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Sample records for apocrine molecular subtype

  1. Molecular pathology of breast apocrine carcinomas

    DEFF Research Database (Denmark)

    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...... between 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...

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

    DEFF Research Database (Denmark)

    Celis, J.E.; Cabezon, T.; Moreira, José; Gromov, P.; Gromova, I.; Timmermans-Wielenga, V.; Iwase, T.; Akiyama, F.; Honma, N.; Rank, F.

    2009-01-01

    apocrine ductal carcinoma in situ (ADCIS), and 33 IACs diagnosed at the Cancer Institute Hospital, Tokyo between 1997 and 2001. Samples were originally classified on the basis of cellular morphology with all cases having more than 90% of the tumour cells exhibiting cytological features typical of apocrine......Invasive apocrine carcinomas (IACs), as defined by morphological features, correspond to 0.3-4% of all invasive ductal carcinomas (IDC), and despite the fact that they are histologically distinct from other breast lesions there are currently no standard molecular criteria available for their...... 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...

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

    Science.gov (United States)

    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

  4. [Molecular Subtypes of Gastric Cancer].

    Science.gov (United States)

    Hatogai, Ken; Doi, Toshihiko

    2016-03-01

    Gastric cancer has been classified based on the pathological characteristics including microscopic configuration and growth pattern. Although these classifications have been used in studies investigating prognosis and recurrence pattern, they are not considered for decisions regarding the therapeutic strategy. In the ToGA study, trastuzumab, an anti-HER2 monoclonal antibody, demonstrated clinical efficacy for gastric cancer with HER2 overexpression or HER2 gene amplification. Based on these findings of the ToGA study, the definition of HER2-positive gastric cancer was established. Thereafter, several molecular targeted agents, including agents targeting other receptor tyrosine kinases, have been investigated in gastric cancer. However, to date no biomarker, except HER2, has been established. Based on the recent technological development in the field of gene analysis, a comprehensive molecular evaluation of gastric cancer was performed as part of The Cancer Genome Atlas (TCGA)project, and a new molecular classification was proposed that divided gastric cancer into the following 4 subtypes: tumors positive for Epstein-Barr virus, microsatellite instability tumors, genomically stable tumors, and tumors with chromosomal instability. Each subtype has specific molecular alterations including gene mutation and amplification, DNA methylation, and protein overexpression. Additionally, some subtypes were suggested to be correlated with the clinicopathological characteristics or as targets of some molecular targeted agents that are currently under development. The new molecular classification is expected to be a roadmap for patient stratification and clinical trials on molecular targeted therapies in gastric cancer. PMID:27067842

  5. 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.

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

    DEFF Research Database (Denmark)

    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...

  7. 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;}

  8. Apocrine Adenocarcinoma of the Vulva

    OpenAIRE

    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...

  9. Molecular Subtyping of Treponema pallidum subsp. pallidum in Lisbon, Portugal▿

    Science.gov (United States)

    Castro, R.; Prieto, E.; Águas, M. J.; Manata, M. J.; Botas, J.; Martins Pereira, F.

    2009-01-01

    The objectives of this study were to evaluate the reproducibility of a molecular method for the subtyping of Treponema pallidum subsp. pallidum and to discriminate strains of this microorganism from strains from patients with syphilis. We studied 212 specimens from a total of 82 patients with different stages of syphilis (14 primary, 7 secondary and 61 latent syphilis). The specimens were distributed as follows: genital ulcers (n = 9), skin and mucosal lesions (n = 7), blood (n = 82), plasma (n = 82), and ear lobe scrapings (n = 32). The samples were assayed by a PCR technique to amplify a segment of the polymerase gene I (polA). Positive samples were typed on the basis of the analysis of two variable genes, tpr and arp. Sixty-two of the 90 samples positive for polA yielded typeable Treponema pallidum DNA. All skin lesions in which T. pallidum was identified (six of six [100%]) were found to contain enough DNA for typing of the organism. It was also possible to type DNA from 7/9 (77.7%) genital ulcer samples, 13/22 (59.1%) blood samples, 20/32 (62.5%) plasma samples, and 16/21 (76.2%) ear lobe scrapings. The same subtype was identified in all samples from the same patient. Five molecular subtypes (subtypes 10a, 14a, 14c, 14f, and 14g) were identified, with the most frequently found subtype being subtype 14a and the least frequently found subtype being subtype 10a. In conclusion, the subtyping technique used in this study seems to have good reproducibility. To our knowledge, subtype 10a was identified for the first time. Further studies are needed to explain the presence of this subtype in Portugal, namely, its relationship to the Treponema pallidum strains circulating in the African countries where Portuguese is spoken. PMID:19494073

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

    DEFF Research Database (Denmark)

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

    2014-01-01

    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...

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

    OpenAIRE

    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...

  12. 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

  13. 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 feline mammary tumors and human breast cancer, reveal that feline can be a valuable model for comparative studies. PMID:27212699

  14. 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

  15. Bilateral multiple axillary apocrine hidrocystomas accompanied by apocrine hyperplasia: a rare presentation.

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    Shukla, Shailaja; Patiri, Karsing; Pujani, Mukta; Komal, Singh Bhawana

    2014-01-01

    Apocrine hidrocystomas (AHC) are uncommon cystic lesions of apocrine glands and are most often solitary. They are usually found in the head and neck region. Multiple AHC have been rarely reported in the literature usually in the eyelids and face. On extensive search of literature, we came across only a single case report of multiple axillary AHC. We report a case of a 31-year-old female who presented with fullness and discomfort in bilateral axillae, so a clinical diagnosis of bilateral accessory breast was made. However on histopathological examination, it turned out to be bilateral multiple AHC associated with apocrine hyperplasia. PMID:24943766

  16. Bilateral multiple axillary apocrine hidrocystomas accompanied by apocrine hyperplasia: A rare presentation

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    Shailaja Shukla

    2014-01-01

    Full Text Available Apocrine hidrocystomas (AHC are uncommon cystic lesions of apocrine glands and are most often solitary. They are usually found in the head and neck region. Multiple AHC have been rarely reported in the literature usually in the eyelids and face. On extensive search of literature, we came across only a single case report of multiple axillary AHC. We report a case of a 31-year-old female who presented with fullness and discomfort in bilateral axillae, so a clinical diagnosis of bilateral accessory breast was made. However on histopathological examination, it turned out to be bilateral multiple AHC associated with apocrine hyperplasia.

  17. Molecular subtyping of DCIS: heterogeneity of breast cancer reflected in pre-invasive disease

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    Clark, S. E.; Warwick, J.; Carpenter, R.; Bowen, R L; Duffy, S W; Jones, J L

    2010-01-01

    Background: Molecular profiling has identified at least four subtypes of invasive breast carcinoma, which exhibit distinct clinical behaviour. There is good evidence now that DCIS represents the non-obligate precursor to invasive breast cancer and therefore it should be possible to identify similar molecular subtypes at this stage. In addition to a limited five-marker system to identify molecular subtypes in invasive breast cancer, it is evident that other biological molecules may identify di...

  18. 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

  19. Genomic analyses identify molecular subtypes of pancreatic cancer.

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    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. PMID:26909576

  20. 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

  1. 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

  2. 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

  3. 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....

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

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    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

  5. 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.

  6. Molecular Epidemiology of HIV Type 1 Subtypes in Rwanda

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    Anastos, Kathryn; Weiser, Barbara; Ramirez, Christina M.; Shi, Qiuhu; Burger, Harold

    2013-01-01

    Abstract HIV-1 infection is characterized by genetic diversity, with multiple subtypes and recombinant variants circulating, particularly in sub-Saharan Africa. During the Rwandan genocide, many women experienced multiple rapes and some became HIV-1 infected. We studied plasma and peripheral blood mononuclear cells (PBMCs) from 30 infected women comprising two exposure groups: those with numerous contacts, raped multiple times, and women with one lifetime sexual partner and no history of rape. Population-based sequences from gag, pol, and env genes were analyzed to determine HIV-1 subtypes and intersubtype recombination. Individual plasma-derived variants from 12 women were also analyzed. Subtype A was found in 24/30 (80%), intersubtype recombination (AC and AD) in 4/30 (13%), and subtypes C and D in 1/30 each. In two subjects, the pattern of HIV-1 recombination differed between plasma and PBMC-derived sequences. Intersubtype recombination was common, although there were no significant differences in subtype or recombination rates between exposure groups. PMID:23458210

  7. Molecular epidemiology of HIV type 1 subtypes in Rwanda.

    Science.gov (United States)

    Kemal, Kimdar S; Anastos, Kathryn; Weiser, Barbara; Ramirez, Christina M; Shi, Qiuhu; Burger, Harold

    2013-06-01

    HIV-1 infection is characterized by genetic diversity, with multiple subtypes and recombinant variants circulating, particularly in sub-Saharan Africa. During the Rwandan genocide, many women experienced multiple rapes and some became HIV-1 infected. We studied plasma and peripheral blood mononuclear cells (PBMCs) from 30 infected women comprising two exposure groups: those with numerous contacts, raped multiple times, and women with one lifetime sexual partner and no history of rape. Population-based sequences from gag, pol, and env genes were analyzed to determine HIV-1 subtypes and intersubtype recombination. Individual plasma-derived variants from 12 women were also analyzed. Subtype A was found in 24/30 (80%), intersubtype recombination (AC and AD) in 4/30 (13%), and subtypes C and D in 1/30 each. In two subjects, the pattern of HIV-1 recombination differed between plasma and PBMC-derived sequences. Intersubtype recombination was common, although there were no significant differences in subtype or recombination rates between exposure groups. PMID:23458210

  8. Apocrine carcinoma of the breast: a case report

    International Nuclear Information System (INIS)

    Apocrine carcinoma is a rare breast cancer and its frequency is about 0.4% of all breast cancers. Little is known about its clinical behavior and prognosis. To our knowledge, few studies have reported the radiologic appearances of apocrine carcinoma in the breast and there has been no such report from Korea. We describe the sonographic findings of a case of apocrine carcinoma in the breast. The sonographic findings are microlobulated heterogeneous hypoechoic lesion that has a central markedly hypoechoic portion and a peripheral mixture of iso and hypoechgenecity

  9. A Complete Molecular Diagnostic Procedure for Applications in Surveillance and Subtyping of Avian Influenza Virus

    OpenAIRE

    Chun-Hsien Tseng; Hsiang-Jung Tsai; Chung-Ming Chang

    2014-01-01

    Introduction. The following complete molecular diagnostic procedure we developed, based on real-time quantitative PCR and traditional PCR, is effective for avian influenza surveillance, virus subtyping, and viral genome sequencing. Method. This study provides a specific and sensitive step-by-step procedure for efficient avian influenza identification of 16 hemagglutinin and 9 neuraminidase avian influenza subtypes. Result and Conclusion. This diagnostic procedure may prove exceedingly useful ...

  10. 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

  11. 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

  12. 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.

  13. 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

  14. Genetic and clinical characteristics of primary and secondary glioblastoma is associated with differential molecular subtype distribution

    OpenAIRE

    Li, Rui; Li, Hailin; Yan, Wei; Yang, Pei; Bao, Zhaoshi; Zhang, Chuanbao; Jiang, Tao; You, Yongping

    2015-01-01

    Glioblastoma multiforme (GBM) is classified into primary (pGBM) or secondary (sGBM) based on clinical progression. However, there are some limits to this classification for insight into genetically and clinically distinction between pGBM and sGBM. The aim of this study is to characterize pGBM and sGBM associating with differential molecular subtype distribution. Whole transcriptome sequencing data was used to assess the distribution of molecular subtypes and genetic alterations in 88 pGBM and...

  15. Healthy dietary patterns and risk of breast cancer by molecular subtype.

    Science.gov (United States)

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

    2016-02-01

    We examined associations between dietary quality indices and breast cancer risk by molecular subtype among 100,643 women in the prospective Nurses' Health Study (NHS) cohort, followed from 1984 to 2006. Dietary quality scores for the Alternative Healthy Eating Index (AHEI), alternate Mediterranean diet (aMED), and Dietary Approaches to Stop Hypertension (DASH) dietary patterns were calculated from semi-quantitative food frequency questionnaires collected every 2-4 years. Breast cancer molecular subtypes were defined according to estrogen receptor (ER), progesterone receptor, human epidermal growth factor 2 (HER2), cytokeratin 5/6 (CK5/6), and epidermal growth factor receptor status from immunostained tumor microarrays in combination with histologic grade. Cox proportional hazards models, adjusted for age and breast cancer risk factors, were used to estimate hazard ratios (HRs) and 95 % confidence intervals (CIs). Competing risk analyses were used to assess heterogeneity by subtype. We did not observe any significant associations between the AHEI or aMED dietary patterns and risk of breast cancer by molecular subtype. However, a significantly reduced risk of HER2-type breast cancer was observed among women in 5th versus 1st quintile of the DASH dietary pattern [n = 134 cases, Q5 vs. Q1 HR (95 % CI) = 0.44 (0.25-0.77)], and the inverse trend across quintiles was significant (p trend = 0.02). We did not observe any heterogeneity in associations between AHEI (p het = 0.25), aMED (p het = 0.71), and DASH (p het = 0.12) dietary patterns and breast cancer by subtype. Adherence to the AHEI, aMED, and DASH dietary patterns was not strongly associated with breast cancer molecular subtypes. PMID:26872903

  16. 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.

  17. 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.

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

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    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.)

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

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    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.

  20. 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...

  1. MRI and pathological features of different molecular subtypes of breast cancers

    International Nuclear Information System (INIS)

    Objective: To investigate the MRI and pathological features of different molecular subtypes of breast cancer. Methods: The data of 202 patients who underwent primary breast cancer resection were retrospectively reviewed. All of the patients had MRI preoperatively. The molecular subtypes of breast cancer defined by immunohistochemistry were classified as basal-like, luminal and HER-2 overexpression. Morphology (including mass or non-mass like enhancement, shape and margin of masses, unifocal or multifocal masses) and enhancement characteristics on MRI, histologic types and grades of tumors were analyzed with Chi-square test, exact test, Fisher exact test, Kruskal-Wallis H test, and Wilcoxon test. Results: Among the 202 patients, 34 were basal-like, 144 were luminal and 24 were HER-2 overexpression. The number of mass cases in each subtype was 29, 133 and 19 respectively,making no significant difference (χ2=4.136, P=0.126). As for the shape of basal-like lesions,8 were round,19 were lobular and 2 were irregular, while this distribution was 23, 58, 52 in luminal subtype and 1, 11, 7 in HER-2 overexpression subtype (χ2=13.391, P<0.05). The margin was also strikingly different among three groups (smooth, spiculate, irregular): 20, 5, 4 respectively in basal-like, 27, 53, 53 respectively in luminal, and 4, 7, 8 respectively in HER-2 overexpression (χ2=28.515, P<0.01). 52.6% (10/19) of HER-2 overexpression cases were multifocal, while only 6.9% (2/29) of luminal and 8.0% (24/133) of basal-like ones were multifocal (χ2=16.140, P<0.01). Characteristics in dynamic contrast-enhanced MRI were statistically different, with homogeneous, heterogeneous, and rim enhancement 0, 13, 16 respectively in basal-like cases, 28, 93, 11 respectively in luminal cases and 2, 11, 6 respectively in HER-2 overexpression cases (P<0.01). However, the difference for enhancement curve did not reach significance (P =0.457). Histologic types were significantly different among molecular subtypes (P

  2. Different molecular patterns in glioblastoma multiforme subtypes upon recurrence

    OpenAIRE

    Martinez, Ramon; Rohde, Veit; Schackert, Gabriele

    2009-01-01

    One of the hallmarks of glioblastoma is its inherent tendency to recur. At this point patients with relapsed GBM show a survival time of only few months. The molecular basis of the recurrence process in GBM is still poorly understood. The aim of the present study was to investigate the genetic profile of relapsed GBM compared to their respective primary tumors. We have included 20 paired GBMs. In all tumor samples, we have analyzed p53 and PTEN status by sequencing analysis, EGFR amplificatio...

  3. 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...

  4. Molecular Subtyping Methods for Detection of Salmonella enterica Serovar Oranienburg Outbreaks

    OpenAIRE

    Kumao, Toshio; Ba-Thein, William; Hayashi, Hideo

    2002-01-01

    This study involved 82 Salmonella enterica serovar Oranienburg isolates from patients with gastroenteritis and/or focal infections, healthy carriers, and cuttlefish chips which were epidemiologically linked to a major outbreak that had affected 1,505 people in Japan between 1998 and 1999. We concurrently investigated four different molecular subtyping methods using human salmonellosis-associated Salmonella serovars and their applicability in detection of serovar Oranienburg in an outbreak. Pu...

  5. 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.

  6. 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

  7. Sonographic and Mammographic Features of Breast Apocrine Metaplasia

    International Nuclear Information System (INIS)

    To evaluate the sonographic and mammographic features of apocrine metaplasia of the breast. We retrospectively evaluated the sonographic and mammographic findings of 16 lesions that were diagnosed with only apocrine metaplasia after mammotome excision. The age ranged from 27 years old to 57 years old (mean age: 40 years old). The sonographic features were interpreted by the ACR BI-RADS(American College of Radiology Breast Imaging Reporting and Data System) for shape, orientation, margin, boundary, echo pattern, posterior acoustic feature, calcification and special cases. The mammographic features were interpreted by the ACR BI-RADS (American College of Radiology Breast Imaging Reporting and Data System) for breast composition, shape, margin, density and calcification. Sonographic features were that the shapes were oval (n = 16) in 100%. The orientation was parallel (n =15) in 94%. The margins were circumscribed (n = 8) in 50% and microlobulated (n = 8) in 50%. The echo patterns were hypoechoic (n = 8) in 50%, complex (n = 5) in 31% and anechoic (n = 3) in 19%. Posterior acoustic enhancement was seen in 69% (n = 11). There was internal microcyst (n = 4) in 25%. There was no calcification. Mammography performed for 12 cases demonstrated negative findings (n = 10) for 83%, obscured hypodense mass (n = 1) for 8% in 11 cases of breast composition 3 and 4, and circumscribed isodense mass (n = 1)for 8% in one case of breast composition 2. There was no calcification. The final assessment was category 4a (n= 7) in 44%, category 3 (n = 6) in 38% and category 2 (n = 3) in 19%. Although sonographic and mammographic features of apocrine metaplasia are occasionally suspicious malignancy such as microlobulation and complex echo. We consider the possibility of apocrine metaplasia if masses show internal microcyst and abrupt boundary

  8. Dermoscopy of apocrine hydrocystoma: A first case report

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    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.

