panama are dominated by subtype B (98.9%. The remaining 1.1% is represented by a diverse collection of recombinant variants including: three URFs_BC, one CRF20_BG, and one CRF28/29_BF, in addition to one subtype F1 and one subtype C, none of which were previously reported in Panama. The non-B subtype variants detected in Panama were probably introduced from Brazil (subtype F1 and CRF28/29_BF, Cuba (CRF20_BG, Dominican Republic (URFs_BC and India (subtype C. Panama is the geographical vertex that connects the North with South America and the Caribbean through trade and cultural relations, which may explain the observed introductions of non-B subtype HIV-1 variants from both the Caribbean and South America into this Central American country.

  7. Molecular epidemiology of HIV-1 in Panama: origin of non-B subtypes in samples collected from 2007 to 2013.

    Science.gov (United States)

    Mendoza, Yaxelis; Bello, Gonzalo; Castillo Mewa, Juan; Martínez, Alexander A; González, Claudia; García-Morales, Claudia; Avila-Ríos, Santiago; Reyes-Terán, Gustavo; Pascale, Juan M

    2014-01-01

    Phylogenetic studies have suggested that the HIV-1 epidemic in the Americas is mainly dominated by HIV subtype B. However, countries of South America and the Caribbean have recently reported changes in their circulating HIV-1 genetic profiles. The aim of this study was to characterize the molecular profile of the HIV-1 epidemic in Panama by the analysis of 655 polymerase gene (pol) sequences that were obtained from HIV-infected Panamanians diagnosed between 1987 and 2013. Blood samples were collected from recently infected, antiretroviral drug-naïve and treatment-experienced subjects since mid-2007 to 2013. Viral RNA from plasma was extracted and sequences of HIV protease and reverse transcriptase genes were obtained. Bootscanning and phylogenetic methods were used for HIV subtyping and to trace the putative origin of non-B subtype strains. Our results showed that HIV-1 infections in Panama are dominated by subtype B (98.9%). The remaining 1.1% is represented by a diverse collection of recombinant variants including: three URFs_BC, one CRF20_BG, and one CRF28/29_BF, in addition to one subtype F1 and one subtype C, none of which were previously reported in Panama. The non-B subtype variants detected in Panama were probably introduced from Brazil (subtype F1 and CRF28/29_BF), Cuba (CRF20_BG), Dominican Republic (URFs_BC) and India (subtype C). Panama is the geographical vertex that connects the North with South America and the Caribbean through trade and cultural relations, which may explain the observed introductions of non-B subtype HIV-1 variants from both the Caribbean and South America into this Central American country.

  8. Why do we have apocrine and sebaceous glands?

    OpenAIRE

    Williams, Edward S

    2001-01-01

    The secretions of sebaceous and apocrine glands fulfil an important thermoregulatory role in cold-stressed and heat-stressed hunter—gatherers. In hot conditions the secretions emulsify eccrine sweat and thus encourage the formation of a sweat sheet and discourage the formation and loss of sweat drops from the skin. In colder conditions sebum changes its nature and repels rain from skin and hair.

  9. Dermoscopy of apocrine hydrocystoma: A first case report

    Directory of Open Access Journals (Sweden)

    Balachandra S. Ankad,

    2015-07-01

    Full Text Available Apocrine hydrocystoma (AH is a translucent, skin-colored to bluish dome shaped cyst on the face. AH mimics basal cell carcinoma (BCC, blue nevus, amelanotic melanoma requiring histopathological confirmation. Dermoscopy shows specific patterns in skin conditions. Dermoscopy of AH is not described in the literature. Authors evaluated dermoscopic patterns in AH and observed characteristic patterns corresponding to histological features. To the best of our knowledge, it is a first report in literature.

  10. The Human Glioblastoma Cell Culture Resource: Validated Cell Models Representing All Molecular Subtypes

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    Yuan Xie

    2015-10-01

    Full Text Available Glioblastoma (GBM is the most frequent and malignant form of primary brain tumor. GBM is essentially incurable and its resistance to therapy is attributed to a subpopulation of cells called glioma stem cells (GSCs. To meet the present shortage of relevant GBM cell (GC lines we developed a library of annotated and validated cell lines derived from surgical samples of GBM patients, maintained under conditions to preserve GSC characteristics. This collection, which we call the Human Glioblastoma Cell Culture (HGCC resource, consists of a biobank of 48 GC lines and an associated database containing high-resolution molecular data. We demonstrate that the HGCC lines are tumorigenic, harbor genomic lesions characteristic of GBMs, and represent all four transcriptional subtypes. The HGCC panel provides an open resource for in vitro and in vivo modeling of a large part of GBM diversity useful to both basic and translational GBM research.

  11. The Human Glioblastoma Cell Culture Resource: Validated Cell Models Representing All Molecular Subtypes.

    Science.gov (United States)

    Xie, Yuan; Bergström, Tobias; Jiang, Yiwen; Johansson, Patrik; Marinescu, Voichita Dana; Lindberg, Nanna; Segerman, Anna; Wicher, Grzegorz; Niklasson, Mia; Baskaran, Sathishkumar; Sreedharan, Smitha; Everlien, Isabelle; Kastemar, Marianne; Hermansson, Annika; Elfineh, Lioudmila; Libard, Sylwia; Holland, Eric Charles; Hesselager, Göran; Alafuzoff, Irina; Westermark, Bengt; Nelander, Sven; Forsberg-Nilsson, Karin; Uhrbom, Lene

    2015-10-01

    Glioblastoma (GBM) is the most frequent and malignant form of primary brain tumor. GBM is essentially incurable and its resistance to therapy is attributed to a subpopulation of cells called glioma stem cells (GSCs). To meet the present shortage of relevant GBM cell (GC) lines we developed a library of annotated and validated cell lines derived from surgical samples of GBM patients, maintained under conditions to preserve GSC characteristics. This collection, which we call the Human Glioblastoma Cell Culture (HGCC) resource, consists of a biobank of 48 GC lines and an associated database containing high-resolution molecular data. We demonstrate that the HGCC lines are tumorigenic, harbor genomic lesions characteristic of GBMs, and represent all four transcriptional subtypes. The HGCC panel provides an open resource for in vitro and in vivo modeling of a large part of GBM diversity useful to both basic and translational GBM research. PMID:26629530

  12. Surgical follow-up results for apocrine adenosis and atypical apocrine adenosis diagnosed on breast core biopsy.

    Science.gov (United States)

    Hou, Yanjun; Chaudhary, Shweta; Gao, Faye F; Li, Zaibo

    2016-10-01

    Apocrine adenosis (AA) and atypical apocrine adenosis (AAA) are uncommon findings in breast biopsies that may be misinterpreted as carcinoma. The clinical significance and risk implications of AAA diagnosed on core biopsy are not well established. This study aimed to determine the frequency of carcinoma on follow-up excision in patients with a diagnosis of AA or AAA on core biopsy. Forty-one breast core biopsies of AA (n=29) and AAA (n=12) were identified during a study period of 12 years. Of the 41 core biopsies with AA or AAA, 10 biopsies showed coexisting/concurrent atypical hyperplasia or carcinoma. In the absence of coexisting/concurrent atypical hyperplasia or carcinoma in core biopsy, none of the follow-up excision specimens after a diagnosis of AA or AAA showed ductal carcinoma in situ or invasive carcinoma. In conclusion, AA or AAA by itself is an uncommon core biopsy diagnosis that may not require surgical excision.

  13. Surgical follow-up results for apocrine adenosis and atypical apocrine adenosis diagnosed on breast core biopsy.

    Science.gov (United States)

    Hou, Yanjun; Chaudhary, Shweta; Gao, Faye F; Li, Zaibo

    2016-10-01

    Apocrine adenosis (AA) and atypical apocrine adenosis (AAA) are uncommon findings in breast biopsies that may be misinterpreted as carcinoma. The clinical significance and risk implications of AAA diagnosed on core biopsy are not well established. This study aimed to determine the frequency of carcinoma on follow-up excision in patients with a diagnosis of AA or AAA on core biopsy. Forty-one breast core biopsies of AA (n=29) and AAA (n=12) were identified during a study period of 12 years. Of the 41 core biopsies with AA or AAA, 10 biopsies showed coexisting/concurrent atypical hyperplasia or carcinoma. In the absence of coexisting/concurrent atypical hyperplasia or carcinoma in core biopsy, none of the follow-up excision specimens after a diagnosis of AA or AAA showed ductal carcinoma in situ or invasive carcinoma. In conclusion, AA or AAA by itself is an uncommon core biopsy diagnosis that may not require surgical excision. PMID:27649945

  14. Prevalence of molecular subtypes and prognosis of invasive breast cancer in north-east of Morocco: retrospective study

    Directory of Open Access Journals (Sweden)

    Bennis Sanae

    2012-08-01

    Full Text Available Abstract Background Breast carcinoma is known as a heterogeneous disease because gene expression analyses identify several subtypes and the molecular profiles are prognostic and predictive for patients. Our aim, in this study, is to estimate the prevalence of breast cancer subtypes and to determine the relationship between clinico-pathological characteristics, overall survival (OS and disease free survival (DFS for patients coming from north-east of Morocco. Methods We reviewed 366 cases of breast cancer diagnosed between January 2007 to June 2010 at the Department of pathology. Age, size tumor, metastatic profile, node involvement profile, OS and DFS were analyzed on 181 patients. These last parameters were estimated by Kaplan-Meier analysis and log-rank test to estimate outcome differences among subgroups. Results The average age was 45 years, our patients were diagnosed late (57% stage III, 17.5% stage IV with a high average tumor size. Luminal A subtype was more prevalent (53.6% associated with favorable clinic-pathological characteristics, followed by luminal B (16.4%, Her2-overexpressing (12.6%, basal-like (12.6% and unclassified subtype (4.9%. Survival analysis showed a significant difference between subtypes. The triple negative tumors were associated with poor prognosis (49% OS, 39% DFS, whereas the luminal A were associated with a better prognosis (88% OS, 59% DFS. The luminal B and the Her2-overexpressing subtypes were associated with an intermediate prognosis (77% and 75% OS, and 41% and 38% DFS respectively. Conclusion This study showed that molecular classification by immunohistochemistry was necessary for therapeutic decision and prognosis of breast carcinoma. The luminal A subtype was associated with favorable biological characteristics and a better prognosis than triple negative tumors that were associated with a poor prognosis and unfavorable clinic-pathological characteristics.

  15. Comparison of molecular subtype distribution in triple-negative inflammatory and non-inflammatory breast cancers

    OpenAIRE

    Masuda, Hiroko; Keith A. Baggerly; Ying WANG; Iwamoto, Takayuki; Brewer, Takae; Pusztai, Lajos; Kai, Kazuharu; Kogawa, Takahiro; Finetti, Pascal; Birnbaum, Daniel; Dirix, Luc; Wendy A Woodward; Reuben, James M.; Krishnamurthy, Savitri; Symmans, W Fraser

    2013-01-01

    Introduction Because of its high rate of metastasis, inflammatory breast cancer (IBC) has a poor prognosis compared with non-inflammatory types of breast cancer (non-IBC). In a recent study, Lehmann and colleagues identified seven subtypes of triple-negative breast cancer (TNBC). We hypothesized that the distribution of TNBC subtypes differs between TN-IBC and TN-non-IBC. We determined the subtypes and compared clinical outcomes by subtype in TN-IBC and TN-non-IBC patients. Methods We determi...

  16. Molecular subtypes in head and neck cancer exhibit distinct patterns of chromosomal gain and loss of canonical cancer genes.

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    Vonn Walter

    Full Text Available Head and neck squamous cell carcinoma (HNSCC is a frequently fatal heterogeneous disease. Beyond the role of human papilloma virus (HPV, no validated molecular characterization of the disease has been established. Using an integrated genomic analysis and validation methodology we confirm four molecular classes of HNSCC (basal, mesenchymal, atypical, and classical consistent with signatures established for squamous carcinoma of the lung, including deregulation of the KEAP1/NFE2L2 oxidative stress pathway, differential utilization of the lineage markers SOX2 and TP63, and preference for the oncogenes PIK3CA and EGFR. For potential clinical use the signatures are complimentary to classification by HPV infection status as well as the putative high risk marker CCND1 copy number gain. A molecular etiology for the subtypes is suggested by statistically significant chromosomal gains and losses and differential cell of origin expression patterns. Model systems representative of each of the four subtypes are also presented.

  17. Molecular analysis of endothelial progenitor cell (EPC subtypes reveals two distinct cell populations with different identities

    Directory of Open Access Journals (Sweden)

    Simpson David A

    2010-05-01

    Full Text Available Abstract Background The term endothelial progenitor cells (EPCs is currently used to refer to cell populations which are quite dissimilar in terms of biological properties. This study provides a detailed molecular fingerprint for two EPC subtypes: early EPCs (eEPCs and outgrowth endothelial cells (OECs. Methods Human blood-derived eEPCs and OECs were characterised by using genome-wide transcriptional profiling, 2D protein electrophoresis, and electron microscopy. Comparative analysis at the transcript and protein level included monocytes and mature endothelial cells as reference cell types. Results Our data show that eEPCs and OECs have strikingly different gene expression signatures. Many highly expressed transcripts in eEPCs are haematopoietic specific (RUNX1, WAS, LYN with links to immunity and inflammation (TLRs, CD14, HLAs, whereas many transcripts involved in vascular development and angiogenesis-related signalling pathways (Tie2, eNOS, Ephrins are highly expressed in OECs. Comparative analysis with monocytes and mature endothelial cells clusters eEPCs with monocytes, while OECs segment with endothelial cells. Similarly, proteomic analysis revealed that 90% of spots identified by 2-D gel analysis are common between OECs and endothelial cells while eEPCs share 77% with monocytes. In line with the expression pattern of caveolins and cadherins identified by microarray analysis, ultrastructural evaluation highlighted the presence of caveolae and adherens junctions only in OECs. Conclusions This study provides evidence that eEPCs are haematopoietic cells with a molecular phenotype linked to monocytes; whereas OECs exhibit commitment to the endothelial lineage. These findings indicate that OECs might be an attractive cell candidate for inducing therapeutic angiogenesis, while eEPC should be used with caution because of their monocytic nature.

  18. 16S rRNA partial gene sequencing for the differentiation and molecular subtyping of Listeria species.

    Science.gov (United States)

    Hellberg, Rosalee S; Martin, Keely G; Keys, Ashley L; Haney, Christopher J; Shen, Yuelian; Smiley, R Derike

    2013-12-01

    Use of 16S rRNA partial gene sequencing within the regulatory workflow could greatly reduce the time and labor needed for confirmation and subtyping of Listeria monocytogenes. The goal of this study was to build a 16S rRNA partial gene reference library for Listeria spp. and investigate the potential for 16S rRNA molecular subtyping. A total of 86 isolates of Listeria representing L. innocua, L. seeligeri, L. welshimeri, and L. monocytogenes were obtained for use in building the custom library. Seven non-Listeria species and three additional strains of Listeria were obtained for use in exclusivity and food spiking tests. Isolates were sequenced for the partial 16S rRNA gene using the MicroSeq ID 500 Bacterial Identification Kit (Applied Biosystems). High-quality sequences were obtained for 84 of the custom library isolates and 23 unique 16S sequence types were discovered for use in molecular subtyping. All of the exclusivity strains were negative for Listeria and the three Listeria strains used in food spiking were consistently recovered and correctly identified at the species level. The spiking results also allowed for differentiation beyond the species level, as 87% of replicates for one strain and 100% of replicates for the other two strains consistently matched the same 16S type.

  19. Molecular Characterization and Subtyping of Blastocystis Species in Irritable Bowel Syndrome Patients from North India.

    Science.gov (United States)

    Das, Rojaleen; Khalil, Shehla; Mirdha, B R; Makharia, Govind K; Dattagupta, Siddharta; Chaudhry, Rama

    2016-01-01

    Blastocystis species has been extensively studied in recent few years to establish its pathogenecity. Present study was designed to identify and examine the association of Blastocystis sp. and its subtypes with Irritable Bowel Syndrome (IBS).Blastocystis sp. detected using wet-mount microscopy, trichrome staining, in-vitro culture and Polymerase Chain Reaction (PCR) assay in a cohort of IBS patients (n = 150) and healthy controls (n = 100). Isolates of Blastocystis sp.were subtyped using Sequence Tagged Site and representative samples were sequenced at SSUrRNA locus.A total of sixty five isolates of Blastocystis sp. were identified [IBS (n = 50); Controls (n = 15)] of which 91% belonged to ST3 and 9% belonged to ST1. No other subtypes could be identified. Statistically significant association was observed between Blastocystis sp. and IBS patients; however no particular subtype could be ascertained to any particular clinical type of IBS.The frequency of occurrence of Blastocystis sp. was more in IBS patients as compared to the controls and ST3 being the most prevalent subtype. The genetic polymorphism of SSU-rRNA gene amongst the different Blastocystis sp.isolates found in this study reinforces the fact that these organisms are genetically highly divergent. PMID:26784888

  20. BRCA1 and TOP2A gene amplification and protein expression in four molecular subtypes of breast cancer

    Directory of Open Access Journals (Sweden)

    Mitrović Olivera

    2013-01-01

    Full Text Available We studied TOP2A amplification (using FISH methods, and TOP2A and BRCA1 protein overexpression (immunohistochemistry in four molecular subtypes of breast cancer. Of 53 patients, 32 showed TOP2A and 38 showed BRCA1 overexpression. The highest percentage of TOP2A amplification (47.8% and deletion (13% was detected in Luminal B subtypes. Of 11 Luminal B tumors with TOP2A amplification, 9 (81.8% overexpressed TOP2A. BRCA1 protein overexpression showed significant positive correlation with TOP2A protein expression. BRCA1 and TOP2A proteins exhibited similar patterns of expression in Luminal B and triple-negative breast cancer, suggesting the same prognosis in those patients. [Projekat Ministarstva nauke Republike Srbije, br. 175053

  1. RNA profiling reveals familial aggregation of molecular subtypes in non-BRCA1/2 breast cancer families

    DEFF Research Database (Denmark)

    Larsen, Martin J; Thomassen, Mads; Tan, Qihua;

    2014-01-01

    BACKGROUND: In more than 70% of families with a strong history of breast and ovarian cancers, pathogenic mutation in BRCA1 or BRCA2 cannot be identified, even though hereditary factors are expected to be involved. It has been proposed that tumors with similar molecular phenotypes also share similar...... underlying pathophysiological mechanisms. In the current study, the aim was to investigate if global RNA profiling can be used to identify functional subgroups within breast tumors from families tested negative for BRCA1/2 germline mutations and how these subgroupings relate to different breast cancer...... cancer subtypes, exist among non-BRCA1/2 breast cancers. The distribution of subtypes was markedly different from the distribution found among BRCA1/2 mutation carriers. From 11 breast cancer families, breast tumor biopsies from more than one affected family member were included in the study. Notably...

  2. Portraying the Expression Landscapes of B-CellLymphoma-Intuitive Detection of Outlier Samples and of Molecular Subtypes

    Directory of Open Access Journals (Sweden)

    Lydia Hopp

    2013-12-01

    Full Text Available We present an analytic framework based on Self-Organizing Map (SOM machine learning to study large scale patient data sets. The potency of the approach is demonstrated in a case study using gene expression data of more than 200 mature aggressive B-cell lymphoma patients. The method portrays each sample with individual resolution, characterizes the subtypes, disentangles the expression patterns into distinct modules, extracts their functional context using enrichment techniques and enables investigation of the similarity relations between the samples. The method also allows to detect and to correct outliers caused by contaminations. Based on our analysis, we propose a refined classification of B-cell Lymphoma into four molecular subtypes which are characterized by differential functional and clinical characteristics.

  3. Management of metastatic apocrine hidradenocarcinoma with chemotherapy and radiation

    Directory of Open Access Journals (Sweden)

    Daniel H. Miller

    2015-10-01

    Full Text Available Hidradenocarcinoma is a rare aggressive form of cutaneous adnexal skin carcinoma originating from the sweat gland. Due to its low incidence, prognostic and treatment strategies are still being explored both for primary and advanced disease. This tumor most often presents as either solid or cystic appearing subcutaneous nodules, which may be associated with pruritus or ulceration. To date the mainstay of treatment for local disease has been surgical excision; however, the paucity of historical data available has shown that these tumors often behave aggressively with high rates of local recurrence, metastasis, and poor overall outcomes. There are few case reports describing the utility of radiation therapy in the treatment of hidradenocarcinoma. Herein, we present a case of metastatic apocrine hidradenocarcinoma in a 32-year-old Caucasian male. The patient initially underwent excisional biopsy which confirmed the diagnosis of poorly differentiated, highly infiltrative, apocrine hidradenocarcinoma. He received systemic chemotherapy for metastatic disease, followed by radiation therapy to areas of grossly palpable adenopathy. Prior to radiation therapy the patient had an enlarged hypermetabolic conglomerate of lymph nodes in the right axilla, and borderline enlarged low activity nodes within the left axilla. He received 3 cycles of chemotherapy followed by tamoxifen and radiation therapy (50.4 Gy in 28 fractions to areas of progressive disease in the bilateral axilla, lower neck, and axillary skin. Following treatment, the patient had complete resolution of skin nodules and improvement of his pruritus. While the role of radiation therapy in the treatment of hidradenocarcinoma has not been well established, this case report demonstrated the potential benefit of external beam radiotherapy in the management of this rare disease

  4. Antimicrobial resistance profiling and molecular subtyping of Campylobacter spp. from processed turkey

    Directory of Open Access Journals (Sweden)

    Sherwood Julie S

    2009-09-01

    Ciprofloxacin and erythromycin resistance in Campylobacter recovered from processed turkey occurred more frequently among C. coli than C. jejuni. Fla-PFGE types were associated with a particular species, antimicrobial resistance profiles, and a specific plant. Molecular subtyping in this study provided more information about the relationships among antimicrobial-resistant Campylobacter at the processing level.

  5. Apocrine Metaplasia in Intraductal Papilloma with Foci of DCIS: A Friend or Foe?

    Science.gov (United States)

    Mallick, Debjani; Aniruna, Aniruna; Gon, Sonia; Ghosh, Gayatri

    2016-01-01

    Malignant papillary neoplasms of the breast comprise a number of microscopically distinct lesions, where apocrine metaplasia is commonly found in papillomas compared to other papillary lesions including papillary carcinomas. However, association of apocrine metaplasia in papilloma with Ductal Carcinoma in Situ (DCIS) is not very well defined. The lesions with apocrine metaplasia are not only difficult to categories, but also there is controversy regarding their relative risk of subsequent carcinoma development. A case of extensive apocrine differentiation in duct papilloma with DCIS developing in the background of papillomatosis, posing a diagnostic dilemma for the pathologist and a therapeutic challenge for the surgeon, is hereby reported for its uniqueness and rarity. Awareness of this association should be kept in mind by both the pathologist as well as clinician for optimal therapeutic intervention. PMID:27499780

  6. Evaluation of gene expression signatures predictive of cytogenetic and molecular subtypes of pediatric acute myeloid leukemia

    NARCIS (Netherlands)

    Balgobind, Brian V.; Van den Heuvel-Eibrink, Marry M.; De Menezes, Renee X.; Reinhardt, Dirk; Hollink, Iris H. I. M.; Arentsen-Peters, Susan T. J. C. M.; van Wering, Elisabeth R.; Kaspers, Gertjan J. L.; Cloos, Jacqueline; de Bont, Evelien S. J. M.; Cayuela, Jean-Michel; Baruchel, Andre; Meyer, Claus; Marschalek, Rolf; Trka, Jan; Stary, Jan; Beverloo, H. Berna; Pieters, Rob; Zwaan, C. Michel; den Boer, Monique L.

    2011-01-01

    Background Pediatric acute myeloid leukemia is a heterogeneous disease characterized by non-random genetic aberrations related to outcome. The genetic subtype is currently detected by different diagnostic procedures which differ in success rate and/or specificity. Design and Methods We examined the

  7. Molecular subtype profiling of invasive breast cancers weakly positive for estrogen receptor.

    Science.gov (United States)

    Sheffield, Brandon S; Kos, Zuzana; Asleh-Aburaya, Karama; Wang, Xiu Qing; Leung, Samuel; Gao, Dongxia; Won, Jennifer; Chow, Christine; Rachamadugu, Rakesh; Stijleman, Inge; Wolber, Robert; Gilks, C Blake; Myles, Nickolas; Thomson, Tom; Hayes, Malcolm M; Bernard, Philip S; Nielsen, Torsten O; Chia, Stephen K L

    2016-02-01

    The estrogen receptor (ER) is a key predictive biomarker in the treatment of breast cancer. There is uncertainty regarding the use of hormonal therapy in the setting of weakly positive ER by immunohistochemistry (IHC). We report intrinsic subtype classification on a cohort of ER weakly positive early-stage breast cancers. Consecutive cases of breast cancer treated by primary surgical resection were retrospectively identified from 4 centers that engage in routine external proficiency testing for breast biomarkers. ER-negative (Allred 0 and 2) and ER weakly positive (Allred 3-5) cases were included. Gene expression profiling was performed using qRT-PCR. Intrinsic subtype prediction was made based upon the PAM50 gene expression signature. 148 cases were included in the series: 60 cases originally diagnosed as ER weakly positive and 88 ER negative. Of the cases originally assessed as ER weakly positive, only 6 (10 %) were confirmed to be of luminal subtype by gene expression profiling; the remaining 90 % of cases were classified as basal-like or HER2-enriched subtypes. This was not significantly different than the fraction of luminal cases identified in the IHC ER-negative cohort (5 (5 %) luminal, 83(95 %) non-luminal). Recurrence-free, and overall, survival rates were similar in both groups (p = 0.4 and 0.5, respectively) despite adjuvant hormonal therapy prescribed in the majority (59 %) of weakly positive ER cases. Weak ER expression by IHC is a poor correlate of luminal subtype in invasive breast cancer. In the setting of highly sensitive and robust IHC methodology, cutoffs for ER status determination and subsequent systemic therapy should be revisited. PMID:26846986

  8. Functional and Developmental Identification of a Molecular Subtype of Brain Serotonergic Neuron Specialized to Regulate Breathing Dynamics

    Directory of Open Access Journals (Sweden)

    Rachael D. Brust

    2014-12-01

    Full Text Available Serotonergic neurons modulate behavioral and physiological responses from aggression and anxiety to breathing and thermoregulation. Disorders involving serotonin (5HT dysregulation are commensurately heterogeneous and numerous. We hypothesized that this breadth in functionality derives in part from a developmentally determined substructure of distinct subtypes of 5HT neurons each specialized to modulate specific behaviors. By manipulating developmentally defined subgroups one by one chemogenetically, we find that the Egr2-Pet1 subgroup is specialized to drive increased ventilation in response to carbon dioxide elevation and acidosis. Furthermore, this subtype exhibits intrinsic chemosensitivity and modality-specific projections—increasing firing during hypercapnic acidosis and selectively projecting to respiratory chemosensory but not motor centers, respectively. These findings show that serotonergic regulation of the respiratory chemoreflex is mediated by a specialized molecular subtype of 5HT neuron harboring unique physiological, biophysical, and hodological properties specified developmentally and demonstrate that the serotonergic system contains specialized modules contributing to its collective functional breadth.

  9. Molecular subtypes of serous borderline ovarian tumor show distinct expression patterns of benign tumor and malignant tumor-associated signatures.

    Science.gov (United States)

    Curry, Edward W J; Stronach, Euan A; Rama, Nona R; Wang, Yuepeng Y P; Gabra, Hani; El-Bahrawy, Mona A

    2014-03-01

    Borderline ovarian tumors show heterogeneity in clinical behavior. Most have excellent prognosis, although a small percentage show recurrence or progressive disease, usually to low-grade serous carcinoma. The aim of this study was to understand the molecular relationship between these entities and identify potential markers of tumor progression and therapeutic targets. We studied gene expression using Affymetrix HGU133plus2 GeneChip microarrays in 3 low-grade serous carcinomas, 13 serous borderline tumors and 8 serous cystadenomas. An independent data set of 18 serous borderline tumors and 3 low-grade serous carcinomas was used for validation. Unsupervised clustering revealed clear separation of benign and malignant tumors, whereas borderline tumors showed two distinct groups, one clustering with benign and the other with malignant tumors. The segregation into benign- and malignant-like borderline molecular subtypes was reproducible on applying the same analysis to an independent publicly available data set. We identified 50 genes that separate borderline tumors into their subgroups. Functional enrichment analysis of genes that separate borderline tumors to the two subgroups highlights a cell adhesion signature for the malignant-like subset, with Claudins particularly prominent. This is the first report of molecular subtypes of borderline tumors based on gene expression profiling. Our results provide the basis for identification of biomarkers for the malignant potential of borderline ovarian tumor and potential therapeutic targets for low-grade serous carcinoma. PMID:23948749

  10. Associations between body mass index and molecular subtypes as well as other clinical characteristics of breast cancer in Chinese women

    Directory of Open Access Journals (Sweden)

    Chen FY

    2013-03-01

    Full Text Available Fei-Yu Chen, Hui-Ying Ou, Shou-Man Wang, Yu-Hui Wu, Guo-Jiao Yan, Li-Li Tang Department of Breast Surgery, Xiangya Hospital, Central South University, Changsha City, Hunan Province, People's Republic of China Background: Several studies have shown a positive association between body mass index (BMI and the development of hormone receptor-positive breast cancer in postmenopausal women; however, the associations between BMI groups and molecular subtypes have yet to be well defined in premenopausal breast cancer patients. Methods: A total of 2465 female breast cancer patients diagnosed at our institution were recruited for this study. Clinicopathologic information (including age, body height and weight, as well as tumor subtypes and stages was collected; analyses of these characteristics and the associations between them were performed. Results: A total of 1951 cases were included in the study. The mean age was 47.3 years, the majority of patients were of normal weight, premenopausal, had stage 2 cancer, and did not present with positive nodes. The prevalence of the luminal A, luminal B, human epidermal growth factor receptor 2+, and triple-negative subtypes were 57.8%, 11.6%, 6.1%, and 24.5%, respectively. There were significant differences in the clinicopathologic features among BMI groups in premenopausal patients. The case-only odds ratio (OR analysis revealed that normal weight patients tended to have luminal B cancer (OR = 1.4, P = 0.206, and overweight and obese patients tended to have triple-negative cancer in premenopausal patients (OR = 2.8, OR = 3.7, respectively; P < 0.001. Conclusion: In Chinese women, breast cancer came with these characteristics: young mean age (premenopause, luminal A subtype, and the majority of them were within a normal weight range. In premenopausal patients, underweight patients tended to have luminal A, lower human epidermal growth factor receptor 2+ expression, stage 1 and no positive node cancer. However

  11. Height and Body Size in Childhood, Adolescence, and Young Adulthood and Breast Cancer Risk According to Molecular Subtype in the Nurses' Health Studies.

    Science.gov (United States)

    Warner, Erica T; Hu, Rong; Collins, Laura C; Beck, Andrew H; Schnitt, Stuart; Rosner, Bernard; Eliassen, A Heather; Michels, Karin B; Willett, Walter C; Tamimi, Rulla M

    2016-09-01

    Height and body size in childhood and young adulthood have been consistently associated with breast cancer risk; whether associations differ across molecular subtypes is unclear. In a pooled analysis of the Nurses' Health Studies, we prospectively examined the association of four exposures: height, body mass index (BMI) at the age of 18 years, childhood and adolescent somatotypes, with breast cancer risk according to molecular subtypes defined by immunohistochemical markers. We used multivariable-adjusted Cox proportional hazards regression to estimate HRs and 95% confidence intervals (CI). We identified 2,983 luminal A, 1,281 luminal B, 318 HER2-enriched, 408 basal-like, and 128 unclassified tumors. Height was positively associated with all subtypes (Pheterogeneity = 0.78). BMI at the age of 18 (Pheterogeneity = 0.001), childhood (Pheterogeneity = 0.51), and adolescent somatotype (Pheterogeneity = 0.046) were inversely associated, but with differences in magnitude of association. BMI at the age of 18 of ≥25 kg/m(2) (compared with 20-21.9 kg/m(2)) was associated with a 52% decreased risk of HER2-enriched (HR, 0.48; 95% CI, 0.26-0.91; Ptrend molecular subtypes. BMI at 18 years and childhood and adolescent were inversely associated with risk of most breast cancer molecular subtypes with somewhat stronger associations with HER2-enriched and basal-like subtypes. Cancer Prev Res; 9(9); 732-8. ©2016 AACR. PMID:27590596

  12. Four-month outbreak of invasive meningococcal disease caused by a rare serogroup B strain, identified through the use of molecular PorA subtyping, England, 2013.

    Science.gov (United States)

    Chatt, C; Gajraj, R; Hawker, J; Neal, K; Tahir, M; Lawrence, M; Gray, S J; Lucidarme, J; Carr, A D; Clark, S A; Fowler, T

    2014-01-01

    Molecular PorA subtyping provides information that increasingly requires the adaptation of standard public health approaches to outbreak management. We report an outbreak of a rare subtype of meningococcal infection not previously identified in the United Kingdom (UK). The outbreak occurred in the Warwickshire area in England between February and June 2013. Molecular subtyping allowed the identification of additional cases, prompting an enhanced public health response that included efforts to identify potential social networks that might benefit from chemoprophylaxis. It also prompted swabbing to define nasopharyngeal carriage in the focal nursery and helped explain the unusual epidemiological pattern. Without subtyping to identify a link, the additional cases would have been managed as sporadic cases in accordance with current UK guidance. PMID:25394258

  13. A Molecular and Chemical Perspective in Defining Melatonin Receptor Subtype Selectivity

    Directory of Open Access Journals (Sweden)

    Yung Hou Wong

    2013-09-01

    Full Text Available Melatonin is primarily synthesized and secreted by the pineal gland during darkness in a normal diurnal cycle. In addition to its intrinsic antioxidant property, the neurohormone has renowned regulatory roles in the control of circadian rhythm and exerts its physiological actions primarily by interacting with the G protein-coupled MT1 and MT2 transmembrane receptors. The two melatonin receptor subtypes display identical ligand binding characteristics and mediate a myriad of signaling pathways, including adenylyl cyclase inhibition, phospholipase C stimulation and the regulation of other effector molecules. Both MT1 and MT2 receptors are widely expressed in the central nervous system as well as many peripheral tissues, but each receptor subtype can be linked to specific functional responses at the target tissue. Given the broad therapeutic implications of melatonin receptors in chronobiology, immunomodulation, endocrine regulation, reproductive functions and cancer development, drug discovery and development programs have been directed at identifying chemical molecules that bind to the two melatonin receptor subtypes. However, all of the melatoninergics in the market act on both subtypes of melatonin receptors without significant selectivity. To facilitate the design and development of novel therapeutic agents, it is necessary to understand the intrinsic differences between MT1 and MT2 that determine ligand binding, functional efficacy, and signaling specificity. This review summarizes our current knowledge in differentiating MT1 and MT2 receptors and their signaling capacities. The use of homology modeling in the mapping of the ligand-binding pocket will be described. Identification of conserved and distinct residues will be tremendously useful in the design of highly selective ligands.

  14. Impact of immunohistochemistry-based molecular subtype on chemosensitivity and survival in Hispanic breast cancer patients following neoadjuvant chemotherapy

    Science.gov (United States)

    Gómez, Rodolfo; Ossa, Carlos Andrés; Montoya, María Elvira; Echeverri, Carolina; Ángel, Gonzalo; Ascuntar, Johana; Borrero, Mauricio; Gil, Mónica; Herrera, Sabrina; Gutiérrez, Eduardo; Herazo, Fernando; Jiménez, Alejo; Madrid, Jorge; Reyes, Pedro Alejandro; Zuluaga, Lina; García, Héctor

    2015-01-01

    Background Neoadjuvant chemotherapy (NAC) is the standard treatment for patients with locally advanced breast cancer, showing improvement in disease-free survival (DFS) and overall survival (OS) rates in patients achieving pathological complete response (pCR). The relationship between immunohistochemistry-based molecular subtyping (IMS), chemo sensitivity and survival is currently a matter of interest. We explore this relationship in a Hispanic cohort of breast cancer patients treated with NAC. Methods A retrospective survival analysis was performed on Colombian females with breast cancer treated at Instituto de Cancerología-Clinica Las Américas between January 2009 and December 2011. Patients were classified according to immunohistochemistry-based subtyping into the following five groups: Luminal A, Luminal B, Luminal B/HER 2+, HER2-enriched, and triple-negative breast cancer. Demographic characteristics, recurrence pattern, and survival rate were reviewed by bivariate and multivariate analysis. Results A total of 328 patients fulfilled the study’s inclusion parameters and the distribution of subtypes were as follows: Luminal A: 73 (22.3%), Luminal B/HER2−: 110 (33.5%), Luminal B/HER2+: 75 (22.9%), HER2-enriched: 30 (9.1%), and triple-negative: 40 (12.2%). The median follow-up was 41 months (interquartile range: 31–52). Pathological response to NAC was as follows: complete pathological response (pCR) in 28 (8.5%) patients, partial 247 (75.3%); stable disease 47 (14.3%), and progression 6 (1.8%) patients. The presence of pCR had a significant DFS and OS in the entire group (p = 0.01) but subtypes had different DFS in Luminal B (p = 0.01) and triple negative (p = 0.02) and also OS in Luminal B (p = 0.01) and triple negative (p = 0.01). Conclusions pCR is associated with an improved overall survival and disease-free survival rates in this group of Hispanics patients. Advanced stages, Luminal B subtypes, triple-negative tumours and non-pCR showed lower DFS

  15. Lineage-restricted OLIG2-RTK signaling governs the molecular subtype of glioma stem-like cells

    Science.gov (United States)

    Kupp, Robert; Shtayer, Lior; Tien, An-Chi; Szeto, Emily; Sanai, Nader; Rowitch, David H.; Mehta, Shwetal

    2016-01-01

    SUMMARY The bHLH transcription factor OLIG2 is a master regulator of oligodendroglial fate decisions and tumorigenic competence of glioma stem-like cells (GSCs). However, the molecular mechanisms underlying dysregulation of OLIG2 function during gliomagenesis remains poorly understood. Here, we show that OLIG2 modulates growth factor signaling in two distinct populations of GSCs, characterized by expression of either the EGFR or PDGFRα. Biochemical analyses of OLIG2 function in normal and malignant neural progenitors reveal a positive feedforward loop between OLIG2 and EGFR to sustain co-expression. Furthermore, loss of OLIG2 function results in mesenchymal transformation in PDGFRαHIGH GSCs, a phenomenon that appears to be circumscribed in EGFRHIGH GSCs. Exploitation of OLIG2’s dual and antithetical, pro-mitotic (EGFR-driven) and lineage-specifying (PDGFRα-driven) functions by glioma cells, appears to be critical for sustaining growth factor signaling and GSC molecular subtype. PMID:27626655

  16. Subtyping sub-Saharan esophageal squamous cell carcinoma by comprehensive molecular analysis

    Science.gov (United States)

    Liu, Wenjin; Snell, Jeff M.; Jeck, William R.; Wilkerson, Matthew D.; Parker, Joel S.; Patel, Nirali; Mlombe, Yohannie B.; Mulima, Gift; Liomba, N. George; Wolf, Lindsey L.; Shores, Carol G.; Gopal, Satish; Sharpless, Norman E.

    2016-01-01

    Esophageal squamous cell carcinoma (ESCC) is endemic in regions of sub-Saharan Africa (SSA), where it is the third most common cancer. Here, we describe whole-exome tumor/normal sequencing and RNA transcriptomic analysis of 59 patients with ESCC in Malawi. We observed similar genetic aberrations as reported in Asian and North American cohorts, including mutations of TP53, CDKN2A, NFE2L2, CHEK2, NOTCH1, FAT1, and FBXW7. Analyses for nonhuman sequences did not reveal evidence for infection with HPV or other occult pathogens. Mutational signature analysis revealed common signatures associated with aging, cytidine deaminase activity (APOBEC), and a third signature of unknown origin, but signatures of inhaled tobacco use, aflatoxin and mismatch repair were notably absent. Based on RNA expression analysis, ESCC could be divided into 3 distinct subtypes, which were distinguished by their expression of cell cycle and neural transcripts. This study demonstrates discrete subtypes of ESCC in SSA, and suggests that the endemic nature of this disease reflects exposure to a carcinogen other than tobacco and oncogenic viruses. PMID:27734031

  17. Non-sentinel lymph node metastasis prediction in breast cancer with metastatic sentinel lymph node: impact of molecular subtypes classification.

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    Fabien Reyal

    Full Text Available INTRODUCTION: To decipher the interaction between the molecular subtype classification and the probability of a non-sentinel node metastasis in breast cancer patients with a metastatic sentinel lymph-node, we applied two validated predictors (Tenon Score and MSKCC Nomogram on two large independent datasets. MATERIALS AND METHODS: Our datasets consisted of 656 and 574 early-stage breast cancer patients with a metastatic sentinel lymph-node biopsy treated at first by surgery. We applied both predictors on the whole dataset and on each molecular immune-phenotype subgroups. The performances of the two predictors were analyzed in terms of discrimination and calibration. Probability of non-sentinel lymph node metastasis was detailed for each molecular subtype. RESULTS: Similar results were obtained with both predictors. We showed that the performance in terms of discrimination was as expected in ER Positive HER2 negative subgroup in both datasets (MSKCC AUC Dataset 1 = 0.73 [0.69-0.78], MSKCC AUC Dataset 2 = 0.71 (0.65-0.76, Tenon Score AUC Dataset 1 = 0.7 (0.65-0.75, Tenon Score AUC Dataset 2 = 0.72 (0.66-0.76. Probability of non-sentinel node metastatic involvement was slightly under-estimated. Contradictory results were obtained in other subgroups (ER negative HER2 negative, HER2 positive subgroups in both datasets probably due to a small sample size issue. We showed that merging the two datasets shifted the performance close to the ER positive HER2 negative subgroup. DISCUSSION: We showed that validated predictors like the Tenon Score or the MSKCC nomogram built on heterogeneous population of breast cancer performed equally on the different subgroups analyzed. Our present study re-enforce the idea that performing subgroup analysis of such predictors within less than 200 samples subgroup is at major risk of misleading conclusions.

  18. Molecular subtype classification is a determinant of non-sentinel lymph node metastasis in breast cancer patients with positive sentinel lymph nodes.

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    Wenbin Zhou

    Full Text Available BACKGROUND: Previous studies suggested that the molecular subtypes were strongly associated with sentinel lymph node (SLN status. The purpose of this study was to determine whether molecular subtype classification was associated with non-sentinel lymph nodes (NSLN metastasis in patients with a positive SLN. METHODOLOGY AND PRINCIPAL FINDINGS: Between January 2001 and March 2011, a total of 130 patients with a positive SLN were recruited. All these patients underwent a complete axillary lymph node dissection. The univariate and multivariate analyses of NSLN metastasis were performed. In univariate and multivariate analyses, large tumor size, macrometastasis and high tumor grade were all significant risk factors of NSLN metastasis in patients with a positive SLN. In univariate analysis, luminal B subgroup showed higher rate of NSLN metastasis than other subgroup (P = 0.027. When other variables were adjusted in multivariate analysis, the molecular subtype classification was a determinant of NSLN metastasis. Relative to triple negative subgroup, both luminal A (P = 0.047 and luminal B (P = 0.010 subgroups showed a higher risk of NSLN metastasis. Otherwise, HER2 over-expression subgroup did not have a higher risk than triple negative subgroup (P = 0.183. The area under the curve (AUC value was 0.8095 for the Cambridge model. When molecular subtype classification was added to the Cambridge model, the AUC value was 0.8475. CONCLUSIONS: Except for other factors, molecular subtype classification was a determinant of NSLN metastasis in patients with a positive SLN. The predictive accuracy of mathematical models including molecular subtype should be determined in the future.

  19. Immunoelectron microscopic localization of epidermal growth factor in the eccrine and apocrine sweat glands.

    Science.gov (United States)

    Saga, K; Takahashi, M

    1992-02-01

    We studied the localization of the epidermal growth factor (EGF) in eccrine and apocrine sweat glands with light microscopic and electron microscopic immunohistochemistry. Anti-human EGF (anti-hEGF) polyclonal antiserum and anti-hEGF monoclonal antibody (MAb) were used for the study. Light microscopic immunohistochemistry with monoclonal and polyclonal antibodies showed that hEGF-like immunoreactivity was strongly positive in the myoepithelial cells and weakly positive in the secretory cells of eccrine sweat glands. In apocrine sweat glands, it was strongly positive in the secretory cells as well as in the myoepithelial cells. Immunoelectron microscopy with polyclonal antibody showed that hEGF-like immunoreactivity was present in secretory granules of apocrine secretory cells. These granules had mitochondrion-like internal structure. No reactivity was observed on the eccrine secretory cells by immunoelectron microscopy. Neither dark cell granules nor mitochondria in eccrine secretory cells were labeled with anti-hEGF antibody. In both eccrine and apocrine sweat glands, hEGF-like immunoreactivity was diffusely present in the cytoplasm of myoepithelial cells. However, nuclei and mitochondria of myoepithelial cells were devoid of immunoreactivity for hEGF. Our observations indicate that apocrine sweat glands may secrete more hEGF in the sweat than eccrine sweat glands.

  20. Unusual anogenital apocrine tumor resembling mammary-like gland adenoma in male perineum: a case report

    OpenAIRE

    Yoshioka Takako; Umekita Yoshihisa; Tanimoto Akihide; Hatanaka Kazuhito; Kanekura Takuro

    2010-01-01

    Abstract A rare case of an apocrine tumor in the male perineal region is reported. A dermal cystic lesion developed in the region between the anus and scrotum of a 74-year-old Japanese male. The cystic lesion, measuring 3.5 × 5.0 cm in size, was lined by columnar or flattened epithelium with occasional apocrine features and supported by a basal myoepithelium lining. A mural nodule, measuring 1 × 1.5 cm in size, protruded into the cystic space and consisted of a solid proliferation of tubular ...

  1. Molecular mechanism of ligand recognition by NR3 subtype glutamate receptors

    Energy Technology Data Exchange (ETDEWEB)

    Yao, Yongneng; Harrison, Chris B.; Freddolino, Peter L.; Schulten, Klaus; Mayer, Mark L. (UIUC); (NIH)

    2008-10-27

    NR3 subtype glutamate receptors have a unique developmental expression profile, but are the least well-characterized members of the NMDA receptor gene family, which have key roles in synaptic plasticity and brain development. Using ligand binding assays, crystallographic analysis, and all atom MD simulations, we investigate mechanisms underlying the binding by NR3A and NR3B of glycine and D-serine, which are candidate neurotransmitters for NMDA receptors containing NR3 subunits. The ligand binding domains of both NR3 subunits adopt a similar extent of domain closure as found in the corresponding NR1 complexes, but have a unique loop 1 structure distinct from that in all other glutamate receptor ion channels. Within their ligand binding pockets, NR3A and NR3B have strikingly different hydrogen bonding networks and solvent structures from those found in NR1, and fail to undergo a conformational rearrangement observed in NR1 upon binding the partial agonist ACPC. MD simulations revealed numerous interdomain contacts, which stabilize the agonist-bound closed-cleft conformation, and a novel twisting motion for the loop 1 helix that is unique in NR3 subunits.

  2. Molecular characterization of H6 subtype influenza viruses in southern China from 2009 to 2011.

    Science.gov (United States)

    Zou, Shumei; Gao, Rongbao; Zhang, Ye; Li, Xiaodan; Chen, Wenbing; Bai, Tian; Dong, Libo; Wang, Dayan; Shu, Yuelong

    2016-01-01

    H6 avian influenza viruses (AIVs), which are prevalent in domestic and wild birds in Eurasian countries, have been isolated from pigs, a dog and a human. Routine virological surveillance at live poultry markets or poultry farms was conducted in southern China from 2009 to 2011. This study investigated the genetic and antigenic characteristics, analyzed the receptor-binding properties and evaluated the kinetics of infectivity of the AIVs in A549, MDCK and PK15 cells. A total of 14 H6N6 and 2 H6N2 isolates were obtained from four provinces in southern China. Genetic analysis indicated two distinct hemagglutinin lineages of the H6 strains cocirculating in southern China, and these strains facilitated active evolution and reassortment among multiple influenza virus subtypes from different avian species in nature. None of these isolates grouped with the novel Taiwan H6N1 virus responsible for human infection. Receptor-binding specificity assays showed that five H6 AIVs may have acquired the ability to recognize human receptors. Growth kinetics experiments showed that EV/HB-JZ/02/10(H6N2) and EV/JX/15/10(H6N6) initially reproduced faster and achieved higher titers than other viruses, suggesting that enhanced binding to α-2,6-linked sialic acids correlated with increased viral replication in mammalian cells. Overall, the results emphasize the need for continued surveillance of H6 outbreaks and extensive characterization of H6 isolates to better understand genetic changes and their implications. PMID:27436363

  3. Molecular Characterization of Subtype H11N9 Avian Influenza Virus Isolated from Shorebirds in Brazil.

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    Renata Hurtado

    Full Text Available Migratory aquatic birds play an important role in the maintenance and spread of avian influenza viruses (AIV. Many species of aquatic migratory birds tend to use similar migration routes, also known as flyways, which serve as important circuits for the dissemination of AIV. In recent years there has been extensive surveillance of the virus in aquatic birds in the Northern Hemisphere; however in contrast only a few studies have been attempted to detect AIV in wild birds in South America. There are major flyways connecting South America to Central and North America, whereas avian migration routes between South America and the remaining continents are uncommon. As a result, it has been hypothesized that South American AIV strains would be most closely related to the strains from North America than to those from other regions in the world. We characterized the full genome of three AIV subtype H11N9 isolates obtained from ruddy turnstones (Arenaria interpres on the Amazon coast of Brazil. For all gene segments, all three strains consistently clustered together within evolutionary lineages of AIV that had been previously described from aquatic birds in North America. In particular, the H11N9 isolates were remarkably closely related to AIV strains from shorebirds sampled at the Delaware Bay region, on the Northeastern coast of the USA, more than 5000 km away from where the isolates were retrieved. Additionally, there was also evidence of genetic similarity to AIV strains from ducks and teals from interior USA and Canada. These findings corroborate that migratory flyways of aquatic birds play an important role in determining the genetic structure of AIV in the Western hemisphere, with a strong epidemiological connectivity between North and South America.

  4. Development of a molecular alternative for classical microbiological subtyping methods, Salmonella phage typing as a case study

    OpenAIRE

    Wuyts, Véronique

    2015-01-01

    Characterisation of pathogens below the subspecies or serovar level, i.e. subtyping, is essential in public health for routine surveillance of pathogens, outbreak detection and timely confinement of an outbreak. An ideal subtyping method is rapid, highly discriminative, inexpensive and robust. The classical subtyping methods for the bacterium Salmonella, a major foodborne pathogen, are phage typing, multiple-locus variable-number of tandem repeats analysis (MLVA) and pulsed-field gel electrop...

  5. Unusual anogenital apocrine tumor resembling mammary-like gland adenoma in male perineum: a case report

    Directory of Open Access Journals (Sweden)

    Yoshioka Takako

    2010-06-01

    Full Text Available Abstract A rare case of an apocrine tumor in the male perineal region is reported. A dermal cystic lesion developed in the region between the anus and scrotum of a 74-year-old Japanese male. The cystic lesion, measuring 3.5 × 5.0 cm in size, was lined by columnar or flattened epithelium with occasional apocrine features and supported by a basal myoepithelium lining. A mural nodule, measuring 1 × 1.5 cm in size, protruded into the cystic space and consisted of a solid proliferation of tubular glands with prominent apocrine secretion and basal myoepithelial cells. Immunohistochemical examination showed that the luminal cells were partially positive for gross cystic disease fluid protein 15 and human milk fat globulin 1, and the basal myoepithelial cells were positive for alpha-smooth muscle actin and S-100 protein. Estrogen and progesterone hormone receptors were focally and weakly positive for luminal epithelium. Although no mammary-like glands were present in the dermis around the tumor, this unusual apocrine tumor has been suggested to be derived from male anogenital mammary-like glands and mimic a mammary-like gland adenoma in the male perineum.

  6. The Molecular Epidemiological Study of HCV Subtypes among Intravenous Drug Users and Non-Injection Drug Users in China.

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    Jun Tao

    Full Text Available More than half of intravenous drug users (IDUs in China suffer from the Hepatitis C virus (HCV. The virus is also more prevalent in non-injection drug users (NIDUs than in the general population. However, not much is known about HCV subtype distribution in these populations.Our research team conducted a cross-sectional study in four provinces in China. We sampled 825 IDUs and 244 NIDUs (1162 total, genotyped each DU's virus, and performed a phylogenetic analysis to differentiate HCV subtypes.Nucleic acid testing (NAT determined that 82% percent (952/1162 of samples were HCV positive; we subtyped 90% (859/952 of these. We found multiple HCV subtypes: 3b (249, 29.0%, 3a (225, 26.2%, 6a (156, 18.2%, 1b (137, 15.9%, 6n (50, 5.9%, 1a (27, 3.1%, and 2a (15, 1.7%. An analysis of subtype distributions adjusted for province found statistically significant differences between HCV subtypes in IDUs and NIDUs.HCV subtypes 3b, 3a, 6a, and 1b were the most common in our study, together accounting for 89% of infections. The subtype distribution differences we found between IDUs and NIDUs suggested that sharing syringes was not the most likely pathway for HCV transmission in NIDUs. However, further studies are needed to elucidate how NIDUs were infected.

  7. In Vivo Molecular Imaging to Diagnose and Subtype Tumors through Receptor-Targeted Optically Labeled Monoclonal Antibodies

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    Yoshinori Koyama

    2007-12-01

    Full Text Available Molecular imaging of cell surface receptors can potentially diagnose tumors based on their distinct expression profiles. Using multifilter spectrally resolved optical imaging with three fluorescently labeled antibodies, we simultaneously imaged three different cell surface receptors to distinguish tumor types noninvasively. We selected tumors overexpressing different subtypes of EGFR receptor: HER-1 (A431 and HER-2 (NIH3T3/HER2+, or interleukin-2 receptor α-subunit receptor (IL-2Rα; SP2/Tac. After tumor establishment, a cocktail of three fluorescently labeled monoclonal antibodies was injected: cetuximab-Cy5 (targeting HER-1, trastuzumab-Cy7 (HER-2, daclizumab-AIexaFluor700 (IL-2Ra. Optical fluorescence imaging was performed after 24 hours with both a red filter set and three successive filter sets (yellow, red, deep red. Spectrally resolved imaging of 10 mice clearly distinguished A431, NIH3T3/HER2+, SP2-Tac tumors based on their distinct optical spectra. Three-filter sets significantly increased the signal-to-background ratio compared to a single-filter set by reducing the background signal, thus significantly improving the differentiation of each of the receptors targeted (P < .022. In conclusion, following multifilter spectrally resolved imaging, different tumor types can be simultaneously distinguished and diagnosed in vivo. Multiple filter sets increase the signal-to-noise ratio by substantially reducing the background signal, may allow more optical dyes to be resolved within the narrow limits of the near-infrared spectrum.

  8. Correlation of Histologic Subtypes and Molecular Alterations in Pulmonary Adenocarcinoma: Therapeutic and Prognostic Implications.

    Science.gov (United States)

    Kim, Jiyoon; Jang, Se Jin; Choi, Chang Min; Ro, Jae Y

    2016-09-01

    Major driver mutations of pulmonary adenocarcinomas have been identified and highlighted as actionable targets for precision cancer medicine. As phenotype is largely determined by genotype, genetic changes associated with morphologic features have recently received more attention from both pathologists and clinicians. The morphologic features of adenocarcinomas with mutations in EGFR or KRAS, or translocated ALK, have rarely been described. Pulmonary adenocarcinomas with EGFR mutations, the most common driver mutation encountered in Asian patients with pulmonary adenocarcinoma, show lepidic or papillary organotypic growth patterns. KRAS-mutated adenocarcinomas demonstrate nonorganotypic growth patterns, especially mucin-containing cells. P53 mutations are associated with aggressiveness rather than growth patterns. HER2 mutations are observed in mucinous adenocarcinoma and adenocarcinoma with micropapillary features. The histologic features of BRAF-mutated adenocarcinomas have not yet been established, but papillary, lepidic, solid, and acinar patterns have been observed. Adenocarcinomas with rearrangement of ALK, ROS1, and RET genes share similar histologic features, such as solid signet-ring cells and cribriform formation. However, adenocarcinomas with NRG1 rearrangements frequently show mucinous morphology. The histologic features and related mutations of adenocarcinomas with expression of programmed cell death-1 and programmed cell death ligands-1 may be helpful in guiding immunotherapeutic treatment. This review describes histopathologic features of adenocarcinomas and their correlation with molecular alterations. PMID:27403614

  9. Molecular characterization of HIV-1 subtype C gp-120 regions potentially involved in virus adaptive mechanisms.

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    Alessandra Cenci

    Full Text Available The role of variable regions of HIV-1 gp120 in immune escape of HIV has been investigated. However, there is scant information on how conserved gp120 regions contribute to virus escaping. Here we have studied how molecular sequence characteristics of conserved C3, C4 and V3 regions of clade C HIV-1 gp120 that are involved in HIV entry and are target of the immune response, are modulated during the disease course. We found an increase of "shifting" putative N-glycosylation sites (PNGSs in the α2 helix (in C3 and in C4 and an increase of sites under positive selection pressure in the α2 helix during the chronic stage of disease. These sites are close to CD4 and to co-receptor binding sites. We also found a negative correlation between electric charges of C3 and V4 during the late stage of disease counteracted by a positive correlation of electric charges of α2 helix and V5 during the same stage. These data allow us to hypothesize possible mechanisms of virus escape involving constant and variable regions of gp120. In particular, new mutations, including new PNGSs occurring near the CD4 and CCR5 binding sites could potentially affect receptor binding affinity and shield the virus from the immune response.

  10. Quantitative molecular analysis of sentinel lymph node may be predictive of axillary node status in breast cancer classified by molecular subtypes.

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    Simonetta Buglioni

    Full Text Available To determine the performance of intraoperative one-step nucleic acid amplification (OSNA assay in detecting sentinel lymph node metastases compared to postoperative histology taking into account breast cancer molecular classification and to evaluate whether the level of cytokeratin 19 mRNA copy number may be useful in predicting the likelihood of a positive axillary lymph node dissection. OSNA assay was performed in a prospective series of 903 consecutive sentinel lymph nodes from 709 breast cancer patients using 2 alternate slices of each sentinel lymph node. The remaining 2 slices were investigated by histology. Cytokeratin 19 mRNA copy number, which distinguishes negative cases (5000 copies, was compared to axillary lymph node dissection status and to the biological tumor profile. Concordance between OSNA and histopathology was 95%, specificity 95% and sensitivity 93%. Multiple Corresponce Analysis and logistic regression evidenced that positive axillary lymph node dissection was significantly associated with a higher cytokeratin 19 mRNA copy number (>5000; p<0.0001, HER2 subtype (p = 0.007 and lymphovascular invasion (p<0.0001. Conversely, breast cancer patients with cytokeratin 19 mRNA copy number <2000 mostly presented a luminal subtype and a negative axillary lymph node dissection. We confirmed that OSNA assay can provide standardized and reproducible results and that it represents a fast and quantitative tool for intraoperative evaluation of sentinel lymph node. Omission of axillary lymph node dissection could be proposed in patients presenting a sentinel lymph node with a cytokeratin 19 mRNA copy number <2000 and a Luminal tumor phenotype.

  11. Prognostic Value of Molecular Subtypes, Ki67 Expression and Impact of Postmastectomy Radiation Therapy in Breast Cancer Patients With Negative Lymph Nodes After Mastectomy

    International Nuclear Information System (INIS)

    Purpose: To determine whether Ki67 expression and breast cancer subtypes could predict locoregional recurrence (LRR) and influence the postmastectomy radiotherapy (PMRT) decision in breast cancer (BC) patients with pathologic negative lymph nodes (pN0) after modified radical mastectomy (MRM). Methods and Materials: A total of 699 BC patients with pN0 status after MRM, treated between 2001 and 2008, were identified from a prospective database in a single institution. Tumors were classified by intrinsic molecular subtype as luminal A or B, HER2+, and triple-negative (TN) using estrogen, progesterone, and HER2 receptors. Multivariate Cox analysis was used to determine the risk of LRR associated with intrinsic subtypes and Ki67 expression, adjusting for known prognostic factors. Results: At a median follow-up of 56 months, 17 patients developed LRR. Five-year LRR-free survival and overall survival in the entire population were 97%, and 94.7%, respectively, with no difference between the PMRT (n=191) and no-PMRT (n=508) subgroups. No constructed subtype was associated with an increased risk of LRR. Ki67 >20% was the only independent prognostic factor associated with increased LRR (hazard ratio, 4.18; 95% CI, 1.11-15.77; P<.0215). However, PMRT was not associated with better locoregional control in patients with proliferative tumors. Conclusions: Ki67 expression but not molecular subtypes are predictors of locoregional recurrence in breast cancer patients with negative lymph nodes after MRM. The benefit of adjuvant RT in patients with proliferative tumors should be further investigated in prospective studies.

  12. Prognostic Value of Molecular Subtypes, Ki67 Expression and Impact of Postmastectomy Radiation Therapy in Breast Cancer Patients With Negative Lymph Nodes After Mastectomy

    Energy Technology Data Exchange (ETDEWEB)

    Selz, Jessica, E-mail: chaumontjessica@yahoo.fr [Department of Radiation Oncology, Institut Curie, Hopital Rene Huguenin, Saint Cloud (France); Stevens, Denise; Jouanneau, Ludivine [Department of Medical Statistics, Institut Curie, Hopital Rene Huguenin, Saint Cloud (France); Labib, Alain [Department of Radiation Oncology, Institut Curie, Hopital Rene Huguenin, Saint Cloud (France); Le Scodan, Romuald [Department of Radiation Oncology, Centre Hospitalier Prive Saint Gregoire, Saint Gregoire (France)

    2012-12-01

    Purpose: To determine whether Ki67 expression and breast cancer subtypes could predict locoregional recurrence (LRR) and influence the postmastectomy radiotherapy (PMRT) decision in breast cancer (BC) patients with pathologic negative lymph nodes (pN0) after modified radical mastectomy (MRM). Methods and Materials: A total of 699 BC patients with pN0 status after MRM, treated between 2001 and 2008, were identified from a prospective database in a single institution. Tumors were classified by intrinsic molecular subtype as luminal A or B, HER2+, and triple-negative (TN) using estrogen, progesterone, and HER2 receptors. Multivariate Cox analysis was used to determine the risk of LRR associated with intrinsic subtypes and Ki67 expression, adjusting for known prognostic factors. Results: At a median follow-up of 56 months, 17 patients developed LRR. Five-year LRR-free survival and overall survival in the entire population were 97%, and 94.7%, respectively, with no difference between the PMRT (n=191) and no-PMRT (n=508) subgroups. No constructed subtype was associated with an increased risk of LRR. Ki67 >20% was the only independent prognostic factor associated with increased LRR (hazard ratio, 4.18; 95% CI, 1.11-15.77; P<.0215). However, PMRT was not associated with better locoregional control in patients with proliferative tumors. Conclusions: Ki67 expression but not molecular subtypes are predictors of locoregional recurrence in breast cancer patients with negative lymph nodes after MRM. The benefit of adjuvant RT in patients with proliferative tumors should be further investigated in prospective studies.

  13. Functional and molecular evidence for Kv7 channel subtypes in human detrusor from patients with and without bladder outflow obstruction.

    Directory of Open Access Journals (Sweden)

    Julie Svalø

    Full Text Available The aim of the study was to investigate whether Kv7 channels and their ancillary β-subunits, KCNE, are functionally expressed in the human urinary bladder. Kv7 channels were examined at the molecular level and by functional studies using RT-qPCR and myography, respectively. We found mRNA expression of KCNQ1, KCNQ3-KCNQ5 and KCNE1-5 in the human urinary bladder from patients with normal bladder function (n = 7 and in patients with bladder outflow obstruction (n = 3. Interestingly, a 3.4-fold up-regulation of KCNQ1 was observed in the latter. The Kv7 channel subtype selective modulators, ML277 (activator of Kv7.1 channels, 10 μM and ML213 (activator of Kv7.2, Kv7.4, Kv7.4/7.5 and Kv7.5 channels, 10 μM, reduced the tone of 1 μM carbachol pre-constricted bladder strips. XE991 (blocker of Kv7.1-7.5 channels, 10 μM had opposing effects as it increased contractions achieved with 20 mM KPSS. Furthermore, we investigated if there is interplay between Kv7 channels and β-adrenoceptors. Using cumulative additions of isoprenaline (β-adrenoceptor agonist and forskolin (adenylyl cyclase activator in combination with the Kv7 channel activator and blocker, retigabine and XE991, we did not find interplay between Kv7 channels and β-adrenoceptors in the human urinary bladder. The performed gene expression analysis combined with the organ bath studies imply that compounds that activate Kv7 channels could be useful for treatment of overactive bladder syndrome.

  14. Alcohol consumption and risk of breast cancer by molecular subtype: Prospective analysis of the nurses' health study after 26 years of follow-up.

    Science.gov (United States)

    Hirko, Kelly A; Chen, Wendy Y; Willett, Walter C; Rosner, Bernard A; Hankinson, Susan E; Beck, Andrew H; Tamimi, Rulla M; Eliassen, A Heather

    2016-03-01

    Alcohol consumption is a consistent risk factor for breast cancer, although it is unclear whether the association varies by breast cancer molecular subtype. We investigated associations between cumulative average alcohol intake and risk of breast cancer by molecular subtype among 105,972 women in the prospective Nurses' Health Study cohort, followed from 1980 to 2006. Breast cancer molecular subtypes were defined according to estrogen receptor (ER), progesterone receptor, human epidermal growth factor 2 (HER2), cytokeratin 5/6, and epidermal growth factor status from immunostained tumor microarrays in combination with histologic grade. Multivariable Cox proportional hazards models were used to estimate hazard ratios (HR) and 95% confidence intervals (CI). Competing risk analyses were used to assess heterogeneity by subtype. We observed suggestive heterogeneity in associations between alcohol and breast cancer by subtype (phet  = 0.06). Alcohol consumers had an increased risk of luminal A breast cancers [n = 1,628 cases, per 10 g/day increment HR (95%CI) = 1.10(1.05-1.15)], and an increased risk that was suggestively stronger for HER2-type breast cancer [n = 160 cases, HR (95%CI) = 1.16(1.02-1.33)]. We did not observe statistically significant associations between alcohol and risk of luminal B [n = 631 cases, HR (95%CI) = 1.08(0.99-1.16)], basal-like [n = 254 cases, HR (95%CI) = 0.90(0.77-1.04)], or unclassified [n = 87 cases, HR (95%CI) = 0.90(0.71-1.14)] breast cancer. Alcohol consumption was associated with increased risk of luminal A and HER2-type breast cancer, but not significantly associated with other subtypes. Given that ERs are expressed in luminal A but not in HER2-type tumors, our findings suggest that other mechanisms may play a role in the association between alcohol and breast cancer.

  15. Reproductive risk factors in relation to molecular subtypes of breast cancer: Results from the nurses' health studies.

    Science.gov (United States)

    Sisti, Julia S; Collins, Laura C; Beck, Andrew H; Tamimi, Rulla M; Rosner, Bernard A; Eliassen, A Heather

    2016-05-15

    Several intrinsic breast cancer subtypes, possibly representing unique etiologic processes, have been identified by gene expression profiles. Evidence suggests that associations with reproductive risk factors may vary by breast cancer subtype. In the Nurses' Health Studies, we prospectively examined associations of reproductive factors with breast cancer subtypes defined using immunohistochemical staining of tissue microarrays. Multivariate-adjusted Cox proportional hazard models were used to estimate hazard ratios (HRs) and 95% confidence intervals (CIs). Over follow-up, we identified 2,063 luminal A, 1,008 luminal B, 209 HER2-enriched, 378 basal-like and 110 unclassified tumors. Many factors appeared associated with luminal A tumors, including ages at menarche (p(heterogeneity) = 0.65) and menopause (p(heterogeneity) = 0.05), and current HT use (p(heterogeneity) = 0.33). Increasing parity was not associated with any subtype (p(heterogeneity) = 0.76), though age at first birth was associated with luminal A tumors only (per 1-year increase HR = 1.03 95%CI (1.02-1.05), p(heterogeneity)  = 0.04). Though heterogeneity was not observed, duration of lactation was inversely associated with risk of basal-like tumors only (7+ months vs. never HR = 0.65 95%CI (0.49-0.87), ptrend = 0.02), p(heterogeneity) = 0.27). Years between menarche and first birth was strongly positively associated with luminal A and non-luminal subtypes (e.g. 22-year interval vs. nulliparous HR = 1.80, 95%CI (1.08-3.00) for basal-like tumors; p(heterogeneity) = 0.003), and evidence of effect modification by breastfeeding was observed. In summary, many reproductive risk factors for breast cancer appeared most strongly associated with the luminal A subtype. Our results support previous reports that lactation is protective against basal-like tumors, representing a potential modifiable risk factor for this aggressive subtype. PMID:26684063

  16. Reproductive risk factors in relation to molecular subtypes of breast cancer: Results from the nurses' health studies.

    Science.gov (United States)

    Sisti, Julia S; Collins, Laura C; Beck, Andrew H; Tamimi, Rulla M; Rosner, Bernard A; Eliassen, A Heather

    2016-05-15

    Several intrinsic breast cancer subtypes, possibly representing unique etiologic processes, have been identified by gene expression profiles. Evidence suggests that associations with reproductive risk factors may vary by breast cancer subtype. In the Nurses' Health Studies, we prospectively examined associations of reproductive factors with breast cancer subtypes defined using immunohistochemical staining of tissue microarrays. Multivariate-adjusted Cox proportional hazard models were used to estimate hazard ratios (HRs) and 95% confidence intervals (CIs). Over follow-up, we identified 2,063 luminal A, 1,008 luminal B, 209 HER2-enriched, 378 basal-like and 110 unclassified tumors. Many factors appeared associated with luminal A tumors, including ages at menarche (p(heterogeneity) = 0.65) and menopause (p(heterogeneity) = 0.05), and current HT use (p(heterogeneity) = 0.33). Increasing parity was not associated with any subtype (p(heterogeneity) = 0.76), though age at first birth was associated with luminal A tumors only (per 1-year increase HR = 1.03 95%CI (1.02-1.05), p(heterogeneity)  = 0.04). Though heterogeneity was not observed, duration of lactation was inversely associated with risk of basal-like tumors only (7+ months vs. never HR = 0.65 95%CI (0.49-0.87), ptrend = 0.02), p(heterogeneity) = 0.27). Years between menarche and first birth was strongly positively associated with luminal A and non-luminal subtypes (e.g. 22-year interval vs. nulliparous HR = 1.80, 95%CI (1.08-3.00) for basal-like tumors; p(heterogeneity) = 0.003), and evidence of effect modification by breastfeeding was observed. In summary, many reproductive risk factors for breast cancer appeared most strongly associated with the luminal A subtype. Our results support previous reports that lactation is protective against basal-like tumors, representing a potential modifiable risk factor for this aggressive subtype.