  9. 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

  10. 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.

  11. 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

  12. 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.

  13. 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

  14. 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

    includes 15-prostaglandin dehydrogenase (15-PGDH), a protein that is expressed by all benign apocrine lesions, and markers that are highly overexpressed by pure invasive apocrine carcinomas such as MRP14 (S100A9), psoriasin (S100A7), and p53 to identify precancerous lesions in sclerosing adenosis (SA) with...

  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. Apocrine Ductal Carcinoma In Situ of the Breast Presented Mass with Morphological Change on Follow-Up Ultrasound: A Report of Case

    Energy Technology Data Exchange (ETDEWEB)

    Seo, Gi Young; Kim Soo Jin; Park, Sung Hee; Lee, Sun Jin; Ryu, Han Suk; Jung, Yoon Yang [Chung-Ang University Hospital, Seoul (Korea, Republic of)

    2012-11-15

    Apocrine carcinoma in situ of breast is a rare, unique, and morphologically distinct type of breast carcinoma. Low-grade apocrine ductal carcinoma in situ (DCIS) and apocrine metaplasia with atypia are the pathologic spectrum of apocrine breast lesions. Differentiating these two lesions is difficult due to partial microscopic overlap. We describe a case of apocrine DCIS which presented an asymptomatic hypoechoic mass with morphological change on a follow up ultrasonography.

  17. Apocrine Ductal Carcinoma In Situ of the Breast Presented Mass with Morphological Change on Follow-Up Ultrasound: A Report of Case

    International Nuclear Information System (INIS)

    Apocrine carcinoma in situ of breast is a rare, unique, and morphologically distinct type of breast carcinoma. Low-grade apocrine ductal carcinoma in situ (DCIS) and apocrine metaplasia with atypia are the pathologic spectrum of apocrine breast lesions. Differentiating these two lesions is difficult due to partial microscopic overlap. We describe a case of apocrine DCIS which presented an asymptomatic hypoechoic mass with morphological change on a follow up ultrasonography.

  18. Phenotypic and molecular characterization of the intrinsic molecular subtypes of breast cancer

    OpenAIRE

    Prat Aparicio, Aleix

    2014-01-01

    La implementación de programas de cribaje y/o de prevención junto a terapias innovadoras está disminuyendo la mortalidad por cáncer de mama. Ahora bien, más de 120.000 muertes anuales ocurren en Estados Unidos y en Europa por esta causa. Una explicación de este hecho es que aún nos falta obtener una fotografía completa de la heterogeneidad biológica del cáncer de mama con respeto a sus alteraciones moleculares, sensibilidad al tratamiento, y composición celular. De hecho, esta complejidad no ...

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

    Directory of Open Access Journals (Sweden)

    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.

  20. 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

  1. 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

  2. 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.

  3. Molecular Subtyping of Treponema pallidum during a Local Syphilis Epidemic in Men Who Have Sex with Men in Melbourne, Australia

    Science.gov (United States)

    Ryan, Norbert; Fyfe, Janet; Leslie, David E.

    2012-01-01

    Treponema pallidum is the causative agent of syphilis, a sexually transmitted infection of significant public health importance. Since 2000 there has been a marked increase in the number of cases of syphilis infections notified in Victoria, Australia, with the majority of cases occurring in men who have sex with men (MSM) and the highest incidence being in HIV-infected MSM. The molecular subtyping method described by Pillay et al. (A. Pillay et al., Sex. Transm. Dis. 25:408–414, 1998) has been used in this study to determine the diversity of T. pallidum subtypes circulating locally and to look for any relationship between T. pallidum subtypes and HIV status over a 6-year period (2004 to 2009). Treponema pallidum DNA was detected in 303 patient specimens (n = 3,652), and full subtyping profiles were obtained from 90 of these (from 88 patients). A total of 11 T. pallidum subtypes were identified: types 14e (28, 31.1%), 14d (15, 16.7%), 14k (13, 14.4%), 14p (12, 13.3%), 14i (7, 7.8%) 14b (6, 6.7%), 14l (5, 5.6%), and 12i, 13b, 13i, and 13e (1 each, 1.1%). This study showed a similar level of variation among circulating T. pallidum strains compared with that in other studies using the same methodology. A different mix of strains and different predominating strains have been found at each geographical study location, with type 14e emerging as the predominant local strain in Victoria. There was no detectable trend between T. pallidum subtypes and the specimen collection site or stage of syphilis (where known), nor was there any relationship between particular strains and HIV status. PMID:22422857

  4. A Comparative Analysis of Bio marker Expression and Molecular Subtypes of Pure Ductal Carcinoma In Situ and Invasive Breast Carcinoma by Image Analysis: Relationship of the Subtypes with Histologic Grade, Ki67, p53 Overexpression, and DNA Ploidy

    International Nuclear Information System (INIS)

    There is a paucity of data regarding molecular subtypes of pure ductal carcinoma in situ (pDCIS). We evaluated the expression of ER, PR, HER2, Ki67, and p53 and DNA ploidy in 118 pDCIS and 100 invasive breast carcinomas (IBCAs) by routine IHC and classified them according to molecular subtypes. Quantification of bio markers and DNA ploidy was performed by image analysis. Expression of ER, PR, and high ki67 was more frequent in pDCIS compared to IBCA. High-grade tumors had lower ER and PR expression, high Ki67, overexpression of HER2 and p53, and DNA aneuploidy. Luminal A and HER2 subtypes were more common in pDCIS, and triple negative was more prevalent in IBCA. In both groups, HER2 and triple negative subtypes were characterized by high ki67, overexpression of p53, and DNA aneuploidy compared to luminal subtypes. Molecular subtypes of IBCA are distinct from those of pDCIS. Invasion is characterized by change in phenotype in some tumors.Pathology.Pathology.Bio marker staining nuclei, and staining intensity expression

  5. Molecular Stratification of Clear Cell Renal Cell Carcinoma by Consensus Clustering Reveals Distinct Subtypes and Survival Patterns

    OpenAIRE

    Brannon, A. Rose; Reddy, Anupama; Seiler, Michael; Arreola, Alexandra; Moore, Dominic T.; Pruthi, Raj S.; Wallen, Eric M.; Nielsen, Matthew E; Liu, Huiqing; Nathanson, Katherine L.; Ljungberg, Börje; Zhao, Hongjuan; BROOKS, JAMES D.; Ganesan, Shridar; Bhanot, Gyan

    2010-01-01

    Clear cell renal cell carcinoma (ccRCC) is the predominant RCC subtype, but even within this classification, the natural history is heterogeneous and difficult to predict. A sophisticated understanding of the molecular features most discriminatory for the underlying tumor heterogeneity should be predicated on identifiable and biologically meaningful patterns of gene expression. Gene expression microarray data were analyzed using software that implements iterative unsupervised consensus cluste...

  6. Molecular subtyping of Salmonella enterica serovar Typhi isolates from Colombia and Argentina.

    Science.gov (United States)

    Salve, Angela; Pichel, Mariana; Wiesner, Magdalena; Hidalgo, Marylin; Terragno, Raquel; Alvarez, Adriana; Agudelo, Clara Inés; Castañeda, Elizabeth; Binsztein, Norma

    2006-01-01

    Salmonella Typhi is the etiological agent of typhoid fever with 16 million annual cases estimated worldwide. In Colombia and Argentina it is a notifiable disease but many cases have only a clinical diagnosis. Molecular subtyping of S. Typhi is necessary to complement epidemiologic analysis of typhoid fever. The aims of this study were to determine the genetic relationships between the strains circulating in both countries and to evaluate possible variations in the distribution of 12 virulence genes. A total of 136 isolates were analyzed by pulsed-field gel electrophoresis (PFGE) with XbaI following PulseNet protocols and analysis guidelines. Eighty-three different PFGE patterns were identified, showing high diversity among the strains from both countries. Three outbreaks, two in Colombia and one in Argentina, were caused by strains of different PFGE types. In Colombia, two PFGE patterns were found predominantly, which included 36.6% of the isolates from that country. No association was found between the PFGE patterns and the year or place of isolation of the strains, the age of the patients or type of sample. However, several clusters were detected, which included isolates recovered predominantly either from Colombia or Argentina. Most of the strains (97%) exhibited a single virulence profile, suggesting that the pathogenicity markers analyzed are of limited value for strain discrimination and do not correlate with the origin of the isolates (intestinal vs. extra-intestinal). Since the creation of PulseNet Latin America, this was the first international study conducted in South America. The PFGE types identified were incorporated into the Regional S. Typhi PulseNet Database and are now available for comparison with those of strains isolated in other regions. This information will be used for active surveillance, future studies, and outbreak investigations. PMID:16602990

  7. Tumour-associated endothelial-FAK correlated with molecular sub-type and prognostic factors in invasive breast cancer

    International Nuclear Information System (INIS)

    Breast cancer is a heterogeneous disease that can be classified into one of 4 main molecular sub-types: luminal A, luminal B, Her2 over-expressing and basal-like (BL). These tumour sub-types require different treatments and have different risks of disease progression. BL cancers can be considered a sub-group of Triple negative (TN) cancers since they lack estrogen (ER), progesterone (PR) and Her2 expression. No targeted treatment currently exists for TN/BL cancers. Thus it is important to identify potential therapeutic targets and describe their relationship with established prognostic factors. Focal adhesion kinase (FAK) is upregulated in several human cancers and also plays a functional role in tumour angiogenesis. However, the association between breast cancer sub-types and tumour endothelial-FAK expression is unknown. Using immunofluorescence, we quantified FAK expression in tumour endothelial and tumour cell compartments in 149 invasive breast carcinomas and correlated expression with clinical, pathological and molecular parameters. Low endothelial-FAK expression was independently associated with luminal A tumours at univariate (p < 0.001) and multivariate (p = 0.001) analysis. There was a positive correlation between FAK expression in the vascular and tumour cell compartments (Spearman’s correlation co-efficient = 0.394, p < 0.001). Additionally, endothelial and tumour cell FAK expression were significantly increased in TN tumours (p = 0.043 and p = 0.033 respectively), in tumours with negative ER and PR status, and in high grade tumours at univariate analysis. Our findings establish a relationship between endothelial-FAK expression levels and the molecular sub-type of invasive breast cancer, and suggest that endothelial-FAK expression is potentially more clinically relevant than tumour cell FAK expression in breast cancer

  8. Development of a new molecular subtyping tool for Salmonella enterica serovar Enteritidis based on single nucleotide polymorphism genotyping using PCR.

    Science.gov (United States)

    Ogunremi, Dele; Kelly, Hilary; Dupras, Andrée Ann; Belanger, Sebastien; Devenish, John

    2014-12-01

    The lack of a sufficiently discriminatory molecular subtyping tool for Salmonella enterica serovar Enteritidis has hindered source attribution efforts and impeded regulatory actions required to disrupt its food-borne transmission. The underlying biological reason for the ineffectiveness of current molecular subtyping tools such as pulsed-field gel electrophoresis (PFGE) and phage typing appears to be related to the high degree of clonality of S. Enteritidis. By interrogating the organism's genome, we previously identified single nucleotide polymorphisms (SNP) distributed throughout the chromosome and have designed a highly discriminatory PCR-based SNP typing test based on 60 polymorphic loci. The application of the SNP-PCR method to DNA samples from S. Enteritidis strains (n = 55) obtained from a variety of sources has led to the differentiation and clustering of the S. Enteritidis isolates into 12 clades made up of 2 to 9 isolates per clade. Significantly, the SNP-PCR assay was able to further differentiate predominant PFGE types (e.g., XAI.0003) and phage types (e.g., phage type 8) into smaller subsets. The SNP-PCR subtyping test proved to be an accurate, precise, and quantitative tool for evaluating the relationships among the S. Enteritidis isolates tested in this study and should prove useful for clustering related S. Enteritidis isolates involved in outbreaks. PMID:25297333

  9. 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.

  10. 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.

  11. 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

  12. 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

  13. 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.

  14. 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

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

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    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

  16. 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

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

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    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.

  18. Multiple eyelid apocrine hidrocystoma in a domestic short-haired cat : clinical communication

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    A. Sivagurunathan

    2010-05-01

    Full Text Available A 12-year-old domestic short-haired cat was referred for evaluation of periocular masses. The tail had similar masses and was amputated previously by the referring veterinarian. On examination, multiple pigmented nodules, 3-15 mm in diameter, were found in the periocular skin, primarily involving the palpebral eyelid margin. A wedge excisional biopsy revealed small cuboidal cells forming multiple tubular and cystic structures indicative of apocrine cystadenomas, similar to apocrine hidrocystomas described in humans. The nodules were lanced followed by liquid nitrogen cryofreezing.

  19. 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 ...

  20. Long-term use of metformin and the molecular subtype in invasive breast carcinoma patients – a retrospective study of clinical and tumor characteristics

    International Nuclear Information System (INIS)

    Metformin may exhibit inhibitory effects on cancer cells by inhibiting mTOR signaling pathway. The aim of our retrospective study was to examine if patients with breast carcinoma (BC) and diabetes mellitus (DM) receiving metformin have a lower stage of carcinoma in comparison to patients not receiving metformin, and if the use of metformin correlates with the molecular subtype of BC. A chart review of 253 patients with invasive BC and DM (128 on metformin and 125 not on metformin) was performed. Control group consisted of 320 consecutive patients with invasive BC without DM. BC subtypes were classified by immunohistochemical surrogates as luminal A (estrogen receptor [ER] + and/or progesterone receptor [PR]+, HER-2-), luminal B (ER + and/or PR+, HER-2+), HER-2 (ER-, PR-, HER-2+), triple-negative/basal (ER-, PR-, HER-2-). Patients on metformin had a lower proportion of T3 or T4 tumors than patients who were not receiving metformin (16% vs. 26%; p = 0.035). No statistical difference was found between the two study groups in N stage. Patients with DM on metformin, with DM not on metformin and the control group had different molecular subtypes of BC (p = 0.01): the luminal A subtype was found in 78%, 83% and 71%, the luminal B in 12.6%, 9% and 11%, HER-2 in 0.8%, 1.6% and 8%, and the triple-negative/basal-like subtype in 8.6%, 6.4% and 10%, respectively. Our data indicate that long-term use of metformin use correlates with molecular subtype of BC in diabetics on metformin in comparison to diabetics not on metformin and patients without DM. However, most likely, different distribution of the molecular subtypes of BC in these three groups of patients was caused by other risk factors for breast carcinoma, such as age of patients or obesity

  1. 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.

  2. 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.

  3. 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.

  4. 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

  5. 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.

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

    Science.gov (United States)

    Hurtado, Renata; Fabrizio, Thomas; Vanstreels, Ralph Eric Thijl; Krauss, Scott; Webby, Richard J.; Webster, Robert G.; Durigon, Edison Luiz

    2015-01-01

    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. PMID:26689791

  7. Molecular Subtypes of Breast Cancer Are Not Associated with the Clinical Under- or Overstaging of Breast Cancer.

    Science.gov (United States)

    Espinola, Juliana Pinho; Peres, Raquel Mary Rodrigues; Serra, Kátia Piton; Derchain, Sophie Françoise Mauricette; Sarian, Luis Otávio

    2016-05-01

    Purpose to evaluate the agreement between the clinical and pathological stagings of breast cancer based on clinical and molecular features. Methods this was a cross-sectional study, in which clinical, epidemiological and pathological data were collected from 226 patients who underwent surgery at the Prof. Dr. José Aristodemo Pinotti Women's Hospital (CAISM/Unicamp) from January 2008 to September 2010. Patients were staged clinically and pathologically, and were classified as: understaged, when the clinical staging was lower than the pathological staging; correctly staged, when the clinical staging was the same as the pathological one; and overstaged, when the clinical staging was greater than the pathological staging. Results understaged patients were younger (52.2 years; p < 0.01) and more symptomatic at diagnosis (p = 0.04) when compared with correctly or overstaged patients. Clinicopathological surrogate subtype, menopausal status, parity, hormone replace therapy and histology were not associated with differences in staging. Women under 57 years of age were clinically understaged mainly due to underestimation of T (tumor staging) (p < 0.001), as were the premenopausal women (p < 0.01). Patients whose diagnosis was made due to clinical complaints, and not by screening, were clinically understaged due to underestimation of N (lymph nodes staging) (p < 0.001). Conclusion the study shows that the clinicopathological surrogate subtype is not associated with differences in staging, while younger women diagnosed because of clinical complaints tend to have their breast tumors understaged during clinical evaluation. PMID:27187929

  8. 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...

  9. How many molecular subtypes? Implications of the unique tumor principle in personalized medicine

    OpenAIRE

    Ogino, Shuji; FUCHS, CHARLES S.; Giovannucci, Edward

    2012-01-01

    Cancers are complex multifactorial diseases. For centuries, conventional organ-based classification system (i.e., breast cancer, lung cancer, colon cancer, colorectal cancer, prostate cancer, lymphoma, leukemia, and so on) has been utilized. Recently, molecular diagnostics has become an essential component in clinical decision-making. However, tumor evolution and behavior cannot accurately be predicted, despite numerous research studies reporting promising tumor biomarkers. To advance molecul...

  10. Presentation of Apocrine Breast Carcinoma in a Woman with Bilateral Silicone Prosthesis

    International Nuclear Information System (INIS)

    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

  11. 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.

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

    Directory of Open Access Journals (Sweden)

    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.

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

    Directory of Open Access Journals (Sweden)

    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.

  14. Sensitivity of Human Intrahepatic Cholangiocarcinoma Subtypes to Chemotherapeutics and Molecular Targeted Agents: A Study on Primary Cell Cultures

    Science.gov (United States)

    Fraveto, Alice; Cardinale, Vincenzo; Bragazzi, Maria Consiglia; Giuliante, Felice; De Rose, Agostino Maria; Grazi, Gian Luca; Napoletano, Chiara; Semeraro, Rossella; Lustri, Anna Maria; Costantini, Daniele; Nevi, Lorenzo; Di Matteo, Sabina; Renzi, Anastasia; Carpino, Guido; Gaudio, Eugenio; Alvaro, Domenico

    2015-01-01

    We investigated the sensitivity of intrahepatic cholangiocarcinoma (IHCCA) subtypes to chemotherapeutics and molecular targeted agents. Primary cultures of mucin- and mixed-IHCCA were prepared from surgical specimens (N. 18 IHCCA patients) and evaluated for cell proliferation (MTS assay) and apoptosis (Caspase 3) after incubation (72 hours) with increasing concentrations of different drugs. In vivo, subcutaneous human tumor xenografts were evaluated. Primary cultures of mucin- and mixed-IHCCA were characterized by a different pattern of expression of cancer stem cell markers, and by a different drug sensitivity. Gemcitabine and the Gemcitabine-Cisplatin combination were more active in inhibiting cell proliferation in mixed-IHCCA while Cisplatin or Abraxane were more effective against mucin-IHCCA, where Abraxane also enhances apoptosis. 5-Fluoracil showed a slight inhibitory effect on cell proliferation that was more significant in mixed- than mucin-IHCCA primary cultures and, induced apoptosis only in mucin-IHCCA. Among Hg inhibitors, LY2940680 and Vismodegib showed slight effects on proliferation of both IHCCA subtypes. The tyrosine kinase inhibitors, Imatinib Mesylate and Sorafenib showed significant inhibitory effects on proliferation of both mucin- and mixed-IHCCA. The MEK 1/2 inhibitor, Selumetinib, inhibited proliferation of only mucin-IHCCA while the aminopeptidase-N inhibitor, Bestatin was more active against mixed-IHCCA. The c-erbB2 blocking antibody was more active against mixed-IHCCA while, the Wnt inhibitor, LGK974, similarly inhibited proliferation of mucin- and mixed-IHCCA. Either mucin- or mixed-IHCCA showed high sensitivity to nanomolar concentrations of the dual PI3-kinase/mTOR inhibitor, NVP-BEZ235. In vivo, in subcutaneous xenografts, either NVP-BEZ235 or Abraxane, blocked tumor growth. In conclusion, mucin- and mixed-IHCCA are characterized by a different drug sensitivity. Cisplatin, Abraxane and the MEK 1/2 inhibitor, Selumetinib were more

  15. 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

  16. Molecular subtyping of bladder cancer using Kohonen self-organizing maps.

    Science.gov (United States)

    Borkowska, Edyta M; Kruk, Andrzej; Jedrzejczyk, Adam; Rozniecki, Marek; Jablonowski, Zbigniew; Traczyk, Magdalena; Constantinou, Maria; Banaszkiewicz, Monika; Pietrusinski, Michal; Sosnowski, Marek; Hamdy, Freddie C; Peter, Stefan; Catto, James W F; Kaluzewski, Bogdan

    2014-10-01

    Kohonen self-organizing maps (SOMs) are unsupervised Artificial Neural Networks (ANNs) that are good for low-density data visualization. They easily deal with complex and nonlinear relationships between variables. We evaluated molecular events that characterize high- and low-grade BC pathways in the tumors from 104 patients. We compared the ability of statistical clustering with a SOM to stratify tumors according to the risk of progression to more advanced disease. In univariable analysis, tumor stage (log rank P = 0.006) and grade (P < 0.001), HPV DNA (P < 0.004), Chromosome 9 loss (P = 0.04) and the A148T polymorphism (rs 3731249) in CDKN2A (P = 0.02) were associated with progression. Multivariable analysis of these parameters identified that tumor grade (Cox regression, P = 0.001, OR.2.9 (95% CI 1.6-5.2)) and the presence of HPV DNA (P = 0.017, OR 3.8 (95% CI 1.3-11.4)) were the only independent predictors of progression. Unsupervised hierarchical clustering grouped the tumors into discreet branches but did not stratify according to progression free survival (log rank P = 0.39). These genetic variables were presented to SOM input neurons. SOMs are suitable for complex data integration, allow easy visualization of outcomes, and may stratify BC progression more robustly than hierarchical clustering. PMID:25142434

  17. 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.

  18. 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.

  19. 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

  20. 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

  1. Pharmacological and molecular studies on the interaction of varenicline with different nicotinic acetylcholine receptor subtypes. Potential mechanism underlying partial agonism at human α4β2 and α3β4 subtypes.

    Science.gov (United States)

    Arias, Hugo R; Feuerbach, Dominik; Targowska-Duda, Katarzyna; Kaczor, Agnieszka A; Poso, Antti; Jozwiak, Krzysztof

    2015-02-01

    To determine the structural components underlying differences in affinity, potency, and selectivity of varenicline for several human (h) nicotinic acetylcholine receptors (nAChRs), functional and structural experiments were performed. The Ca2+ influx results established that: (a) varenicline activates (μM range) nAChR subtypes with the following rank sequence: hα7>hα4β4>hα4β2>hα3β4>hα1β1γδ; (b) varenicline binds to nAChR subtypes with the following affinity order (nM range): hα4β2~hα4β4>hα3β4>hα7>Torpedo α1β1γδ. The molecular docking results indicating that more hydrogen bond interactions are apparent for α4-containing nAChRs in comparison to other nAChRs may explain the observed higher affinity; and that (c) varenicline is a full agonist at hα7 (101%) and hα4β4 (93%), and a partial agonist at hα4β2 (20%) and hα3β4 (45%), relative to (±)-epibatidine. The allosteric sites found at the extracellular domain (EXD) of hα3β4 and hα4β2 nAChRs could explain the partial agonistic activity of varenicline on these nAChR subtypes. Molecular dynamics simulations show that the interaction of varenicline to each allosteric site decreases the capping of Loop C at the hα4β2 nAChR, suggesting that these allosteric interactions limit the initial step in the gating process. In conclusion, we propose that in addition to hα4β2 nAChRs, hα4β4 nAChRs can be considered as potential targets for the clinical activity of varenicline, and that the allosteric interactions at the hα3β4- and hα4β2-EXDs are alternative mechanisms underlying partial agonism at these nAChRs. PMID:25475645

  2. 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

  3. Primary apocrine adenocarcinoma of scrotum suspected as urothelial carcinoma metastasis: A clinical and pathological dilemma

    Directory of Open Access Journals (Sweden)

    Sean Huang

    2015-01-01

    Full Text Available A 78-year-old man presented with an enlarging, tender mass in the scrotum separate to the testes. This was on the background of radical cystoprostatectomy, urethrectomy, and ileal conduit formation for high-grade urothelial carcinoma of the bladder invading submucosa 3 years prior. Examination revealed a 4 × 5 cm lesion, which was hard, fixed to the overlying skin and nodular to palpation. Ultrasound confirmed a solid mass in the scrotum extending into the perineum. Computerized tomography of the chest, abdomen, and pelvis revealed enlargement of inguinal lymph nodes but no other metastases. Complete resection of the scrotal lesion and selective removal of regional lymph nodes was performed. Rather than a cutaneous scrotal metastasis from the bladder urothelial carcinoma, histological examination suggested a primary apocrine adenocarcinoma of the scrotum. This case report explores the clinical and pathological features associated with both of these unusual differential diagnoses.

  4. Primary apocrine adenocarcinoma of scrotum suspected as urothelial carcinoma metastasis: A clinical and pathological dilemma.

    Science.gov (United States)

    Huang, Sean; Frydenberg, Mark; Pham, Alan; Grummet, Jeremy P

    2015-01-01

    A 78-year-old man presented with an enlarging, tender mass in the scrotum separate to the testes. This was on the background of radical cystoprostatectomy, urethrectomy, and ileal conduit formation for high-grade urothelial carcinoma of the bladder invading submucosa 3 years prior. Examination revealed a 4 × 5 cm lesion, which was hard, fixed to the overlying skin and nodular to palpation. Ultrasound confirmed a solid mass in the scrotum extending into the perineum. Computerized tomography of the chest, abdomen, and pelvis revealed enlargement of inguinal lymph nodes but no other metastases. Complete resection of the scrotal lesion and selective removal of regional lymph nodes was performed. Rather than a cutaneous scrotal metastasis from the bladder urothelial carcinoma, histological examination suggested a primary apocrine adenocarcinoma of the scrotum. This case report explores the clinical and pathological features associated with both of these unusual differential diagnoses. PMID:25657556

  5. Apocrine carcinoma of the scalp – A case report and highlights for diagnosis

    Directory of Open Access Journals (Sweden)

    Arden RL

    2014-07-01

    Full Text Available Apocrine sweat gland carcinoma is a rare cutaneous adnexal neoplasm that may occur in the scalp, eyelid, and ear canal. More often, it presents as an asymptomatic, slow-growing, solid or cystic mass with variable color. The clinical appearance may be confused with basal cell carcinoma and the pathologic appearance with metastatic breast carcinoma. Supportive morphologic and immunohistochemical findings, together with careful clinicopathologic correlation, aid in diagnosis. The mainstay of treatment is wide local excision and neck dissection for node positive disease. The role of elective neck dissection and adjuvant radiotherapy remain controversial. Chemotherapy has been used for palliation in disseminated disease. This case report offers an algorithm that can aid the clinician in differential diagnosis of this often elusive neoplasm.

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

    Directory of Open Access Journals (Sweden)

    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.

  7. 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.

  8. Clinical evaluation of microRNA-145 expression in renal cell carcinoma: a promising molecular marker for discriminating and staging the clear cell histological subtype.

    Science.gov (United States)

    Papadopoulos, Emmanuel I; Petraki, Constantina; Gregorakis, Alkiviadis; Fragoulis, Emmanuel G; Scorilas, Andreas

    2016-06-01

    The vast majority of malignancies detected in renal parenchyma are diagnosed as renal cell carcinoma (RCC), whose subtype discrimination and determination of prognosis may contribute to the selection of the adequate therapy. Recently, a new class of small non-coding RNAs, known as microRNAs, has proven to be among the most promising biomarkers for providing this information. Herein, we sought to add up to this knowledge by evaluating the expression levels of microRNA-145 (miR-145) in RCC. For that purpose, total RNA from 58 cancerous and 44 adjacent non-cancerous renal tissues was firstly extracted and then polyadenylated and reverse transcribed to cDNA. MiR-145 levels were finally analyzed by developing and applying a highly sensitive real-time PCR protocol, while their clinical significance was determined via comprehensive statistical analysis. Our data showed that miR-145 was significantly downregulated in cancerous samples and could discriminate between clear cell and non-clear cell subtypes. Moreover, miR-145 expression was found to be correlated with primary tumor staging of cancerous samples, something also noticed in the clear cell RCC subset, in which miR-145 levels were negatively correlated with tumor size as well. Overall, these results indicate that miR-145 might constitute a promising molecular marker for RCC classification and staging. PMID:26866880

  9. 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 ...

  10. Molecular portrait of breast cancer in China reveals comprehensive transcriptomic likeness to Caucasian breast cancer and low prevalence of luminal A subtype

    International Nuclear Information System (INIS)

    The recent dramatic increase in breast cancer incidence across China with progressive urbanization and economic development has signaled the urgent need for molecular and clinical detailing of breast cancer in the Chinese population. Our analyses of a unique transethnic collection of breast cancer frozen specimens from Shanghai Fudan Cancer Center (Chinese Han) profiled simultaneously with an analogous Caucasian Italian series revealed consistent transcriptomic data lacking in batch effects. The prevalence of Luminal A subtype was significantly lower in Chinese series, impacting the overall prevalence of estrogen receptor (ER)-positive disease in a large cohort of Chinese/Caucasian patients. Unsupervised and supervised comparison of gene and microRNA (miRNA) profiles of Chinese and Caucasian samples revealed extensive similarity in the comprehensive taxonomy of transcriptional elements regulating breast cancer biology. Partition of gene expression data using gene lists relevant to breast cancer as “intrinsic” and “extracellular matrix” genes identified Chinese and Caucasian subgroups with equivalent global gene and miRNA profiles. These findings indicate that in the Chinese and Caucasian groups, breast neoplasia and the surrounding stromal characteristics undergo the same differentiation and molecular processes. Transcriptional similarity across transethnic cohorts may simplify translational medicine approaches and clinical management of breast cancer patients worldwide

  11. Functional and Molecular Evidence for Kv7 Channel Subtypes in Human Detrusor from Patients with and without Bladder Outflow Obstruction

    DEFF Research Database (Denmark)

    Svalø, Julie; Sheykhzade, Majid; Nordling, Jørgen; Matras, Christina; Bouchelouche, Pierre

    2015-01-01

    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 expressi...

  12. Molecular characterisation of cell line models for triple-negative breast cancers

    Directory of Open Access Journals (Sweden)

    Grigoriadis Anita

    2012-11-01

    Full Text Available Abstract Background Triple-negative breast cancers (BC represent a heterogeneous subtype of BCs, generally associated with an aggressive clinical course and where targeted therapies are currently limited. Target validation studies for all BC subtypes have largely employed established BC cell lines, which have proven to be effective tools for drug discovery. Results Given the lines of evidence suggesting that BC cell lines are effective tools for drug discovery, we assessed the similarities between triple-negative BCs and cell lines, to identify in vitro representatives, modelling the diversity within this BC subtype. 25 BC cell lines, enriched for those lacking ER, PR and HER2 expression, were subjected to transcriptomic, genomic and epigenomic profiling analyses and comparisons were made to existing knowledge of corresponding perturbations in triple-negative BCs. Transcriptional analysis segregated ER-negative BC cell lines into three groups, displaying distinctive abundances for genes involved in epithelial-mesenchymal transition, apocrine and high-grade carcinomas. DNA copy number aberrations of triple-negative BCs were well represented in cell lines and genes with coordinately altered gene expression showed similar patterns in tumours and cell lines. Methylation events in triple-negative BCs were mostly retained in epigenomes of cell lines. Combined methylation and gene expression analyses revealed a subset of genes characteristic of the Claudin-low BC subtype, exhibiting epigenetic-regulated gene expression in BC cell lines and tumours, suggesting that methylation patterns are likely to underpin subtype-specificity. Conclusion Here, we provide a comprehensive analysis of triple-negative BC features on several molecular levels in BC cell lines, thereby creating an in-depth resource to access the suitability of individual lines as experimental models for studying BC tumour biology, biomarkers and possible therapeutic targets in the context of

  13. 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

  14. 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...... and provide evidence for epigenetic inactivation of BRCA1 in three of the tumors. In addition, 7 BRCA2-like tumors were found. CONCLUSIONS: Our finding indicates involvement of hereditary factors in non-BRCA1/2 breast cancer families in which family members may carry genetic susceptibility not just to...... 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...

  15. 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

  16. 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

  17. 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

  18. 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...

  19. 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...

  20. 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.

  1. 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

  2. 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.

  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. Uroplakin II Expression in Breast Carcinomas Showing Apocrine Differentiation: Putting Some Emphasis on Invasive Pleomorphic Lobular Carcinoma as a Potential Mimic of Urothelial Carcinoma at Metastatic Sites

    Directory of Open Access Journals (Sweden)

    Shogo Tajima

    2016-01-01

    Full Text Available Uroplakin II antibody is exclusively specific for urothelial carcinoma. Nonurothelial carcinoma has not been reported to be immunoreactive for uroplakin II. In the present study, we hypothesized that breast carcinoma showing apocrine differentiation, such as invasive pleomorphic lobular carcinoma (IPLC and apocrine carcinoma (AC, stains positive for uroplakin II. We identified 6 cases of IPLC between 2000 and 2014 by searching a computerized pathological database. We randomly selected 10 cases of each classic invasive lobular carcinoma (cILC and AC and five cases of apocrine metaplasia (AM that coexisted in a surgically resected breast carcinoma specimen. Immunohistochemistry was performed for uroplakin II, GATA3, CK7, CK20, and other representative markers positive for urothelial carcinoma. All cases of IPLC, AC, and AM, except those of cILC, showed immunoreactivity for uroplakin II. Poorly differentiated urothelial carcinoma sometimes shows similar morphology to IPLC with the following immunophenotype: CK7+, CK20−, GATA3+, and uroplakin II+. In the present study, this immunophenotype was observed in all the cases of IPLC and AC. Therefore, when studying metastatic, poorly differentiated carcinoma showing the aforementioned immunophenotype, we should consider the possibility of it being IPLC in addition to metastatic urothelial carcinoma.

  5. 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

  6. 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...

  7. 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

  8. 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.

  9. 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…

  10. Value of Breast Cancer Molecular Subtypes and Ki67 Expression for the Prediction of Efficacy and Prognosis of Neoadjuvant Chemotherapy in a Chinese Population

    Science.gov (United States)

    Wang, Jiayu; Sang, Die; Xu, Binghe; Yuan, Peng; Ma, Fei; Luo, Yang; Li, Qing; Zhang, Pin; Cai, Ruigang; Fan, Ying; Chen, Shanshan; Li, Qiao

    2016-01-01

    Abstract The aim of the study was to determine the predictive role of breast cancer subtypes in the efficacy and prognosis of neoadjuvant chemotherapy (NCT) regimens combining taxanes and anthracyclines. Data from 240 patients with breast cancer who received surgery after 4 to 6 weeks of NCT were retrospectively analyzed. The patients were classified into luminal A, luminal B, HER2 overexpression, and triple negative breast cancer (TNBC) as well as low Ki67 (≤ 14%) and high Ki67 (> 14%) expression groups using immunohistochemistry. NCT outcome parameters were pathological complete response (pCR), clinical complete response (CR), partial response (PR), stable disease (SD), and progressive disease (PD) 4 weeks after surgery. Long-term outcome parameters were disease-free survival (DFS) with a follow-up time of 3 to 56 months. pCR rates were 1.6%, 13.4%, 22.6%, and 23.8% in patients with luminal A, luminal B, HER2, and TNBC cancers, respectively. High pCR rates correlated with high Ki67 expression (> 40%) (P the DFS rate of luminal A breast cancer was the highest compared to all other groups, but only significantly higher compared to luminal B (P = 0.035, HR = 1.480, 95% CI: 1.060–1.967) patients and correlated with Ki67 expression > 40% (P = 0.005). Luminal A type patients derived the least benefit from neoadjuvant chemotherapy but had better long-term prognoses. ER status and Ki67 expression served as efficacy predictors for NCT, whereas only Ki67 expression > 40% correlated with long-term treatment outcomes. PMID:27149453

  11. 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.

  12. 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

  13. 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.