  17. Pharmacogenetics of human ABC transporter ABCC11:new insights into apocrine gland growth and metabolite secretion

    Directory of Open Access Journals (Sweden)

    Toshihisa eIshikawa

    2013-01-01

    Full Text Available Cell secretion is an important physiological process that ensures smooth metabolic activities and tissue repair as well as growth and immunological functions in the body. Apocrine secretion occurs when the secretory process is accomplished with a partial loss of cell cytoplasm. The secretory materials are contained within secretory vesicles and are released during secretion as cytoplasmic fragments into the glandular lumen or interstitial space. The recent finding that the nonsynonymous SNP 538G>A (rs17822931; Gly180Arg in the ABCC11 gene determines the type of earwax in humans has shed light on the novel function of this ABC transporter in apocrine glands. The wild type (Gly180 of ABCC11 is associated with wet-type earwax, axillary osmidrosis, and colostrum secretion from the mammary gland as well as the potential risk of mastopathy. Furthermore, the SNP (538G>A in the ABCC11 gene is suggested to be a clinical biomarker for the prediction of chemotherapeutic efficacy. The aim of this review article is to provide an overview on the discovery and characterization of genetic polymorphisms in the human ABCC11 gene and to explain the impact of ABCC11 538G>A on the apocrine phenotype as well as the anthropological aspect of this SNP in the ABCC11 gene and patients’ response to nucleoside-based chemotherapy.

  18. Luminal B tumors are the most frequent molecular subtype in breast cancer of North African women: an immunohistochemical profile study from Morocco

    Directory of Open Access Journals (Sweden)

    El Fatemi Hinde

    2012-12-01

    Full Text Available Abstract Background Breast cancer may be classified into luminal A, luminal B, HER2+/ER-, basal-like and normal-like subtypes based on gene expression profiling or immunohistochemical (IHC characteristics. The aim of our study is to show the molecular profile characteristic of breast cancer in the North African population of Morocco. This work showed preliminary results and correlations with clinicopathological and histological parameters. Three hundred and ninety primary breast carcinomas tumor tissues were immunostained for ER, PR, HER2, CK5/6, CK8/18 and Ki67 using paraffin tissue. Methods We reviewed 390 cases of breast cancer diagnosed on January 2008 to December 2011 at the Department of pathology, Hassan II teaching hospital, Fez, Morocco. Age, size tumor, metastatic profile, node involvement profile, histological type and immunohistochemical profile were studied. Results The average age was 46 years; our patients were diagnosed late with a high average tumor size. Luminal B subtype was more prevalent (41.8%, followed by luminal A (30.5%, basal-like (13, 6%, Her2-overexpressing (9, 2%, and unclassified subtype (4.9%. Conclusion This study showed that molecular classification and biological profile may be different according to geographical distribution, to encourage further studies to know the genomic profile of tumors and the environment. Virtual slide http://www.diagnosticpathology.diagnomx.eu/vs/1675272504826544

  19. In Silico Prediction of Estrogen Receptor Subtype Binding Affinity and Selectivity Using Statistical Methods and Molecular Docking with 2-Arylnaphthalenes and 2-Arylquinolines

    Directory of Open Access Journals (Sweden)

    Yonghua Wang

    2010-09-01

    Full Text Available Over the years development of selective estrogen receptor (ER ligands has been of great concern to researchers involved in the chemistry and pharmacology of anticancer drugs, resulting in numerous synthesized selective ER subtype inhibitors. In this work, a data set of 82 ER ligands with ERα and ERβ inhibitory activities was built, and quantitative structure-activity relationship (QSAR methods based on the two linear (multiple linear regression, MLR, partial least squares regression, PLSR and a nonlinear statistical method (Bayesian regularized neural network, BRNN were applied to investigate the potential relationship of molecular structural features related to the activity and selectivity of these ligands. For ERα and ERβ, the performances of the MLR and PLSR models are superior to the BRNN model, giving more reasonable statistical properties (ERα: for MLR, Rtr2 = 0.72, Qte2 = 0.63; for PLSR, Rtr2 = 0.92, Qte2 = 0.84. ERβ: for MLR, Rtr2 = 0.75, Qte2 = 0.75; for PLSR, Rtr2 = 0.98, Qte2 = 0.80. The MLR method is also more powerful than other two methods for generating the subtype selectivity models, resulting in Rtr2 = 0.74 and Qte2 = 0.80. In addition, the molecular docking method was also used to explore the possible binding modes of the ligands and a relationship between the 3D-binding modes and the 2D-molecular structural features of ligands was further explored. The results show that the binding affinity strength for both ERα and ERβ is more correlated with the atom fragment type, polarity, electronegativites and hydrophobicity. The substitutent in position 8 of the naphthalene or the quinoline plane and the space orientation of these two planes contribute the most to the subtype selectivity on the basis of similar hydrogen bond interactions between binding ligands and both ER subtypes. The QSAR models built together with the docking procedure should be of great advantage for screening and designing ER ligands with improved affinity

  20. Molecular epidemiology of 58 new African human T-cell leukemia virus type 1 (HTLV-1) strains: identification of a new and distinct HTLV-1 molecular subtype in Central Africa and in Pygmies.

    Science.gov (United States)

    Mahieux, R; Ibrahim, F; Mauclere, P; Herve, V; Michel, P; Tekaia, F; Chappey, C; Garin, B; Van Der Ryst, E; Guillemain, B; Ledru, E; Delaporte, E; de The, G; Gessain, A

    1997-02-01

    To gain new insights on the origin, evolution, and modes of dissemination of human T-cell leukemia virus type I (HTLV-1), we performed a molecular analysis of 58 new African HTLV-1 strains (18 from West Africa, 36 from Central Africa, and 4 from South Africa) originating from 13 countries. Of particular interest were eight strains from Pygmies of remote areas of Cameroon and the Central African Republic (CAR), considered to be the oldest inhabitants of these regions. Eight long-term activated T-cell lines producing HTLV-1 gag and env antigens were established from peripheral blood mononuclear cell cultures of HTLV-1 seropositive individuals, including three from Pygmies. A fragment of the env gene encompassing most of the gp21 transmembrane region was sequenced for the 58 new strains, while the complete long terminal repeat (LTR) region was sequenced for 9 strains, including 4 from Pygmies. Comparative sequence analyses and phylogenetic studies performed on both the env and LTR regions by the neighbor-joining and DNA parsimony methods demonstrated that all 22 strains from West and South Africa belong to the widespread cosmopolitan subtype (also called HTLV-1 subtype A). Within or alongside the previously described Zairian cluster (HTLV-1 subtype B), we discovered a number of new HTLV-1 variants forming different subgroups corresponding mainly to the geographical origins of the infected persons, Cameroon, Gabon, and Zaire. Six of the eight Pygmy strains clustered together within this Central African subtype, suggesting a common origin. Furthermore, three new strains (two originating from Pygmies from Cameroon and the CAR, respectively, and one from a Gabonese individual) were particularly divergent and formed a distinct new phylogenetic cluster, characterized by specific mutations and occupying in most analyses a unique phylogenetic position between the large Central African genotype (HTLV-1 subtype B) and the Melanesian subtype (HTLV-1 subtype C). We have

  1. The Related Study of Sentinel Lymph Node Metastasis of Breast Cancer and Molecular Subtypes%乳腺癌前哨淋巴结转移与分子亚型的相关研究

    Institute of Scientific and Technical Information of China (English)

    康淑娟; 马立辉; 王助新; 孟庆来; 张宏旭; 王明辉; 张杰; 胡大为

    2016-01-01

    Objective Investigate the relationship between molecular subtypes and sentinel lymph node metastasis of breast cancer.Methods A retrospective analysis was conducted from January 2014 to May 2015 among 167 patients with breast cancer diagnosis,all patients with sentinel lymph node biopsy and with complete immunohistochemical data,and classification of molecular subtypes of breast cancer patients was based on the immunohistochemistry results:Luminal A subtype,Luminal B(HER2-)subtype,Luminal B(HER2+)subtype,HER2 overexpression subtype,triple negative subtype.Results The probability of sentinel lymph node metastasis of HER2 overexpression subtype was the highest as while of the Luminal A subtype was the lowest.Conclusion Sentinel lymph node metastasis of breast cancer has a correlation with breast cancer molecular subtypes,research on different molecular subtypes of breast cancer has a certain characteristic clinical significance.%目的:探讨早期乳腺癌前哨淋巴结转移与乳腺癌分子亚型间的关系。方法回顾性分析本科2013年11月~2015年2月确诊的153例早期乳腺癌患者,所有患者均进行前哨淋巴结活检术,并具有完整的免疫组化资料,依据免疫组化结果对这些早期患者进行乳腺癌分子亚型分类:Luminal A型、Luminal B(HER2-)型、Luminal B(HER2+)型、HER2过表达型、三阴型。结果HER2过表达型前哨淋巴结转移率最高;Luminal A型前哨淋巴结转移率最低。结论乳腺癌前哨淋巴结转移与分子亚型间存在相关性,对不同分子亚型乳腺癌特点的研究有一定临床意义。

  2. Subtype-independent near full-length HIV-1 genome sequencing and assembly to be used in large molecular epidemiological studies and clinical management

    Directory of Open Access Journals (Sweden)

    Sebastian Grossmann

    2015-06-01

    Full Text Available Introduction: HIV-1 near full-length genome (HIV-NFLG sequencing from plasma is an attractive multidimensional tool to apply in large-scale population-based molecular epidemiological studies. It also enables genotypic resistance testing (GRT for all drug target sites allowing effective intervention strategies for control and prevention in high-risk population groups. Thus, the main objective of this study was to develop a simplified subtype-independent, cost- and labour-efficient HIV-NFLG protocol that can be used in clinical management as well as in molecular epidemiological studies. Methods: Plasma samples (n=30 were obtained from HIV-1B (n=10, HIV-1C (n=10, CRF01_AE (n=5 and CRF01_AG (n=5 infected individuals with minimum viral load >1120 copies/ml. The amplification was performed with two large amplicons of 5.5 kb and 3.7 kb, sequenced with 17 primers to obtain HIV-NFLG. GRT was validated against ViroSeqTM HIV-1 Genotyping System. Results: After excluding four plasma samples with low-quality RNA, a total of 26 samples were attempted. Among them, NFLG was obtained from 24 (92% samples with the lowest viral load being 3000 copies/ml. High (>99% concordance was observed between HIV-NFLG and ViroSeqTM when determining the drug resistance mutations (DRMs. The N384I connection mutation was additionally detected by NFLG in two samples. Conclusions: Our high efficiency subtype-independent HIV-NFLG is a simple and promising approach to be used in large-scale molecular epidemiological studies. It will facilitate the understanding of the HIV-1 pandemic population dynamics and outline effective intervention strategies. Furthermore, it can potentially be applicable in clinical management of drug resistance by evaluating DRMs against all available antiretrovirals in a single assay.

  3. Clasificación en subtipos moleculares de tumores de mama de pequeños animales mediante métodos inmunohistoquímicos Classification in molecular subtypes of breast tumors of small animals through immunohistochemical methods

    Directory of Open Access Journals (Sweden)

    Mª V. Ortega García

    2013-03-01

    methods in mammary tumors of small animals to classify them in molecular subtypes and their association with the invasion, grade and histological type of the malignancies. Material and Methods: samples of malignant mammary tumors, 10 from canine species and 3 from feline ones. Internal positive control: non-tumoral mammary gland adjacent to the malignancy. Results: 23% (3/13 of the tumors were of the luminal B subtype, 23% (3/13 were HER2 positive, 46% (6/13 were basal types and 7,6% (1/13 were unclassifiable because they did not express any of the tested tumor markers. None of the cases belonged to the luminal A subtype. The 6 basal tumors were grade II or III and presented only stromal infiltration or vascular invasion as well. Two thirds of the HER2 positive tumors presented stromal infiltration and half the tumors were grade II. Two thirds of luminal B tumors were grade II or III. All internal controls were positive. There were no significant differences in the distribution of the molecular subtypes among the different groups of the invasion (p-value=0.26 and malignancy grade variables (p-value=0.42. There were differences of borderline statistical significance in the distribution of the molecular subtypes among the different groups of the histological type variable (p-value=0.08. Conclusions: the application of the antibodies panel has allowed to find 4 (luminal B, HER2, basal and unclassified out of 5 possible molecular subtypes.

  4. Apocrine Sweat Gland Ductal Adenoma with Sebaceous Differentiation in a Dog

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    Masaki Michishita

    2013-01-01

    Full Text Available A 7-year-old male, Border Collie, developed a firm mass, measuring approximately 1 cm in diameter, in the left buccal skin. Histologically, the mass was composed of ductal structures lined by bilayered luminal epithelial and basaloid tumor cells along with a few nests of sebaceous cells. Immunohistochemical staining revealed that the luminal epithelial tumor cells were positive for cytokeratin (CK, CAM5.2 and CK19 but not for CK14 or p63. In contrast, the basaloid tumor cells were positive for CK14, p63, and αSMA but not for CK19 or CAM5.2. CK8 expression was observed in both luminal epithelial and basaloid tumor cells. The tumor cells with sebaceous differentiation were positive for CK14 but not for the other markers. This is the first case of an apocrine sweat gland ductal adenoma with sebaceous differentiation occurring in the buccal skin of a dog.

  5. Molecular Subtypes in Head and Neck Cancer Exhibit Distinct Patterns of Chromosomal Gain and Loss of Canonical Cancer Genes

    OpenAIRE

    Walter, Vonn; Yin, Xiaoying; Wilkerson, Matthew D.; Christopher R Cabanski; Zhao, Ni; Du, Ying; Ang, Mei Kim; Hayward, Michele C.; Salazar, Ashley H.; Hoadley, Katherine A; Fritchie, Karen; Sailey, Charles G.; Weissler, Mark C.; William W Shockley; Zanation, Adam M.

    2013-01-01

    Head and neck squamous cell carcinoma (HNSCC) is a frequently fatal heterogeneous disease. Beyond the role of human papilloma virus (HPV), no validated molecular characterization of the disease has been established. Using an integrated genomic analysis and validation methodology we confirm four molecular classes of HNSCC (basal, mesenchymal, atypical, and classical) consistent with signatures established for squamous carcinoma of the lung, including deregulation of the KEAP1/NFE2L2 oxidative ...

  6. Classifications within molecular subtypes enables identification of BRCA1/BRCA2 mutation carriers by RNA tumor profiling.

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    Martin J Larsen

    Full Text Available Pathogenic germline mutations in BRCA1 or BRCA2 are detected in less than one third of families with a strong history of breast cancer. It is therefore expected that mutations still remain undetected by currently used screening methods. In addition, a growing number of BRCA1/2 sequence variants of unclear pathogen significance are found in the families, constituting an increasing clinical challenge. New methods are therefore needed to improve the detection rate and aid the interpretation of the clinically uncertain variants. In this study we analyzed a series of 33 BRCA1, 22 BRCA2, and 128 sporadic tumors by RNA profiling to investigate the classification potential of RNA profiles to predict BRCA1/2 mutation status. We found that breast tumors from BRCA1 and BRCA2 mutation carriers display characteristic RNA expression patterns, allowing them to be distinguished from sporadic tumors. The majority of BRCA1 tumors were basal-like while BRCA2 tumors were mainly luminal B. Using RNA profiles, we were able to distinguish BRCA1 tumors from sporadic tumors among basal-like tumors with 83% accuracy and BRCA2 from sporadic tumors among luminal B tumors with 89% accuracy. Furthermore, subtype-specific BRCA1/2 gene signatures were successfully validated in two independent data sets with high accuracies. Although additional validation studies are required, indication of BRCA1/2 involvement ("BRCAness" by RNA profiling could potentially be valuable as a tool for distinguishing pathogenic mutations from benign variants, for identification of undetected mutation carriers, and for selecting patients sensitive to new therapeutics such as PARP inhibitors.

  7. Short Communication: Phylogenetic and Molecular Characterization of Six Full-Length HIV-1 Genomes from India Reveals a Monophyletic Lineage of Indian Sub-Subtype A1.

    Science.gov (United States)

    Pandey, Sudhanshu Shekhar; Cherian, Sarah; Thakar, Madhuri; Paranjape, Ramesh S

    2016-05-01

    Although HIV-1 epidemic in India is mainly driven by subtype C, subtype A has been reported for over two decades. This is the first comprehensive analysis of sequences of HIV-1 subtype A from India, based on the near full-length genome sequences of six different HIV-1 subtype A Indian isolates along with available partial gene sequences from India and global sequences. The phylogenetic analyses revealed the convergence of all Indian whole-genome sequences and majority of the partial gene sequences to a single node with the sequences most closely related to African sub-subtype A1. The presence of the signature motifs consistent with those observed in subtype A and CTL epitopes characterized specifically for subtype A1 were observed among the study sequences. Deletion of LY amino acid of LYPXnL motif of p6gag and one amino acid in V3 loop have been observed among the study isolates, which have also been observed in a few sequences from East Africa. Overall, the results are indicative of a monophyletic lineage or founder effect of the Indian epidemic due to sub-subtype A1 and supportive of a possible migration of subtype A1 into India from East Africa. PMID:26756665

  8. Molecular sub-typing suggests that the environment of rehabilitation centers may be a potential source of Aspergillus fumigatus infecting rehabilitating seabirds.

    Science.gov (United States)

    Burco, Julia D; Etienne, Kizee A; Massey, J Gregory; Ziccardi, Michael H; Balajee, S Arunmozhi

    2012-01-01

    Aspergillosis remains a major cause of infection-related avian mortality in birds that are debilitated and undergoing rehabilitation for release into the wild. This study was designed to understand the source of avian aspergillosis in seabirds undergoing rehabilitation at selected northern California aquatic bird rehabilitation centers. Air, surface and water sampling was performed between August 2007 and July 2008 in three such centers and selected natural seabird loafing sites. Average air Aspergillus fumigatus counts were at least nine times higher in samples obtained from the rehabilitation sites (M = 7.34, SD = 9.78 CFU/m(3)), when compared to those found at natural sites (M = 0.76, SD = 2.24 CFU/m(3)), t (205) = -5.99, P < 0.001. A total of 37 A. fumigatus isolates from birds with confirmed aspergillosis and 42 isolates from environmental samples were identified using both morphological and molecular methods, and subsequently sub-typed using an eight-locus microsatellite panel with the neighbor joining algorithm. Results of the study demonstrated the presence of five clonal groups, 13 genotypically related clusters, and 59 distinct genotypes. Six of the 13 genotypically related clusters contained matching genotypes between clinical isolates and local environmental isolates from the rehabilitation center in which these birds were housed. We present evidence that the environment of rehabilitation centers may be a source for A. fumigatus infection in rehabilitated seabirds. PMID:21756021

  9. The expression pattern of small nucleolar and small Cajal body-specific RNAs characterizes distinct molecular subtypes of multiple myeloma

    International Nuclear Information System (INIS)

    Small nucleolar RNAs (snoRNAs) and small Cajal body-specific RNAs (scaRNAs) are non-coding RNAs involved in the maturation of other RNA molecules and generally located in the introns of host genes. It is now emerging that altered sno/scaRNAs expression may have a pathological role in cancer. This study elucidates the patterns of sno/scaRNAs expression in multiple myeloma (MM) by profiling purified malignant plasma cells from 55 MMs, 8 secondary plasma cell leukemias (sPCLs) and 4 normal controls. Overall, a global sno/scaRNAs downregulation was found in MMs and, even more, in sPCLs compared with normal plasma cells. Whereas SCARNA22 resulted the only sno/scaRNA characterizing the translocation/cyclin D4 (TC4) MM, TC2 group displayed a distinct sno/scaRNA signature overexpressing members of SNORD115 and SNORD116 families located in a region finely regulated by an imprinting center at 15q11, which, however, resulted overall hypomethylated in MMs independently of the SNORD115 and SNORD116 expression levels. Finally, integrative analyses with available gene expression and genome-wide data revealed the occurrence of significant sno/scaRNAs/host genes co-expression and the putative influence of allelic imbalances on specific snoRNAs expression. Our data extend the current view of sno/scaRNAs deregulation in cancer and add novel information to the bio-molecular complexity of plasma cell dyscrasias

  10. The expression pattern of small nucleolar and small Cajal body-specific RNAs characterizes distinct molecular subtypes of multiple myeloma

    Science.gov (United States)

    Ronchetti, D; Todoerti, K; Tuana, G; Agnelli, L; Mosca, L; Lionetti, M; Fabris, S; Colapietro, P; Miozzo, M; Ferrarini, M; Tassone, P; Neri, A

    2012-01-01

    Small nucleolar RNAs (snoRNAs) and small Cajal body-specific RNAs (scaRNAs) are non-coding RNAs involved in the maturation of other RNA molecules and generally located in the introns of host genes. It is now emerging that altered sno/scaRNAs expression may have a pathological role in cancer. This study elucidates the patterns of sno/scaRNAs expression in multiple myeloma (MM) by profiling purified malignant plasma cells from 55 MMs, 8 secondary plasma cell leukemias (sPCLs) and 4 normal controls. Overall, a global sno/scaRNAs downregulation was found in MMs and, even more, in sPCLs compared with normal plasma cells. Whereas SCARNA22 resulted the only sno/scaRNA characterizing the translocation/cyclin D4 (TC4) MM, TC2 group displayed a distinct sno/scaRNA signature overexpressing members of SNORD115 and SNORD116 families located in a region finely regulated by an imprinting center at 15q11, which, however, resulted overall hypomethylated in MMs independently of the SNORD115 and SNORD116 expression levels. Finally, integrative analyses with available gene expression and genome-wide data revealed the occurrence of significant sno/scaRNAs/host genes co-expression and the putative influence of allelic imbalances on specific snoRNAs expression. Our data extend the current view of sno/scaRNAs deregulation in cancer and add novel information to the bio-molecular complexity of plasma cell dyscrasias. PMID:23178508

  11. Clinical Significance of Approximated Molecular Subtypes of Invasive Breast Cancer%浸润性乳腺癌近似分子亚型的临床意义

    Institute of Scientific and Technical Information of China (English)

    耿其荣; 刘冬耕; 史艳侠; 向锦; 吕跃

    2009-01-01

    [Objective] To investigate the clinical significance of approximated molecular subtype.[Methods] Four different subtypes were defined by immunohistochemical (IHC) markers as estrogen receptor (ER),progesterone receptor (PR) and HER2.Clinical characteristics as distribution,age,menopausal status,histopathologic type and grading,tumor size,lymph node status,time to and place of first tumor recurrence were analyzed.[Results] Among all 703 cases,Luminal A was the majority (51.5%) and the least were Luminal B and HER2+.90.8% the patients were less than 59 years old with Luminal A.Different subtype has different histopathologic grading.Luminal A was more than others among grading 1 tumors and it has more T1 tumors,while T4 tumors was most among HER2+ ones.Lymph nodes metastasis has no significant difference between different groups,other than high proportion tendency of N3 stage in Luminal B and HER2+.In addition,Luminal A has the longest time to the first recurrence while HER2+ was the shortest.Moreover,HER2+ and Basal-like have high rates of lung metastasis.Different from foreign reports,the distribution of the first recurrent place and distant metastases have no significant difference.[Conclusion] The classification of breast cancer approximated molecular subtype defined by IHC markers was feasible.The distribution is similar to other countries.Luminal A has rather better clinical characteristics while HER2+ and Basal-like have high rates of lung metastasis.However,Luminal A has the highest proportion of young patients,which is different from other countries.%[目的] 探讨浸润性乳腺癌近似分子亚型的临床意义. [方法] 回顾性分析浸润性乳腺癌患者,依据免疫组化雌激素受体(ER)、孕激素受体(PR)、HER2水平将其近似划分为Luminal A (ER+ 和/或 PR+,HER2-)、Luminal B (ER+ 和/或 PR+,HER2+)、HER2+(EP-,PR-,HER2+)和Basal-like(EP-,PR-,HER2-) 4个分子亚型,各362、107、86和148例,对比分析该4型患者的分布比例

  12. 乳腺癌的分子分型与临床病理特征及预后的关系%Correlation of molecular subtypes with clinicopathologic features and prognosis in breast cancer

    Institute of Scientific and Technical Information of China (English)

    曹静; 吕志排; 雷冬梅; 楚天骄; 郝志伟

    2013-01-01

    Objective:To investigate the correlation between molecular subtypes,clinicopathologic features and prognosis in breast carcinoma.Methods:Data from 324 female patients with primary breast cancer admitted from Jan.2007 to Dec.2007 were retrospectively analyzed.According to immunohistochemical markers,324 cases of breast cancer were classified into four different subtypes:Luminal A,Luminal B,HER2/neu and basal-like subtype.Relationships between molecular subtypes and clinicopathological characteristics were analyzed,and the disease free survival (DFS) was studied.Results:Molecular subtypes had no correlation with age,tumors size,lymph node metastasis in patients with primary breast cancer (P>0.05).However,there was a correlation of molecular subtypes with histological grade (P<0.05).Patients were followed up for 11~72 months.DFS had a correlation with lymph node metastasis and molecular subtypes (P<0.05),and had no correlation with age,tumors size and histological grade (P>0.05).There was a significant difference in DFS between different molecular subtypes (,P<0.05).Conclusions:Molecular classification can predict the prognosis of patient.Luminal A had a better prognosis than the other three types,and HER2/neu was the worst.%目的:探讨乳腺癌分子分型与临床病理特征及预后之间的关系.方法:回顾性分析2007年我院324例原发性乳腺癌患者的临床病理资料.根据免疫组化结果,将乳腺癌分为Luminal A型、Luminal B型、HER2/neu型及basal-like型.观察乳腺癌分子分型与临床病理特征间的相互关系,比较各型患者术后的无病生存期.结果:乳腺癌的分子分型与年龄分组、肿瘤直径、淋巴结转移无关,与组织学分级相关(P<0.05).患者随访11~72个月,无病生存期与年龄分组、组织学分级无关,与淋巴结转移状态、分子分型相关.不同分子分型患者间的无病生存期存在统计学差异.结论:乳腺癌的分

  13. The endogenous and reactive depression subtypes revisited: integrative animal and human studies implicate multiple distinct molecular mechanisms underlying major depressive disorder

    OpenAIRE

    Malki, Karim; Keers, Robert; Tosto, Maria Grazia; Lourdusamy, Anbarasu; Carboni, Lucia; Domenici, Enrico; Uher, Rudolf; McGuffin, Peter; Schalkwyk, Leonard C

    2014-01-01

    Background Traditional diagnoses of major depressive disorder (MDD) suggested that the presence or absence of stress prior to onset results in either ‘reactive’ or ‘endogenous’ subtypes of the disorder, respectively. Several lines of research suggest that the biological underpinnings of ‘reactive’ or ‘endogenous’ subtypes may also differ, resulting in differential response to treatment. We investigated this hypothesis by comparing the gene-expression profiles of three animal models of ‘reacti...

  14. Clinicopathologic and molecular features of 122 Brazilian cases of nodal and extranodal NK/T-cell lymphoma, nasal type, with EBV subtyping analysis.

    Science.gov (United States)

    Gualco, Gabriela; Domeny-Duarte, Pollyanna; Chioato, Lucimara; Barber, Glen; Natkunam, Yasodha; Bacchi, Carlos E

    2011-08-01

    Extranodal natural killer/T-cell lymphoma, nasal type (NK/TCL) is more prevalent in Asia and in some areas of South and Central America, but it is rarely seen in the United States and Europe. In this study, a series of 122 cases of NK/TCL from Brazil was analyzed with respect to clinicopathologic features. Clinical characteristics and geographic distribution were evaluated in 97 cases of nasal/nasopharyngeal region and 23 cases in extranasal sites including 6 nodal cases. Clinical staging and follow-up information was available in a subset of 21 patients. All cases harbored Epstein-Barr virus (EBV), 95% and 85% expressed cytoplasmic CD3 and CD56, respectively, and all cases were positive for at least 1 marker for cytotoxic granules. The global distribution of EBV subtypes showed predominance of strain subtype A, 89%, and subtype B, 11%. No dual infections were detected. TCR-γ TCR-gene rearrangement was observed in 7 cases; all of them extranodal. Three of TCR-γ(+) cases showed EBV subtype A. Two TCR-γ(+)/CD56(+) cases showed EBV subtype B. Geographic distribution of NK/TCL showed higher frequency in the southeast and northeast regions of Brazil. Striking differences among geographic regions were seen with the vast majority of EBV subtype B (86%) occurring in the south and southeast regions.

  15. The identification value of diffusion weighted imaging in different molecular subtypes for breast cancer classification%磁共振 DWI 对乳腺癌分子亚型的鉴别诊断应用价值

    Institute of Scientific and Technical Information of China (English)

    金观桥; 苏丹柯; 罗殿中; 赖少侣; 罗宁斌; 康巍; 黄向阳; 方献柳

    2015-01-01

    目的:探讨 MR 扩散加权成像(DWI)对乳腺癌不同分子亚型的鉴别诊断价值。方法乳腺癌患者依据 ER、Ki-67、PR、HER2的组化结果分成4种分子亚型,即 Luminal A、Luminal B、人类表皮生长因子受体2(HER2-OE)阳性和三阴型(triple nega-tive breast cancer,TNBC)。所有患者于乳腺癌手术/活检至少前2周进行 MR 检查,测定肿瘤最大横断面的 ADC 值(包括最大ADC 值、最小 ADC 值、平均 ADC 值)。采用单因素方差分析、LSD-t 进行统计学分析。结果72例乳腺癌中,Luninal A 亚型21例,Luminal B 亚型22例,HER2-OE 亚型17例,TNBC 亚型12例。4种亚型中,年龄、瘤灶大小均数的差异无统计学意义(P >0.05)。经 AVONA 统计,Luminal A,Luminal B,HER2-OE 和 TNBC 亚型的最大 ADC 值、平均 ADC 值以及最小 ADC 值的均数之间差异有统计学意义(P =0.025,0.039,0.041)。Luminal A,Luminal B,HER2-OE 和 TNBC 亚型的最大 ADC 值、平均 ADC 值以及最小 ADC 值的均数多重比较中,每一个均数两两比较差异不能同时均有统计学意义。结论手术或活检前,MR DWI 对乳腺癌不同分子亚型的鉴别诊断价值具有一定局限性。%Objective To investigate the value of diffusion weighted imaging (DWI)in identification of different molecular sub-types for breast cancer classifications.Methods All patients with breast cancer were divided into four subtypes groups by immuno-histochemistry results including Luminal A subtype,Luminal B subtype,HER2-over expressing (HER2-OE)subtype,and triple negative breast cancer (TNBC),respectively.The means of maximum,average,and minimum ADC of the lesions in all patients were recorded.The analysis of ANOVA and least significant difference test (LSD-t )were used for the statistical evaluation.Results There were significant differences in maximum ADC,average ADC,and minimum ADC among Luminal A subtype (n=21),Lu-minal B subtype (n=22),HER2-OE subtype (n=1 7)and TNBC subtype (n=12)groups (P

  16. Molecular subtyping methods for campylobacter

    Science.gov (United States)

    Campylobacter jejuni is a major cause worldwide of foodborne bacterial gastroenteritis. The continued development of more effective and informative typing methods is necessary to improve our understanding of the epidemiology and population dynamics of this important pathogen. Comparative genome ind...

  17. Prevention of mother-to-child HIV-1 transmission in Burkina Faso: evaluation of vertical transmission by PCR, molecular characterization of subtypes and determination of antiretroviral drugs resistance

    Science.gov (United States)

    Sagna, Tani; Bisseye, Cyrille; Compaore, Tegewende R.; Kagone, Therese S.; Djigma, Florencia W.; Ouermi, Djeneba; Pirkle, Catherine M.; Zeba, Moctar T. A.; Bazie, Valerie J. T.; Douamba, Zoenabo; Moret, Remy; Pietra, Virginio; Koama, Adjirita; Gnoula, Charlemagne; Sia, Joseph D.; Nikiema, Jean-Baptiste; Simpore, Jacques

    2015-01-01

    Background Vertical human immunodeficiency virus (HIV) transmission is a public health problem in Burkina Faso. The main objective of this study on the prevention of mother-to-child HIV-1 transmission was to determine the residual risk of HIV transmission in infants born to mothers receiving highly active antiretroviral therapy (HAART). Moreover, we detect HIV antiretroviral (ARV) drug resistance among mother–infant pairs and identify subtypes and circulating recombinant forms (CRF) in Burkina Faso. Design In this study, 3,215 samples of pregnant women were analyzed for HIV using rapid tests. Vertical transmission was estimated by polymerase chain reaction in 6-month-old infants born to women who tested HIV positive. HIV-1 resistance to ARV, subtypes, and CRFs was determined through ViroSeq kit using the ABI PRISM 3,130 sequencer. Results In this study, 12.26% (394/3,215) of the pregnant women were diagnosed HIV positive. There was 0.52% (2/388) overall vertical transmission of HIV, with rates of 1.75% (2/114) among mothers under prophylaxis and 0.00% (0/274) for those under HAART. Genetic mutations were also isolated that induce resistance to ARV such as M184V, Y115F, K103N, Y181C, V179E, and G190A. There were subtypes and CRF of HIV-1 present, the most common being: CRF06_CPX (58.8%), CRF02_AG (35.3%), and subtype G (5.9%). Conclusions ARV drugs reduce the residual rate of HIV vertical transmission. However, the virus has developed resistance to ARV, which could limit future therapeutic options when treatment is needed. Resistance to ARV therefore requires a permanent interaction between researchers, physicians, and pharmacists, to strengthen the network of monitoring and surveillance of drug resistance in Burkina Faso. PMID:25630709

  18. Prevention of mother-to-child HIV-1 transmission in Burkina Faso: evaluation of vertical transmission by PCR, molecular characterization of subtypes and determination of antiretroviral drugs resistance

    Directory of Open Access Journals (Sweden)

    Tani Sagna

    2015-01-01

    Full Text Available Background: Vertical human immunodeficiency virus (HIV transmission is a public health problem in Burkina Faso. The main objective of this study on the prevention of mother-to-child HIV-1 transmission was to determine the residual risk of HIV transmission in infants born to mothers receiving highly active antiretroviral therapy (HAART. Moreover, we detect HIV antiretroviral (ARV drug resistance among mother–infant pairs and identify subtypes and circulating recombinant forms (CRF in Burkina Faso. Design: In this study, 3,215 samples of pregnant women were analyzed for HIV using rapid tests. Vertical transmission was estimated by polymerase chain reaction in 6-month-old infants born to women who tested HIV positive. HIV-1 resistance to ARV, subtypes, and CRFs was determined through ViroSeq kit using the ABI PRISM 3,130 sequencer. Results: In this study, 12.26% (394/3,215 of the pregnant women were diagnosed HIV positive. There was 0.52% (2/388 overall vertical transmission of HIV, with rates of 1.75% (2/114 among mothers under prophylaxis and 0.00% (0/274 for those under HAART. Genetic mutations were also isolated that induce resistance to ARV such as M184V, Y115F, K103N, Y181C, V179E, and G190A. There were subtypes and CRF of HIV-1 present, the most common being: CRF06_CPX (58.8%, CRF02_AG (35.3%, and subtype G (5.9%. Conclusions: ARV drugs reduce the residual rate of HIV vertical transmission. However, the virus has developed resistance to ARV, which could limit future therapeutic options when treatment is needed. Resistance to ARV therefore requires a permanent interaction between researchers, physicians, and pharmacists, to strengthen the network of monitoring and surveillance of drug resistance in Burkina Faso.

  19. Subtipos moleculares del cáncer de mama: implicaciones pronósticas y características clínicas e inmunohistoquímicas Molecular subtypes of breast cancer: prognostic implications and clinical and immunohistochemical characteristics

    Directory of Open Access Journals (Sweden)

    M.A. Arrechea Irigoyen

    2011-08-01

    pronóstico.Background. Breast carcinomas are a heterogeneous group of tumours, in both their clinical behavior and their prognosis. The aim of this article is to classify breast carcinomas according to molecular subtypes by means of immunohistochemical markers and to analyse the clinicopathological and immunohistochemical characteristics and the patterns of survival and relapse of the different subtypes. Methods. Two hundred and seventy-two patients diagnosed with breast cancer were classified into five subtypes: breast carcinomas of the basal type, HER2 type, luminal A type, luminal B type and normal. Results. The most frequent breast carcinomas were: luminal A type carcinomas (62.5%, luminal B type carcinomas (18%, HER2 type carcinomas (9.9%, basal type carcinomas (8.4% and normal phenotype carcinomas (1.4%. Significantly and with greater frequency, the luminal type breast carcinomas proved to be well differentiated tumours, of small tumoral size, with negative axillary lymph nodes, at an early stage at the time of diagnosis, with high levels of BCL-2 and a low Ki-67 proliferation index. On the contrary, the basal type and HER2 carcinomas presented larger tumours, poorly differentiated, greater ganglionar involvement and more advanced stages at the time of diagnosis. They expressed high Ki-67 proliferation indexes with greater frequency and were the subtypes that showed a worse prognosis on global survival and progression-free survival curves. Conclusion. Breast cancer classification based on immunohistochemical (IHC parameters makes a better prognostic definition possible. Both the basal type and the HER2 type breast carcinomas present more unfavourable histopathological and IHC characteristics, as well as a worse survival and less relapse time, while the luminal type breast carcinomas show more benign characteristics and a better prognosis.

  20. Molecular epidemiology of HIV-1 subtypes in Shenzhen of 2010%深圳市2010年HIV-1分子流行病学调查

    Institute of Scientific and Technical Information of China (English)

    石向东; 陈琳; 杨峥嵘; 王晓辉; 赵锦; 王芳

    2012-01-01

    Objective To study the prevalence status of human immunodeficiency virus-1 (HIV-1)subtypes in Shenzhen and study their source in order to predict the epidemic trend. Methods Samples were collected from 150 newly reported HIV-1 infected in Shenzhen in 2010. HIV-1 env gene and gag gene were amplified by nested-PCR from RNA .The C2-V3 region of HIV-1 env and P24 region were sequenced for analyses. Results Among 128 samples,there were 6 HIV-1 strains including CRF01_AE,CRF08-BC,CRF07-BC 3 circulating recombinant forms (CRFs)and B',C,A1 3 subtypes. Subtyping showed that 63.3% (81/128)were CRF01-AE, 14.1% (18/128)were subtype B',13.3% (17/128)were CRF07_BC,7.0%( 10/122)were CRF08_BC,0.8%( 1/128)were subtype C, 1.6%(2/128)were subtype A1. And CRF01_AE strain mainly from injecting drug users (IDUs)and heterosexuals and homosexuals. CRF07_BC and CRF08_BC strains mainly from heterosexual and homosexual. Subtype B' were mainly from heterosexuals and homosexuals,blood donors and mothers to children. And subtype Al was first found in IDUs. Conclusion CRF01_AE、subtype B',CRF07_BC and CRF08_BC of HIV-1 strains were mainly epidemic subtypes in Shenzhen in 2010. Subtype C and Al were also circulating in Shenzhen region. CRF01_AE recombinant was largely predominant among all transmitting population. And the proportion of CRF01_AE in various groups of population is higher than that in other regions of China.%目的 了解2010年艾滋病病毒-1型(HIV-1)毒株亚型在深圳市的流行情况,为预防和控制HIV在本市的流行提供有价值的资料.方法 收集2010年深圳市HIV-1确认为阳性的样本150例,应用巢式聚合酶链反应(nested-PCR)技术,对该样本膜蛋白基因(env基因)和核心蛋白(gag基因)进行扩增,并对各基因区核苷酸序列进行测定和分析. 结果 共有128份样本获得分型结果,其中CRF01_AE重组株占63.3%(81/128),B’亚型占14.1%(18/128),CRF07_BC重组株占13.3%(17/128),CRF08_BC重组株占7.0%(9

  1. Breast cancer subtype predictors revisited: from consensus to concordance?

    OpenAIRE

    MJ. Sontrop, Herman; JT. Reinders, Marcel; D. Moerland, Perry

    2016-01-01

    Background At the molecular level breast cancer comprises a heterogeneous set of subtypes associated with clear differences in gene expression and clinical outcomes. Single sample predictors (SSPs) are built via a two-stage approach consisting of clustering and subtype predictor construction based on the cluster labels of individual cases. SSPs have been criticized because their subtype assignments for the same samples were only moderately concordant (Cohen’s κ0.8). Interestingly, for a given...

  2. 女性外阴基底细胞癌并发大汗腺汗囊瘤%Vulval basal cell carcinoma associated with apocrine hidrocystoma

    Institute of Scientific and Technical Information of China (English)

    常建民; 刘春燕; 杨敏

    2012-01-01

    A case of vulval basal cell carcinoma associated with apocrine hidrocystoma is reported . The patient presented to the clinic with a blue-gray dome-shaped lesion near the right labia majora without subjective symptom. The lesion was excised and histopathologic examination showed nodular basal cell carcinoma associated with apocrine hidrocystoma.%报告1例女性外阴基底细胞癌并发大汗腺汗囊瘤.患者女,56岁.外阴肿块1年,呈蓝褐色球状,无自觉症状.肿块切除后组织病理检查证实为结节型基底细胞癌并发大汗腺汗囊瘤.

  3. Presentation of Apocrine Breast Carcinoma in a Woman with Bilateral Silicone Prosthesis; Presentacion de un carcinoma apocrino de mama en una mujer con protesis bilateral de silicona

    Energy Technology Data Exchange (ETDEWEB)

    Alonso, J. A.; Salvador, R.; Salvador, M.; Barranco, C.

    2003-07-01

    We present a case of apocrine breast carcinoma in a 45 year-old woman with bilateral silicone breast prosthesis whose clinical manifestations and mammography were that of a palpable nodule-high glandular density, rounded and with imprecise borders devoid of any visible microcalcifications. A bibliographical revision confirmed the infrequent association of this type of tumor with the presence of silicone breast implants, precisely in which we consider its radiological interest to lie. (Author) 11 refs.

  4. Analysis of pulsed-field gel electrophoresis molecular subtyping of Shigella strains in Shenzhen%深圳市志贺菌脉冲场电泳分子分型分析

    Institute of Scientific and Technical Information of China (English)

    兰全学; 扈庆华; 石晓路; 王冰; 林一曼; 程锦泉; 张顺祥

    2008-01-01

    目的 分析深圳市2001-2006年分离志贺菌菌株之间的相关性,初步建立志贺菌的脉冲场电泳(pulsed-field gel electrophoresis,PFGE)分子分型监测网络.方法 55株志贺菌基因组DNA经Xba Ⅰ酶切,通过PFGE获得电泳图谱,利用BioNumerics软件对图谱进行聚类分析.结果 55株志贺菌被分为41种PFGE图谱,聚类分析显示32株细菌谱型属于同一个群,其余菌株谱型差异较大.结论 深圳地区存在遗传紧密相关的志贺菌流行克隆,也存在遗传不相关克隆.PFGE分子分型监测网络的建立,有助于细菌性痢疾的主动监测、暴发调查和传染源追踪.%Objective To analyze the genetic relations of Shigella isolated from Shenzhen in 2001-2006 and develop primary molecular subtyping surveillance network of Shigella. Methods Chromosomal DNAs from 55 isolated in agarose were digested with the restriction enzyme Xba Ⅰ , and then were analyzed by pulsed-field gel electrophoresis. Pulsed-field gel electrophoresis (PFGE) patterns were clustered using BioNumerics software. Results All 41 distinctive PFGE patterns were identified among 55 strains. 32 strains belonged to one cluster. Differences were observed in other strains. Conclusion Both genetic-related clones and non-related clones of Shigella existed in Shenzhen. The development of PFGE molecular subtyping surveillance network would contribute to the active surveillance, outbreak investigation and source tracking for Shigellosis.

  5. TCGA researchers identify 4 subtypes of stomach cancer

    Science.gov (United States)

    Stomach cancers fall into four distinct molecular subtypes, researchers with The Cancer Genome Atlas (TCGA) Network have found. Scientists report that this discovery could change how researchers think about developing treatments for stomach cancer, also c

  6. Pathological Gambling Subtypes

    Science.gov (United States)

    Vachon, David D.; Bagby, R. Michael

    2009-01-01

    Although pathological gambling (PG) is regarded in the 4th edition of the "Diagnostic and Statistical Manual of Mental Disorders" (American Psychiatric Association, 1994) as a unitary diagnostic construct, it is likely composed of distinct subtypes. In the current report, the authors used cluster analyses of personality traits with a…

  7. Molecular Surface of JZTX-V (β-Theraphotoxin-Cj2a Interacting with Voltage-Gated Sodium Channel Subtype NaV1.4

    Directory of Open Access Journals (Sweden)

    Ji Luo

    2014-07-01

    Full Text Available Voltage-gated sodium channels (VGSCs; NaV1.1–NaV1.9 have been proven to be critical in controlling the function of excitable cells, and human genetic evidence shows that aberrant function of these channels causes channelopathies, including epilepsy, arrhythmia, paralytic myotonia, and pain. The effects of peptide toxins, especially those isolated from spider venom, have shed light on the structure–function relationship of these channels. However, most of these toxins have not been analyzed in detail. In particular, the bioactive faces of these toxins have not been determined. Jingzhaotoxin (JZTX-V (also known as β-theraphotoxin-Cj2a is a 29-amino acid peptide toxin isolated from the venom of the spider Chilobrachys jingzhao. JZTX-V adopts an inhibitory cysteine knot (ICK motif and has an inhibitory effect on voltage-gated sodium and potassium channels. Previous experiments have shown that JZTX-V has an inhibitory effect on TTX-S and TTX-R sodium currents on rat DRG cells with IC50 values of 27.6 and 30.2 nM, respectively, and is able to shift the activation and inactivation curves to the depolarizing and the hyperpolarizing direction, respectively. Here, we show that JZTX-V has a much stronger inhibitory effect on NaV1.4, the isoform of voltage-gated sodium channels predominantly expressed in skeletal muscle cells, with an IC50 value of 5.12 nM, compared with IC50 values of 61.7–2700 nM for other heterologously expressed NaV1 subtypes. Furthermore, we investigated the bioactive surface of JZTX-V by alanine-scanning the effect of toxin on NaV1.4 and demonstrate that the bioactive face of JZTX-V is composed of three hydrophobic (W5, M6, and W7 and two cationic (R20 and K22 residues. Our results establish that, consistent with previous assumptions, JZTX-V is a Janus-faced toxin which may be a useful tool for the further investigation of the structure and function of sodium channels.

  8. Highly pathogenic avian influenza virus subtype H5N1 in Africa: a comprehensive phylogenetic analysis and molecular characterization of isolates.

    Directory of Open Access Journals (Sweden)

    Giovanni Cattoli

    Full Text Available Highly pathogenic avian influenza virus A/H5N1 was first officially reported in Africa in early 2006. Since the first outbreak in Nigeria, this virus spread rapidly to other African countries. From its emergence to early 2008, 11 African countries experienced A/H5N1 outbreaks in poultry and human cases were also reported in three of these countries. At present, little is known of the epidemiology and molecular evolution of A/H5N1 viruses in Africa. We have generated 494 full gene sequences from 67 African isolates and applied molecular analysis tools to a total of 1,152 A/H5N1 sequences obtained from viruses isolated in Africa, Europe and the Middle East between 2006 and early 2008. Detailed phylogenetic analyses of the 8 gene viral segments confirmed that 3 distinct sublineages were introduced, which have persisted and spread across the continent over this 2-year period. Additionally, our molecular epidemiological studies highlighted the association between genetic clustering and area of origin in a majority of cases. Molecular signatures unique to strains isolated in selected areas also gave us a clearer picture of the spread of A/H5N1 viruses across the continent. Mutations described as typical of human influenza viruses in the genes coding for internal proteins or associated with host adaptation and increased resistance to antiviral drugs have also been detected in the genes coding for transmembrane proteins. These findings raise concern for the possible human health risk presented by viruses with these genetic properties and highlight the need for increased efforts to monitor the evolution of A/H5N1 viruses across the African continent. They further stress how imperative it is to implement sustainable control strategies to improve animal and public health at a global level.

  9. Ovarian carcinoma subtypes are different diseases: implications for biomarker studies.

    Directory of Open Access Journals (Sweden)

    Martin Köbel

    2008-12-01

    Full Text Available BACKGROUND: Although it has long been appreciated that ovarian carcinoma subtypes (serous, clear cell, endometrioid, and mucinous are associated with different natural histories, most ovarian carcinoma biomarker studies and current treatment protocols for women with this disease are not subtype specific. With the emergence of high-throughput molecular techniques, distinct pathogenetic pathways have been identified in these subtypes. We examined variation in biomarker expression rates between subtypes, and how this influences correlations between biomarker expression and stage at diagnosis or prognosis. METHODS AND FINDINGS: In this retrospective study we assessed the protein expression of 21 candidate tissue-based biomarkers (CA125, CRABP-II, EpCam, ER, F-Spondin, HE4, IGF2, K-Cadherin, Ki-67, KISS1, Matriptase, Mesothelin, MIF, MMP7, p21, p53, PAX8, PR, SLPI, TROP2, WT1 in a population-based cohort of 500 ovarian carcinomas that was collected over the period from 1984 to 2000. The expression of 20 of the 21 biomarkers differs significantly between subtypes, but does not vary across stage within each subtype. Survival analyses show that nine of the 21 biomarkers are prognostic indicators in the entire cohort but when analyzed by subtype only three remain prognostic indicators in the high-grade serous and none in the clear cell subtype. For example, tumor proliferation, as assessed by Ki-67 staining, varies markedly between different subtypes and is an unfavourable prognostic marker in the entire cohort (risk ratio [RR] 1.7, 95% confidence interval [CI] 1.2%-2.4% but is not of prognostic significance within any subtype. Prognostic associations can even show an inverse correlation within the entire cohort, when compared to a specific subtype. For example, WT1 is more frequently expressed in high-grade serous carcinomas, an aggressive subtype, and is an unfavourable prognostic marker within the entire cohort of ovarian carcinomas (RR 1.7, 95% CI 1

  10. Analysis of pulsed-field gel electrophoresis molecular subtyping and serotyping of Vibrio parahaemolyticus in food%食品中副溶血弧菌血清学分型与分子分型的研究

    Institute of Scientific and Technical Information of China (English)

    贺连华; 吴平芳; 陈妙玲; 王冰; 林爱红; 吕东月

    2011-01-01

    目的 分析深圳市2007~2010年监测食品中副溶血弧菌存在的优势血清型与基因型之间的相似性,初步建立深圳市食源性副溶血弧菌脉冲场凝胶电泳分子分型监测网络.方法 选择2007~2010年监测食品中分离出来的副溶血孤菌主要血清群(O1-O4)55株,基因组DNA经Sfi1酶切,通过脉冲场凝胶电泳PFGE获得图谱,利用BioNumerics 分析软件对图谱进行聚类分析.结果 相似性在90%以上的有15株,其中有9株相似性为100%,分别是2株O2:K28;1株O1:KUT与1株O4:K42;5株O3:K6,其余菌株谱型差异较大.结论 监测食品中分离的副溶血弧菌PFGE型别多,且相互之间关系分散.PFGE分子分型监测网络的建立,有助于食源性疾病发生时的主动监测,爆发调查和传染源追踪.%Objective To analyze the relationship between genotype and serotype of Vibrio parahaemolyticus isolated from food in Shenzhen from 2007 to 2010 and develop primary molecular subtyping surveillance network of Vibrio parahaemolyticus. Methods The 55 strains of Vibrio parahaemolylicus isolated from diarrhea patients containing important serotype O1-O4,chromosomal DNAs were digested with the restriction enzyme Sfil.and then were analyzed by pulsed-field gel electrophoresis. Results The similarity of the 15 strains was over 90% and 9 strains with 100% similarity including 2 strains O2:K28,1 strain 01:KUT and 1 strain O4:K42,5 strains O3:K6. Other strains showed prominent difference. Conclusion Various Vibrio parahaemolyticus patterns exist in food and the relationship is scattered. The development of PFGE molecular subtyping surveillance network would contribute to the surveillance,outbreak investigation and source tracking for Vibrio parahaemolyticus infection.

  11. Comparison between resection and curettage on removing apocrine sweat glands%刮除法和剪除法去除腋窝大汗腺的比较

    Institute of Scientific and Technical Information of China (English)

    黄威; 邱涛; 李淼

    2012-01-01

    目的 比较两种常用治疗腋臭的手术方法即刮除法和剪除法的疗效.方法 在患者的腋部注射肿胀麻醉液,在腋窝中央切开长约1cm的切口,用剪刀进行腋窝皮下分离.用刮匙进行皮下搔刮至皮肤呈现紫色,然后将切口适当延长,皮肤翻转.观察大汗腺刮除情况,沿切口边缘剪除1.5mm宽的一小条皮肤做组织学检查.用剪刀剪除大汗腺和部分真皮至形成厚中厚皮片.止血后缝合伤口,剥离区域打包加压包扎.结果 自2009年7月至2011年12月,用此种方法进行42例手术.刮除手术完成后,翻转皮瓣时均可见真皮层深面有粉红色的大汗腺组织残留;病理检查也发现刮除后有腺体残留.术后随访经过刮除和剪除法治疗的患者3~12个月,有效率为97.6%.出现血肿3例,伤口延期愈合4例,复发1例.结论 应用剪刀剪除法比单纯刮除法去除大汗腺更彻底.%Objective To compare the results of removing apocrine sweat glands by resection and curettage for osmidrosis treatment. Methods Under tnmescent anesthesia, 1 cm incision was made at the middle line of axillary fossa. The subcutaneous dissecton was performed by scissors and scraping was made by a curette to present purple color of skin. After scraping apocrine sweat glands, the incision was lengthcned and the flap was turned over. A piece of skin, 1.5 mm width, was harvested for histology examination. Then the flap was cut into full thickness skin. The wound was sutured and performed the pressure dressing after hemostasis. Re-salts From July 2009 to December 2011, 42 patients underwent this operation. There were some apocrine sweat glands residue through macroscopic examination and histological examination after scraping. These apo-crine sweat glands showed pink color underncath dermis. These patients were followed up for 3 to 12 months, and the efficacy of apocrine sweat glanel resection was 97. 6%. There were a few complications except for 3 ca-ses with

  12. Hidrocistomas múltiplos apócrinos: um diagnóstico clínico confuso Multiple apocrine hidrocystomas: a confusing clinical diagnosis

    Directory of Open Access Journals (Sweden)

    Shyam B. Verma

    2010-04-01

    Full Text Available Este é um relato de caso seguido por uma breve revisão da literatura sobre hidrocistomas apócrinos. Uma senhora de 67 anos de idade foi à clínica anteriormente citada apresentando lesões papulocísticas múltiplas, translúcidas e assintomáticas na face que pioravam durante o verão. Uma biopsia mostrou uma cavidade cística única contornada por duas camadas de pequenas células epiteliais cubóides. Diferenciação apócrina caracterizada por remoção de secreção foi observada. Foi feito um diagnóstico de hidrocistomas múltiplos apócrinos. Tratamento pode ser tentado com excisão individual de lesões ou laser. Atropina tópica e escopolamina também foram tentadas com sucesso variável. Nossa paciente não quis nenhum tratamento uma vez que a natureza benigna da condição foi confirmada.This is a case report followed by a short review of literature of apocrine hidrocystomas. A 67 year old lady came to this clinic with multiple translucent, asymptomatic papulocystic lesions on the face which got worse in summer. A biopsy showed a single cystic cavity lined by two layers of small cuboial epithelial cells was seen. Apocrine differentiation characterised by decapitation secretion was seen. A diagnosis of multiple apocrine hidrocystomas was made. Treatment can be attempted with individual excision of lesions or lasers. Topical atropine and scopolamine too have been tried with variable success. Our patient did not wish any treatment once the benign nature of the condition was confirmed.

  13. Particle infectivity of HIV-1 full-length genome infectious molecular clones in a subtype C heterosexual transmission pair following high fidelity amplification and unbiased cloning

    Energy Technology Data Exchange (ETDEWEB)

    Deymier, Martin J., E-mail: mdeymie@emory.edu [Emory Vaccine Center, Yerkes National Primate Research Center, 954 Gatewood Road NE, Atlanta, GA 30329 (United States); Claiborne, Daniel T., E-mail: dclaibo@emory.edu [Emory Vaccine Center, Yerkes National Primate Research Center, 954 Gatewood Road NE, Atlanta, GA 30329 (United States); Ende, Zachary, E-mail: zende@emory.edu [Emory Vaccine Center, Yerkes National Primate Research Center, 954 Gatewood Road NE, Atlanta, GA 30329 (United States); Ratner, Hannah K., E-mail: hannah.ratner@emory.edu [Emory Vaccine Center, Yerkes National Primate Research Center, 954 Gatewood Road NE, Atlanta, GA 30329 (United States); Kilembe, William, E-mail: wkilembe@rzhrg-mail.org [Zambia-Emory HIV Research Project (ZEHRP), B22/737 Mwembelelo, Emmasdale Post Net 412, P/BagE891, Lusaka (Zambia); Allen, Susan, E-mail: sallen5@emory.edu [Zambia-Emory HIV Research Project (ZEHRP), B22/737 Mwembelelo, Emmasdale Post Net 412, P/BagE891, Lusaka (Zambia); Department of Pathology and Laboratory Medicine, Emory University, Atlanta, GA (United States); Hunter, Eric, E-mail: eric.hunter2@emory.edu [Emory Vaccine Center, Yerkes National Primate Research Center, 954 Gatewood Road NE, Atlanta, GA 30329 (United States); Department of Pathology and Laboratory Medicine, Emory University, Atlanta, GA (United States)

    2014-11-15

    The high genetic diversity of HIV-1 impedes high throughput, large-scale sequencing and full-length genome cloning by common restriction enzyme based methods. Applying novel methods that employ a high-fidelity polymerase for amplification and an unbiased fusion-based cloning strategy, we have generated several HIV-1 full-length genome infectious molecular clones from an epidemiologically linked transmission pair. These clones represent the transmitted/founder virus and phylogenetically diverse non-transmitted variants from the chronically infected individual's diverse quasispecies near the time of transmission. We demonstrate that, using this approach, PCR-induced mutations in full-length clones derived from their cognate single genome amplicons are rare. Furthermore, all eight non-transmitted genomes tested produced functional virus with a range of infectivities, belying the previous assumption that a majority of circulating viruses in chronic HIV-1 infection are defective. Thus, these methods provide important tools to update protocols in molecular biology that can be universally applied to the study of human viral pathogens. - Highlights: • Our novel methodology demonstrates accurate amplification and cloning of full-length HIV-1 genomes. • A majority of plasma derived HIV variants from a chronically infected individual are infectious. • The transmitted/founder was more infectious than the majority of the variants from the chronically infected donor.

  14. Structural characterization of the binding interactions of various endogenous estrogen metabolites with human estrogen receptor α and β subtypes: a molecular modeling study.

    Directory of Open Access Journals (Sweden)

    Pan Wang

    Full Text Available In the present study, we used the molecular docking approach to study the binding interactions of various derivatives of 17β-estradiol (E2 with human estrogen receptor (ER α and β. First, we determined the suitability of the molecular docking method to correctly predict the binding modes and interactions of two representative agonists (E2 and diethylstilbesterol in the ligand binding domain (LBD of human ERα. We showed that the docked structures of E2 and diethylstilbesterol in the ERα LBD were almost exactly the same as the known crystal structures of ERα in complex with these two estrogens. Using the same docking approach, we then characterized the binding interactions of 27 structurally similar E2 derivatives with the LBDs of human ERα and ERβ. While the binding modes of these E2 derivatives are very similar to that of E2, there are distinct subtle differences, and these small differences contribute importantly to their differential binding affinities for ERs. In the case of A-ring estrogen derivatives, there is a strong inverse relationship between the length of the hydrogen bonds formed with ERs and their binding affinity. We found that a better correlation between the computed binding energy values and the experimentally determined logRBA values could be achieved for various A-ring derivatives by re-adjusting the relative weights of the van der Waals interaction energy and the Coulomb interaction energy in computing the overall binding energy values.

  15. Particle infectivity of HIV-1 full-length genome infectious molecular clones in a subtype C heterosexual transmission pair following high fidelity amplification and unbiased cloning

    International Nuclear Information System (INIS)

    The high genetic diversity of HIV-1 impedes high throughput, large-scale sequencing and full-length genome cloning by common restriction enzyme based methods. Applying novel methods that employ a high-fidelity polymerase for amplification and an unbiased fusion-based cloning strategy, we have generated several HIV-1 full-length genome infectious molecular clones from an epidemiologically linked transmission pair. These clones represent the transmitted/founder virus and phylogenetically diverse non-transmitted variants from the chronically infected individual's diverse quasispecies near the time of transmission. We demonstrate that, using this approach, PCR-induced mutations in full-length clones derived from their cognate single genome amplicons are rare. Furthermore, all eight non-transmitted genomes tested produced functional virus with a range of infectivities, belying the previous assumption that a majority of circulating viruses in chronic HIV-1 infection are defective. Thus, these methods provide important tools to update protocols in molecular biology that can be universally applied to the study of human viral pathogens. - Highlights: • Our novel methodology demonstrates accurate amplification and cloning of full-length HIV-1 genomes. • A majority of plasma derived HIV variants from a chronically infected individual are infectious. • The transmitted/founder was more infectious than the majority of the variants from the chronically infected donor

  16. Oligonucleotide microchip for subtyping of influenza A virus

    Science.gov (United States)

    Fesenko, Eugeny E.; Kireyev, Dmitry E.; Gryadunov, Dmitry A.; Mikhailovich, Vladimir M.; Grebennikova, Tatyana V.; L’vov, Dmitry K.; Zasedatelev, Alexander S.

    2007-01-01

    Background  Influenza A viruses are classified into subtypes depending on the antigenic properties of their two outer glycoproteins, hemagglutinin (HA) and neuraminidase (NA). Sixteen subtypes of HA and nine of NA are known. Lately, the circulation of some subtypes (H7N7, H5N1) has been closely watched because of the epidemiological threat they present. Objectives  This study assesses the potential of using gel‐based microchip technology for fast and sensitive molecular subtyping of the influenza A virus. Methods  The method employs a microchip of 3D gel‐based elements containing immobilized probes. Segments of the HA and NA genes are amplified using multiplex RT‐PCR and then hybridized with the microchip. Results  The developed microchip was validated using a panel of 21 known reference strains of influenza virus. Selected strains represented different HA and NA subtypes derived from avian, swine and human hosts. The whole procedure takes 10 hours and enables one to identify 15 subtypes of HA and two subtypes of NA. Forty‐one clinical samples isolated during the poultry fall in Novosibirsk (Russia, 2005) were successfully identified using the proposed technique. The sensitivity and specificity of the method were 76% and 100%, respectively, compared with the ‘gold standard’ techniques (virus isolation with following characterization by immunoassay). Conclusions  We conclude that the method of subtyping using gel‐based microchips is a promising approach for fast detection and identification of influenza A, which may greatly improve its monitoring. PMID:19453417

  17. Comprehensive gene expression profiling and immunohistochemical studies support application of immunophenotypic algorithm for molecular subtype classification in diffuse large B-cell lymphoma

    DEFF Research Database (Denmark)

    Visco, C; Xu-Monette, Z Y; Miranda, R N;

    2012-01-01

    Gene expression profiling (GEP) has stratified diffuse large B-cell lymphoma (DLBCL) into molecular subgroups that correspond to different stages of lymphocyte development-namely germinal center B-cell like and activated B-cell like. This classification has prognostic significance, but GEP...... is expensive and not readily applicable into daily practice, which has lead to immunohistochemical algorithms proposed as a surrogate for GEP analysis. We assembled tissue microarrays from 475 de novo DLBCL patients who were treated with rituximab-CHOP chemotherapy. All cases were successfully profiled by GEP...... on formalin-fixed, paraffin-embedded tissue samples. Sections were stained with antibodies reactive with CD10, GCET1, FOXP1, MUM1 and BCL6 and cases were classified following a rationale of sequential steps of differentiation of B cells. Cutoffs for each marker were obtained using receiver...

  18. Study on molecular subtyping of Enterohemorrhagic Escherichia coil O157 ∶H7 in Jiangsu%江苏省肠出血性大肠杆菌0157∶H7 PFGE分子分型研究

    Institute of Scientific and Technical Information of China (English)

    顾玲; 周璐; 董晨; 崔志刚; 谈忠鸣; 张艺飓

    2013-01-01

    Objective: To analyze the association of isolates of Enterohemorrhagic Escherichia coli 0157 :H7 from different sources in Jiangsu during 1999 -2009. Methods: Pulse -field gel electrophoresis (PFGE) using restriction enzyme Xbal was employed for the molecular subtyping of Enterohemorrhagic Escherichia coli 0157 :H7 isolated from 1999 to 2009, and PFGE patterns were analyzed by BioNumerics Version 4.0 software to perform cluster analysis. Pattern profiles were compared by utilizing Dice coefficient and UPGMA ( unweighted pair group method with a-rithmetic averages). Results: PFGE subtyping after Xbal DNA digestion produced a total of 39 distinct restriction endonuclease digestion profiles among the 74 strains. Some isolates from different sources at the same area at the same time had indistinguishable Xbal patterns. Part of isolates from distinct areas at the same time shared the identical Xbal patterns. Some isolates from different time also had indistinguishable Xbal patterns. Conclusion: Many clones of Enterohemorrhagic Escherichia coli 0157:H7 were shed by the feces of animals in Jiangsu and the strains from the identical clones had been spread in wide range in Jiangsu. Some of clones occurred in outbreak in 1999 had stably exited among animals for long time and disseminated to human.%目的:对我省历年分离的不同地区和来源EHEC O157∶H7菌株之间的同源性进行分析.方法:用限制性内切酶XbaI,对分离菌株进行PFGE分型,并使用BioNumerics Version 4.0软件(Dice系数和UPGMA法)进行聚类分析.结果:74株O157∶H7分离株可分为39个型,同一年份同一地区不同来源菌株之间有相同的XbaI酶切带型,同一年份不同地区分离菌株之间有相同酶切带型,不同年份部分菌株之间酶切带型不可区分.结论:我省宿主动物携带多个O157∶H7克隆,来自同一个克隆的O157∶H7已在较广泛的区域内传播,某些在1999年暴发流行的克隆长期稳定存在于我省

  19. A comparison of AMPV subtypes A and B full genomes, gene transcripts and proteins led to reverse-genetics systems rescuing both subtypes.

    Science.gov (United States)

    Laconi, Andrea; Clubbe, Jayne; Falchieri, Marco; Lupini, Caterina; Cecchinato, Mattia; Catelli, Elena; Listorti, Valeria; Naylor, Clive J

    2016-06-01

    Avian metapneumovirus (AMPV) infection of poultry causes serious disease in most countries and subtype A reverse-genetic (RG) systems have allowed a generation of viruses of known sequence, and proved useful in developments towards better control by live vaccines. While subtype B viruses are more prevalent, bacterial cloning issues made subtype B RG systems difficult to establish. A molecular comparison of subtype A and B viruses was undertaken to assess whether subtype A RG components could be partially or fully substituted. AMPV subtype A and B gene-end sequences leading to polyadenylation are, to our knowledge, reported for the first time, as well as several leader and trailer sequences. After comparing these alongside previously reported gene starts and protein sequences, it was concluded that subtype B genome copies would be most likely rescued by a subtype A support system, and this assertion was supported when individual subtype A components were successfully substituted. Application of an advanced cloning plasmid permitted eventual completion of a fully subtype B RG system, and proved that all subtype-specific components could be freely exchanged between A and B systems. PMID:26958846

  20. Efficacy of trimming apocrine glands in the treatment of osmidrosis%大汗腺修剪法治疗腋臭89例疗效评价

    Institute of Scientific and Technical Information of China (English)

    周朝晖; 杨天赤; 阮瑛; 陈劲琳; 信凤娇

    2015-01-01

    Objective:To assess the efficacy of trimming apocrine glands in the treatment of osmidrosis. Methods: Incision along the axillary sheath was made in 89 patients with osmidrosis and the sweat glands were excised. Pressure bandaging was performed after surgery. Results:Twenty patients were cured completely and there was slight odor after sport in 69 patients. The effective rate was 100%. There was no relapse in all patients after 2 years' follow -up. Conclusion: Trimming apocrine glands is effective in the treatment of os-midrosis.%目的::评价大汗腺修剪法治疗腋臭的疗效。方法:89例腋臭患者沿腋横纹作切口,直视下剪除大汗腺后打包加压包扎。结果:89例患者中20例完全根治,有效69例(剧烈运动后有轻微臭味),总有效率100%。随访2年无复发。结论:直视下修剪大汗腺治疗腋臭疗效确切。

  1. Racial difference in histologic subtype of renal cell carcinoma

    International Nuclear Information System (INIS)

    In the United States, renal cell carcinoma (RCC) has rapidly increased in incidence for over two decades. The most common histologic subtypes of RCC, clear cell, papillary, and chromophobe have distinct genetic and clinical characteristics; however, epidemiologic features of these subtypes have not been well characterized, particularly regarding any associations between race, disease subtypes, and recent incidence trends. Using data from the Surveillance, Epidemiology, and End Results (SEER) Program, we examined differences in the age-adjusted incidence rates and trends of RCC subtypes, including analysis focusing on racial differences. Incidence rates increased over time (2001–2009) for all three subtypes. However, the proportion of white cases with clear cell histology was higher than among blacks (50% vs. 31%, respectively), whereas black cases were more likely than white cases to have papillary RCC (23% vs. 9%, respectively). Moreover, papillary RCC incidence increased more rapidly for blacks than whites (P < 0.01) over this period. We also observed that increased incidence of papillary histology among blacks is not limited to the smallest size strata. We observed racial differences in proportionate incidence of RCC subtypes, which appear to be increasing over time; this novel finding motivates further etiologic, clinical, molecular, and genetic studies. Using national data, we observed a higher proportion of black renal cell carcinoma (RCC) cases with papillary histology compared to Caucasian cases. We also observed time trends in black-white incidence differences in histologic RCC subtypes, with rapid increases in the disproportionate share of black cases with papillary histology

  2. The consensus molecular subtypes of colorectal cancer

    NARCIS (Netherlands)

    Guinney, Justin; Dienstmann, Rodrigo; Wang, Xin; de Reyniès, Aurélien; Schlicker, Andreas; Soneson, Charlotte; Marisa, Laetitia; Roepman, Paul; Nyamundanda, Gift; Angelino, Paolo; Bot, Brian M; Morris, Jeffrey S; Simon, Iris M; Gerster, Sarah; Fessler, Evelyn; De Sousa E Melo, Felipe; Missiaglia, Edoardo; Ramay, Hena; Barras, David; Homicsko, Krisztian; Maru, Dipen; Manyam, Ganiraju C; Broom, Bradley; Boige, Valerie; Perez-Villamil, Beatriz; Laderas, Ted; Salazar, Ramon; Gray, Joe W; Hanahan, Douglas; Tabernero, Josep; Bernards, Rene; Friend, Stephen H; Laurent-Puig, Pierre; Medema, Jan Paul; Sadanandam, Anguraj; Wessels, Lodewyk; Delorenzi, Mauro; Kopetz, Scott; Vermeulen, Louis; Tejpar, Sabine

    2015-01-01

    Colorectal cancer (CRC) is a frequently lethal disease with heterogeneous outcomes and drug responses. To resolve inconsistencies among the reported gene expression-based CRC classifications and facilitate clinical translation, we formed an international consortium dedicated to large-scale data shar

  3. Cis-regulatory mechanisms of left/right asymmetric neuron-subtype specification in C. elegans

    OpenAIRE

    Etchberger, John F.; Eileen B Flowers; Poole, Richard J.; Bashllari, Enkelejda; Hobert, Oliver

    2008-01-01

    Anatomically and functionally defined neuron types are sometimes further classified into individual subtypes based on unique functional or molecular properties. To better understand how developmental programs controlling neuron type specification are mechanistically linked to programs controlling neuronal subtype specification, we have analyzed a neuronal subtype specification program that occurs across the left/right axis in the nervous system of the nematode C. elegans. A terminal selector ...