  14. Cardiac potassium channel subtypes

    DEFF Research Database (Denmark)

    Schmitt, Nicole; Grunnet, Morten; Olesen, Søren-Peter

    2014-01-01

    About 10 distinct potassium channels in the heart are involved in shaping the action potential. Some of the K(+) channels are primarily responsible for early repolarization, whereas others drive late repolarization and still others are open throughout the cardiac cycle. Three main K(+) channels...... drive the late repolarization of the ventricle with some redundancy, and in atria this repolarization reserve is supplemented by the fairly atrial-specific KV1.5, Kir3, KCa, and K2P channels. The role of the latter two subtypes in atria is currently being clarified, and several findings indicate that...... they could constitute targets for new pharmacological treatment of atrial fibrillation. The interplay between the different K(+) channel subtypes in both atria and ventricle is dynamic, and a significant up- and downregulation occurs in disease states such as atrial fibrillation or heart failure. The...

  15. Subtyping adolescents with bulimia nervosa.

    Science.gov (United States)

    Chen, Eunice Y; Le Grange, Daniel

    2007-12-01

    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" subtype (62.5%) using the Beck Depression Inventory, Rosenberg Self-Esteem Scale and Eating Disorder Examination Restraint subscale. The "dietary-depressive" subtype compared to the "dietary" subtype was significantly more likely to: (1) report co-occurring disorders, (2) greater eating and weight concerns, and (3) less vomiting abstinence at post-treatment (all p'svalidity, yielding more distinct groups than subtyping by vomiting frequency. In order to assess the reliability of the subtyping scheme, a larger sample of adolescents with mixed eating and weight disorders in an outpatient eating disorder clinic (N=149) was subtyped, yielding similar subtypes. These results support the validity and reliability of the subtyping strategy in two adolescent samples. PMID:17949682

  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. 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

  18. 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.

  19. Potential of Diffusion-Weighted Imaging in the Characterization of Malignant, Benign, and Healthy Breast Tissues and Molecular Subtypes of Breast Cancer

    Science.gov (United States)

    Sharma, Uma; Sah, Rani G.; Agarwal, Khushbu; Parshad, Rajinder; Seenu, Vurthaluru; Mathur, Sandeep R.; Hari, Smriti; Jagannathan, Naranamangalam R.

    2016-01-01

    The role of apparent diffusion coefficient (ADC) in the diagnosis of breast cancer and its association with molecular biomarkers was investigated in 259 patients with breast cancer, 67 with benign pathology, and 54 healthy volunteers using diffusion-weighted imaging (DWI) at 1.5 T. In 59 breast cancer patients, dynamic contrast-enhanced MRI (DCEMRI) was also acquired. Mean ADC of malignant lesions was significantly lower (1.02 ± 0.17 × 10−3 mm2/s) compared to benign (1.57 ± 0.26 × 10−3 mm2/s) and healthy (1.78 ± 0.13 × 10−3 mm2/s) breast tissues. A cutoff ADC value of 1.23 × 10−3 mm2/s (sensitivity 92.5%; specificity 91.1%; area under the curve 0.96) to differentiate malignant from benign diseases was arrived by receiver operating curve analysis. In 10/59 breast cancer patients, indeterminate DCE curve was seen, while their ADC value was indicative of malignancy, implying the potential of the addition of DWI in increasing the specificity of DCEMRI data. Further, the association of ADC with tumor volume, stage, hormonal receptors [estrogen receptor (ER), progesterone receptor (PR), and human epidermal growth factor (HER2)], and menopausal status was investigated. A significant difference was seen in tumor volume between breast cancer patients of stages IIA and IIIA, IIB and IIIA, and IIB and III (B + C), respectively (P < 0.05). Patients with early breast cancer (n = 52) had significantly lower ADC and tumor volume than those with locally advanced breast cancer (n = 207). No association was found in ADC and tumor volume with the menopausal status. Breast cancers with ER−, PR−, and triple-negative (TN) status showed a significantly larger tumor volume compared to ER+, PR+, and non-triple-negative (nTN) cancers, respectively. Also, TN tumors showed a significantly higher ADC compared to ER+, PR+, and nTN cancers. Patients with ER− and TN cancers were younger than those with ER+ and nTN cancers

  20. 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

  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. Lobular breast cancer - the most common special subtype or a most special common subtype?

    OpenAIRE

    Lehmann, Ulrich

    2015-01-01

    Lobular breast cancer is not only the second most common breast cancer subtype, known for decades, but also a tumour entity that still poses many unresolved questions. These include questions about the targets and cooperation partners of E-cadherin, the best model systems for translational research, and the best tools for detection, surveillance and therapy. Leading experts review the molecular and cellular bases, the model systems, the histopathology and profiling approaches, risk factors, i...

  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. 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.

  7. 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.

  8. 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.

  9. 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...

  10. 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

  11. Demographic variation in incidence of adult glioma by subtype, United States, 1992-2007

    OpenAIRE

    Darefsky Amy S; Dubrow Robert

    2011-01-01

    Abstract Background We hypothesized that race/ethnic group, sex, age, and/or calendar period variation in adult glioma incidence differs between the two broad subtypes of glioblastoma (GBM) and non-GBM. Primary GBM, which constitute 90-95% of GBM, differ from non-GBM with respect to a number of molecular characteristics, providing a molecular rationale for these two broad glioma subtypes. Methods We utilized data from the Surveillance, Epidemiology, and End Results Program for 1992-2007, ages...

  12. Opposing Role for Egr3 in Nucleus Accumbens Cell Subtypes in Cocaine Action

    OpenAIRE

    Chandra, Ramesh; Francis, T. Chase; Konkalmatt, Prasad; Amgalan, Ariunzaya; Gancarz, Amy M.; Dietz, David M.; Lobo, Mary Kay

    2015-01-01

    An imbalance in molecular signaling cascades and transcriptional regulation in nucleus accumbens (NAc) medium spiny neuron (MSN) subtypes, those enriched in dopamine D1 versus D2 receptors, is implicated in the behavioral responses to psychostimulants. To provide further insight into the molecular mechanisms occurring in MSN subtypes by cocaine, we examined the transcription factor early growth response 3 (Egr3). We evaluated Egr3 because it is a target of critical cocaine-mediated signaling ...

  13. 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...

  14. Frontotemporal dementia and its subtypes

    DEFF Research Database (Denmark)

    Ferrari, Raffaele; Hernandez, Dena G; Nalls, Michael A;

    2014-01-01

    from 2154 patients with FTD and 4308 controls), we did separate association analyses for each FTD subtype (behavioural variant FTD, semantic dementia, progressive non-fluent aphasia, and FTD overlapping with motor neuron disease [FTD-MND]), followed by a meta-analysis of the entire dataset. We carried...

  15. 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.

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

    International Nuclear Information System (INIS)

    We previously reported that an envelope (Env) glycoprotein immunogen (o-gp140ΔV2SF162) 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 SHIVSF162P4 virus. Extending our studies to subtype C isolate TV1, we have purified o-gp140ΔV2TV1 (subtype C ΔV2 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 ΔV2 trimer; however, we did not observe significant binding for the b12 mAb. The molecular mass of subtype C ΔV2 trimer was found to be 450 kDa, and the hydrodynamic radius was found to be 10.87 nm. Our data suggest that subtype C ΔV2 trimer binds to CD4 with an affinity comparable to o-gp140ΔV2SF162 (subtype B ΔV2 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 ΔV2 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

  17. 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

  18. Analysis of HIV subtypes and the phylogenetic tree in HIV-positive samples from Saudi Arabia

    International Nuclear Information System (INIS)

    Objective was to assess the prevalence of HIV-1 genetic subtypes in Saudi Arabia in samples that are serologically positive for HIV-1 and compare the HIV-1 genetic subtypes prevalent in Saudi Arabia with the subtypes prevalent in other countries. Thirty-nine HIV-1 positive samples were analyzed for HIV-1 subtypes using molecular techniques. The study is retrospective study that was conducted in Dammam, Kingdom of Saudi Arabia and in Abbott laboratories (United States of America) from2004 to 2007. All samples were seropositive for HIV-1 group M. Of the 39 seropositive samples, only 12 were polymerase chain reaction positive. Subtype C is the most common virus strain as it occurred in 58% of these samples; subtype B occurred in 17%; subtypes A, D and G were found in 8% each. The phylogenetic tree was also identified for the isolates. Detection of HIV subtypes is important for epidemiological purposes and may help in tracing the source of HIV infections in the Kingdom of Saudi Arabia. (author)

  19. 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

  20. Rhinitis Subtypes, Endotypes, and Definitions.

    Science.gov (United States)

    Papadopoulos, Nikolaos G; Guibas, George V

    2016-05-01

    Rhinitis is often seen as posing a small burden. However, rhinitis is a complex disease that is underpinned by a plethora of different mechanisms and causes. Rhinitis is frequently associated with other comorbid conditions but, by itself, is a source of considerable morbidity for patients and creates a significant financial burden on health systems worldwide. This article approaches this condition from both a phenotypic and mechanistic standpoint, focusing on the complexity of characterizing these subtypes. Developing a clearer demarcation of the currently obscure rhinitis phenotypes and endotypes will substantially improve their future prevention and treatment. PMID:27083098

  1. 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

  2. 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.

  3. 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

  4. 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.

  5. 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.

  6. Peculiarities of diagnostics and clinical course of different immunohistochemical subtypes of breast cancer

    Directory of Open Access Journals (Sweden)

    El Khazhzh M.Kh.

    2014-09-01

    Full Text Available Modern global guidelines in oncology consider treatment of various forms of breast cancer according to molecular tumor subtype. Steroid receptors, epidermal growth factor receptors, p53, Ki67 proliferative activity index and others are the key indicators of aggressiveness of malignant breast tumors. The material for this study was the retrospective study of the standard set of breast cancer immuno¬histochemical markers (estrogen receptors, progesterone, epidermal growth factor type 2 in 8171 patients. 4 groups of patients - luminal A, luminal B, triple negative and HER2-neu positive subtypes of tumors were identified according to immunohistochemical status. We analyzed overall survival without relapse in 491 patients with breast cancer, clinical data and data of immunohistochemical studies were matched. Based on the investigation it was determined that in the early stages of the disease (1-2 luminal A subtype of cancer is often diagnosed. In the late stages the most common subtype is HER2-neu positive breast cancer. Herewith, patients with luminal A subtype of cancer have the best performance of the overall survival (OS (32,91±2,33 months, and the worst results were found in patients with HER2 - neu positive breast cancer (22,58±1,28 months. The data obtained determine HER2 - neu positive subtype as the most aggressive type of breast cancer, and the luminal A subtype – as the least aggressive one.

  7. Virtual microdissection identifies distinct tumor- and stroma-specific subtypes of pancreatic ductal adenocarcinoma

    Science.gov (United States)

    Moffitt, Richard A.; Marayati, Raoud; Flate, Elizabeth L.; Volmar, Keith E.; Loeza, S. Gabriela Herrera; Hoadley, Katherine A.; Rashid, Naim U.; Williams, Lindsay A.; Eaton, Samuel C.; Chung, Alexander H.; Smyla, Jadwiga K.; Anderson, Judy M.; Kim, Hong Jin; Bentrem, David J.; Talamonti, Mark S.; Iacobuzio-Donahue, Christine A.; Hollingsworth, Michael A.; Yeh, Jen Jen

    2016-01-01

    Pancreatic ductal adenocarcinoma (PDAC) remains a lethal disease with a 5-year survival of 4%. A key hallmark of PDAC is extensive stromal involvement, which makes capturing precise tumor-specific molecular information difficult. Here, we have overcome this problem by applying blind source separation to a diverse collection of PDAC gene expression microarray data, which includes primary, metastatic, and normal samples. By digitally separating tumor, stroma, and normal gene expression, we have identified and validated two tumor-specific subtypes including a “basal-like” subtype which has worse outcome, and is molecularly similar to basal tumors in bladder and breast cancer. Furthermore, we define “normal” and “activated” stromal subtypes which are independently prognostic. Our results provide new insight into the molecular composition of PDAC which may be used to tailor therapies or provide decision support in a clinical setting where the choice and timing of therapies is critical. PMID:26343385

  8. SUBTYPES OF JUVENILE SYSTEMIC SCLERODERMA

    Directory of Open Access Journals (Sweden)

    M N Slarovoitova

    2001-04-01

    Full Text Available Aim: to allot clinical forms of juvenile systemic scleroderma (JSSD. Material and methods: investigation and dynamic observation of 60 patients aged 14-54 (mean age 25.1 ±7.2 with onset of disease in child's and adolescent’s ages from 1 to 16 years old ( in average 11. 4±3.8 year old and disease duration from 1 to 39 years (in average 13.1 ±7.9. Results: 55% of patients demonstrated JSSD subtype with focal cutaneous lesion of different localization. The possibility of overlap-syndrome development in JSSD patients with onset in adolescent age typical for SSD-rheumatoid arthritis, SSD-polymvositis should be underlined. Conclusion: knowledge of different clinical forms and courses of the disease, modern diagnostics and early beginning of differential JSSD treatment will enable us to improve the prognosis and disease outcome.

  9. 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 ...

  10. 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

  11. 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.

  12. Depression in Diagnostic Subtypes of Delinquent Boys.

    Science.gov (United States)

    Kashani, Javad H.; And Others

    1982-01-01

    Delinquent boys (18 percent of 120) were found to be depressed when DSM III criteria for Major Depressive Disorder were utilized. Results indicated the prevalence of depression was not significantly more frequent among socialized, undersocialized, aggressive or nonaggressive subtypes. (Author)

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

    Directory of Open Access Journals (Sweden)

    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.

  14. 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

  15. 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

  16. 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...

  17. Panic Disorder Subtypes: Deceptive Somatic Impersonators

    OpenAIRE

    Sansone, Randy A.; Sansone, Lori A.

    2009-01-01

    Traditional panic attacks are characterized by multiple somatic symptoms involving the cardiac, respiratory, gastrointestinal, and vestibular systems. However, on occasion, panic disorder symptoms may congeal into one predominant system. These atypical presentations, in which symptoms manifest in a single system, are described as panic disorder subtypes. Four subtypes are commonly reported: 1) cardiac, 2) respiratory, 3) gastrointestinal, and 4) vestibular. In this edition of The Interface, w...

  18. 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...

  19. 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

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

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    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.

  1. 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

  2. Differential involvement of RASSF2 hypermethylation in breast cancer subtypes and their prognosis

    Science.gov (United States)

    Perez-Janices, Noemi; Blanco-Luquin, Idoia; Torrea, Natalia; Liechtenstein, Therese; Escors, David; Cordoba, Alicia; Vicente-Garcia, Francisco; Jauregui, Isabel; De La Cruz, Susana; Illarramendi, José Juan; Coca, Valle; Berdasco, Maria; Kochan, Grazyna; Ibañez, Berta; Lera, José Miguel; Guerrero-Setas, David

    2015-01-01

    Breast cancer is a heterogeneous disease that can be subdivided into clinical, histopathological and molecular subtypes (luminal A-like, luminal B-like/HER2-negative, luminal B-like/HER2-positive, HER2-positive, and triple-negative). The study of new molecular factors is essential to obtain further insights into the mechanisms involved in the tumorigenesis of each tumor subtype. RASSF2 is a gene that is hypermethylated in breast cancer and whose clinical value has not been previously studied. The hypermethylation of RASSF1 and RASSF2 genes was analyzed in 198 breast tumors of different subtypes. The effect of the demethylating agent 5-aza-2′-deoxycytidine in the re-expression of these genes was examined in triple-negative (BT-549), HER2 (SK-BR-3), and luminal cells (T-47D). Different patterns of RASSF2 expression for distinct tumor subtypes were detected by immunohistochemistry. RASSF2 hypermethylation was much more frequent in luminal subtypes than in non-luminal tumors (p = 0.001). The re-expression of this gene by lentiviral transduction contributed to the differential cell proliferation and response to antineoplastic drugs observed in luminal compared with triple-negative cell lines. RASSF2 hypermethylation is associated with better prognosis in multivariate statistical analysis (P = 0.039). In conclusion, RASSF2 gene is differently methylated in luminal and non-luminal tumors and is a promising suppressor gene with clinical involvement in breast cancer. PMID:26284587

  3. 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

  4. 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 ...

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

    Directory of Open Access Journals (Sweden)

    L.K.H. Cunha

    2012-02-01

    Full Text Available 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.

  6. 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...

  7. Is the Inattentive Subtype of ADHD Different from the Combined/Hyperactive Subtype?

    Science.gov (United States)

    Grizenko, Natalie; Paci, Michael; Joober, Ridha

    2010-01-01

    Objective: To compare the ADHD combined/hyperactive subtype (ADHD/CH) to the ADHD inattentive subtype (ADHD/I) on the level of comorbidity, treatment response, and possible etiological factors. Method: A total of 371 clinically referred children diagnosed with ADHD aged between 6 and 12 years are recruited for a double-blind, placebo-controlled…

  8. 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.

  9. Gene expression analysis uncovers similarity and differences among Burkitt lymphoma subtypes

    DEFF Research Database (Denmark)

    Piccaluga, Pier Paolo; De Falco, Giulia; Kustagi, Manjunath;

    2011-01-01

    Burkitt lymphoma (BL) is classified into 3 clinical subsets: endemic, sporadic, and immunodeficiency-associated BL. So far, possible differences in their gene expression profiles (GEPs) have not been investigated. We studied GEPs of BL subtypes, other B-cell lymphomas, and B lymphocytes; first, we...... found that BL is a unique molecular entity, distinct from other B-cell malignancies. Indeed, by unsupervised analysis all BLs clearly clustered apart of other lymphomas. Second, we found that BL subtypes presented slight differences in GEPs. Particularly, they differed for genes involved in cell cycle...

  10. 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

  11. 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.