  4. Subtyping adolescents with bulimia nervosa

    OpenAIRE

    Chen, Eunice Yu; le Grange, Daniel

    2007-01-01

    Cluster analyses of eating disorder patients have yielded a “dietary-depressive” subtype, typified by greater negative affect, and a “dietary” subtype, typified by dietary restraint. This study aimed to replicate these findings in an adolescent sample with bulimia nervosa (BN) from a randomized controlled trial and to examine the validity and reliability of this methodology. In the sample of BN adolescents (N=80), cluster analysis revealed a “dietary-depressive” subtype (37.5%) and a “dietary...

  5. Clasificación en subtipos moleculares de tumores de mama de pequeños animales mediante métodos inmunohistoquímicos Classification in molecular subtypes of breast tumors of small animals through immunohistochemical methods

    OpenAIRE

    Mª V. Ortega García; J.A. Galán Torres; Y. Millán Ruiz; R. Sánchez Céspedes; J. Martín de las Mulas González-Albo

    2013-01-01

    Antecedentes y Objetivos: Aplicar un panel de anticuerpos (anti -receptor de progesterona, -receptor de estrógenos, -receptor del factor de crecimiento epidérmico humano 2 y -citoqueratina 14) utilizando métodos inmunohistoquímicos en tumores mamarios de pequeños animales para analizar su clasificación en subtipos moleculares y su asociación con la invasión, el grado y el tipo histológico de las neoplasias. Material y Métodos: Muestras de tumores mamarios malignos, 10 de la especie canina y 3...

  6. Cryptosporidium parvum GP60 subtypes in dairy cattle from Buenos Aires, Argentina

    Science.gov (United States)

    Cryptosporidium parvum from 73 dairy calves less than two months old from Buenos Aires province (Argentina) were molecularly characterized using sequence analysis of the GP60 gene. Seventy five sequences were obtained, and seven different subtypes were identified, all belonging to the IIa subtype f...

  7. Novel Human Herpesvirus 8 Subtype D Strains in Vanuatu, Melanesia

    OpenAIRE

    Cassar, Olivier; Afonso, Philippe V; Bassot, Sylviane; Plancoulaine, Sabine; Duprez, Renan; Capuano, Corinne; Abel, Myriam; Martin, Paul M V; Gessain, Antoine

    2007-01-01

    International audience We show human herpesvirus 8 with diverse molecular subtype D variants to be highly endemic among the Ni-Vanuatu population. Most K1 genes were nearly identical to Polynesian strains, although a few clustered with Australian or Taiwanese strains. These results suggest diverse origins of the Ni-Vanuatu population and raise questions about the ancient human population movements in Melanesia.

  8. Molecular subtyping and antibiotic resistance of nontyphoidal Salmonella isolated from food in Beijing%北京市食源性非伤寒沙门菌的分子分型和耐药性研究

    Institute of Scientific and Technical Information of China (English)

    张晓嫒; 王迪; 陈倩

    2015-01-01

    Objective To investigate the molecular characteristics and antibiotic resistance of nontyphoidal Salmonella isolated from food in Beijing.Methods A total of 100 strains were isolated from foodborne pathogenic bacteria monitoring network in Beijing from 2004 to 2010,and were analyzed by PFGE and antimicrobial susceptibility test.Results The isolates were divided into 62 PFGE pattern,and each contains 1-11 strains.The result of antimicrobial susceptibility test showed that 55 strains were resistant to at least one antibiotic,including 15 multidrug resistant strains.The resistance rate to the eight antibiotics were nalidixic acid (40%),tetracycline (30%),chloramphenicol (15%),gentamicin (10%),trimethoprim/sulfamethoxazole (10%),ciprofloxacin (9%),cefoxitin (1%),and cefotaxime (0%).Conclusion PFGE profiles,antibiotic resistance patterns and serotypes of Salmonella showed high consistency.The antibiotic resistance of foodborne nontyphoidal Salmonella in Beijing was serious,and enhancing the joint monitoring of molecular subtyping and antibiotic resistance has significant importance.%目的 了解北京市食源性非伤寒沙门菌的分子特征及耐药情况.方法 对2004-2010年北京市食源性致病菌监测网收集的100株沙门菌进行脉冲场凝胶电泳(PFGE)分型和抗生素敏感性检测.结果 100株非伤寒沙门菌通过PFGE分型分为62个不同的带型,每个带型包含1~11株菌.抗生素敏感性结果显示,100株菌中有55株菌表现为对至少1种抗生素耐药,其中多重耐药菌株15株.菌株对各抗生素的耐药率为萘啶酸40%、四环素30%、氯霉素15%、庆大霉素10%、甲氧苄啶/磺胺甲恶唑10%、环丙沙星9%、头孢西丁1%、头孢噻肟0%.结论 沙门菌PFGE带型和耐药谱均与血清型存在很高的一致性.提示北京市食源性非伤寒沙门菌的耐药情况比较严重,开展对该菌分子分型与耐药特征分析的联合监测意义重大.

  9. HIV-1 Subtype distribution in morocco based on national sentinel surveillance data 2004-2005

    Directory of Open Access Journals (Sweden)

    Akrim Mohammed

    2012-02-01

    Full Text Available Abstract Background Little is known about HIV-1 subtype distribution in Morocco. Some data suggest an emergence of new HIV subtypes. We conducted phylogenetic analysis on a nationally representative sample of 60 HIV-1 viral specimens collected during 2004-2005 through the Morocco national HIV sentinel surveillance survey. Results While subtype B is still the most prevalent, 23.3% of samples represented non-B subtypes, the majority of which were classified as CRF02_AG (15%. Molecular clock analysis confirmed that the initial introduction of HIV-1B in Morocco probably came from Europe in the early 1980s. In contrast, the CRF02_AG strain appeared to be introduced from sub-Saharan Africa in two separate events in the 1990s. Conclusions Subtype CRF02_AG has been emerging in Morocco since the 1990s. More information about the factors introducing HIV subtype-specific transmission will inform the prevention strategy in the region.

  10. Diagnosis Molekuler Virus Flu Burung-A Subtipe H5 Berdasarkan Amplifikasi Gen M dan H5 dengan Metode Onestep Simplex RT-PCR (MOLECULAR DIAGNOSIS OF AVIAN INFLUENZA VIRUS TYPE A AND SUBTYPE H5 BY AMPLIFICATION OF ITS M AND H5 GENES USING ONE STEP SIMPLEX R

    Directory of Open Access Journals (Sweden)

    Aris Haryanto

    2014-08-01

    Full Text Available Influenza A viruses which belong to the Family of Orthomyxoviridae are a group of viruses withsegmented ssRNA genome. The viruses can be subgroupped into many subtypes on the basis of theirsurface glycoproteins, hemagglutinin (HA and neuraminidase (NA proteins. Among the HA subtypes, H5and H7 have been found to be the most pathogenic. Conventional diagnosis of the viruses is usuallyperformed by isolation of the viruses in embryonated eggs, and hemagglutination (HA and hemagglutinationinhibition test. Although those methods are sensitive and accurate, they are time consuming and requirelaboratory facilities with high biosafety level. Commercial methods such as emzyme-linked immonosorbentassay (ELISA and immunoflurescense assay also provide a rapid result but less sensitive and specificthan conventional methods. Molecular diagnosis by amplification of M and H5 genes using one strepsimplex reverse transcriptase-polymerase chain eraction (RT-PCR provices a rapid and accurate diagnosisfor the viruses. A study was therefore conducted to evaluate the accurate and rapidity of such the moleculartests for diagnosis of avian influenza A virus, subtype H5. As many as 10 sample of the virus isolateswhich were available at the Animal Desease investigation Center in Wates, Yogyakarta, were uses in thisstudy. The virus isolates were firstly propagated in specific antigen negative (SAN chicken embryos andtested by HA/HI test. The viruses were then subjected for the RT-PCR test with varying annealingtemperatures of 500C and 520C. The result showed that all 10 isolates were type A influenza virus and 8out of 10 were influenza A subtype H5 influenza virus. RT-PCR used in this study appears to be moresensitive, rapid and accurate as compared to those by serological and isolation of the virus in embryonatedeggs.

  11. Technical validation of an RT-qPCR in vitro diagnostic test system for the determination of breast cancer molecular subtypes by quantification of ERBB2, ESR1, PGR and MKI67 mRNA levels from formalin-fixed paraffin-embedded breast tumor specimens

    OpenAIRE

    Laible, Mark; Schlombs, Kornelia; Kaiser, Katharina; Veltrup, Elke; Herlein, Stefanie; Lakis, Sotiris; Stöhr, Robert; Eidt, Sebastian; Hartmann, Arndt; Wirtz, Ralph M.; Sahin, Ugur

    2016-01-01

    Background MammaTyper is a novel CE-marked in vitro diagnostic RT-qPCR assay which assigns routinely processed breast cancer specimens into the molecular subtypes Luminal A-like, Luminal B-like (HER2 positive or negative), HER2 positive (non-luminal) and Triple negative (ductal) according to the mRNA expression of ERBB2, ESR1, PGR and MKI67 and the St Gallen consensus surrogate clinical definition. Until now and regarding formalin-fixed, paraffin-embedded material (FFPE), this has been a task...

  12. 甲型副伤寒沙门菌的抗生素耐药性及分子分型研究%Drug resistance and molecular subtyping of almonella paratyphi A by PFGE

    Institute of Scientific and Technical Information of China (English)

    赖植发; 张勇; 曾华书; 侯红斌; 李波; 刘哲民

    2013-01-01

    目的 了解2008年深圳市福田区腹泻病人中分离的甲型副伤寒沙门菌的耐药性及分子分型特征.方法 从辖区内医院腹泻病人中分离得到11株甲型副伤寒沙门菌,选择10种抗生素,用K-B纸片扩散法进行药物敏感试验;细菌基因组DNA经限制性内切酶XbaⅠ酶切,用脉冲场凝胶电泳进行分子分型,使用Quantity-One TM软件成像并使用BioNumerics 6.1软件对其相似性进行分析比较.结果 11株甲型副伤寒沙门菌对氨苄西林、诺氟沙星、替卡西林等8种抗生素敏感率均为100%,对其余抗生素则出现中介或耐药菌株.对复方新诺明和氨苄西林敏感率为81.8%,四环素敏感率达90.9%.11株受试菌株的PFGE图谱经软件分析,可分为5个PFGE型,其相似性系数在93%以上.结论 本次研究的甲型副伤寒沙门菌对大多数抗生素敏感;菌株问有较高的同源性.%Objective To survey the resistance to antibiotics and typing characteristics of Salmonella paratyphi A isolated in diarrhea patient of Futian District,Shenzhen in 2008.Methods Eleven strains of Salmonella paratyphi A were isolated and identified from diarrhea patient of Futian District,and antimicrobial susceptibility test of the strains were conducted on by Kirby-Bauer methods using 10 kinds of antibiotics.Bacterial cells were lysised to release the bacteria genomic DNA,digested with restriction endonuclease Xba I.and then subjected to molecular subtyping by PFGE.Profiles were obtained with Quantity-One TM software and their homological analysis was conducted by BioNumerics 6.1 software.Results Eleven strains of Salmonella paratyphi A were all susceptible to eight antibiotics,such as ticarcillin,amikacin,norfloxacin,piperacillin,et al.And intermediate or low resistance to other antibiotics.The susceptibility of the 11 strains to co-trimoxazole and anpicillin were 81.8% and 90.9%.Analysis of the PFGE profiles of the 11 strains of Salmonella paratyphi A

  13. Assessing the genetic architecture of epithelial ovarian cancer histological subtypes.

    Science.gov (United States)

    Cuellar-Partida, Gabriel; Lu, Yi; Dixon, Suzanne C; Fasching, Peter A; Hein, Alexander; Burghaus, Stefanie; Beckmann, Matthias W; Lambrechts, Diether; Van Nieuwenhuysen, Els; Vergote, Ignace; Vanderstichele, Adriaan; Doherty, Jennifer Anne; Rossing, Mary Anne; Chang-Claude, Jenny; Rudolph, Anja; Wang-Gohrke, Shan; Goodman, Marc T; Bogdanova, Natalia; Dörk, Thilo; Dürst, Matthias; Hillemanns, Peter; Runnebaum, Ingo B; Antonenkova, Natalia; Butzow, Ralf; Leminen, Arto; Nevanlinna, Heli; Pelttari, Liisa M; Edwards, Robert P; Kelley, Joseph L; Modugno, Francesmary; Moysich, Kirsten B; Ness, Roberta B; Cannioto, Rikki; Høgdall, Estrid; Høgdall, Claus; Jensen, Allan; Giles, Graham G; Bruinsma, Fiona; Kjaer, Susanne K; Hildebrandt, Michelle A T; Liang, Dong; Lu, Karen H; Wu, Xifeng; Bisogna, Maria; Dao, Fanny; Levine, Douglas A; Cramer, Daniel W; Terry, Kathryn L; Tworoger, Shelley S; Stampfer, Meir; Missmer, Stacey; Bjorge, Line; Salvesen, Helga B; Kopperud, Reidun K; Bischof, Katharina; Aben, Katja K H; Kiemeney, Lambertus A; Massuger, Leon F A G; Brooks-Wilson, Angela; Olson, Sara H; McGuire, Valerie; Rothstein, Joseph H; Sieh, Weiva; Whittemore, Alice S; Cook, Linda S; Le, Nhu D; Blake Gilks, C; Gronwald, Jacek; Jakubowska, Anna; Lubiński, Jan; Kluz, Tomasz; Song, Honglin; Tyrer, Jonathan P; Wentzensen, Nicolas; Brinton, Louise; Trabert, Britton; Lissowska, Jolanta; McLaughlin, John R; Narod, Steven A; Phelan, Catherine; Anton-Culver, Hoda; Ziogas, Argyrios; Eccles, Diana; Campbell, Ian; Gayther, Simon A; Gentry-Maharaj, Aleksandra; Menon, Usha; Ramus, Susan J; Wu, Anna H; Dansonka-Mieszkowska, Agnieszka; Kupryjanczyk, Jolanta; Timorek, Agnieszka; Szafron, Lukasz; Cunningham, Julie M; Fridley, Brooke L; Winham, Stacey J; Bandera, Elisa V; Poole, Elizabeth M; Morgan, Terry K; Goode, Ellen L; Schildkraut, Joellen M; Pearce, Celeste L; Berchuck, Andrew; Pharoah, Paul D P; Webb, Penelope M; Chenevix-Trench, Georgia; Risch, Harvey A; MacGregor, Stuart

    2016-07-01

    Epithelial ovarian cancer (EOC) is one of the deadliest common cancers. The five most common types of disease are high-grade and low-grade serous, endometrioid, mucinous and clear cell carcinoma. Each of these subtypes present distinct molecular pathogeneses and sensitivities to treatments. Recent studies show that certain genetic variants confer susceptibility to all subtypes while other variants are subtype-specific. Here, we perform an extensive analysis of the genetic architecture of EOC subtypes. To this end, we used data of 10,014 invasive EOC patients and 21,233 controls from the Ovarian Cancer Association Consortium genotyped in the iCOGS array (211,155 SNPs). We estimate the array heritability (attributable to variants tagged on arrays) of each subtype and their genetic correlations. We also look for genetic overlaps with factors such as obesity, smoking behaviors, diabetes, age at menarche and height. We estimated the array heritabilities of high-grade serous disease ([Formula: see text] = 8.8 ± 1.1 %), endometrioid ([Formula: see text] = 3.2 ± 1.6 %), clear cell ([Formula: see text] = 6.7 ± 3.3 %) and all EOC ([Formula: see text] = 5.6 ± 0.6 %). Known associated loci contributed approximately 40 % of the total array heritability for each subtype. The contribution of each chromosome to the total heritability was not proportional to chromosome size. Through bivariate and cross-trait LD score regression, we found evidence of shared genetic backgrounds between the three high-grade subtypes: serous, endometrioid and undifferentiated. Finally, we found significant genetic correlations of all EOC with diabetes and obesity using a polygenic prediction approach. PMID:27075448

  14. Markers of subtypes in inflammatory breast cancer studied by immunohistochemistry: Prominent expression of P-cadherin

    OpenAIRE

    Viens Patrice; Xerri Luc; Esterni Benjamin; Ben Arab Saïda; Charafe-Jauffret Emmanuelle; Mrad Karima; Labidi Intidhar S; Ben Hamida Azza; Bertucci François; Birnbaum Daniel; Jacquemier Jocelyne

    2008-01-01

    Abstract Background Inflammatory breast cancer (IBC) is a distinct and aggressive form of locally-advanced breast cancer with high metastatic potential. In Tunisia, IBC is associated with a high death rate. Among the major molecular subtypes, basal breast carcinomas are poorly differentiated, have metastatic potential and poor prognosis, but respond relatively well to chemotherapy. The aim of this study was to determine the distribution of molecular subtypes in IBC and identify factors that m...

  15. 小切口大汗腺清除术治疗肛门瘙痒症%The apocrine sweat gland small incision dissection technique in the treatment of pruritus ani

    Institute of Scientific and Technical Information of China (English)

    秦宇伯; 梁德森; 汪大伟

    2012-01-01

    Objective To introduce the clinical experience on the curing of pruritus ani by using the method of apocrine sweat gland small incision dissection. Methods A retrospective analysis was made on the clinical, 2010-May. 2012 of 85 cases of people who is suffering from pruritus ani. Results All of the patients with the apocrine sweat gland dissection surgery were effective, 75 patients were cured. Conclusion Treatment of pruritus aniby destroying apocrine sweat gland with small incision was feasible, the effect is good, less pain, fewer complications.%目的 介绍小切口大汗腺清除术治疗肛门瘙痒症的临床经验.方法 对2010年1月至2012年5月期间治疗的85例肛门瘙痒症患者的临床资料进行回顾性分析.结果 85例全部有效,75例治愈.结论 采取小切口大汗腺清除术治疗肛门瘙痒症,方法有效,术后痛苦小,并发症少.

  16. Electrophysiological Correlates of Dyslexic Subtypes.

    Science.gov (United States)

    Flynn, Jane M.; And Others

    1992-01-01

    The construct validity of Boder's typology of dyslexia was investigated using quantified electroencephalography with 39 children (ages 7-11) during a reading task and at rest. Results supported beta frequency differences in anticipated regions by dyslexia subtype during the reading task. However, the direction of difference hypothesis was not…

  17. Increasing heterosexual transmission of HIV-1 subtype C in Inland Central Western Brazil.

    Science.gov (United States)

    Alcântara, Keila Correia; Reis, Monica Nogueira Guarda; Cardoso, Ludimila Paula Vaz; Bello, Gonzalo; Stefani, Mariane Martins Araújo

    2013-03-01

    The molecular epidemiology of HIV-1 in Brazil is complex and heterogeneous because several subtypes co-circulate with some important regional differences. This study evaluated HIV-1 subtypes amongst pregnant women living in the metropolitan area and in the interior cities from central western Brazil. From June 2008 to June 2010, 86.9% of confirmed cases of HIV-1 infection amongst pregnant women (172 out of 198 cases) were recruited in Goiania/Goias state. The HIV-1 pol gene was sequenced after nested-PCR. HIV-1 subtypes were assigned by REGA, phylogenetic, and bootscan analyses. The median age of participants was 26 years (15-41 years range); 58.7% of participants were diagnosed during prenatal care and 51.7% of participants came from >50 interior cities within Goias state. Amongst the 131 HIV-1 pol sequences, 64.9% were subtype B, 13.0% were BF1 recombinant, 11.4% were subtype C, 7.6% were subtype F1, and 2.3% were BC recombinant. According to the HIV-1 diagnosis date (1994-2010), a significant increase in subtype C and a decrease of BF1 mosaics were observed over time. All subtype C patients lived in interior cities where the highest prevalence of subtype C outside southern Brazil was observed (18.4%). Phylogenetic analysis revealed multiple independent introductions of the Brazilian subtype C clade from the southern/southeastern regions of Brazil. The HIV-1 epidemic in women from central western Brazil infected by the heterosexual route is characterized by an unexpectedly high prevalence of subtype C viruses highly related to those circulating in southern/southeastern Brazil. These findings highlight the importance of molecular surveillance programs outside large metropolitan regions in Brazil.

  18. Integrated Genomic Analysis Identifies Clinically Relevant Subtypes of Glioblastoma Characterized by Abnormalities in PDGFRA, IDH1, EGFR, and NF1

    Energy Technology Data Exchange (ETDEWEB)

    Verhaak, Roel GW; Hoadley, Katherine A; Purdom, Elizabeth; Wang, Victoria; Qi, Yuan; Wilkerson, Matthew D; Miller, C Ryan; Ding, Li; Golub, Todd; Mesirov, Jill P; Alexe, Gabriele; Lawrence, Michael; O' Kelly, Michael; Tamayo, Pablo; Weir, Barbara A; Gabriel, Stacey; Winckler, Wendy; Gupta, Supriya; Jakkula, Lakshmi; Feiler, Heidi S; Hodgson, J Graeme; James, C David; Sarkaria, Jann N; Brennan, Cameron; Kahn, Ari; Spellman, Paul T; Wilson, Richard K; Speed, Terence P; Gray, Joe W; Meyerson, Matthew; Getz, Gad; Perou, Charles M; Hayes, D Neil; Network, The Cancer Genome Atlas Research

    2009-09-03

    The Cancer Genome Atlas Network recently cataloged recurrent genomic abnormalities in glioblastoma multiforme (GBM). We describe a robust gene expression-based molecular classification of GBM into Proneural, Neural, Classical, and Mesenchymal subtypes and integrate multidimensional genomic data to establish patterns of somatic mutations and DNA copy number. Aberrations and gene expression of EGFR, NF1, and PDGFRA/IDH1 each define the Classical, Mesenchymal, and Proneural subtypes, respectively. Gene signatures of normal brain cell types show a strong relationship between subtypes and different neural lineages. Additionally, response to aggressive therapy differs by subtype, with the greatest benefit in the Classical subtype and no benefit in the Proneural subtype. We provide a framework that unifies transcriptomic and genomic dimensions for GBM molecular stratification with important implications for future studies.

  19. Molecular pharmacology of the calcium channel: evidence for subtypes, multiple drug-receptor sites, channel subunits, and the development of a radioiodinated 1,4-dihydropyridine calcium channel label, (/sup 125/I)iodipine

    Energy Technology Data Exchange (ETDEWEB)

    Glossmann, H.; Ferry, D.R.; Goll, A.; Rombusch, M.

    1984-01-01

    Radiolabeled Ca2+ antagonists (1,4-dihydropyridines, verapamil, and D-cis-diltiazem) were used to study voltage-operated Ca2+ channels in different excitable tissues. The concept of three subtypes of Ca2+ channels, represented by brain, heart, and skeletal-muscle isoreceptors for 1,4-dihydropyridines, is developed. The three subtypes are characterized by a variety of criteria. Despite the biochemical differences between the subtypes, they have the same Mr in situ by target-size analysis (Mr approximately equal to 180,000, when evaluated by (/sub 3/H)nimodipine). The concept of the metalloprotein nature of the channel and the interaction of channel drugs with the Me2+ binding sites of the ionic pore is demonstrated. Distinct but interacting drug-receptor sites of the Ca2+ channel are found by direct labeling as well as indirectly by drug competition studies. The authors distinguish between the 1,4-dihydropyridine site, the verapamil site, and the D-cis-diltiazem site. Each receptor site can exist in high and low-affinity state; the distribution of receptor sites in these states is regulated by temperature, ions, and drugs. The concept of intrinsic activity of drugs to stabilize the high-affinity state is exemplified for the 1,4-dihydropyridines. A change in the channel architecture is induced by binding of D-cis-diltiazem to its drug receptor site. This is proven by target-size analysis of the channel in situ. Partially purified t-tubule membranes from skeletal muscle are an extremely rich source of Ca2+ channel drug-receptor sites. The stoichiometry was determined in this preparation and found to be four verapamil:two 1,4-dihydropyridine:one D-cis-diltiazem site. A novel Ca2+ channel probe, (/sup 125/I)iodipine (2,200 Ci/mmol), was synthetized, and the properties of this ligand are presented.

  20. Multipotent nestin-positive stem cells reside in the stroma of human eccrine and apocrine sweat glands and can be propagated robustly in vitro.

    Directory of Open Access Journals (Sweden)

    Sabine Nagel

    Full Text Available Human skin harbours multiple different stem cell populations. In contrast to the relatively well-characterized niches of epidermal and hair follicle stem cells, the localization and niches of stem cells in other human skin compartments are as yet insufficiently investigated. Previously, we had shown in a pilot study that human sweat gland stroma contains Nestin-positive stem cells. Isolated sweat gland stroma-derived stem cells (SGSCs proliferated in vitro and expressed Nestin in 80% of the cells. In this study, we were able to determine the precise localization of Nestin-positive cells in both eccrine and apocrine sweat glands of human axillary skin. We established a reproducible isolation procedure and characterized the spontaneous, long-lasting multipotent differentiation capacity of SGSCs. Thereby, a pronounced ectodermal differentiation was observed. Moreover, the secretion of prominent cytokines demonstrated the immunological potential of SGSCs. The comparison to human adult epidermal stem cells (EpiSCs and bone marrow stem cells (BMSCs revealed differences in protein expression and differentiation capacity. Furthermore, we found a coexpression of the stem cell markers Nestin and Iα6 within SGSCs and human sweat gland stroma. In conclusion the initial results of the pilot study were confirmed, indicating that human sweat glands are a new source of unique stem cells with multilineage differentiation potential, high proliferation capacity and remarkable self renewal. With regard to the easy accessibility of skin tissue biopsies, an autologous application of SGSCs in clinical therapies appears promising.

  1. 不同分子分型乳腺癌长期预后及治疗对预后的影响:上海乳腺癌生存研究%Long-term survival analysis of different breast cancer molecular subtypes: Shanghai Breast Cancer Survival Study

    Institute of Scientific and Technical Information of China (English)

    鲍萍萍; 彭鹏; 顾凯; 吴春晓; 黄哲宙; 龚杨明; 张敏璐; 郑莹

    2015-01-01

    Objectives To analyze the survival of breast cancer molecular subtypes and to examine the effect of therapy on the long-term prognosis of different subtypes.Methods This study included 3 586 breast cancer patients with estrogen receptor (ER),progesterone receptor (PR) and human epidermal growth factor receptor-2 (HER2) information in Shanghai Breast Cancer Survival Study,a population-based prospective cohort study established in 2002.Molecular subtypes,based on immunohistochemistry were categorized as follows:Luminal A,Luminal B,HER2,and triple-negative subtype.Characteristics and clinical data were collected through questionnaires and medical records at baseline survey and sequential follow-up surveys.Survival rates of different molecular subtypes were analyzed and compared with Log-rank tests.Multiple Cox regression models were used to evaluate the effect of therapy on long-term prognosis of different molecular subtypes.Results Among the 3 586 cases,Luminal A,Luminal B,HER2 and triple-negative breast cancer subtypes accounted for 54.5%,16.6%,13.9%,and 14.9%,respectively.With a median follow-up of 10.3 years (ranging 0.6 to 12.8 years),the 10-year overall survival (OS) rates for the four subtypes were 82.7% (95% CI:80.9% to 84.4%),77.7%(95% CI:74.1% to80.8%),76.3% (95% CI:72.3% to79.8%),and74.8% (95% CI:70.9% to 78.3%),respectively.The 10-year disease to free survival (DFS) rates were 79.0% (95% CI:76.7% to 81.0%),76.0% (95% CI:71.9% to79.5%),73.6% (95% CI:68.9% to 77.7%),and 74.5% (95% CI:69.4% to 78.9%),respectively.Significant difference in survival among four subtypes was observed (Log-rank test,P < 0.01).Multivariate Cox regression indicated that hormonal therapy can significantly reduce the long-term risk of total mortality and recurrence breast cancer specific mortality among Luminal A subtype patients.Adjuvant chemotherapy could improve the long-term prognosis of triple

  2. Polymorphism of HLA-B27: 105 subtypes currently known.

    Science.gov (United States)

    Khan, Muhammad Asim

    2013-10-01

    HLA-B27 has a high degree of genetic polymorphism, with 105 known subtypes, named HLA-B*27:01 to HLA-B*27:106, encoded by 132 alleles. The most common subtypes associated with ankylosing spondylitis are HLA-B*27:05 (Caucasians), HLA-B*27:04 (Chinese), and HLA-B*27:02 (Mediterranean populations). For Chinese populations, HLA-B*27:04 is associated with a greater ankylosing spondylitis risk than HLA-B*27:05. Two subtypes, HLA-B27*06 and HLA-B27*09, seem to have no disease association. These differential disease associations of HLA-B27 subtypes, and the recent discovery that ERAP1 is associated with ankylosing spondylitis for patients with HLA-B27, have increased attempts to determine the function of HLA-B27 in disease pathogenesis by studying hemodynamic features of its protein structure, alterations of its peptidome, aberrant peptide handling, and associated molecular events. However, after 40 years we still do not fully know how HLA-B27 predisposes to ankylosing spondylitis and related spondyloarthritis. PMID:23990399

  3. Distribution of apocrine sweat glands in axillary region of patients with axillary osmidrosis%腋臭患者腋区顶泌汗腺的分布特点

    Institute of Scientific and Technical Information of China (English)

    邢卫斌; 刘文芳; 赵子申; 彭军; 李兴文; 马玉枝; 王娜

    2014-01-01

    目的 检测腋臭患者腋区顶泌汗腺在深度、广度的分布,探讨其范围内的分布差异性.方法 2010年9-12月间的15例腋臭患者,行直视下顶泌汗腺剪除术,切取切口处宽约2 mm的全层皮肤,深度达腋浅筋膜浅层,用于判明顶泌汗腺分布的深度.留取腋中心(点1)、距腋中心1 cm(点2)、距腋毛边缘内1cm(点3)、腋毛边缘(点4)、距腋毛边缘外1 cm(点5)共5个标记点对应的皮下暗红色粗大的颗粒状组织,用于判明顶泌汗腺的分布范围及分布规律.结果 顶泌汗腺分泌部主要分布于真皮网状层和皮下脂肪浅层,表皮层、真皮乳头层及腋浅筋膜浅层均无顶泌汗腺分布.顶泌汗腺广度分布与腋毛范围基本一致,腋中心部可见大量顶泌汗腺组织,腋毛边缘处仍有少量顶泌汗腺分布,腋毛边缘外1.0 cm处已无顶泌汗腺分布.5个点顶泌汗腺面积占整块组织面积的百分比平均值分别为74.1%、46.6%、25.3%、2.1%和0,相邻两点进行t检验,点1、2之间f=29.78,P< 0.01;点2、3之间t=9.76,P< 0.01;点3、4之间t=20.83,P< 0.01;点4、5之间t=1.96,P> 0.05.结论 手术治疗腋臭时,清除范围深度达真皮网状层和浅层脂肪层,广度到腋毛范围即可,没有必要过度扩大清除范围.%Objective To determine the distribution profile of apocrine sweat glands in axillary region of patients with axillary osmidrosis,and to compare their distribution at different sites.Methods Fifteen patients with axillary osmidrosis were enrolled in this study from September to December 2010.All the patients underwent surgical removal of apocrine sweat glands under direct vision.Full-thickness skin tissue measuring 2 mm in width was excised down to the axillary superficial fascia at the incisional surgical sites from five patients.Five points,which were at the center of axillary region (point 1),1 cm away from the center of axillary region (point 2),1 cm inside the edge of axillary

  4. Distribution of human immunodeficiency virus type 1 subtypes in the State of Amazonas, Brazil, and subtype C identification

    Energy Technology Data Exchange (ETDEWEB)

    Cunha, L.K.H. [Departamento de Parasitologia, Universidade Federal do Amazonas, Manaus, AM (Brazil); Kashima, S.; Amarante, M.F.C.; Haddad, R.; Rodrigues, E.S. [Laboratório de Biologia Molecular, Hemocentro de Ribeirão Preto, Faculdade de Medicina de Ribeirão Preto, Universidade de São Paulo, Ribeirão Preto, SP (Brazil); Silva, K.L.T.; Lima, T.A.; Castro, D.B.; Brito, F.C.; Almeida, E.G. [Diretoria de Ensino e Pesquisa,Fundação de Hematologia e Hemoterapia do Amazonas, Manaus, AM (Brazil); Covas, D.T. [Laboratório de Biologia Molecular, Hemocentro de Ribeirão Preto, Faculdade de Medicina de Ribeirão Preto, Universidade de São Paulo, Ribeirão Preto, SP (Brazil); Malheiro, A. [Departamento de Parasitologia, Universidade Federal do Amazonas, Manaus, AM (Brazil); Diretoria de Ensino e Pesquisa,Fundação de Hematologia e Hemoterapia do Amazonas, Manaus, AM (Brazil)

    2012-01-20

    Few studies have reported the molecular epidemiological characterization of HIV-1 in the Northern region of Brazil. The present study reports the molecular and epidemiological characterization of 31 HIV-1 isolates from blood donors from the State of Amazonas who donated blood between April 2006 and March 2007. Serum/plasma samples from all donors were screened for HIV antibodies by ELISA and the results confirmed by Western blot analysis. Genomic DNA was extracted from the buffy coat using the Super Quik-Gene-DNA Isolation kit. Nested PCR was performed on the env, gag, and pol regions of HIV-1 using the Gene Amp PCR System 9700. Sequencing reactions were performed using the inner PCR primers and the DYEnamic™ ET Dye Terminator Kit, and phylogenetic analysis was performed using the gag, pol, and env gene sequences. We collected samples from 31 blood donors who tested positive for HIV-1 in confirmatory experiments. The male:female ratio of blood donors was 3.4:1, and the mean age was 32.4 years (range: 19 to 61 years). Phylogenetic analysis showed that subtype B is the most prevalent among Northern Brazilian HIV-1-seropositive blood donors. One HIV-1 subtype C and one circulating recombinant form (CRF-BF) of HIV-1 were identified in the State of Amazonas. This is the first study showing the occurrence of a possible “homogenous” subtype C in this region of Brazil. This finding could contribute to a better characterization of the HIV-1 strains that circulate in the country. Key words: HIV-1; Subtypes; Phylogenetic analysis; Blood donors; Molecular and epidemiological characterization.

  5. Distribution of human immunodeficiency virus type 1 subtypes in the State of Amazonas, Brazil, and subtype C identification

    International Nuclear Information System (INIS)

    Few studies have reported the molecular epidemiological characterization of HIV-1 in the Northern region of Brazil. The present study reports the molecular and epidemiological characterization of 31 HIV-1 isolates from blood donors from the State of Amazonas who donated blood between April 2006 and March 2007. Serum/plasma samples from all donors were screened for HIV antibodies by ELISA and the results confirmed by Western blot analysis. Genomic DNA was extracted from the buffy coat using the Super Quik-Gene-DNA Isolation kit. Nested PCR was performed on the env, gag, and pol regions of HIV-1 using the Gene Amp PCR System 9700. Sequencing reactions were performed using the inner PCR primers and the DYEnamic™ ET Dye Terminator Kit, and phylogenetic analysis was performed using the gag, pol, and env gene sequences. We collected samples from 31 blood donors who tested positive for HIV-1 in confirmatory experiments. The male:female ratio of blood donors was 3.4:1, and the mean age was 32.4 years (range: 19 to 61 years). Phylogenetic analysis showed that subtype B is the most prevalent among Northern Brazilian HIV-1-seropositive blood donors. One HIV-1 subtype C and one circulating recombinant form (CRF-BF) of HIV-1 were identified in the State of Amazonas. This is the first study showing the occurrence of a possible “homogenous” subtype C in this region of Brazil. This finding could contribute to a better characterization of the HIV-1 strains that circulate in the country. Key words: HIV-1; Subtypes; Phylogenetic analysis; Blood donors; Molecular and epidemiological characterization

  6. Origin and dynamics of HIV-1 subtype C infection in India.

    Directory of Open Access Journals (Sweden)

    Chengli Shen

    Full Text Available OBJECTIVE: To investigate the geographical origin and evolution dynamics of HIV-1 subtype C infection in India. DESIGN: Ninety HIV-1 subtype C env gp120 subtype C sequences from India were compared with 312 env gp120 reference subtype C sequences from 27 different countries obtained from Los Alamos HIV database. All the HIV-1 subtype C env gp120 sequences from India were used for the geographical origin analysis and 61 subtype C env gp120 sequences with known sampling year (from 1991 to 2008 were employed to determine the origin of HIV infection in India. METHODS: Phylogenetic analysis of HIV-1 env sequences was used to investigate the geographical origin and tMRCA of Indian HIV-1 subtype C. Evolutionary parameters including origin date and demographic growth patterns of Indian subtype C were estimated using a Bayesian coalescent-based approach under relaxed molecular clock models. FINDINGS: The majority of the analyzed Indian and South African HIV-1 subtype C sequences formed a single monophyletic cluster. The most recent common ancestor date was calculated to be 1975.56 (95% HPD, 1968.78-1981.52. Reconstruction of the effective population size revealed three phases of epidemic growth: an initial slow growth, followed by exponential growth, and then a plateau phase approaching present time. Stabilization of the epidemic growth phase correlated with the foundation of National AIDS Control Organization in India. INTERPRETATION: Indian subtype C originated from a single South African lineage in the middle of 1970s. The current study emphasizes not only the utility of HIV-1 sequence data for epidemiological studies but more notably highlights the effectiveness of community or government intervention strategies in controlling the trend of the epidemic.

  7. Assessing Interpersonal Subtypes in Depression.

    Science.gov (United States)

    Simon, Sarah; Cain, Nicole M; Wallner Samstag, Lisa; Meehan, Kevin B; Muran, J Christopher

    2015-01-01

    The context-free diagnoses outlined by the Diagnostic and Statistical Manual of Mental Disorders might not provide enough information to represent the heterogeneity observed in depressed patients. Interpersonal factors have been linked to depression in a mutually influencing pathoplastic relationship where certain problems, like submissiveness, are related to symptom chronicity. This study evaluated interpersonal pathoplasticity in a range of depressive presentations. We examined archival data collected from 407 participants who met criteria for major depressive disorder (MDD), dysthymic disorder (DD), or subthreshold depression (sD). Latent profile analysis (LPA) identified 5 interpersonal subtypes (vindictive, intrusive, socially avoidant, exploitable, and cold). Apart from gender, the subtypes did not differ significantly on demographic characteristics, psychiatric comorbidity, or self-report depression severity. Socially avoidant participants were more likely to meet criteria for a clinical depression diagnosis (MDD or DD), whereas vindictive participants were more likely to have sD. Our results indicate that interpersonal problems could account for heterogeneity observed in depression. PMID:25803309

  8. Discovery and validation of breast cancer subtypes

    Directory of Open Access Journals (Sweden)

    Bukholm Ida RK

    2006-09-01

    Full Text Available Abstract Background Previous studies demonstrated breast cancer tumor tissue samples could be classified into different subtypes based upon DNA microarray profiles. The most recent study presented evidence for the existence of five different subtypes: normal breast-like, basal, luminal A, luminal B, and ERBB2+. Results Based upon the analysis of 599 microarrays (five separate cDNA microarray datasets using a novel approach, we present evidence in support of the most consistently identifiable subtypes of breast cancer tumor tissue microarrays being: ESR1+/ERBB2-, ESR1-/ERBB2-, and ERBB2+ (collectively called the ESR1/ERBB2 subtypes. We validate all three subtypes statistically and show the subtype to which a sample belongs is a significant predictor of overall survival and distant-metastasis free probability. Conclusion As a consequence of the statistical validation procedure we have a set of centroids which can be applied to any microarray (indexed by UniGene Cluster ID to classify it to one of the ESR1/ERBB2 subtypes. Moreover, the method used to define the ESR1/ERBB2 subtypes is not specific to the disease. The method can be used to identify subtypes in any disease for which there are at least two independent microarray datasets of disease samples.

  9. Analysis of dinucleotide signatures in HIV-1 subtype B genomes

    Indian Academy of Sciences (India)

    Aridaman Pandit; Jyothirmayi Vadlamudi; Somdatta Sinha

    2013-12-01

    Dinucleotide usage is known to vary in the genomes of organisms. The dinucleotide usage profiles or genome signatures are similar for sequence samples taken from the same genome, but are different for taxonomically distant species. This concept of genome signatures has been used to study several organisms including viruses, to elucidate the signatures of evolutionary processes at the genome level. Genome signatures assume greater importance in the case of host–pathogen interactions, where molecular interactions between the two species take place continuously, and can influence their genomic composition. In this study, analyses of whole genome sequences of the HIV-1 subtype B, a retrovirus that caused global pandemic of AIDS, have been carried out to analyse the variation in genome signatures of the virus from 1983 to 2007.We show statistically significant temporal variations in some dinucleotide patterns highlighting the selective evolution of the dinucleotide profiles of HIV-1 subtype B, possibly a consequence of host specific selection.

  10. HIV-1 epidemiology and circulating subtypes in the countryside of South Brazil

    Directory of Open Access Journals (Sweden)

    Carina Sperotto Librelotto

    2015-06-01

    Full Text Available INTRODUCTION: Human immunodeficiency virus type 1 (HIV-1 has spread worldwide, with several subtypes and circulating recombinant forms. Brazil has an incidence of 20.5 HIV-1/acquired immunodeficiency syndrome (AIDS patients per 100,000 inhabitants; however, the Southernmost State of Rio Grande do Sul (RS has more than twice the number of HIV-1-infected people (41.3/100,000 inhabitants and a different pattern of subtype frequencies, as previously reported in studies conducted in the capital (Porto Alegre and its metropolitan region. This study examined HIV-1/AIDS epidemiological and molecular aspects in the countryside of Rio Grande do Sul. METHODS: Socio-demographic, clinical and risk behavioral characteristics were obtained from HIV-1-positive adult patients using a structured questionnaire. HIV-1 subtypes were determined by nested-polymerase chain reaction (PCR and sequencing of the pol and env genes. RESULTS: The study sample included 149 (55% women patients with a mean age of 41.8 ± 11.9 years. Most (73.8% patients had a low education level and reported heterosexual practices as the most (91.9% probable transmission route. HIV-1 subtypes were detected in 26 patients: 18 (69.2% infected with subtype C, six (23.1% infected with subtype B and two (7.7% infected with BC recombinant forms. CONCLUSIONS: These data highlight the increasing number of HIV-1 subtype C infections in the countryside of South Brazil.

  11. Transsexual subtypes : Clinical and theoretical significance

    NARCIS (Netherlands)

    Smith, YLS; van Goozen, SHM; Kuiper, AJ; Cohen-Kettenis, PT

    2005-01-01

    The present study was designed to investigate whether transsexuals can be validly subdivided into subtypes on the basis of sexual orientation, and whether differences between subtypes of transsexuals are similar for male-to-female (ME) and female-to-male transsexuals (FMs). Within a large transsexua

  12. Serum proteomic profiles of depressive subtypes.

    Science.gov (United States)

    Lamers, F; Bot, M; Jansen, R; Chan, M K; Cooper, J D; Bahn, S; Penninx, B W J H

    2016-01-01

    Depression is a highly heterogeneous disorder. Accumulating evidence suggests biological and genetic differences between subtypes of depression that are homogeneous in symptom presentation. We aimed to evaluate differences in serum protein profiles between persons with atypical and melancholic depressive subtypes, and compare these profiles with serum protein levels of healthy controls. We used the baseline data from the Netherlands Study of Depression and Anxiety on 414 controls, 231 persons with a melancholic depressive subtype and 128 persons with an atypical depressive subtype for whom the proteomic data were available. Depressive subtypes were previously established using a data-driven analysis, and 171 serum proteins were measured on a multi-analyte profiling platform. Linear regression models were adjusted for several covariates and corrected for multiple testing using false discovery rate q-values. We observed differences in analytes between the atypical and melancholic subtypes (9 analytes, qcommunication and signal transduction, and immune response. No markers differed significantly between the melancholic subtype and controls. To conclude, although some uncertainties exist in our results as a result of missing data imputation and lack of proteomic replication samples, many of the identified analytes are inflammatory or metabolic markers, which supports the notion of atypical depression as a syndrome characterized by metabolic disturbances and inflammation, and underline the importance and relevance of subtypes of depression in biological and genetic research, and potentially in the treatment of depression. PMID:27404283

  13. Discovery and validation of breast cancer subtypes

    OpenAIRE

    Bukholm Ida RK; Noh Dong-Young; Han Wonshik; Børresen-Dale Anne-Lise; Langerød Anita; Jeffrey Stefanie S; Kapp Amy V; Nicolau Monica; Brown Patrick O; Tibshirani Robert

    2006-01-01

    Background Previous studies demonstrated breast cancer tumor tissue samples could be classified into different subtypes based upon DNA microarray profiles. The most recent study presented evidence for the existence of five different subtypes: normal breast-like, basal, luminal A, luminal B, and ERBB2+. Results Based upon the analysis of 599 microarrays (five separate cDNA microarray datasets) using a ...

  14. ADHD-hyperactive/impulsive subtype in adults

    Directory of Open Access Journals (Sweden)

    Stephen V. Faraone

    2010-01-01

    Full Text Available This is the first study to evaluate ADHD-hyperactive/impulsive subtype in a large clinical sample of adults with ADHD. The Quality of Life, Effectiveness, Safety and Tolerability (QuEST study included 725 adults who received clinician diagnoses of any ADHD subtype. Cross-sectional baseline data from 691 patients diagnosed with the hyperactive/impulsive (HI, inattentive (IA and combined subtypes were used to compare the groups on the clinician administered ADHD-RS, clinical features and health-related quality of life. A consistent pattern of differences was found between the ADHD-I and combined subtypes, with the combined subtype being more likely to be diagnosed in childhood, more severe symptom severity and lower HRQL. Twenty-three patients out of the total sample of 691 patients (3% received a clinician diagnosis of ADHD - hyperactive/impulsive subtype. Review of the ratings on the ADHD-RS-IV demonstrated, however, that this group had ratings of inattention comparable to the inattentive group. There were no significant differences found between the ADHD-HI and the other subtypes in symptom severity, functioning or quality of life. The hyperactive/impulsive subtype group identified by clinicians in this study was not significantly different from the rest of the sample. By contrast, significant differences were found between the inattentive and combined types. This suggests that in adults, hyperactivity declines and inattention remains significant, making the hyperactive/impulsive subtype as defined by childhood criteria a very rare condition and raising questions as to the validity of the HI subtype in adults.

  15. Nominal and Structural Subtyping in Component-Based Programming

    DEFF Research Database (Denmark)

    Ostermann, Klaus

    2007-01-01

    type. We analyze structural and different flavors of nominal subtyping from the perspective of component-based programming, where issues such as blame assignment and modular extensibility are important. Our analysis puts various existing subtyping mechanisms into a common frame of reference...... and delineates the frontiers of the subtyping design space. In addition, we propose a new subtyping definition in one particularly interesting corner of the design space which combines the safety of nominal subtyping with the flexibility of structural subtyping....

  16. 桥式双切口顶泌汗腺修剪术治疗腋臭176例临床分析%Clinical analysis of 176 bromhidrosis cases accepted apocrine sweat glands two-incision bridge trim

    Institute of Scientific and Technical Information of China (English)

    任杰; 代永霞; 李歌; 李振鲁

    2014-01-01

    ObjectiveTo evaluate the efficacy and adverse reactions of apocrine sweat glands two-incision bridge trim in the treatment of bromhidrosis.MethodsOne hundred and seventy-six patients with axillary bromhidrosis were treated with apocrine sweat glands two-incision bridge trim. The efifcacy and adverse reactions were assessed using the method of visual analog score a year after the treatment.ResultsFor the total 176 cases, cured 164 cases (93%), effective 12 cases(7%), the total effective rate was 100%. Superifcial ulcers of incision and delayed healing occurred in 4 cases, which leaded to the formation of slight scar. All the patients showed armpit hair and sweat reduced, no infection and hematoma occurred, and the local skin was soft.ConclusionThe operation of apocrine sweat glands two-incision bridge trim is convenient, with reliable curative effect, beautiful incision and less adverse reactions , which is worthy of clinical generalization.%目的:评价桥式双切口顶泌汗腺修剪术治疗腋臭的疗效及不良反应。方法采用桥式双切口顶泌汗腺修剪术治疗176例腋臭患者,用视觉模拟评分法(VAS)于术后1年评估其疗效及不良反应。结果176例患者中,治愈164例(93%),有效12例(7%),总有效率100%。其中有4例患者切口发生表浅溃疡,延期愈合,留下轻微瘢痕。全组腋毛均减少,出汗减少,皮肤质地柔软,无感染、无血肿。结论桥式双切口顶泌汗腺修剪术操作方便,切口美观,不良反应少。

  17. 微切口皮下搔刮清除大汗腺治疗腋臭若干问题探讨%Problems discussion of micro-incision subcutaneous curettage of apocrine sweat glands therapy for axillary bromhidrosis

    Institute of Scientific and Technical Information of China (English)

    张志千

    2011-01-01

    objective To discuss the micro-incision subcutaneous curettage of apocrine sweat glands therapy for axillary bromhidrosis. Methods 1023 cases with axillary bromhidrosis were treated with micro-incision subcutaneous curettage of apocrine sweat glands therapy .Analyze the causes of patients with incompletely clear and suggest effect methods to solve problems. Results 1023 patients were followed-up for six months to one year.Treatment total effective power were up to 100%.986 cases were pleased with odour disappearance.satisfaction rate up to 96.4% .3.6% patients still remained slightly odour and were treated with the same therapy.All have achieved satisfactory results. Conclusion The micro -incision subcutaneous curettage of apocrine sweat glands therapy for axillary bromhidrosis has such advantages as high efficiency, minimal invasion,faster recovery,less pain,no scars and not affect arm function.ln addition,the therapy could reduce the growth of armpit hair with the cosmetic results,be favored by women and treat axillary hyperhidrosis.%目的:对于微切口皮下搔刮清除大汗腺治疗腋臭出现的问题进行探讨.方法:对1023例患者采用腋部微切口皮下搔刮清除大汗腺治疗腋臭,出现清除不彻底原因进行分析,提出关键有效的方法.结果:1023例腋臭患者,术后随访6个月~1年,总有效率为100%,其中986例臭味消失为满意,满意率96.4%,仍有轻度臭味者37例,占3.6%,半年后采用相同方法清除达到满意效果.结论:微切口皮下搔刮清除大汗腺治疗腋臭疗效确切,损伤小、恢复快、痛苦少、无瘢痕不影响手臂功能,兼有减少腋毛生长的美容效果,同时还能治疗腋部多汗症.

  18. Genetic background may contribute to PAM50 gene expression breast cancer subtype assignments.

    Directory of Open Access Journals (Sweden)

    Ying Hu

    Full Text Available Recent advances in genome wide transcriptional analysis have provided greater insights into the etiology and heterogeneity of breast cancer. Molecular signatures have been developed that stratify the conventional estrogen receptor positive or negative categories into subtypes that are associated with differing clinical outcomes. It is thought that the expression patterns of the molecular subtypes primarily reflect cell-of-origin or tumor driver mutations. In this study however, using a genetically engineered mouse mammary tumor model we demonstrate that the PAM50 subtype signature of tumors driven by a common oncogenic event can be significantly influenced by the genetic background on which the tumor arises. These results have important implications for interpretation of "snapshot" expression profiles, as well as suggesting that incorporation of genetic background effects may allow investigation into phenotypes not initially anticipated in individual mouse models of cancer.

  19. Hepatitis C virus (HCV genotype 1 subtype identification in new HCV drug development and future clinical practice.

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    Stéphane Chevaliez

    Full Text Available BACKGROUND: With the development of new specific inhibitors of hepatitis C virus (HCV enzymes and functions that may yield different antiviral responses and resistance profiles according to the HCV subtype, correct HCV genotype 1 subtype identification is mandatory in clinical trials for stratification and interpretation purposes and will likely become necessary in future clinical practice. The goal of this study was to identify the appropriate molecular tool(s for accurate HCV genotype 1 subtype determination. METHODOLOGY/PRINCIPAL FINDINGS: A large cohort of 500 treatment-naïve patients eligible for HCV drug trials and infected with either subtype 1a or 1b was studied. Methods based on the sole analysis of the 5' non-coding region (5'NCR by sequence analysis or reverse hybridization failed to correctly identify HCV subtype 1a in 22.8%-29.5% of cases, and HCV subtype 1b in 9.5%-8.7% of cases. Natural polymorphisms at positions 107, 204 and/or 243 were responsible for mis-subtyping with these methods. A real-time PCR method using genotype- and subtype-specific primers and probes located in both the 5'NCR and the NS5B-coding region failed to correctly identify HCV genotype 1 subtype in approximately 10% of cases. The second-generation line probe assay, a reverse hybridization assay that uses probes targeting both the 5'NCR and core-coding region, correctly identified HCV subtypes 1a and 1b in more than 99% of cases. CONCLUSIONS/SIGNIFICANCE: In the context of new HCV drug development, HCV genotyping methods based on the exclusive analysis of the 5'NCR should be avoided. The second-generation line probe assay is currently the best commercial assay for determination of HCV genotype 1 subtypes 1a and 1b in clinical trials and practice.

  20. A novel subtype classification and risk of breast cancer by histone modification profiling.

    Science.gov (United States)

    Chen, Xiaohua; Hu, Hanyang; He, Lin; Yu, Xueyuan; Liu, Xiangyu; Zhong, Rong; Shu, Maoguo

    2016-06-01

    Breast cancer has been classified into several intrinsic molecular subtypes on the basis of genetic and epigenetic factors. However, knowledge about histone modifications that contribute to the classification and development of biologically distinct breast cancer subtypes remains limited. Here we compared the genome-wide binding patterns of H3K4me3 and H3K27me3 between human mammary epithelial cells and three breast cancer cell lines representing the luminal, HER2, and basal subtypes. We characterized thousands of unique binding events as well as bivalent chromatin signatures unique to each cancer subtype, which were involved in different epigenetic regulation programs and signaling pathways in breast cancer progression. Genes linked to the unique histone mark features exhibited subtype-specific expression patterns, both in cancer cell lines and primary tumors, some of which were confirmed by qPCR in our primary cancer samples. Finally, histone mark-based gene classifiers were significantly correlated with relapse-free survival outcomes in patients. In summary, we have provided a valuable resource for the identification of novel biomarkers of subtype classification and clinical prognosis evaluation in breast cancers. PMID:27178334

  1. High-resolution subtyping of Staphylococcus aureus strains by means of Fourier-transform infrared spectroscopy.

    Science.gov (United States)

    Johler, Sophia; Stephan, Roger; Althaus, Denise; Ehling-Schulz, Monika; Grunert, Tom

    2016-05-01

    Staphylococcus aureus causes a variety of serious illnesses in humans and animals. Subtyping of S. aureus isolates plays a crucial role in epidemiological investigations. Metabolic fingerprinting by Fourier-transform infrared (FTIR) spectroscopy is commonly used to identify microbes at species as well as subspecies level. In this study, we aimed to assess the suitability of FTIR spectroscopy as a tool for S. aureus subtyping. To this end, we compared the subtyping performance of FTIR spectroscopy to other subtyping methods such as pulsed field gel electrophoresis (PFGE) and spa typing in a blinded experimental setup and investigated the ability of FTIR spectroscopy for identifying S. aureus clonal complexes (CC). A total of 70 S. aureus strains from human, animal, and food sources were selected, for which clonal complexes and a unique virulence and resistance gene pattern had been determined by DNA microarray analysis. FTIR spectral analysis resulted in high discriminatory power similar as obtained by spa typing and PFGE. High directional concordance was found between FTIR spectroscopy based subtypes and capsular polysaccharide expression detected by FTIR spectroscopy and the cap specific locus, reflecting strain specific expression of capsular polysaccharides and/or other surface glycopolymers, such as wall teichoic acid, peptidoglycane, and lipoteichoic acid. Supervised chemometrics showed only limited possibilities for differentiation of S. aureus CC by FTIR spectroscopy with the exception of CC45 and CC705. In conclusion, FTIR spectroscopy represents a valuable tool for S. aureus subtyping, which complements current molecular and proteomic strain typing. PMID:27021524

  2. Identification of logic relationships between genes and subtypes of non-small cell lung cancer.

    Directory of Open Access Journals (Sweden)

    Yansen Su

    Full Text Available Non-small cell lung cancer (NSCLC has two major subtypes: adenocarcinoma (AC and squamous cell carcinoma (SCC. The diagnosis and treatment of NSCLC are hindered by the limited knowledge about the pathogenesis mechanisms of subtypes of NSCLC. It is necessary to research the molecular mechanisms related with AC and SCC. In this work, we improved the logic analysis algorithm to mine the sufficient and necessary conditions for the presence states (presence or absence of phenotypes. We applied our method to AC and SCC specimens, and identified [Formula: see text] lower and [Formula: see text] higher logic relationships between genes and two subtypes of NSCLC. The discovered relationships were independent of specimens selected, and their significance was validated by statistic test. Compared with the two earlier methods (the non-negative matrix factorization method and the relevance analysis method, the current method outperformed these methods in the recall rate and classification accuracy on NSCLC and normal specimens. We obtained [Formula: see text] biomarkers. Among [Formula: see text] biomarkers, [Formula: see text] genes have been used to distinguish AC from SCC in practice, and other six genes were newly discovered biomarkers for distinguishing subtypes. Furthermore, NKX2-1 has been considered as a molecular target for the targeted therapy of AC, and [Formula: see text] other genes may be novel molecular targets. By gene ontology analysis, we found that two biological processes ('epidermis development' and 'cell adhesion' were closely related with the tumorigenesis of subtypes of NSCLC. More generally, the current method could be extended to other complex diseases for distinguishing subtypes and detecting the molecular targets for targeted therapy.

  3. Precise subtyping for synchronous multiparty sessions

    OpenAIRE

    Dezani-Ciancaglini, Mariangiola; Ghilezan, Silvia; Jakšić, Svetlana; Pantović, Jovanka; Yoshida, Nobuko

    2016-01-01

    The notion of subtyping has gained an important role both in theoretical and applicative domains: in lambda and concurrent calculi as well as in programming languages. The soundness and the completeness, together referred to as the preciseness of subtyping, can be considered from two different points of view: operational and denotational. The former preciseness has been recently developed with respect to type safety, i.e. the safe replacement of a term of a smaller type when a term of a bigge...

  4. Verified Subtyping with Traits and Mixins

    OpenAIRE

    Sharma, Asankhaya

    2014-01-01

    Traits allow decomposing programs into smaller parts and mixins are a form of composition that resemble multiple inheritance. Unfortunately, in the presence of traits, programming languages like Scala give up on subtyping relation between objects. In this paper, we present a method to check subtyping between objects based on entailment in separation logic. We implement our method as a domain specific language in Scala and apply it on the Scala standard library. We have verified that 67% of mi...

  5. 乳腺癌分子分型与多西他赛密集新辅助化疗疗效及预后的关系研究%Relationship of Molecular Subtypes and Therapeutic Effect and Prognosis of Dose Dense Docetaxel Neoadjuvant Chemotherapy in Breast Cancer

    Institute of Scientific and Technical Information of China (English)

    刘秋明; 曹亚丽; 吴晓波; 夏勇; 涂剑宏; 欧阳倩雯; 周平; 胡平华; 陈军

    2012-01-01

    Objective To investigate the relationship between different molecular subtypes and the therapeutic effect and prognosis of dose dense docetaxel neoadjuvant chemotherapy in breast cancer. Methods 82 breast cancer patients admitted to our hospital from March 2007 to March 2010 were given four cycles of docetaxel chemotherapy ( 75 mg/m , with two weeks as a cycle ), followed by surgical operation. After operation, the patients were given four cycles of EC chemotherapy ( with EPI 75 mg/m , CTX 600 mg/m and two weeks as a cycle ) . Immunohistochemical studies and fluorescence in -situ hybridization were performed to detect the expression of estrogen receptor ( ER ), progesterone receptor ( PR ), Her - 2 and Ki67 of breast cancer before treatment. The patients were classified into 4 subtypes: luminal A, luminal B, Her -2 + and triple negative. The therapeutic effect and prognosis of the four subtypes after dose dense docetaxel neoadjuvant chemotherapy were analyzed. Results Of the total 82 patients, the overall response rate ( RR ) was 89. 0% ( 73/82 ), including 17 cases of complete response ( CR ), 56 cases of partial response ( PR ), 9 cases of stable disease ( SD ) and no progression of disease ( PD ) . FISH were performed to detect 11 cases of IHC scores of 2 + . There were 5 cases for the overexpression of Her -2. According to the results of immunohis- tochemical studies and FISH method on the expression of ER, PR, Her -2 and Ki67, there were 39 cases ( 47. 6% ) of Luminal A, 19 cases ( 23. 2% ) of Luminal B, 11 cases ( 13. 4% ) of Her - 2 + and 13 cases ( 15. 9% ) of triple negative. The age, tumor size, lymph node metastasis, histological type and surgical style among breast cancer patients with different molecular subtypes showed no statistically significant differences ( P > 0. 05 ) . The RR of luminal A, luminal B, Her - 2 + and triple negative were 84. 6% ( 33/39 ), 84. 2% ( 16/19 ), 100. 0% ( 11/11 ) and 100. 0% ( 13/13 ) respectively, and the difference was

  6. Zebrafish Mnx proteins specify one motoneuron subtype and suppress acquisition of interneuron characteristics

    Directory of Open Access Journals (Sweden)

    Seredick Steve D

    2012-11-01

    Full Text Available Abstract Background Precise matching between motoneuron subtypes and the muscles they innervate is a prerequisite for normal behavior. Motoneuron subtype identity is specified by the combination of transcription factors expressed by the cell during its differentiation. Here we investigate the roles of Mnx family transcription factors in specifying the subtypes of individually identified zebrafish primary motoneurons. Results Zebrafish has three Mnx family members. We show that each of them has a distinct and temporally dynamic expression pattern in each primary motoneuron subtype. We also show that two Mnx family members are expressed in identified VeLD interneurons derived from the same progenitor domain that generates primary motoneurons. Surprisingly, we found that Mnx proteins appear unnecessary for differentiation of VeLD interneurons or the CaP motoneuron subtype. Mnx proteins are, however, required for differentiation of the MiP motoneuron subtype. We previously showed that MiPs require two temporally-distinct phases of Islet1 expression for normal development. Here we show that in the absence of Mnx proteins, the later phase of Islet1 expression is initiated but not sustained, and MiPs become hybrids that co-express morphological and molecular features of motoneurons and V2a interneurons. Unexpectedly, these hybrid MiPs often extend CaP-like axons, and some MiPs appear to be entirely transformed to a CaP morphology. Conclusions Our results suggest that Mnx proteins promote MiP subtype identity by suppressing both interneuron development and CaP axon pathfinding. This is, to our knowledge, the first report of transcription factors that act to distinguish CaP and MiP subtype identities. Our results also suggest that MiP motoneurons are more similar to V2 interneurons than are CaP motoneurons.

  7. Carcinoma apócrino na glândula parótida e na região submandibular Apocrine carcinoma in the parotid gland and in the submandibular region

    Directory of Open Access Journals (Sweden)

    Jairo S. Francisco

    2005-04-01

    Full Text Available Os objetivos deste trabalho consistem na apresentação de um caso de carcinoma apócrino e na discussão de aspectos relacionados ao seu diagnóstico, tratamento e prognóstico. Os carcinomas com diferenciação apócrina que não correspondem aos casos de doença extramamária de Paget, de carcinoma ductal de mama, de adenocarcinoma das glândulas de Moll e de carcinoma ceruminal são tumores muito raros. Relatamos o caso de uma paciente do sexo feminino, negra, com 51 anos, na qual duas lesões de carcinoma apócrino acometeram a parótida esquerda (processo inicial e recidiva e uma lesão envolveu a pele da região submandibular do mesmo lado. O exame histopatológico destas lesões mostrou a presença de neoplasia epitelial glandular infiltrativa com pleomorfismo celular e nuclear moderados; apresentando células poligonais ou arredondadas, com núcleos grandes e citoplasma eosinofílico e granular. Destacou-se a presença de secreção por decapitação apical na maior parte das células tumorais voltadas para a luz das estruturas císticas neoplásicas. Adicionalmente, foi encontrada a presença de focos de comedo-necrose e de material corado pelo PAS com e sem diastase. Apesar de não podermos definir com certeza qual a sede do tumor primário, com base nos aspectos histopatológicos compatíveis com o carcinoma apócrino cutâneo, consideramos que tenha sido, provavelmente, a lesão retirada da pele da região submandibular. A paciente foi submetida a tratamentos cirúrgicos e não apresentou alterações após um ano de acompanhamento, depois da retirada do tumor recidivante na parótida.The objectives of this paper are to report a case of apocrine carcinoma and the discussion of aspects related to its diagnosis, treatment, and prognosis. Carcinomas with apocrine differentiation not related to extramammary Paget's disease, ductal breast carcinoma, Moll's glands adenocarcinoma and ceruminous glands carcinoma are very uncommon tumors. We

  8. Luminal B breast cancer subtype displays a dicotomic epigenetic pattern.

    Science.gov (United States)

    Bediaga, Naiara G; Beristain, Elena; Calvo, Borja; Viguri, María A; Gutierrez-Corres, Borja; Rezola, Ricardo; Ruiz-Diaz, Irune; Guerra, Isabel; de Pancorbo, Marian M

    2016-01-01

    Luminal B breast tumors have aggressive clinical and biological features, and constitute the most heterogeneous molecular subtype, both clinically and molecularly. Unfortunately, the immunohistochemistry correlate of the luminal B subtype remains still imprecise, and it has now become of paramount importance to define a classification scheme capable of segregating luminal tumors into clinically meaningful subgroups that may be used clinically to guide patient management. With the aim of unraveling the DNA methylation profiles of the luminal subtypes currently being most used in the clinical setting, we have quantified the DNA methylation level of 27,578 CpG sites in 17 luminal B (ER+, Ki67 ≥ 20 % or PgR  20 %) and 4 luminal B-HER2+ (ER+ and HER2+) breast cancer samples by using the Illumina Infinium methylation microarray approach. Unsupervised hierarchical clustering revealed that DNA methylation stratifies luminal B samples in two categories with differing epigenetic and clinical features. One subgroup of luminal B samples showed a methylator phenotype and clustered with the lumB-HER tumors, while the other showed less methylated events, clustered with the luminal A. A 3 CpG marker panel capable of discriminating methylator versus non-methylator luminal B samples was identified and further validated in an independent cohort of patients. Our results provide evidence that DNA methylation and, more specifically, a panel of 3 CpG markers, enables the stratification of luminal B samples in two categories with differing epigenetic and clinical features and support the utilization of this panel for therapeutic stratification of patients with luminal breast cancer. PMID:27330889

  9. Sputum mast cell subtypes relate to eosinophilia and corticosteroid response in asthma.

    Science.gov (United States)

    Wang, Gang; Baines, Katherine J; Fu, Juan Juan; Wood, Lisa G; Simpson, Jodie L; McDonald, Vanessa M; Cowan, Douglas C; Taylor, D Robin; Cowan, Jan O; Gibson, Peter G

    2016-04-01

    Mast cells are a resident inflammatory cell of the airways, involved in both the innate and adaptive immune response. The relationship between mast cells and inflammatory phenotypes and treatment response of asthma is not clear.Clinical characteristics of subjects with stable asthma (n=55), inflammatory cell counts and gene expression microarrays in induced sputum were analysed. Sputum mast cell subtypes were determined by molecular phenotyping based on expression of mast cell biomarkers (tryptase (TPSAB1), chymase (CMA1) and carboxypeptidase A3 (CPA3)). Effects of mast cell subtypes on steroid response were observed in a prospective cohort study (n=50).MCT(n=18) and MCT/CPA3(mRNA expression ofTPSAB1andCPA3; n=29) subtypes were identified, as well as a group without mast cell gene expression (n=8). The MCT/CPA3subtype had elevated exhaled nitric oxide fraction, sputum eosinophils, bronchial sensitivity and reactivity, and poorer asthma control. This was accompanied by upregulation of 13 genes. Multivariable logistic regression identifiedCPA3(OR 1.21, p=0.004) rather thanTPSAB1(OR 0.92, p=0.502) as a determinant of eosinophilic asthma. The MCT/CPA3subtype had a better clinical response and reduced signature gene expression with corticosteroid treatment.Sputum mast cell subtypes of asthma can be defined by a molecular phenotyping approach. The MCT/CPA3subtype demonstrated increased bronchial sensitivity and reactivity, and signature gene expression, which was associated with airway eosinophilia and greater corticosteroid responsiveness. PMID:26699720

  10. Comparative evaluation of trimeric envelope glycoproteins derived from subtype C and B HIV-1 R5 isolates.

    Science.gov (United States)

    Srivastava, Indresh K; Kan, Elaine; Sun, Yide; Sharma, Victoria A; Cisto, Jimna; Burke, Brian; Lian, Ying; Hilt, Susan; Biron, Zohar; Hartog, Karin; Stamatatos, Leonidas; Diaz-Avalos, Ruben; Cheng, R Holland; Ulmer, Jeffrey B; Barnett, Susan W

    2008-03-15

    We previously reported that an envelope (Env) glycoprotein immunogen (o-gp140DeltaV2SF162) containing a partial deletion in the second variable loop (V2) derived from the R5-tropic HIV-1 isolate SF162 partially protected vaccinated rhesus macaques against pathogenic SHIV(SF162P4) virus. Extending our studies to subtype C isolate TV1, we have purified o-gp140DeltaV2TV1 (subtype C DeltaV2 trimer) to homogeneity, performed glycosylation analysis, and determined its ability to bind CD4, as well as a panel of well-characterized neutralizing monoclonal antibodies (mAb). In general, critical epitopes are preserved on the subtype C DeltaV2 trimer; however, we did not observe significant binding for the b12 mAb. The molecular mass of subtype C DeltaV2 trimer was found to be 450 kDa, and the hydrodynamic radius was found to be 10.87 nm. Our data suggest that subtype C DeltaV2 trimer binds to CD4 with an affinity comparable to o-gp140DeltaV2SF162 (subtype B DeltaV2 trimer). Using isothermal titration calorimetric (ITC) analysis, we demonstrated that all three CD4 binding sites (CD4-BS) in both subtype C and B trimers are exposed and accessible. However, compared to subtype B trimer, the three CD4-BS in subtype C trimer have different affinities for CD4, suggesting a cooperativity of CD4 binding in subtype C trimer but not in subtype B trimer. Negative staining electron microscopy of the subtype C DeltaV2 trimer has demonstrated that it is in fact a trimer. These results highlight the importance of studying subtype C Env, and also of developing appropriate subtype C-specific reagents that may be used for better immunological characterization of subtype C Env for developing an AIDS vaccine.

  11. Relationship of c-FLIP (L) protein expression with molecular subtyping and clinical prognosis in invasive breast cancer%凋亡调节因子c-FLIP (L)与浸润性乳腺癌分子分型及预后的相关性

    Institute of Scientific and Technical Information of China (English)

    臧凤琳; 魏熙胤; 孙保存

    2014-01-01

    Objective To investigate the expression of apoptotic regulator c-FLIP(L) in invasive breast carcinoma tissues,and to evaluate its correlation with molecular subtyping and clinical prognosis.Methods Immunohistochemistry using EnVision staining for c-FLIP (L) was performed in 264 cases of invasive breast carcinomas and matched adjacent normal breast tissue samples from January 1996 to December 1999.ER,PR,HER2,Ki-67,CK5/6 and EGFR were evaluated by immunohistochemistry in order to classify the tumors into five molecular subtypes and the difference of c-FLIP(L) expression in these molecular subtypes was also analyzed.The influence of c-FLIP(L) expression on prognosis was evaluated by Kaplan-Meier curves and multi-factor Cox proportional risk model.Results High expression of c-FLIP(L) was observed in 84.5% (223/264) of cases of invasive breast carcinomas which were significantly higher than the 45.1% (119/264) of cases in adjacent normal epithelium of breast (x2 =89.78,P =0.000).The expression of c-FLIP(L) in luminal B (HER2 positive) and basal-like breast cancers was 78.1% (25/32) and 46.2% (18/39),respectively,with significant difference (P < 0.05).Moreover,the expression of c-FLIP(L) in luminal B (HER2 positive) was higher than in luminal A cancers (P < 0.05),and the expression of c-FLIP(L) in HER2 positive cancers was higher than in basal-like cancers (P <0.01).C-FLIP(L) showed deep yellow staining in node positive breast cancer with a high-expression rate of 93.1% (134/144); whereas the expression was sporadic and light yellow in node negative breast cancer with a lower high-expressed rate of 72.5% (87/120,P < 0.01).C-FLIP(L) expression had significant influence on disease-free survival time,with c-FLIP(L)-positive patients showing poor prognosis (P < 0.01).Multifactor Cox proportional risk model analysis showed that expression of c-FLIP (L),lymph nodes status and molecular subtypes were independent prognostic factors for invasive breast

  12. An evaluation protocol for subtype-specific breast cancer event prediction

    NARCIS (Netherlands)

    Sontrop, H.M.J.; Verhaegh, W.F.J.; Reinders, M.J.T.; Moerland, P.

    2011-01-01

    Motivation: In recent years increasing evidence appeared that breastcancer may not constitute a single disease at the molecular level,but comprises a heterogeneous set of subtypes. This suggests that instead of building a single predictor, better predictors might be constructed that solely target sa

  13. Removing apocrine sweat glands and keeping subdermal vascular plexus by micro-incision in treating bromhidrosis%小切口保留真皮下血管网皮瓣大汗腺清除术治疗腋臭

    Institute of Scientific and Technical Information of China (English)

    刘登河; 丁美胜

    2012-01-01

    Objective To evaluate the effect and complications of removing apocrine sweat glands and keeping subdermal vascular plexus through micro-incision in treating bromhidrosis.Methods The clinical data of 58 cases of bromhidrosis received the method of removing apocrine sweat glands and keeping subdermal vascular through micro-incision were retrospectively analyzed.Results The odors in all the patients were disappeared or decreased after 6-24 months follow-up,there was no flap necrosis,no obvious scar or complication of upper limbs dysfunction.Conclusions The surgical technique is simple,has inconspicuous incision,fine appearance,less complications and without dysfunction by standardizing the operations and adopting corresponding measures.%目的 探讨小切口保留真皮下血管网皮瓣大汗腺清除治疗腋臭的疗效和并发症防治.方法 对58例采用小切口保留真皮下血管网皮瓣大汗腺清除术腋臭患者的资料进行回顾性分析.结果 术后随访6~24个月,异味消失或明显减轻,皮瓣无坏死,瘢痕不明显,上肢功能未受影响.结论 对腋臭患者行小切口保留真皮下血管网皮瓣大汗腺清除术,手术操作简单,只要规范操作和采取相应措施,可以达到治疗彻底、并发症少、外形美观、无功能损伤的效果.

  14. Response features of parvalbumin-expressing interneurons suggest precise roles for subtypes of inhibition in visual cortex

    OpenAIRE

    Runyan, Caroline A.; Schummers, James; Van Wart, Audra; Kuhlman, Sandra J.; Nathan R. Wilson; Huang, Z. Josh; Sur, Mriganka

    2010-01-01

    Inhibitory interneurons in the cerebral cortex include a vast array of subtypes, varying in their molecular signatures, electrophysiological properties, and connectivity patterns. This diversity suggests that individual inhibitory classes have unique roles in cortical circuits; however, their characterization to date has been limited to broad classifications including many subtypes. We used the Cre/LoxP system, specifically labeling parvalbumin(PV)-expressing interneurons in visual cortex of ...

  15. Comparative pathogenesis of a subtype A with a subtype B avian pneumovirus in turkeys.

    Science.gov (United States)

    Van de Zande, S; Nauwynck, H; De Jonghe, S; Pensaert, M

    1999-06-01

    This paper describes a study in which the pathogenesis of avian pneumovirus strains, isolated in Belgium, and belonging to the two subtypes A and B, were compared in 2-week-old turkeys. After oculonasal inoculation, animals were either observed for clinical signs or killed for pathological and virological examination. Virus titration and immunofluorescence were performed on the conjunctivae, turbinates, sinuses, upper and lower part of the trachea, lungs and air sacs. No differences were seen between the two subtypes concerning respiratory signs, or macroscopic and microscopic lesions in the respiratory tract. Slight variations were found in site and extent of virus replication. First, only subtype A was able to invade the lower parts of the respiratory tract (bronchi), whereas viral antigens were not detected in the lungs with subtype B. Secondly, the subtype A strain infected two times more epithelial cells at all levels of the upper respiratory tract compared to subtype B. Thirdly, the amount of virus produced at different sites along the respiratory tract was lower in subtype B-inoculated turkeys than in subtype A-inoculated ones.

  16. Ovarian cancer cell line panel (OCCP: clinical importance of in vitro morphological subtypes.

    Directory of Open Access Journals (Sweden)

    Corine M Beaufort

    Full Text Available Epithelial ovarian cancer is a highly heterogeneous disease and remains the most lethal gynaecological malignancy in the Western world. Therapeutic approaches need to account for inter-patient and intra-tumoural heterogeneity and detailed characterization of in vitro models representing the different histological and molecular ovarian cancer subtypes is critical to enable reliable preclinical testing. There are approximately 100 publicly available ovarian cancer cell lines but their cellular and molecular characteristics are largely undescribed. We have characterized 39 ovarian cancer cell lines under uniform conditions for growth characteristics, mRNA/microRNA expression, exon sequencing, drug response for clinically-relevant therapeutics and collated all available information on the original clinical features and site of origin. We tested for statistical associations between the cellular and molecular features of the lines and clinical features. Of the 39 ovarian cancer cell lines, 14 were assigned as high-grade serous, four serous-type, one low-grade serous and 20 non-serous type. Three morphological subtypes: Epithelial (n = 21, Round (n = 7 and Spindle (n = 12 were identified that showed distinct biological and molecular characteristics, including overexpression of cell movement and migration-associated genes in the Spindle subtype. Comparison with the original clinical data showed association of the spindle-like tumours with metastasis, advanced stage, suboptimal debulking and poor prognosis. In addition, the expression profiles of Spindle, Round and Epithelial morphologies clustered with the previously described C1-stromal, C5-mesenchymal and C4 ovarian subtype expression profiles respectively. Comprehensive profiling of 39 ovarian cancer cell lines under controlled, uniform conditions demonstrates clinically relevant cellular and genomic characteristics. This data provides a rational basis for selecting models to develop

  17. Genetic and molecular changes in ovarian cancer

    Science.gov (United States)

    Hollis, Robert L; Gourley, Charlie

    2016-01-01

    Epithelial ovarian cancer represents the most lethal gynecological malignancy in the developed world, and can be divided into five main histological subtypes: high grade serous, endometrioid, clear cell, mucinous and low grade serous. These subtypes represent distinct disease entities, both clinically and at the molecular level. Molecular analysis has revealed significant genetic heterogeneity in ovarian cancer, particularly within the high grade serous subtype. As such, this subtype has been the focus of much research effort to date, revealing molecular subgroups at both the genomic and transcriptomic level that have clinical implications. However, stratification of ovarian cancer patients based on the underlying biology of their disease remains in its infancy. Here, we summarize the molecular changes that characterize the five main ovarian cancer subtypes, highlight potential opportunities for targeted therapeutic intervention and outline priorities for future research.

  18. Subtype-specific micro-RNA expression signatures in breast cancer progression.

    Science.gov (United States)

    Haakensen, Vilde D; Nygaard, Vegard; Greger, Liliana; Aure, Miriam R; Fromm, Bastian; Bukholm, Ida R K; Lüders, Torben; Chin, Suet-Feung; Git, Anna; Caldas, Carlos; Kristensen, Vessela N; Brazma, Alvis; Børresen-Dale, Anne-Lise; Hovig, Eivind; Helland, Åslaug

    2016-09-01

    Robust markers of invasiveness may help reduce the overtreatment of in situ carcinomas. Breast cancer is a heterogeneous disease and biological mechanisms for carcinogenesis vary between subtypes. Stratification by subtype is therefore necessary to identify relevant and robust signatures of invasive disease. We have identified microRNA (miRNA) alterations during breast cancer progression in two separate datasets and used stratification and external validation to strengthen the findings. We analyzed two separate datasets (METABRIC and AHUS) consisting of a total of 186 normal breast tissue samples, 18 ductal carcinoma in situ (DCIS) and 1,338 invasive breast carcinomas. Validation in a separate dataset and stratification by molecular subtypes based on immunohistochemistry, PAM50 and integrated cluster classifications were performed. We propose subtype-specific miRNA signatures of invasive carcinoma and a validated signature of DCIS. miRNAs included in the invasive signatures include downregulation of miR-139-5p in aggressive subtypes and upregulation of miR-29c-5p expression in the luminal subtypes. No miRNAs were differentially expressed in the transition from DCIS to invasive carcinomas on the whole, indicating the need for subtype stratification. A total of 27 miRNAs were included in our proposed DCIS signature. Significant alterations of expression included upregulation of miR-21-5p and the miR-200 family and downregulation of let-7 family members in DCIS samples. The signatures proposed here can form the basis for studies exploring DCIS samples with increased invasive potential and serum biomarkers for in situ and invasive breast cancer. PMID:27082076

  19. Genetic and phylogenetic evolution of HIV-1 in a low subtype heterogeneity epidemic: the Italian example

    Directory of Open Access Journals (Sweden)

    Tornesello Maria

    2007-05-01

    Full Text Available Abstract The Human Immunodeficiency Virus type 1 (HIV-1 is classified into genetic groups, subtypes and sub-subtypes which show a specific geographic distribution pattern. The HIV-1 epidemic in Italy, as in most of the Western Countries, has traditionally affected the Intra-venous drug user (IDU and Homosexual (Homo risk groups and has been sustained by the genetic B subtype. In the last years, however, the HIV-1 transmission rate among heterosexuals has dramatically increased, becoming the prevalent transmission route. In fact, while the traditional risk groups have high levels of knowledge and avoid high-risk practices, the heterosexuals do not sufficiently perceive the risk of HIV-1 infection. This misperception, linked to the growing number of immigrants from non-Western Countries, where non-B clades and circulating recombinant forms (CRFs are prevalent, is progressively introducing HIV-1 variants of non-B subtype in the Italian epidemic. This is in agreement with reports from other Western European Countries. In this context, the Italian HIV-1 epidemic is still characterized by low subtype heterogeneity and represents a paradigmatic example of the European situation. The continuous molecular evolution of the B subtype HIV-1 isolates, characteristic of a long-lasting epidemic, together with the introduction of new subtypes as well as recombinant forms may have significant implications for diagnostic, treatment, and vaccine development. The study and monitoring of the genetic evolution of the HIV-1 represent, therefore, an essential strategy for controlling the local as well as global HIV-1 epidemic and for developing efficient preventive and therapeutic strategies.

  20. Pathway-based classification of cancer subtypes

    Directory of Open Access Journals (Sweden)

    Kim Shinuk

    2012-07-01

    Full Text Available Abstract Background Molecular markers based on gene expression profiles have been used in experimental and clinical settings to distinguish cancerous tumors in stage, grade, survival time, metastasis, and drug sensitivity. However, most significant gene markers are unstable (not reproducible among data sets. We introduce a standardized method for representing cancer markers as 2-level hierarchical feature vectors, with a basic gene level as well as a second level of (more stable pathway markers, for the purpose of discriminating cancer subtypes. This extends standard gene expression arrays with new pathway-level activation features obtained directly from off-the-shelf gene set enrichment algorithms such as GSEA. Such so-called pathway-based expression arrays are significantly more reproducible across datasets. Such reproducibility will be important for clinical usefulness of genomic markers, and augment currently accepted cancer classification protocols. Results The present method produced more stable (reproducible pathway-based markers for discriminating breast cancer metastasis and ovarian cancer survival time. Between two datasets for breast cancer metastasis, the intersection of standard significant gene biomarkers totaled 7.47% of selected genes, compared to 17.65% using pathway-based markers; the corresponding percentages for ovarian cancer datasets were 20.65% and 33.33% respectively. Three pathways, consisting of Type_1_diabetes mellitus, Cytokine-cytokine_receptor_interaction and Hedgehog_signaling (all previously implicated in cancer, are enriched in both the ovarian long survival and breast non-metastasis groups. In addition, integrating pathway and gene information, we identified five (ID4, ANXA4, CXCL9, MYLK, FBXL7 and six (SQLE, E2F1, PTTG1, TSTA3, BUB1B, MAD2L1 known cancer genes significant for ovarian and breast cancer respectively. Conclusions Standardizing the analysis of genomic data in the process of cancer staging

  1. 腋窝顶泌汗腺的应用解剖与组织病理学观察%Anatomy and histopathology of apocrine sweat glands in axillary fossa

    Institute of Scientific and Technical Information of China (English)

    王擎; 柳大烈; 王晋煌; 陈兵; 陈伯华

    2011-01-01

    目的 研究腋臭顶泌汗腺的分布范围与层次,为治疗腋臭提供应用解剖与病理学依据.方法 对2具腋臭,8具非腋臭10%甲醛固定成人尸体,进行腋窝应用解剖;对25例重度腋臭患者予以顶泌汗腺去除手术的组织病理学观察.结果 顶泌汗腺分泌部肉眼清晰可见,呈粟粒样颗粒;尸体上呈黑褐色,活体上为粉红色;主要分布在腋毛区域内,可超过腋毛区域外,但未超过1.0 cm;以腋窝中央横皱襞处最为密集,外围呈散在分布.顶泌汗腺分泌部位于真皮网状层与腋浅筋膜之间的浅层脂肪组织内,在真皮网状层下方已移行为导管部.在靠近真皮网状层处,其被结缔组织缠绕,形成完整、坚韧、不易刮除的膜状结构;在下方与腋浅筋膜连接紧密,不易分离.真皮面上白色突起颗粒为皮脂腺毛囊复合体.结论 直视下去除真皮下粉红色粟粒样组织和腋浅筋膜,干净去除顶泌汗腺分泌部;结合紧贴真皮面剪除毛囊处理导管部,可根治腋臭.手术范围不可过宽,以腋毛区域外1.0 cm为宜.%Objective To investigate the distribution range and depth of the apocrine sweat glands of the axillary fossa,in order to supply with anatomic and histopathologic basis in the treatment on axillarv osmidrosis.Methods From December 2008 to ()ctober 2010,2 biopsy samples(with axillary osmidrosis),8 biopsy samples(normal,without axillary osmidrosis),were employed into the axillarv anatomy study. 25 patients with severe axillary osmidrosis were observed both maerographicallv and microscopically by using of operation and histopathological methods.Results Secretory portion of apocrine sweat glands was seen clearly,it was pitchy millet-like granules on axillary osmidrosis corpse,and pink millet-like granules in vivo.Secretory portions distributed most within the armpit hair area,exceeded the edge of armpit hair line,but not surpassed the edge of armpit hair line 1.0 cm.The depth of the apocrine

  2. Chronic Obstructive Pulmonary Disease Subtypes. Transitions over Time

    Science.gov (United States)

    Esteban, Cristóbal; Arostegui, Inmaculada; Aburto, Myriam; Moraza, Javier; Quintana, José M.; García-Loizaga, Amaia; Basualdo, Luis V.; Aramburu, Amaia; Aizpiri, Susana; Uranga, Ane; Capelastegui, Alberto

    2016-01-01

    Background Although subtypes of chronic obstructive pulmonary disease are recognized, it is unknown what happens to these subtypes over time. Our objectives were to assess the stability of cluster-based subtypes in patients with stable disease and explore changes in clusters over 1 year. Methods Multiple correspondence and cluster analysis were used to evaluate data collected from 543 stable patients included consecutively from 5 respiratory outpatient clinics. Results Four subtypes were identified. Three of them, A, B, and C, had marked respiratory profiles with a continuum in severity of several variables, while the fourth, subtype D, had a more systemic profile with intermediate respiratory disease severity. Subtype A was associated with less dyspnea, better health-related quality of life and lower Charlson comorbidity scores, and subtype C with the most severe dyspnea, and poorer pulmonary function and quality of life, while subtype B was between subtypes A and C. Subtype D had higher rates of hospitalization the previous year, and comorbidities. After 1 year, all clusters remained stable. Generally, patients continued in the same subtype but 28% migrated to another cluster. Together with movement across clusters, patients showed changes in certain characteristics (especially exercise capacity, some variables of pulmonary function and physical activity) and changes in outcomes (quality of life, hospitalization and mortality) depending on the new cluster they belonged to. Conclusions Chronic obstructive pulmonary disease clusters remained stable over 1 year. Most patients stayed in their initial subtype cluster, but some moved to another subtype and accordingly had different outcomes. PMID:27611911

  3. Subtypes of Aggressive Behaviors: A Developmental Perspective

    Science.gov (United States)

    Vitaro, Frank; Brendgen, Mara; Barker, Edward D.

    2006-01-01

    Aggressive behaviors in children and adolescents have undergone important conceptual and definitional modifications in the past two decades. In particular, subtypes of aggression have been proposed that separate the form and the function of the aggressive behaviors (i.e., social vs. physical aggression; reactive vs. proactive aggression).…

  4. A Taxometric Investigation of Developmental Dyslexia Subtypes

    Science.gov (United States)

    O'Brien, Beth A.; Wolf, Maryanne; Lovett, Maureen W.

    2012-01-01

    Long-standing issues with the conceptualization, identification and subtyping of developmental dyslexia persist. This study takes an alternative approach to examine the heterogeneity of developmental dyslexia using taxometric classification techniques. These methods were used with a large sample of 671 children ages 6-8 who were diagnosed with…

  5. Molecular signatures define alopecia areata subtypes and transcriptional biomarkers

    Directory of Open Access Journals (Sweden)

    Ali Jabbari

    2016-05-01

    Full Text Available Alopecia areata (AA is an autoimmune disease typified by nonscarring hair loss with a variable clinical course. In this study, we conducted whole genome gene expression analysis of 96 human scalp skin biopsy specimens from AA or normal control subjects. Based on gene expression profiling, samples formed distinct clusters based on the presence or absence of disease as well as disease phenotype (patchy disease compared with alopecia totalis or universalis. Differential gene expression analysis allowed us to robustly demonstrate graded immune activity in samples of increasing phenotypic severity and generate a quantitative gene expression scoring system that classified samples based on interferon and cytotoxic T lymphocyte immune signatures critical for disease pathogenesis.

  6. Small Incision Deep Dermal Excision of Apocrine Glands in Treatment of Axillary Osmidrosis%小切口真皮深层摘除大汗腺治疗腋臭

    Institute of Scientific and Technical Information of China (English)

    陈飞; 孙大华

    2014-01-01

    Objective To investigate the clinical ef icacy of small incision deep dermal excision of apocrine glands in treatment of axil ary osmidrosis. Methods 172 patients with bromhidrosis patients in our hospital in 2012 December~2013 year in December were divided into two groups, the observation group of 86 patients with smal incision extirpation operation method of deep dermal big sweat glands, the control group with conventional operation method of the skin and subcutaneous tissue ablation. Results The two groups of patients after half a year follow-up, the total ef ective rate of treatment group was 100%(86/86);the control group the total ef ective rate was 90.7%(78/86), clinical curative effect is obviously bet er than the observation group in the control group, there was statistical y significant ( <0.05). Conclusion The smal incision deep dermal excision of apocrine glands in treatment of axil ary osmidrosis and remarkable curative ef ect, smal trauma, is worthy of clinical use.%目的探讨小切口真皮深层摘除大汗腺治疗腋臭的临床疗效。方法将我院2012年12月~2013年12月收治的172例腋臭患者分为两组,观察组86例患者采用小切口真皮深层摘除大汗腺的手术方法,对照组则采用常规皮肤和皮下组织切除的手术方法。结果两组患者术后都半年随访,治疗组总有效率为100%(86/86);对照组总有效率为90.7%(78/86),观察组的临床疗效明显优于对照组,有统计学意义(P<0.05)。结论小切口真皮深层摘除大汗腺治疗腋臭疗效显著,且创伤小,值得临床推广使用。

  7. MORPHOMETRIC SUBTYPING FOR A PANEL OF BREAST CANCER CELL LINES

    Energy Technology Data Exchange (ETDEWEB)

    Han, Ju; Chang, Hang; Fontenay, Gerald; Wang, Nicholas J.; Gray, Joe W.; Parvin, Bahram

    2009-05-08

    A panel of cell lines of diverse molecular background offers an improved model system for high-content screening, comparative analysis, and cell systems biology. A computational pipeline has been developed to collect images from cell-based assays, segment individual cells and colonies, represent segmented objects in a multidimensional space, and cluster them for identifying distinct subpopulations. While each segmentation strategy can vary for different imaging assays, representation and subpopulation analysis share a common thread. Application of this pipeline to a library of 41 breast cancer cell lines is demonstrated. These cell lines are grown in 2D and imaged through immunofluorescence microscopy. Subpopulations in this panel are identified and shown to correlate with previous subtyping literature that was derived from transcript data.

  8. The discovery and development of P2 receptor subtypes.

    Science.gov (United States)

    Kennedy, C

    2000-07-01

    Extracellular purine and pyrimidine nucleotides modulate cellular activity by acting at P2 receptors. The first receptor to be identified was the P(2)-purinoceptor, which was characterised and named in 1978. In the 1980s this site was subdivided into P(2X) and P(2Y) purinoceptors on the basis of pharmacological criteria in functional studies on native receptors. Subsequently, a similar approach led to the characterisation of the P(2T), P(2Z), P(2U) and P(2D) purinoceptors. In the 1990s a molecular biological approach has led to the cloning and functional expression of at least 12 mammalian P2 receptor subtypes. The challenge now is to relate these recombinant receptors to native receptors present within a wide range of tissues.

  9. Subtypes of depression in cancer patients : An empirically driven approach

    NARCIS (Netherlands)

    Zhu, Lei; Ranchor, Adelita V; van der Lee, Marije; Garssen, Bert; Sanderman, Robbert; Schroevers, Maya J

    2016-01-01

    PURPOSE: This study aimed to (1) identify subgroups of cancer patients with distinct subtypes of depression before the start of psychological care, (2) examine whether socio-demographic and medical characteristics distinguished these subtypes, and (3) examine whether people with distinct subtypes re

  10. Subtypes of depression in cancer patients : an empirically driven approach

    NARCIS (Netherlands)

    Zhu, Lei; Ranchor, Adelita V.; van der Lee, Marije; Garssen, Bert; Sanderman, Robbert; Schroevers, Maya J.

    2016-01-01

    This study aimed to (1) identify subgroups of cancer patients with distinct subtypes of depression before the start of psychological care, (2) examine whether socio-demographic and medical characteristics distinguished these subtypes, and (3) examine whether people with distinct subtypes reported di

  11. Subtypes of depression in cancer patients: an empirically driven approach

    NARCIS (Netherlands)

    Zhu, Lei; Ranchor, A.V.; Lee, van der Marije; Garssen, Bert; Sanderman, Robbert; Schroevers, Maya J.

    2016-01-01

    Purpose This study aimed to (1) identify subgroups of cancer patients with distinct subtypes of depression before the start of psychological care, (2) examine whether socio-demographic and medical characteristics distinguished these subtypes, and (3) examine whether people with distinct subtypes rep

  12. Muscarinic acetylcholine receptor subtypes: localization and structure/function

    DEFF Research Database (Denmark)

    Brann, M R; Ellis, J; Jørgensen, H;

    1993-01-01

    Based on the sequence of the five cloned muscarinic receptor subtypes (m1-m5), subtype selective antibody and cDNA probes have been prepared. Use of these probes has demonstrated that each of the five subtypes has a markedly distinct distribution within the brain and among peripheral tissues. The...

  13. Greater absolute risk for all subtypes of breast cancer in the US than Malaysia.

    Science.gov (United States)

    Horne, Hisani N; Beena Devi, C R; Sung, Hyuna; Tang, Tieng Swee; Rosenberg, Philip S; Hewitt, Stephen M; Sherman, Mark E; Anderson, William F; Yang, Xiaohong R

    2015-01-01

    Hormone receptor (HR) negative breast cancers are relatively more common in low-risk than high-risk countries and/or populations. However, the absolute variations between these different populations are not well established given the limited number of cancer registries with incidence rate data by breast cancer subtype. We, therefore, used two unique population-based resources with molecular data to compare incidence rates for the 'intrinsic' breast cancer subtypes between a low-risk Asian population in Malaysia and high-risk non-Hispanic white population in the National Cancer Institute's surveillance, epidemiology, and end results 18 registries database (SEER 18). The intrinsic breast cancer subtypes were recapitulated with the joint expression of the HRs (estrogen receptor and progesterone receptor) and human epidermal growth factor receptor-2 (HER2). Invasive breast cancer incidence rates overall were fivefold greater in SEER 18 than in Malaysia. The majority of breast cancers were HR-positive in SEER 18 and HR-negative in Malaysia. Notwithstanding the greater relative distribution for HR-negative cancers in Malaysia, there was a greater absolute risk for all subtypes in SEER 18; incidence rates were nearly 7-fold higher for HR-positive and 2-fold higher for HR-negative cancers in SEER 18. Despite the well-established relative breast cancer differences between low-risk and high-risk countries and/or populations, there was a greater absolute risk for HR-positive and HR-negative subtypes in the US than Malaysia. Additional analytical studies are sorely needed to determine the factors responsible for the elevated risk of all subtypes of breast cancer in high-risk countries like the United States.

  14. HIV-1 subtype D infections among Caucasians from Northwestern Poland--phylogenetic and clinical analysis.

    Directory of Open Access Journals (Sweden)

    Miłosz Parczewski

    Full Text Available BACKGROUND: HIV-1 subtype D infections, which are associated with a faster rate of progression and lymphocyte CD4 decline, cognitive deficit and higher mortality, have rarely been found in native Europeans. In Northwestern Poland, however, infections with this subtype had been identified. This study aimed to analyze the sequence and clinical data for patients with subtype D using molecular phylogeography and identify transmission clusters and ancestry, as well as drug resistance, baseline HIV tropism and antiretroviral treatment efficacy. METHODS: Phylogenetic analyses of local HIV-1 subtype D sequences were performed, with time to the most recent common ancestor inferred using bayesian modeling. Sequence and drug resistance data were linked with the clinical and epidemiological information. RESULTS: Subtype D was found in 24 non-immigrant Caucasian, heterosexually infected patients (75% of females, median age at diagnosis of 49.5 years; IQR: 29-56 years. Partial pol sequences clustered monophyletically with the clades of Ugandan origin and no evidence of transmission from other European countries was found. Time to the most common recent ancestor was 1989.24 (95% HPD: 1968.83-1994.46. Baseline drug resistance to nucleoside reverse transcriptase inhibitors was observed in 54.5% of cases (mutations: M41L, K103N, T215S/D with evidence of clustering, no baseline integrase or protease resistance and infrequent non-R5 tropism (13.6%. Virologic failure was observed in 60% of cases and was associated with poor adherence (p<0.001 and subsequent development of drug resistance (p = 0.008, OR: 20 (95%CI: 1.7-290. CONCLUSIONS: Local subtype D represented an independently transmitted network with probably single index case, high frequency of primary drug resistance and evidence of transmission clusters.

  15. Agonist discrimination between AMPA receptor subtypes

    DEFF Research Database (Denmark)

    Coquelle, T; Christensen, J K; Banke, T G;

    2000-01-01

    The lack of subtype-selective compounds for AMPA receptors (AMPA-R) led us to search for compounds with such selectivity. Homoibotenic acid analogues were investigated at recombinant GluR1o, GluR2o(R), GluR3o and GluR1o + 3o receptors expressed in Sf9 insect cells and affinities determined in [3H......]AMPA radioligand binding experiments. (S)-4-bromohomoibotenic acid (BrHIBO) exhibited a 126-fold selectivity for GluR1o compared to GluR3o. Xenopus laevis oocytes were used to express functional homomeric and heteromeric recombinant AMPA-R and to determine BrHIBO potency (EC50) at these channels. (R......,S)-BrHIBO exhibited a 37-fold selectivity range amongst the AMPA-R. It is hoped that BrHIBO can be used as a lead structure for the development of other subtype-selective compounds....

  16. Proteomic maps of breast cancer subtypes

    DEFF Research Database (Denmark)

    Tyanova, Stefka; Albrechtsen, Reidar; Kronqvist, Pauliina;

    2016-01-01

    Systems-wide profiling of breast cancer has almost always entailed RNA and DNA analysis by microarray and sequencing techniques. Marked developments in proteomic technologies now enable very deep profiling of clinical samples, with high identification and quantification accuracy. We analysed 40...... oestrogen receptor positive (luminal), Her2 positive and triple negative breast tumours and reached a quantitative depth of >10,000 proteins. These proteomic profiles identified functional differences between breast cancer subtypes, related to energy metabolism, cell growth, mRNA translation and cell......-cell communication. Furthermore, we derived a signature of 19 proteins, which differ between the breast cancer subtypes, through support vector machine (SVM)-based classification and feature selection. Remarkably, only three proteins of the signature were associated with gene copy number variations and eleven were...

  17. Subtyping Obsessive-Compulsive Disorder: Neuropsychological Correlates

    Directory of Open Access Journals (Sweden)

    Catherine L. Harris

    2003-01-01

    Full Text Available We administered neuropsychological measures considered sensitive to prefrontal dysfunction (both orbitofrontal and dorsolateral prefrontal neocortex to obsessive-compulsive disorder (OCD patients and control subjects. OCD subjects exhibited performance deficits, in comparison to community controls, on three measures sensitive to orbitofrontal neocortex dysfunction. Contrary to expectation, OCD patients also exhibited performance deficits on measures sensitive to dorsolateral prefrontal neocortex dysfunction. However, distinct neurocognitive profiles emerged when we examined the impact of comorbid schizotypal personality features on neuropsychological test performance. Primary OCD patients displayed impaired performance on measures sensitive to orbitofrontal dysfunction; however, they did not differ from control subjects on tests of dorsolateral function. OCD subjects presenting with schizotypal personality features performed poorly not only on tests sensitive to orbitofrontal dysfunction, but also on tests sensitive to dorsolateral dysfunction. Findings suggest that OCD can be subdivided into clinical subtypes, and distinct prefrontal subsystems may be differentially involved in these subtypes.

  18. Epidemiology of subtypes of hypothyroidism in Denmark

    DEFF Research Database (Denmark)

    Carlé, Allan; Laurberg, Peter; Pedersen, Inge B.;

    2006-01-01

    Objective: Studies of hypothyroidism are often based on referred patients. and limited information is available on the incidence rates of subtypes of hypothyroidism in the general population. We therefore studied incidences of subtypes of primary. overt hypothyroidism in a Danish population cohort...... and compared incidences in two subcohorts with different levels of iodine intake. Design: A prospective population-based study, monitoring a well-defined cohort representative of the Danish population. Methods: The Danish Investigation of Iodine Intake and Thyroid Diseases registry of hyper- and hypothyroidism...... was established as part of the monitoring of the iodine fortification of salt in Denmark. A computer-based system linked to laboratory databases identified all patients diagnosed with new. biochemically overt hypothyroidism in populations living in Aalborg (moderate iodine deficiency, n = 311 102) and Copenhagen...

  19. Global DNA methylation of ischemic stroke subtypes.

    Directory of Open Access Journals (Sweden)

    Carolina Soriano-Tárraga

    Full Text Available Ischemic stroke (IS, a heterogeneous multifactorial disorder, is among the leading causes of mortality and long-term disability in the western world. Epidemiological data provides evidence for a genetic component to the disease, but its epigenetic involvement is still largely unknown. Epigenetic mechanisms, such as DNA methylation, change over time and may be associated with aging processes and with modulation of the risk of various pathologies, such as cardiovascular disease and stroke. We analyzed 2 independent cohorts of IS patients. Global DNA methylation was measured by luminometric methylation assay (LUMA of DNA blood samples. Univariate and multivariate regression analyses were used to assess the methylation differences between the 3 most common IS subtypes, large-artery atherosclerosis (LAA, small-artery disease (SAD, and cardio-aortic embolism (CE. A total of 485 IS patients from 2 independent hospital cohorts (n = 281 and n = 204 were included, distributed across 3 IS subtypes: LAA (78/281, 59/204, SAD (97/281, 53/204, and CE (106/281, 89/204. In univariate analyses, no statistical differences in LUMA levels were observed between the 3 etiologies in either cohort. Multivariate analysis, adjusted by age, sex, hyperlipidemia, and smoking habit, confirmed the lack of differences in methylation levels between the analyzed IS subtypes in both cohorts. Despite differences in pathogenesis, our results showed no global methylation differences between LAA, SAD, and CE subtypes of IS. Further work is required to establish whether the epigenetic mechanism of methylation might play a role in this complex disease.

  20. Non motor subtypes and Parkinson's disease.

    Science.gov (United States)

    Sauerbier, Anna; Jenner, Peter; Todorova, Antoniya; Chaudhuri, K Ray

    2016-01-01

    Non motor symptoms (NMS) represent a significant burden in Parkinson's disease (PD) with numerous studies highlighting the importance of NMS both in "pre-motor" phase of PD as well as throughout the course of disease. In part this has led the international Parkinson and Movement Disorder Society (IPMDS) task force to attempt a re-definition of PD incorporating NMS and not base the diagnosis solely on motor symptoms. While motor subtypes within PD have been recognized and researched, recent clinical and neurobiological research suggests the existence of discrete non motor subtypes in PD, particularly in untreated (drug naïve) and early PD patients. Several independent observers have reported specific "clusters of NMS dominant PD" using a data driven approach in early and untreated PD patients while others have reported on the burden of NMS in untreated PD and specific NMS dominant phenotypes in untreated or treated PD using observational case series based data. In this review we report on specific NMS dominant phenotypes of PD as described in the literature using clinical observational studies and address pathophysiological concepts. A proposal for several NMS subtypes are reported combining clinical reports with, where possible, evidence base supporting probable biomarkers.

  1. Non motor subtypes and Parkinson's disease.

    Science.gov (United States)

    Sauerbier, Anna; Jenner, Peter; Todorova, Antoniya; Chaudhuri, K Ray

    2016-01-01

    Non motor symptoms (NMS) represent a significant burden in Parkinson's disease (PD) with numerous studies highlighting the importance of NMS both in "pre-motor" phase of PD as well as throughout the course of disease. In part this has led the international Parkinson and Movement Disorder Society (IPMDS) task force to attempt a re-definition of PD incorporating NMS and not base the diagnosis solely on motor symptoms. While motor subtypes within PD have been recognized and researched, recent clinical and neurobiological research suggests the existence of discrete non motor subtypes in PD, particularly in untreated (drug naïve) and early PD patients. Several independent observers have reported specific "clusters of NMS dominant PD" using a data driven approach in early and untreated PD patients while others have reported on the burden of NMS in untreated PD and specific NMS dominant phenotypes in untreated or treated PD using observational case series based data. In this review we report on specific NMS dominant phenotypes of PD as described in the literature using clinical observational studies and address pathophysiological concepts. A proposal for several NMS subtypes are reported combining clinical reports with, where possible, evidence base supporting probable biomarkers. PMID:26459660

  2. Comparative biochemical analysis of recombinant reverse transcriptase enzymes of HIV-1 subtype B and subtype C

    Directory of Open Access Journals (Sweden)

    Moisi Daniella

    2010-10-01

    Full Text Available Abstract Background HIV-1 subtype C infections account for over half of global HIV infections, yet the vast focus of HIV-1 research has been on subtype B viruses which represent less than 12% of the global pandemic. Since HIV-1 reverse transcriptase (RT is a major target of antiviral therapy, and since differential drug resistance pathways have been observed among different HIV subtypes, it is important to study and compare the enzymatic activities of HIV-1 RT derived from each of subtypes B and C as well as to determine the susceptibilities of these enzymes to various RT inhibitors in biochemical assays. Methods Recombinant subtype B and C HIV-1 RTs in heterodimeric form were purified from Escherichia coli and enzyme activities were compared in cell-free assays. The efficiency of (- ssDNA synthesis was measured using gel-based assays with HIV-1 PBS RNA template and tRNA3Lys as primer. Processivity was assayed under single-cycle conditions using both homopolymeric and heteropolymeric RNA templates. Intrinsic RNase H activity was compared using 5'-end labeled RNA template annealed to 3'-end recessed DNA primer in a time course study in the presence and absence of a heparin trap. A mis-incorporation assay was used to assess the fidelity of the two RT enzymes. Drug susceptibility assays were performed both in cell-free assays using recombinant enzymes and in cell culture phenotyping assays. Results The comparative biochemical analyses of recombinant subtype B and subtype C HIV-1 reverse transcriptase indicate that the two enzymes are very similar biochemically in efficiency of tRNA-primed (- ssDNA synthesis, processivity, fidelity and RNase H activity, and that both enzymes show similar susceptibilities to commonly used NRTIs and NNRTIs. Cell culture phenotyping assays confirmed these results. Conclusions Overall enzyme activity and drug susceptibility of HIV-1 subtype C RT are comparable to those of subtype B RT. The use of RT inhibitors (RTIs

  3. Peptide handling by HLA-B27 subtypes influences their biological behavior, association with ankylosing spondylitis and susceptibility to endoplasmic reticulum aminopeptidase 1 (ERAP1).

    Science.gov (United States)

    García-Medel, Noel; Sanz-Bravo, Alejandro; Alvarez-Navarro, Carlos; Gómez-Molina, Patricia; Barnea, Eilon; Marcilla, Miguel; Admon, Arie; de Castro, José A López

    2014-12-01

    HLA-B27 is strongly associated with ankylosing spondylitis (AS). We analyzed the relationship between structure, peptide specificity, folding, and stability of the seven major HLA-B27 subtypes to determine the role of their constitutive peptidomes in the pathogenicity of this molecule. Identification of large numbers of ligands allowed us to define the differences among subtype-bound peptidomes and to elucidate the peptide features associated with AS and molecular stability. The peptides identified only in AS-associated or high thermostability subtypes with identical A and B pockets were longer and had bulkier and more diverse C-terminal residues than those found only among non-AS-associated/lower-thermostability subtypes. Peptides sequenced from all AS-associated subtypes and not from non-AS-associated ones, thus strictly correlating with disease, were very rare. Residue 116 was critical in determining peptide binding, thermodynamic properties, and folding, thus emerging as a key feature that unified HLA-B27 biology. HLA-B27 ligands were better suited to TAP transport than their N-terminal precursors, and AS-associated subtype ligands were better than those from non-AS-associated subtypes, suggesting a particular capacity of AS-associated subtypes to bind epitopes directly produced in the cytosol. Peptides identified only from AS-associated/high-thermostability subtypes showed a higher frequency of ERAP1-resistant N-terminal residues than ligands found only in non-AS-associated/low-thermostability subtypes, reflecting a more pronounced effect of ERAP1 on the former group. Our results reveal the basis for the relationship between peptide specificity and other features of HLA-B27, provide a unified view of HLA-B27 biology and pathogenicity, and suggest a larger influence of ERAP1 polymorphism on AS-associated than non-AS-associated subtypes. PMID:25187574

  4. Expression of eag1 channel associated with the aggressive clinicopathological features and subtype of breast cancer

    OpenAIRE

    Liu, Guang-Xu; Yu, Yun-Cui; He, Xiang-ping; Ren, Sheng-Nan; Fang, Xue-Dong; Liu, Fen; He, Yan

    2015-01-01

    Backgrounds: Expression of eag1 channel (Eag1) is associated with cell malignant transformation, tumor cell metastasis and poor prognosis of the patient. This study aimed at examining whether expression of the Eag1 associated with aggressive clinicopathological feature and the molecular subtype of breast cancer. Materials and Methods: 109 patients who received breast cancer operation during January 2009 to December 2010 in Chinese-Japanese Friendship Hospital of Jilin University were recruite...

  5. Quantitative classification of somatostatin-positive neocortical interneurons identifies three interneuron subtypes

    OpenAIRE

    McGarry, Laura M.; Packer, Adam M.; Elodie Fino; Volodymyr Nikolenko; Tanya Sippy; Rafael Yuste

    2010-01-01

    Deciphering the circuitry of the neocortex requires knowledge of its components, making a systematic classification of neocortical neurons necessary. GABAergic interneurons contribute most of the morphological, electrophysiological and molecular diversity of the cortex, yet interneuron subtypes are still not well defined. To quantitatively identify classes of interneurons, 59 GFP-positive interneurons from a somatostatin-positive mouse line were characterized by whole-cell recordings and anat...

  6. Subtyping of new Brazilian avian metapneumovirus isolates from chickens and turkeys by reverse transcriptase-nested-polymerase chain reaction.

    Science.gov (United States)

    D'Arce, Regina C F; Coswig, Lia T; Almeida, Renata S; Trevisol, Iara M; Monteiro, Maria C B; Rossini, Lavínia I; Di Fabio, José; Hafez, Hafez M; Arns, Clarice W

    2005-04-01

    The aim of this study was to improve a reverse transcriptase (RT)-nested-polymerase chain reaction (PCR) able to differentiate avian pneumovirus (APV) subtypes A and B, and to characterize new Brazilian isolates. Representative APV strains and clinical field samples from chickens and turkey flocks were amplified in the chicken embryo-related cell line. Viral RNA was extracted from harvested cells, and submitted to cDNA synthesis. The primers utilized for RT-PCR were compatible with the G gene of both the A and B subtypes of APV, while the nested primers were subtype specific. This approach showed that three new APVs from chickens and one from turkeys were subtype A, confirmed by sequencing. This is the first report of APV isolation from turkeys in Brazil. Four other APVs were detected and classified as subtype A by RT-nested-PCR. These optimized techniques could be useful for differentiation of APV subtypes A and B, proving to be a valuable molecular epidemiological tool.

  7. Integrated genomics identifies five medulloblastoma subtypes with distinct genetic profiles, pathway signatures and clinicopathological features.

    Directory of Open Access Journals (Sweden)

    Marcel Kool

    Full Text Available BACKGROUND: Medulloblastoma is the most common malignant brain tumor in children. Despite recent improvements in cure rates, prediction of disease outcome remains a major challenge and survivors suffer from serious therapy-related side-effects. Recent data showed that patients with WNT-activated tumors have a favorable prognosis, suggesting that these patients could be treated less intensively, thereby reducing the side-effects. This illustrates the potential benefits of a robust classification of medulloblastoma patients and a detailed knowledge of associated biological mechanisms. METHODS AND FINDINGS: To get a better insight into the molecular biology of medulloblastoma we established mRNA expression profiles of 62 medulloblastomas and analyzed 52 of them also by comparative genomic hybridization (CGH arrays. Five molecular subtypes were identified, characterized by WNT signaling (A; 9 cases, SHH signaling (B; 15 cases, expression of neuronal differentiation genes (C and D; 16 and 11 cases, respectively or photoreceptor genes (D and E; both 11 cases. Mutations in beta-catenin were identified in all 9 type A tumors, but not in any other tumor. PTCH1 mutations were exclusively identified in type B tumors. CGH analysis identified several fully or partly subtype-specific chromosomal aberrations. Monosomy of chromosome 6 occurred only in type A tumors, loss of 9q mostly occurred in type B tumors, whereas chromosome 17 aberrations, most common in medulloblastoma, were strongly associated with type C or D tumors. Loss of the inactivated X-chromosome was highly specific for female cases of type C, D and E tumors. Gene expression levels faithfully reflected the chromosomal copy number changes. Clinicopathological features significantly different between the 5 subtypes included metastatic disease and age at diagnosis and histology. Metastatic disease at diagnosis was significantly associated with subtypes C and D and most strongly with subtype E

  8. Breast Cancer Survival Defined by the ER/PR/HER2 Subtypes and a Surrogate Classification according to Tumor Grade and Immunohistochemical Biomarkers

    Directory of Open Access Journals (Sweden)

    Carol A. Parise

    2014-01-01

    Full Text Available Introduction. ER, PR, and HER2 are routinely available in breast cancer specimens. The purpose of this study is to contrast breast cancer-specific survival for the eight ER/PR/HER2 subtypes with survival of an immunohistochemical surrogate for the molecular subtype based on the ER/PR/HER2 subtypes and tumor grade. Methods. We identified 123,780 cases of stages 1–3 primary female invasive breast cancer from California Cancer Registry. The surrogate classification was derived using ER/PR/HER2 and tumor grade. Kaplan-Meier survival analysis and Cox proportional hazards modeling were used to assess differences in survival and risk of mortality for the ER/PR/HER2 subtypes and surrogate classification within each stage. Results. The luminal B/HER2− surrogate classification had a higher risk of mortality than the luminal B/HER2+ for all stages of disease. There was no difference in risk of mortality between the ER+/PR+/HER2− and ER+/PR+/HER2+ in stage 3. With one exception in stage 3, the ER-negative subtypes all had an increased risk of mortality when compared with the ER-positive subtypes. Conclusions. Assessment of survival using ER/PR/HER2 illustrates the heterogeneity of HER2+ subtypes. The surrogate classification provides clear separation in survival and adjusted mortality but underestimates the wide variability within the subtypes that make up the classification.

  9. Understanding the undelaying mechanism of HA-subtyping in the level of physic-chemical characteristics of protein.

    Directory of Open Access Journals (Sweden)

    Mansour Ebrahimi

    Full Text Available The evolution of the influenza A virus to increase its host range is a major concern worldwide. Molecular mechanisms of increasing host range are largely unknown. Influenza surface proteins play determining roles in reorganization of host-sialic acid receptors and host range. In an attempt to uncover the physic-chemical attributes which govern HA subtyping, we performed a large scale functional analysis of over 7000 sequences of 16 different HA subtypes. Large number (896 of physic-chemical protein characteristics were calculated for each HA sequence. Then, 10 different attribute weighting algorithms were used to find the key characteristics distinguishing HA subtypes. Furthermore, to discover machine leaning models which can predict HA subtypes, various Decision Tree, Support Vector Machine, Naïve Bayes, and Neural Network models were trained on calculated protein characteristics dataset as well as 10 trimmed datasets generated by attribute weighting algorithms. The prediction accuracies of the machine learning methods were evaluated by 10-fold cross validation. The results highlighted the frequency of Gln (selected by 80% of attribute weighting algorithms, percentage/frequency of Tyr, percentage of Cys, and frequencies of Try and Glu (selected by 70% of attribute weighting algorithms as the key features that are associated with HA subtyping. Random Forest tree induction algorithm and RBF kernel function of SVM (scaled by grid search showed high accuracy of 98% in clustering and predicting HA subtypes based on protein attributes. Decision tree models were successful in monitoring the short mutation/reassortment paths by which influenza virus can gain the key protein structure of another HA subtype and increase its host range in a short period of time with less energy consumption. Extracting and mining a large number of amino acid attributes of HA subtypes of influenza A virus through supervised algorithms represent a new avenue for

  10. Interaction pattern of Arg 62 in the A-pocket of differentially disease-associated HLA-B27 subtypes suggests distinct TCR binding modes.

    Directory of Open Access Journals (Sweden)

    Elisa Nurzia

    Full Text Available The single amino acid replacement Asp116His distinguishes the two subtypes HLA-B*2705 and HLA-B*2709 which are, respectively, associated and non-associated with Ankylosing Spondylitis, an autoimmune chronic inflammatory disease. The reason for this differential association is so far poorly understood and might be related to subtype-specific HLA:peptide conformations as well as to subtype/peptide-dependent dynamical properties on the nanoscale. Here, we combine functional experiments with extensive molecular dynamics simulations to investigate the molecular dynamics and function of the conserved Arg62 of the α1-helix for both B27 subtypes in complex with the self-peptides pVIPR (RRKWRRWHL and TIS (RRLPIFSRL, and the viral peptides pLMP2 (RRRWRRLTV and NPflu (SRYWAIRTR. Simulations of HLA:peptide systems suggest that peptide-stabilizing interactions of the Arg62 residue observed in crystal structures are metastable for both B27 subtypes under physiological conditions, rendering this arginine solvent-exposed and, probably, a key residue for TCR interaction more than peptide-binding. This view is supported by functional experiments with conservative (R62K and non-conservative (R62A B*2705 and B*2709 mutants that showed an overall reduction in their capability to present peptides to CD8+ T cells. Moreover, major subtype-dependent differences in the peptide recognition suggest distinct TCR binding modes for the B*2705 versus the B*2709 subtype.

  11. Identification of Personalized Chemoresistance Genes in Subtypes of Basal-Like Breast Cancer Based on Functional Differences Using Pathway Analysis.

    Directory of Open Access Journals (Sweden)

    Tong Wu

    Full Text Available Breast cancer is a highly heterogeneous disease that is clinically classified into several subtypes. Among these subtypes, basal-like breast cancer largely overlaps with triple-negative breast cancer (TNBC, and these two groups are generally studied together as a single entity. Differences in the molecular makeup of breast cancers can result in different treatment strategies and prognoses for patients with different breast cancer subtypes. Compared with other subtypes, basal-like and other ER+ breast cancer subtypes exhibit marked differences in etiologic factors, clinical characteristics and therapeutic potential. Anthracycline drugs are typically used as the first-line clinical treatment for basal-like breast cancer subtypes. However, certain patients develop drug resistance following chemotherapy, which can lead to disease relapse and death. Even among patients with basal-like breast cancer, there can be significant molecular differences, and it is difficult to identify specific drug resistance proteins in any given patient using conventional variance testing methods. Therefore, we designed a new method for identifying drug resistance genes. Subgroups, personalized biomarkers, and therapy targets were identified using cluster analysis of differentially expressed genes. We found that basal-like breast cancer could be further divided into at least four distinct subgroups, including two groups at risk for drug resistance and two groups characterized by sensitivity to pharmacotherapy. Based on functional differences among these subgroups, we identified nine biomarkers related to drug resistance: SYK, LCK, GAB2, PAWR, PPARG, MDFI, ZAP70, CIITA and ACTA1. Finally, based on the deviation scores of the examined pathways, 16 pathways were shown to exhibit varying degrees of abnormality in the various subgroups, indicating that patients with different subtypes of basal-like breast cancer can be characterized by differences in the functional status of

  12. Subtype distribution of Blastocystis isolates from synanthropic and zoo animals and identification of a new subtype

    DEFF Research Database (Denmark)

    Stensvold, C. R.; Alfellani, M. A.; Nørskov-Lauritsen, S.;

    2009-01-01

    Blastocystis isolates from 56 Danish synanthropic and zoo animals, 62 primates primarily from United Kingdom (UK) collections and 16 UK primate handlers were subtyped by PCR, sequencing and phylogenetic analysis. A new subtype (ST) from primates and artiodactyls was identified and designated...... as Blastocystis sp. ST10. STs isolated from non-human primates (n = 70) included ST3 (33%), ST8 (21%). ST2 (16%), ST5 (13%), ST1 (10%), ST4 (4%) and ST10(3%). A high prevalence of ST8 was seen among primate handlers (25%). This ST is normally very rare in humans, suggesting that acquisition of Blastocystis ST8...

  13. Telomerase-Independent Paths to Immortality in Predictable Cancer Subtypes

    Directory of Open Access Journals (Sweden)

    Stephen T Durant

    2012-01-01

    Full Text Available The vast majority of cancers commandeer the activity of telomerase - the remarkable enzyme responsible for prolonging cellular lifespan by maintaining the length of telomeres at the ends of chromosomes. Telomerase is only normally active in embryonic and highly proliferative somatic cells. Thus, targeting telomerase is an attractive anti-cancer therapeutic rationale currently under investigation in various phases of clinical development. However, previous reports suggest that an average of 10-15% of all cancers lose the functional activity of telomerase and most of these turn to an Alternative Lengthening of Telomeres pathway (ALT. ALT-positive tumours will therefore not respond to anti-telomerase therapies and there is a real possibility that such drugs would be toxic to normal telomerase-utilising cells and ultimately select for resistant cells that activate an ALT mechanism. ALT exploits certain DNA damage response (DDR components to counteract telomere shortening and rapid trimming. ALT has been reported in many cancer subtypes including sarcoma, gastric carcinoma, central nervous system malignancies, subtypes of kidney (Wilm's Tumour and bladder carcinoma, mesothelioma, malignant melanoma and germ cell testicular cancers to name but a few. A recent heroic study that analysed ALT in over six thousand tumour samples supports this historical spread, although only reporting an approximate 4% prevalence. This review highlights the various methods of ALT detection, unravels several molecular ALT models thought to promote telomere maintenance and elongation, spotlights the DDR components known to facilitate these and explores why certain tissues are more likely to subvert DDR away from its usually protective functions, resulting in a predictive pattern of prevalence in specific cancer subsets.

  14. Peptide Handling by HLA-B27 Subtypes Influences Their Biological Behavior, Association with Ankylosing Spondylitis and Susceptibility to Endoplasmic Reticulum Aminopeptidase 1 (ERAP1)*

    OpenAIRE

    García-Medel, Noel; Sanz-Bravo, Alejandro; Alvarez-Navarro, Carlos; Gómez-Molina, Patricia; Barnea, Eilon; Marcilla, Miguel; Admon, Arie; de Castro, José A. López

    2014-01-01

    HLA-B27 is strongly associated with ankylosing spondylitis (AS). We analyzed the relationship between structure, peptide specificity, folding, and stability of the seven major HLA-B27 subtypes to determine the role of their constitutive peptidomes in the pathogenicity of this molecule. Identification of large numbers of ligands allowed us to define the differences among subtype-bound peptidomes and to elucidate the peptide features associated with AS and molecular stability. The peptides iden...

  15. Deciphering Subtype-Selective Modulations in TRPA1 Biosensor Channels.

    Science.gov (United States)

    Kozai, Daisuke; Sakaguchi, Reiko; Ohwada, Tomohiko; Mori, Yasuo

    2015-01-01

    The transient receptor potential (TRP) proteins are a family of ion channels that act as cellular sensors. Several members of the TRP family are sensitive to oxidative stress mediators. Among them, TRPA1 is remarkably susceptible to various oxidants, and is known to mediate neuropathic pain and respiratory, vascular and gastrointestinal functions, making TRPA1 an attractive therapeutic target. Recent studies have revealed a number of modulators (both activators and inhibitors) that act on TRPA1. Endogenous mediators of oxidative stress and exogenous electrophiles activate TRPA1 through oxidative modification of cysteine residues. Non-electrophilic compounds also activate TRPA1. Certain non-electrophilic modulators may act on critical non-cysteine sites in TRPA1. However, a method to achieve selective modulation of TRPA1 by small molecules has not yet been established. More recently, we found that a novel N-nitrosamine compound activates TRPA1 by S-nitrosylation (the addition of a nitric oxide (NO) group to cysteine thiol), and does so with significant selectivity over other NO-sensitive TRP channels. It is proposed that this subtype selectivity is conferred through synergistic effects of electrophilic cysteine transnitrosylation and molecular recognition of the non-electrophilic moiety on the N-nitrosamine. In this review, we describe the molecular pharmacology of these TRPA1 modulators and discuss their modulatory mechanisms. PMID:26411770

  16. Campylobacter spp.isolation, its toxin genes detection and molecular subtyping in diarrhea patients in Shanghai in 2014%上海市2014年腹泻患者弯曲菌分离、毒力基因检测及分子分型结果

    Institute of Scientific and Technical Information of China (English)

    屠丽红; 陈洪友; 陈敏

    2015-01-01

    [目的] 了解上海市2014年腹泻患者中弯曲菌感染现状,并分析弯曲菌的毒力基因及分子分型特征.[方法] 采用膜过滤法对2014年上海市2 235例腹泻患者肛拭标本进行弯曲菌检测,并用常规生化试验和PCR方法鉴定分离菌株. 采用PCR检测弯曲菌分离株的6种毒力相关基因,包括鞭毛蛋白基因flaA,细胞溶涨毒素cdt基因簇cdtA、cdtB、cdtC,pVir质粒virB同源性基因virB11,外膜蛋白基因cadF. 采用脉冲场凝胶电泳(PFGE)法对弯曲菌分离株进行分子分型. [结果] 2 235例腹泻患者的肛拭标本中共检出弯曲菌43株,阳性率为1.9%. 其中空肠弯曲菌占95.3%(41/43),结肠弯曲菌占4.7%(2/43). 毒力相关基因检测显示,100.0%(43/43)的弯曲菌菌株flaA基因和cadF基因阳性,93.0%(40/43)的弯曲菌菌株cdtA基因和cdtB基因阳性,88.4%(38/43)的弯曲菌菌株cdtC基因阳性,只有7.0%(3/43)的弯曲菌菌株virB11基因阳性. 43株弯曲菌经PFGE分型,共分为6个聚类. [结论]上海市腹泻患者中分离的弯曲菌普遍存在flaA和cadF基因,cdtA、cdtB、cdtC基因携带率高,virB11携带率略低. 弯曲菌分子分型呈多样化和复杂化特征,其引起的腹泻以散发为主.%[ Objective] To investigate the status quo of Campylobacter spp.infection in Shanghai and study its molecular characteristics and virulence and toxin genes. [ Methods ] Stool samples collected from diarrheal patients were cultured for bacterial pathogens using membrane filter method.The strains were identified by biochemical tests and PCR.PCR was applied to detect six virulence and toxin genes including flaA,cdtA,cdtB,cdtC,virB11,cadF.Pulsed-field gel electrophoresis ( PFGE) was carried out for subtyping. [Results] A total of 43 Campylobacter spp.(1.9%) were collected from 2 235 stool samples in Shanghai in 2014 including 41 Campylobacter jejuni isolates(95.3%) and 2 Campylobacter coli isolates(4.7%) .The data showed 100.0%(43/43) of the isolates were

  17. Identifying subtypes of spousal assaulters Using the B-SAFER.

    Science.gov (United States)

    Thijssen, Jill; de Ruiter, Corine

    2011-05-01

    In the present study, a structured risk assessment instrument for intimate partner violence, the Brief Spousal Assault Form for the Evaluation of Risk (B-SAFER), was coded for 146 files of spousal assault cases from the Dutch probation service, dating from 2004 and 2005. The aim of the study was twofold: (a) to validate Holtzworth-Munroe and Stuart's typology using the risk factors of the B-SAFER and (b) to examine the relationship between the subtypes found and recidivism rates. Four subtypes of assaulters were identified: family only, generally violent/antisocial, low-level antisocial, and psychopathology. These subtypes were comparable to the subtypes found in previous studies. The generally violent/antisocial subtype had the highest recidivism rate, although not significantly different from the other three subtypes. PMID:20522890

  18. A CONTRAST ANALYSIS OF 135 CASES OF OSMIDROSIS TREATED BY RESECTING APOCRINE SWEAT GLAND WITH SKIN FLAP METHOD%皮瓣法微创腋臭切除术135例分析

    Institute of Scientific and Technical Information of China (English)

    孙卫海; 张宝成; 郭莉; 李燕; 吴小会; 陈潮

    2012-01-01

    目的 通过历史对照探索微孔引流术在皮瓣法腋臭切除术中的作用.方法 腋臭患者76例采用微孔引流行皮瓣法腋臭切除术作为治疗组,去除大汗腺及毛囊后在皮瓣上用尖刀片沿皮纹戳数个长约3mm的微孔进行引流,缝合切口后用弹力绷带包扎压迫手术区敷料.未采用微孔引流术的腋臭患者59例作为对照组进行历史对照研究,术后3d及7d换药,10d拆线并观察皮瓣成活情况,术后3~6个月进行随访.结果 2组患者均未发生切口感染.对照组出现血肿7例,其中皮肤坏死5例,出现瘢痕增生18例,腋窝皮肤皱褶9例及腋臭根治不彻底12例.治疗组出现表皮水疱8例,切口瘢痕增生6例,腋窝皮肤皱褶2例,无复发病例.治疗组治愈率明显高于对照组(P<0.01),治疗组血肿、瘢痕形成及复发率明显低于对照组(P<0.01).结论 微孔引流术可提高皮瓣法腋臭切除术疗效,而且并发症较少.%Objective To investigate the effects of resecting apocrine sweat gland with skin flap method in treating osmidrosis. Methods Seventy - six patients with osmidrosis were treated using skin flap method,named treatment group,which was punctured with sharp scalpel. The micropores were used for drainage, and the width was just 3mm. After removing apocrine sweat glands and hair follicles, the incision was sewed up. Gauze under both of axilla were pressed with 8 - shaped elastic bandage. Another 59 cases of osmidrosis, treated in the past with the same method only without micropore drainage, were named as control group. Historical case - control study was conducted. The incisions were examined at the 3d and 7d respectively, and the sutures were removed at the lOd. Follow - up study was carried out in all the patients between 3 and 6 months after the operation. Results No incision infection was found in both groups. There were 7 cases of hematoma,5 cases of skin necrosis, 18 cases of scar,9 cases of wrinkled skin,and 12

  19. Subtypes of depression in cancer patients: an empirically driven approach

    OpenAIRE

    Zhu, Lei; Ranchor, A. V.; Lee, van der, R.; Garssen, Bert; Sanderman, Robbert; Schroevers, Maya J

    2016-01-01

    PURPOSE: This study aimed to (1) identify subgroups of cancer patients with distinct subtypes of depression before the start of psychological care, (2) examine whether socio-demographic and medical characteristics distinguished these subtypes, and (3) examine whether people with distinct subtypes reported differential courses of depression during psychological care. METHOD: This naturalistic, longitudinal study included cancer patients who sought psychological care at specialized psycho-oncol...

  20. Presence of avian pneumovirus subtypes A and B in Japan.

    Science.gov (United States)

    Mase, Masaji; Yamaguchi, Shigeo; Tsukamoto, Kenji; Imada, Tadao; Imai, Kunitoshi; Nakamura, Kikuyasu

    2003-01-01

    Four avian pneumovirus (APV) isolates from chickens clinically diagnosed with swollen head syndrome were genetically characterized as to the subtypes of the virus in Japan. The results of reverse transcriptase-polymerase chain reactions based on subtype-specific primers and direct sequence analysis of G genes indicated subtypes A and B but not C or D of APV were present in Japan. Several routes or sources are conceivable for APV to invade into Japan.

  1. Identification of Novel Breast Cancer Subtype-Specific Biomarkers by Integrating Genomics Analysis of DNA Copy Number Aberrations and miRNA-mRNA Dual Expression Profiling

    Directory of Open Access Journals (Sweden)

    Dongguo Li

    2015-01-01

    Full Text Available Breast cancer is a heterogeneous disease with well-defined molecular subtypes. Currently, comparative genomic hybridization arrays (aCGH techniques have been developed rapidly, and recent evidences in studies of breast cancer suggest that tumors within gene expression subtypes share similar DNA copy number aberrations (CNA which can be used to further subdivide subtypes. Moreover, subtype-specific miRNA expression profiles are also proposed as novel signatures for breast cancer classification. The identification of mRNA or miRNA expression-based breast cancer subtypes is considered an instructive means of prognosis. Here, we conducted an integrated analysis based on copy number aberrations data and miRNA-mRNA dual expression profiling data to identify breast cancer subtype-specific biomarkers. Interestingly, we found a group of genes residing in subtype-specific CNA regions that also display the corresponding changes in mRNAs levels and their target miRNAs’ expression. Among them, the predicted direct correlation of BRCA1-miR-143-miR-145 pairs was selected for experimental validation. The study results indicated that BRCA1 positively regulates miR-143-miR-145 expression and miR-143-miR-145 can serve as promising novel biomarkers for breast cancer subtyping. In our integrated genomics analysis and experimental validation, a new frame to predict candidate biomarkers of breast cancer subtype is provided and offers assistance in order to understand the potential disease etiology of the breast cancer subtypes.

  2. Obesity and risk of ovarian cancer subtypes

    DEFF Research Database (Denmark)

    Olsen, Catherine M; Nagle, Christina M; Whiteman, David C;

    2013-01-01

    Whilst previous studies have reported that higher BMI increases a woman's risk of developing ovarian cancer, associations for the different histological subtypes have not been well defined. As the prevalence of obesity has increased dramatically, and classification of ovarian histology has improv......, it does not increase risk of high-grade invasive serous cancers, and reducing BMI is therefore unlikely to prevent the majority of ovarian cancer deaths. Other modifiable factors must be identified to control this disease.......Whilst previous studies have reported that higher BMI increases a woman's risk of developing ovarian cancer, associations for the different histological subtypes have not been well defined. As the prevalence of obesity has increased dramatically, and classification of ovarian histology has improved...... in the last decade, we sought to examine the association in a pooled analysis of recent studies participating in the Ovarian Cancer Association Consortium. We evaluated the association between BMI (recent, maximum and in young adulthood) and ovarian cancer risk using original data from 15 case...

  3. From pluripotency to distinct cardiomyocyte subtypes.

    Science.gov (United States)

    David, Robert; Franz, Wolfgang-Michael

    2012-06-01

    Differentiated adult cardiomyocytes (CMs) lack significant regenerative potential, which is one reason why degenerative heart diseases are the leading cause of death in the western world. For future cardiac repair, stem cell-based therapeutic strategies may become alternatives to donor heart transplantation. The principle of reprogramming adult terminally differentiated cells (iPSC) had a major impact on stem cell biology. One can now generate autologous pluripotent cells that highly resemble embryonic stem cells (ESC) and that are ethically inoffensive as opposed to human ESC. Yet, due to genetic and epigenetic aberrations arising during the full reprogramming process, it is questionable whether iPSC will enter the clinic in the near future. Therefore, the recent achievement of directly reprogramming fibroblasts into cardiomyocytes via a milder approach, thereby avoiding an initial pluripotent state, may become of great importance. In addition, various clinical scenarios will depend on the availability of specific cardiac cellular subtypes, for which a first step was achieved via our own programming approach to achieve cardiovascular cell subtypes. In this review, we discuss recent progress in the cardiovascular stem cell field addressing the above mentioned aspects. PMID:22689787

  4. Contribution of Blastocystishominis subtypes and associated inflammatory factors in development of irritable bowel syndrome.