  12. Role of HIV-1 subtype C envelope V3 to V5 regions in viral entry, coreceptor utilization and replication efficiency in primary T-lymphocytes and monocyte-derived macrophages

    Directory of Open Access Journals (Sweden)

    Gopalan Sarla

    2007-11-01

    Full Text Available Abstract Background Several subtypes of HIV-1 circulate in infected people worldwide, including subtype B in the United States and subtype C in Africa and India. To understand the biological properties of HIV-1 subtype C, including cellular tropism, virus entry, replication efficiency and cytopathic effects, we reciprocally inserted our previously characterized envelope V3–V5 regions derived from 9 subtype C infected patients from India into a subtype B molecular clone, pNL4-3. Equal amounts of the chimeric viruses were used to infect T-lymphocyte cell lines (A3.01 and MT-2, coreceptor cell lines (U373-MAGI-CCR5/CXCR4, primary blood T-lymphocytes (PBL and monocyte-derived macrophages (MDM. Results We found that subtype C envelope V3–V5 region chimeras failed to replicate in T-lymphocyte cell lines but replicated in PBL and MDM. In addition, these chimeras were able to infect U373MAGI-CD4+-CCR5+ but not U373MAGI-CD4+-CXCR4+ cell line, suggesting CCR5 coreceptor utilization and R5 phenotypes. These subtype C chimeras were unable to induce syncytia in MT-2 cells, indicative of non-syncytium inducing (NSI phenotypes. More importantly, the subtype C envelope chimeras replicated at higher levels in PBL and MDM compared with subtype B chimeras and isolates. Furthermore, the higher levels subtype C chimeras replication in PBL and MDM correlated with increased virus entry in U373MAGI-CD4+-CCR5+. Conclusion Taken together, these results suggest that the envelope V3 to V5 regions of subtype C contributed to higher levels of HIV-1 replication compared with subtype B chimeras, which may contribute to higher viral loads and faster disease progression in subtype C infected individuals than other subtypes as well as rapid HIV-1 subtype C spread in India.

  13. 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).…

  14. 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…

  15. Molecular signatures define alopecia areata subtypes and transcriptional biomarkers

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    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.

  16. 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......In nominal type systems, the subtype relation is between names of types, and subtype links are explicitly declared. In structural type systems, names are irrelevant; in determining type compatibility, only the structure of types is considered, and a type name is just an abbreviation for the full...... 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....

  17. 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.

  18. 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...... are described, as well as the implied structures of these functional domains....

  19. 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

  20. 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

  1. 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

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

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    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.

  3. 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....

  4. 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.

  5. An effective tool for identifying HIV-1 subtypes B, C, CRF01_AE, their recombinant forms, and dual infections in Southeast Asia by the multi-region subtype specific PCR (MSSP) assay.

    Science.gov (United States)

    Sakkhachornphop, Supachai; Kijak, Gustavo H; Beyrer, Chris; Razak, Myat Htoo; Sanders-Buell, Eric; Jittiwutikarn, Jaroon; Suriyanon, Vinai; Robb, Merlin L; Kim, Jerome H; Celentano, David D; McCutchan, Francine E; Tovanabutra, Sodsai

    2015-06-01

    The RV144 Thai vaccine trial has been the only vaccine study to show efficacy in preventing HIV infection. Ongoing molecular surveillance of HIV-1 in Southeast Asia is vital for vaccine development and evaluation. In this study a novel tool, the multi-region subtype specific PCR (MSSP) assay, that was able to identify subtypes B, C, CRF01_AE for Thailand, other Southeast Asian countries, India and China is described. The MSSP assay is based on a nested PCR strategy and amplifies eight short regions distributed along the HIV-1 genome using subtype-specific primers. A panel of 41 clinical DNA samples obtained primarily from opiate users in northern Thailand was used to test the assay performance. The MSSP assay provided 73-100% sensitivity and 100% specificity for the three subtypes in each genome region. The assay was then field-tested on 337 sera from HIV infected northern Thai drug users collected between 1999 and 2002. Subtype distribution was CRF01_AE 77.4% (n=261), subtype B 3.3% (n=11), CRF01_AE/B recombinant 12.2% (n=41), CRF01_AE/C recombinant 0.6% (n=2), and non-typeable 6.5% (n=22). The MSSP assay is a simple, cost-effective, and accurate genotyping tool for laboratory settings with limited resources and is sensitive enough to capture the recombinant genomes and dual infections. PMID:25725414

  6. 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.

  7. Efficacy of lacosamide by focal seizure subtype.

    Science.gov (United States)

    Sperling, Michael R; Rosenow, Felix; Faught, Edward; Hebert, David; Doty, Pamela; Isojärvi, Jouko

    2014-10-01

    The purpose of this post hoc exploratory analysis was to determine the effects of the antiepileptic drug, lacosamide, on focal (partial-onset) seizure subtypes. Patient data from the three lacosamide pivotal trials were grouped and pooled by focal seizure subtype at Baseline: simple partial seizures (SPS), complex partial seizures (CPS), and secondarily generalized partial seizures (SGPS). Both efficacy outcomes (median percent change from Baseline to Maintenance Phase in seizure frequency per 28 days and the proportion of patients experiencing at least a 50% reduction in seizures) were evaluated by lacosamide dose (200, 400, or 600 mg/day) compared to placebo for each seizure subtype. An additional analysis was performed to determine whether a shift from more severe focal seizure subtypes to less severe occurred upon treatment with lacosamide. In patients with CPS or SGPS at Baseline, lacosamide 400 mg/day (maximum recommended daily dose) and 600 mg/day reduced the frequency of CPS and SGPS compared to placebo. Likewise, a proportion of patients with CPS and SGPS at Baseline experienced at least a 50% reduction in the frequency of CPS and SGPS (≥50% responder rate) in the lacosamide 400 and 600 mg/day groups compared with placebo. For both outcomes, numerically greatest responses were observed in the lacosamide 600 mg/day group among patients with SGPS at Baseline. In patients with SPS at Baseline, no difference between placebo and lacosamide was observed for either efficacy outcome. An additional exploratory analysis suggests that in patients with SPS at Baseline, CPS and SGPS may have been shifted to less severe SPS upon treatment with lacosamide. The results of these exploratory analyses revealed reductions in CPS and SGPS frequency with adjunctive lacosamide. Reduction in CPS and SGPS may confound assessment of SPS since the CPS or SGPS may possibly change to SPS by effective treatment. PMID:25082395

  8. Subtypes of children with attention disabilities

    OpenAIRE

    Brand, E.F.J.M.; Das-Smaal, E.A.; Jong, de, Franciska

    1996-01-01

    Subtypes of children with attentional problems were investigated using cluster analysis. Subjects were 9-year-old-elementary school children (N = 443). The test battery administered to these children comprised a comprehensive set of common attention tests, covering different aspects of attentional functioning, and a test of reading comprehension. Cluster analysis of these data yielded eight stable and reproducible clus¬ters. The test profiles of two subgroups were indicative of distinct atten...

  9. Proteomic maps of breast cancer subtypes.

    Science.gov (United States)

    Tyanova, Stefka; Albrechtsen, Reidar; Kronqvist, Pauliina; Cox, Juergen; Mann, Matthias; Geiger, Tamar

    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 also reflected on the mRNA level. These breast cancer features revealed by our work provide novel insights that may ultimately translate to development of subtype-specific therapeutics. PMID:26725330

  10. 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

  11. Recent Insight Into the Subtypes of Social Anxiety Disorder.

    Science.gov (United States)

    D'Avanzato, Catherine; Dalrymple, Kristy L

    2016-05-01

    Systems for subtyping individuals with social anxiety disorder have been the focus of much research attention as a means to improve assessment and treatment of the disorder. This article highlights recent revisions to social anxiety disorder (SAD) subtypes from the Diagnostic and Statistical Manual of Mental Disorders, Fourth Edition (DSM-IV) to DSM-V, reviewing empirical evidence that served as the impetus for the revisions. Recent research examining the validity of the DSM-V system and alternative subtyping systems is reviewed. Overall, there appears to be greater empirical support for a dimensional subtyping system. Concerns therefore remain with the DSM-V system, which retained a categorical system but replaced the previous subtypes with a subtype of individuals fearing only performance situations. Recommendations for future research are discussed, as well as alternate options for capturing the variability in SAD presentations, including the possibility of eliminating subtyping altogether. PMID:27017831

  12. 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

  13. 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

  14. Opposing role for Egr3 in nucleus accumbens cell subtypes in cocaine action.

    Science.gov (United States)

    Chandra, Ramesh; Francis, T Chase; Konkalmatt, Prasad; Amgalan, Ariunzaya; Gancarz, Amy M; Dietz, David M; Lobo, Mary Kay

    2015-05-20

    An imbalance in molecular signaling cascades and transcriptional regulation in nucleus accumbens (NAc) medium spiny neuron (MSN) subtypes, those enriched in dopamine D1 versus D2 receptors, is implicated in the behavioral responses to psychostimulants. To provide further insight into the molecular mechanisms occurring in MSN subtypes by cocaine, we examined the transcription factor early growth response 3 (Egr3). We evaluated Egr3 because it is a target of critical cocaine-mediated signaling pathways and because Egr3-binding sites are found on promoters of key cocaine-associated molecules. We first used a RiboTag approach to obtain ribosome-associated transcriptomes from each MSN subtype and found that repeated cocaine administration induced Egr3 ribosome-associated mRNA in NAc D1-MSNs while reducing Egr3 in D2-MSNs. Using Cre-inducible adeno-associated viruses combined with D1-Cre and D2-Cre mouse lines, we observed that Egr3 overexpression in D1-MSNs enhances rewarding and locomotor responses to cocaine, whereas overexpression in D2-MSNs blunts these behaviors. miRNA knock-down of Egr3 in MSN subtypes produced opposite behavioral responses from those observed with overexpression. Finally, we found that repeated cocaine administration altered Egr3 binding to promoters of genes that are important for cocaine-mediated cellular and behavioral plasticity. Genes with increased Egr3 binding to promoters, Camk2α, CREB, FosB, Nr4a2, and Sirt1, displayed increased mRNA in D1-MSNs and, in some cases, a reduction in D2-MSNs. Histone and the DNA methylation enzymes G9a and Dnmt3a displayed reduced Egr3 binding to their promoters and reduced mRNA in D1-MSNs. Our study provides novel insight into an opposing role of Egr3 in select NAc MSN subtypes in cocaine action. PMID:25995477

  15. 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...

  16. 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...

  17. 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

  18. 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.

  19. Phylogenetic Analysis of the p24-p7 Region of the Human Immunodeficiency Virus Type 1 gag Gene To Determine Subtype Distribution among Female Sex Workers in Calcutta, India

    OpenAIRE

    Sengupta, Satarupa; Jana, Smarajit; Roy, Pratim; Sarkar, Kamalesh; Bhattacharya, Sujit K; Chakrabarti, Sekhar

    2005-01-01

    Human immunodeficiency virus type 1 (HIV-1) subtype C, based on the envelope region, has been reported to be predominant in India. We sequenced the p24-p7 gag region from 51 HIV-1 seropositive female sex workers in Calcutta, India, for more-detailed molecular characterization. Subtype C was found to be prevalent, although no strong monophyletic cluster was observed.

  20. 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

  1. Molecular Typing of Treponema pallidum in South Africa: Cross-Sectional Studies

    OpenAIRE

    Pillay, A; Liu, H; Ebrahim, S; Chen, C Y; Lai, W.; Fehler, G; Ballard, R C; Steiner, B.; Sturm, A W; Morse, S A

    2002-01-01

    We evaluated a molecular subtyping system for Treponema pallidum for its ability to differentiate between strains obtained from male patients with primary syphilis in South Africa. Of 201 T. pallidum-positive specimens, 161 were typeable, revealing 35 subtypes. The unique subtypes identified in Durban, Cape Town, and Carletonville and the total number of subtypes suggested that the strain population was very diverse and varied geographically.

  2. 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.

  3. 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

  4. Use of FISH analysis for diagnosis of Renal Cell Carcinoma Subtypes

    International Nuclear Information System (INIS)

    Cytogenetic and molecular genetic techniques have been used in demonstrating the chromsomal abnormalities which characterize specific subtypes of renal cell carcinoma (RCC). The aim this study was to determine the efficiency of fluorescent in situ hybridization (FISH) technique in characterizing various subtypes of RCC based on the presence of specific chromosome abnormalities found in each RCC subtype. FISH was performed on touch imprint smears from eight renal cell carcinomas histologically confirmed by established criteria. In four tumors with histologic features of chromophobe renal cell carcinoma (ChRCC), interphase fish was performed using centrometric probes for chrosomes 1, 2, 6, 10, 12, 17 and 21. All four ChRCC tumors showed one FIISH signal corresponding to one copy number for each of these chromosomes. Two papillary RCCs included in this study showed trisomy 7 and 17, and loss of chromosome Y, using the corresponding chromosome centrometric probes. Similarly, we tested two clear cell RCCs for chromosome 3 short arm deletion with DNA probe 3p21.3. Both tumors showed loss of 3p21.3 signal. We conclude that interphase fish performed on touch imprint smears is a relatively simple, rapid and reliable method for detecting chromosome abnormalities which are specific for various subtypes of RCC. (author)

  5. 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.

  6. 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...

  7. Subtype selective kainic acid receptor agonists

    DEFF Research Database (Denmark)

    Bunch, Lennart; Krogsgaard-Larsen, Povl

    2009-01-01

    (S)-Glutamic acid (Glu) is the major excitatory neurotransmitter in the mammalian central nervous system, activating the plethora of glutamate receptors (GluRs). In broad lines, the GluRs are divided into two major classes: the ionotropic Glu receptors (iGluRs) and the metabotropic Glu receptors ....... In total, over 100 compounds are described by means of chemical structure and available pharmacological data. With this perspective review, it is our intention to ignite and stimulate inspiration for future design and synthesis of novel subtype selective KA receptor agonists....

  8. 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

  9. 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

  10. Subtyping pathological gamblers based on impulsivity, depression and anxiety

    OpenAIRE

    Ledgerwood, David M.; Petry, Nancy M.

    2010-01-01

    This study examined putative subtypes of pathological gamblers (PGs) based on the Pathways Model, and it also evaluated whether the subtypes would benefit differentially from treatment. Treatment-seeking PGs (N = 229) were categorized into Pathways subtypes based on scores from questionnaires assessing anxiety, depression and impulsivity. The Addiction Severity Index Gambling assessed severity of gambling problems at baseline, post-treatment and 12-month follow-up. Compared with Behaviorally ...

  11. Master Regulators, Regulatory Networks, and Pathways of Glioblastoma Subtypes

    OpenAIRE

    Serdar Bozdag; Aiguo Li; Mehmet Baysan; Fine, Howard A.

    2014-01-01

    Glioblastoma multiforme (GBM) is the most common malignant brain tumor. GBM samples are classified into subtypes based on their transcriptomic and epigenetic profiles. Despite numerous studies to better characterize GBM biology, a comprehensive study to identify GBM subtype- specific master regulators, gene regulatory networks, and pathways is missing. Here, we used FastMEDUSA to compute master regulators and gene regulatory networks for each GBM subtype. We also ran Gene Set Enrichment Analy...

  12. 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...

  13. 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.

  14. Molecular Typing of Treponema pallidum Clinical Strains from Lisbon, Portugal▿

    Science.gov (United States)

    Florindo, C.; Reigado, V.; Gomes, J. P.; Azevedo, J.; Santo, I.; Borrego, M. J.

    2008-01-01

    A molecular system was used to subtype Portuguese Treponema pallidum clinical strains isolated from both skin lesions and blood. The study with this system constitutes the first typing study in a European country. Three T. pallidum subtypes were found: subtypes 14a (50%), 14d (45.2%), and 14f (4.8%). Further studies are needed to better characterize the isolates involved in syphilis outbreaks. PMID:18753355

  15. Molecular Typing of Treponema pallidum Clinical Strains from Lisbon, Portugal▿

    OpenAIRE

    Florindo, C.; Reigado, V.; Gomes, J. P.; Azevedo, J.; Santo, I; Borrego, M.J.

    2008-01-01

    A molecular system was used to subtype Portuguese Treponema pallidum clinical strains isolated from both skin lesions and blood. The study with this system constitutes the first typing study in a European country. Three T. pallidum subtypes were found: subtypes 14a (50%), 14d (45.2%), and 14f (4.8%). Further studies are needed to better characterize the isolates involved in syphilis outbreaks.

  16. 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

  17. 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...

  18. 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

  19. 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

  20. A multiplex oligonucleotide ligation-PCR as a complementary tool for subtyping of Salmonella Typhimurium.

    Science.gov (United States)

    Wuyts, Véronique; Mattheus, Wesley; Roosens, Nancy H C; Marchal, Kathleen; Bertrand, Sophie; De Keersmaecker, Sigrid C J

    2015-10-01

    Subtyping below the serovar level is essential for surveillance and outbreak detection and investigation of Salmonella enterica subsp. enterica serovar Typhimurium (S. Typhimurium) and its monophasic variant 1,4,[5],12:i:- (S. 1,4,[5],12:i:-), frequent causes of foodborne infections. In an attempt to overcome the intrinsic shortcomings of currently used subtyping techniques, a multiplex oligonucleotide ligation-PCR (MOL-PCR) assay was developed which combines different types of molecular markers in a high-throughput microsphere suspension array. The 52 molecular markers include prophage genes, amplified fragment length polymorphism (AFLP) elements, Salmonella genomic island 1 (SGI1), allantoinase gene allB, MLVA locus STTR10, antibiotic resistance genes, single nucleotide polymorphisms (SNPs) and phase 2 flagellar gene fljB. The in vitro stability of these markers was confirmed in a serial passage experiment. The validation of the MOL-PCR assay for subtyping of S. Typhimurium and S. 1,4,[5],12:i:- on 519 isolates shows that the method is rapid, reproducible, flexible, accessible, easy to use and relatively inexpensive. Additionally, a 100 % typeability and a discriminatory power equivalent to that of phage typing were observed, and epidemiological concordance was assessed on isolates of 2 different outbreaks. Furthermore, a data analysis method is provided so that the MOL-PCR assay allows for objective, computerised data analysis and data interpretation of which the results can be easily exchanged between different laboratories in an international surveillance network. PMID:26205523

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

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    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.

  2. Gene Signature in Sessile Serrated Polyps Identifies Colon Cancer Subtype.

    Science.gov (United States)

    Kanth, Priyanka; Bronner, Mary P; Boucher, Kenneth M; Burt, Randall W; Neklason, Deborah W; Hagedorn, Curt H; Delker, Don A

    2016-06-01

    Sessile serrated colon adenoma/polyps (SSA/P) are found during routine screening colonoscopy and may account for 20% to 30% of colon cancers. However, differentiating SSA/Ps from hyperplastic polyps (HP) with little risk of cancer is challenging and complementary molecular markers are needed. In addition, the molecular mechanisms of colon cancer development from SSA/Ps are poorly understood. RNA sequencing (RNA-Seq) was performed on 21 SSA/Ps, 10 HPs, 10 adenomas, 21 uninvolved colon, and 20 control colon specimens. Differential expression and leave-one-out cross-validation methods were used to define a unique gene signature of SSA/Ps. Our SSA/P gene signature was evaluated in colon cancer RNA-Seq data from The Cancer Genome Atlas (TCGA) to identify a subtype of colon cancers that may develop from SSA/Ps. A total of 1,422 differentially expressed genes were found in SSA/Ps relative to controls. Serrated polyposis syndrome (n = 12) and sporadic SSA/Ps (n = 9) exhibited almost complete (96%) gene overlap. A 51-gene panel in SSA/P showed similar expression in a subset of TCGA colon cancers with high microsatellite instability. A smaller 7-gene panel showed high sensitivity and specificity in identifying BRAF-mutant, CpG island methylator phenotype high, and MLH1-silenced colon cancers. We describe a unique gene signature in SSA/Ps that identifies a subset of colon cancers likely to develop through the serrated pathway. These gene panels may be utilized for improved differentiation of SSA/Ps from HPs and provide insights into novel molecular pathways altered in colon cancer arising from the serrated pathway. Cancer Prev Res; 9(6); 456-65. ©2016 AACR. PMID:27026680

  3. Correlating Preoperative Imaging with Histologic Subtypes of Renal Cell Carcinoma and Common Mimickers.

    Science.gov (United States)

    Gordetsky, Jennifer; Zarzour, Jessica

    2016-07-01

    Renal cell carcinoma (RCC) consists of distinct subtypes that have unique pathologic and imaging features as well as specific cytogenetic and molecular characteristics. As the prognosis and therapeutic strategies may differ for each subtype, correlation of the preoperative imaging with the pathologic findings is of great clinical relevance. In addition, differentiation of RCC from benign entities is ideal in order to prevent overtreatment. However, a noninvasive diagnosis with imaging alone is not always straightforward due to the overlapping appearance of RCC with benign lesions such as fat-poor angiomyolipoma and oncocytoma. With new imaging modalities, there have been significant improvements in correlating preoperative imaging with pathologic characteristics. These new discoveries are able to aid in a more specific, noninvasive, diagnosis that in turn helps direct patient management. PMID:27154238

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

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    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

  5. 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

  6. 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.

  7. 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.

  8. Head and neck cancer subtypes with biological and clinical relevance: Meta-analysis of gene-expression data.

    Science.gov (United States)

    De Cecco, Loris; Nicolau, Monica; Giannoccaro, Marco; Daidone, Maria Grazia; Bossi, Paolo; Locati, Laura; Licitra, Lisa; Canevari, Silvana

    2015-04-20

    Head and neck squamous cell carcinoma (HNSCC) is a disease with heterogeneous clinical behavior and response to therapies. Despite the introduction of multimodality treatment, 40-50% of patients with advanced disease recur. Therefore, there is an urgent need to improve the classification beyond the current parameters in clinical use to better stratify patients and the therapeutic approaches. Following a meta-analysis approach we built a large training set to whom we applied a Disease-Specific Genomic Analysis (DSGA) to identify the disease component embedded into the tumor data. Eleven independent microarray datasets were used as validation sets. Six different HNSCC subtypes that summarize the aberrant alterations occurring during tumor progression were identified. Based on their main biological characteristics and de-regulated signaling pathways, the subtypes were designed as immunoreactive, inflammatory, human papilloma virus (HPV)-like, classical, hypoxia associated, and mesenchymal. Our findings highlighted a more aggressive behavior for mesenchymal and hypoxia-associated subtypes. The Genomics Drug Sensitivity Project was used to identify potential associations with drug sensitivity and significant differences were observed among the six subtypes. To conclude, we report a robust molecularly defined subtype classification in HNSCC that can improve patient selection and pave the way to the development of appropriate therapeutic strategies. PMID:25821127

  9. 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....

  10. 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.…

  11. Gene profiling suggests a common evolution of bladder cancer subtypes

    OpenAIRE

    Hansel, Donna E.; Zhang, ZhongFa; Petillo, David; Teh, Bin T.

    2013-01-01

    Abstract Background Bladder cancer exists as several distinct subtypes, including urothelial carcinoma (UCa), squamous cell carcinoma (SCCa), adenocarcinoma and small cell carcinoma. These entities, despite showing distinct morphology and clinical behavior, arise from the urothelial lining and are often accompanied by similar precursor/in situ findings. The relationship between these subtypes has not been explored in detail. ...

  12. 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....

  13. 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...

  14. Osteoclastic finger arthrosis - a subtype of polyarthrosis of the hand; Osteoklastische Fingerarthrose - Subtyp der Handpolyarthrose

    Energy Technology Data Exchange (ETDEWEB)

    Dihlmann, W. [Radiologische Praxis, Hamburg-Barmbek (Germany); Dihlmann, A. [Berufsgenossenschaftliches Unfallkrankenhaus Hamburg (Germany)

    1998-02-01

    Aim: Description of a subtype of arthrosis deformans of the hand which is characterised as osteoclastic arthrosis. Patients and methods: Retrospective analysis of radiographs of the hands of 150 women and 100 men with radiological findings of arthrosis deformans. Results: 5% of women and 2% of men showed at least one digital joint with subchondral osteolysis of one or both articulating bones involving at least a third of the phalanx. This subchondral osteolysis far exceeds the cysts which are situated in the epiphyseal part of the articular region. It may develop within a year. Conclusion: Osteoclastic arthrosis of the finger is a subtype of polyarthrosis of the hand. Serial observations suggest that an osteoclast stimulating substance is produced by the cysts or arises directly from the synovial fluid; this enters the subchondral part of the bone through clefts which may or may not be visible radiologically and that this produces osteoclastic activity. The most important differential diagnoses are chronic tophacious gout and a benign tumor. (orig.) [Deutsch] Ziel: Beschreibung eines Subtyps der Arthrosis deformans an der Hand, der als osteoklastische Arthrose bezeichnet wird. Patienten und Methode: Retrospektive Analyse der Handroentgenaufnahmen von 150 Frauen und 100 Maennern mit Roentgenbefunden der Arthrosis deformans. Ergebnisse: 5% der Frauen und 2% der maennlichen Patienten des durchgesehenen Krankenguts zeigten an mindestens einem Fingergelenk eine Arthrose mit subchondralen Osteolysen an einem oder beiden artikulierenden Knochen, die mindestens ein Drittel der Phalanxlaenge erfasst hatten. Diese subchondralen Osteolysen gehen ueber die Groesse und Form der arthrotischen Geroellzysten, die lediglich im knoechernen (epiphysaeren) Gelenksockel sitzen, weit hinaus. Sie koennen innerhalb eines Jahres entstehen. Schlussfolgerung: Die osteoklastische Arthrose der Finger ist ein Subtyp der Handpolyarthrose. Nach Verlaufsbeobachtungen wird vermutet, dass eine

  15. 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.

  16. 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.

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

    International Nuclear Information System (INIS)

    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. 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. 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. Protein and lipid profiles accurately distinguish tumor from adjacent normal tissue and classify breast cancers according to the intrinsic subtype

  18. 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.

  19. 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

  20. 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.

  1. 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.

  2. 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. PMID:25706932

  3. 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.

  4. Prehospital Identification of Stroke Subtypes in Chinese Rural Areas

    Directory of Open Access Journals (Sweden)

    Hai-Qiang Jin

    2016-01-01

    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.

  5. ADHD Symptoms and Subtypes: Relationship between Childhood and Adolescent Symptoms

    Science.gov (United States)

    Hurtig, Tuula; Ebeling, Hanna; Taanila, Anja; Miettunen, Jouko; Smalley, Susan L.; McGough, James J.; Loo, Sandra K.; Jarvelin, Marjo-Riitta; Moilanen, Irma K.

    2007-01-01

    A study aims to examine attention-deficit/hyperactivity disorder(ADHD) symptoms and subtypes in childhood and adolescence. The results conclude the persistence of ADHD from childhood to adolescence with specific symptoms contributing to persistent ADHD.

  6. Risk Factors for Invasive Epithelial Ovarian Cancer by Histologic Subtype

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    Quirk JT

    2004-10-01

    Full Text Available It is unclear whether the different histologic subtypes of epithelial ovarian carcinoma have different risk factors. We investigated the relationships between selected epidemiologic variables (i.e., parity, family history of ovarian cancer, oral contraceptive use, a history of tubal ligation and noncontraceptive estrogen use and the major histologic subtypes of epithelial ovarian cancer in a hospital-based case-control study of adult women at Roswell Park Cancer Institute in Buffalo, NY, USA. Multivariate unconditional logistic regression models were used for statistical analysis. We observed a pattern of increased risk associated with family history and a pattern of risk reduction associated with parity, noncontraceptive estrogen use and tubal ligation across all histologic subtype groups. However, we did not observe a consistent pattern of risk associated with oral contraceptive use. These results provide some additional support for the hypothesis that the effects of various ovarian cancer risk factors may differ according to the histologic subtype.

  7. 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

  8. 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

  9. 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. PMID:26549332

  10. 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

  11. 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

  12. 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....

  13. 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

  14. Expression, purification and preliminary X-ray crystallographic studies of the human immunodeficiency virus 1 subtype C protease

    International Nuclear Information System (INIS)

    Crystals of the human immunodeficiency virus 1 subtype C protease complexed with indinavir and nelfinavir have been grown in the monoclinic space group P21 and shown to diffract X-rays to 2.3 Å resolution. Crystals of the human immunodeficiency virus 1 (HIV-1) subtype C protease (PR) complexed with the clinically used inhibitors indinavir (IDV) and nelfinavir (NFV) have been grown in the monoclinic space group P21, with mean unit-cell parameters a = 46.7 (±0.1), b = 59.8 (±0.3), c = 87.0 (±0.4) Å, β = 95.2 (±0.5)°. The crystals of both complexes have been shown to diffract X-rays to 2.3 Å resolution. The diffraction data for the subtype C PR complexes with IDV and NFV were subsequently processed and reduced, with overall Rsym values of 8.4 and 11.4%, respectively. Based on the unit-cell volumes, molecular-replacement results and packing considerations, there are two protease homodimers per crystallographic asymmetric unit in each of the complexes. The data were initially phased using a model based on the crystal structure of HIV-1 subtype B PR; the structures have been determined and further refinement and analysis are in progress. These structures and subsequent studies with other inhibitors will greatly aid in correlating the amino-acid variation between the different HIV PRs and understanding their differential sensitivity and resistance to current drug therapy

  15. Utilization of USDA subtyping data as a surveillance and investigation tool: Salmonella Newport-MDR-Amp-C infections associated with ground beef

    Science.gov (United States)

    Background: The USDA Food Safety and Inspection Service (FSIS), Centers for Disease Control and Prevention (CDC), and USDA Agricultural Research Service (ARS) have developed mechanisms to routinely compare molecular subtyping information on bacterial isolates of public health concern from PulseNet a...

  16. 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.

  17. 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

  18. Choice of adjuvant drug therapy on the basis of the molecular classification of breast cancer

    OpenAIRE

    N. S. Besova

    2014-01-01

    Molecular genetic analysis identified some biological subtypes of breast cancer (BC): luminal A, luminal B, HER2 positive, and basal-like (including triple negative). The surrogate clinical and morphological criteria including the immunohistochemical determination of estrogen and progesterone receptors, the hyperexpression and/or amplification of HER2, Ki-67, or tumor grade (G) are used to identify the biological subtypes of BC in clinical practice. The biological subtypes are distinguished b...

  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. 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.

  4. Performance Characteristics of Human Immunodeficiency Virus Type 1 (HIV-1) Genotyping Systems in Sequence-Based Analysis of Subtypes Other than HIV-1 Subtype B

    OpenAIRE

    Jagodzinski, Linda L; Cooley, John D.; Weber, Mark; Michael, Nelson L.

    2003-01-01

    Given the diversity of human immunodeficiency virus type 1 (HIV-1) subtypes and the emergence of subtypes other than HIV-1 subtype B in the United States, genotypic assays must be capable of delivering sequence data on diverse HIV-1 subtypes. We evaluated the performance of Visible Genetics TRUGENE HIV-1 genotyping kit and Applied Biosystems ViroSeq HIV-1 genotyping system on a panel of 34 well-characterized HIV-1 viral stocks (subtypes A through H). Both assays perform well on diverse HIV-1 ...

  5. Identification of Multiple Subtypes of Campylobacter jejuni in Chicken Meat and the Impact on Source Attribution

    Directory of Open Access Journals (Sweden)

    John A. Hudson

    2013-09-01

    Full Text Available Most source attribution studies for Campylobacter use subtyping data based on single isolates from foods and environmental sources in an attempt to draw epidemiological inferences. It has been suggested that subtyping only one Campylobacter isolate per chicken carcass incurs a risk of failing to recognise the presence of clinically relevant, but numerically infrequent, subtypes. To investigate this, between 21 and 25 Campylobacter jejuni isolates from each of ten retail chicken carcasses were subtyped by pulsed-field gel electrophoresis (PFGE using the two restriction enzymes SmaI and KpnI. Among the 227 isolates, thirteen subtypes were identified, the most frequently occurring subtype being isolated from three carcasses. Six carcasses carried a single subtype, three carcasses carried two subtypes each and one carcass carried three subtypes. Some subtypes carried by an individual carcass were shown to be potentially clonally related. Comparison of C. jejuni subtypes from chickens with isolate subtypes from human clinical cases (n = 1248 revealed seven of the thirteen chicken subtypes were indistinguishable from human cases. None of the numerically minor chicken subtypes were identified in the human data. Therefore, typing only one Campylobacter isolate from individual chicken carcasses may be adequate to inform Campylobacter source attribution.

  6. Abundance of intrinsic structural disorder in the histone H1 subtypes.

    Science.gov (United States)

    Kowalski, Andrzej

    2015-12-01

    The intrinsically disordered proteins consist of partially structured regions linked to the unstructured stretches, which consequently form the transient and dynamic conformational ensembles. They undergo disorder to order transition upon binding their partners. Intrinsic disorder is attributed to histones H1, perceived as assemblers of chromatin structure and the regulators of DNA and proteins activity. In this work, the comparison of intrinsic disorder abundance in the histone H1 subtypes was performed both by the analysis of their amino acid composition and by the prediction of disordered stretches, as well as by identifying molecular recognition features (MoRFs) and ANCHOR protein binding regions (APBR) that are responsible for recognition and binding. Both human and model organisms-animals, plants, fungi and protists-have H1 histone subtypes with the properties typical of disordered state. They possess a significantly higher content of hydrophilic and charged amino acid residues, arranged in the long regions, covering over half of the whole amino acid residues in chain. Almost complete disorder corresponds to histone H1 terminal domains, including MoRFs and ANCHOR. Those motifs were also identified in a more ordered histone H1 globular domain. Compared to the control (globular and fibrous) proteins, H1 histones demonstrate the increased folding rate and a higher proportion of low-complexity segments. The results of this work indicate that intrinsic disorder is an inherent structural property of histone H1 subtypes and it is essential for establishing a protein conformation which defines functional outcomes affecting on DNA- and/or partner protein-dependent cell processes. PMID:26366527

  7. Analysis of a local HIV-1 epidemic in portugal highlights established transmission of non-B and non-G subtypes.

    Science.gov (United States)

    Carvalho, Alexandre; Costa, Patrício; Triunfante, Vera; Branca, Fernando; Rodrigues, Fernando; Santos, Catarina L; Correia-Neves, Margarida; Saraiva, Margarida; Lecour, Henrique; Castro, António G; Pedrosa, Jorge; Osório, Nuno S

    2015-05-01

    The existing data support Portugal as the western European country with the highest HIV-1 subtype diversity. However, detailed phylogenetic studies of Portuguese HIV-1 epidemics are still scarce. Thus, our main goal was to analyze the phylodynamics of a local HIV-1 infection in the Portuguese region of Minho. Molecular epidemiological analysis was applied to data from 289 HIV-1-infected individuals followed at the reference hospital of the province of Minho, Portugal, at which isolated viruses had been sequenced between 2000 and 2012. Viruses of the G (29.1%) and B (27.0%) subtypes were the most frequent, followed by recombinant forms (17.6%) and the C (14.5%), F1 (7.3%), and A1 (4.2%) subtypes. Multinomial logistic regression revealed that the odds of being infected with the A1 and F1 subtypes increased over the years compared with those with B, G, or C subtypes or recombinant viruses. As expected, polyphyletic patterns suggesting multiple and old introductions of the B and G subtypes were found. However, transmission clusters of non-B and non-G viruses among native individuals were also found, with the dates of the most recent common ancestor estimated to be in the early 2000s. Our study supports that the HIV-1 subtype diversity in the Portuguese region of Minho is high and has been increasing in a manner that is apparently driven by factors other than immigration and international travel. Infections with A1 and F1 viruses in the region of Minho are becoming established and are mainly found in sexually transmitted clusters, reinforcing the need for more efficacious control measures targeting this infection route. PMID:25694526

  8. Hepatitis C Virus Subtype and Evolution Characteristic Among Drug Users, Men Who Have Sex With Men, and the General Population in Beijing, China.