    Science.gov (United States)

    Azizian, Marzieh; Basati, Gholam; Abangah, Ghobad; Mahmoudi, Mohammad Reza; Mirzaei, Asad

    2016-05-01

    Blastocystis hominis with worldwide distribution is a human intestinal protozoa found in all countries. There have been differences in the severity of the pathogenesis of various Blastocystis spp. and a concomitant variation in the plasma concentration of the cytokines in patients with irritable bowel syndrome. In the present study, we aimed to demonstrate the contribution of B. hominis subtypes in the development of irritable bowel syndrome. Stool samples were collected from patients with gastrointestinal disorders. All samples were evaluated through native-lugol method. Total DNA was extracted. A PCR protocol was developed to amplify a specific region of the SSU ribosomal DNA (rDNA) gene. Serum levels of IL-6 and TNF-α were determined by immunoassay methods. The ClustalW algorithm was applied to align and blast the nucleotide sequences of the amplified region of the SSU rDNA gene. To evaluate the phylogenetic and molecular evolutionary of the nucleotide sequences, we used the MEGA software. In this study, we found 26 haplotypes of B. hominis in the studied samples which were collectively belong to five subtypes (ST1, ST2 in patients without irritable bowel syndrome vs. ST3 and two unknown subtypes in patients with irritable bowel syndrome). Result of ELISA showed a high level of IL-6 and TNF-α in the serum of patients with irritable bowel syndrome. The genetic heterogeneity of B. hominis and the existence of different subtypes of the protozoan in patients with IBS may shed light to the fact that some subtypes of parasites may involve in the pathogenesis of IBS. PMID:26841770

  5. Prognostic evaluation of the B cell/IL-8 metagene in different intrinsic breast cancer subtypes.

    Science.gov (United States)

    Hanker, Lars C; Rody, Achim; Holtrich, Uwe; Pusztai, Lajos; Ruckhaeberle, Eugen; Liedtke, Cornelia; Ahr, Andre; Heinrich, Tomas M; Sänger, Nicole; Becker, Sven; Karn, Thomas

    2013-01-01

    We recently reported that a ratio of high B cell and low IL-8 metagene expression identified 32 % of triple negative breast cancers (TNBC) with good prognosis and was the only significant predictor in multivariate analysis including routine clinicopathological variables. However, the clinical relevance of this signature in other breast cancer subtypes remains unclear. We compiled Affymetrix gene expression datasets from 4,467 primary breast cancer samples and excluded 329 triple negative samples which were used as discovery cohort in our previous study. Molecular classification of the remaining 4,138 samples was performed by two methods, including single genes (ER, PgR, HER2, and Ki67) and a centroid-based method using the intrinsic gene list. The prognostic value within the respective subtypes was assessed by analyzing the event-free survival of patients as a function of the B cell/IL-8 metagene ratio using previously published cutoff. ER-negative subtypes had the highest expression of the B cell and the IL-8 metagenes. The IL-8/B cell signature assigned a considerable fraction of samples (range 20.7-42.0 %) into the "good prognosis" group. However, a significant prognostic value was only observed in the subgroup of triple negative breast cancer (P = 0.035). The prognostic value of the B cell/IL-8 ratio is mainly confined to the basal-like and TNBC subtypes of breast cancer. This result underlines the importance of subtype-specific analyses and suggests a sequential multistep approach to developing and applying outcome predictors in the clinic.

  6. Common genetic variation in adiponectin, leptin, and leptin receptor and association with breast cancer subtypes.

    Science.gov (United States)

    Nyante, Sarah J; Gammon, Marilie D; Kaufman, Jay S; Bensen, Jeannette T; Lin, Dan Yu; Barnholtz-Sloan, Jill S; Hu, Yijuan; He, Qianchuan; Luo, Jingchun; Millikan, Robert C

    2011-09-01

    Adipocytokines are produced by visceral fat, and levels may be associated with breast cancer risk. We investigated whether single nucleotide polymorphisms (SNPs) in adipocytokine genes adiponectin (ADIPOQ), leptin (LEP), and the leptin receptor (LEPR) were associated with basal-like or luminal A breast cancer subtypes. 104 candidate and tag SNPs were genotyped in 1776 of 2022 controls and 1972 (200 basal-like, 679 luminal A) of 2311 cases from the Carolina Breast Cancer Study (CBCS), a population-based case-control study of whites and African Americans. Breast cancer molecular subtypes were determined by immunohistochemistry. Genotype odds ratios (ORs) and 95% confidence intervals (CIs) were estimated using unconditional logistic regression. Haplotype ORs and 95% CIs were estimated using Hapstat. Interactions with waist-hip ratio were evaluated using a multiplicative interaction term. Ancestry was estimated from 144 ancestry informative markers (AIMs), and included in models to control for population stratification. Candidate SNPs LEPR K109R (rs1137100) and LEPR Q223R (rs1137101) were positively associated with luminal A breast cancer, whereas ADIPOQ +45 T/G (rs2241766), ADIPOQ +276 G/T (rs1501299), and LEPR K656N (rs8129183) were not associated with either subtype. Few patterns were observed among tag SNPs, with the exception of 3 LEPR SNPs (rs17412175, rs9436746, and rs9436748) that were in moderate LD and inversely associated with basal-like breast cancer. However, no SNP associations were statistically significant after adjustment for multiple comparisons. Haplotypes in LEP and LEPR were associated with both basal-like and luminal A subtypes. There was no evidence of interaction with waist-hip ratio. Data suggest associations between LEPR candidate SNPs and luminal A breast cancer in the CBCS and LEPR intron 2 tag SNPs and basal-like breast cancer. Replication in additional studies where breast cancer subtypes have been defined is necessary to confirm these

  7. Revisiting the Derivation of Batterer Subtypes: Towards Profiling the Abuser.

    Science.gov (United States)

    Brasfield, Rebecca

    2015-12-01

    Research directed toward profiling an abuser to develop effective treatment modalities should consider the framework for how batterer subtypes were developed. This article evaluates a seminal work in batterer typology for a review of its method and findings. Findings indicate that the formation of batterer subtypes rely on unstable theory and methods: (a) Variables were not held constant, (b) Theoretical constructs lack clarity, (c) There were unclear boundaries for subtypes. A re-evaluation of this particular line of typology research should address the utility and relevance of these batterer subtypes in an effort to address methodological implications that may help profile and treat abusers. PMID:25516132

  8. Markers of subtypes in inflammatory breast cancer studied by immunohistochemistry: Prominent expression of P-cadherin

    Directory of Open Access Journals (Sweden)

    Viens Patrice

    2008-01-01

    Full Text Available Abstract Background Inflammatory breast cancer (IBC is a distinct and aggressive form of locally-advanced breast cancer with high metastatic potential. In Tunisia, IBC is associated with a high death rate. Among the major molecular subtypes, basal breast carcinomas are poorly differentiated, have metastatic potential and poor prognosis, but respond relatively well to chemotherapy. The aim of this study was to determine the distribution of molecular subtypes in IBC and identify factors that may explain the poor prognosis of IBC. Methods To determine breast cancer subtypes we studied by immunohistochemistry the expression of 12 proteins in a series of 91 Tunisian IBC and 541 non-IBC deposited in tissue microarrays. Results We considered infiltrating ductal cases only. We found 33.8% of basal cases in IBC vs 15.9% in non-IBC (p Conclusion Tunisian IBCs are characterized by frequent basal and ERBB2 phenotypes. Surprisingly, luminal IBC also express the basal marker P-cadherin. This profile suggests a specificity that needs further investigation.

  9. Genetic heterogeneity and subtyping of human Hepatitis E virus isolates from Uruguay.

    Science.gov (United States)

    Mirazo, Santiago; Ramos, Natalia; Russi, José Carlos; Arbiza, Juan

    2013-05-01

    Hepatitis E virus (HEV) infection is an important public health concern in many developing countries causing waterborne outbreaks, as well as sporadic autochthonous hepatitis. It is transmitted primarily by the fecal-oral route. However, zoonotic transmission from animal reservoirs to human has also been suggested. Genotype 3 is the most frequent genotype found in South America and the HEV epidemiology in this region seems to be very complex. However, data about the molecular characterization of HEV isolates of the region is still lacking and further investigation is needed. Our study characterized human HEV strains detected in a 1-year period in Uruguay, by extensive sequence analysis of three regions of the HEV genome. Uruguayan strains were closely related to a set of European strains and in turn, were dissimilar to Brazilian, Argentinean and Bolivian isolates. Additionally, the co-circulation of viral subtypes 3i and 3h was observed. Circulation of subtype 3i had been reported in Argentina and Bolivia whereas sequences of subtype 3h are rare and had never been reported in Latin America. In order to contribute to shedding light over the molecular epidemiology of this emergent infection in the region, we thoroughly analyzed the genetic variability of HEV strains detected in Uruguay, providing the largest dataset of sequences of HEV ever reported in a country in South America.

  10. Comprehensive molecular portraits of human breast tumours.

    Science.gov (United States)

    2012-10-01

    We analysed primary breast cancers by genomic DNA copy number arrays, DNA methylation, exome sequencing, messenger RNA arrays, microRNA sequencing and reverse-phase protein arrays. Our ability to integrate information across platforms provided key insights into previously defined gene expression subtypes and demonstrated the existence of four main breast cancer classes when combining data from five platforms, each of which shows significant molecular heterogeneity. Somatic mutations in only three genes (TP53, PIK3CA and GATA3) occurred at >10% incidence across all breast cancers; however, there were numerous subtype-associated and novel gene mutations including the enrichment of specific mutations in GATA3, PIK3CA and MAP3K1 with the luminal A subtype. We identified two novel protein-expression-defined subgroups, possibly produced by stromal/microenvironmental elements, and integrated analyses identified specific signalling pathways dominant in each molecular subtype including a HER2/phosphorylated HER2/EGFR/phosphorylated EGFR signature within the HER2-enriched expression subtype. Comparison of basal-like breast tumours with high-grade serous ovarian tumours showed many molecular commonalities, indicating a related aetiology and similar therapeutic opportunities. The biological finding of the four main breast cancer subtypes caused by different subsets of genetic and epigenetic abnormalities raises the hypothesis that much of the clinically observable plasticity and heterogeneity occurs within, and not across, these major biological subtypes of breast cancer.

  11. Age and the means of bypassing stasis are determinants of the intrinsic subtypes of immortalized human mammary epithelial cells

    Directory of Open Access Journals (Sweden)

    Jonathan K Lee

    2015-03-01

    Full Text Available Based on molecular features, breast cancers are grouped into intrinsic subtypes that have different prognoses and therapeutic response profiles. With increasing age, breast cancer incidence increases, with hormone receptor-positive and other luminal-like subtype tumors comprising a majority of cases. It is not known at what stage of tumor progression subtype specification occurs, nor how the process of aging affects the intrinsic subtype. We examined subtype markers in immortalized human mammary epithelial cell lines established following exposure of primary cultured cell strains to a two-step immortalization protocol that targets the two main barriers to immortality: stasis (stress-associated senescence and replicative senescence. Cell lines derived from epithelial cells obtained from non-tumorous pre- and post-menopausal breast surgery tissues were compared. Additionally, comparisons were made between lines generated using two different genetic interventions to bypass stasis: transduction of either an shRNA that down-regulated p16INK4A, or overexpressed constitutive active cyclin D1/CDK2. In all cases, the replicative senescence barrier was bypassed by transduction of c-Myc. Cells from all resulting immortal lines exhibited normal karyotypes. Immunofluorescence, flow cytometry, and gene expression analyses of lineage-specific markers were used to categorize the intrinsic subtypes of the immortalized lines. Bypassing stasis with p16 shRNA in young strains generated cell lines that were invariably basal-like, but the lines examined from older strains exhibited some luminal features such as keratin 19 and estrogen receptor expression. Overexpression of cyclin D1/CDK2 resulted in keratin 19 positive, luminal-like cell lines from both young and old strains, and the lines examined from older strains exhibited estrogen receptor expression. Thus age and the method of bypassing stasis are independent determinants of subtype in immortalized human

  12. Age and the means of bypassing stasis influence the intrinsic subtype of immortalized human mammary epithelial cells.

    Science.gov (United States)

    Lee, Jonathan K; Garbe, James C; Vrba, Lukas; Miyano, Masaru; Futscher, Bernard W; Stampfer, Martha R; LaBarge, Mark A

    2015-01-01

    Based on molecular features, breast cancers are grouped into intrinsic subtypes that have different prognoses and therapeutic response profiles. With increasing age, breast cancer incidence increases, with hormone receptor-positive and other luminal-like subtype tumors comprising a majority of cases. It is not known at what stage of tumor progression subtype specification occurs, nor how the process of aging affects the intrinsic subtype. We examined subtype markers in immortalized human mammary epithelial cell lines established following exposure of primary cultured cell strains to a two-step immortalization protocol that targets the two main barriers to immortality: stasis (stress-associated senescence) and replicative senescence. Cell lines derived from epithelial cells obtained from non-tumorous pre- and post-menopausal breast surgery tissues were compared. Additionally, comparisons were made between lines generated using two different genetic interventions to bypass stasis: transduction of either an shRNA that down-regulated p16(INK4A), or overexpressed constitutive active cyclin D1/CDK2. In all cases, the replicative senescence barrier was bypassed by transduction of c-Myc. Cells from all resulting immortal lines exhibited normal karyotypes. Immunofluorescence, flow cytometry, and gene expression analyses of lineage-specific markers were used to categorize the intrinsic subtypes of the immortalized lines. Bypassing stasis with p16 shRNA in young strains generated cell lines that were invariably basal-like, but the lines examined from older strains exhibited some luminal features such as keratin 19 and estrogen receptor expression. Overexpression of cyclin D1/CDK2 resulted in keratin 19 positive, luminal-like cell lines from both young and old strains, and the lines examined from older strains exhibited estrogen receptor expression. Thus age and the method of bypassing stasis independently influence the subtype of immortalized human mammary epithelial cells

  13. Complex trait subtypes identification using transcriptome profiling reveals an interaction between two QTL affecting adiposity in chicken

    Directory of Open Access Journals (Sweden)

    Blum Yuna

    2011-11-01

    Full Text Available Abstract Background Integrative genomics approaches that combine genotyping and transcriptome profiling in segregating populations have been developed to dissect complex traits. The most common approach is to identify genes whose eQTL colocalize with QTL of interest, providing new functional hypothesis about the causative mutation. Another approach includes defining subtypes for a complex trait using transcriptome profiles and then performing QTL mapping using some of these subtypes. This approach can refine some QTL and reveal new ones. In this paper we introduce Factor Analysis for Multiple Testing (FAMT to define subtypes more accurately and reveal interaction between QTL affecting the same trait. The data used concern hepatic transcriptome profiles for 45 half sib male chicken of a sire known to be heterozygous for a QTL affecting abdominal fatness (AF on chromosome 5 distal region around 168 cM. Results Using this methodology which accounts for hidden dependence structure among phenotypes, we identified 688 genes that are significantly correlated to the AF trait and we distinguished 5 subtypes for AF trait, which are not observed with gene lists obtained by classical approaches. After exclusion of one of the two lean bird subtypes, linkage analysis revealed a previously undetected QTL on chromosome 5 around 100 cM. Interestingly, the animals of this subtype presented the same q paternal haplotype at the 168 cM QTL. This result strongly suggests that the two QTL are in interaction. In other words, the "q configuration" at the 168 cM QTL could hide the QTL existence in the proximal region at 100 cM. We further show that the proximal QTL interacts with the previous one detected on the chromosome 5 distal region. Conclusion Our results demonstrate that stratifying genetic population by molecular phenotypes followed by QTL analysis on various subtypes can lead to identification of novel and interacting QTL.

  14. Subtype classification of Iranian HIV-1 sequences registered in the HIV databases, 2006-2013.

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    Kazem Baesi

    Full Text Available BACKGROUND: The rate of human immunodeficiency virus type 1 (HIV-1 infection in Iran has increased dramatically in the past few years. While the earliest cases were among hemophiliacs, injection drug users (IDUs fuel the current epidemic. Previous molecular epidemiological analysis found that subtype A was most common among IDUs but more recent studies suggest CRF_35AD may be more prevalent now. To gain a better understanding of the molecular epidemiology of HIV-1 infection in Iran, we analyzed all Iranian HIV sequence data from the Los Alamos National Laboratory. METHODS: All Iranian HIV sequences from subtyping studies with pol, gag, env and full-length HIV-1 genome sequences registered in the HIV databases (www.hiv.lanl.gov between 2006 and 2013 were downloaded. Phylogenetic trees of each region were constructed using Neighbor-Joining (NJ and Maximum Parsimony methods. RESULTS: A total of 475 HIV sequences were analyzed. Overall, 78% of sequences were CRF_35AD. By gene region, CRF_35AD comprised 83% of HIV-1 pol, 62% of env, 78% of gag, and 90% of full-length genome sequences analyzed. There were 240 sequences re-categorized as CRF_AD. The proportion of CRF_35AD sequences categorized by the present study is nearly double the proportion of what had been reported. CONCLUSIONS: Phylogenetic analysis indicates HIV-1 subtype CRF_35AD is the predominant circulating strain in Iran. This result differed from previous studies that reported subtype A as most prevalent in HIV- infected patients but confirmed other studies which reported CRF_35AD as predominant among IDUs. The observed epidemiological connection between HIV strains circulating in Iran and Afghanistan may be due to drug trafficking and/or immigration between the two countries. This finding suggests the possible origins and transmission dynamics of HIV/AIDS within Iran and provides useful information for designing control and intervention strategies.

  15. High Prevalence and Onward Transmission of Non-Pandemic HIV-1 Subtype B Clades in Northern and Northeastern Brazilian Regions

    Science.gov (United States)

    Divino, Flavia; de Lima Guerra Corado, Andre; Gomes Naveca, Felipe; Stefani, Mariane M. A.; Bello, Gonzalo

    2016-01-01

    The Human immunodeficiency virus type-1 (HIV-1) epidemic in Brazil is mainly driven by the subtype B pandemic lineage (BPANDEMIC), while Caribbean non-pandemic subtype B clades (BCAR) seem to account for a very low fraction of HIV-infections in this country. The molecular characteristics of the HIV-1 subtype B strains disseminated in the Northern and Northeastern Brazilian regions, however, have not been explored so far. In this study, we estimate the prevalence of the HIV-1 BPANDEMIC and BCAR clades across different Brazilian regions and we reconstruct the spatiotemporal dynamics of dissemination of the major Brazilian BCAR clades. A total of 2,682 HIV-1 subtype B pol sequences collected from 21 different Brazilian states from the five country regions between 1998 and 2013 were analyzed. Maximum Likelihood phylogenetic analyses revealed that the BCAR strains reached 16 out 21 Brazilian states here analyzed. The BCAR clades comprise a low fraction (<10%) of subtype B infections in most Brazilian states analyzed, with exception of Roraima (41%), Amazonas (14%) and Maranhão (14%). Bayesian phylogeographic analyses indicate that BCAR strains originally from the Hispaniola and Trinidad and Tobago were introduced at multiple times into different states from all Brazilian regions and a few of those strains, probably introduced into Roraima, Maranhão and São Paulo between the late 1970s and the early 1980s, established secondary outbreaks in the Brazilian population. These results support that the HIV-1 subtype B epidemics in some Brazilian states from the Northern and Northeastern regions display a unique molecular pattern characterized by the high prevalence of BCAR lineages, which probably reflects a strong epidemiological link with the HIV-1 epidemics in the Caribbean region. PMID:27603317

  16. Subtype classification for prediction of prognosis of breast cancer from a biomarker panel: correlations and indications

    Directory of Open Access Journals (Sweden)

    Chen C

    2014-02-01

    positive correlation (P<0.001 between the estrogen receptor and the progesterone receptor (r=0.588, but a significant negative correlation (P<0.001, r=-0.618 with the HHR subtype. There were significant differences between the estrogen receptor, progesterone receptor, and HER2 subtypes with regard to total HER2 load and hormone receptor subtypes. The rates of androgen receptor and p53 positivity were 46.3% and 57.0%, respectively. Other than the androgen receptor, differences in expression of Ki67, EGFR, and p53 did not achieve statistical significance (P>0.05 between the five subtypes. EGFR and Ki67 had prognostic significance for 5-year disease-free survival in univariate analysis, but the androgen receptor and p53 did not. Multivariate analysis identified that EGFR expression had predictive significance for 5-year disease-free survival in hormone-receptor positive patients and in those with the lymph node-positive breast cancer subtype. Conclusion: Hormone receptor expression was indeed one of the molecular profiles in the subtypes identified by quantitative HER2 and vice versa. EGFR status may provide discriminative prognostic information in addition to HER2 and hormone receptor status, and should be integrated into routine practice to help formulate more specific prediction of the prognosis and appropriate individualized treatment. Keywords: quantum dots, breast cancer, molecular classification, prognosis, prediction

  17. Is Rett Syndrome a Subtype of Pervasive Developmental Disorders?

    Science.gov (United States)

    Tsai, Luke Y.

    1992-01-01

    This paper reviews whether Rett syndrome is a subtype of pervasive developmental disorders (PDD). The paper analyzes internal and external diagnostic validity and discusses whether Rett syndrome is a neurological disorder or a mental disorder. The paper concludes that data support the idea of classifying Rett syndrome as a subtype of PDD.…

  18. Preoperative subtyping of meningiomas by perfusion MR imaging

    NARCIS (Netherlands)

    Zhang, Hao; Roediger, Lars A.; Shen, Tianzhen; Miao, Jingtao; Oudkerk, Matthijs

    2008-01-01

    Introduction This paper aims to evaluate the value of perfusion magnetic resonance (MR) imaging in the preoperative subtyping of meningiomas by analyzing the relative cerebral blood volume (rCBV) of three benign subtypes and anaplastic meningiomas separately. Materials and methods Thirty-seven menin

  19. Genetic overlap between diagnostic subtypes of ischemic stroke

    NARCIS (Netherlands)

    E.G. Holliday (Elizabeth); M. Traylor (Matthew); R. Malik (Rainer); S. Bevan (Steve); G.J. Falcone (Guido J.); J. Hopewell; Y.-C. Cheng (Yu-Ching); I. Cotlarciuc (Ioana); J.C. Bis (Joshua); E.A. Boerwinkle (Eric); G. Boncoraglio (Giorgio Battista); R. Clarke (Robert); J.W. Cole (John W.); M. Fornage (Myriam); K.L. Furie (Karen); M.A. Ikram (Arfan); J. Jannes (Jim); T. Kittner (Thomas); L.F. Lincz (Lisa); J.M. Maguire (Jane); J.F. Meschia (James F.); T.H. Mosley (Thomas H.); M.A. Nalls (Michael); C. Oldmeadow (Christopher); E.A. Parati (Eugenio A.); B.M. Psaty (Bruce); P.M. Rothwell (Peter); S. Seshadri (Sudha); R.J. Scott (Rodney J.); P. Sharma (Pankaj); C. Sudlow (Cathie); K.L. Wiggins (Kerri); B.B. Worrall (Bradford B.); J. Rosand (Jonathan); B.D. Mitchell (Braxton); C. Kubisch (Christian); H.S. Markus (Hugh); C. Levi (Christopher); J. Attia (John); N.R. Wray (Naomi)

    2015-01-01

    textabstractBackground and Purpose: Despite moderate heritability, the phenotypic heterogeneity of ischemic stroke has hampered gene discovery, motivating analyses of diagnostic subtypes with reduced sample sizes. We assessed evidence for a shared genetic basis among the 3 major subtypes: large arte

  20. The Association between Physical Morbidity and Subtypes of Severe Depression

    DEFF Research Database (Denmark)

    Østergaard, Søren Dinesen; Petrides, Georgio; Dinesen, Peter Thisted;

    2013-01-01

    Physical illness and depression are related, but the association between specific physical diseases and diagnostic subtypes of depression remains poorly understood. This study aimed to clarify the relationship between a number of physical diseases and the nonpsychotic and psychotic subtype of sev...

  1. Subtypes of irritable bowel syndrome in children and adolescents

    Science.gov (United States)

    Pharmacologic treatments for irritable bowel syndrome (IBS) and medical management of symptoms are increasingly based on IBS subtype, so it is important to accurately differentiate patients. Few studies have classified subtypes of pediatric IBS, and conclusions have been challenged by methodologic l...

  2. Simple Identification of Complex ADHD Subtypes Using Current Symptom Counts

    Science.gov (United States)

    Volk, Heather E.; Todorov, Alexandre A.; Hay, David A.; Todd, Richard D.

    2009-01-01

    The results of the assessment of the accuracy of simple rules based on symptom count for assigning youths to attention deficit hyperactivity disorder subtypes show that having six or more total symptoms and fewer than three hyperactive-impulsive symptoms is an accurate predictor for the latent class sever inattentive subtype.

  3. Tubal ligation and risk of ovarian cancer subtypes

    DEFF Research Database (Denmark)

    Sieh, Weiva; Salvador, Shannon; McGuire, Valerie;

    2013-01-01

    Tubal ligation is a protective factor for ovarian cancer, but it is unknown whether this protection extends to all invasive histological subtypes or borderline tumors. We undertook an international collaborative study to examine the association between tubal ligation and ovarian cancer subtypes....

  4. Cigarette smoking and risk of Hodgkin lymphoma and its subtypes

    DEFF Research Database (Denmark)

    Kamper-Jørgensen, Mads; Rostgaard, K; Glaser, S L;

    2013-01-01

    The etiology of Hodgkin lymphoma (HL) remains incompletely characterized. Studies of the association between smoking and HL have yielded ambiguous results, possibly due to differences between HL subtypes.......The etiology of Hodgkin lymphoma (HL) remains incompletely characterized. Studies of the association between smoking and HL have yielded ambiguous results, possibly due to differences between HL subtypes....

  5. Distinct subtypes of knee osteoarthritis : data from the Osteoarthritis Initiative

    NARCIS (Netherlands)

    Waarsing, Jan H; Bierma-Zeinstra, Sita M A; Weinans, Harrie

    2015-01-01

    OBJECTIVE: OA is suspected to be a collection of distinct subtypes, each with different aetiology and clinical characteristics. We aimed to explore the existence of different subtypes of knee OA, using cluster analysis of the data of the OA Initiative. METHODS: We used latent class cluster analysis

  6. The validity and utility of subtyping bulimia nervosa

    NARCIS (Netherlands)

    van Hoeken, Daphne; Veling, Wim; Sinke, Sjoukje; Mitchell, James E.; Hoek, Hans W.

    2009-01-01

    Objective: To review the evidence for the validity and utility of subtyping bulimia nervosa (BN) into a purging (BN-P) and a nonpurging subtype (BN-NP), and of distinguishing BN-NP from binge eating disorder (BED), by comparing course, complications, and treatment. Method: A literature search of psy

  7. Microbial forensics: fiber optic microarray subtyping of Bacillus anthracis

    Science.gov (United States)

    Shepard, Jason R. E.

    2009-05-01

    The past decade has seen increased development and subsequent adoption of rapid molecular techniques involving DNA analysis for detection of pathogenic microorganisms, also termed microbial forensics. The continued accumulation of microbial sequence information in genomic databases now better positions the field of high-throughput DNA analysis to proceed in a more manageable fashion. The potential to build off of these databases exists as technology continues to develop, which will enable more rapid, cost effective analyses. This wealth of genetic information, along with new technologies, has the potential to better address some of the current problems and solve the key issues involved in DNA analysis of pathogenic microorganisms. To this end, a high density fiber optic microarray has been employed, housing numerous DNA sequences simultaneously for detection of various pathogenic microorganisms, including Bacillus anthracis, among others. Each organism is analyzed with multiple sequences and can be sub-typed against other closely related organisms. For public health labs, real-time PCR methods have been developed as an initial preliminary screen, but culture and growth are still considered the gold standard. Technologies employing higher throughput than these standard methods are better suited to capitalize on the limitless potential garnered from the sequence information. Microarray analyses are one such format positioned to exploit this potential, and our array platform is reusable, allowing repetitive tests on a single array, providing an increase in throughput and decrease in cost, along with a certainty of detection, down to the individual strain level.

  8. Sequence analysis of mutations and translocations across breast cancer subtypes

    Science.gov (United States)

    Banerji, Shantanu; Cibulskis, Kristian; Rangel-Escareno, Claudia; Brown, Kristin K.; Carter, Scott L.; Frederick, Abbie M.; Lawrence, Michael S.; Sivachenko, Andrey Y.; Sougnez, Carrie; Zou, Lihua; Cortes, Maria L.; Fernandez-Lopez, Juan C.; Peng, Shouyong; Ardlie, Kristin G.; Auclair, Daniel; Bautista-Piña, Veronica; Duke, Fujiko; Francis, Joshua; Jung, Joonil; Maffuz-Aziz, Antonio; Onofrio, Robert C.; Parkin, Melissa; Pho, Nam H.; Quintanar-Jurado, Valeria; Ramos, Alex H.; Rebollar-Vega, Rosa; Rodriguez-Cuevas, Sergio; Romero-Cordoba, Sandra L.; Schumacher, Steven E.; Stransky, Nicolas; Thompson, Kristin M.; Uribe-Figueroa, Laura; Baselga, Jose; Beroukhim, Rameen; Polyak, Kornelia; Sgroi, Dennis C.; Richardson, Andrea L.; Jimenez-Sanchez, Gerardo; Lander, Eric S.; Gabriel, Stacey B.; Garraway, Levi A.; Golub, Todd R.; Melendez-Zajgla, Jorge; Toker, Alex; Getz, Gad; Hidalgo-Miranda, Alfredo; Meyerson, Matthew

    2014-01-01

    Breast carcinoma is the leading cause of cancer-related mortality in women worldwide with an estimated 1.38 million new cases and 458,000 deaths in 2008 alone1. This malignancy represents a heterogeneous group of tumours with characteristic molecular features, prognosis, and responses to available therapy2–4. Recurrent somatic alterations in breast cancer have been described including mutations and copy number alterations, notably ERBB2 amplifications, the first successful therapy target defined by a genomic aberration5. Prior DNA sequencing studies of breast cancer genomes have revealed additional candidate mutations and gene rearrangements 6–10. Here we report the whole-exome sequences of DNA from 103 human breast cancers of diverse subtypes from patients in Mexico and Vietnam compared to matched-normal DNA, together with whole-genome sequences of 22 breast cancer/normal pairs. Beyond confirming recurrent somatic mutations in PIK3CA11, TP536, AKT112, GATA313, and MAP3K110, we discovered recurrent mutations in the CBFB transcription factor gene and deletions of its partner RUNX1. Furthermore, we have identified a recurrent MAGI3-AKT3 fusion enriched in triple-negative breast cancer lacking estrogen and progesterone receptors and ERBB2 expression. The Magi3-Akt3 fusion leads to constitutive activation of Akt kinase, which is abolished by treatment with an ATP-competitive Akt small-molecule inhibitor. PMID:22722202

  9. Divergent genomic and epigenomic landscapes of lung cancer subtypes underscore the selection of different oncogenic pathways during tumor development.

    Directory of Open Access Journals (Sweden)

    William W Lockwood

    Full Text Available For therapeutic purposes, non-small cell lung cancer (NSCLC has traditionally been regarded as a single disease. However, recent evidence suggest that the two major subtypes of NSCLC, adenocarcinoma (AC and squamous cell carcinoma (SqCC respond differently to both molecular targeted and new generation chemotherapies. Therefore, identifying the molecular differences between these tumor types may impact novel treatment strategy. We performed the first large-scale analysis of 261 primary NSCLC tumors (169 AC and 92 SqCC, integrating genome-wide DNA copy number, methylation and gene expression profiles to identify subtype-specific molecular alterations relevant to new agent design and choice of therapy. Comparison of AC and SqCC genomic and epigenomic landscapes revealed 778 altered genes with corresponding expression changes that are selected during tumor development in a subtype-specific manner. Analysis of >200 additional NSCLCs confirmed that these genes are responsible for driving the differential development and resulting phenotypes of AC and SqCC. Importantly, we identified key oncogenic pathways disrupted in each subtype that likely serve as the basis for their differential tumor biology and clinical outcomes. Downregulation of HNF4α target genes was the most common pathway specific to AC, while SqCC demonstrated disruption of numerous histone modifying enzymes as well as the transcription factor E2F1. In silico screening of candidate therapeutic compounds using subtype-specific pathway components identified HDAC and PI3K inhibitors as potential treatments tailored to lung SqCC. Together, our findings suggest that AC and SqCC develop through distinct pathogenetic pathways that have significant implication in our approach to the clinical management of NSCLC.

  10. Protein and lipid MALDI profiles classify breast cancers according to the intrinsic subtype

    Directory of Open Access Journals (Sweden)

    Yoo Chong

    2011-10-01

    Full Text Available Abstract Background Matrix-assisted laser desorption/ionization (MALDI mass spectrometry (MS has been demonstrated to be useful for molecular profiling of common solid tumors. Using recently developed MALDI matrices for lipid profiling, we evaluated whether direct tissue MALDI MS analysis on proteins and lipids may classify human breast cancer samples according to the intrinsic subtype. Methods Thirty-four pairs of frozen, resected breast cancer and adjacent normal tissue samples were analyzed using histology-directed, MALDI MS analysis. Sinapinic acid and 2,5-dihydroxybenzoic acid/α-cyano-4-hydroxycinnamic acid were manually deposited on areas of each tissue section enriched in epithelial cells to identify lipid profiles, and mass spectra were acquired using a MALDI-time of flight instrument. Results Protein and lipid profiles distinguish cancer from adjacent normal tissue samples with the median prediction accuracy of 94.1%. Luminal, HER2+, and triple-negative tumors demonstrated different protein and lipid profiles, as evidenced by permutation P values less than 0.01 for 0.632+ bootstrap cross-validated misclassification rates with all classifiers tested. Discriminatory proteins and lipids were useful for classifying tumors according to the intrinsic subtype with median prediction accuracies of 80.0-81.3% in random test sets. Conclusions Protein and lipid profiles accurately distinguish tumor from adjacent normal tissue and classify breast cancers according to the intrinsic subtype.

  11. Evaluation of MetriGenix custom 4D™ arrays applied for detection of breast cancer subtypes

    Directory of Open Access Journals (Sweden)

    Naume Bjørn

    2006-03-01

    Full Text Available Abstract Background Previously, a total of five breast cancer subtypes have been identified based on variation in gene expression patterns. These expression profiles were also shown to be associated with different prognostic value. In this study tumour samples from 27 breast cancer patients, previously subtyped by expression analysis using DNA microarrays, and four controls from normal breast tissue were included. A new MetriGenix 4D™ array proposed for diagnostic use was evaluated. Methods We applied MetriGenix custom 4D™ arrays for the detection of previously defined molecular subtypes of breast cancer. MetriGenix 4D™ arrays have special features including probe immobilization in microchannels with chemiluminescence detection that enable shorter hybridization time. Results The MetriGenix 4D™ array platform was evaluated with respect to both the accuracy in classifying the samples as well as the performance of the system itself. In a cross validation analysis using "Nearest Shrunken Centroid classifier" and the PAM software, 77% of the samples were classified correctly according to earlier classification results. Conclusion The system shows potential for fast screening; however, improvements are needed.

  12. Appreciating HIV-1 diversity: subtypic differences in ENV

    Energy Technology Data Exchange (ETDEWEB)

    Gnanakaran, S [Los Alamos National Laboratory; Shen, Tongye [Los Alamos National Laboratory; Lynch, Rebecca M [NON LANL; Derdeyn, Cynthia A [NON LANL

    2008-01-01

    Human immunodeficiency virus type 1 (HIV-1) group M is responsible for the current AIDS pandemic and exhibits exceedingly high levels of viral genetic diversity around the world, necessitating categorization of viruses into distinct lineages, or subtypes. These subtypes can differ by around 35% in the envelope (Env) glycoproteins of the virus, which are displayed on the surface of the virion and are targets for both neutralizing antibody and cell-mediated immune responses. This diversity reflects the remarkable ability of the virus to adapt to selective pressures, the bulk of which is applied by the host immune response, and represents a serious obstacle for developing an effective vaccine with broad coverage. Thus, it is important to understand the underlying biological consequences of inter-subtype diversity. Recent studies have revealed that the HIV-1 subtypes exhibit phenotypic differences that result from subtle differences in Env structure, particularly within the highly immunogenic V3 domain, which participates directly in viral entry. This review will therefore explore current research that describes subtypic differences in Env at the genetic and phenotypic level, focusing in particular on V3, and highlighting recent discoveries about the unique features of subtype C Env, which is the most prevalent subtype globally.

  13. Coupling of angiogenesis and osteogenesis by a specific vessel subtype in bone

    Science.gov (United States)

    Adams, Ralf H.

    2016-01-01

    Summary The mammalian skeletal system harbours a hierarchical system of mesenchymal stem cells, osteoprogenitors and osteoblasts sustaining lifelong bone formation. Osteogenesis is indispensable for the homeostatic renewal of bone as well as regenerative fracture healing, but these processes frequently decline in ageing organisms leading to loss of bone mass and increased fracture incidence. There is evidence indicating that the growth of blood vessels in bone and osteogenesis are coupled, but relatively little is known about the underlying cellular and molecular mechanisms. Here we identify a new capillary subtype in the murine skeletal system with distinct morphological, molecular and functional properties. These vessels are found in specific locations, mediate growth of the bone vasculature, generate distinct metabolic and molecular microenvironments, maintain perivascular osteoprogenitors, and couple angiogenesis to osteogenesis. The abundance of these vessels and associated osteoprogenitors was strongly reduced in bone from aged animals, which was pharmacologically reversible to restore bone mass. PMID:24646994

  14. Oligonucleotide microarray for subtyping of influenza A viruses

    Science.gov (United States)

    Klotchenko, S. A.; Vasin, A. V.; Sandybaev, N. T.; Plotnikova, M. A.; Chervyakova, O. V.; Smirnova, E. A.; Kushnareva, E. V.; Strochkov, V. M.; Taylakova, E. T.; Egorov, V. V.; Koshemetov, J. K.; Kiselev, O. I.; Sansyzbay, A. R.

    2012-02-01

    Influenza is one of the most widespread respiratory viral diseases, infecting humans, horses, pigs, poultry and some other animal populations. Influenza A viruses (IAV) are classified into subtypes on the basis of the surface hemagglutinin (H1 to H16) and neuraminidase (N1 to N9) glycoproteins. The correct determination of IAV subtype is necessary for clinical and epidemiological studies. In this article we propose an oligonucleotide microarray for subtyping of IAV using universal one-step multisegment RT-PCR fluorescent labeling of viral gene segments. It showed to be an advanced approach for fast detection and identification of IAV.

  15. Oligonucleotide microarray for subtyping of influenza A viruses

    International Nuclear Information System (INIS)

    Influenza is one of the most widespread respiratory viral diseases, infecting humans, horses, pigs, poultry and some other animal populations. Influenza A viruses (IAV) are classified into subtypes on the basis of the surface hemagglutinin (H1 to H16) and neuraminidase (N1 to N9) glycoproteins. The correct determination of IAV subtype is necessary for clinical and epidemiological studies. In this article we propose an oligonucleotide microarray for subtyping of IAV using universal one-step multisegment RT-PCR fluorescent labeling of viral gene segments. It showed to be an advanced approach for fast detection and identification of IAV.

  16. Immunogenic Subtypes of Breast Cancer Delineated by Gene Classifiers of Immune Responsiveness.

    Science.gov (United States)

    Miller, Lance D; Chou, Jeff A; Black, Michael A; Print, Cristin; Chifman, Julia; Alistar, Angela; Putti, Thomas; Zhou, Xiaobo; Bedognetti, Davide; Hendrickx, Wouter; Pullikuth, Ashok; Rennhack, Jonathan; Andrechek, Eran R; Demaria, Sandra; Wang, Ena; Marincola, Francesco M

    2016-07-01

    The abundance and functional orientation of tumor-infiltrating lymphocytes in breast cancer is associated with distant metastasis-free survival, yet how this association is influenced by tumor phenotypic heterogeneity is poorly understood. Here, a bioinformatics approach defined tumor biologic attributes that influence this association and delineated tumor subtypes that may differ in their ability to sustain durable antitumor immune responses. A large database of breast tumor expression profiles and associated clinical data was compiled, from which the ability of phenotypic markers to significantly influence the prognostic performance of a classification model that incorporates immune cell-specific gene signatures was ascertained. Markers of cell proliferation and intrinsic molecular subtype reproducibly distinguished two breast cancer subtypes that we refer to as immune benefit-enabled (IBE) and immune benefit-disabled (IBD). The IBE tumors, comprised mostly of highly proliferative tumors of the basal-like, HER2-enriched, and luminal B subtypes, could be stratified by the immune classifier into significantly different prognostic groups, while IBD tumors could not, indicating the potential for productive engagement of metastasis-protective immunity in IBE tumors, but not in IBD tumors. The prognostic stratification in IBE was independent of conventional variables. Gene network analysis predicted the activation of TNFα/IFNγ signaling pathways in IBE tumors and the activation of the transforming growth factor-β pathway in IBD tumors. This prediction supports a model in which breast tumors can be distinguished on the basis of their potential for metastasis-protective immune responsiveness. Whether IBE and IBD represent clinically relevant contexts for evaluating sensitivity to immunotherapeutic agents warrants further investigation. Cancer Immunol Res; 4(7); 600-10. ©2016 AACR. PMID:27197066

  17. An overview of mice models: a key for understanding subtypes of mania

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    Jorge Mauricio Cuartas Arias

    2016-09-01

    Full Text Available Animal models have been broadly used in the study of pathophysiology and molecular and neurochemical pathways in neuropsychiatric diseases. Different approaches have used both consanguineous and non-consanguineous mice models to model behavioral patterns associated with the maniac spectrum. However, the disadvantages of validating clinical and experimental protocols have hindered the replication of these studies. In this article, the advantages and disadvantages of using consanguineous lines and non-consanguineous stocks in mice animal models for the study of mania and its subtypes are discussed. Additionally, new experimental alternatives to advance the pathogenesis and pharmacogenetics of mania using animal models are proposed and analyzed.

  18. CRISPR-cas subtype I-Fb in Acinetobacter baumannii: evolution and utilization for strain subtyping.

    Science.gov (United States)

    Karah, Nabil; Samuelsen, Ørjan; Zarrilli, Raffaele; Sahl, Jason W; Wai, Sun Nyunt; Uhlin, Bernt Eric

    2015-01-01

    Clustered regularly interspaced short palindromic repeats (CRISPR) are polymorphic elements found in the genome of some or all strains of particular bacterial species, providing them with a system of acquired immunity against invading bacteriophages and plasmids. Two CRISPR-Cas systems have been identified in Acinetobacter baumannii, an opportunistic pathogen with a remarkable capacity for clonal dissemination. In this study, we investigated the mode of evolution and diversity of spacers of the CRISPR-cas subtype I-Fb locus in a global collection of 76 isolates of A. baumannii obtained from 14 countries and 4 continents. The locus has basically evolved from a common ancestor following two main lineages and several pathways of vertical descent. However, this vertical passage has been interrupted by occasional events of horizontal transfer of the whole locus between distinct isolates. The isolates were assigned into 40 CRISPR-based sequence types (CST). CST1 and CST23-24 comprised 18 and 9 isolates, representing two main sub-clones of international clones CC1 and CC25, respectively. Epidemiological data showed that some of the CST1 isolates were acquired or imported from Iraq, where it has probably been endemic for more than one decade and occasionally been able to spread to USA, Canada, and Europe. CST23-24 has shown a remarkable ability to cause national outbreaks of infections in Sweden, Argentina, UAE, and USA. The three isolates of CST19 were independently imported from Thailand to Sweden and Norway, raising a concern about the prevalence of CST19 in Thailand. Our study highlights the dynamic nature of the CRISPR-cas subtype I-Fb locus in A. baumannii, and demonstrates the possibility of using a CRISPR-based approach for subtyping a significant part of the global population of A. baumannii.

  19. CRISPR-cas subtype I-Fb in Acinetobacter baumannii: evolution and utilization for strain subtyping.

    Directory of Open Access Journals (Sweden)

    Nabil Karah

    Full Text Available Clustered regularly interspaced short palindromic repeats (CRISPR are polymorphic elements found in the genome of some or all strains of particular bacterial species, providing them with a system of acquired immunity against invading bacteriophages and plasmids. Two CRISPR-Cas systems have been identified in Acinetobacter baumannii, an opportunistic pathogen with a remarkable capacity for clonal dissemination. In this study, we investigated the mode of evolution and diversity of spacers of the CRISPR-cas subtype I-Fb locus in a global collection of 76 isolates of A. baumannii obtained from 14 countries and 4 continents. The locus has basically evolved from a common ancestor following two main lineages and several pathways of vertical descent. However, this vertical passage has been interrupted by occasional events of horizontal transfer of the whole locus between distinct isolates. The isolates were assigned into 40 CRISPR-based sequence types (CST. CST1 and CST23-24 comprised 18 and 9 isolates, representing two main sub-clones of international clones CC1 and CC25, respectively. Epidemiological data showed that some of the CST1 isolates were acquired or imported from Iraq, where it has probably been endemic for more than one decade and occasionally been able to spread to USA, Canada, and Europe. CST23-24 has shown a remarkable ability to cause national outbreaks of infections in Sweden, Argentina, UAE, and USA. The three isolates of CST19 were independently imported from Thailand to Sweden and Norway, raising a concern about the prevalence of CST19 in Thailand. Our study highlights the dynamic nature of the CRISPR-cas subtype I-Fb locus in A. baumannii, and demonstrates the possibility of using a CRISPR-based approach for subtyping a significant part of the global population of A. baumannii.

  20. High Prevalence and Onward Transmission of Non-Pandemic HIV-1 Subtype B Clades in Northern and Northeastern Brazilian Regions.

    Science.gov (United States)

    Divino, Flavia; de Lima Guerra Corado, Andre; Gomes Naveca, Felipe; Stefani, Mariane M A; Bello, Gonzalo

    2016-01-01

    The Human immunodeficiency virus type-1 (HIV-1) epidemic in Brazil is mainly driven by the subtype B pandemic lineage (BPANDEMIC), while Caribbean non-pandemic subtype B clades (BCAR) seem to account for a very low fraction of HIV-infections in this country. The molecular characteristics of the HIV-1 subtype B strains disseminated in the Northern and Northeastern Brazilian regions, however, have not been explored so far. In this study, we estimate the prevalence of the HIV-1 BPANDEMIC and BCAR clades across different Brazilian regions and we reconstruct the spatiotemporal dynamics of dissemination of the major Brazilian BCAR clades. A total of 2,682 HIV-1 subtype B pol sequences collected from 21 different Brazilian states from the five country regions between 1998 and 2013 were analyzed. Maximum Likelihood phylogenetic analyses revealed that the BCAR strains reached 16 out 21 Brazilian states here analyzed. The BCAR clades comprise a low fraction (Amazonas (14%) and Maranhão (14%). Bayesian phylogeographic analyses indicate that BCAR strains originally from the Hispaniola and Trinidad and Tobago were introduced at multiple times into different states from all Brazilian regions and a few of those strains, probably introduced into Roraima, Maranhão and São Paulo between the late 1970s and the early 1980s, established secondary outbreaks in the Brazilian population. These results support that the HIV-1 subtype B epidemics in some Brazilian states from the Northern and Northeastern regions display a unique molecular pattern characterized by the high prevalence of BCAR lineages, which probably reflects a strong epidemiological link with the HIV-1 epidemics in the Caribbean region. PMID:27603317

  1. Human alpha 2-adrenergic receptor subtype distribution: widespread and subtype-selective expression of alpha 2C10, alpha 2C4, and alpha 2C2 mRNA in multiple tissues.

    Science.gov (United States)

    Eason, M G; Liggett, S B

    1993-07-01

    At present, molecular cloning and pharmacological studies have delineated three human alpha 2-adrenergic receptor (alpha 2AR) subtypes, alpha 2C10, alpha 2C4, and alpha 2C2. Assignment of the alpha 2AR subtypes to specific functions has been limited by an unclear definition of tissue alpha 2AR expression outside of the central nervous system. It has been suggested that alpha 2C4 expression is confined to the brain, that alpha 2C2 expression is only in the liver and kidney, and that there is nearly ubiquitous expression of alpha 2C10. However, this is based on studies of a limited number of rat tissues or on studies using non-species-specific approaches. Therefore, to define alpha 2C10, alpha 2C4, and alpha 2C2 tissue expression, we used reverse transcription of total RNA isolated from 20 human tissues, followed by amplification of alpha 2AR cDNA using the polymerase chain reaction. This technique provided two advantages: high sensitivity and, with the use of subtype-specific oligonucleotide primers and probes, differentiation between the alpha 2AR subtypes. The tissues studied were aorta, vena cava, heart (epicardium and endocardium), lung, skeletal muscle, liver, pancreas (head and tail), fat (perinephric and subcutaneous), kidney (cortex and medulla), prostate, stomach, ileum, jejunum, colon, adrenal gland, and spleen. We found that the majority of these tissues expressed alpha 2C10, with the exceptions being the head of the pancreas, subcutaneous fat, colon, and spleen. In marked distinction to other studies, however, we found a prolific expression of the alpha 2C4 and alpha 2C2 subtypes. Expression of alpha 2C4 was found in all tissues with the exception of liver, fat, stomach, and colon, and a virtually ubiquitous expression of alpha 2C2 was found, with the exception of epicardium. Of all tissues studied, only colon and subcutaneous fat expressed a single alpha 2AR subtype, which was alpha 2C2. Thus, the alpha 2AR subtypes do not have a confined expression but

  2. Human alpha 2-adrenergic receptor subtype distribution: widespread and subtype-selective expression of alpha 2C10, alpha 2C4, and alpha 2C2 mRNA in multiple tissues.

    Science.gov (United States)

    Eason, M G; Liggett, S B

    1993-07-01

    At present, molecular cloning and pharmacological studies have delineated three human alpha 2-adrenergic receptor (alpha 2AR) subtypes, alpha 2C10, alpha 2C4, and alpha 2C2. Assignment of the alpha 2AR subtypes to specific functions has been limited by an unclear definition of tissue alpha 2AR expression outside of the central nervous system. It has been suggested that alpha 2C4 expression is confined to the brain, that alpha 2C2 expression is only in the liver and kidney, and that there is nearly ubiquitous expression of alpha 2C10. However, this is based on studies of a limited number of rat tissues or on studies using non-species-specific approaches. Therefore, to define alpha 2C10, alpha 2C4, and alpha 2C2 tissue expression, we used reverse transcription of total RNA isolated from 20 human tissues, followed by amplification of alpha 2AR cDNA using the polymerase chain reaction. This technique provided two advantages: high sensitivity and, with the use of subtype-specific oligonucleotide primers and probes, differentiation between the alpha 2AR subtypes. The tissues studied were aorta, vena cava, heart (epicardium and endocardium), lung, skeletal muscle, liver, pancreas (head and tail), fat (perinephric and subcutaneous), kidney (cortex and medulla), prostate, stomach, ileum, jejunum, colon, adrenal gland, and spleen. We found that the majority of these tissues expressed alpha 2C10, with the exceptions being the head of the pancreas, subcutaneous fat, colon, and spleen. In marked distinction to other studies, however, we found a prolific expression of the alpha 2C4 and alpha 2C2 subtypes. Expression of alpha 2C4 was found in all tissues with the exception of liver, fat, stomach, and colon, and a virtually ubiquitous expression of alpha 2C2 was found, with the exception of epicardium. Of all tissues studied, only colon and subcutaneous fat expressed a single alpha 2AR subtype, which was alpha 2C2. Thus, the alpha 2AR subtypes do not have a confined expression but

  3. Multi-Scale Molecular Deconstruction of the Serotonin Neuron System.

    Science.gov (United States)

    Okaty, Benjamin W; Freret, Morgan E; Rood, Benjamin D; Brust, Rachael D; Hennessy, Morgan L; deBairos, Danielle; Kim, Jun Chul; Cook, Melloni N; Dymecki, Susan M

    2015-11-18

    Serotonergic (5HT) neurons modulate diverse behaviors and physiology and are implicated in distinct clinical disorders. Corresponding diversity in 5HT neuronal phenotypes is becoming apparent and is likely rooted in molecular differences, yet a comprehensive approach characterizing molecular variation across the 5HT system is lacking, as is concomitant linkage to cellular phenotypes. Here we combine intersectional fate mapping, neuron sorting, and genome-wide RNA-seq to deconstruct the mouse 5HT system at multiple levels of granularity-from anatomy, to genetic sublineages, to single neurons. Our unbiased analyses reveal principles underlying system organization, 5HT neuron subtypes, constellations of differentially expressed genes distinguishing subtypes, and predictions of subtype-specific functions. Using electrophysiology, subtype-specific neuron silencing, and conditional gene knockout, we show that these molecularly defined 5HT neuron subtypes are functionally distinct. Collectively, this resource classifies molecular diversity across the 5HT system and discovers sertonergic subtypes, markers, organizing principles, and subtype-specific functions with potential disease relevance.

  4. Comparison of lung cancer cell lines representing four histopathological subtypes with gene expression profiling using quantitative real-time PCR

    Directory of Open Access Journals (Sweden)

    Kawaguchi Makoto

    2010-01-01

    Full Text Available Abstract Background Lung cancers are the most common type of human malignancy and are intractable. Lung cancers are generally classified into four histopathological subtypes: adenocarcinoma (AD, squamous cell carcinoma (SQ, large cell carcinoma (LC, and small cell carcinoma (SC. Molecular biological characterization of these subtypes has been performed mainly using DNA microarrays. In this study, we compared the gene expression profiles of these four subtypes using twelve human lung cancer cell lines and the more reliable quantitative real-time PCR (qPCR. Results We selected 100 genes from public DNA microarray data and examined them by DNA microarray analysis in eight test cell lines (A549, ABC-1, EBC-1, LK-2, LU65, LU99, STC 1, RERF-LC-MA and a normal control lung cell line (MRC-9. From this, we extracted 19 candidate genes. We quantified the expression of the 19 genes and a housekeeping gene, GAPDH, with qPCR, using the same eight cell lines plus four additional validation lung cancer cell lines (RERF-LC-MS, LC-1/sq, 86-2, and MS-1-L. Finally, we characterized the four subtypes of lung cancer cell lines using principal component analysis (PCA of gene expression profiling for 12 of the 19 genes (AMY2A, CDH1, FOXG1, IGSF3, ISL1, MALL, PLAU, RAB25, S100P, SLCO4A1, STMN1, and TGM2. The combined PCA and gene pathway analyses suggested that these genes were related to cell adhesion, growth, and invasion. S100P in AD cells and CDH1 in AD and SQ cells were identified as candidate markers of these lung cancer subtypes based on their upregulation and the results of PCA analysis. Immunohistochemistry for S100P and RAB25 was closely correlated to gene expression. Conclusions These results show that the four subtypes, represented by 12 lung cancer cell lines, were well characterized using qPCR and PCA for the 12 genes examined. Certain genes, in particular S100P and CDH1, may be especially important for distinguishing the different subtypes. Our results

  5. 小切口修剪联合多功能电离子清除顶泌汗腺治疗腋臭%Trim a small incision combined with multi-function ion therapeutic machine remove apocrine sweat glands in treatment of osmidrosis

    Institute of Scientific and Technical Information of China (English)

    吴永柏; 颜培娥; 潘现波; 崔立华; 张丽艳

    2015-01-01

    目的:探讨小切口修剪联合多功能电离子清除顶泌汗腺治疗腋臭的疗效。方法:2009年1月至20015年3月笔者应用小切口修剪联合多功能电离子清除顶泌汗腺治疗腋臭258例(女性158例,男性100例),术后术区碎纱布团缝线压迫固定外用弹力绷带包扎固定。所有患者均获随访,最短时间为3个月。结果:258例中,235例(91.1%)患者获满意疗效,无臭味残留;10例(3.9%)出现切口边缘5mm以内皮肤坏死;8例(3.1%)发生单侧血肿;5例(1.9%)单侧气味残留。结论:小切口修剪联合多功能电离子清除顶泌汗腺治疗腋臭获得满意疗效,术区局部形态良好。%Objective To investigate effects of a small incision triming combined with multi-function ion therapeutic machine remove apocrine sweat glands in treatment of osmidrosis. Methods 258 cases(158 female,100 male)of osmidrosis were treated by a small incision triming combined with multi-function ion therapeutic machine remove apocrine sweat glands from January 2009 to March 2015.Postoperative area was oppressed by broken gauze group and was fixed externally by elastic bandage.All patients were followed up for three months at least. Results All cases,there were 235 patients(91.1%)were satisfactory and none odor residual,10 cases(3.9%)occured skin necrosis within 5mm incision edge,8 cases(3.1%)occured unilateral hematoma,5 cases(1.9%)occured unilateral residual odor. Conclusion Trim a small incision combined with multi- function iontherapeutic machine remove apocrine sweat glands in treatment of osmidrosis obtain satisfactory effect and partial shape are good in the surgical area.

  6. 顺腋皱襞小切口直视下清除大汗腺治疗腋臭的临床体会%Clinical Comprehension of Orthophoric Apocrine Sweat Gland Curettage with Minimal Incision Along Axillary Fold for Osmidrosis

    Institute of Scientific and Technical Information of China (English)

    陈守菊; 王国军; 彭军

    2015-01-01

    Objective To approach the clinical ef icacy and comprehension of orthophoric apocrine sweat gland curet age with minimal incision along axil ary fold for osmidrosis. Methods 99 osmidrosis patients were underwent orthophoric apocrine sweat glands curet age with minimal incision along axil ary fold, and then their therapeutic ef icacy and clincal reactive manifest were observed and analysed. Results 92 of 99 osmidrosis patients had healed primarily with concealed tiny scar. 7 of 99 cases had healed secondly, but 5 patients occur enced haematoma and 2 patients appeared necrosis at the incisal edge.Al patients were fol owed up by outpatients or phone asking after 6 months underwent the curet age.And 76 patients with the healing wel ,17 suf erers with excel ent ef ect, 2 victims only ef ective,but regret 4 patients were loss vist.Al patients hadn't relapsed osmidrosis and without other complications occur enced, so they feel content with this way of surgery treatment . Conclusion The curative ef ects were content with the orthophoric apocrine sweat gland curet age by minimal incision along axil ary fold for osmidrosis,and the scar were tiny,so it would be deserved to spread using.%目的探讨顺腋皱襞小切口直视下清除大汗腺治疗腋臭的临床效果和体会。方法对我科门诊99例腋臭患者应用顺腋皱襞皮纹小切口直视下修剪清除大汗腺治疗,对其疗效及临床表现进行观察分析。结果99例患者Ⅰ期愈合92例,瘢痕细小、隐蔽。Ⅱ期愈合7例,其中5例血肿形成、2例皮缘坏死。术后6个月后门诊随访或电话随访,治愈者76例、显效17例、有效2例、失访4例。患者无腋臭复发及其他并发症发生、效果满意。结论顺腋皱襞皮纹小切口直视下修剪清除大汗腺治疗腋臭疗效满意、瘢痕细小、值得推广。

  7. Application effect observation of kangfuxin solution in incision of axillary furrow by apocrine sweat gland resection%康复新液在腋皱襞切口大汗腺切除术中的应用效果观察

    Institute of Scientific and Technical Information of China (English)

    孙辉; 吴海斌; 陈华

    2015-01-01

    目的:观察康复新液在腋皱襞切口大汗腺切除术中的临床应用效果。方法选择本院2013年1月~2014年6月收治的72例腋臭患者为研究对象,均接受腋皱襞切口大汗腺切除术,随机将其分为两组,各36例,对照组术后常规治疗,观察组术后给予康复新液治疗,术后6个月复诊,比较两组临床疗效、并发症发生率、切口愈合时间及住院时间。结果观察组并发症发生率为5.56%,与对照组的22.22%比较,差异有统计学意义(P0.05)。结论腋皱襞切口大汗腺切除术治疗腋臭疗效明确,术后用康复新液能明显促进切口愈合,缩短住院时间,降低并发症发生率,值得临床推广。%Objective To observe the clinical application effect of kangfuxin solution in incision of axillary furrow by apocrine sweat gland resection. Methods From January 2013 to June 2014,72 patients with bromhidrosis treated in our hospital were selected as research objects.They were undergone apocrine sweat gland resection through incision of axil-lary furrow and evenly divided into two groups in random.In control group,routine treatment was provided after surgery, while in observation group,kangfuxin solution was applied after surgery.Further consultation was needed 6 months after surgery.The clinical efficacy,incidence of complication,healing time of incision,and hospital stay between two groups was compared respectively. Results The incidence of complications in observation group was 5.56%,while the incidence in control group was 22.22%,with a statistical difference (P0.05). Con-clusion Apocrine sweat gland resection through incision of axillary furrow can obtain a definite effect on treating bromhidrosis.Postoperative application of kangfuxin solution can remarkably promote incision healing, shorten hospital stay,and reduce incidence of complications,which is worthy of clinical expansion.

  8. Molecular epidemiology of Blastocystis

    Directory of Open Access Journals (Sweden)

    Fadime Eroğlu

    2015-12-01

    Full Text Available Blastocystis pathogenicity and classification was newly illuminated with molecular genetic studies and recently the parasite was found in the focus of many researchers. Several molecular methods such as; polymerase chain reaction (PCR, PCR-restriction fragment length polymorphism, random amplified polymorphic DNA, real-time polymerase chain reaction and DNA sequencing analyses can be used in genotyping of Blastocystis. Blastocystis parasites may cause diarrhea, abdominal pain, bloating, gas, irritability, anorexia, cramps, vomiting, dehydration, insomnia, nausea, loss of appetite, weight loss, fatigue symptoms and also could be asymptomatic cases. In this review, it was aimed to summarize the associations between Blastocystis subtypes and pathogenicity.

  9. The HIV-1 epidemic in Bolivia is dominated by subtype B and CRF12_BF "family" strains

    Directory of Open Access Journals (Sweden)

    Guimarães Monick L

    2012-01-01

    Full Text Available Abstract Background Molecular epidemiological studies of HIV-1 in South America have revealed the occurrence of subtypes B, F1 and BF1 recombinants. Even so, little information concerning the HIV-1 molecular epidemiology in Bolivia is available. In this study we performed phylogenetic analyses from samples collected in Bolivia at two different points in time over a 10 year span. We analyzed these samples to estimate the trends in the HIV subtype and recombinant forms over time. Materials and methods Fifty one HIV-1 positive samples were collected in Bolivia over two distinct periods (1996 and 2005. These samples were genetically characterized based on partial pol protease/reverse transcriptase (pr/rt and env regions. Alignment and neighbor-joining (NJ phylogenetic analyses were established from partial env (n = 37 and all pol sequences using Mega 4. The remaining 14 env sequences from 1996 were previously characterized based on HMA-env (Heteroduplex mobility assay. The Simplot v.3.5.1 program was used to verify intragenic recombination, and SplitsTree 4.0 was employed to confirm the phylogenetic relationship of the BF1 recombinant samples. Results Phylogenetic analysis of both env and pol regions confirmed the predominance of "pure" subtype B (72.5% samples circulating in Bolivia and revealed a high prevalence of BF1 genotypes (27.5%. Eleven out of 14 BF1 recombinants displayed a mosaic structure identical or similar to that described for the CRF12_BF variant, one sample was classified as CRF17_BF, and two others were F1pol/Benv. No "pure" HIV-1 subtype F1 or B" variant of subtype B was detected in the present study. Of note, samples characterized as CRF12_BF-related were depicted only in 2005. Conclusion HIV-1 genetic diversity in Bolivia is mostly driven by subtype B followed by BF1 recombinant strains from the CRF12_BF "family". No significant temporal changes were detected between the mid-1990s and the mid-2000s for subtype B (76.2% vs 70

  10. Short-term stability of subtypes in the irritable bowel syndrome

    DEFF Research Database (Denmark)

    Engsbro, A L; Simren, M; Bytzer, P

    2012-01-01

    In irritable bowel syndrome (IBS) subtyping is used in research and clinical practice. Knowledge of subtype stability is needed for proper design of trials and treatment strategies.......In irritable bowel syndrome (IBS) subtyping is used in research and clinical practice. Knowledge of subtype stability is needed for proper design of trials and treatment strategies....

  11. Gene Set−Based Integrative Analysis Revealing Two Distinct Functional Regulation Patterns in Four Common Subtypes of Epithelial Ovarian Cancer

    Science.gov (United States)

    Chang, Chia-Ming; Chuang, Chi-Mu; Wang, Mong-Lien; Yang, Yi-Ping; Chuang, Jen-Hua; Yang, Ming-Jie; Yen, Ming-Shyen; Chiou, Shih-Hwa; Chang, Cheng-Chang

    2016-01-01

    Clear cell (CCC), endometrioid (EC), mucinous (MC) and high-grade serous carcinoma (SC) are the four most common subtypes of epithelial ovarian carcinoma (EOC). The widely accepted dualistic model of ovarian carcinogenesis divided EOCs into type I and II categories based on the molecular features. However, this hypothesis has not been experimentally demonstrated. We carried out a gene set-based analysis by integrating the microarray gene expression profiles downloaded from the publicly available databases. These quantified biological functions of EOCs were defined by 1454 Gene Ontology (GO) term and 674 Reactome pathway gene sets. The pathogenesis of the four EOC subtypes was investigated by hierarchical clustering and exploratory factor analysis. The patterns of functional regulation among the four subtypes containing 1316 cases could be accurately classified by machine learning. The results revealed that the ERBB and PI3K-related pathways played important roles in the carcinogenesis of CCC, EC and MC; while deregulation of cell cycle was more predominant in SC. The study revealed that two different functional regulation patterns exist among the four EOC subtypes, which were compatible with the type I and II classifications proposed by the dualistic model of ovarian carcinogenesis. PMID:27527159

  12. Specific expression and methylation of SLIT1, SLIT2, SLIT3, and miR-218 in gastric cancer subtypes.

    Science.gov (United States)

    Kim, Mirang; Kim, Jong-Hwan; Baek, Su-Jin; Kim, Seon-Young; Kim, Yong Sung

    2016-06-01

    SLIT has been suggested as a key regulator of cancer development and a promising therapeutic target for cancer treatment. Herein, we analyzed expression and methylation of SLIT1/SLIT2/SLIT3 in 11 gastric cancer cell lines, 96 paired gastric tumors and adjacent normal gastric tissues, and 250 gastric cancers provided by The Cancer Genome Atlas. Methylation of SLIT1/SLIT2/SLIT3 was found both in early gastric cancers, and in advanced gastric cancers. Even normal gastric tissue showed increased methylation of SLIT1 and SLIT3 that correlated with patient age. Furthermore, epigenetic inactivation of SLIT occurred in a gastric cancer subtype-dependent manner. SLIT2 and SLIT3 expression was reduced in Epstein-Barr virus-positive and microsatellite instability subtypes, but increased in the genomically stable subtype. Expression of miR‑218 correlated negatively with methylation of SLIT2 or SLIT3. These findings suggest that a molecular subtype-specific therapeutic strategy is needed for targeting SLITs and miR-218 in treatment of gastric cancer.

  13. CSF Proteomics Identifies Specific and Shared Pathways for Multiple Sclerosis Clinical Subtypes.

    Directory of Open Access Journals (Sweden)

    Timucin Avsar

    Full Text Available Multiple sclerosis (MS is an immune-mediated, neuro-inflammatory, demyelinating and neurodegenerative disease of the central nervous system (CNS with a heterogeneous clinical presentation and course. There is a remarkable phenotypic heterogeneity in MS, and the molecular mechanisms underlying it remain unknown. We aimed to investigate further the etiopathogenesis related molecular pathways in subclinical types of MS using proteomic and bioinformatics approaches in cerebrospinal fluids of patients with clinically isolated syndrome, relapsing remitting MS and progressive MS (n=179. Comparison of disease groups with controls revealed a total of 151 proteins that are differentially expressed in clinically different MS subtypes. KEGG analysis using PANOGA tool revealed the disease related pathways including aldosterone-regulated sodium reabsorption (p=8.02x10-5 which is important in the immune cell migration, renin-angiotensin (p=6.88x10-5 system that induces Th17 dependent immunity, notch signaling (p=1.83x10-10 pathway indicating the activated remyelination and vitamin digestion and absorption pathways (p=1.73x10-5. An emerging theme from our studies is that whilst all MS clinical forms share common biological pathways, there are also clinical subtypes specific and pathophysiology related pathways which may have further therapeutic implications.

  14. Expression patterns of GATA3 and the androgen receptor are strongly correlated in patients with triple-negative breast cancer.

    Science.gov (United States)

    Kim, Sewha; Moon, Byung-In; Lim, Woosung; Park, Sanghui; Cho, Min Sun; Sung, Sun Hee

    2016-09-01

    GATA-binding protein 3 (GATA3) is a diagnostically useful immunohistochemical marker of breast cancer. Because of its strong association with estrogen receptor expression, GATA3 has markedly reduced sensitivity in triple-negative breast cancer (TNBC). We constructed a tissue microarray using a large series of TNBCs and evaluated GATA3 expression by TNBC subtype as defined by surrogate immunohistochemical markers. A total of 205 TNBCs were classified into cancers of the molecular apocrine type (n=23, 11.2%), claudin-low type (n=21, 10.2%), basal-like type (n=91, 44.4%), mixed type (n=62, 30.2%), and null type (n=8, 3.9%). The GATA3 scores (staining intensity × proportion) were categorized as negative (0), focally positive (1-10), or positive (11-300). GATA3 staining was negative in 153 cancers (74.6%), focally positive in 11 (5.4%), and positive in 41 (20.0%). The rate of focal positivity or positivity for GATA3 was significantly higher in the molecular apocrine type (73.9%, 17/23) than in other types of TNBCs (P=.001). The mean GATA3 score of molecular apocrine-type TNBC was significantly higher than that of the other types (P=.001) and differed significantly between androgen receptor (AR)-positive and AR-negative TNBCs (P<.001). In conclusion, GATA3 expression was correlated strongly with AR-positive, molecular apocrine-type TNBCs. Co-expression of AR and GATA3 is a specific feature of molecular apocrine-type TNBC, which may serve as a diagnostic aid for cancer of unknown primary. PMID:27184484

  15. ADHD Subtype Differences in Reinforcement Sensitivity and Visuospatial Working Memory.

    Science.gov (United States)

    Dovis, Sebastiaan; Van der Oord, Saskia; Wiers, Reinout W; Prins, Pier J M

    2015-01-01

    Both cognitive and motivational deficits are thought to give rise to the problems in the combined (ADHD-C) and inattentive subtype (ADHD-I) of attention-deficit hyperactivity disorder (ADHD). In both subtypes one of the most prominent cognitive weaknesses appears to be in visuospatial working memory (WM), which is composed of short-term memory (STM) and a central executive (CE). In children with ADHD-C, both STM and the CE seem impaired, and together with motivational impairments, give rise to their deficits in visuospatial WM. In children with ADHD-I, no studies investigated these WM components and their interplay with motivational impairments. Effects of a standard (feedback only) and a high level of reinforcement (feedback + 10 euros) on visuospatial WM-, STM-, and CE performance were examined in 27 children with ADHD-I (restrictive-subtype), 70 children with ADHD-C, and 40 typically developing controls (aged 9-12). In both ADHD-subtypes CE and WM performance was worse than in controls. STM performance of children with ADHD-I was, in contrast to that of children with ADHD-C, not different from controls. STM and WM performance was worse in ADHD-C than in ADHD-I, whereas CE-related performance did not differ. High reinforcement improved STM and WM performance in both subtypes but not in controls. This improvement was equally pronounced in both subtypes. High reinforcement did not improve CE-related performance. Both subtypes have equally pronounced motivational deficits, which have detrimental effects on their visuospatial STM and WM performance. In contrast to children with ADHD-C, children with ADHD-I seem unimpaired on visuospatial STM; only an impaired CE and motivational impairments give rise to their deficits in visuospatial WM.