    Science.gov (United States)

    Jiao, Yang; Zhang, Xiaoxi; Wang, Chen; Li, Li; Liu, Jie; Bar, Katharine J; Wei, Huamian; Hu, Yao; Huang, Ping; Zeng, Zhaoli; Jiang, Shulin; Du, Jialiang; Shao, Yiming; Metzger, David; Li, Shuming; Ma, Liying

    2016-02-01

    The aim of this study was to characterize the current molecular epidemiology of hepatitis C virus (HCV) infection and evaluate the evolutionary patterns of HCV subtypes in Beijing, China, among different subpopulations.The whole blood samples and behavioral data were collected from a total of 10,354 subjects, including drug users (DUs), men who have sex with men (MSM), and the general population, in Beijing from 2010 to 2011. Samples were tested for HCV infection using both enzyme-linked immunosorbent assay (ELISA) and real-time PCR. All viremic subjects were then sequenced by nested PCR over core/E1 and NS5B regions. Phylogenetic and phylogeographic analysis was performed by BEAST software.In total, 217 subjects (2.1%) were tested positive for HCV by antibody or vRNA-based testing. HCV prevalence rates for DUs, MSM, and the general population were 26.2%, 0.54%, and 0.37%, respectively. The 156 HCV RNA-positive samples were sequenced. Nine HCV genotypes, including 1a, 1b, 2a, 3a, 3b, 6a, 6n, 6u and 6v, were detected. The most prevalent subtypes were 3b (36.09%), 1b (32.54%), and 3a (16.57%). Bayesian evolutionary analysis estimated that the time of introduction of subtype 1b into Beijing was 2004 (95% CI: 1997.7, 2007.7), with subtypes 3a and 3b being introduced later in 2006. Evolutionary analyses further suggested that subtype 1b from Beijing and Shanghai were closely related, whereas subtype 3a sequences were more similar with sequences from Yunnan, Guangzhou, Hong Kong, and Jiangsu. Subtype 3b sequences were closely related to those from Yunnan, Guangdong, and Hong Kong.Thus, the current HCV epidemic in Beijing is complex, heavily affecting DUs, and involving multiple genotypes that likely spread from different regions in China with its large migrant population. PMID:26871798

  9. 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

  10. Subtyping of Streptococcus uberis by DNA amplification fingerprinting.

    OpenAIRE

    Jayarao, B. M.; Bassam, B J; Caetano-Anollés, G; Gresshoff, P M; Oliver, S P

    1992-01-01

    Total DNA of Streptococcus uberis from cows with mastitis was analyzed by DNA amplification fingerprinting (DAF) and compared with restriction endonuclease fingerprinting (REF). DAF grouped 22 strains into 15 distinct patterns, while REF grouped them into 12 patterns. These results suggest that DAF is a useful technique for subtyping strains of S. uberis.

  11. 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.

  12. Central Timing Deficits in Subtypes of Primary Speech Disorders

    Science.gov (United States)

    Peter, Beate; Stoel-Gammon, Carol

    2008-01-01

    Childhood apraxia of speech (CAS) is a proposed speech disorder subtype that interferes with motor planning and/or programming, affecting prosody in many cases. Pilot data (Peter & Stoel-Gammon, 2005) were consistent with the notion that deficits in timing accuracy in speech and music-related tasks may be associated with CAS. This study replicated…

  13. 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…

  14. 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…

  15. 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…

  16. 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

    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...

  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. Brief Report: Further Evidence of Sensory Subtypes in Autism

    Science.gov (United States)

    Lane, Alison E.; Dennis, Simon J.; Geraghty, Maureen E.

    2011-01-01

    Distinct sensory processing (SP) subtypes in autism have been reported previously. This study sought to replicate the previous findings in an independent sample of thirty children diagnosed with an Autism Spectrum Disorder. Model-based cluster analysis of parent-reported sensory functioning (measured using the Short Sensory Profile) confirmed the…

  19. Salmonella Source Attribution in Japan by a Microbiological Subtyping Approach

    DEFF Research Database (Denmark)

    Toyofuku, Hajime; Pires, Sara Monteiro; Hald, Tine

    In order to estimate the number of human Salmonella infections attributable to each of major animal-food source, and help identifying the best Salmonella intervention strategies, a microbial subtyping approach for source attribution was applied. We adapted a Bayesian model that attributes illness...

  20. The subtype of VSD and the angiographic differentiation

    International Nuclear Information System (INIS)

    VSD is the most common congenital cardiac malformation and the natural history depends not only on the age of patients and the size of defect but the subtype of VSD as well, important factor in clinical management of those patients. In 110 patients, with surgically repaired VSD in Yonsei Medical Center in 1984, the subtype of VSDs evaluated by surgical observation were correlated with LV angiogram findings to verify the incidence of subtype in Korean and the diagnostic accuracy to predict the subtype by angiogram. 1. 110 patients included 64 boys and 46 girls, the age ranged from 3 months to 14 years (average 4.6 years old). 2. Angiographic findings were interpreted as follows; a. Perimembranous defects were profiled in LAO 60 .deg. LV angiogram and located below the aortic valve. In inlet excavation the shunted blood opacified the recess between septal leaflet of tricuspid valve and interventricular septum in early phase, in infundibular excavation opacified the recess between anterior leaflet of TV and anterior free wall of RV and in trabecular excavation the shunted blood traversed anterior portion of TV ring, opacified trabecular portion of RV cavity. b. Subarterial types were profiled in RAO 30 .deg. LV angiogram, just below aortic valve as well as pulmonic valve. Total infundibular defects were profiled in RAO 30 .deg. and LAO 60 .deg. LV angiogram subaortic in location in both views. c. In muscular VSD the profiled angle was varied according to the subtype but the defects were separated from the aortic valve as muscular septum interposed between the aortic valve and the defect. 3. The incidence of subtype of VSDs evaluated by surgical observation were as follows. Subarterial type : 32 cases (29.1%) Total infundibular defect : 5 cases (4.5%) Perimembranous type : 73 cases (66.3%) Infundibular excavation : 32 cases (29.2%) Trabecular excavation : 28 cases (25.5%) Inlet excavation : 10 cases (9.1%) Mixed : 3 cases (2.7%) Muscular type : 1 cases (0.9%) Total 63

  1. 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.

  2. 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

  3. Prehospital Identification of Stroke Subtypes in Chinese Rural Areas

    Science.gov (United States)

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

    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. PMID:27098788

  4. Comparing two basic subtypes in OCD across three large community samples: a pure compulsive versus a mixed obsessive-compulsive subtype.

    Science.gov (United States)

    Rodgers, Stephanie; Ajdacic-Gross, Vladeta; Kawohl, Wolfram; Müller, Mario; Rössler, Wulf; Hengartner, Michael P; Castelao, Enrique; Vandeleur, Caroline; Angst, Jules; Preisig, Martin

    2015-12-01

    Due to its heterogeneous phenomenology, obsessive-compulsive disorder (OCD) has been subtyped. However, these subtypes are not mutually exclusive. This study presents an alternative subtyping approach by deriving non-overlapping OCD subtypes. A pure compulsive and a mixed obsessive-compulsive subtype (including subjects manifesting obsessions with/without compulsions) were analyzed with respect to a broad pattern of psychosocial risk factors and comorbid syndromes/diagnoses in three representative Swiss community samples: the Zurich Study (n = 591), the ZInEP sample (n = 1500), and the PsyCoLaus sample (n = 3720). A selection of comorbidities was examined in a pooled database. Odds ratios were derived from logistic regressions and, in the analysis of pooled data, multilevel models. The pure compulsive subtype showed a lower age of onset and was characterized by few associations with psychosocial risk factors. The higher social popularity of the pure compulsive subjects and their families was remarkable. Comorbidities within the pure compulsive subtype were mainly restricted to phobias. In contrast, the mixed obsessive-compulsive subtype had a higher prevalence and was associated with various childhood adversities, more familial burden, and numerous comorbid disorders, including disorders characterized by high impulsivity. The current comparison study across three representative community surveys presented two basic, distinct OCD subtypes associated with differing psychosocial impairment. Such highly specific subtypes offer the opportunity to learn about pathophysiological mechanisms specifically involved in OCD. PMID:25827623

  5. 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...

  6. HIV type 1 group M subtype G in Cameroon: five genome sequences.

    Science.gov (United States)

    Yamaguchi, Julie; Ndembi, Nicaise; Ngansop, Charlotte; Mbanya, Dora; Kaptué, Lazare; Gürtler, Lutz G; Devare, Sushil G; Brennan, Catherine A

    2009-04-01

    Near full-length viral genome sequences were obtained for five putative subtype G candidates identified in HIV-infected Cameroonian blood donors, based on partial genome sequences for the gag, pol, and env regions. Phylogenetic analysis of the genome sequences shows that all five strains are pure subtype G with no indication of intersubtype recombination. The Cameroon subtype G sequences did not form a geographically based subcluster and were intermixed within the subtype G branch with isolates from several different countries. HIV-1 group M subtype G accounts for only 4.5% of HIV infections in Cameroon. However, genome segments of subtype G are present in 67% of all infections and 80% of infections due to intersubtype recombinant strains in Cameroon. The addition of five subtype G genome sequences to the HIV database may contribute to a better understanding of the origins and classification of HIV-1 subtypes and CRFs. PMID:19361281

  7. Molecular epidemiology of HIV-1 in Rio Grande, RS, Brazil

    OpenAIRE

    Martínez Ana Maria Barral de; Barbosa Edel Figueirêdo; Ferreira Paulo César Pelegrino; Cardoso Fabiola Adriene; Silveira Jussara; Sassi Gabriela; Silva Cláudio Moss da; Mendonça-Signorini Vera; Antunes Carlos Maurício de Figueiredo

    2002-01-01

    We conducted a molecular epidemiological study to investigate HIV-1 strains in Rio Grande, southern Brazil, searching for an association with transmission mode and risk behavior. Patients (185) identified at an AIDS treatment reference Hospital, from 1994 to 1997, were included; from which 107 blood samples were obtained. Nested PCR was realized once for each sample; for amplified samples (69) HIV subtypes were classified using the heteroduplex mobility assay. Subtypes identified were B (75%)...

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

    Science.gov (United States)

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

    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. PMID:25133021

  9. 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.

  10. 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.

  11. RNA-binding protein VICKZ is expressed in a germinal center associated pattern among lymphoma subtypes

    DEFF Research Database (Denmark)

    Natkunam, Y.; Vainer, G.; Zhao, S.C.;

    2005-01-01

    Recent effort in the molecular characterization of diffuse large B-cell lymphoma (DLBCL) has led to the recognition that patients with DLBCL of germinal center origin exhibit a better overall survival. Thus, identification and characterization of markers of germinal center derivation are of...... tumorigenesis/metastasis. We generated an antibody that recognizes all three isoforms of VICKZ protein and characterized its expression in normal lymphoid tissue and in lymphoma subtypes. In normal tonsils, VICKZ protein showed a germinal center-specific pattern of expression with staining localized to the....... Among T cell lymphoma, anaplastic large cell lymphoma were positive (75%, 6/9). Additional work is in progress to correlate VICKZ protein expression with other germinal center markers such as HGAL, BCL6 and CD10 as well as with prognostic subclasses of DLBCL. The differential expression pattern of VICKZ...

  12. 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.

  13. 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

  14. Molecular epidemiology of HIV-1 in Rio Grande, RS, Brazil Epidemiologia molecular do HIV-1 em Rio Grande, RS, Brasil

    OpenAIRE

    Ana Maria Barral de Martínez; Edel Figueirêdo Barbosa; Paulo César Pelegrino Ferreira; Fabiola Adriene Cardoso; Jussara Silveira; Gabriela Sassi; Cláudio Moss da Silva; Vera Mendonça-Signorini; Carlos Maurício de Figueiredo Antunes

    2002-01-01

    We conducted a molecular epidemiological study to investigate HIV-1 strains in Rio Grande, southern Brazil, searching for an association with transmission mode and risk behavior. Patients (185) identified at an AIDS treatment reference Hospital, from 1994 to 1997, were included; from which 107 blood samples were obtained. Nested PCR was realized once for each sample; for amplified samples (69) HIV subtypes were classified using the heteroduplex mobility assay. Subtypes identified were B (75%)...

  15. How Subtyping Shapes Perception: Predictable Exceptions to the Rule Reduce Attention to Stereotype-Associated Dimensions

    OpenAIRE

    Deutsch, Roland; Fazio, Russell H.

    2008-01-01

    Two experiments examined the relation between stereotype disconfirmation and attentional processes. Using an instrumental learning-paradigm, we successfully simulated stereotype acquisition and the subsequent subtyping of disconfirming exemplars. While replicating established markers of subtyping, the present research demonstrates a hitherto neglected cognitive consequence of subtyping: Predictable stereotype disconfirmation increased attention to features that facilitated discriminating betw...

  16. 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…

  17. 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

  18. 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

  19. 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.

  20. Cognitive process-based subtypes of developmental coordination disorder (DCD).

    Science.gov (United States)

    Asonitou, Katerina; Koutsouki, Dimitra

    2016-06-01

    The purpose of the study was to identify the cognitive subtypes demonstrated by children with developmental coordination disorder (DCD) using the Planning-Attention-Simultaneous-Successive Processing (PASS) theory and the Cognitive Assessment System (D-N CAS). Participants were 108 children aged 5- and 6-years old, 54 with DCD and 54 without DCD, all attending typical kindergartens. They were examined on 31 cognitive-motor variables. Hierarchical-agglomerative and iterative partitioning cluster analyses including 9 motor and 7 cognitive variables revealed the following six subtypes: It is well known that DCD is a heterogeneous condition. However, whenever cognitive processes were lower than average, cognitive-motor relationship was evident in subgroups C1, C4, C5 and C6. Early identification of task-specific cognitive-motor difficulties may be essential for early educational intervention practices in order to anticipate and improve learning, academic and performing difficulties. PMID:26991728

  1. 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

  2. Refining developmental coordination disorder subtyping with multivariate statistical methods

    Directory of Open Access Journals (Sweden)

    Lalanne Christophe

    2012-07-01

    Full Text Available Abstract Background With a large number of potentially relevant clinical indicators penalization and ensemble learning methods are thought to provide better predictive performance than usual linear predictors. However, little is known about how they perform in clinical studies where few cases are available. We used Random Forests and Partial Least Squares Discriminant Analysis to select the most salient impairments in Developmental Coordination Disorder (DCD and assess patients similarity. Methods We considered a wide-range testing battery for various neuropsychological and visuo-motor impairments which aimed at characterizing subtypes of DCD in a sample of 63 children. Classifiers were optimized on a training sample, and they were used subsequently to rank the 49 items according to a permuted measure of variable importance. In addition, subtyping consistency was assessed with cluster analysis on the training sample. Clustering fitness and predictive accuracy were evaluated on the validation sample. Results Both classifiers yielded a relevant subset of items impairments that altogether accounted for a sharp discrimination between three DCD subtypes: ideomotor, visual-spatial and constructional, and mixt dyspraxia. The main impairments that were found to characterize the three subtypes were: digital perception, imitations of gestures, digital praxia, lego blocks, visual spatial structuration, visual motor integration, coordination between upper and lower limbs. Classification accuracy was above 90% for all classifiers, and clustering fitness was found to be satisfactory. Conclusions Random Forests and Partial Least Squares Discriminant Analysis are useful tools to extract salient features from a large pool of correlated binary predictors, but also provide a way to assess individuals proximities in a reduced factor space. Less than 15 neuro-visual, neuro-psychomotor and neuro-psychological tests might be required to provide a sensitive and

  3. Subtype Differences in Pre-Coupling of Muscarinic Acetylcholine Receptors

    Czech Academy of Sciences Publication Activity Database

    Jakubík, Jan; Janíčková, Helena; Randáková, Alena; El-Fakahany, E. E.; Doležal, Vladimír

    2011-01-01

    Roč. 6, č. 11 (2011), e27732. E-ISSN 1932-6203 R&D Projects: GA ČR(CZ) GA305/09/0681; GA AV ČR(CZ) IAA500110703; GA MŠk(CZ) LC554 Institutional research plan: CEZ:AV0Z50110509 Keywords : acetylcholine muscarinic receptors * G proteins * subtype differences Subject RIV: ED - Physiology Impact factor: 4.092, year: 2011

  4. 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...

  5. 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...

  6. 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

  7. 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

  8. 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...

  9. 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

    disease. 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......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...

  10. 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

  11. The implications of breast cancer molecular phenotype for radiation oncology

    Directory of Open Access Journals (Sweden)

    ShirinSioshansi

    2011-06-01

    Full Text Available The identification of distinct molecular subtypes of breast cancer has advanced the understanding and treatment of breast cancer by providing insight into prognosis, patterns of recurrence and effectiveness of therapy. The prognostic significance of molecular phenotype with regard to distant recurrences and overall survival are well established in the literature and has been readily incorporated into systemic therapy management decisions. However, despite the accumulating data suggesting similar prognostic significance for locoregional recurrence, integration of molecular phenotype into local management decision making has lagged. Although there are some conflicting reports, collectively the literature supports a low risk of local recurrence in the hormone receptor positive luminal subtypes compared to hormone receptor negative subtypes (triple negative and HER2-enriched. The development of targeted therapies, such as trastuzumab for the treatment of HER2-enriched subtype, has been shown to mitigate the increased risk of local recurrence. Unfortunately, no such remedy exists to address the increased risk of local recurrence for patients with triple negative tumors, making it a clinical challenge for radiation oncologists. In this review we discuss the correlation between molecular subtype and local recurrence following either breast conservation therapy or mastectomy. We also explore the possible mechanisms for increased local recurrence in triple negative breast cancer and radiotherapeutic implications for this population, such as the safety of breast conservation, consideration of dose escalation and the appropriateness of accelerated partial breast irradiation.

  12. 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.

  13. 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.

  14. 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

  15. 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.

  16. Independent Component Analysis Uncovers the Landscape of the Bladder Tumor Transcriptome and Reveals Insights into Luminal and Basal Subtypes

    Directory of Open Access Journals (Sweden)

    Anne Biton

    2014-11-01

    Full Text Available Extracting relevant information from large-scale data offers unprecedented opportunities in cancerology. We applied independent component analysis (ICA to bladder cancer transcriptome data sets and interpreted the components using gene enrichment analysis and tumor-associated molecular, clinicopathological, and processing information. We identified components associated with biological processes of tumor cells or the tumor microenvironment, and other components revealed technical biases. Applying ICA to nine cancer types identified cancer-shared and bladder-cancer-specific components. We characterized the luminal and basal-like subtypes of muscle-invasive bladder cancers according to the components identified. The study of the urothelial differentiation component, specific to the luminal subtypes, showed that a molecular urothelial differentiation program was maintained even in those luminal tumors that had lost morphological differentiation. Study of the genomic alterations associated with this component coupled with functional studies revealed a protumorigenic role for PPARG in luminal tumors. Our results support the inclusion of ICA in the exploitation of multiscale data sets.

  17. 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

  18. 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.

  19. 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.

  20. 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.

  1. 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...

  2. Gene-set and multivariate genome-wide association analysis of oppositional defiant behavior subtypes in attention-deficit/hyperactivity disorder.