  16. Subtyping novel zoonotic pathogen Cryptosporidium chipmunk genotype I.

    Science.gov (United States)

    Guo, Yaqiong; Cebelinski, Elizabeth; Matusevich, Christine; Alderisio, Kerri A; Lebbad, Marianne; McEvoy, John; Roellig, Dawn M; Yang, Chunfu; Feng, Yaoyu; Xiao, Lihua

    2015-05-01

    Cryptosporidium chipmunk genotype I is an emerging zoonotic pathogen in humans. The lack of subtyping tools makes it impossible to determine the role of zoonotic transmission in epidemiology. To identify potential subtyping markers, we sequenced the genome of a human chipmunk genotype I isolate. Altogether, 9,509,783 bp of assembled sequences in 853 contigs were obtained, with an N50 of 117,886 bp and >200-fold coverage. Based on the whole-genome sequence data, two genetic markers encoding the 60-kDa glycoprotein (gp60) and a mucin protein (ortholog of cgd1_470) were selected for the development of a subtyping tool. The tool was used for characterizing chipmunk genotype I in 25 human specimens from four U.S. states and Sweden, one specimen each from an eastern gray squirrel, a chipmunk, and a deer mouse, and 4 water samples from New York. At the gp60 locus, although different subtypes were seen among the animals, water, and humans, the 15 subtypes identified differed mostly in the numbers of trinucleotide repeats (TCA, TCG, or TCT) in the serine repeat region, with only two single nucleotide polymorphisms in the nonrepeat region. Some geographic differences were found in the subtype distribution of chipmunk genotype I from humans. In contrast, only two subtypes were found at the mucin locus, which differed from each other in the numbers of a 30-bp minisatellite repeat. Thus, Cryptosporidium chipmunk genotype I isolates from humans and wildlife are genetically similar, and zoonotic transmission might play a potential role in human infections. PMID:25762767

  17. Is PIGD a legitimate motor subtype in Parkinson disease?

    Science.gov (United States)

    Kotagal, Vikas

    2016-06-01

    Parkinson disease is a chronic progressive syndrome with a broad array of clinical features. Different investigators have suggested the heterogeneous motor manifestations of early Parkinson disease can be conceptualized through a taxonomy of clinical subtypes including tremor-predominant and postural instability and gait difficulty-predominant subtypes. Although it is theoretically valuable to distinguish subtypes of Parkinson disease, the reality is that few patients fit these discrete categories well and many transition from exhibiting elements of one subtype to elements of another. In the time since the initial description of the postural instability and gait difficulty-predominant subtype, Parkinson disease clinical research has blossomed in many ways - including an increased emphasis on the role of medical comorbidities and extranigral pathologies in Parkinson disease as markers of prognostic significance. By conceptualizing the pathogenesis of an expansive disease process in the limited terms of categorical motor subtypes, we run the risk of overlooking or misclassifying clinically significant pathogenic risk factors that lead to the development of motor milestones such as falls and related axial motor disability. Given its critical influence on quality of life and overall prognosis, we are in need of a model of postural instability and gait difficulty-predominant features in Parkinson disease that emphasizes the overlooked pathological influence of aging and medical comorbidities on the development of axial motor burden and postural instability and gait difficulty-predominant features. This Point of View proposes thinking of postural instability and gait difficulties in Parkinson disease not as a discrete subtype, but rather as multidimensional continuum influenced by several overlapping age-related pathologies.

  18. Breast cancer pathology: the impact of molecular taxonomy on morphological taxonomy.

    Science.gov (United States)

    Masuda, Shinobu

    2012-05-01

    The concept of having an 'intrinsic subtype,' or a molecular taxonomy, lets us clearly recognize that breast cancers have characteristically different patterns of gene expression, thus giving newfound significance to morphological taxonomy. In this review, the concept of the 'intrinsic subtype' is discussed, research questions are introduced to refine the significance of morphological taxonomy, and a corresponding example is presented between microarray analysis and 'immunohistochemical subtype,' or histological taxonomy.

  19. Molecular imaging in neuroendocrine tumors : Molecular uptake mechanisms and clinical results

    NARCIS (Netherlands)

    Koopmans, Klaas P.; Neels, Oliver N.; Kema, Ido P.; Elsinga, Philip H.; Links, Thera P.; de Vries, Elisabeth G. E.; Jager, Pieter L.

    2009-01-01

    Neuroendocrine tumors can originate almost everywhere in the body and consist of a great variety of subtypes. This paper focuses on molecular imaging methods using nuclear medicine techniques in neuroendocrine tumors, coupling molecular uptake mechanisms of radiotracers with clinical results. A non-

  20. Molecular classification of gastric cancer.

    Science.gov (United States)

    Chia, N-Y; Tan, P

    2016-05-01

    Gastric cancer (GC), a heterogeneous disease characterized by epidemiologic and histopathologic differences across countries, is a leading cause of cancer-related death. Treatment of GC patients is currently suboptimal due to patients being commonly treated in a uniform fashion irrespective of disease subtype. With the advent of next-generation sequencing and other genomic technologies, GCs are now being investigated in great detail at the molecular level. High-throughput technologies now allow a comprehensive study of genomic and epigenomic alterations associated with GC. Gene mutations, chromosomal aberrations, differential gene expression and epigenetic alterations are some of the genetic/epigenetic influences on GC pathogenesis. In addition, integrative analyses of molecular profiling data have led to the identification of key dysregulated pathways and importantly, the establishment of GC molecular classifiers. Recently, The Cancer Genome Atlas (TCGA) network proposed a four subtype classification scheme for GC based on the underlying tumor molecular biology of each subtype. This landmark study, together with other studies, has expanded our understanding on the characteristics of GC at the molecular level. Such knowledge may improve the medical management of GC in the future. PMID:26861606

  1. Data on alteration of hormone and growth factor receptor profiles over progressive passages of breast cancer cell lines representing different clinical subtypes.

    Science.gov (United States)

    Nair, Madhumathy G; Desai, Krisha; Prabhu, Jyothi S; Hari, P S; Remacle, Jose; Sridhar, T S

    2016-09-01

    Human breast cancers are a highly heterogeneous group of tumours consisting of several molecular subtypes with a variable profile of hormone, growth factor receptors and cytokeratins [1]. Here, the data shows immunofluorescence profiling of four different cell lines belonging to distinct clinical subtypes of breast cancer. Post revival, the cell lines were passaged in culture and immunophenotyping was done for ER, HER-2, AR and EGFR. Data for the markers from early passage (5th) through passages as late as 25 for the different cell lines is presented. PMID:27508248

  2. Single assay for simultaneous detection and differential identification of human and avian influenza virus types, subtypes, and emergent variants.

    Directory of Open Access Journals (Sweden)

    David Metzgar

    Full Text Available For more than four decades the cause of most type A influenza virus infections of humans has been attributed to only two viral subtypes, A/H1N1 or A/H3N2. In contrast, avian and other vertebrate species are a reservoir of type A influenza virus genome diversity, hosting strains representing at least 120 of 144 combinations of 16 viral hemagglutinin and 9 viral neuraminidase subtypes. Viral genome segment reassortments and mutations emerging within this reservoir may spawn new influenza virus strains as imminent epidemic or pandemic threats to human health and poultry production. Traditional methods to detect and differentiate influenza virus subtypes are either time-consuming and labor-intensive (culture-based or remarkably insensitive (antibody-based. Molecular diagnostic assays based upon reverse transcriptase-polymerase chain reaction (RT-PCR have short assay cycle time, and high analytical sensitivity and specificity. However, none of these diagnostic tests determine viral gene nucleotide sequences to distinguish strains and variants of a detected pathogen from one specimen to the next. Decision-quality, strain- and variant-specific pathogen gene sequence information may be critical for public health, infection control, surveillance, epidemiology, or medical/veterinary treatment planning. The Resequencing Pathogen Microarray (RPM-Flu is a robust, highly multiplexed and target gene sequencing-based alternative to both traditional culture- or biomarker-based diagnostic tests. RPM-Flu is a single, simultaneous differential diagnostic assay for all subtype combinations of type A influenza viruses and for 30 other viral and bacterial pathogens that may cause influenza-like illness. These other pathogen targets of RPM-Flu may co-infect and compound the morbidity and/or mortality of patients with influenza. The informative specificity of a single RPM-Flu test represents specimen-specific viral gene sequences as determinants of virus type, A

  3. Molecular heterogeneity in glioblastoma: potential clinical implications

    Directory of Open Access Journals (Sweden)

    Nicole Renee Parker

    2015-03-01

    Full Text Available Glioblastomas, (grade 4 astrocytomas, are aggressive primary brain tumors characterized by histopathological heterogeneity. High resolution sequencing technologies have shown that these tumors also feature significant inter-tumoral molecular heterogeneity. Molecular subtyping of these tumors has revealed several predictive and prognostic biomarkers. However, intra-tumoral heterogeneity may undermine the use of single biopsy analysis for determining tumor genotype and has implications for potential targeted therapies. The clinical relevance and theories of tumoral molecular heterogeneity in glioblastoma are discussed.

  4. Parkinson's disease severity and motor subtype influence physical capacity components

    Directory of Open Access Journals (Sweden)

    Marcelo Pinto Pereira

    2013-09-01

    Full Text Available The severity of Parkinson's disease (PD and PD's motor subtypes influence the components of physical capacity. The aim of this study was to investigate the impact of both PD severity and motor subtype in the performance of these components. Thirty-six PD patients were assigned into four groups: Tremor (TD initial and TD mild, akinetic-rigid (AR initial, and AR mild. Patients' strength, balance, coordination, mobility and aerobic capacity were evaluated and groups were compared using a two-way ANOVA (severity and subtype as factors. AR presents a poorer performance than TD in almost all tests. Also this performance was worsened with the advance of the disease in AR, contrary to TD. We conclude that AR and TD subgroups are different about their performance on physical capacity components, moreover, this performance worsens with the advance of the disease of the AR group, but not for TD.

  5. HLA-B27 subtypes among the Chukotka native groups

    Energy Technology Data Exchange (ETDEWEB)

    Krylov, M.Y.; Alexeeva, L.I.; Erdesz, S.; Benevolenskaya, L.I. [Akademiya Meditsinskikh Nauk SSSR, Moscow (Russian Federation). Inst. Revmatizma; Reveille, J.D.; Arnett, F.C. [Texas Univ., Houston, TX (United States). Health Science Center

    1995-12-31

    The purpose of this study was to assess the relative frequency of the known HLA-B27 subtypes in HLA-B27 positive Chukotka natives, which have higher frequencies of HLA-B27 (to 40%) and spondylarthropathies (to 2%) than the Russian Caucasian population. Using oligotyping of the polymerase-chain reaction amplified second and third exons of the HLA-B27 gene in 86 DNA samples from HLA-B27 positive individuals were successfully typed. All had HLA-B*2705, including 4 patients with Reiter`s syndrome and 5 with ankylosing spondyloarthritis, except one Eskimo who had HLA-B*2702. None had HLA-B*2704, a frequent subtype in Orientals. With respect to HLA-B27 subtypes the indigenous populations from the eastern part of the Chukotka Peninsula are genetically more closely related to Caucasians than to Orientals. (author). 18 refs, 1 fig., 2 tabs.

  6. Mixed Nipple Infections Caused by Variant of BPV3 and a Putative New Subtype of BPV in Cattle.

    Science.gov (United States)

    He, Z; Meng, Q; Qiao, J; Peng, Y; Xie, K; Liu, Y; Cai, X; Zhang, J; Chen, C

    2016-02-01

    Bovine papilloma is a chronic and proliferative skin and mucosal wart caused by Bovine papillomavirus (BPV). In June, 2013, a leaf-and flat-shaped wart disease was observed on the nipple skins in a cattle farm in Xinjiang. To diagnose the disease, we collected the diseased skins for pathological biopsy and DNA analysis by PCR amplification using a pair of degenerate primers FAP59 and FAP64. Sequencing and phylogenetic analysis showed that the infection was caused by a variant of BPV3 and putatively a new subtype of BPV (BPV/CHI-SW1, belonging to the Xi papillomavirus genus). This is the first report of mixed infection caused by variant of BPV3 and BPV (putatively new subtype) in China, and would be of importance for the molecular epidemiological study of the disease.

  7. Maximiscin Induces DNA Damage, Activates DNA Damage Response Pathways, and Has Selective Cytotoxic Activity against a Subtype of Triple-Negative Breast Cancer.

    Science.gov (United States)

    Robles, Andrew J; Du, Lin; Cichewicz, Robert H; Mooberry, Susan L

    2016-07-22

    Triple-negative breast cancers are highly aggressive, and patients with these types of tumors have poor long-term survival. These breast cancers do not express estrogen or progesterone receptors and do not have gene amplification of human epidermal growth factor receptor 2; therefore, they do not respond to available targeted therapies. The lack of targeted therapies for triple-negative breast cancers stems from their heterogeneous nature and lack of a clear definition of driver defects. Studies have recently identified triple-negative breast cancer molecular subtypes based on gene expression profiling and representative cell lines, allowing for the identification of subtype-specific drug leads and molecular targets. We previously reported the identification of a new fungal metabolite named maximiscin (1) identified through a crowdsourcing program. New results show that 1 has selective cytotoxic efficacy against basal-like 1 MDA-MB-468 cells compared to cell lines modeling other triple-negative breast cancer molecular subtypes. This compound also exhibited antitumor efficacy in a xenograft mouse model. The mechanisms of action of 1 in MDA-MB-468 cells were investigated to identify potential molecular targets and affected pathways. Compound 1 caused accumulation of cells in the G1 phase of the cell cycle, suggesting induction of DNA damage. Indeed, treatment with 1 caused DNA double-strand breaks with concomitant activation of the DNA damage response pathways, indicated by phosphorylation of p53, Chk1, and Chk2. Collectively, these results suggest basal-like triple-negative breast cancer may be inherently sensitive to DNA-damaging agents relative to other triple-negative breast cancer subtypes. These results also demonstrate the potential of our citizen crowdsourcing program to identify new lead molecules for treating the subtypes of triple-negative breast cancer. PMID:27310425

  8. [Interaction of the Siberian and Far Eastern subtypes of tick-borne encephalitis virus in mammals with mixed infection. Competition of the subtypes in acute and inapparent infection].

    Science.gov (United States)

    Gerasimov, S G; Pogodina, V V; Koliasnikova, N M; Karan', L S; Malenko, G V; Levina, L S

    2011-01-01

    Long-term monitoring of natural tick-borne encephalitis virus (TBEV) populations could reveal the change of TBEV subtypes, the displacement of the Far Eastern (FE) subtype, and its substitution for the Siberian (Sib) subtype. Acute and inapparent mixed infections were studied in Syrian hamsters to understand this phenomenon. The animals were inoculated with the Sib subtype and then with the FE one of TBEV (JQ845440-YaroslavI-Aver-08 and Fj214132-Kemerovo-Phateev-1954 strains). The inapparent form developed more frequently in mixed infection. Viral progeny was genotyped by reverse transcription polymerase chain reaction and hybridization fluorescence detection using genotype-specific probes. Independent reproduction of strains in the brain gave way to competition. The FE subtype dominated in hamster youngsters with acute infection. The Sib subtype had selective benefits in asymptomatic infection (adult hamsters infected intracerebrally and subcutaneously and youngsters infected subcutaneously). The competition of the subtypes was imperfect.

  9. A simplified approach for the molecular classification of glioblastomas.

    Directory of Open Access Journals (Sweden)

    Marie Le Mercier

    Full Text Available Glioblastoma (GBM is the most common malignant primary brain tumors in adults and exhibit striking aggressiveness. Although GBM constitute a single histological entity, they exhibit considerable variability in biological behavior, resulting in significant differences in terms of prognosis and response to treatment. In an attempt to better understand the biology of GBM, many groups have performed high-scale profiling studies based on gene or protein expression. These studies have revealed the existence of several GBM subtypes. Although there remains to be a clear consensus, two to four major subtypes have been identified. Interestingly, these different subtypes are associated with both differential prognoses and responses to therapy. In the present study, we investigated an alternative immunohistochemistry (IHC-based approach to achieve a molecular classification for GBM. For this purpose, a cohort of 100 surgical GBM samples was retrospectively evaluated by immunohistochemical analysis of EGFR, PDGFRA and p53. The quantitative analysis of these immunostainings allowed us to identify the following two GBM subtypes: the "Classical-like" (CL subtype, characterized by EGFR-positive and p53- and PDGFRA-negative staining and the "Proneural-like" (PNL subtype, characterized by p53- and/or PDGFRA-positive staining. This classification represents an independent prognostic factor in terms of overall survival compared to age, extent of resection and adjuvant treatment, with a significantly longer survival associated with the PNL subtype. Moreover, these two GBM subtypes exhibited different responses to chemotherapy. The addition of temozolomide to conventional radiotherapy significantly improved the survival of patients belonging to the CL subtype, but it did not affect the survival of patients belonging to the PNL subtype. We have thus shown that it is possible to differentiate between different clinically relevant subtypes of GBM by using IHC

  10. Clinically relevant characterization of lung adenocarcinoma subtypes based on cellular pathways: an international validation study.

    Directory of Open Access Journals (Sweden)

    Christopher M Bryant

    Full Text Available Lung adenocarcinoma (AD represents a predominant type of lung cancer demonstrating significant morphologic and molecular heterogeneity. We sought to understand this heterogeneity by utilizing gene expression analyses of 432 AD samples and examining associations between 27 known cancer-related pathways and the AD subtype, clinical characteristics and patient survival. Unsupervised clustering of AD and gene expression enrichment analysis reveals that cell proliferation is the most important pathway separating tumors into subgroups. Further, AD with increased cell proliferation demonstrate significantly poorer outcome and an increased solid AD subtype component. Additionally, we find that tumors with any solid component have decreased survival as compared to tumors without a solid component. These results lead to the potential to use a relatively simple pathological examination of a tumor in order to determine its aggressiveness and the patient's prognosis. Additional results suggest the ability to use a similar approach to determine a patient's sensitivity to targeted treatment. We then demonstrated the consistency of these findings using two independent AD cohorts from Asia (N = 87 and Europe (N = 89 using the identical analytic procedures.

  11. Close phylogenetic relationship between Angolan and Romanian HIV-1 subtype F1 isolates

    Science.gov (United States)

    Guimarães, Monick L; Vicente, Ana Carolina P; Otsuki, Koko; da Silva, Rosa Ferreira FC; Francisco, Moises; da Silva, Filomena Gomes; Serrano, Ducelina; Morgado, Mariza G; Bello, Gonzalo

    2009-01-01

    Background Here, we investigated the phylogenetic relationships of the HIV-1 subtype F1 circulating in Angola with subtype F1 strains sampled worldwide and reconstructed the evolutionary history of this subtype in Central Africa. Methods Forty-six HIV-1-positive samples were collected in Angola in 2006 and subtyped at the env-gp41 region. Partial env-gp120 and pol-RT sequences and near full-length genomes from those env-gp41 subtype F1 samples were further generated. Phylogenetic analyses of partial and full-length subtype F1 strains isolated worldwide were carried out. The onset date of the subtype F1 epidemic in Central Africa was estimated using a Bayesian Markov chain Monte Carlo approach. Results Nine Angolan samples were classified as subtype F1 based on the analysis of the env-gp41 region. All nine Angolan sequences were also classified as subtype F1 in both env-gp120 and pol-RT genomic regions, and near full-length genome analysis of four of these samples confirmed their classification as "pure" subtype F1. Phylogenetic analyses of subtype F1 strains isolated worldwide revealed that isolates from the Democratic Republic of Congo (DRC) were the earliest branching lineages within the subtype F1 phylogeny. Most strains from Angola segregated in a monophyletic group together with Romanian sequences; whereas South American F1 sequences emerged as an independent cluster. The origin of the subtype F1 epidemic in Central African was estimated at 1958 (1934–1971). Conclusion "Pure" subtype F1 strains are common in Angola and seem to be the result of a single founder event. Subtype F1 sequences from Angola are closely related to those described in Romania, and only distantly related to the subtype F1 lineage circulating in South America. Original diversification of subtype F1 probably occurred within the DRC around the late 1950s. PMID:19386115

  12. Identifying Psychopathy Subtypes on the Basis of Personality Structure

    Science.gov (United States)

    Hicks, Brian M.; Markon, Kristian E.; Patrick, Christopher J.; Krueger, Robert F.; Newman, Joseph P.

    2004-01-01

    The authors used model-based cluster analysis to identify subtypes of criminal psychopaths on the basis of differences in personality structure. Participants included 96 male prisoners diagnosed as psychopathic, using the Psychopathy Checklist Revised (PCL-R; R. D. Hare, 1991). Personality was assessed using the brief form of the Multidimensional…

  13. Phonological and Surface Subtypes among University Students with Dyslexia

    Science.gov (United States)

    Wolff, Ulrika

    2009-01-01

    The prevalence of phonological and surface dyslexia subtypes among Swedish university students with dyslexia (n = 40) was examined using both the regression method, developed by Castles and Coltheart, and latent profile analysis. When an academic-level control group was used as a reference group in a regression, eight students with phonological…

  14. Longitudinal Stability of Phonological and Surface Subtypes of Developmental Dyslexia

    Science.gov (United States)

    Peterson, Robin L.; Pennington, Bruce F.; Olson, Richard K.; Wadsworth, Sally J.

    2014-01-01

    Limited evidence supports the external validity of the distinction between developmental phonological and surface dyslexia. We previously identified children ages 8 to 13 meeting criteria for these subtypes (Peterson, Pennington, & Olson, 2013) and now report on their reading and related skills approximately 5 years later. Longitudinal…

  15. Cognitive subtypes of mathematics learning difficulties in primary education.

    Science.gov (United States)

    Bartelet, Dimona; Ansari, Daniel; Vaessen, Anniek; Blomert, Leo

    2014-03-01

    It has been asserted that children with mathematics learning difficulties (MLD) constitute a heterogeneous group. To date, most researchers have investigated differences between predefined MLD subtypes. Specifically MLD children are frequently categorized a priori into groups based on the presence or absence of an additional disorder, such as a reading disorder, to examine cognitive differences between MLD subtypes. In the current study 226 third to six grade children (M age=131 months) with MLD completed a selection of number specific and general cognitive measures. The data driven approach was used to identify the extent to which performance of the MLD children on these measures could be clustered into distinct groups. In particular, after conducting a factor analysis, a 200 times repeated K-means clustering approach was used to classify the children's performance. Results revealed six distinguishable clusters of MLD children, specifically (a) a weak mental number line group, (b) weak ANS group, (c) spatial difficulties group, (d) access deficit group, (e) no numerical cognitive deficit group and (f) a garden-variety group. These findings imply that different cognitive subtypes of MLD exist and that these can be derived from data-driven approaches to classification. These findings strengthen the notion that MLD is a heterogeneous disorder, which has implications for the way in which intervention may be tailored for individuals within the different subtypes.

  16. Associations among Empathy, Social Competence, & Reactive/Proactive Aggression Subtypes

    Science.gov (United States)

    Mayberry, Megan L.; Espelage, Dorothy L.

    2007-01-01

    Differences between proactive and reactive aggression subtypes on self-reported measures of empathy, social competence, and expectation for reward were examined among 433 middle school students (65.4% White, 33.9% Black). As hypothesized, males scored higher on proactive and reactive aggression scales and lower on empathy measures than females.…

  17. Sensory Processing Subtypes in Autism: Association with Adaptive Behavior

    Science.gov (United States)

    Lane, Alison E.; Young, Robyn L.; Baker, Amy E. Z.; Angley, Manya T.

    2010-01-01

    Children with autism are frequently observed to experience difficulties in sensory processing. This study examined specific patterns of sensory processing in 54 children with autistic disorder and their association with adaptive behavior. Model-based cluster analysis revealed three distinct sensory processing subtypes in autism. These subtypes…

  18. The Boder Test: Neuropsychological and Demographic Features of Dyslexic Subtypes.

    Science.gov (United States)

    Telzrow, Cathy F.; And Others

    1983-01-01

    Investigated the demographic and neuropsychological characteristics of 30 children in reading categories defined by performance on the Boder Test. Provided evidence that the Boder Test may be a nonbiased valid screening test for the identification of dyslexia and dyslexic subtypes. (JAC)

  19. Racial Differences by Ischemic Stroke Subtype: A Comprehensive Diagnostic Approach

    Directory of Open Access Journals (Sweden)

    Sarah Song

    2012-01-01

    Full Text Available Background. Previous studies have suggested that black populations have more small-vessel and fewer cardioembolic strokes. We sought to analyze racial differences in ischemic stroke subtype employing a comprehensive diagnostic workup with magnetic resonance-imaging-(MRI- based evaluation including diffusion-weighted imaging (DWI. Methods. 350 acute ischemic stroke patients admitted to an urban hospital with standardized comprehensive diagnostic evaluations were retrospectively analyzed. Ischemic stroke subtype was determined by three Trial of Org 10172 in Acute Stroke Treatment (TOAST classification systems. Results. We found similar proportions of cardioembolic and lacunar strokes in the black and white cohort. The only subtype category with a significant difference by race was “stroke of other etiology,” more common in whites. Black stroke patients were more likely to have an incomplete evaluation, but this did not reach significance. Conclusions. We found similar proportions by race of cardioembolic and lacunar strokes when employing a full diagnostic evaluation including DWI MRI. The relatively high rate of cardioembolism may have been underappreciated in black stroke patients when employing a CT approach to stroke subtype diagnosis. Further research is required to better understand the racial differences in frequency of “stroke of other etiology” and explore disparities in the extent of diagnostic evaluations.

  20. Gene specific actions of thyroid hormone receptor subtypes.

    Directory of Open Access Journals (Sweden)

    Jean Z Lin

    Full Text Available There are two homologous thyroid hormone (TH receptors (TRs α and β, which are members of the nuclear hormone receptor (NR family. While TRs regulate different processes in vivo and other highly related NRs regulate distinct gene sets, initial studies of TR action revealed near complete overlaps in their actions at the level of individual genes. Here, we assessed the extent that TRα and TRβ differ in target gene regulation by comparing effects of equal levels of stably expressed exogenous TRs +/- T(3 in two cell backgrounds (HepG2 and HeLa. We find that hundreds of genes respond to T(3 or to unliganded TRs in both cell types, but were not able to detect verifiable examples of completely TR subtype-specific gene regulation. TR actions are, however, far from identical and we detect TR subtype-specific effects on global T(3 response kinetics in HepG2 cells and many examples of TR subtype specificity at the level of individual genes, including effects on magnitude of response to TR +/- T(3, TR regulation patterns and T(3 dose response. Cycloheximide (CHX treatment confirms that at least some differential effects involve verifiable direct TR target genes. TR subtype/gene-specific effects emerge in the context of widespread variation in target gene response and we suggest that gene-selective effects on mechanism of TR action highlight differences in TR subtype function that emerge in the environment of specific genes. We propose that differential TR actions could influence physiologic and pharmacologic responses to THs and selective TR modulators (STRMs.

  1. Patient-specific data fusion defines prognostic cancer subtypes.

    Directory of Open Access Journals (Sweden)

    Yinyin Yuan

    2011-10-01

    Full Text Available Different data types can offer complementary perspectives on the same biological phenomenon. In cancer studies, for example, data on copy number alterations indicate losses and amplifications of genomic regions in tumours, while transcriptomic data point to the impact of genomic and environmental events on the internal wiring of the cell. Fusing different data provides a more comprehensive model of the cancer cell than that offered by any single type. However, biological signals in different patients exhibit diverse degrees of concordance due to cancer heterogeneity and inherent noise in the measurements. This is a particularly important issue in cancer subtype discovery, where personalised strategies to guide therapy are of vital importance. We present a nonparametric Bayesian model for discovering prognostic cancer subtypes by integrating gene expression and copy number variation data. Our model is constructed from a hierarchy of Dirichlet Processes and addresses three key challenges in data fusion: (i To separate concordant from discordant signals, (ii to select informative features, (iii to estimate the number of disease subtypes. Concordance of signals is assessed individually for each patient, giving us an additional level of insight into the underlying disease structure. We exemplify the power of our model in prostate cancer and breast cancer and show that it outperforms competing methods. In the prostate cancer data, we identify an entirely new subtype with extremely poor survival outcome and show how other analyses fail to detect it. In the breast cancer data, we find subtypes with superior prognostic value by using the concordant results. These discoveries were crucially dependent on our model's ability to distinguish concordant and discordant signals within each patient sample, and would otherwise have been missed. We therefore demonstrate the importance of taking a patient-specific approach, using highly-flexible nonparametric

  2. Prehospital Identification of Stroke Subtypes in Chinese Rural Areas

    Institute of Scientific and Technical Information of China (English)

    Hai-Qiang Jin; Jin-Chao Wang; Yong-An Sun; Pu Lyu; Wei Cui; Yuan-Yuan Liu; Zhi-Gang Zhen

    2016-01-01

    Background:Differentiating intracerebral hemorrhage (ICH) from cerebral infarction as early as possible is vital for the timely initiation of different treatments.This study developed an applicable model for the ambulance system to differentiate stroke subtypes.Methods:From 26,163 patients initially screened over 4 years,this study comprised 1989 consecutive patients with potential first-ever acute stroke with sudden onset of the focal neurological deficit,conscious or not,and given ambulance transport for admission to two county hospitals in Yutian County of Hebei Province.All the patients underwent cranial computed tomography (CT) or magnetic resonance imaging to confirm the final diagnosis based on stroke criteria.Correlation with stroke subtype clinical features was calculated and Bayes' discriminant model was applied to discriminate stroke subtypes.Results:Among the 1989 patients,797,689,109,and 394 received diagnoses of cerebral infarction,ICH,subarachnoid hemorrhage,and other forms of nonstroke,respectively.A history of atrial fibrillation,vomiting,and diabetes mellitus were associated with cerebral infarction,while vomiting,systolic blood pressure ≥180 mmHg,and age <65 years were more typical of ICH.For noncomatose stroke patients,Bayes' discriminant model for stroke subtype yielded a combination of multiple items that provided 72.3% agreement in the test model and 79.3% in the validation model; for comatose patients,corresponding agreement rates were 75.4% and 73.5%.Conclusions:The model herein presented,with multiple parameters,can predict stroke subtypes with acceptable sensitivity and specificity before CT scanning,either in alert or comatose patients.This may facilitate prehospital management for patients with stroke.

  3. Association between endometriosis and risk of histological subtypes of ovarian cancer

    DEFF Research Database (Denmark)

    Pearce, Celeste Leigh; Templeman, Claire; Rossing, Mary Anne;

    2012-01-01

    Endometriosis is a risk factor for epithelial ovarian cancer; however, whether this risk extends to all invasive histological subtypes or borderline tumours is not clear. We undertook an international collaborative study to assess the association between endometriosis and histological subtypes...

  4. Low penetrance breast cancer susceptibility loci are associated with specific breast tumor subtypes

    DEFF Research Database (Denmark)

    Broeks, Annegien; Schmidt, Marjanka K; Sherman, Mark E;

    2011-01-01

    Breast cancers demonstrate substantial biological, clinical and etiological heterogeneity. We investigated breast cancer risk associations of eight susceptibility loci identified in GWAS and two putative susceptibility loci in candidate genes in relation to specific breast tumor subtypes. Subtype...

  5. Review to better understand the macroscopic subtypes and histogenesis of intrahepatic cholangiocarcinoma

    Institute of Scientific and Technical Information of China (English)

    Yuichi; Sanada; Yujo; Kawashita; Satomi; Okada; Takashi; Azuma; Shigetoshi; Matsuo

    2014-01-01

    Intrahepatic cholangiocarcinoma is macroscopically classified into three subtypes, mass-forming-type, periductal infiltrating-type, and intraductal growth-type. Each subtype should be preoperatively differentiated to perform the valid surgical resection. Recent researches have revealed the clinical, radiologic, pathobiological characteristics of each subtype. We reviewed recently published studies covering various aspects of intrahepatic cholangiocarcinoma(ICC), focusing especially on the macroscopic subtypes and stem cell features to better understand the pathophysiology of ICC and to establish the valid therapeutic strategy.

  6. Preparation of Anti-Idiotypic Antibody against Avian Influenza Virus Subtype H9

    Institute of Scientific and Technical Information of China (English)

    BaoquanLi; JunPeng; ZhongxiangNiu; XunheYin; FaxiaoLiu

    2005-01-01

    To generate monoclonal anti-idiotypic antibodies (mAb2) against avian influenza virus subtype H9 (H9 AIV), BALB/c mice were immunized with purified chicken anti-H9-AIV IgG and the splenocytes of immunized mice were fused with myeloma cells NS-1. Hybridoma cells were screened by indirect enzyme-linked immunosorbent assays with both chicken and rabbit anti-H9-AIV IgG as coating antigens. One hybridoma cell clone secreting monoclonal antibody against idiotypes shared by both chicken and rabbit anti-H9-AIV IgG was established. Experiments demonstrated the mAb2 was able to inhibit the binding of hemagglutinin to anti-H9-AIV IgG and to induce chickens to generate hemagglutination inhibition antibodies, indicating this anti-species-sharing-idiotypic antibody bore the internal image of hemagglutinin on avian influenza virus. Cellular & Molecular Immunology. 2005;2(2):155-157.

  7. Preparation of Anti-Idiotypic Antibody against Avian Influenza Virus Subtype H9

    Institute of Scientific and Technical Information of China (English)

    Baoquan Li; Jun Peng; Zhongxiang Niu; Xunhe Yin; Faxiao Liu

    2005-01-01

    To generate monoclonal anti-idiotypic antibodies (mAb2) against avian influenza virus subtype H9 (H9 AIV),BALB/c mice were immunized with purified chicken anti-H9-AIV IgG and the splenocytes of immunized mice were fused with myeloma cells NS-1. Hybridoma cells were screened by indirect enzyme-linked immunosorbent assays with both chicken and rabbit anti-H9-AIV IgG as coating antigens. One hybridoma cell clone secreting monoclonal antibody against idiotypes shared by both chicken and rabbit anti-H9-AIV IgG was established. Experiments demonstrated the mAb2 was able to inhibit the binding of hemagglutinin to anti-H9-AIV IgG and to induce chickens to generate hemagglutination inhibition antibodies, indicating this anti-species-sharing-idiotypic antibody bore the internal image of hemagglutinin on avian influenza virus. Cellular & Molecular Immunology. 2005;2(2):155-157.

  8. Dkk4 and Eda regulate distinctive developmental mechanisms for subtypes of mouse hair.

    Directory of Open Access Journals (Sweden)

    Chang-Yi Cui

    Full Text Available The mouse hair coat comprises protective "primary" and thermo-regulatory "secondary" hairs. Primary hair formation is ectodysplasin (Eda dependent, but it has been puzzling that Tabby (Eda(-/y mice still make secondary hair. We report that Dickkopf 4 (Dkk4, a Wnt antagonist, affects an auxiliary pathway for Eda-independent development of secondary hair. A Dkk4 transgene in wild-type mice had no effect on primary hair, but secondary hairs were severely malformed. Dkk4 action on secondary hair was further demonstrated when the transgene was introduced into Tabby mice: the usual secondary follicle induction was completely blocked. The Dkk4-regulated secondary hair pathway, like the Eda-dependent primary hair pathway, is further mediated by selective activation of Shh. The results thus reveal two complex molecular pathways that distinctly regulate subtype-based morphogenesis of hair follicles, and provide a resolution for the longstanding puzzle of hair formation in Tabby mice lacking Eda.

  9. Dkk4 and Eda regulate distinctive developmental mechanisms for subtypes of mouse hair.

    Science.gov (United States)

    Cui, Chang-Yi; Kunisada, Makoto; Piao, Yulan; Childress, Victoria; Ko, Minoru S H; Schlessinger, David

    2010-01-01

    The mouse hair coat comprises protective "primary" and thermo-regulatory "secondary" hairs. Primary hair formation is ectodysplasin (Eda) dependent, but it has been puzzling that Tabby (Eda(-/y)) mice still make secondary hair. We report that Dickkopf 4 (Dkk4), a Wnt antagonist, affects an auxiliary pathway for Eda-independent development of secondary hair. A Dkk4 transgene in wild-type mice had no effect on primary hair, but secondary hairs were severely malformed. Dkk4 action on secondary hair was further demonstrated when the transgene was introduced into Tabby mice: the usual secondary follicle induction was completely blocked. The Dkk4-regulated secondary hair pathway, like the Eda-dependent primary hair pathway, is further mediated by selective activation of Shh. The results thus reveal two complex molecular pathways that distinctly regulate subtype-based morphogenesis of hair follicles, and provide a resolution for the longstanding puzzle of hair formation in Tabby mice lacking Eda. PMID:20386733

  10. Impact of Breast Cancer Subtype Defined by Immunohistochemistry Hormone Receptor and HER2 Status on the Incidence of Immediate Postmastectomy Reconstruction.

    Science.gov (United States)

    Wu, Wei; Cheng, Shi; Deng, Heran; Wu, Jiannan; Mao, Kai; Cao, Minghui

    2016-01-01

    Immediate postmastectomy reconstruction has become an increasingly popular choice for breast cancer patients recently. However, whether molecular subtype of cancer impacts the incidence of breast reconstruction is unclear. We aimed to investigate the association between breast cancer subtype defined by immunohistochemistry hormone receptor (HR) and human epidermal growth factor receptor 2 (HER2) status and recent rates of immediate postmastectomy reconstruction in the United States.The National Cancer Institute's Surveillance, Epidemiology, and End Results (SEER) database was used to evaluate stage I-III breast cancer patients with different subtypes who underwent either mastectomy alone or mastectomy plus reconstruction between 2010 and 2012. Univariate and multivariate analyses were conducted to identify factors influencing the incidence of immediate reconstruction.Of 47,123 women included, 33.1% (10,712/32,376) of HR+/HER2-, 33.1% (1912/5768) of HR+/HER2+, 29.6% (850/2875) of HR-/HER2+, and 27.7% (1689/6104) of triple negative breast cancer patients received immediate breast reconstruction (chi-square test, P breast cancer patients received significantly less breast reconstruction. After adjusting for demographic, socioeconomic, geographic, or clinicopathologic factors, HER2-overexpressing (OR 0.896, 95% CI 0.817-0.984) and triple negative (OR 0.806, 95% CI 0.751-0.866) breast cancer patients remained less likely to undergo immediate postmastectomy reconstruction compared with HR+/HER2- or HR+/HER2+ patients. No significant difference was found in the type of reconstruction among different subtypes. Subgroup analysis showed that the difference of breast reconstruction rates among distinct subtypes varied with different grade and stage groups, and the association between breast cancer subtype and the reconstruction rate was not significant in low grade and early stage patients.This population-based study determined that breast cancer subtype was an independent

  11. Empirically Derived Learning Disability Subtypes: A Replication Attempt and Longitudinal Patterns over 15 Years.

    Science.gov (United States)

    Spreen, Otfried; Haaf, Robert G.

    1986-01-01

    Test scores of two groups of learning disabled children (N=63 and N=96) were submitted to cluster analysis in an attempt to replicate previously described subtypes. All three subtypes (visuo-perceptual, linguistic, and articulo-graphomotor types) were identified along with minimally and severely impaired subtypes. Similar clusters in the same…

  12. Genome-wide analysis for identification of adaptive diversification between hepatitis C virus subtypes 1a and 1b.

    Science.gov (United States)

    Li, Yan; Wang, Ruirui; Du, Xiaogang; Zhang, Mingwang; Xie, Meng

    2016-07-01

    Hepatitis C virus (HCV) is a major cause of liver disease and has been estimated to infect approximately 2%-3% of the world's population. HCV genotype 1 is the subject of intense research and clinical investigations because of its worldwide prevalence and poor access to treatment for patients in developing countries and marginalized populations. The predominant subtypes 1a and 1b of HCV genotype 1 present considerable differences in epidemiological features. However, the genetic signature underlying such phenotypic functional divergence is still an open question. Here, we performed a genome-wide evolutionary study on HCV subtypes 1a and 1b. The results show that adaptive selection has driven the diversification between these subtypes. Furthermore, the major adaptive divergence-related changes have occurred on proteins E1, NS4B, NS5A, and NS5B. Structurally, a number of adaptively selected sites cluster in functional regions potentially relevant to (i) membrane attachment and (ii) the interactions with viral and host cell factors and the genome template. These results might provide helpful hints about the molecular determinants of epidemiological divergence between HCV 1a and 1b.

  13. Markers of subtypes in inflammatory breast cancer studied by immunohistochemistry: Prominent expression of P-cadherin

    International Nuclear Information System (INIS)

    Inflammatory breast cancer (IBC) is a distinct and aggressive form of locally-advanced breast cancer with high metastatic potential. In Tunisia, IBC is associated with a high death rate. Among the major molecular subtypes, basal breast carcinomas are poorly differentiated, have metastatic potential and poor prognosis, but respond relatively well to chemotherapy. The aim of this study was to determine the distribution of molecular subtypes in IBC and identify factors that may explain the poor prognosis of IBC. To determine breast cancer subtypes we studied by immunohistochemistry the expression of 12 proteins in a series of 91 Tunisian IBC and 541 non-IBC deposited in tissue microarrays. We considered infiltrating ductal cases only. We found 33.8% of basal cases in IBC vs 15.9% in non-IBC (p < 0.001), 33.3% of ERBB2-overexpressing cases in IBC vs 14.5% in non-IBC (p < 0.001), and 29.3% of luminal cases in IBC vs 59.9% in non-IBC (p < 0.001). The most differentially-expressed protein between IBCs and non-IBCs was P-cadherin. P-cadherin expression was found in 75.9% of all IBC vs 48.2% of all non-IBC (p < 0.001), 95% of IBC vs 69% of non-IBC (p = 0.02) in basal cases, and 82% of IBC vs 43% of non-IBC (p < 0.001) in luminal cases. Logistic regression determined that the most discriminating markers between IBCs and non-IBCs were P-cadherin (OR = 4.9, p = 0.0019) MIB1 (OR = 3.6, p = 0.001), CK14 (OR = 2.7, p = 0.02), and ERBB2 (OR = 2.3, p = 0.06). Tunisian IBCs are characterized by frequent basal and ERBB2 phenotypes. Surprisingly, luminal IBC also express the basal marker P-cadherin. This profile suggests a specificity that needs further investigation

  14. The homeodomain-containing transcription factors Arx and Pax4 control enteroendocrine subtype specification in mice.

    Directory of Open Access Journals (Sweden)

    Anthony Beucher

    Full Text Available Intestinal hormones are key regulators of digestion and energy homeostasis secreted by rare enteroendocrine cells. These cells produce over ten different hormones including GLP-1 and GIP peptides known to promote insulin secretion. To date, the molecular mechanisms controlling the specification of the various enteroendocrine subtypes from multipotent Neurog3(+ endocrine progenitor cells, as well as their number, remain largely unknown. In contrast, in the embryonic pancreas, the opposite activities of Arx and Pax4 homeodomain transcription factors promote islet progenitor cells towards the different endocrine cell fates. In this study, we thus investigated the role of Arx and Pax4 in enteroendocrine subtype specification. The small intestine and colon of Arx- and Pax4-deficient mice were analyzed using histological, molecular, and lineage tracing approaches. We show that Arx is expressed in endocrine progenitors (Neurog3(+ and in early differentiating (ChromograninA(- GLP-1-, GIP-, CCK-, Sct- Gastrin- and Ghrelin-producing cells. We noted a dramatic reduction or a complete loss of all these enteroendocrine cell types in Arx mutants. Serotonin- and Somatostatin-secreting cells do not express Arx and, accordingly, the differentiation of Serotonin cells was not affected in Arx mutants. However, the number of Somatostatin-expressing D-cells is increased as Arx-deficient progenitor cells are redirected to the D-cell lineage. In Pax4-deficient mice, the differentiation of Serotonin and Somatostatin cells is impaired, as well as of GIP and Gastrin cells. In contrast, the number of GLP-1 producing L-cells is increased concomitantly with an upregulation of Arx. Thus, while Arx and Pax4 are necessary for the development of L- and D-cells respectively, they conversely restrict D- and L-cells fates suggesting antagonistic functions in D/L cell allocation. In conclusion, these finding demonstrate that, downstream of Neurog3, the specification of a subset of

  15. Clinical contrast study of micro-invasive curettage and apocrine sweat gland pruning in the treatment of osmidrosis%微创刮除术与大汗腺修剪术治疗腋臭的临床对比研究

    Institute of Scientific and Technical Information of China (English)

    樊雁

    2014-01-01

    目的:比较微创刮除术与大汗腺修剪术治疗腋臭的临床疗效及安全性。方法2011年3月至2012年3月,拟行手术治疗的腋臭患者114例共211侧,按照随机数字表分为两组,一组56例共104侧,采用微创大汗腺刮除术;另一组58例107侧,行小切口皮下大汗腺修剪术。平均随访1.4年,比较两组术后并发症发生率、切口加压包扎时间、疤痕长度及复发率差异。结果刮除术组术后并发症发生率低于修剪术组(4.8%vs.12.1%,χ2=4.409, P=0.035),复发率高于修剪术组(12.5%vs.3.7%,χ2=5.465, P=0.019);刮除术组加压包扎时间、疤痕长度均低于修剪术组[(2.8±0.2)天 vs.(7.1±0.5)天, t=82.436, P<0.001;(1.0±0.4)cm vs.(4.3±0.9) cm, t=34.577, P<0.001]。结论微创刮除术术后并发症少,而大汗腺修剪术术后复发率低,两种手术治疗腋臭均安全有效。%Objective To compare the clinical efficacy and safety of micro-invasive curettage and apocrine sweat gland pruning for the treat-ment of osmidrosis. Methods 211 sides of 114 patients with osmidrosis from Mar. 2011 to Mar. 2012 were randomly divided into two groups , a group of 56 cases with a total of 104 side were treated with micro-invasive curettage; another group of 58 cases with a total of 107 sides were treated with small incision subcutaneous apocrine pruning. The average follow up period was 1.4 years, the differences of postoperative complication rate, time, length of incision of pressurized bandaging scar and recurrence rate between two groups was compared. Results The postoperative complica-tion rate in curettage group was lower than that in pruning group (4.8%vs.12.1%,χ2=4.409, P=0.035), and the recurrence rate was higher than that of pruning group (12.5%vs. 3.7%,χ2=5.465, P=0.019). The pressure dressing time, scar length in curettage group were lower than those in pruning group ((2.8±0.2)d vs. (7.1±0.5)d, t=82.436, P<0

  16. CD44 isoforms are heterogeneously expressed in breast cancer and correlate with tumor subtypes and cancer stem cell markers

    International Nuclear Information System (INIS)

    The CD44 cell adhesion molecule is aberrantly expressed in many breast tumors and has been implicated in the metastatic process as well as in the putative cancer stem cell (CSC) compartment. We aimed to investigate potential associations between alternatively spliced isoforms of CD44 and CSCs as well as to various breast cancer biomarkers and molecular subtypes. We used q-RT-PCR and exon-exon spanning assays to analyze the expression of four alternatively spliced CD44 isoforms as well as the total expression of CD44 in 187 breast tumors and 13 cell lines. ALDH1 protein expression was determined by IHC on TMA. Breast cancer cell lines showed a heterogeneous expression pattern of the CD44 isoforms, which shifted considerably when cells were grown as mammospheres. Tumors characterized as positive for the CD44+/CD24- phenotype by immunohistochemistry were associated to all isoforms except the CD44 standard (CD44S) isoform, which lacks all variant exons. Conversely, tumors with strong expression of the CSC marker ALDH1 had elevated expression of CD44S. A high expression of the CD44v2-v10 isoform, which retain all variant exons, was correlated to positive steroid receptor status, low proliferation and luminal A subtype. The CD44v3-v10 isoform showed similar correlations, while high expression of CD44v8-v10 was correlated to positive EGFR, negative/low HER2 status and basal-like subtype. High expression of CD44S was associated with strong HER2 staining and also a subgroup of basal-like tumors. Unsupervised hierarchical cluster analysis of CD44 isoform expression data divided tumors into four main clusters, which showed significant correlations to molecular subtypes and differences in 10-year overall survival. We demonstrate that individual CD44 isoforms can be associated to different breast cancer subtypes and clinical markers such as HER2, ER and PgR, which suggests involvement of CD44 splice variants in specific oncogenic signaling pathways. Efforts to link CD44 to CSCs

  17. MLST subtypes and population genetic structure of Cryptosporidium andersoni from dairy cattle and beef cattle in northeastern China's Heilongjiang Province.

    Directory of Open Access Journals (Sweden)

    Wei Zhao

    Full Text Available Cattle are the main reservoir host of C. andersoni, which shows a predominance in yearlings and adults of cattle. To understand the subtypes of C. andersoni and the population genetic structure in Heilongjiang Province, fecal specimens were collected from 420 dairy cattle and 405 beef cattle at the age of 12-14 months in eight cattle farms in five areas within this province and were screened for the presence of Cryptosporidium oocysts by microscopy after Sheather's sugar flotation technique. The average prevalence of Cryptosporidium spp. was 19.15% (158/825 and all the Cryptosporidium isolates were identified as C. andersoni by the SSU rRNA gene nested PCR-RFLP using SspI, VspI and MboII restriction enzymes. A total of 50 C. andersoni isolates were randomly selected and sequenced to confirm the RFLP results before they were subtyped by multilocus sequence typing (MLST at the four microsatellite/minisatellite loci (MS1, MS2, MS3 and MS16. Four, one, two and one haplotypes were obtained at the four loci, respectively. The MLST subtype A4,A4,A4,A1 showed an absolute predominance and a wide distribution among the six MLST subtypes obtained in the investigated areas. Linkage disequilibrium analysis showed the presence of a clonal population genetic structure of C. andersoni in cattle, suggesting the absence of recombination among lineages. The finding of a clonal population genetic structure indicated that the prevalence of C. andersoni in cattle in Heilongjiang Province is not attributed to the introduction of cattle. Thus, prevention and control strategies should be focused on making stricter measures to avoid the occurrence of cross-transmission and re-infection between cattle individuals. These molecular data will also be helpful to explore the source attribution of infection/contamination of C. andersoni and to elucidate its transmission dynamics in Heilongjiang Province, even in China.

  18. Differential drug resistance acquisition in HIV-1 of subtypes B and C.

    Directory of Open Access Journals (Sweden)

    Esmeralda A J M Soares

    Full Text Available BACKGROUND: Subtype C is the most prevalent HIV-1 subtype in the world, mainly in countries with the highest HIV prevalence. However, few studies have evaluated the impact of antiretroviral therapy on this subtype. In southern Brazil, the first developing country to offer free and universal treatment, subtypes B and C co-circulate with equal prevalence, allowing for an extensive evaluation of this issue. METHODS AND FINDINGS: Viral RNA of 160 HIV-1+ patients was extracted, and the protease and reverse transcriptase genes were sequenced, subtyped and analyzed for ARV mutations. Sequences were grouped by subtype, and matched to type (PI, NRTI and NNRTI and time of ARV exposure. Statistical analyses were performed to compare differences in the frequency of ARV-associated mutations. There were no significant differences in time of treatment between subtypes B and C groups, although they showed distinct proportions of resistant strains at different intervals for two of three ARV classes. For PI, 26% of subtype B strains were resistant, compared to only 8% in subtype C (p = 0.0288, Fisher's exact test. For NRTI, 54% of subtype B strains were resistant versus 23% of subtype C (p = 0.0012. Differences were significant from 4 years of exposure, and remained so until the last time point analyzed. The differences observed between both subtypes were independent of time under rebound viremia in cases of virologic failure and of the number of HAART regimens used by treated patients. CONCLUSIONS: Our results pointed out to a lower rate of accumulation of mutations conferring resistance to ARV in subtype C than in subtype B. These findings are of crucial importance for current initiatives of ARV therapy roll-out in developing countries, where subtype is C prevalent.

  19. Human islets contain four distinct subtypes of β cells.

    Science.gov (United States)

    Dorrell, Craig; Schug, Jonathan; Canaday, Pamela S; Russ, Holger A; Tarlow, Branden D; Grompe, Maria T; Horton, Tamara; Hebrok, Matthias; Streeter, Philip R; Kaestner, Klaus H; Grompe, Markus

    2016-01-01

    Human pancreatic islets of Langerhans contain five distinct endocrine cell types, each producing a characteristic hormone. The dysfunction or loss of the insulin-producing β cells causes diabetes mellitus, a disease that harms millions. Until now, β cells were generally regarded as a single, homogenous cell population. Here we identify four antigenically distinct subtypes of human β cells, which we refer to as β1-4, and which are distinguished by differential expression of ST8SIA1 and CD9. These subpopulations are always present in normal adult islets and have diverse gene expression profiles and distinct basal and glucose-stimulated insulin secretion. Importantly, the β cell subtype distribution is profoundly altered in type 2 diabetes. These data suggest that this antigenically defined β cell heterogeneity is functionally and likely medically relevant. PMID:27399229

  20. Psychopathy Subtypes among African American County Jail Inmates

    OpenAIRE

    Swogger, Marc T.; Walsh, Zach; Kosson, David S.

    2008-01-01

    There is evidence that the classification of “psychopath” captures a heterogeneous group of offenders. Although several studies have provided evidence for two distinct psychopath subtypes, these studies have inadequately addressed potentially important ethnic differences. A recent taxonomic study found evidence for primary and secondary psychopath subgroups in a sample of European American offenders (Swogger & Kosson, 2007). The present study used cluster analysis to attempt to replicate thos...

  1. Maltreatment and psychopathy subtypes in high-risk adolescent females

    OpenAIRE

    Coupland, Ruth Louise

    2011-01-01

    Psychopathy is often viewed as a unitary construct, however, research with adults and adolescent males has revealed two heterogeneous subtypes. Primary psychopathy is presumed to have biological underpinnings and is associated with low levels of anxiety and psychological distress. In contrast, secondary psychopathy is believed to result from exposure to adversity, including childhood maltreatment, and is associated with emotional reactivity, impulsivity, and comorbid psychological problems. T...

  2. Memory Processes in Learning Disability Subtypes of Children Born Preterm

    OpenAIRE

    McCoy, Thomasin E; Conrad, Amy L.; Richman, Lynn C.; Nopoulos, Peg C.; Bell, Edward F.

    2012-01-01

    The purpose of this study was to evaluate immediate auditory and visual memory processes in learning disability subtypes of 40 children born preterm. Three subgroups of children were examined: (a) primary language disability group (n = 13), (b) perceptual-motor disability group (n = 14), and (c) no learning disability diagnosis group without identified language or perceptual-motor learning disability (n = 13). Between-group comparisons indicate no significant differences in immediate auditory...

  3. Brain metastases free survival differs between breast cancer subtypes

    Science.gov (United States)

    Berghoff, A; Bago-Horvath, Z; De Vries, C; Dubsky, P; Pluschnig, U; Rudas, M; Rottenfusser, A; Knauer, M; Eiter, H; Fitzal, F; Dieckmann, K; Mader, R M; Gnant, M; Zielinski, C C; Steger, G G; Preusser, M; Bartsch, R

    2012-01-01

    Background: Brain metastases (BM) are frequently diagnosed in patients with HER-2-positive metastatic breast cancer; in addition, an increasing incidence was reported for triple-negative tumours. We aimed to compare brain metastases free survival (BMFS) of breast cancer subtypes in patients treated between 1996 until 2010. Methods: Brain metastases free survival was measured as the interval from diagnosis of extracranial breast cancer metastases until diagnosis of BM. HER-2 status was analysed by immunohistochemistry and reanalysed by fluorescent in situ hybridisation if a score of 2+ was gained. Oestrogen-receptor (ER) and progesterone-receptor (PgR) status was analysed by immunohistochemistry. Brain metastases free survival curves were estimated with the Kaplan–Meier method and compared with the log-rank test. Results: Data of 213 patients (46 luminal/124 HER-2/43 triple-negative subtype) with BM from breast cancer were available for the analysis. Brain metastases free survival differed significantly between breast cancer subtypes. Median BMFS in triple-negative tumours was 14 months (95% CI: 11.34–16.66) compared with 18 months (95% CI: 14.46–21.54) in HER-2-positive tumours (P=0.001) and 34 months (95% CI: 23.71–44.29) in luminal tumours (P=0.001), respectively. In HER-2-positive patients, co-positivity for ER and HER-2 prolonged BMFS (26 vs 15 m; P=0.033); in luminal tumours, co-expression of ER and PgR was not significantly associated with BMFS. Brain metastases free survival in patients with lung metastases was significantly shorter (17 vs 21 months; P=0.014). Conclusion: Brain metastases free survival in triple-negative breast cancer, as well as in HER-2-positive/ER-negative, is significantly shorter compared with HER-2/ER co-positive or luminal tumours, mirroring the aggressiveness of these breast cancer subtypes. PMID:22233926

  4. HIV-1 subtype B: Traces of a pandemic.

    Science.gov (United States)

    Junqueira, Dennis Maletich; Almeida, Sabrina Esteves de Matos

    2016-08-01

    Human migration is a major process that shaped the origin and dissemination of HIV. Within HIV-1, subtype B (HIV-1B) is the most disseminated variant and it is assumed to be the causative agent in approximately 11% of all cases of HIV worldwide. Phylogenetic studies have revealed that HIV-1B emerged in Kinshasa (Africa) and was introduced into the Caribbean region via Haiti in or around 1966 by human migration. After localized dispersion, the virus was brought to the United States of America via homosexual/bisexual contact around 1969. Inside USA, the incidence of HIV-1B infection increased exponentially and it became established in the population, affecting not only homosexual individuals but also heterosexual individuals and injecting drug users. Soon after, the virus was disseminated and became established in other regions, including Europe, Asia, Latin America, and Australia. Recent studies suggest that, in addition to this pandemic clade, several lineages have emerged from Haiti and reached other Caribbean and Latin American countries via short-distance dissemination. Different subtype B genetic variants have also been detected in these epidemics. Four genetic variants have been described to date: subtype B', which mainly circulates in Thailand and other Asian countries; a specific variant mainly found in Trinidad and Tobago; the GPGS variant, which is primarily detected in Korea; and the GWGR variant, which is mainly detected in Brazil. This paper reviews the evolution of HIV-1B and its impact on the human population. PMID:27228177

  5. Expression of subtypes of somatostatin receptors in hepatic stellate cells

    Institute of Scientific and Technical Information of China (English)

    Sheng-Han Song; Xi-Sheng Leng; Tao Li; Zhi-Zhong Qin; Ji-Run Peng; Li Zhao; Yu-Hua Wei; Xin Yu

    2004-01-01

    AIM: To elucidate the mechanism by which somatostatin and its analogue exert the influence on liver fibrosis, and to investigate the mRNA expression of somatostatin receptors subtypes (SSTRs) and the distribution of somatostatin analogue octreotide in rat hepatic stellate cells (HSCs).METHODS: HSCs were isolated from Sprague Dawley (SD)rats byin situ perfusion and density gradient centrifugation.After several passages, the mRNA expression of 5 subtypes of SSTRs were assessed by reverse transcription-polymerase chain reaction (RT-PCR). HSCs were planted on coverslip and co-cultured with octreotide tagged by FITC. Then the distribution of FITC fluorescence was observed under laser scanning confocal microscope (LSCM) in 12-24 h.RESULTS: There were mRNA expression of SSTR2, SSTR3and SSTR5 but not SSTR1 and SSTR4 in SD rat HSCs. The mRNA expression level of SSTR2 was significantly higher than that of other subtypes (P<0.01). FITC fluorescence of octreotide was clearly observed on the surface and in the cytoplasm, but not in the nuclei of HSCs under LSCM.CONCLUSION: The effect exerted by somatostatin and its analogues on HSCs may mainly depend on the expression of SSTR2, SSTR3 and SSTR5. Octreotide can perfectly combine with HSCs, and thereby exerts its biological activity on regulating the characters of active HSCs. This provides a potential prevention and management against liver fibrosis.

  6. HIV-1 subtype B: Traces of a pandemic.

    Science.gov (United States)

    Junqueira, Dennis Maletich; Almeida, Sabrina Esteves de Matos

    2016-08-01

    Human migration is a major process that shaped the origin and dissemination of HIV. Within HIV-1, subtype B (HIV-1B) is the most disseminated variant and it is assumed to be the causative agent in approximately 11% of all cases of HIV worldwide. Phylogenetic studies have revealed that HIV-1B emerged in Kinshasa (Africa) and was introduced into the Caribbean region via Haiti in or around 1966 by human migration. After localized dispersion, the virus was brought to the United States of America via homosexual/bisexual contact around 1969. Inside USA, the incidence of HIV-1B infection increased exponentially and it became established in the population, affecting not only homosexual individuals but also heterosexual individuals and injecting drug users. Soon after, the virus was disseminated and became established in other regions, including Europe, Asia, Latin America, and Australia. Recent studies suggest that, in addition to this pandemic clade, several lineages have emerged from Haiti and reached other Caribbean and Latin American countries via short-distance dissemination. Different subtype B genetic variants have also been detected in these epidemics. Four genetic variants have been described to date: subtype B', which mainly circulates in Thailand and other Asian countries; a specific variant mainly found in Trinidad and Tobago; the GPGS variant, which is primarily detected in Korea; and the GWGR variant, which is mainly detected in Brazil. This paper reviews the evolution of HIV-1B and its impact on the human population.

  7. Laboratory-induced hyperventilation differentiates female sexual arousal disorder subtypes.

    Science.gov (United States)

    Brotto, Lori A; Klein, Carolin; Gorzalka, Boris B

    2009-08-01

    The effects of heightened sympathetic nervous system (SNS) activity via laboratory-induced hyperventilation (LIH) on subjective and physiological sexual arousal were examined in a heterogeneous group of women with Sexual Arousal Disorder (SAD; n = 60), as well as across subtypes of SAD, in comparison to a control group of women without sexual difficulties (n = 42). Participants took part in 2 min of rapid breathing, a technique previously found to increase SNS activity, immediately prior to viewing erotic stimuli. Physiological arousal (i.e., vaginal pulse amplitude; VPA) was measured via the vaginal photoplethysmograph and subjective arousal was measured via self-report questionnaires. LIH differentiated women with SAD from those in the control group, with LIH increasing VPA in the latter, but having no significant effect in the heterogeneous SAD group. However, among subtypes of SAD, LIH differentiated women with genital (n = 16) and subjective (n = 16) subtypes of SAD from women with combined SAD (n = 28) and women without sexual difficulties. Specifically, women in the control group and those with combined SAD had a significant increase in VPA whereas women with genital or subjective SAD had a significant decrease in VPA following LIH. There was no significant effect of LIH on any self-report measure of sexual arousal following erotic stimuli. Implications of the results for the conceptualization, diagnosis, and treatment of SAD are discussed. PMID:18343989

  8. Strategies for subtyping influenza viruses circulating in the Danish pig population

    DEFF Research Database (Denmark)

    Breum, Solvej Østergaard; Hjulsager, Charlotte Kristiane; Trebbien, Ramona;

    2010-01-01

    Influenza viruses are endemic in the Danish pig population and the dominant circulating subtypes are H1N1, a Danish H1N2 reassortant, and H3N2. Here we present our current and future strategies for influenza virus subtyping. For diagnostic and surveillance of influenza subtypes circulating...... in the Danish pig population functional and rapid subtyping assays are required. The conventional RT-PCR influenza subtyping assays developed by Chiapponi et al. (2003) have been implemented and used for typing of influenza viruses found positive in a pan influenza A real time RT-PCR assay. The H1 and N1 assays...... were specific when applied on Danish influenza positive samples, whereas the N2 assay consistently showed several unspecific PCR products. A subset of positive influenza samples detected by the real time RT-PCR screening assay could not be subtyped using these assays. Therefore, new influenza subtyping...

  9. Novel Multiplex PCR Assay for Characterization and Concomitant Subtyping of Staphylococcal Cassette Chromosome mec Types I to V in Methicillin-Resistant Staphylococcus aureus

    OpenAIRE

    Zhang, Kunyan; McClure, Jo-Ann; Elsayed, Sameer; Louie, Thomas; Conly, John M

    2005-01-01

    Staphylococcal cassette chromosome mec (SCCmec) typing is essential for understanding the molecular epidemiology of methicillin-resistant Staphylococcus aureus (MRSA). SCCmec elements are currently classified into types I to V based on the nature of the mec and ccr gene complexes, and are further classified into subtypes according to their junkyard region DNA segments. Previously described traditional SCCmec PCR typing schemes require multiple primer sets and PCR experiments, while a previous...

  10. Assessing the Differences in Public Health Impact of Salmonella Subtypes Using a Bayesian Microbial Subtyping Approach for Source Attribution

    DEFF Research Database (Denmark)

    Pires, Sara Monteiro; Hald, Tine

    2010-01-01

    . These differences presumably represent multiple factors, such as differences in survivability through the food chain and/or pathogenicity. The relative importance of the source-dependent factors varied considerably over the years, reflecting, among others, variability in the surveillance programs for the different......Salmonella is a major cause of human gastroenteritis worldwide. To prioritize interventions and assess the effectiveness of efforts to reduce illness, it is important to attribute salmonellosis to the responsible sources. Studies have suggested that some Salmonella subtypes have a higher health...... impact than others. Likewise, some food sources appear to have a higher impact than others. Knowledge of variability in the impact of subtypes and sources may provide valuable added information for research, risk management, and public health strategies. We developed a Bayesian model that attributes...

  11. Alcohol and breast cancer tumor subtypes in a Spanish Cohort.

    Science.gov (United States)

    Gago-Dominguez, Manuela; Castelao, J Esteban; Gude, Francisco; Fernandez, Maite Peña; Aguado-Barrera, Miguel E; Ponte, Sara Miranda; Redondo, Carmen M; Castelo, Manuel Enguix; Dominguez, Alejandro Novo; Garzón, Víctor Muñoz; Carracedo, Angel; Martínez, María Elena

    2016-01-01

    Although alcohol intake is an established risk factor for overall breast cancer, few studies have looked at the relationship between alcohol use and breast cancer risk by the four major subtypes of breast cancer and very few data exist in the alcohol-breast cancer relationship in Spanish women. A population-based case-control study was conducted in Galicia, Spain. A total of 1766 women diagnosed with invasive breast cancer between 1997 and 2014 and 833 controls participated in the study. Data on demographics, breast cancer risk factors, and clinico-pathological characteristics were collected. We examined the alcohol-breast cancer association according to the major breast cancer subtypes [hormone-receptor-positive, HER2-negative (luminal A); hormone-receptor-positive, HER2-positive (luminal B); hormone-receptor-negative, HER2-negative (TNBC); and hormone-receptor-negative, HER2-positive (HER2 overexpressing)] as well as grade and morphology in Spanish women. With the exception of HER2 overexpressing, the risk of all subtypes of breast cancer significantly increased with increasing alcohol intake. The association was similar for hormonal receptor positive breast cancer, i.e., luminal A and luminal B breast cancer (odds ratio, OR 2.16, 95 % confidence interval, CI 1.55-3.02; and OR 1.98, 95 % CI 1.11-3.53, respectively), and for TNBC (TNBC: OR 1.93, 95 % CI 1.07-3.47). The alcohol-breast cancer association was slightly more pronounced among lobular breast cancer (OR 2.76, 95 % CI 1.62-4.69) than among ductal type breast cancers (OR 2.21, 95 % CI 1.61-3.03). In addition, significant associations were shown for all grades, I, II and III breast cancer (OR 1.98, 95 % CI 1.26-3.10; OR 2.34, 95 % CI 1.66-3.31; and OR 2.16, 95 % CI 1.44-3.25 for Grades I, II and III, respectively). To our knowledge, this is the first study to examine the association of breast cancer subtypes and alcohol intake in Spanish women. Our findings indicate that breast cancer risk increased

  12. Use of ER/PR/HER2 subtypes in conjunction with the 2007 St Gallen Consensus Statement for early breast cancer

    Directory of Open Access Journals (Sweden)

    Parise Carol

    2010-05-01

    (ER-/PR-/HER2-; and (e ER-negativity appeared to be a stronger predictor of poor survival than HER2-positivity. Conclusion The use of ER/PR/HER2 subtype highlights the marked heterogeneity of the Intermediate and High Risk categories of the 2007 St Gallen statements. The use of ER/PR/HER2 subtypes and correlation with molecular classification of breast cancer is recommended.

  13. Relationship between detection of circulating tumor cells and molecular subtypes in breast cancer patients%联合多标志物检测乳腺癌外周血循环肿瘤细胞与分子分型的相关性及临床意义

    Institute of Scientific and Technical Information of China (English)

    吴娜萍; 肇毅; 王珏; 崇梅红; 薛旦旦; 凌立君; 王水

    2014-01-01

    Objective To investigate the correlation between circulating tumor cells (CTCs) and the predefined molecular classification of patients with breast cancer.Methods We used real-time quanti-tative reverse transcription-polymerase chain reaction (RT-qPCR) to detect cytokeratin 19 (CK19),human mammaglobin (hMAM),and small breast epithelial mucin (SBEM) mRNA expression levels in 285 cases of breast cancer and 123 controls.Statistical analyses were additionally performed to examine the correlation between the mRNA expression levels of these markers with the clinicopathological features of breast cancer patients.Results The sensitivity of these three mRNA markers of the patients with breast cancer was 33.3%,17.9%,and 18.2% respectively,which was significantly higher than the control group (P < 0.05).The sensitivity of these three markers combined was 47%,which was significantly higher than that of single marker detection (P < 0.05).However,no significant difference in CTC detection was noted among the predefined molecular classifications.Statistical analysis demonstrated that high expression levels of CTC were correlated with the age and menopause status (P < 0.05).In addition,overexpression of these three mRNA markers was positively correlated with tumor size (P < 0.05).Conclusion Combined detection of three markers (CK19,hMAM and SBEM) based on a RT-qPCR platform has higher sensitivity to detect CTC in peripheral blood of breast cancer patients.Although CTC have no clear correla-tion with breast cancer molecular subgroups,but close correlation with age,postmenopausal status and tumor size of patients with breast cancer.%目的 运用实时定量逆转录聚合酶链反应(RT-qPCR)法联合多标志物检测乳腺癌患者外周血循环肿瘤细胞(CTC),探讨其与乳腺癌分子分型的相关性.方法 通过RT-qPCR检测123例健康志愿者和乳腺良性疾病患者外周血细胞角蛋白19(CK19)、乳珠蛋白(hMAM)

  14. The prevalence and prognostic significance of KRAS mutation subtypes in lung adenocarcinomas from Chinese populations

    Directory of Open Access Journals (Sweden)

    Zheng DF

    2016-02-01

    Full Text Available Difan Zheng,1,2,* Rui Wang,1,2,* Yang Zhang,1,2 Yunjian Pan,1,2 Xinghua Cheng,3 Chao Cheng,1,2 Shanbo Zheng,1,2 Hang Li,1,2 Ranxia Gong,1,2 Yuan Li,2,4 Xuxia Shen,2,4 Yihua Sun,1,2 Haiquan Chen1–3,51Department of Thoracic Surgery, Fudan University Shanghai Cancer Center, 2Department of Oncology, Shanghai Medical College, Fudan University, 3Shanghai Chest Hospital, Shanghai Jiao Tong University, 4Department of Pathology, Fudan University Shanghai Cancer Center, 5Institutes of Biomedical Sciences, Fudan University, Shanghai, People’s Republic of China*These authors contributed equally to this workBackground: We performed this retrospective study to identify the prevalence of KRAS mutation in Chinese populations and make a comprehensive investigation of the clinicopathological features of KRAS mutation in these patients.Patients and methods: Patients from 2007 to 2013 diagnosed with primary lung adenocarcinoma who received a radical resection were examined for KRAS, EGFR, HER2, BRAF mutations, and ALK, RET, and ROS1 fusions. Clinicopathological features, including sex, age, tumor–lymph node–metastasis stage, tumor differentiation, smoking status, histological subtypes, and survival information were analyzed.Result: KRAS mutation was detected in 113 of 1,368 patients. Nine different subtypes of KRAS mutation were identified in codon 12, codon 13, and codon 61. KRAS mutation was more frequently found in male patients and former/current smoker patients. Tumors with KRAS mutation had poorer differentiation. Invasive mucinous adenocarcinoma predominant and solid predominant subtypes were more frequent in KRAS mutant patients. No statistical significance was found in relapse-free survival or overall survival between patients with KRAS mutation and patients with other mutations.Conclusion: In Chinese populations, we identified KRAS mutation in 8.3% (113/1,368 of the patients with lung adenocarcinoma. KRAS mutation defines a molecular subset of

  15. Subtype specific elevated expression of hyaluronidase-1 (HYAL-1 in epithelial ovarian cancer.

    Directory of Open Access Journals (Sweden)

    Paule Héléna Yoffou

    Full Text Available BACKGROUND: Epithelial ovarian cancer (EOC is morphologically heterogeneous being classified as serous, endometrioid, clear cell, or mucinous. Molecular genetic analysis has suggested a role for tumor suppressor genes located at chromosome 3p in serous EOC pathogenesis. Our objective was to evaluate the expression of HYAL1, located at chromosome 3p21.3, in these EOC subtypes, and to investigate its correlation with the expression of steroid hormone receptors. METHODOLOGY/PRINCIPAL FINDINGS: We determined the mRNA expression of HYAL1, estrogen receptor (ER-α, ERβ and progesterone receptor (PR in EOC tumor samples and cell lines using quantitative RT-PCR. We also examined the expression of these genes in a publicly available microarray dataset. HYAL-1 enzyme activity was measured in EOC cell lines and in plasma samples from patients. We found that HYAL1 mRNA expression was elevated in clear cell and mucinous EOC tissue samples, but not in serous and endometrioid samples, normal ovaries or benign tumors. Similar results were obtained by two different techniques and with tissue sample cohorts from two independent institutions. Concordantly, HYAL1 mRNA levels and enzymatic activity were elevated only in EOC cell lines derived from clear cell and mucinous subtypes. We also showed that HYAL1 mRNA was inversely correlated to that of ERα specifically in clear cell and mucinous EOCs. Additionally, ectopic expression of ERα in a clear cell EOC cell line (ER- and PR-negative induced 50% reduction of HYAL1 mRNA expression, supporting a role of ERα in HYAL1 gene regulation. Significantly, HYAL-1 activity was also high in the plasma of patients with these EOC subtypes. CONCLUSIONS/SIGNIFICANCE: This is the first report showing high HYAL-1 levels in EOC and demonstrating HYAL1 gene repression by ERα. Our results identify Hyaluronidase-1 as a potential target/biomarker for clear cell and mucinous EOCs and especially in tumors with low ERα levels.

  16. β-Adrenergic receptor subtype signaling in heart:From bench to bedside

    Institute of Scientific and Technical Information of China (English)

    Anthony Yiu Ho WOO; Rui-ping XIAO

    2012-01-01

    β-Adrenergic receptor (βAR) stimulation by the sympathetic nervous system or circulating catecholamines is broadly involved in peripheral blood circulation,metabolic regulation,muscle contraction,and central neural activities.In the heart,acute βAR stimulation serves as the most powerful means to regulate cardiac output in response to a fight-or-flight situation,whereas chronic βAR stimulation plays an important role in physiological and pathological cardiac remodeling.There are three βAR subtypes,β1AR,β2AR and β3AR,in cardiac myocytes.Over the past two decades,we systematically investi-gated the molecular and cellular mechanisms underlying the different even opposite functional roles of β1AR and β2AR subtypes in regulating cardiac structure and function,with keen interest in the development of novel therapies based on our discoveries.We have made three major discoveries,including (1) dual coupling of β2AR to Gs and Gi proteins in cardiomyocytes,(2) cardioprotection by β2AR signaling in improving cardiac function and myocyte viability,and (3) PKA-independent,CaMKII-mediated β1AR apoptotic and maladaptive remodeling signaling in the heart.Based on these discoveries and salutary effects of β1AR blockade on patients with heart failure,we envision that activation of β2AR in combination with clinically used β1AR blockade should provide a safer and more effective therapy for the treatment of heart failure.

  17. Data Perturbation Independent Diagnosis and Validation of Breast Cancer Subtypes Using Clustering and Patterns

    Directory of Open Access Journals (Sweden)

    G. Alexe

    2006-01-01

    Full Text Available Molecular stratification of disease based on expression levels of sets of genes can help guide therapeutic decisions if such classifications can be shown to be stable against variations in sample source and data perturbation. Classifications inferred from one set of samples in one lab should be able to consistently stratify a different set of samples in another lab. We present a method for assessing such stability and apply it to the breast cancer (BCA datasets of Sorlie et al. 2003 and Ma et al. 2003. We find that within the now commonly accepted BCA categories identified by Sorlie et al. Luminal A and Basal are robust, but Luminal B and ERBB2+ are not. In particular, 36% of the samples identified as Luminal B and 55% identified as ERBB2+ cannot be assigned an accurate category because the classification is sensitive to data perturbation. We identify a “core cluster” of samples for each category, and from these we determine “patterns” of gene expression that distinguish the core clusters from each other. We find that the best markers for Luminal A and Basal are (ESR1, LIV1, GATA-3 and (CCNE1, LAD1, KRT5, respectively. Pathways enriched in the patterns regulate apoptosis, tissue remodelling and the immune response. We use a different dataset (Ma et al. 2003 to test the accuracy with which samples can be allocated to the four disease subtypes. We find, as expected, that the classification of samples identified as Luminal A and Basal is robust but classification into the other two subtypes is not.

  18. Reviewing the history of HIV-1: spread of subtype B in the Americas.

    Science.gov (United States)

    Junqueira, Dennis Maletich; de Medeiros, Rúbia Marília; Matte, Maria Cristina Cotta; Araújo, Leonardo Augusto Luvison; Chies, Jose Artur Bogo; Ashton-Prolla, Patricia; Almeida, Sabrina Esteves de Matos

    2011-01-01

    The dispersal of HIV-1 subtype B (HIV-1B) is a reflection of the movement of human populations in response to social, political, and geographical issues. The initial dissemination of HIV-1B outside Africa seems to have included the passive involvement of human populations from the Caribbean in spreading the virus to the United States. However, the exact pathways taken during the establishment of the pandemic in the Americas remain unclear. Here, we propose a geographical scenario for the dissemination of HIV-1B in the Americas, based on phylogenetic and genetic statistical analyses of 313 available sequences of the pol gene from 27 countries. Maximum likelihood and bayesian inference methods were used to explore the phylogenetic relationships between HIV-1B sequences, and molecular variance estimates were analyzed to infer the genetic structure of the viral population. We found that the initial dissemination and subsequent spread of subtype B in the Americas occurred via a single introduction event in the Caribbean around 1964 (1950-1967). Phylogenetic trees present evidence of several primary outbreaks in countries in South America, directly seeded by the Caribbean epidemic. Cuba is an exception insofar as its epidemic seems to have been introduced from South America. One clade comprising isolates from different countries emerged in the most-derived branches, reflecting the intense circulation of the virus throughout the American continents. Statistical analysis supports the genetic compartmentalization of the virus among the Americas, with a close relationship between the South American and Caribbean epidemics. These findings reflect the complex establishment of the HIV-1B pandemic and contribute to our understanding between the migration process of human populations and virus diffusion.

  19. KLK6-regulated miRNA networks activate oncogenic pathways in breast cancer subtypes.

    Science.gov (United States)

    Sidiropoulos, Konstantinos G; Ding, Qiang; Pampalakis, Georgios; White, Nicole M A; Boulos, Peter; Sotiropoulou, Georgia; Yousef, George M

    2016-08-01

    KLK6 is expressed in normal mammary tissues and is aberrantly regulated in breast cancer. At physiological levels of expression, i.e. those found in normal mammary tissues, KLK6 acts as a tumor suppressor in human breast cancer. However, aberrant overexpression of KLK6 (i.e. 50-100-fold higher than normal), a characteristic of a subset of human breast cancers is associated with increased tumorigenicity (Pampalakis et al. Cancer Res 69:3779-3787, 2009). Here, we stably transfected KLK6-non-expressing MDA-MB-231 breast cancer cells with the full-length KLK6 cDNA to overexpress KLK6 at levels comparable to those observed in patients, and investigated potential oncogenic miRNA networks regulated by these abnormally high KLK6 expression levels and increased activity of this serine protease. A number of miRNAs that are upregulated (e.g. miR-146a) or downregulated (e.g. miR-34a) via KLK6-induced alterations in the miRNA biogenesis machinery were identified. Integrated experimental and bioinformatics analyses identified convergent miRNA networks targeting the cell cycle, MYC, MAPK, and other signaling pathways. In large clinical datasets, significant correlations between KLK6 and downstream MAPK and MYC targets at both the RNA and protein levels was confirmed, as well as negative correlation with GATA3. It was also demonstrated that KLK6 overexpression and likely its proteolytic activity is associated with alterations in downstream miRNAs and their targets, and these differ with the molecular subtypes of breast cancer. The data partly explains the different characteristics of breast cancer subtypes. Importantly, we introduce a combined KLK6-CDKN1B+MYC+CDKN1C score for prediction of long-term patient survival outcomes, with higher scores indicating poor survival. PMID:27093921

  20. Duration of cross-protection between subtypes A and B avian pneumovirus in turkeys.

    Science.gov (United States)

    Van de Zande, S; Nauwynck, H; Naylor, C; Pensaert, M

    2000-07-29

    The degree and duration of clinical and virological cross-protection between avian pneumovirus subtypes A and B were examined in two-week-old pneumovirus antibody-free turkeys. The turkeys were inoculated with either a virulent subtype A (Belgian isolate A/T6/96), a virulent subtype B (Belgian isolate B/T9/96), an attenuated subtype A or an attenuated subtype B, and challenged homologously and heterologously with virulent avian pneumovirus two, five and 11 weeks after inoculation. Birds inoculated with virulent A or B virus showed typical respiratory signs from three to seven days after inoculation. After challenge, no clinical signs were observed in any of the groups, and no virus was isolated from the turkeys that had been initially inoculated with a virulent strain. Virulent virus was recovered from the birds that had been initially inoculated with attenuated subtypes and challenged five and/or 11 weeks later with a heterologous virulent strain. Birds challenged after five weeks showed a serological booster reaction only when they had been inoculated initially with a virulent or attenuated subtype B and challenged with subtype A. Seroconversion was observed in all the groups challenged after 11 weeks except when they had been inoculated initially with attenuated subtype B and challenged with subtype B.

  1. In silico modification of oseltamivir as neuraminidase inhibitor of influenza A virus subtype H1N1

    Institute of Scientific and Technical Information of China (English)

    Usman Sumo Friend Tambunan; Rizky Archintya Rachmania; Arli Aditya Parikesit

    2015-01-01

    This research focused on the modification of the functional groups of oseltamivir as neuraminidase inhibitor against influenza A virus subtype H1N1.Interactions of three of the best ligands were evaluated in the hydrated state using molecular dynamics simulation at two different temperatures.The docking result showed that AD3BF2D ligand (N-[(1S,6R)-5-amino-5-{[(2R,3S,4S)-3,4-dihydroxy-4-(hydroxymethyl) tetrahydrofuran-2-yl]oxy}-4-formylcyclohex-3-en-l-yl]acetamide-3-(1-ethylpropoxy)-1-cyclohexene-1-carboxylate) had better binding energy values than standard oseltamivir.AD3BF2D had several interactions,including hydrogen bonds,with the residues in the catalytic site of neuraminidase as identified by molecular dynamics simulation.The results showed that AD3BF2D ligand can be used as a good candidate for neuraminidase inhibitor to cope with influenza A virus subtype H1N1.

  2. Response features of parvalbumin-expressing interneurons suggest precise roles for subtypes of inhibition in visual cortex

    Science.gov (United States)

    Runyan, Caroline A.; Schummers, James; Wart, Audra Van; Kuhlman, Sandra J.; Wilson, Nathan R.; Huang, Z. Josh; Sur, Mriganka

    2010-01-01

    Summary Inhibitory interneurons in the cerebral cortex include a vast array of subtypes, varying in their molecular signatures, electrophysiological properties, and connectivity patterns. This diversity suggests that individual inhibitory classes have unique roles in cortical circuits; however, their characterization to date has been limited to broad classifications including many subtypes. We used the Cre/LoxP system, specifically labeling parvalbumin(PV)-expressing interneurons in visual cortex of PV-Cre mice with red fluorescent protein (RFP), followed by targeted loose-patch recordings and two-photon imaging of calcium responses in vivo to characterize the visual receptive field properties of these cells. Despite their relative molecular and morphological homogeneity, we find that PV+ neurons have a diversity of feature-specific visual responses that include sharp orientation and direction-selectivity, small receptive fields, and bandpass spatial frequency tuning. These results suggest that subsets of parvalbumin interneurons are components of specific cortical networks, and that perisomatic inhibition contributes to the generation of precise response properties. PMID:20826315

  3. Salmonella serotyping and molecular subtyping analysis on diarrhea cases in Hongkou District of Shanghai, in 2010-2012 ZHANG Jing1,SHEN Jing1,TANG Yi-ling1,CHEN Zhen1,YAO Hong1,WANG%上海市虹口区2010-2012年腹泻病例沙门菌监测及分子型特征

    Institute of Scientific and Technical Information of China (English)

    张静; 沈静; 唐漪灵; 陈真; 姚红; 王斌; 汤显; 陈洪友; 许学斌

    2015-01-01

    Objective ] To study the molecular characteristics and antibiotic resistance of Salmonella diarrhea cases in sentinel hospitals through active surveillance system conducted by public health laboratory. [ Methods] Two sentinel hospitals were chosen for collection of stool specimens from food-borne infectious diarrhea cases and for Salmonella separation and detection immediately following serotyping and antimicrobial susceptible test ( AST ) on those isolates .Moreover , pulsed field gel electrophoresis ( PFGE) was used for the genetic homology analysis . [ Results] A total of 2 579 diarrhea specimens were collected and analyzed from 2010 to 2012, with 185 Salmonella isolates, covering 23 different serotypes (annual positive rates were 9.1%, 6.8%, 5.1%, with an average 7.2%).Salmonella enterica serovar Enteritidis(S.Enteritidis) and Typhimurium(S.Typhimurium) were the most common serotypes, of which 68.9% cases were seen in those aged 21 to 60 and 21.4% cases in those over 60 years old. 27.7%-96.9%S.Enteritidis and 2.6%-63.2% S.Typhimurium(P all <0.05) proved resistant to Nalidixic acid, Sultisoxazole, Streptomycin, Sulfamethoxydiazine, Gentamicinand Tetracycline. PFGE analysis on 22 S.Enteritidis strains showed 11 different clusters , while 20 S.Typhimurium strians showed 6. [Conclusion] S.Enteritidis and S.Typhimurium are the most common Salmonella serotypes, and molecular typing indicates the existence of clustering and sporadic outbreaks caused by dominance clones . We should be alert to early warnings on potential outbreaks of multiple-drug-resistant ( MDR ) S.Enteritidis.Active surveillance system based on public health laboratory should play an important role in the control of food-borne infectious diseases .%[目的]研究基于公共卫生实验室主动监测哨点医院沙门菌腹泻及优势菌型的耐药性和分子型特征。[方法]选择辖区内2家医院作为主动监测哨点,甄别食源性感染性腹泻的病

  4. Genomic instability influences the transcriptome and proteome in endometrial cancer subtypes

    Directory of Open Access Journals (Sweden)

    Habermann Jens K

    2011-10-01

    Full Text Available Abstract Background In addition to clinical characteristics, DNA aneuploidy has been identified as a prognostic factor in epithelial malignancies in general and in endometrial cancers in particular. We mapped ploidy-associated chromosomal aberrations and identified corresponding gene and protein expression changes in endometrial cancers of different prognostic subgroups. Methods DNA image cytometry classified 25 endometrioid cancers to be either diploid (n = 16 or aneuploid (n = 9, and all uterine papillary serous cancers (UPSC to be aneuploid (n = 8. All samples were subjected to comparative genomic hybridization and gene expression profiling. Identified genes were subjected to Ingenuity pathway analysis (IPA and were correlated to protein expression changes. Results Comparative genomic hybridization revealed ploidy-associated specific, recurrent genomic imbalances. Gene expression analysis identified 54 genes between diploid and aneuploid endometrioid carcinomas, 39 genes between aneuploid endometrioid cancer and UPSC, and 76 genes between diploid endometrioid and aneuploid UPSC to be differentially expressed. Protein profiling identified AKR7A2 and ANXA2 to show translational alterations consistent with the transcriptional changes. The majority of differentially expressed genes and proteins belonged to identical molecular functions, foremost Cancer, Cell Death, and Cellular Assembly and Organization. Conclusions We conclude that the grade of genomic instability rather than the histopathological subtype correlates with specific gene and protein expression changes. The identified genes and proteins might be useful as molecular targets for improved diagnostic and therapeutic intervention and merit prospective validation.

  5. Rate of renal cell carcinoma subtypes in different races

    Directory of Open Access Journals (Sweden)

    Alexander Sankin

    2011-02-01

    Full Text Available PURPOSE: We sought to identify racial differences among histological subtypes of renal cell carcinoma (RCC between black and non-black patients in an equal-access health care system. MATERIALS AND METHODS: We established a multi-institutional, prospective database of patients undergoing partial or radical nephrectomy between January 1, 2000 and Sept 31, 2009. For the purposes of this study, data captured included age at diagnosis, race, tumor size, presence of lymphovascular invasion, presence of capsular invasion, margin status, and tumor histology. RESULTS: 204 kidney tumors were identified (Table-1. Of these, 117 (57.4% were in black patients and 87 (42.6% were in non-black patients. Age at surgery ranged from 37 to 87 with a median of 62. Tumor size ranged from 1.0 to 22.0 cm with a median of 5.0 cm. Overall, tumors were composed of clear cell RCC in 97 cases (47.5%, papillary RCC in 65 cases (31.9%, chromophobe RCC in 13 cases (6.4%, collecting duct/medullary RCC in 2 cases (1.0%, RCC with multiple histological subtypes in 8 cases (3.9%, malignant tumors of other origin in 6 cases (2.9%, and benign histology in 13 cases (6.4%. Among black patients, papillary RCC was seen in 56 cases (47.9%, compared to 9 cases (10.3% among non-black patients (p < 0.001 (Table-2. Clear cell RCC was present in 38 (32.5% of black patients and in 59 (67.8% of non-blacks (p < 0.001. CONCLUSIONS: In our study, papillary RCC had a much higher occurrence among black patients compared to non-black patients. This is the first study to document such a great racial disparity among RCC subtypes.

  6. Differences in oxidative stress dependence between gastric adenocarcinoma subtypes

    Institute of Scientific and Technical Information of China (English)

    Brigitte Bancel; Jacques Estève; Jean-Christophe Souquet; Shinya Toyokuni; Hiroshi Ohshima; Brigitte Pignatelli

    2006-01-01

    AIM: To investigate the extent of oxidative stress in preneoplastic and neoplastic gastric mucosa in relation to their pathological criteria and histological subtypes.METHODS: A total of 104 gastric adenocarcinomas from 98 patients (88 infiltrative and 16 intraepithelial tumors)were assessed immunohistochemically for expression of iNOS and occurrence of nitrotyrosine (NTYR)-containing proteins and 8-hydroxy-2'-deoxyguanosine (8-OHdG)-containing DNA, as markers of NO production and damages to protein and DNA.RESULTS: Tumor cells staining for iNOS, NTYR and 8-OH-dG were detected in 41%, 62% and 50% of infiltrative carcinoma, respectively. The three markers were shown for the first time in intraepithelial carcinoma.The expression of iNOS was significantly more frequent in tubular carcinoma (TC) compared to diffuse carcinoma (DC) (54% vs 18%; P=0.008) or in polymorphous carcinoma (PolyC) (54% vs 21%; P=0.04). NTYR staining was obviously more often found in TC than that in PolyC (72% vs 30%; P=0.03). There was a tendency towards a higher rate of iNOS staining when distant metastasis (pM) was present. In infiltrative TC, the presence of oxidative stress markers was not significantly correlated with histological grade, density of inflammation, the depth of infiltration (pT), lymph nodes dissemination (pN) and pathological stages (pTNM).CONCLUSION: The iNOS-oxidative pathway may play an important role in TC, but moderately in PolyC and DC.DNA oxidation and protein nitration occur in the three subtypes. Based on the significant differences of NTYR levels, TC and PolyC appear as two distinct subtypes.

  7. Classification of Neuronal Subtypes in the Striatum and the Effect of Neuronal Heterogeneity on the Activity Dynamics

    OpenAIRE

    Bekkouche, Bo

    2016-01-01

    Clustering of single-cell RNA sequencing data is often used to show what states and subtypes cells have. Using this technique, striatal cells were clustered into subtypes using different clustering algorithms. Previously known subtypes were confirmed and new subtypes were found. One of them is a third medium spiny neuron subtype. Using the observed heterogeneity, as a second task, this project questions whether or not differences in individual neurons have an impact on the network dynamics. B...

  8. Applicable advances in the molecular pathology of glioblastoma.

    Science.gov (United States)

    Ranjit, Melissa; Motomura, Kazuya; Ohka, Fumiharu; Wakabayashi, Toshihiko; Natsume, Atsushi

    2015-07-01

    Comprising more than 80% of malignant brain tumors, glioma has proven to be a daunting cause of mortality in a vast majority of the human population. Progressive and extensive research on malignant glioma has substantially enhanced our understanding of glioma cell biology and molecular pathology. Subtypes of glioma such as astrocytoma and oligodendroglioma are currently grouped together into one pathological class, where they show many differences in histology and molecular etiology. This indicates that it may be beneficial to consider a new and radical subclassification. Thus, we summarize recent developments in glioblastoma multiforme (GBM) subtypes, immunohistochemical analyses useful for diagnoses and the biological evaluation and therapeutic implications of gliomas in this review.

  9. Alcohol and breast cancer tumor subtypes in a Spanish Cohort

    OpenAIRE

    Gago-Dominguez, Manuela; Castelao, J.Esteban; Gude, Francisco; Fernandez, Maite Peña; Miguel E. Aguado-Barrera; Ponte, Sara Miranda; Carmen M Redondo; Castelo, Manuel Enguix; Dominguez, Alejandro Novo; Garzón, Víctor Muñoz; Carracedo, Angel; Martínez, María Elena

    2016-01-01

    Although alcohol intake is an established risk factor for overall breast cancer, few studies have looked at the relationship between alcohol use and breast cancer risk by the four major subtypes of breast cancer and very few data exist in the alcohol-breast cancer relationship in Spanish women. A population-based case-control study was conducted in Galicia, Spain. A total of 1766 women diagnosed with invasive breast cancer between 1997 and 2014 and 833 controls participated in the study. Data...

  10. Subtyping of breast cancer using reverse phase protein arrays.

    Science.gov (United States)

    Sonntag, Johanna; Schlüter, Kerstin; Bernhardt, Stephan; Korf, Ulrike

    2014-12-01

    Reverse phase protein arrays (RPPAs) present a robust and sensitive high capacity platform for targeted proteomics that relies on highly specific antibodies to obtain a quantitative readout regarding phosphorylation state and abundance of proteins of interest. This review summarizes the current state of RPPA-based proteomic profiling of breast cancer in the context of existing preanalytical strategies and sample preparation protocols. RPPA-based subtypes identified so far are compared to those obtained by other approaches such as immunohistochemistry, genomics and transcriptomics. Special attention is given to discussing the potential of RPPA for biomarker discovery and biomarker validation. PMID:25400094

  11. CRISPR adaptation in Escherichia coli subtypeI-E system.

    Science.gov (United States)

    Kiro, Ruth; Goren, Moran G; Yosef, Ido; Qimron, Udi

    2013-12-01

    The CRISPRs (clustered regularly interspaced short palindromic repeats) and their associated Cas (CRISPR-associated) proteins are a prokaryotic adaptive defence system against foreign nucleic acids. The CRISPR array comprises short repeats flanking short segments, called 'spacers', which are derived from foreign nucleic acids. The process of spacer insertion into the CRISPR array is termed 'adaptation'. Adaptation allows the system to rapidly evolve against emerging threats. In the present article, we review the most recent studies on the adaptation process, and focus primarily on the subtype I-E CRISPR-Cas system of Escherichia coli.

  12. Substance Use Disorders and Suicide Attempts in Bipolar Subtypes

    OpenAIRE

    Sublette, M Elizabeth; Carballo, Juan J; Moreno, Carmen; Galfalvy, Hanga C.; Brent, David A.; BIRMAHER, BORIS; Mann, J. John; OQUENDO, MARIA A.

    2008-01-01

    Bipolar disorder (BD) is associated with high rates of suicide attempt and completion. Substance use disorders (SUD) have been identified as potent risk factors for suicidal behavior in BD. However, little is known concerning differences between BD subtypes with regard to SUD as a risk factor for suicidal behavior. We studied previous suicidal behavior in adults with a major depressive episode in context of BD type I (BD-I; N=96) or BD type II (BD-II; N=42), with and without history of SUD. L...

  13. Gene expression patterns unveil a new level of molecular heterogeneity in colorectal cancer.

    Science.gov (United States)

    Budinska, Eva; Popovici, Vlad; Tejpar, Sabine; D'Ario, Giovanni; Lapique, Nicolas; Sikora, Katarzyna Otylia; Di Narzo, Antonio Fabio; Yan, Pu; Hodgson, John Graeme; Weinrich, Scott; Bosman, Fred; Roth, Arnaud; Delorenzi, Mauro

    2013-09-01

    The recognition that colorectal cancer (CRC) is a heterogeneous disease in terms of clinical behaviour and response to therapy translates into an urgent need for robust molecular disease subclassifiers that can explain this heterogeneity beyond current parameters (MSI, KRAS, BRAF). Attempts to fill this gap are emerging. The Cancer Genome Atlas (TGCA) reported two main CRC groups, based on the incidence and spectrum of mutated genes, and another paper reported an EMT expression signature defined subgroup. We performed a prior free analysis of CRC heterogeneity on 1113 CRC gene expression profiles and confronted our findings to established molecular determinants and clinical, histopathological and survival data. Unsupervised clustering based on gene modules allowed us to distinguish at least five different gene expression CRC subtypes, which we call surface crypt-like, lower crypt-like, CIMP-H-like, mesenchymal and mixed. A gene set enrichment analysis combined with literature search of gene module members identified distinct biological motifs in different subtypes. The subtypes, which were not derived based on outcome, nonetheless showed differences in prognosis. Known gene copy number variations and mutations in key cancer-associated genes differed between subtypes, but the subtypes provided molecular information beyond that contained in these variables. Morphological features significantly differed between subtypes. The objective existence of the subtypes and their clinical and molecular characteristics were validated in an independent set of 720 CRC expression profiles. Our subtypes provide a novel perspective on the heterogeneity of CRC. The proposed subtypes should be further explored retrospectively on existing clinical trial datasets and, when sufficiently robust, be prospectively assessed for clinical relevance in terms of prognosis and treatment response predictive capacity. Original microarray data were uploaded to the ArrayExpress database (http

  14. Relationship between the prognostic and predictive value of the intrinsic subtypes and a validated gene profile predictive of loco-regional control and benefit from post-mastectomy radiotherapy in patients with high-risk breast cancer

    DEFF Research Database (Denmark)

    Tramm, Trine; Kyndi, Marianne; Myhre, Simen;

    2014-01-01

    BACKGROUND: Breast cancer is characterized by great molecular heterogeneity demonstrated, e.g. by the intrinsic subtypes. Administration of post-mastectomy radiotherapy (PMRT) does, however, not reflect this heterogeneity. A gene profile (DBCG-RT profile) has recently been developed and validated...... of triple negative patients with high risk of LRR and significant benefit from PMRT. Agreement in the different assignments of tumors to the subtypes was suboptimal, and the clinical outcome and predicted benefit from PMRT varied according to the method used for assignment. CONCLUSION: The prognostic...

  15. Internalizing and Externalizing Subtypes in Female Sexual Assault Survivors: Implications for the Understanding of Complex PTSD

    OpenAIRE

    Miller, Mark W.; Resick, Patricia A.

    2006-01-01

    This study replicated and extended findings of internalizing and externalizing subtypes of posttraumatic psychopathology (Miller, M. W., Greif, J. L., & Smith, A. A. (2003). Multidimensional Personality Questionnaire profiles of veterans with traumatic combat exposure: Internalizing and externalizing subtypes. Psychological Assessment, 15, 205–215; Miller, M. W., Kaloupek, D. G., Dillon, A. L., & Keane, T.M. (2004). Externalizing and internalizing subtypes of combat-related PTSD: A replicatio...

  16. Respiratory panic disorder subtype and sensitivity to the carbon dioxide challenge test

    OpenAIRE

    A.M. Valença; A.E. Nardi; Nascimento, I.; W.A. Zin; M. Versiani

    2002-01-01

    The aim of the present study was to verify the sensitivity to the carbon dioxide (CO2) challenge test of panic disorder (PD) patients with respiratory and nonrespiratory subtypes of the disorder. Our hypothesis is that the respiratory subtype is more sensitive to 35% CO2. Twenty-seven PD subjects with or without agoraphobia were classified into respiratory and nonrespiratory subtypes on the basis of the presence of respiratory symptoms during their panic attacks. The tests were carried out in...

  17. A comparison of agonist-specific coupling of cloned human α2-adrenoceptor subtypes

    OpenAIRE

    Rudling, Jane E; Richardson, Jo; Evans, Peter D.

    2000-01-01

    The agonist-specific coupling properties of the three cloned human α2-adrenoceptor subtypes have been compared, when expressed at similar levels in Chinese hamster ovary (CHO) cell lines, using noradrenaline and (±)-meta-octopamine as agonists.Noradrenaline can couple the receptor to both the inhibition and stimulation of forskolin-stimulated cyclic AMP production in all three receptor subtypes, with the relative strength of the coupling to the pathways varying for each of the receptor subtyp...

  18. Reproductive History and Risk of Three Breast Cancer Subtypes Defined by Three Biomarkers

    OpenAIRE

    Phipps, Amanda I.; Buist, Diana S. M.; Malone, Kathleen E.; Barlow, William E.; Porter, Peggy L.; Kerlikowske, Karla; Li, Christopher I.

    2010-01-01

    Breast cancer subtypes defined by estrogen-receptor (ER), progesterone-receptor (PR), and HER2 expression are biologically distinct and, thus, may have distinct etiologies. In particular, it is plausible that risk factors operating through hormonal mechanisms are differentially related to risk of such tumor subtypes. Using data from the Breast Cancer Surveillance Consortium, we explored associations between reproductive history and three breast cancer subtypes. Data on parity and age at first...

  19. The Association of Anxiety With the Subtypes of Premature Ejaculation: A Chart Review

    OpenAIRE

    Rajkumar, Ravi Philip; Kumaran, Arun Kumar

    2014-01-01

    Objective: Premature ejaculation is one of the most common forms of male sexual dysfunction. Recent clinical and genetic evidence suggests that it can be classified into 4 subtypes, which may have distinct clinical profiles. Psychological factors, such as anxiety, may play a specific role in the acquired subtype. The objective of this study was to assess the association between psychological factors, particularly anxiety and marital disharmony, and the various subtypes of premature ejaculation.

  20. Associations between subtypes of major depressive episodes and substance use disorders

    OpenAIRE

    Marmorstein, Naomi R.

    2010-01-01

    The goal of this study was to examine whether certain subtypes of major depressive episodes (MDEs)—defined by their particular constellations of symptoms—were more strongly associated with substance use disorders (SUDs), compared to other subtypes of MDEs. Participants were adults in the National Comorbidity Survey-Replication sample who met DSM criteria for at least one lifetime MDE (n=1829). Diagnostic assessments were conducting using structured interviews. The following MDE subtypes were ...

  1. Listeria monocytogenes: Strain Heterogeneity, Methods, and Challenges of Subtyping.

    Science.gov (United States)

    Nyarko, Esmond B; Donnelly, Catherine W

    2015-12-01

    Listeria monocytogenes is a food-borne bacterial pathogen that is associated with 20% to 30% case fatality rate. L. monocytogenes is a genetically heterogeneous species, with a small fraction of strains (serotypes 1/2a, 1/2b, 4b) implicated in human listeriosis. Monitoring and source tracking of L. monocytogenes involve the use of subtyping methods, with the performance of genetic-based methods found to be superior to phenotypic-based ones. Various methods have been used to subtype L. monocytogenes isolates, with the pulsed-field gel electrophoresis (PFGE) being the gold standard. Although PFGE has had a massive impact on food safety through the establishment of the PulseNet, there is no doubt that whole genome sequence (WGS) typing is accurate, has a discriminatory power superior to any known method, and allows genome-wide differences between strains to be quantified through the comparison of nucleotide sequences. This review focuses on the different techniques that have been used to type L. monocytogenes strains, their performance challenges, and the tremendous impact WGS typing could have on the food safety landscape. PMID:26588067

  2. Adult interpersonal features of subtypes of sexual offenders.

    Science.gov (United States)

    Sigre-Leirós, Vera; Carvalho, Joana; Nobre, Pedro J

    2015-08-01

    Although the role of interpersonal factors on sexual offending is already recognized, there is a need for further investigation on the psychosocial correlates of pedophilic behavior. This study aimed to examine the relationship between adult interpersonal features and subtypes of sexual offending. The study involved the participation of a total of 164 male convicted offenders namely 50 rapists, 63 child molesters (20 pedophilic and 43 nonpedophilic), and 51 nonsexual offenders. All participants were assessed using the Adult Attachment Scale, the Interpersonal Behavior Survey, the Brief Symptom Inventory, and the Socially Desirable Response Set Measure. Results from sets of multinomial logistic regression analyses showed that pedophilic offenders were more likely to present anxiety in adult relationships compared to nonsex offenders. Likewise, nonpedophilic child molesters were less likely to be generally aggressive compared to rapists and nonsex offenders, as well as less generally assertive than rapists. Overall, findings indicated that certain interpersonal features characterized subtypes of offenders, thus providing some insight on their particular therapeutic needs. Further replications with larger samples particularly of pedophilic child molesters are required. PMID:26165651

  3. Subtype Identification of Avian Influenza Virus on DNA Microarray

    Institute of Scientific and Technical Information of China (English)

    WANG Xiu-rong; YU Kang-zhen; DENG Guo-hua; SHI Rui; LIU Li-ling; QIAO Chuan-ling; BAO Hong-mei; KONG Xian-gang; CHEN Hua-lan

    2005-01-01

    We have developed a rapid microarray-based assay for the reliable detection of H5, H7 and H9 subtypes of avian influenza virus (AIV). The strains used in the experiment were A/Goose/Guangdong/1/96 (H5N1), A/African starling/983/79 (H7N1) and A/Turkey/Wiscosin/1/66 (H9N2). The capture DNAs clones which encoding approximate 500-bp avian influenza virus gene fragments obtained by RT-PCR, were spotted on a slide-bound microarray. Cy5-1abeled fluorescent cDNAs,which generated from virus RNA during reverse transcription were hybridized to these capture DNAs. These capture DNAs contained multiple fragments of the hemagglutinin and matrix protein genes of AIV respectively, for subtyping and typing AIV. The arrays were scanned to determine the probe binding sites. The hybridization pattern agreed approximately with the known grid location of each target. The results show that DNA microarray technology provides a useful diagnostic method for AIV.

  4. CT assessment of subtypes of pulmonary emphysema in females

    International Nuclear Information System (INIS)

    We performed a retrospective study examining the prevalence and subtypes of pulmonary emphysema (PE) identified by computed tomography (CT) in females. We reviewed the records of 1,687 female subjects who had undergone CT. They were divided into the following 2 age groups: group A (<50 years) and group B (≥50 years). PE was diagnosed by the presence of low-attenuation areas using visual assessment (grades 0-3) on CT images. Two subtypes of PE were observed: centrilobular emphysema (CLE) and paraseptal emphysema (PSE). PE was divided into the following 3 categories: I (CLE or CLE-predominant); II (CLE and PSE of equal extent); and III (PSE or PSE-predominant). PE was found in 64 of 274 smokers (23.3%) and 54 of 1,413 non-smokers (3.8%). In smoking subjects, when grades 1 and 2 were grouped together as mild PE, the mean age for CT grade 3 (severe PE) was significantly higher than that for mild PE. In group A, category III predominated, whereas category I was more prevalent in group B, in both smoking and non-smoking subjects. A high incidence of PE was found in smoking subjects as compared with non-smoking subjects. PSE predominated in younger subjects, whereas CLE predominated in older subjects. (author)

  5. CT Assessment of Subtypes of Pulmonary Emphysema in Females

    Directory of Open Access Journals (Sweden)

    Togami,Taro

    2011-02-01

    Full Text Available We performed a retrospective study examining the prevalence and subtypes of pulmonary emphysema (PE identified by computed tomography (CT in females. We reviewed the records of 1,687 female subjects who had undergone CT. They were divided into the following 2 age groups:group A (<50 years and group B (>_50 years. PE was diagnosed by the presence of low-attenuation areas using visual assessment (grades 0-3 on CT images. Two subtypes of PE were observed:centrilobular emphysema (CLE and paraseptal emphysema (PSE. PE was divided into the following 3 categories:I (CLE or CLE-predominant;II (CLE and PSE of equal extent;and III (PSE or PSE-predominant. PE was found in 64 of 274 smokers (23.3% and 54 of 1,413 non-smokers (3.8%. In smoking subjects, when grades 1 and 2 were grouped together as mild PE, the mean age for CT grade 3 (severe PE was significantly higher than that for mild PE. In group A, category III predominated, whereas category I was more prevalent in group B, in both smoking and non-smoking subjects. A high incidence of PE was found in smoking subjects as compared with non-smoking subjects. PSE predominated in younger subjects, whereas CLE predominated in older subjects.

  6. Immunological responses to envelope glycoprotein 120 from subtypes of human immunodeficiency virus type 1.

    Science.gov (United States)

    Gilljam, G; Svensson, A; Ekström, A; Wahren, B

    1999-07-01

    The outer envelope glycoprotein (gp120) from subtypes A-E of HIV-1 was purified using a specific high mannose-binding lectin, Galanthus nivalis agglutinin. All isolates were grown in peripheral blood lymphocyte cells in order to avoid selection in cell lines. A comparison of the reactivities of the envelope proteins was made using sera from patients infected with the different subtypes. In this study, the B and C subtype envelope glycoproteins showed the strongest immunological reactivity, when reacted with sera from patients infected with the same subtype of virus. On the other hand, sera of patients infected with subtype A or C virus had the strongest and broadest reactivities, to envelope glycoproteins of many subtypes. The purified gp120 proteins from all five subtypes stimulated mononuclear cells from HIV-1 (subtype B)-infected patients, indicating conserved T cell-activating epitopes. The immunological reactivities indicate that strong antigenicity does not always predict the broadest immunogenicity of an envelope glycoprotein. Glycoprotein 120 from foreign subtypes may serve to induce strong cross-reactive immune responses.

  7. Genetic variability of the envelope gene of Type D simian retrovirus-2 (SRV-2 subtypes associated with SAIDS-related retroperitoneal fibromatosis in different macaque species

    Directory of Open Access Journals (Sweden)

    Tsai Che-Chung

    2006-03-01

    Full Text Available Abstract Background D-type simian retrovirus-2 (SRV-2 causes an AIDS-like immune deficiency syndrome (SAIDS in various macaque species. SAIDS is often accompanied by retroperitoneal fibromatosis (RF, an aggressive fibroproliferative disorder reminiscent of Kaposi's sarcoma in patients with HIV-induced AIDS. In order to determine the association of SRV-2 subtypes with SAIDS-RF, and study the evolution and transmission of SRV-2 in captive macaque populations, we have molecularly characterized the env gene of a number of SRV-2 isolates from different macaque species with and without RF. Results We sequenced the env gene from eighteen SRV-2 isolates and performed sequence comparisons and phylogenetic analyses. Our studies revealed the presence of six distinct subtypes of SRV-2, three of which were associated with SAIDS-RF cases. We found no association between SRV-2 subtypes and a particular macaque species. Little sequence variation was detected in SRV-2 isolates from the same individual, even after many years of infection, or from macaques housed together or related by descent from a common infected parent. Seventy-two amino acid changes were identified, most occurring in the larger gp70 surface protein subunit. In contrast to the lentiviruses, none of the amino acid variations involved potential N-linked glycosylation sites. Structural analysis of a domain within the gp22/gp20 transmembrane subunit that was 100% conserved between SRV-2 subtypes, revealed strong similarities to a disulfide-bonded loop that is crucial for virus-cell fusion and is found in retroviruses and filoviruses. Conclusion Our study suggests that separate introductions of at least six parental SRV-2 subtypes into the captive macaque populations in the U.S. have occurred with subsequent horizontal transfer between macaque species and primate centers. No specific association of a single SRV-2 subtype with SAIDS-RF was seen. The minimal genetic variability of the env gene within

  8. A large multi-centre European study validates high-sensitivity C-reactive protein (hsCRP) as a clinical biomarker for the diagnosis of diabetes subtypes

    DEFF Research Database (Denmark)

    Thanabalasingham, G.; Shah, N.; Vaxillaire, M.;

    2011-01-01

    An accurate molecular diagnosis of diabetes subtype confers clinical benefits; however, many individuals with monogenic diabetes remain undiagnosed. Biomarkers could help to prioritise patients for genetic investigation. We recently demonstrated that high-sensitivity C-reactive protein (hs......CRP) levels are lower in UK patients with hepatocyte nuclear factor 1 alpha (HNF1A)-MODY than in other diabetes subtypes. In this large multi-centre study we aimed to assess the clinical validity of hsCRP as a diagnostic biomarker, examine the genotype-phenotype relationship and compare different hsCRP assays....... High-sensitivity CRP levels were analysed in individuals with HNF1A-MODY (n = 457), glucokinase (GCK)-MODY (n = 404), hepatocyte nuclear factor 4 alpha (HNF4A)-MODY (n = 54) and type 2 diabetes (n = 582) from seven European centres. Three common assays for hsCRP analysis were evaluated. We excluded 121...

  9. Molecular characterisation of clinical and environmental isolates of Mycobacterium kansasii isolates from South African gold mines.

    Science.gov (United States)

    Kwenda, Geoffrey; Churchyard, Gavin J; Thorrold, Catherine; Heron, Ian; Stevenson, Karen; Duse, Adriano G; Marais, Elsé

    2015-03-01

    Mycobacterium kansasii (M. kansasii) is a major cause of non-tuberculous mycobacterial pulmonary disease in the South African gold-mining workforce, but the source of infection and molecular epidemiology are unknown. This study investigated the presence of M. kansasii in gold and coal mine and associated hostel water supplies and compared the genetic diversity of clinical and environmental isolates of M. kansasii. Five M. kansasii and ten other potentially pathogenic mycobacteria were cultured mainly from showerhead biofilms. Polymerase chain reaction-restriction analysis of the hsp65 gene on 196 clinical and environmental M. kansasii isolates revealed 160 subtype I, eight subtype II and six subtype IV strains. Twenty-two isolates did not show the typical M. kansasii restriction patterns, suggesting that these isolates may represent new subtypes of M. kansasii. In contrast to the clonal population structure found amongst the subtype I isolates from studies in other countries, DNA fingerprinting of 114 clinical and three environmental subtype I isolates demonstrated genetic diversity amongst the isolates. This study demonstrated that showerheads are possible sources of M. kansasii and other pathogenic non-tuberculous mycobacterial infection in a gold-mining region, that subtype I is the major clinical isolate of M. kansasii strain and that this subtype exhibits genetic diversity. PMID:25719478

  10. Different frequencies of drug resistance mutations among HIV-1 subtypes circulating in China: a comprehensive study.

    Directory of Open Access Journals (Sweden)

    Hongshuai Sui

    Full Text Available The rapid spreading of HIV drug resistance is threatening the overall success of free HAART in China. Much work has been done on drug-resistant mutations, however, most of which were based on subtype B. Due to different genetic background, subtypes difference would have an effect on the development of drug-resistant mutations, which has already been proved by more and more studies. In China, the main epidemic subtypes are CRF07_BC, CRF08_BC, Thai B and CRF01_AE. The depiction of drug resistance mutations in those subtypes will be helpful for the selection of regimens for Chinese. In this study, the distributions difference of amino acids at sites related to HIV drug resistance were compared among subtype B, CRF01_AE, CRF07_BC and CRF08_BC strains prevalent in China. The amino acid composition of sequences belonging to different subtypes, which were obtained from untreated and treated individuals separately, were also compared. The amino acids proportions of 19 sites in RT among subtype B, CRF01_AE and CRF08_BC have significant difference in drug resistance groups (chi-square test, p<0.05. Genetic barriers analysis revealed that sites 69, 138, 181, 215 and 238 were significantly different among subtypes (Kruskal Wallis test, p<0.05. All subtypes shared three highest prevalent drug resistance sites 103, 181 and 184 in common. Many drug resistant sites in protease show surprising high proportions in almost all subtypes in drug-naïve patients. This is the first comprehensive study in China on different development of drug resistance among different subtypes. The detailed data will lay a foundation for HIV treatment regimens design and improve HIV therapy in China.

  11. Neutrality, cross-immunity and subtype dominance in avian influenza viruses.

    Directory of Open Access Journals (Sweden)

    Vicki L Brown

    Full Text Available Avian influenza viruses (AIVs are considered a threat for their potential to seed human influenza pandemics. Despite their acknowledged importance, there are significant unknowns regarding AIV transmission dynamics in their natural hosts, wild birds. Of particular interest is the difference in subtype dynamics between human and bird populations-in human populations, typically only two or three subtypes cocirculate, while avian populations are capable of simultaneously hosting a multitude of subtypes. One species in particular-ruddy turnstones (Arenaria interpres--has been found to harbour a very wide range of AIV subtypes, which could make them a key player in the spread of new subtypes in wild bird populations. Very little is known about the mechanisms that drive subtype dynamics in this species, and here we address this gap in our knowledge. Taking advantage of two independent sources of data collected from ruddy turnstones in Delaware Bay, USA, we examine patterns of subtype diversity and dominance at this site. We compare these patterns to those produced by a stochastic, multi-strain transmission model to investigate possible mechanisms that are parsimonious with the observed subtype dynamics. We find, in agreement with earlier experimental work, that subtype differences are unnecessary to replicate the observed dynamics, and that neutrality alone is sufficient. We also evaluate the role of subtype cross-immunity and find that it is not necessary to generate patterns consistent with observations. This work offers new insights into the mechanisms behind subtype diversity and dominance in a species that has the potential to be a key player in AIV dynamics in wild bird populations.

  12. Frequent intra-subtype recombination among HIV-1 circulating in Tanzania.

    Directory of Open Access Journals (Sweden)

    Ireen E Kiwelu

    Full Text Available The study estimated the prevalence of HIV-1 intra-subtype recombinant variants among female bar and hotel workers in Tanzania. While intra-subtype recombination occurs in HIV-1, it is generally underestimated. HIV-1 env gp120 V1-C5 quasispecies from 45 subjects were generated by single-genome amplification and sequencing (median (IQR of 38 (28-50 sequences per subject. Recombination analysis was performed using seven methods implemented within the recombination detection program version 3, RDP3. HIV-1 sequences were considered recombinant if recombination signals were detected by at least three methods with p-values of ≤0.05 after Bonferroni correction for multiple comparisons. HIV-1 in 38 (84% subjects showed evidence for intra-subtype recombination including 22 with HIV-1 subtype A1, 13 with HIV-1 subtype C, and 3 with HIV-1 subtype D. The distribution of intra-patient recombination breakpoints suggested ongoing recombination and showed selective enrichment of recombinant variants in 23 (60% subjects. The number of subjects with evidence of intra-subtype recombination increased from 29 (69% to 36 (82% over one year of follow-up, although the increase did not reach statistical significance. Adjustment for intra-subtype recombination is important for the analysis of multiplicity of HIV infection. This is the first report of high prevalence of intra-subtype recombination in the HIV/AIDS epidemic in Tanzania, a region where multiple HIV-1 subtypes co-circulate. HIV-1 intra-subtype recombination increases viral diversity and presents additional challenges for HIV-1 vaccine design.

  13. Frequent intra-subtype recombination among HIV-1 circulating in Tanzania.

    Science.gov (United States)

    Kiwelu, Ireen E; Novitsky, Vladimir; Margolin, Lauren; Baca, Jeannie; Manongi, Rachel; Sam, Noel; Shao, John; McLane, Mary F; Kapiga, Saidi H; Essex, M

    2013-01-01

    The study estimated the prevalence of HIV-1 intra-subtype recombinant variants among female bar and hotel workers in Tanzania. While intra-subtype recombination occurs in HIV-1, it is generally underestimated. HIV-1 env gp120 V1-C5 quasispecies from 45 subjects were generated by single-genome amplification and sequencing (median (IQR) of 38 (28-50) sequences per subject). Recombination analysis was performed using seven methods implemented within the recombination detection program version 3, RDP3. HIV-1 sequences were considered recombinant if recombination signals were detected by at least three methods with p-values of ≤0.05 after Bonferroni correction for multiple comparisons. HIV-1 in 38 (84%) subjects showed evidence for intra-subtype recombination including 22 with HIV-1 subtype A1, 13 with HIV-1 subtype C, and 3 with HIV-1 subtype D. The distribution of intra-patient recombination breakpoints suggested ongoing recombination and showed selective enrichment of recombinant variants in 23 (60%) subjects. The number of subjects with evidence of intra-subtype recombination increased from 29 (69%) to 36 (82%) over one year of follow-up, although the increase did not reach statistical significance. Adjustment for intra-subtype recombination is important for the analysis of multiplicity of HIV infection. This is the first report of high prevalence of intra-subtype recombination in the HIV/AIDS epidemic in Tanzania, a region where multiple HIV-1 subtypes co-circulate. HIV-1 intra-subtype recombination increases viral diversity and presents additional challenges for HIV-1 vaccine design. PMID:23940702

  14. Effect of HIV-1 subtypes on disease progression in rural Uganda: a prospective clinical cohort study.

    Directory of Open Access Journals (Sweden)

    Deogratius Ssemwanga

    Full Text Available We examined the association of HIV-1 subtypes with disease progression based on three viral gene regions.A prospective HIV-1 clinical cohort study in rural Uganda.Partial gag, env and pol genes were sequenced. Cox proportional hazard regression modelling was used to estimate adjusted hazard ratios (aHRs of progression to: CD4≤250, AIDS onset and death, adjusted for sex, age and CD4 count at enrolment.Between 1990 and 2010, 292 incident cases were subtyped: 25% had subtype A, 45% had D, 26% had A/D recombinants, 1% had C and 4% were other recombinant forms. Of the 278 incident cases included in the disease progression analysis, 62% progressed to CD4≤250, 32% to AIDS, and 34% died with a higher proportion being among subtype D cases. The proportions of individuals progressing to the three endpoints were significantly higher among individuals infected with subtype D. Throughout the study period, individuals infected with subtype D progressed faster to CD4≤250, adjusted HR (aHR, (95% CI = 1.72 (1.16-2.54, but this was mainly due to events in the period before antiretroviral therapy (ART introduction, when individuals infected with subtype D significantly progressed faster to CD4≤250 than subtype A cases; aHR (95% CI = 1.78 (1.01-3.14.In this population, HIV-1 subtype D was the most prevalent and was associated with faster HIV-1 disease progression than subtype A. Further studies are needed to examine the effect of HIV-1 subtypes on disease progression in the ART period and their effect on the virological and immunological ART outcomes.

  15. Retinoic acid receptor subtype-specific transcriptotypes in the early zebrafish embryo.

    Science.gov (United States)

    Samarut, Eric; Gaudin, Cyril; Hughes, Sandrine; Gillet, Benjamin; de Bernard, Simon; Jouve, Pierre-Emmanuel; Buffat, Laurent; Allot, Alexis; Lecompte, Odile; Berekelya, Liubov; Rochette-Egly, Cécile; Laudet, Vincent

    2014-02-01

    Retinoic acid (RA) controls many aspects of embryonic development by binding to specific receptors (retinoic acid receptors [RARs]) that regulate complex transcriptional networks. Three different RAR subtypes are present in vertebrates and play both common and specific roles in transducing RA signaling. Specific activities of each receptor subtype can be correlated with its exclusive expression pattern, whereas shared activities between different subtypes are generally assimilated to functional redundancy. However, the question remains whether some subtype-specific activity still exists in regions or organs coexpressing multiple RAR subtypes. We tackled this issue at the transcriptional level using early zebrafish embryo as a model. Using morpholino knockdown, we specifically invalidated the zebrafish endogenous RAR subtypes in an in vivo context. After building up a list of RA-responsive genes in the zebrafish gastrula through a whole-transcriptome analysis, we compared this panel of genes with those that still respond to RA in embryos lacking one or another RAR subtype. Our work reveals that RAR subtypes do not have fully redundant functions at the transcriptional level but can transduce RA signal in a subtype-specific fashion. As a result, we define RAR subtype-specific transcriptotypes that correspond to repertoires of genes activated by different RAR subtypes. Finally, we found genes of the RA pathway (cyp26a1, raraa) the regulation of which by RA is highly robust and can even resist the knockdown of all RARs. This suggests that RA-responsive genes are differentially sensitive to alterations in the RA pathway and, in particular, cyp26a1 and raraa are under a high pressure to maintain signaling integrity. PMID:24422634

  16. Molecular Subtype Analyses of Campylobacter spp. from Arkansas and California Poultry Operations

    OpenAIRE

    Hiett, K. L; Stern, N. J.; Fedorka-Cray, P.; Cox, N. A.; Musgrove, M. T.; Ladely, S.

    2002-01-01

    Campylobacter isolates from diverse samples within broiler production and processing environments were typed by using flaA short variable region DNA sequence analysis. Sixteen flocks from four different farms representing two broiler producers in Arkansas and California were analyzed. Fourteen of the flocks (87.5%) were Campylobacter-positive; two remained negative throughout the 6-week rearing period. In general, multiple clones were present within a flock. Additionally, clones found within ...

  17. ABC transporter activity linked to radiation resistance and molecular subtype in pediatric medulloblastoma

    OpenAIRE

    Ingram, Wendy J; Crowther, Lisa M.; Little, Erica B; Freeman, Ruth; Harliwong, Ivon; Veleva, Desi; Hassall, Timothy E; Remke, Marc; Taylor, Michael D.; Hallahan, Andrew R

    2013-01-01

    Background Resistance to radiation treatment remains a major clinical problem for patients with brain cancer. Medulloblastoma is the most common malignant brain tumor of childhood, and occurs in the cerebellum. Though radiation treatment has been critical in increasing survival rates in recent decades, the presence of resistant cells in a substantial number of medulloblastoma patients leads to relapse and death. Methods Using the established medulloblastoma cell lines UW228 and Daoy, we devel...

  18. Molecular cloning of a new bombesin receptor subtype expressed in uterus during pregnancy

    OpenAIRE

    Gorboulev, Valentin; Akhundova, Aida; Büchner, Hubert; Fahrenholz, Falk

    2011-01-01

    The homology screening approach has been used to clone a new member of the guanine-nucleotidebinding-protein-coupled receptor superfamily from guinea pig uterus. The cloned cDNA encodes a 399-amino-acid protein and shows the highest amino acid similarity to members of the bombesin receptor family; 52% and 47% similarity to the gastrin-releasing-peptide (GRP) receptor and the neuromedin-B receptor, respectively. Bindingexperiments with the stably transfected LLC-PK1 cell line expressing the ne...

  19. Subtype specific genetic associations for juvenile idiopathic arthritis: ERAP1 with the enthesitis related arthritis subtype and IL23R with juvenile psoriatic arthritis

    OpenAIRE

    Hinks, Anne; Martin, Paul; Flynn, Edward; Eyre, Steve; Packham, Jon; Barton, Anne; Worthington, Jane; Thomson, Wendy

    2011-01-01

    Introduction Juvenile idiopathic arthritis (JIA) is an umbrella term for all chronic childhood arthropathies and can be divided into seven subtypes. It includes the enthesitis related arthritis (ERA) subtype which displays symptoms similar to ankylosing spondylitis (AS) and juvenile-onset psoriatic arthritis which has similarities to psoriatic arthritis (PsA) and psoriasis (Ps). We, therefore, hypothesized that two well-established susceptibility loci for AS and Ps, ERAP1 and IL23R, could als...

  20. Diversity of Blastocystis subtypes in dogs in different geographical settings

    DEFF Research Database (Denmark)

    Wang, Wenqi; Cuttell, Leigh; Bielefeldt-Ohmann, Helle;

    2013-01-01

    Background: Blastocystis is a ubiquitous, globally distributed intestinal protist infecting humans and a wide range of animals. Several studies have shown that Blastocystis is a potentially zoonotic parasite. A 1996 study reported a 70% Blastocystis prevalence in Brisbane pound dogs while another...... study found that pet dogs/cats of 11 symptomatic Blastocystis infected patients harboured at least one Blastocystis subtype (ST) in common with the patient. These results raised the possibility that dogs might be natural hosts of Blastocystis. In this study, we aimed to investigate this hypothesis...... by estimating the prevalence of Blastocystis carriage and characterising the diversity of STs in dogs from three different environmental settings and comparing these STs with the range that humans harbour. Methods: Two hundred and forty faecal samples from dogs from three different geographical regions...

  1. Toward an immune-mediated subtype of autism spectrum disorder.

    Science.gov (United States)

    McDougle, Christopher J; Landino, Samantha M; Vahabzadeh, Arshya; O'Rourke, Julia; Zurcher, Nicole R; Finger, Beate C; Palumbo, Michelle L; Helt, Jessica; Mullett, Jennifer E; Hooker, Jacob M; Carlezon, William A

    2015-08-18

    A role for immunological involvement in autism spectrum disorder (ASD) has long been hypothesized. This review includes four sections describing (1) evidence for a relationship between familial autoimmune disorders and ASD; (2) results from post-mortem and neuroimaging studies that investigated aspects of neuroinflammation in ASD; (3) findings from animal model work in ASD involving inflammatory processes; and (4) outcomes from trials of anti-inflammatory/immune-modulating drugs in ASD that have appeared in the literature. Following each section, ideas are provided for future research, suggesting paths forward in the continuing effort to define the role of immune factors and inflammation in the pathophysiology of a subtype of ASD. This article is part of a Special Issue entitled SI: Neuroimmunology in Health And Disease. PMID:25445995

  2. Prevalence of dementia and major subtypes in Europe

    DEFF Research Database (Denmark)

    Lobo, A; Launer, L J; Fratiglioni, L;

    2000-01-01

    The last comparison of prevalence figures of dementia across European studies was 10 years ago. Using studies conducted in the 1990s, the authors compare the age- and sex-specific prevalence of dementia, AD, and vascular dementia (VaD) across European population-based studies of persons 65 years....... In the VaD subtype, a large variation across studies was observed, as well as a difference in prevalence between men and women that was age dependent. Dementia is more prevalent in women, and AD is the main contributor to the steep increase of prevalence with age....... and older. Data from these studies were also pooled to obtain stable estimates of age- and sex-specific prevalence. A total of 2346 cases of mild to severe dementia were identified in 11 cohorts. Age-standardized prevalence was 6.4% for dementia (all causes), 4.4% for AD, and 1.6% for VaD. The prevalence...

  3. Geographic distribution of human Blastocystis subtypes in South America.

    Science.gov (United States)

    Ramírez, Juan David; Sánchez, Angie; Hernández, Carolina; Flórez, Carolina; Bernal, María Consuelo; Giraldo, Julio Cesar; Reyes, Patricia; López, Myriam Consuelo; García, Lineth; Cooper, Philip J; Vicuña, Yosselin; Mongi, Florencia; Casero, Rodolfo D

    2016-07-01

    Blastocystis is a cosmopolitan enteric protist colonizing probably more than 1 billion people. This protozoan exhibits genetic diversity and is subdivided into subtypes (STs). The aim of this study was to determine the distribution of Blastocystis STs in symptomatic and asymptomatic human samples from different countries of South America. A total of 346 fecal samples were genotyped by SSU rDNA showing ST1 (28.3%), ST2 (22.2%), ST3 (36.7%), ST4 (2%), ST5 (2.3%), ST6 (2%), ST7 (2.3%), ST8 (0.6%), ST12 (0.9%) and a novel ST (2.7%). These findings update the epidemiology of Blastocystis in South America and expand our knowledge of the phylogeographic differences exhibited by this stramenopile. PMID:27034056

  4. Incidence of dementia and major subtypes in Europe

    DEFF Research Database (Denmark)

    Fratiglioni, L; Launer, L J; Andersen, K;

    2000-01-01

    ,996 person-years of follow-up. In all studies a higher proportion of cases were diagnosed with AD (60 to 70% of all demented cases) than vascular dementia (VaD). The incidence of dementia and AD continued to increase with age up to age 85 years, after which rates increased in women but not men....... There was a large variation in VaD incidence across studies. In the pooled analysis, the incidence rates increased with age without any substantial difference between men and women. Surprisingly, higher incidence rates of dementia and AD were found in the very old in northwest countries than in southern countries......The authors examined the association of incident dementia and subtypes with age, sex, and geographic area in Europe. Incidence data from eight population-based studies carried out in seven European countries were compared and pooled. The pooled data included 835 mild to severe dementia cases and 42...

  5. Antisocial personality disorder--stable and unstable subtypes.

    Science.gov (United States)

    Ullrich, Simone; Coid, Jeremy

    2010-04-01

    There have been criticisms that the criteria for antisocial personality disorder (ASPD) are over-dependent on criminal behavior. This study aimed to identify unrelated criteria of social and behavioral problems and instability, and to investigate their associations in a representative household sample of adults in the UK. Approximately one third of adults with ASPD did not fulfill any of the criteria for instability. They were less aggressive and involved in illegal activities but expressed less remorse for their behaviors. Instability in ASPD was mediated primarily through comorbid anxiety disorders and borderline personality disorder. The concept of Secondary Psychopathy, which has not generally been applied to ASPD, demonstrated many similarities to the unstable subtype.

  6. Subtypes of Pathological Gambling with Concurrent Illegal Behaviors.

    Science.gov (United States)

    Granero, Roser; Fernández-Aranda, Fernando; Aymamí, Neus; Gómez-Peña, Mónica; Fagundo, Ana Beatriz; Sauchelli, Sarah; Del Pino-Gutiérrez, Amparo; Moragas, Laura; Savvidou, Lamprini G; Islam, Mohammed A; Tàrrega, Salomé; Menchón, José M; Jiménez-Murcia, Susana

    2015-12-01

    The aims of this study are: to explore empirical clusters in a sample of individuals with a gambling disorder (GD) according to the presence of illegal behaviors, to describe the subgroups at a clinical level and to examine whether a temporal change has taken place across the last 9 years. The sample consisted of 378 patients with a GD who consecutively received outpatient treatment, and who reported the presence of the DSM-IV criteria "presence of illegal behavior". Two-step clustering procedure revealed the existence of four empirical groups, which differed in both sociodemographic and clinical profiles. The patients, who have committed illegal acts due to their gambling behavior, are a heterogeneous group in which it is possible to identify different subtypes, based on sociodemographic, psychopathological, clinical and personality characteristics.

  7. Molecular epidemiology of HIV-1 strains in the south-east and east of Turkey

    Directory of Open Access Journals (Sweden)

    Mustafa Kemal Çelen

    2015-09-01

    Conclusions: HIV molecular epidemiology studies are necessary to determine transmission patterns and spread. Subtype B and CRF01_AE, CRF02_AG are the most prevalent strains in the south-east of Turkey. However, subtype C, sub-subtypes A1 and F1 are of low prevalence but persist in the south-east of Turkey. In the near future, changing of HIV epidemiology will be possible in Turkey due to migration movement in border lines and resistance testing will play an important role in HIV management.

  8. Different subtypes of impulsivity differentiate uncontrolled eating and dietary restraint.

    Science.gov (United States)

    Leitch, Margaret A; Morgan, Michael J; Yeomans, Martin R

    2013-10-01

    The current study explored the relationship between three subtypes of impulsivity (Reflection Impulsivity, Impulsive Choice, and Impulsive Action) and measures of uncontrolled eating (TFEQ-D) and restraint (TFEQ-R). Eighty women classified as scoring higher or lower on TFEQ-D and TFEQ-R completed the Matching Familiar Figures Test (MFFT20), Delay Discounting Task (DDT), a Go No Go task, Balloon Analogue Risk Task (BART), and the Barrett Impulsivity Scale-11 (BIS-11). To test whether these relationships were affected by enforced controls overeating, half of the participants fasted the night before and ate breakfast in the laboratory before testing and half had no such control. Women scoring higher on the TFEQ-D were significantly more impulsive on the MFFT20 and BIS-11 overall but not on DDT, Go No Go or BART. Women scoring higher on TFEQ-R were significantly less impulsive on the Go No Go task but did not differ on other measures. The eating manipulation modulated responses on the BART and BIS-11 non-planning scale depending on TFEQ-D classification. These results confirm recent data that high scores on TFEQ-D are related to impulsivity, but imply this relates more to Reflection Impulsivity rather than Impulsive Choice or Action. In contrast restrained eating was associated with better inhibitory control. Taken together, these results suggest that subtypes of impulsivity further differentiate uncontrolled eating and restraint, and suggest that a poor ability to reflect on decisions may underlie some aspects of overeating. PMID:23702263

  9. Resolving bovine viral diarrhea virus subtypes from persistently infected US beef calves with complete genome sequence

    Science.gov (United States)

    Bovine viral diarrhea virus (BVDV) is classified into 2 genotypes, BVDV-1 and BVDV-2, each of which contains distinct subtypes with genetic and antigenic differences. Currently, three major subtypes circulate in the United States: BVDV-1a, 1b, and 2a. In addition, a single case of BVDV-2b infection ...

  10. Development of an abbreviated version of the delirium motor subtyping scale (DMSS-4)

    NARCIS (Netherlands)

    Meagher, D; Adamis, D; Leonard, M; Trzepacz, P; Grover, S; Jabbar, F; Meehan, K; O'Connor, M; Cronin, C; Reynolds, P; Fitzgerald, J; O'Regan, N; Timmons, S; Slor, C; de Jonghe, J; de Jonghe, A; van Munster, B C; de Rooij, S E; Maclullich, A

    2014-01-01

    BACKGROUND: Delirium is a common neuropsychiatric syndrome with considerable heterogeneity in clinical profile. Identification of clinical subtypes can allow for more targeted clinical and research efforts. We sought to develop a brief method for clinical subtyping in clinical and research settings.

  11. Respiratory panic disorder subtype and sensitivity to the carbon dioxide challenge test

    Directory of Open Access Journals (Sweden)

    A.M. Valença

    2002-07-01

    Full Text Available The aim of the present study was to verify the sensitivity to the carbon dioxide (CO2 challenge test of panic disorder (PD patients with respiratory and nonrespiratory subtypes of the disorder. Our hypothesis is that the respiratory subtype is more sensitive to 35% CO2. Twenty-seven PD subjects with or without agoraphobia were classified into respiratory and nonrespiratory subtypes on the basis of the presence of respiratory symptoms during their panic attacks. The tests were carried out in a double-blind manner using two mixtures: 1 35% CO2 and 65% O2, and 2 100% atmospheric compressed air, 20 min apart. The tests were repeated after 2 weeks during which the participants in the study did not receive any psychotropic drugs. At least 15 of 16 (93.7% respiratory PD subtype patients and 5 of 11 (43.4% nonrespiratory PD patients had a panic attack during one of two CO2 challenges (P = 0.009, Fisher exact test. Respiratory PD subtype patients were more sensitive to the CO2 challenge test. There was agreement between the severity of PD measured by the Clinical Global Impression (CGI Scale and the subtype of PD. Higher CGI scores in the respiratory PD subtype could reflect a greater sensitivity to the CO2 challenge due to a greater severity of PD. Carbon dioxide challenges in PD may define PD subtypes and their underlying mechanisms.

  12. Variation in Campylobacter MLST Subtypes Detected from Chickens on Three Different Plating Media

    Science.gov (United States)

    The objective of this study was to compare subtypes of Campylobacter jejuni and coli detected on three discreet selective Campylobacter plating media to determine if different media select for different subtypes. Fifty ceca and fifty carcasses (n=100, representing 50 flocks) were collected from the...

  13. Clinical characteristics and prognosis of three rare and poor-prognostic subtypes of primary liver carcinoma

    Institute of Scientific and Technical Information of China (English)

    李智宇

    2014-01-01

    Objective To explore the clinicopathological features and prognostic factors of three rare and poor-prognostic pathological subtypes of primary liver carcinoma,and to improve the clinical diagnosis and surgical treatment.Methods A retrospective analysis of clinicopathological data of 69 patients with rare pathological subtypes of primary liver carcinoma,diagnosed by postoperative

  14. Plasma metabolomics combined with personalized diagnosis guided by Chinese medicine reveals subtypes of chronic heart failure

    Directory of Open Access Journals (Sweden)

    Juan Wang

    2015-04-01

    Conclusion: This study suggests that combining metabolomics with traditional Chinese medicine diagnosis can reveal metabolic signatures for CHF syndrome subtypes. The plasma metabolites identified might be of special clinical relevance for subtypes of CHF, which could lead to further understanding of mechanisms involved and an improvement in personalized treatment for CHF.

  15. Predictors of Stability of Attention-Deficit/Hyperactivity Disorder Subtypes from Childhood to Young Adulthood

    Science.gov (United States)

    Todd, Richard D.; Huang, Hongyan; Todorov, Alexandre A.; Neuman, Rosalind J.; Reiersen, Angela M.; Henderson, Cynthia A.; Reich, Wendy C.

    2008-01-01

    A 5-year prospective study attempts to determine the predictors of stability of attention-deficit/hyperactivity disorder (ADHD) subtypes from childhood to young adulthood. The results conclude that population-defined ADHD subtype criteria indicate improved diagnostic stability over 5 years.

  16. PTSD personality subtypes in women exposed to intimate-partner violence.

    Science.gov (United States)

    Carleton, R Nicholas; Mulvogue, Myriah K; Duranceau, Sophie

    2015-03-01

    There is considerable research implicating posttraumatic stress disorder (PTSD) as a common reaction to intimate-partner violence (IPV; Golding, 1999). PTSD is categorized as a single disorder; however, there is significant heterogeneity in its symptom-presentation patterns (Dickstein, Suvak, Litz, & Adler, 2010). Researchers have posited underlying personality characteristics as potentiating different expressions of PTSD (Miller, Greif, & Smith, 2003). Specifically, a model with 3 personality subtypes (i.e., externalizing, internalizing, and simple) has been proposed to explain PTSD symptom-pattern heterogeneity (Miller, 2003; Miller & Resick, 2007). The current study tested the PTSD personality-subtype model in a sample of 129 women exposed to a range of IPV experiences. Temperament patterns of women reporting clinically significant PTSD symptoms replicated the 3 personality-subtype patterns found in previous investigations (i.e., an externalizing subtype group characterized by high negative emotionality and low disinhibition, an internalizing subtype group characterized by high negative emotionality and low positive emotionality, and a simple subtype group characterized by midrange scores across the temperament variables; Miller et al., 2003; Miller, Kaloupek, Dillon, & Keane, 2004; Miller & Resick, 2007). Differences between personality-subtype groups and women without clinically significant PTSD symptoms were found (p personality patterns consistent with the internalizing and externalizing subtype groups exhibiting higher comorbid personality pathology and psychological difficulties. Implications are discussed for personality as a risk or resiliency factor in PTSD and as contributing to explaining PTSD symptom heterogeneity. PMID:25793691

  17. Clinical Implications of DSM-IV Subtyping of Bipolar Disorders in Referred Children and Adolescents

    Science.gov (United States)

    Masi, Gabriele; Perugi, Giulio; Millepiedi, Stefania; Mucci, Maria; Pari, Cinzia; Pfanner, Chiara; Berloffa, Stefano; Toni, Cristina

    2007-01-01

    Objective: According to DSM-IV, bipolar disorders (BDs) include four subtypes, BD I, BD II, cyclothymic disorder, and BD not otherwise specified (NOS). We explore the clinical implications of this subtyping in a naturalistic sample of referred youths with BD I, BD II, and BD-NOS. Method: The sample consisted of 217 patients, 135 males and 82…

  18. Hyperspectral multiplex single-particle tracking of different receptor subtypes labeled with quantum dots in live neurons

    Science.gov (United States)

    Labrecque, Simon; Sylvestre, Jean-Philippe; Marcet, Stephane; Mangiarini, Francesca; Bourgoin, Brice; Verhaegen, Marc; Blais-Ouellette, Sébastien; De Koninck, Paul

    2016-04-01

    The efficacy of existing therapies and the discovery of innovative treatments for central nervous system (CNS) diseases have been limited by the lack of appropriate methods to investigate complex molecular processes at the synaptic level. To improve our capability to investigate complex mechanisms of synaptic signaling and remodeling, we designed a fluorescence hyperspectral imaging platform to simultaneously track different subtypes of individual neurotransmitter receptors trafficking in and out of synapses. This imaging platform allows simultaneous image acquisition of at least five fluorescent markers in living neurons with a high-spatial resolution. We used quantum dots emitting at different wavelengths and functionalized to specifically bind to single receptors on the membrane of living neurons. The hyperspectral imaging platform enabled the simultaneous optical tracking of five different synaptic proteins, including subtypes of glutamate receptors (mGluR and AMPAR) and postsynaptic signaling proteins. It also permitted the quantification of their mobility after treatments with various pharmacological agents. This technique provides an efficient method to monitor several synaptic proteins at the same time, which could accelerate the screening of effective compounds for treatment of CNS disorders.

  19. Differential affinity of mammalian histone H1 somatic subtypes for DNA and chromatin

    Directory of Open Access Journals (Sweden)

    Mora Xavier

    2007-05-01

    Full Text Available Abstract Background Histone H1 is involved in the formation and maintenance of chromatin higher order structure. H1 has multiple isoforms; the subtypes differ in timing of expression, extent of phosphorylation and turnover rate. In vertebrates, the amino acid substitution rates differ among subtypes by almost one order of magnitude, suggesting that each subtype might have acquired a unique function. We have devised a competitive assay to estimate the relative binding affinities of histone H1 mammalian somatic subtypes H1a-e and H1° for long chromatin fragments (30–35 nucleosomes in physiological salt (0.14 M NaCl at constant stoichiometry. Results The H1 complement of native chromatin was perturbed by adding an additional amount of one of the subtypes. A certain amount of SAR (scaffold-associated region DNA was present in the mixture to avoid precipitation of chromatin by excess H1. SAR DNA also provided a set of reference relative affinities, which were needed to estimate the relative affinities of the subtypes for chromatin from the distribution of the subtypes between the SAR and the chromatin. The amounts of chromatin, SAR and additional H1 were adjusted so as to keep the stoichiometry of perturbed chromatin similar to that of native chromatin. H1 molecules freely exchanged between the chromatin and SAR binding sites. In conditions of free exchange, H1a was the subtype of lowest affinity, H1b and H1c had intermediate affinities and H1d, H1e and H1° the highest affinities. Subtype affinities for chromatin differed by up to 19-fold. The relative affinities of the subtypes for chromatin were equivalent to those estimated for a SAR DNA fragment and a pUC19 fragment of similar length. Avian H5 had an affinity ~12-fold higher than H1e for both DNA and chromatin. Conclusion H1 subtypes freely exchange in vitro between chromatin binding sites in physiological salt (0.14 M NaCl. The large differences in relative affinity of the H1 subtypes for

  20. Molecular Typing in Public Health Laboratories: From an Academic Indulgence to an Infection Control Imperative

    OpenAIRE

    Allerberger, Franz

    2012-01-01

    Using three Austrian case studies, the variegated applications of molecular typing in today's public health laboratories are discussed to help illustrate preventive management strategies relying on DNA subtyping. DNA macrorestriction analysis by pulsed field gel electrophoresis has become the gold standard for subtyping of food borne pathogens like listeria, salmonella, campylobacter and Bacillus cereus. Using a Salmonella Mbandaka outbreak from the year 2010 as example, it is shown how the c...

  1. A single subtype of avian pneumovirus circulates among Minnesota turkey flocks.

    Science.gov (United States)

    Dar, Arshud M; Munir, Shirin; Goyal, Sagar M; Kapur, Vivek

    2002-09-01

    The recent emergence of avian pneumovirus (APV) infection among US turkey flocks has resulted in a major economic threat to the turkey industry. In order to elucidate the molecular epidemiology of APV, comparative sequence analysis of the fusion (F) protein gene of APV was performed for 3 cell culture-adapted isolates and 10 APV positive clinical samples recovered from US turkey flocks. Relatively modest levels of nucleotide and amino acid sequence divergence were identified, suggesting the prevalence of a single lineage of APV among US turkey flocks. Additionally, numerous polymorphisms were identified that were only represented in the clinical samples but not in the in vitro propagated isolates of APV. Phylogenetic analyses confirm that the subtype of APV circulating in the upper Midwestern United States is evolutionarily related to, but distinct from, European APV subgroups A and B. Overall, the results of the present investigation suggest that there has been only a single recent introduction of APV into US turkey populations in the upper Midwestern United States.

  2. CRISPR typing and subtyping for improved laboratory surveillance of Salmonella infections.

    Directory of Open Access Journals (Sweden)

    Laëtitia Fabre

    Full Text Available Laboratory surveillance systems for salmonellosis should ideally be based on the rapid serotyping and subtyping of isolates. However, current typing methods are limited in both speed and precision. Using 783 strains and isolates belonging to 130 serotypes, we show here that a new family of DNA repeats named CRISPR (clustered regularly interspaced short palindromic repeats is highly polymorphic in Salmonella. We found that CRISPR polymorphism was strongly correlated with both serotype and multilocus sequence type. Furthermore, spacer microevolution discriminated between subtypes within prevalent serotypes, making it possible to carry out typing and subtyping in a single step. We developed a high-throughput subtyping assay for the most prevalent serotype, Typhimurium. An open web-accessible database was set up, providing a serotype/spacer dictionary and an international tool for strain tracking based on this innovative, powerful typing and subtyping tool.

  3. GENETIC SUBTYPES OF BLASTOCYSTIS ISOLATED FROM THAI HOSPITALIZED PATIENTS IN NORTHEASTERN THAILAND.

    Science.gov (United States)

    Sanpool, Oranuch; Laoraksawong, Pokkamol; Janwan, Penchom; Intapan, Pewpan M; Sawanyawisuth, Kittisak; Thanchomnang, Tongjit; Changtrakul, Yossombat; Maleewong, Wanchai

    2015-03-01

    Blastocystis sp is probably the most common intestinal protozoan of humans. This taxon is known to include more than 17 subtypes, some of which likely cause human disease. We investigated the distribution of Blastocystis subtypes in Thai patients admitted for a variety of conditions at a hospital in northeastern Thailand. Fresh fecal samples, positive for Blastocystis by microscopy, were individually cultured in Jones' medium (n = 20) and each sample was used for amplification and sequencing a fragment of 18S rDNA. BLAST search and phylogenetic analysis demonstrated that Blastocystis subtypes ST1 (20%), ST3 (60%), ST6 (10%) and ST7 (10%) were present. No clear link between gastro-intestinal symptoms and any particular subtype of Blastocystis was apparent. Thus, there is a need to extend the work to evaluate clinical signs and subtypes in a larger cohort of patients. PMID:26513920

  4. Low penetrance breast cancer susceptibility loci are associated with specific breast tumor subtypes

    DEFF Research Database (Denmark)

    Broeks, Annegien; Schmidt, Marjanka K; Sherman, Mark E;

    2011-01-01

    Breast cancers demonstrate substantial biological, clinical and etiological heterogeneity. We investigated breast cancer risk associations of eight susceptibility loci identified in GWAS and two putative susceptibility loci in candidate genes in relation to specific breast tumor subtypes. Subtype...... stratification might help in the identification and characterization of novel risk factors for breast cancer subtypes. This may eventually result in further improvements in prevention, early detection and treatment.......Breast cancers demonstrate substantial biological, clinical and etiological heterogeneity. We investigated breast cancer risk associations of eight susceptibility loci identified in GWAS and two putative susceptibility loci in candidate genes in relation to specific breast tumor subtypes. Subtypes...... were defined by five markers (ER, PR, HER2, CK5/6, EGFR) and other pathological and clinical features. Analyses included up to 30 040 invasive breast cancer cases and 53 692 controls from 31 studies within the Breast Cancer Association Consortium. We confirmed previous reports of stronger associations...

  5. Phenotypic and genotypic characterisation of Blastocystis hominis isolates implicates subtype 3 as a subtype with pathogenic potential.

    Science.gov (United States)

    Tan, T C; Suresh, K G; Smith, H V

    2008-12-01

    Despite frequent reports on the presence of Blastocystis hominis in human intestinal tract, its pathogenicity remains a matter of intense debate. These discrepancies may be due to the varying pathogenic potential or virulence of the isolates studied. The present study represents the first to investigate both phenotypic and genotypic characteristics of B. hominis obtained from symptomatic and asymptomatic individuals. Symptomatic isolates had a significantly greater size range and lower growth rate in Jones' medium than asymptomatic isolates. The parasite cells of symptomatic isolates exhibited rougher surface topography and greater binding affinity to Canavalia ensiformis (ConA) and Helix pomatia (HPA). The present study also identifies further phenotypic characteristics, which aided in differentiating the pathogenic forms from the non-pathogenic forms of B. hominis. Blastocystis subtype 3 was found to be correlated well with the disease. PMID:18795333

  6. Immunophenotyping invasive breast cancer: paving the road for molecular imaging.

    NARCIS (Netherlands)

    Vermeulen, J.F.; Brussel, A.S. van; Groep, P. van der; Morsink, F.H.; Bult, P.; Wall, E. van der; Diest, P.J. van

    2012-01-01

    ABSTRACT: BACKGROUND: Mammographic population screening in The Netherlands has increased the number of breast cancer patients with small and non-palpable breast tumors. Nevertheless, mammography is not ultimately sensitive and specific for distinct subtypes. Molecular imaging with targeted tracers m

  7. Subtype diversity associated with the development of HIV-1 resistance to integrase inhibitors.

    Science.gov (United States)

    Brenner, Bluma G; Lowe, Matthew; Moisi, Daniela; Hardy, Isabelle; Gagnon, Simon; Charest, Hugues; Baril, Jean Guy; Wainberg, Mark A; Roger, Michel

    2011-05-01

    We used genotypic and phylogenetic analysis to determine integrase diversity among subtypes, and studied natural polymorphisms and mutations implicated in resistance to integrase inhibitors (INI) in treatment-naïve persons (n = 220) and -experienced individuals (n = 24). Phylogenetics revealed 7 and 10% inter-subtype diversity in the integrase and reverse transcriptase (RT)/protease regions, respectively. Integrase sequencing identified a novel A/B recombinant in which all viruses in a male-sex-male (MSM) transmission cluster (n = 12) appeared to possess subtype B in integrase and subtype A in the remainder of the pol region. Natural variations and signature polymorphisms were observed at codon positions 140, 148, 151, 157, and 160 among HIV subtypes. These variations predicted higher genetic barriers to G140S and G140C in subtypes C, CRF02_AG, and A/CRF01_AE, as well as higher genetic barriers toward acquisition of V151I in subtypes CRF02_AG and A/CRF01_AE. The E157Q and E160Q mutational motif was observed in 35% of INI-naïve patients harboring subtype C infections, indicating intra-subtype variations. Thirteen patients failed raltegravir (RAL)-containing regimens within 8 ± 1 months, in association with the major Q148K/R/H and G140A/S (n = 8/24) or N155H (n = 5/24) mutational pathways. Of note, the remaining patients on RAL regimens for 14 ± 3 months harbored no or only minor integrase mutations/polymorphisms (T66I, T97A, H114P, S119P, A124S, G163R, I203M, R263K). These results demonstrate the importance of understanding subtype variability in the development of resistance to INIs. PMID:21360548

  8. Histological subtype of lung cancer in relation to socio-economic deprivation in South East England

    International Nuclear Information System (INIS)

    Previous studies have found differences in the histological subtypes of lung cancers affecting males and females. Our objective was to investigate trends in the incidence of histological subtypes of lung cancer in males and females in relation to socio-economic deprivation in South East England. Data on 48,031 males and 30,454 females diagnosed with lung cancer between 1995 and 2004 were extracted from the Thames Cancer Registry database. Age-standardised incidence rates for histological subtypes were calculated for each year, using the European standard population. Using the Income Domain of the Multiple Index of Deprivation 2004, patients diagnosed between 2000 and 2004 were classified into quintiles of socio-economic deprivation based on their postcode of residence. Age-standardised rates for each histological subtype were then calculated for each deprivation quintile. A Poisson regression model was fitted to the data for males and females separately to test the hypothesis that the relationship between socio-economic deprivation and adenocarcinoma was less strong than for other subtypes. In males all specific histological subtypes except adenocarcinoma declined in incidence. Squamous cell carcinoma remained the most common specific subtype and large cell carcinoma the least common. In females squamous cell carcinoma was initially most common, but its incidence declined slightly and that for adenocarcinoma increased. In both sexes the overall age-standardised incidence rate of lung cancer increased with increasing deprivation. However, these trends were less strong for adenocarcinoma than for the other subtypes in both males (p < 0.001) and females (p = 0.003). The temporal trends and distribution of histological subtypes of lung cancer in males and females are similar to that reported from other western populations. In both males and females, adenocarcinoma was less strongly related to deprivation than other subtypes. This may be because its development is less

  9. Subtype diversity associated with the development of HIV-1 resistance to integrase inhibitors.

    Science.gov (United States)

    Brenner, Bluma G; Lowe, Matthew; Moisi, Daniela; Hardy, Isabelle; Gagnon, Simon; Charest, Hugues; Baril, Jean Guy; Wainberg, Mark A; Roger, Michel

    2011-05-01

    We used genotypic and phylogenetic analysis to determine integrase diversity among subtypes, and studied natural polymorphisms and mutations implicated in resistance to integrase inhibitors (INI) in treatment-naïve persons (n = 220) and -experienced individuals (n = 24). Phylogenetics revealed 7 and 10% inter-subtype diversity in the integrase and reverse transcriptase (RT)/protease regions, respectively. Integrase sequencing identified a novel A/B recombinant in which all viruses in a male-sex-male (MSM) transmission cluster (n = 12) appeared to possess subtype B in integrase and subtype A in the remainder of the pol region. Natural variations and signature polymorphisms were observed at codon positions 140, 148, 151, 157, and 160 among HIV subtypes. These variations predicted higher genetic barriers to G140S and G140C in subtypes C, CRF02_AG, and A/CRF01_AE, as well as higher genetic barriers toward acquisition of V151I in subtypes CRF02_AG and A/CRF01_AE. The E157Q and E160Q mutational motif was observed in 35% of INI-naïve patients harboring subtype C infections, indicating intra-subtype variations. Thirteen patients failed raltegravir (RAL)-containing regimens within 8 ± 1 months, in association with the major Q148K/R/H and G140A/S (n = 8/24) or N155H (n = 5/24) mutational pathways. Of note, the remaining patients on RAL regimens for 14 ± 3 months harbored no or only minor integrase mutations/polymorphisms (T66I, T97A, H114P, S119P, A124S, G163R, I203M, R263K). These results demonstrate the importance of understanding subtype variability in the development of resistance to INIs.

  10. Comparison of Sequencing (Barcode Region) and Sequence-Tagged-Site PCR for Blastocystis Subtyping

    Science.gov (United States)

    2013-01-01

    Blastocystis is the most common nonfungal microeukaryote of the human intestinal tract and comprises numerous subtypes (STs), nine of which have been found in humans (ST1 to ST9). While efforts continue to explore the relationship between human health status and subtypes, no consensus regarding subtyping methodology exists. It has been speculated that differences detected in subtype distribution in various cohorts may to some extent reflect different approaches. Blastocystis subtypes have been determined primarily in one of two ways: (i) sequencing of small subunit rRNA gene (SSU-rDNA) PCR products and (ii) PCR with subtype-specific sequence-tagged-site (STS) diagnostic primers. Here, STS primers were evaluated against a panel of samples (n = 58) already subtyped by SSU-rDNA sequencing (barcode region), including subtypes for which STS primers are not available, and a small panel of DNAs from four other eukaryotes often present in feces (n = 18). Although the STS primers appeared to be highly specific, their sensitivity was only moderate, and the results indicated that some infections may go undetected when this method is used. False-negative STS results were not linked exclusively to certain subtypes or alleles, and evidence of substantial genetic variation in STS loci was obtained. Since the majority of DNAs included here were extracted from feces, it is possible that STS primers may generally work better with DNAs extracted from Blastocystis cultures. In conclusion, due to its higher applicability and sensitivity, and since sequence information is useful for other forms of research, SSU-rDNA barcoding is recommended as the method of choice for Blastocystis subtyping. PMID:23115257

  11. Seroprevalence of antibodies to Venezuelan equine encephalitis complex (subtypes IAB and VI in humans from General Belgrano Island, Formosa, Argentina

    Directory of Open Access Journals (Sweden)

    Cámara Alicia

    2003-01-01

    Full Text Available This work presents the results of the detection of antibodies (immunoglobulin G for subtypes I and VI of VEE viruses complex (Togaviridae family in people from the General Belgrano island, Formosa province (Argentina. The prevalence of neutralizing (NT antibodies for subtype VI was from 30% to 70% and the prevalence of antibodies inhibitory of hemagglutination (HI was of 0% in the first and second inquiry respectively. For the subtype IAB the prevalence of NT antibodies was from 13% to 3.6%, similar to the prevalence total for both subtypes. HI antibodies were not detected in any inquiries for any subtype. It was observed that both subtypes circulate simultaneously, while subtype VI remains constant with some peaks, subtype I was found in low level.

  12. A novel broadly applicable PCR-RFLP method for rapid identification and subtyping of H58 Salmonella Typhi.

    Science.gov (United States)

    Murgia, Manuela; Rubino, Salvatore; Wain, John; Gaind, Rajni; Paglietti, Bianca

    2016-08-01

    Salmonella Typhi (S. Typhi), the human-adapted agent of typhoid fever, is genetically monomorphic. SNPs accumulation divided the S. Typhi population in 85 haplotypes (H) of which one, H58, has undergone a clonal expansion. The surveillance of H58 S. Typhi is particularly important, especially in areas where typhoid fever is endemic. We developed a simple PCR and PCR-RFLP method to detect and subtype H58 S. Typhi based on the presence of genomic deletion and specific SNPs. The method was validated against 39 S. Typhi isolates of known haplotype, showing 100% of specificity and high sensitivity, and then used to screen a collection of 99 S. Typhi from Asia, demonstrating a high incidence of H58 S. Typhi in Jordan and India. Our method is designed to be applied in all laboratories with basic molecular biology equipment and few financial resources and allows the surveillance of H58 S. Typhi in resource poor settings. PMID:27319376

  13. Genetic identification of Entamoeba polecki subtype 3 from pigs in Japan and characterisation of its pathogenic role in ulcerative colitis.

    Science.gov (United States)

    Matsubayashi, Makoto; Murakoshi, Naoko; Komatsu, Tetsuya; Tokoro, Masaharu; Haritani, Makoto; Shibahara, Tomoyuki

    2015-12-01

    To date, three Entamoeba spp. (E. suis, zoonotic E. polecki and E. histolytica) have been identified in pigs, but their pathogenicity and molecular classification have not been fully determined. Examination and pathological analysis of pigs (n=3) with diarrhoea was conducted and revealed the presence of Entamoeba organisms. We performed a genetic analysis of the isolate using the small-subunit ribosomal RNA (SSU rRNA) gene region to identify the species. A severe ulcerative colitis was observed histopathologically with inflammatory cells, including macrophages and neutrophils, infiltrating the mucous membranes of the cecum and colon. Many Entamoeba trophozoites were found at the erosion site or at ulcerative lesions. Pathogenic viruses or bacteria were not detected. The SSU rRNA sequence of the Entamoeba isolate was found to be completely homologous to that of E. polecki subtype 3.

  14. Molecular epidemiology of HIV-1 strains in the south-east and east of Turkey

    Institute of Scientific and Technical Information of China (English)

    Mustafa; Kemal; ?elen; Murat; Sayan; Tuba; Dal; Celal; Ayaz; Alicem; Tekin; Tuncer; ?zekinci; Suda; Tekin; Koruk; Tunga; Barcin; Recep; Tekin; Mehmet; Sinan; Dal; Sevgi; Kalkanl?

    2015-01-01

    Objective:To detect the subtype characterization and drug-resistant mutations in HIV-1 strains after the refugee movement from Syria to Turkey between 2011 and 2014 in south east border lines. Methods: A total of 65 patients were included in this study, of which 57(88%) patients were antiretroviral therapy-naive patients. HIV-1 RNA was detected and quantii ed by realtime PCR assay. HIV-1 subtypes and circulating recombinant forms(CRFs) were identii ed by phylogenetic analysis(neighbor-joining method), and drug-resistant mutations were analyzed.Results: Three major HIV groups were indicated. Two of these groups were located in subtype B. The other group showed heterogeneity. Subtype B(48/65, 73.8%), followed by CRFs(12/65, 18.5%) was the most common strain. Subtype of CRFs consisted of CRF01_AE(9/65, 13.8%) and CRF02_AG(3/65, 4.6%). Subtype C(1/65, 1.5%), sub-subtypes A1(2/65, 3.1%) and F1(2/65, 3.1%) were also detected with low prevalence. The rate of overall primary antiretroviral resistance was 4.9%(3/61). Drug-resistant rate for non-nucleoside reverse transcriptase inhibitors was 4.9%. The thymidine analogue mutation rate was 13.1%(8/61).Conclusions: HIV molecular epidemiology studies are necessary to determine transmission patterns and spread. Subtype B and CRF01_AE, CRF02_AG are the most prevalent strains in the south-east of Turkey. However, subtype C, sub-subtypes A1 and F1 are of low prevalence but persist in the south-east of Turkey. In the near future, changing of HIV epidemiology will be possible in Turkey due to migration movement in border lines and resistance testing will play an important role in HIV management.

  15. Molecular epidemiology of HIV-1 strains in the south-east and east of Turkey

    Institute of Scientific and Technical Information of China (English)

    Mustafa Kemal elen; Mehmet Sinan Dal; Sevgi Kalkanl; Murat Sayan; Tuba Dal; Celal Ayaz; Alicem Tekin; Tuncer zekinci; Suda Tekin Koruk; Tunga Barcin; Recep Tekin

    2015-01-01

    To detect the subtype characterization and drug-resistant mutations in HIV-1 strains after the refugee movement from Syria to Turkey between 2011 and 2014 in south east border lines. Methods: A total of 65 patients were included in this study, of which 57 (88%) patients were antiretroviral therapy-naive patients. HIV-1 RNA was detected and quantified by real-time PCR assay. HIV-1 subtypes and circulating recombinant forms (CRFs) were identified by phylogenetic analysis (neighbor-joining method), and drug-resistant mutations were analyzed. Results: Three major HIV groups were indicated. Two of these groups were located in subtype B. The other group showed heterogeneity. Subtype B (48/65, 73.8%), followed by CRFs (12/65, 18.5%) was the most common strain. Subtype of CRFs consisted of CRF01_AE (9/65, 13.8%) and CRF02_AG (3/65, 4.6%). Subtype C (1/65, 1.5%), sub-subtypes A1 (2/65, 3.1%) and F1 (2/65, 3.1%) were also detected with low prevalence. The rate of overall primary antiretroviral resistance was 4.9% (3/61). Drug-resistant rate for non-nucleoside reverse transcriptase inhibitors was 4.9%. The thymidine analogue mutation rate was 13.1% (8/61). Conclusions: HIV molecular epidemiology studies are necessary to determine transmission patterns and spread. Subtype B and CRF01_AE, CRF02_AG are the most prevalent strains in the south-east of Turkey. However, subtype C, sub-subtypes A1 and F1 are of low prevalence but persist in the south-east of Turkey. In the near future, changing of HIV epidemiology will be possible in Turkey due to migration movement in border lines and resistance testing will play an important role in HIV management.

  16. Analysis of the Differentiation of Kenyon Cell Subtypes Using Three Mushroom Body-Preferential Genes during Metamorphosis in the Honeybee (Apis mellifera L.)

    Science.gov (United States)

    Okude, Genta; Fujiyuki, Tomoko; Shirai, Kenichi; Kubo, Takeo

    2016-01-01

    The adult honeybee (Apis mellifera L.) mushroom bodies (MBs, a higher center in the insect brain) comprise four subtypes of intrinsic neurons: the class-I large-, middle-, and small-type Kenyon cells (lKCs, mKCs, and sKCs, respectively), and class-II KCs. Analysis of the differentiation of KC subtypes during metamorphosis is important for the better understanding of the roles of KC subtypes related to the honeybee behaviors. In the present study, aiming at identifying marker genes for KC subtypes, we used a cDNA microarray to comprehensively search for genes expressed in an MB-preferential manner in the honeybee brain. Among the 18 genes identified, we further analyzed three genes whose expression was enriched in the MBs: phospholipase C epsilon (PLCe), synaptotagmin 14 (Syt14), and discs large homolog 5 (dlg5). Quantitative reverse transcription-polymerase chain reaction analysis revealed that expression of PLCe, Syt14, and dlg5 was more enriched in the MBs than in the other brain regions by approximately 31-, 6.8-, and 5.6-fold, respectively. In situ hybridization revealed that expression of both Syt14 and dlg5 was enriched in the lKCs but not in the mKCs and sKCs, whereas expression of PLCe was similar in all KC subtypes (the entire MBs) in the honeybee brain, suggesting that Syt14 and dlg5, and PLCe are available as marker genes for the lKCs, and all KC subtypes, respectively. In situ hybridization revealed that expression of PLCe is already detectable in the class-II KCs at the larval fifth instar feeding stage, indicating that PLCe expression is a characteristic common to the larval and adult MBs. In contrast, expression of both Syt14 and dlg5 became detectable at the day three pupa, indicating that Syt14 and dlg5 expressions are characteristic to the late pupal and adult MBs and the lKC specific molecular characteristics are established during the late pupal stages. PMID:27351839

  17. Neurophysiological mechanisms of emotion regulation for subtypes of externalizing children

    Science.gov (United States)

    Stieben, James

    Children referred for externalizing behavior problems may not represent a homogeneous population. The objective of this study was to assess the neural mechanisms of emotion regulation that might distinguish subtypes of externalizing children from each other and from their typically developing age-mates. Children with pure externalizing (EXT) problems were compared with children comorbid for externalizing and internalizing (MIXED) problems and with age-matched controls. Only boys were included in the analysis because so few girls were referred for treatment. A go/no-go task with a negative emotion induction was used to examine dense-array EEG data together with behavioral measures of performance. Four event-related potential (ERP) components tapping inhibitory control or self-monitoring were assessed including the inhibitory N2, the error-related negativity (ERN), the error positivity (Pe) and the frontal inhibitory P3 (iP3). Source models were constructed estimating the cortical generators of these components. The MIXED children's N2s increased in response to the emotion induction, resulting in greater amplitudes than EXT children in the following trial block. MIXED and EXT children showed increased N2 latencies compared to controls. ERN amplitudes were greatest for control children and smallest for EXT children with MIXED children in between, but only prior to the emotion induction. N2 component latencies were shorter for controls but only before and after the induction block with a significantly faster N2 for controls only in block C relative to MIXED children. Latencies for the ERN component were longer for the EXT children in blocks A and B relative to both MIXED and controls. Mixed results were found for both the Pe and frontal P3 amplitude. Pe amplitudes were smallest for control children in blocks A and B relative to both clinical groups. Pe latencies were consistent across groups with the exception of block B where EXT children showed an increase in

  18. Does Subtype Matter? Assessing the Effects of Maltreatment on Functioning in Preadolescent Youth in Out-of-Home Care

    Science.gov (United States)

    Petrenko, Christie L. M.; Friend, Angela; Garrido, Edward F.; Taussig, Heather N.; Culhane, Sara E.

    2012-01-01

    Objectives: Attempts to understand the effects of maltreatment subtypes on childhood functioning are complicated by the fact that children often experience multiple subtypes. This study assessed the effects of maltreatment subtypes on the cognitive, academic, and mental health functioning of preadolescent youth in out-of-home care using both…

  19. Characterization of a novel influenza A virus hemagglutinin subtype (H16) obtained from black-headed gulls.

    NARCIS (Netherlands)

    R.A.M. Fouchier (Ron); V.J. Munster (Vincent); A. Wallensten (Anders); T.M. Bestebroer (Theo); S. Herfst (Sander); D.R. Smith (Derek Richard); G.F. Rimmelzwaan (Guus); B. Olsen (Björn); A.D.M.E. Osterhaus (Albert)

    2005-01-01

    textabstractIn wild aquatic birds and poultry around the world, influenza A viruses carrying 15 antigenic subtypes of hemagglutinin (HA) and 9 antigenic subtypes of neuraminidase (NA) have been described. Here we describe a previously unidentified antigenic subtype of HA (H16), detected in viruses c

  20. Outcome of R-CHOP or CHOP Regimen for Germinal Center and Nongerminal Center Subtypes of Diffuse Large B-Cell Lymphoma of Chinese Patients

    Directory of Open Access Journals (Sweden)

    Ying Huang

    2012-01-01

    Full Text Available Diffuse large B-cell lymphoma (DLBCL can be molecularly subtyped as either germinal center B-cell (GCB or non-GCB. The role of rituximab(R in these two groups remains unclear. We studied 204 patients with de novo DLBCL (107 treated with first-line CHOP; 97 treated with first-line R-CHOP, patients being stratified into GCB and non-GCB on the basis of BCL-6, CD10, and MUM1 protein expression. The relationships between clinical characteristics, survival data, and immunophenotype (IHC were studied. The 5-year overall survival (OS in the CHOP and R-CHOP groups was 50.4% and 66.6% (P=0.031, respectively. GCB patients had a better 5-year OS than non-GCB patients whether treated with CHOP or not (65.0% versus 40.9%; P=0.011. In contrast, there is no difference in the 5-year OS for the GCB and non-GCB with R-CHOP (76.5% versus 61.3%; P=0.141. In non-GCB subtype, additional rituximab improved survival better than CHOP (61.3% versus 40.9%; P=0.0303. These results indicated that addition of rituximab to standard chemotherapy eliminates the prognostic value of IHC-defined GCB and non-GCB phenotypes in DLBCL by improving the prognostic value of non-GCB subtype of DLBCL.

  1. Molecular basis of the triple negative breast cancer

    OpenAIRE

    Ayse Feyda Nursal

    2015-01-01

    Breast cancer is the most common type of cancer in women and more than 1 million breast cancer cases are diagnosed each year all over the world. Breast cancer is a complex and heterogeneous disease in terms of its molecular structure, mutation type, metastase properties, clinical course and therapeutic response. Breast cancer is divided into subtypes based on expression properties of molecular markers as estrogen receptor, progestron receptor, human epidermal growth factor receptor 2. Triple-...

  2. Personality subtypes in male patients with eating disorder: validation of a classification approach.

    Science.gov (United States)

    Claes, Laurence; Fernandez-Aranda, Fernando; Jiménez-Murcia, Susana; Agüera, Zaida; Granero, Roser; Sánchez, Isabel; Menchón, Jose Manuel

    2012-10-01

    In the present study, we investigated personality subtypes and their correlates in a sample of 132 male patients with eating disorder (ED). All patients filled out the Temperament and Character Inventory-Revised, the Eating Disorder Inventory-2, and the Symptom Checklist-90-Revised. Three personality subtypes emerged. Cluster 1, the adaptive-like subtype, was characterized by a high prevalence of eating-disorder-not-otherwise-specified and low levels of ED and general psychopathology. Cluster 2, the average or socially detached subtype, showed a high prevalence of eating-disorder-not-otherwise-specified, more social problems, less motivation for treatment, and an intermediate position on the psychopathology dimension between patients of clusters 1 and 3. Finally, cluster 3, the maladaptive subtype, was characterized the highest prevalence of bulimia nervosa and the highest scores on ED and general psychopathology. Our data support the presence of the 3 personality subtypes in male patients with ED. Future studies need to address whether patients of different subtypes differ with respect to therapy outcome.

  3. The Origin and Evolutionary History of HIV-1 Subtype C in Senegal

    Science.gov (United States)

    Jung, Matthieu; Leye, Nafissatou; Vidal, Nicole; Fargette, Denis; Diop, Halimatou; Toure Kane, Coumba; Gascuel, Olivier; Peeters, Martine

    2012-01-01

    Background The classification of HIV-1 strains in subtypes and Circulating Recombinant Forms (CRFs) has helped in tracking the course of the HIV pandemic. In Senegal, which is located at the tip of West Africa, CRF02_AG predominates in the general population and Female Sex Workers (FSWs). In contrast, 40% of Men having Sex with Men (MSM) in Senegal are infected with subtype C. In this study we analyzed the geographical origins and introduction dates of HIV-1 C in Senegal in order to better understand the evolutionary history of this subtype, which predominates today in the MSM population Methodology/Principal Findings We used a combination of phylogenetic analyses and a Bayesian coalescent-based approach, to study the phylogenetic relationships in pol of 56 subtype C isolates from Senegal with 3,025 subtype C strains that were sampled worldwide. Our analysis shows a significantly well supported cluster which contains all subtype C strains that circulate among MSM in Senegal. The MSM cluster and other strains from Senegal are widely dispersed among the different subclusters of African HIV-1 C strains, suggesting multiple introductions of subtype C in Senegal from many different southern and east African countries. More detailed analyses show that HIV-1 C strains from MSM are more closely related to those from southern Africa. The estimated date of the MRCA of subtype C in the MSM population in Senegal is estimated to be in the early 80's. Conclusions/Significance Our evolutionary reconstructions suggest that multiple subtype C viruses with a common ancestor originating in the early 1970s entered Senegal. There was only one efficient spread in the MSM population, which most likely resulted from a single introduction, underlining the importance of high-risk behavior in spread of viruses. PMID:22470456

  4. Molecular physics

    CERN Document Server

    Williams, Dudley

    2013-01-01

    Methods of Experimental Physics, Volume 3: Molecular Physics focuses on molecular theory, spectroscopy, resonance, molecular beams, and electric and thermodynamic properties. The manuscript first considers the origins of molecular theory, molecular physics, and molecular spectroscopy, as well as microwave spectroscopy, electronic spectra, and Raman effect. The text then ponders on diffraction methods of molecular structure determination and resonance studies. Topics include techniques of electron, neutron, and x-ray diffraction and nuclear magnetic, nuclear quadropole, and electron spin reson

  5. Functional subtyping of muscarinic receptors on canine esophageal mucosa.

    Science.gov (United States)

    Lad, R; Donoff, B; Rangachari, P K

    1991-09-01

    Serosal addition of muscarinic agonists elicited rapid changes in electrical parameters across the isolated canine esophageal epithelium set up in vitro. Both carbachol and the M1-selective agonist, McNeil A343 (McN), increased transmucosal potential differences (PDs), decreased transmucosal resistances (R), and increased short-circuit currents (Isc). Carbachol was more potent and more effective than McN. Muscarinic antagonists were used to define the muscarinic receptor involved. The pA2 values obtained with Schild plots were as follows: atropine 9.14, 4-DAMP 8.98, AFDX-116 6.71, and pirenzepine 7.12. Low concentrations of pirenzepine (10(-8) M), produced a rightward shift in the dose-response curve to McN, without inhibiting responses to carbachol. Thus the receptor subtype is clearly not an M2. As in other glandular systems, M3 receptors are present. Whether M1 receptors also exist requires better definition of receptor densities-reserves in this tissue. Carbachol induced net secretion of Na and Cl and converted a predominantly absorptive tissue to a secretory one. PMID:1716057

  6. Functional characterization of serotonin receptor subtypes in human duodenal secretion

    DEFF Research Database (Denmark)

    Engelmann, Bodil Elisabeth; Bindslev, Niels; Poulsen, Steen Seier;

    2006-01-01

    Serotonin (5-HT) stimulates ion secretion in the gastrointestinal tract and the sensitivity for 5-HT might be altered in dyspeptic patients infected with Helicobacter pylori. The purpose of the present study was to characterize the 5-HT-induced electrogenic ion transport in the duodenum of dyspep......Serotonin (5-HT) stimulates ion secretion in the gastrointestinal tract and the sensitivity for 5-HT might be altered in dyspeptic patients infected with Helicobacter pylori. The purpose of the present study was to characterize the 5-HT-induced electrogenic ion transport in the duodenum...... of dyspeptic patients with or without Helicobacter pylori infection, and to determine the 5-HT receptor subtypes functionally involved. Biopsies from the second part of duodenum were obtained from 43 dyspeptic patients during routine endoscopy. Biopsies were mounted in modified Ussing chambers with air suction...... for measurements of short-circuit current by a previously validated technique. Short-circuit current was measured before and after application of graded cumulative doses of 5-HT and a single dose of bumetanide (an inhibitor of chloride/bicarbonate transport), or one of the selective 5-HT receptor antagonists...

  7. Cherry-picked ligands at histamine receptor subtypes.

    Science.gov (United States)

    Sadek, Bassem; Stark, Holger

    2016-07-01

    Histamine, a biogenic amine, is considered as a principle mediator of multiple physiological effects through binding to its H1, H2, H3, and H4 receptors (H1-H4Rs). Currently, the HRs have gained attention as important targets for the treatment of several diseases and disorders ranging from allergy to Alzheimer's disease and immune deficiency. Accordingly, medicinal chemistry studies exploring histamine-like molecules and their physicochemical properties by binding and interacting with the four HRs has led to the development of a diversity of agonists and antagonists that display selectivity for each HR subtype. An overview on H1-R4Rs and developed ligands representing some key steps in development is provided here combined with a short description of structure-activity relationships for each class. Main chemical diversities, pharmacophores, and pharmacological profiles of most innovative H1-H4R agonists and antagonists are highlighted. Therefore, this overview should support the rational choice for the optimal ligand selection based on affinity, selectivity and efficacy data in biochemical and pharmacological studies. This article is part of the Special Issue entitled 'Histamine Receptors'. PMID:26581501

  8. Adrenergic receptor subtypes in the cerebral circulation of newborn piglets

    Energy Technology Data Exchange (ETDEWEB)

    Wagerle, L.C.; Delivoria-Papadopoulos, M.

    1987-06-01

    The purpose of this study was to identify the ..cap alpha..-adrenergic receptor subtype mediating cerebral vasoconstriction during sympathetic nerve stimulation in the newborn piglet. The effect of ..cap alpha../sub 1/- and ..cap alpha../sub 2/-antagonists prazosin and yohimbine on the cerebrovascular response to unilateral electrical stimulation (15 Hz, 15 V) of the superior cervical sympathetic trunk was studied in 25 newborn piglets. Regional cerebral blood flow was measured with tracer microspheres. Sympathetic stimulation decreased blood flow to the ipsilateral cerebrum hippocampus, choroid plexus, and masseter muscle. ..cap alpha../sub 1/-Adrenergic receptor blockade with prazosin inhibited the sympathetic vasoconstriction in the cerebrum, hippocampus, and masseter muscle and abolished it in the choroid plexus. ..cap alpha../sub s/-Adrenergic receptor blockade with yohimbine had no effect. Following the higher dose of yohimbine, however, blood flow to all brain regions was increased by approximately two-fold, possibly due to enhanced cerebral metabolism. These data demonstrate that vascular ..cap alpha../sub 1/-adrenergic receptors mediate vasoconstriction to neuroadrenergic stimulation in cerebral resistance vessels in the newborn piglet.

  9. Homicide-Complex Suicide: A Rare Subtype of Dyadic Death

    Directory of Open Access Journals (Sweden)

    Ramazan Akçan

    2016-06-01

    Full Text Available Homicide-suicide, a subtype of dyadic death, is described as murderer’s suicide following committing a homicide. Here, we present a case of homicide-suicide which is relatively rare because of involving complex suicide as suicide method of perpetrator. A 30 year-old male and 38 year-old female were found dead in an apartment. Post­mortem investigation of man revealed that wrist cutting and hanging were used as suicide methods compatibly with complex suicide. Postmortem investigation of wom­an showed extensive traumatic lesions compatible with manual strangulation on neck structures and the mode of death was homicide. In the light of all findings case was concluded to be a dyadic death involving homicide-com­plex. The presented case is rare in terms of combination of rare methods of dyadic death, and committed complex suicide by perpetrator. While determining mode of death, detailed case history and witness statements should be taken into account along with forensic autopsy findings.

  10. Subtypes of GABAergic neurons project axons in the neocortex

    Directory of Open Access Journals (Sweden)

    Shigeyoshi Higo

    2009-11-01

    Full Text Available γ-aminobutyric acid (GABAergic neurons in the neocortex have been regarded as interneurons and speculated to modulate the activity of neurons locally. Recently, however, several experiments revealed that neuronal nitric oxide synthase (nNOS-positive GABAergic neurons project cortico-cortically with long axons. In this study, we illustrate Golgi-like images of the nNOS-positive GABAergic neurons using a nicotinamide adenine dinucleotide phosphate diaphorase (NADPH-d reaction and follow the emanating axon branches in cat brain sections. These axon branches projected cortico-cortically with other non-labeled arcuate fibers, contra-laterally via the corpus callosum and anterior commissure. The labeled fibers were not limited to the neocortex but found also in the fimbria of the hippocampus. In order to have additional information on these GABAergic neuron projections, we investigated green fluorescent protein (GFP-labeled GABAergic neurons in GAD67-Cre knock-in / GFP Cre-reporter mice. GFP-labeled axons emanate densely, especially in the fimbria, a small number in the anterior commissure, and very sparsely in the corpus callosum. These two different approaches confirm that not only nNOS-positive GABAergic neurons but also other subtypes of GABAergic neurons project long axons in the cerebral cortex and are in a position to be involved in information processing.

  11. Do neurocognitive deficits in decision making differentiate conduct disorder subtypes?

    Science.gov (United States)

    Fanti, Kostas A; Kimonis, Eva R; Hadjicharalambous, Maria-Zoe; Steinberg, Laurence

    2016-09-01

    The present study aimed to test whether neurocognitive deficits involved in decision making underlie subtypes of conduct-disorder (CD) differentiated on the basis of callous-unemotional (CU) traits. Eighty-five participants (M age = 10.94 years) were selected from a sample of 1200 children based on repeated assessment of CD and CU traits. Participants completed a multi-method battery of well-validated measures of risky decision making and associated constructs of selective attention and future orientation (Stroop, Stoplight, and Delay-Discounting Tasks). Findings indicated that impaired decision making, selective attention, and future orientation contribute to the antisocial presentations displayed by children with CD, irrespective of level of CU traits. Youth high on CU traits without CD showed less risky decision making, as indicated by their performance on the Stoplight laboratory task, than those high on both CD and CU traits, suggesting a potential protective factor against the development of antisocial behavior. PMID:26832949

  12. Oxidatively Modified Proteins in the Serous Subtype of Ovarian Carcinoma

    Directory of Open Access Journals (Sweden)

    Sharifeh Mehrabi

    2014-01-01

    Full Text Available Serous subtype of ovarian cancer is considered to originate from fallopian epithelium mucosa that has been exposed to physiological changes resulting from ovulation. Ovulation influences an increased in inflammation of epithelial ovarian cells as results of constant exposure of cells to ROS. The imbalance between ROS and antioxidant capacities, as well as a disruption of redox signaling, causes a wide range of damage to DNA, proteins, and lipids. This study applied spectrophotometric, dinitrophenylhydrazone (DNPH assay, two-dimensional gel electrophoresis, and Western blot analyses to assess the levels of oxidatively modified proteins in 100 primary serous epithelial ovarian carcinoma and normal/surrounding tissues. These samples were obtained from 56 Caucasian and 44 African-American patients within the age range of 61±10 years. Analyses showed that the levels of reactive protein carbonyl groups increased as stages progressed to malignancy. Additionally, the levels of protein carbonyls in serous ovarian carcinoma among African Americans are 40% (P<0.05 higher relative to Caucasian at similar advanced stages. Results suggest that oxidative stress is involved in the modification of carbonyl protein groups, leading to increased aggressiveness of epithelial ovarian tumors and may contribute to the disease's invasiveness among African Americans.

  13. T Cell Transcriptomes Describe Patient Subtypes in Systemic Lupus Erythematosus.

    Directory of Open Access Journals (Sweden)

    Sean J Bradley

    Full Text Available T cells regulate the adaptive immune response and have altered function in autoimmunity. Systemic Lupus Erythematosus (SLE has great diversity of presentation and treatment response. Peripheral blood component gene expression affords an efficient platform to investigate SLE immune dysfunction and help guide diagnostic biomarker development for patient stratification.Gene expression in peripheral blood T cell samples for 14 SLE patients and 4 controls was analyzed by high depth sequencing. Unbiased clustering of genes and samples revealed novel patterns related to disease etiology. Functional annotation of these genes highlights pathways and protein domains involved in SLE manifestation.We found transcripts for hundreds of genes consistently altered in SLE T cell samples, for which DAVID analysis highlights induction of pathways related to mitochondria, nucleotide metabolism and DNA replication. Fewer genes had reduced mRNA expression, and these were linked to signaling, splicing and transcriptional activity. Gene signatures associated with the presence of dsDNA antibodies, low complement levels and nephritis were detected. T cell gene expression also indicates the presence of several patient subtypes, such as having only a minimal expression phenotype, male type, or severe with or without induction of genes related to membrane protein production.Unbiased transcriptome analysis of a peripheral blood component provides insight on autoimmune pathophysiology and patient variability. We present an open source workflow and richly annotated dataset to support investigation of T cell biology, develop biomarkers for patient stratification and perhaps help indicate a source of SLE immune dysfunction.

  14. Mild cognitive impairment in Parkinson's disease: subtypes and motor characteristics.

    Science.gov (United States)

    Sollinger, Ann B; Goldstein, Felicia C; Lah, James J; Levey, Allan I; Factor, Stewart A

    2010-03-01

    The aims of this project were to determine the risk factors for and clinical characteristics of mild cognitive impairment (MCI) in Parkinson's disease (PD). We performed a retrospective record review of 72 non-demented PD patients (age: 57.79 +/- 10.57, duration of PD: 7.32 +/- 4.97) who completed a standardized neurological assessment, including a full neuropsychological battery, as part of their diagnostic work-up. Of these participants, 47.2% were cognitively normal and 52.8% met criteria for MCI. The majority of MCI patients had single domain MCI (23/38), the affected domains being memory (n = 9), executive function (n = 6), visuospatial skills (n = 6), and language (n = 2). The MCI group had longer duration of disease and higher postural instability and gait disorder subscale scores than the cognitively normal group. This report provides further support for use of the concept of MCI in PD research. There may be certain disease characteristics that could alert practitioners to the emergence of cognitive changes in patients. Future studies should focus on additional risk factors for MCI subtypes and their possible progression to frank dementia.

  15. Identifying Cancer Subtypes from miRNA-TF-mRNA Regulatory Networks and Expression Data.

    Directory of Open Access Journals (Sweden)

    Taosheng Xu

    Full Text Available Identifying cancer subtypes is an important component of the personalised medicine framework. An increasing number of computational methods have been developed to identify cancer subtypes. However, existing methods rarely use information from gene regulatory networks to facilitate the subtype identification. It is widely accepted that gene regulatory networks play crucial roles in understanding the mechanisms of diseases. Different cancer subtypes are likely caused by different regulatory mechanisms. Therefore, there are great opportunities for developing methods that can utilise network information in identifying cancer subtypes.In this paper, we propose a method, weighted similarity network fusion (WSNF, to utilise the information in the complex miRNA-TF-mRNA regulatory network in identifying cancer subtypes. We firstly build the regulatory network where the nodes represent the features, i.e. the microRNAs (miRNAs, transcription factors (TFs and messenger RNAs (mRNAs and the edges indicate the interactions between the features. The interactions are retrieved from various interatomic databases. We then use the network information and the expression data of the miRNAs, TFs and mRNAs to calculate the weight of the features, representing the level of importance of the features. The feature weight is then integrated into a network fusion approach to cluster the samples (patients and thus to identify cancer subtypes. We applied our method to the TCGA breast invasive carcinoma (BRCA and glioblastoma multiforme (GBM datasets. The experimental results show that WSNF performs better than the other commonly used computational methods, and the information from miRNA-TF-mRNA regulatory network contributes to the performance improvement. The WSNF method successfully identified five breast cancer subtypes and three GBM subtypes which show significantly different survival patterns. We observed that the expression patterns of the features in some mi

  16. Structure-Based Evolution of Subtype-Selective Neurotensin Receptor Ligands

    OpenAIRE

    Schaab, Carolin; Kling, Ralf Christian; Einsiedel, Jürgen; Hübner, Harald; Clark, Tim; Seebach, Dieter; Gmeiner, Peter

    2014-01-01

    Subtype-selective agonists of the neurotensin receptor NTS2 represent a promising option for the treatment of neuropathic pain, as NTS2 is involved in the mediation of μ-opioid-independent anti-nociceptive effects. Based on the crystal structure of the subtype NTS1 and previous structure–activity relationships (SARs) indicating a potential role for the sub-pocket around Tyr11 of NT(8–13) in subtype-specific ligand recognition, we have developed new NTS2-selective ligands. Starting from NT(8–1...

  17. Subtype-specific reduction of olfactory bulb interneurons in Pax6 heterozygous mutant mice.

    Science.gov (United States)

    Haba, Hasumi; Nomura, Tadashi; Suto, Fumikazu; Osumi, Noriko

    2009-09-01

    Interneurons in the olfactory bulb (OB) play essential roles in the processing of olfactory information. They are classified into several subpopulations by the expression of different neurochemical markers. Here we focused on a transcription factor Pax6, and examined its expression and function in distinct subtypes of OB interneurons. We identified Pax6 expression in specific subtypes of interneurons in the external plexiform layer (EPL). The number of these interneuron subtypes was dramatically decreased in Pax6 heterozygous mutant mice. These results indicate that Pax6 is required for differentiation and/or maintenance of EPL interneurons in the adult mouse OB.

  18. Towards a brief definition of burnout syndrome by subtypes: Development of the "Burnout Clinical Subtypes Questionnaire" (BCSQ-12

    Directory of Open Access Journals (Sweden)

    Gili Margarita

    2011-09-01

    Full Text Available Abstract Background Burnout has traditionally been described by means of the dimensions of exhaustion, cynicism and lack of eficacy from the "Maslach Burnout Inventory-General Survey" (MBI-GS. The "Burnout Clinical Subtype Questionnaire" (BCSQ-12, comprising the dimensions of overload, lack of development and neglect, is proposed as a brief means of identifying the different ways this disorder is manifested. The aim of the study is to test the construct and criterial validity of the BCSQ-12. Method A cross-sectional design was used on a multi-occupational sample of randomly selected university employees (n = 826. An exploratory factor analysis (EFA was performed on half of the sample using the maximum likelihood (ML method with varimax orthogonal rotation, while confirmatory factor analysis (CFA was performed on the other half by means of the ML method. ROC curve analysis was preformed in order to assess the discriminatory capacity of BCSQ-12 when compared to MBI-GS. Cut-off points were proposed for the BCSQ-12 that optimized sensitivity and specificity. Multivariate binary logistic regression models were used to estimate effect size as an odds ratio (OR adjusted for sociodemographic and occupational variables. Contrasts for sex and occupation were made using Mann-Whitney U and Kruskall-Wallis tests on the dimensions of both models. Results EFA offered a solution containing 3 factors with eigenvalues > 1, explaining 73.22% of variance. CFA presented the following indices: χ2 = 112.04 (p 2/gl = 2.44, GFI = 0.958, AGFI = 0.929, RMSEA = 0.059, SRMR = 0.057, NFI = 0.958, NNFI = 0.963, IFI = 0.975, CFI = 0.974. The area under the ROC curve for 'overload' with respect to the 'exhaustion' was = 0.75 (95% CI = 0.71-0.79; it was = 0.80 (95% CI = 0.76-0.86 for 'lack of development' with respect to 'cynicism' and = 0.74 (95% CI = 0.70-0.78 for 'neglect' with respect to 'inefficacy'. The presence of 'overload' increased the likelihood of suffering from

  19. Breast Molecular Profiling and Radiotherapy Considerations.

    Science.gov (United States)

    Mahmoud, Omar; Haffty, Bruce G

    2016-01-01

    The last decade has seen major changes in the management of breast cancer. Heterogeneity regarding histology, therapeutic response, dissemination patterns, and patient outcome is evident. Molecular profiling provides an accurate tool to predict treatment outcome compared with classical clinicopathologic features. The genomic profiling unveiled the heterogeneity of breast cancer and identified distinct biologic subtypes. These advanced techniques were integrated into the clinical management; predicting systemic therapy benefit and overall survival. Utilizing genotyping to guide locoregional management decisions needs further characterization. In this chapter we will review available data on molecular classification of breast cancer, their association with locoregional outcome, their radiobiological properties and radiotherapy considerations. PMID:26987532

  20. Breast cancer. From molecular biology to personified therapy

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    Bondarenko I.N.

    2016-03-01

    Full Text Available Advances in molecular biology had changed approaches to systemic treatment of breast cancer. Clinical decisions on the choice of optimal treatment regimens are performing on the basis of immunohistochemical and molecular genetic classifications. Their increasing uses have contributed changes of paradigm for cancer treatment - from the empirical to the individualized and personalized. The basis for such approaches is knowledge of molecular epidemiology, heterogeneity of expression of molecular subtypes, prognostic and predictive biomarkers of breast cancer. Breast cancer is a widely heterogeneous disease with 20 histological types, 8, molecular-genetic, 6 genomic subtypes, which are characterized by specific molecular and biochemical properties, different clinical course and different outcomes. Molecular genetic classification, created not on the basis of clinical, anatomical and morphological heterogeneity of tumor cells, and on the basis of their molecular-genetic heterogeneity is widely used in clinical practice. This allowed to separate the patients with breast cancer to molecular 4 subtypes - luminal A, luminal B, HER / 2 positive and triple-negative. The significant role of immunohistochemical tissue tumor markers, estrogen and progesterone receptors, HER / 2-neu, Ki-67, p53 for selection the optimal treatment strategy is analyzing in this review. To increase the effectiveness of breast cancer treatment is possible, using a differentiated and personalized approach based on new molecular genetic classification of breast cancer (gene profiling or to its analogue - expression classification of breast cancer, based on the principle of diversity of immunohistochemical tumor tissue. Personification of cancer treatment involves a therapy based on the study of individual characteristics of tissue is not only the primary tumor but also its metastases. Citation: Bondarenko IN, Elhajj Mohammad H, Prokhach AV, Zavizion VF, Chebanov KO. [Breast cancer

  1. HIV subtype is not associated with dementia among individuals with moderate and advanced immunosuppression in Kampala, Uganda

    Science.gov (United States)

    Sacktor, Ned; Nakasujja, Noeline; Redd, Andrew D.; Manucci, Jordyn; Laeyendecker, Oliver; Wendel, Sarah K.; Porcella, Stephen F; Martens, Craig; Bruno, Daniel; Skolasky, Richard L.; Okonkwo, Ozioma C.; Robertson, Kevin; Musisi, Seggane; Katabira, Elly; Quinn, Thomas C.

    2014-01-01

    Background HIV-associated neurocognitive disorders (HAND) are a common neurological manifestation of HIV infection. A previous study suggested that HIV dementia may be more common among patients with subtype D virus than among those with subtype A virus among HIV+ individuals with advanced immunosuppression. We conducted a study to evaluate the frequency of HIV dementia, and the association of HIV dementia with HIV subtype and compartmentalization among HIV+ individuals with moderate and advanced immunosuppression (CD4 lymphocyte count >150 cells/μL and < 250 cells/μL). Methods The study enrolled 117 antiretroviral naïve HIV+ individuals in Kampala, Uganda. HIV+ individuals received neurological, neuropsychological testing, and functional assessments, and gag and gp41 regions were subtyped. Subjects were considered infected with a specific subtype if both regions analyzed were from the same subtype. Results 41% of the HIV+ individuals had HIV dementia (mean CD4 lymphocyte count= 233 cells/μL). 67 individuals had subtype A, 25 individuals had subtype D, 24 individuals were classified as A/D recombinants, and one individual had subtype C. There was no difference in the frequency of HIV dementia when stratified by HIV subtype A and D and no association with compartmentalization between the cerebrospinal fluid and peripheral blood. Conclusions These results suggest that HIV dementia is common in HIV+ individuals in Uganda. There was no association between HIV subtype and dementia among HIV+ individuals with moderate and advanced immunosuppression. Future studies should be performed to confirm these results. PMID:24515303

  2. Immunity raised by recent European subtype 1 PRRSV strains allows better replication of East European subtype 3 PRRSV strain Lena than that raised by an older strain

    DEFF Research Database (Denmark)

    Trus, Ivan; Frydas, Ilias S.; Reddy, Vishwanatha R. A. P.;

    2016-01-01

    : 8.3). Reduction of respiratory disease, nasal shedding (mean AUC and mean peak values) and viremia (mean AUC and mean peak values) was more pronounced in 07V063-immune (p animals. Inoculation with subtype 1 PRRSV strains caused priming of the Lena......-specific virus neutralization antibody response. Upon challenge with Lena, we observed a very strong serological booster effect for neutralizing antibodies against strains used for the first inoculation. Our results indicate that inoculation with subtype 1 PRRSV strains can partially protect against...

  3. Most Campylobacter subtypes from sporadic infections can be found in retail poultry products and food animals

    DEFF Research Database (Denmark)

    Nielsen, Eva M.; Fussing, V.; Engberg, J.;

    2006-01-01

    originating from outside the country. The study shows that most C. jejuni subtypes found in poultry food samples, broiler chickens, and cattle were represented in the domestically acquired cases, indicating that C. jejuni from these reservoirs are likely sources of human infections in Denmark.......The subtypes of Campylobacter isolates from human infections in two Danish counties were compared to isolates from retail food samples and faecal samples from chickens, pigs and cattle. During a 1-year period, 1285 Campylobacter isolates from these sources were typed by two methods: 'Penner' heat......-stable serotyping and automated ribotyping (RiboPrinting). C. jejuni was the dominating species, but C. coli was more prevalent among food and chicken isolates (16%) compared to human isolates (4%). In total, 356 different combined sero-ribotypes (subtypes) were found. A large subtype overlap was seen between human...

  4. GDE2 regulates subtype-specific motor neuron generation through inhibition of Notch signaling.

    Science.gov (United States)

    Sabharwal, Priyanka; Lee, Changhee; Park, Sungjin; Rao, Meenakshi; Sockanathan, Shanthini

    2011-09-22

    The specification of spinal interneuron and motor neuron identities initiates within progenitor cells, while motor neuron subtype diversification is regulated by hierarchical transcriptional programs implemented postmitotically. Here we find that mice lacking GDE2, a six-transmembrane protein that triggers motor neuron generation, exhibit selective losses of distinct motor neuron subtypes, specifically in defined subsets of limb-innervating motor pools that correlate with the loss of force-generating alpha motor neurons. Mechanistically, GDE2 is expressed by postmitotic motor neurons but utilizes extracellular glycerophosphodiester phosphodiesterase activity to induce motor neuron generation by inhibiting Notch signaling in neighboring motor neuron progenitors. Thus, neuronal GDE2 controls motor neuron subtype diversity through a non-cell-autonomous feedback mechanism that directly regulates progenitor cell differentiation, implying that subtype specification initiates within motor neuron progenitor populations prior to their differentiation into postmitotic motor neurons.

  5. Species Identification and Subtyping of Ureaplasma Urealyticum from Urine Specimens of Pregnant Women

    Institute of Scientific and Technical Information of China (English)

    郑义; 王辉; 孔繁荣; 王玮蓁; 周海燕

    2001-01-01

    Objective: To investigate U. parvum (previously Ureaplasma urealyticum biovar 1) and U. urealyticum (previously Ureaplasma urealyticum biovar 2) and their subtypes and serovars in urine specimens of pregnant women.Methods: After collecting 151 specimens and inoculating broth, all broth culture positive (urease positive) specimens were amplified, species were identified and subtyped by using general primers, species-specific, and type-specific primers targeting the multiple banded antigen (MBA) gene sequence.Results: U. parvum was identified in 58 of 151 specimens and U. urealyticum in 18 (both were present in 5, and neither were found in 6). Serovars 3, 1, and 6 were the most common among U. parvum isolates and subtypes 1 and 3 were the most common among U. urealyticum. Multiple serovars among clinical isolates were found.Conclusion: This PCR-based typing system could facilitate studies of the relationship between individual ureaplasma species or subtypes and human diseases.

  6. Serum testosterone levels and symptom-based depression subtypes in men

    Directory of Open Access Journals (Sweden)

    Stephanie eRodgers

    2015-05-01

    Full Text Available The main objective of this preliminary study was to further clarify the association between T levels and depression by investigating symptom-based depression subtypes in a sample of 64 men. The data was taken from the ZInEP epidemiology survey. Gonadal hormones of a melancholic (n=25 and an atypical (n=14 depression subtype, derived from latent class analysis, were compared with those of healthy controls (n=18. Serum T was assayed using an ELISA procedure. Analysis of variance, analysis of covariance, non-parametrical tests and generalized linear regression models were performed to examine group differences. The atypical depressive subtype showed significantly lower T levels compared with the melancholic depressives. While accumulative evidence indicates that, beyond psychosocial characteristics, the melancholic and atypical depressive subtypes are also distinguishable by biological correlates, the current study expanded this knowledge to include gonadal hormones. Further longitudinal research is warranted to disclose causality by linking the multiple processes in pathogenesis of depression.

  7. Molecular Classification of Gastric Cancer: A new paradigm

    Science.gov (United States)

    Shah, Manish A.; Khanin, Raya; Tang, Laura; Janjigian, Yelena Y.; Klimstra, David S.; Gerdes, Hans; Kelsen, David P.

    2011-01-01

    Purpose Gastric cancer may be subdivided into three distinct subtypes –proximal, diffuse, and distal gastric cancer– based on histopathologic and anatomic criteria. Each subtype is associated with unique epidemiology. Our aim is to test the hypothesis that these distinct gastric cancer subtypes may also be distinguished by gene expression analysis. Experimental Design Patients with localized gastric adenocarcinoma being screened for a phase II preoperative clinical trial (NCI 5917) underwent endoscopic biopsy for fresh tumor procurement. 4–6 targeted biopsies of the primary tumor were obtained. Macrodissection was performed to ensure >80% carcinoma in the sample. HG-U133A GeneChip (Affymetrix) was used for cDNA expression analysis, and all arrays were processed and analyzed using the Bioconductor R-package. Results Between November 2003 and January 2006, 57 patients were screened to identify 36 patients with localized gastric cancer who had adequate RNA for expression analysis. Using supervised analysis, we built a classifier to distinguish the three gastric cancer subtypes, successfully classifying each into tightly grouped clusters. Leave-one-out cross validation error was 0.14, suggesting that >85% of samples were classified correctly. Gene set analysis with the False Discovery Rate set at 0.25 identified several pathways that were differentially regulated when comparing each gastric cancer subtype to adjacent normal stomach. Conclusions Subtypes of gastric cancer that have epidemiologic and histologic distinction are also distinguished by gene expression data. These preliminary data suggest a new classification of gastric cancer with implications for improving our understanding of disease biology and identification of unique molecular drivers for each gastric cancer subtype. PMID:21430069

  8. Clinical, electrophysiological subtypes and antiganglioside antibodies in childhood Guillain-Barré syndrome

    Directory of Open Access Journals (Sweden)

    Meena A Kannan

    2011-01-01

    Full Text Available Background: Guillain-Barré syndrome (GBS has been the most common cause of flaccid paralysis in children after the decline in the incidence of poliomyelitis. There are not any published data from the Indian subcontinent documenting electrophysiological patterns and antiganglioside antibodies in pediatric GBS. Materials and Methods: The study population included children with GBS referred for electrodiagnostic evaluation and also children with GBS admitted to our institute between August 2006 and July 2007. Nerve conduction studies were done to determine GBS subtypes and serum antiganglioside antibodies were measured using enzyme-linked immunosorbent assay (ELISA. Clinical and electrophysiological features were correlated with antiganglioside antibody results. Results: Of the 43 (male to female ratio = 2.1:1 children studied, 97.6% had motor weakness, 76.7% had cranial nerve palsies, 13.9% had autonomic disturbances and respiratory paralysis was found in 9.3% children. Antecedent illness was recorded in 69.8% children. The GBS subtype distribution was as follows: acute inflammatory demyelinating polyradiculoneuropathy (AIDP in 21 (48.8%, acute motor axonal neuropathy (AMAN in 19 (44.2%, and 3 (6.9% children were unclassified. The severity of illness was similar in both AMAN and AIDP subtypes and the recovery in both the subtypes was complete without any significant difference in the duration of recovery. Preceding diarrheal illness was more common in AMAN subtype as compared to AIDP subtype (57.9% vs. 4.7%, P = 0.007. Sensory symptoms were more common in AIDP subtype than in AMAN subtype (66.6% vs. 21%, P = 0.03}. The commonest ganglioside antibody was IgM GM2. Anti GM3 antibodies were exclusively seen in children with AMAN and IgG GD1b was significantly associated with (36.7 vs. 4%; P = 0.007 AMAN subtype. IgG GT1b was identified in 50% of patients with AIDP as compared to 22.7% in patients with AMAN. Conclusion: In this study, AMAN subtype

  9. Refining personality disorder subtypes and classification using finite mixture modeling.

    Science.gov (United States)

    Yun, Rebecca J; Stern, Barry L; Lenzenweger, Mark F; Tiersky, Lana A

    2013-04-01

    The current Diagnostic and Statistical Manual of Mental Disorders (DSM) diagnostic system for Axis II disorders continues to be characterized by considerable heterogeneity and poor discriminant validity. Such problems impede accurate personality disorder (PD) diagnosis. As a result, alternative assessment tools are often used in conjunction with the DSM. One popular framework is the object relational model developed by Kernberg and his colleagues (J. F. Clarkin, M. F. Lenzenweger, F. Yeomans, K. N. Levy, & O. F. Kernberg, 2007, An object relations model of borderline pathology, Journal of Personality Disorders, Vol. 21, pp. 474-499; O. F. Kernberg, 1984, Severe Personality Disorders, New Haven, CT: Yale University Press; O. F. Kernberg & E. Caligor, 2005, A psychoanalytic theory of personality disorders, in M. F. Lenzenweger & J. F. Clarkin, Eds., Major Theories of Personality Disorder, New York, NY: Guilford Press). Drawing on this model and empirical studies thereof, the current study attempted to clarify Kernberg's (1984) PD taxonomy and identify subtypes within a sample with varying levels of personality pathology using finite mixture modeling. Subjects (N = 141) were recruited to represent a wide range of pathology. The finite mixture modeling results indicated that 3 components were harbored within the variables analyzed. Group 1 was characterized by low