    Science.gov (United States)

    Aebi, Marcel; van Donkelaar, Marjolein M J; Poelmans, Geert; Buitelaar, Jan K; Sonuga-Barke, Edmund J S; Stringaris, Argyris; Consortium, Image; Faraone, Stephen V; Franke, Barbara; Steinhausen, Hans-Christoph; van Hulzen, Kimm J E

    2016-07-01

    Oppositional defiant disorder (ODD) is a frequent psychiatric disorder seen in children and adolescents with attention-deficit-hyperactivity disorder (ADHD). ODD is also a common antecedent to both affective disorders and aggressive behaviors. Although the heritability of ODD has been estimated to be around 0.60, there has been little research into the molecular genetics of ODD. The present study examined the association of irritable and defiant/vindictive dimensions and categorical subtypes of ODD (based on latent class analyses) with previously described specific polymorphisms (DRD4 exon3 VNTR, 5-HTTLPR, and seven OXTR SNPs) as well as with dopamine, serotonin, and oxytocin genes and pathways in a clinical sample of children and adolescents with ADHD. In addition, we performed a multivariate genome-wide association study (GWAS) of the aforementioned ODD dimensions and subtypes. Apart from adjusting the analyses for age and sex, we controlled for "parental ability to cope with disruptive behavior." None of the hypothesis-driven analyses revealed a significant association with ODD dimensions and subtypes. Inadequate parenting behavior was significantly associated with all ODD dimensions and subtypes, most strongly with defiant/vindictive behaviors. In addition, the GWAS did not result in genome-wide significant findings but bioinformatics and literature analyses revealed that the proteins encoded by 28 of the 53 top-ranked genes functionally interact in a molecular landscape centered around Beta-catenin signaling and involved in the regulation of neurite outgrowth. Our findings provide new insights into the molecular basis of ODD and inform future genetic studies of oppositional behavior. © 2015 The Authors. American Journal of Medical Genetics Part B: Neuropsychiatric Genetics Published by Wiley Periodicals, Inc. PMID:26184070

  3. 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

  4. Survival Analysis of Breast Cancer Subtypes in Spinal Metastases Patients

    DEFF Research Database (Denmark)

    Wang, Miao; Jensen, Anders Bonde; Morgen, Soeren Smith;

    2014-01-01

    downgraded from score "5" to "3" in Tokuhashi scoring system and from "slow growth" to "moderate growth" in Tomita scoring system. Spine surgeons should be critical before performing high-risk extensive surgery in patients with ER/HR (-) status, and especially, in those with triple-negative status. LEVEL OF......STUDY DESIGN: We conducted a retrospective cohort study of 151 patients with breast cancer spinal metastases. OBJECTIVE: To investigate the influence of breast cancer subtypes on survival duration of patients with breast cancer spinal metastases, and to aid spine surgeons in selecting treatments on...

  5. 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...

  6. 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...

  7. 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

  8. Functional characteristics of HIV-1 subtype C compatible with increased heterosexual transmissibility

    DEFF Research Database (Denmark)

    Walter, Brandon L; Armitage, Andrew E; Graham, Stephen C;

    2009-01-01

    BACKGROUND: Despite the existence of over 50 subtypes and circulating recombinant forms of HIV-1, subtype C dominates the heterosexual pandemic causing approximately 56% of all infections. OBJECTIVE: To evaluate whether viral genetic factors may contribute to the observed subtype-C predominance....... METHODS: Chimeric viruses were generated using V1-V3 envelope fragments from a subtype-A/C dually infected woman with preferential genital replication of subtype C. Viral adaptation, spread and cell fusion ability were evaluated in vitro using peripheral blood mononuclear cells and HeLa-CD4-CCR5 cell...... mononuclear cell and cell lines with low CCR5 expression. Structural modeling suggested the formation of an additional hydrogen bond between V3 and CCR5. Moreover, we found preferential selection of HIV with 316T and/or extremely short V1-V2 loops in cervices of three women infected with subtypes A/C, B or C...

  9. 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.

  10. 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...

  11. 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...

  12. A review and meta-analysis of the heritability of specific phobia subtypes and corresponding fears

    OpenAIRE

    Houtem, van, C.M.H.H.; Laine, M.L.; D.I. Boomsma; Ligthart, L.; Wijk, van, A.J.; Jongh, de, J.

    2013-01-01

    Evidence from twin studies suggests that genetic factors contribute to the risk of developing a fear or a phobia. The aim of the present study was to review the current literature regarding twin studies describing the genetic basis of specific phobias and their corresponding fears. The analysis included five twin studies on fears and ten twin studies on specific phobias. Heritability estimates of fear subtypes and specific phobia subtypes both varied widely, even within the subtypes. A meta-a...

  13. 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...

  14. 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 ...

  15. 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...

  16. posttraumatic stress disorder: a theoretical model of the hyperarousal subtype

    Directory of Open Access Journals (Sweden)

    CharlesStewartWeston

    2014-04-01

    Full Text Available Posttraumatic stress disorder (PTSD is a frequent and distressing mental disorder, about which much remains to be learned. It is a heterogeneous disorder; the hyperarousal subtype (about 70% of occurrences and simply termed PTSD in this paper is the topic of this article, but the dissociative subtype (about 30% of occurrences and likely involving quite different brain mechanisms is outside its scope. A theoretical model is presented that integrates neuroscience data on diverse brain regions known to be involved in PTSD, and extensive psychiatric findings on the disorder. Specifically, the amygdala is a multifunctional brain region that is crucial to PTSD, and processes peritraumatic hyperarousal on grounded cognition principles to produce hyperarousal symptoms. Amygdala activity also modulates hippocampal function, which is supported by a large body of evidence, and likewise amygdala activity modulates several brainstem regions, visual cortex, rostral anterior cingulate cortex (rACC, and medial orbitofrontal cortex (mOFC, to produce diverse startle, visual, memory, numbing, anger, and recklessness symptoms. Additional brain regions process other aspects of peritraumatic responses to produce further symptoms. These contentions are supported by neuroimaging, neuropsychological, neuroanatomical, physiological, cognitive, and behavioral evidence. Collectively, the model offers an account of how responses at the time of trauma are transformed into an extensive array of the 20 PTSD symptoms that are specified in the Diagnostic and Statistical Manual of Mental Disorders, 5th edition. It elucidates the neural mechanisms of a specific form of psychopathology, and accords with the Research Domain Criteria framework

  17. 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

  18. 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.

  19. ADHD latent class clusters: DSM-IV subtypes and comorbidity.

    Science.gov (United States)

    Elia, Josephine; Arcos-Burgos, Mauricio; Bolton, Kelly L; Ambrosini, Paul J; Berrettini, Wade; Muenke, Maximilian

    2009-12-30

    ADHD (Attention Deficit Hyperactivity Disorder) has a complex, heterogeneous phenotype only partially captured by Diagnostic and Statistical Manual of Mental Disorders (DSM-IV) criteria. In this report, latent class analyses (LCA) are used to identify ADHD phenotypes using K-SADS-IVR (Schedule for Affective Disorders & Schizophrenia for School Age Children-IV-Revised) symptoms and symptom severity data from a clinical sample of 500 ADHD subjects, ages 6-18, participating in an ADHD genetic study. Results show that LCA identified six separate ADHD clusters, some corresponding to specific DSM-IV subtypes while others included several subtypes. DSM-IV comorbid anxiety and mood disorders were generally similar across all clusters, and subjects without comorbidity did not aggregate within any one cluster. Age and gender composition also varied. These results support findings from population-based LCA studies. The six clusters provide additional homogenous groups that can be used to define ADHD phenotypes in genetic association studies. The limited age ranges aggregating in the different clusters may prove to be a particular advantage in genetic studies where candidate gene expression may vary during developmental phases. DSM-IV comorbid mood and anxiety disorders also do not appear to increase cluster heterogeneity; however, longitudinal studies that cover period of risk are needed to support this finding. PMID:19900717

  20. Osteoclastic finger arthrosis - a subtype of polyarthrosis of the hand

    International Nuclear Information System (INIS)

    Aim: Description of a subtype of arthrosis deformans of the hand which is characterised as osteoclastic arthrosis. Patients and methods: Retrospective analysis of radiographs of the hands of 150 women and 100 men with radiological findings of arthrosis deformans. Results: 5% of women and 2% of men showed at least one digital joint with subchondral osteolysis of one or both articulating bones involving at least a third of the phalanx. This subchondral osteolysis far exceeds the cysts which are situated in the epiphyseal part of the articular region. It may develop within a year. Conclusion: Osteoclastic arthrosis of the finger is a subtype of polyarthrosis of the hand. Serial observations suggest that an osteoclast stimulating substance is produced by the cysts or arises directly from the synovial fluid; this enters the subchondral part of the bone through clefts which may or may not be visible radiologically and that this produces osteoclastic activity. The most important differential diagnoses are chronic tophacious gout and a benign tumor. (orig.)

  1. 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)

  2. Hilar cholangiocarcinoma. An evaluation of subtypes with CT and angiography.

    Science.gov (United States)

    Yamashita, Y; Takahashi, M; Kanazawa, S; Charnsangavej, C; Wallace, S

    1992-07-01

    Sixty-seven patients had hilar cholangiocarcinomas which were divided into 3 types based on tumor morphology as observed on cholangiography and CT. The pathology, vascularity, and pattern of tumor spread of these types were compared. Most of the infiltrative tumors (n = 44) were scirrhous adenocarcinomas, which on CT showed poor or no contrast enhancement with frequent lymph node metastases and liver atrophy. At angiography, there was vascular encasement in 52%, in rare cases neovascularity, and tumor stain. The exophytic type (n = 19) was divided into 2 subgroups depending on the main location of the tumor. The nodular subtype (n = 16) was mainly inside the liver and somewhat hypervascular similar to peripheral cholangiocarcinoma, often with intrahepatic metastases. The periductal subtype (n = 3) was hypovascular, similar to the infiltrative cholangiocarcinoma, and had a tendency to spread along the portal vein. The intraductal type (n = 4) was observed as a filling defect on cholangiography. CT revealed an intraluminal low density mass. Histologically, they were papillary adenocarcinomas. The radiologic types of hilar cholangiocarcinoma showed different characteristics with regard to pathologic findings, vascularity, and pattern of spread. PMID:1321653

  3. Hilar cholangiocarcinoma; An evaluation of subtypes with CT and angiography

    Energy Technology Data Exchange (ETDEWEB)

    Yamashita, Y.; Takahashi, M.; Kanazawa, S.; Charnsangavej, C.; Wallace, S. (Dept. of Radiology, Kumamoto University School of Medicine (Japan) Dept. of Radiology, Univ. of Texas, M.D. Anderson Hospital and Tumor Inst., Houston, TX (United States))

    1992-07-01

    Sixty-seven patients had hilar cholangiocarcinomas which were divided into 3 types based on tumor morphology as observed on cholangiography and CT. The pathology, vascularity, and pattern of tumor spread of these types were compared. Most of the infiltrative tumors were scirrhous adenocarcinomas, which on CT showed poor or no contrast enhancement with frequent lymph node metastases and liver atrophy. At angiography, there was vascular encasement in 52%, in rare cases neovascularity, and tumor stain. The exophytic type was divided into 2 subgroups depending on the main location of the tumor. The nodular subtype was mainly inside the liver and somewhat hypervascular similar to peripheral cholangiocarcinoma, often with intrahepatic metastases. The periductal subtype was hypovascular, similar to the infiltrative cholangiocarcinoma, and had a tendency to spread along the portal vein. The intraductal type was observed as a filling defect on cholangiography. CT revealed an intraluminal low density mass. Histologically, they were papillary adenocarcinomas. The radiologic types of hilar cholangiocarcinoma showed different characteristics with regard to pathologic findings, vascularity, and pattern of spread. (orig.).

  4. 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.

  5. All reovirus subtypes show oncolytic potential in primary cells of human high-grade glioma.

    Science.gov (United States)

    Alloussi, S H; Alkassar, M; Urbschat, S; Graf, N; Gärtner, B

    2011-09-01

    Reoviridae are non-human pathogenic viruses. The family of reoviridae consists of 4 different subtypes. Many studies have proven that the Dearing subtype 3 has oncolytic potential. This potential is related to the RAS protein expression in tumour cells. The aim of this study, was to investigate whether all reovirus subtypes have oncolytic potential and whether there are differences in their efficacy, in particular for high-grade glioma. To evaluate the oncolytic potential, we performed an in vitro head-to-head study for all reovirus subtypes in 5 primary cell cultures of high-grade gliomas. The oncolytic activity was determined using end-point titration with observation of the cytopathogenic effect. For measurement of RAS activity, we performed an immunofluorescent detection stain on all cell cultures. For quantification of the virus, an RT-PCR measurement for all subtypes was performed. All reovirus subtypes showed oncolytic activity in the observed glioma biopsies. These observations correlated with RAS overexpression in the observed cells. All glioma biopsies overexpressed the RAS protein. The quantitative oncolytic potential differed in relation to the single observed cell culture and in relation to the chosen reovirus subtype. To our knowledge, this is the first study showing oncolytic activity for all reovirus subtypes. We show the relationship and correlation between RAS protein overexpression and vulnerability of cells to reovirus. Efficacy of the different subtypes is interindividually different and cannot be forecast. PMID:21637921

  6. 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

  7. Global trends in molecular epidemiology of HIV-1 during 2000–2007

    Science.gov (United States)

    Hemelaar, Joris; Gouws, Eleanor; Ghys, Peter D.; Osmanov, Saladin

    2013-01-01

    Objective To estimate the global and regional distribution of HIV-1 subtypes and recombinants between 2000 and 2007. Design Country-specific HIV-1 molecular epidemiology data were combined with estimates of the number of HIV-infected people in each country. Method Cross-sectional HIV-1 subtyping data were collected from 65913 samples in 109 countries between 2000 and 2007. The distribution of HIV-1 subtypes in individual countries was weighted according to the number of HIV-infected people in each country to generate estimates of regional and global HIV-1 subtype distribution for the periods 2000–2003 and 2004–2007. Results Analysis of the global distribution of HIV-1 subtypes and recombinants in the two time periods indicated a broadly stable distribution of HIV-1 subtypes worldwide with a notable increase in the proportion of circulating recombinant forms (CRFs), a decrease in unique recombinant forms (URFs), and an overall increase in recombinants. In 2004–2007, subtype C accounted for nearly half (48%) of all global infections, followed by subtypes A (12%) and B (11%), CRF02_AG (8%), CRF01_AE (5%), subtype G (5%) and D(2%). Subtypes F, H, J and K together cause fewer than 1% of infections worldwide. Other CRFs and URFs are each responsible for 4% of global infections, bringing the combined total of worldwide CRFs to 16% and all recombinants (CRFs plus URFs) to 20%. Conclusions The global and regional distributions of individual subtypes and recombinants are broadly stable, although CRFs may play an increasing role in the HIV pandemic. The global diversity of HIV-1 poses a formidable challenge to HIV vaccine development. PMID:21297424

  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.; Hansen, T.; Tuomi, T.; Gasperikova, D.; Szopa, M.; Tjora, E.; James, T. J.; Kokko, P.; Loiseleur, F.; Andersson, E.; Gaget, S.; Isomaa, B.; Nowak, N.; Raeder, H.; Stanik, J.; Njolstad, P. R.; Malecki, M. T.; Klimes, I.; Groop, L.; Pedersen, O.; Froguel, P.; McCarthy, M. I.; Gloyn, A. L.; Owen, K. R.

    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 (hsCRP......) 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. HIV-1 CRF01_AE and Subtype B Transmission Networks Crossover: A New AE/B Recombinant Identified in Japan.

    Science.gov (United States)

    Hosaka, Masumi; Fujisaki, Seiichiro; Masakane, Aki; Hattori, Junko; Shiino, Teiichiro; Gatanaga, Hiroyuki; Shigemi, Urara; Okazaki, Reiko; Hachiya, Atsuko; Matsuda, Masakazu; Ibe, Shiro; Iwatani, Yasumasa; Yokomaku, Yoshiyuki; Sugiura, Wataru

    2016-05-01

    The major circulating HIV-1 strains in Japan have been subtype B (B) followed by CRF01_AE (AE) in newly diagnosed HIV/AIDS cases. These two subtypes have distinct epidemiological characteristics; B predominates in men who have sex with men, while AE is observed mostly in heterosexuals engaging in high-risk sex. However, transmission networks of these two high-risk populations appear to be crossing over and diffusing. Here we report the emergence of previously unidentified HIV-1 AE/B recombinants in Japan. We initially identified 13 cases with discordant subtyping results with AE (gag MA)/B (pol PR-RT)/AE (env C2V3) by molecular phylogenetic analysis of 1,070 cases who visited Nagoya Medical Center from 1997 to 2012. Genetic characterization of full-length sequences demonstrated that they shared an identical recombinant structure, and was designated as CRF69_01B by the Los Alamos HIV National Laboratory. By reviewing gag, pol, and env sequences collected in the Japanese Drug Resistance HIV-1 Surveillance Network, we found five other CRF69_01B probable cases from different areas in Japan, suggesting that the strain is transmitted widely throughout the country. The time of the most recent common ancestor analyses estimated that CRF69_01B emerged between 1991 and 1995, soon after AE was introduced from neighboring countries in the mid-1990s. Understanding the current epidemic strains is important for the diagnosis and treatment of HIV/AIDS, as well as for the development of globally effective HIV vaccines. PMID:26571151

  10. 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.

  11. 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

  12. 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.

  13. Bovine Staphylococcus aureus: Subtyping, evolution, and zoonotic transfer.

    Science.gov (United States)

    Boss, R; Cosandey, A; Luini, M; Artursson, K; Bardiau, M; Breitenwieser, F; Hehenberger, E; Lam, Th; Mansfeld, M; Michel, A; Mösslacher, G; Naskova, J; Nelson, S; Podpečan, O; Raemy, A; Ryan, E; Salat, O; Zangerl, P; Steiner, A; Graber, H U

    2016-01-01

    Staphylococcus aureus is globally one of the most important pathogens causing contagious mastitis in cattle. Previous studies using ribosomal spacer (RS)-PCR, however, demonstrated in Swiss cows that Staph. aureus isolated from bovine intramammary infections are genetically heterogeneous, with Staph. aureus genotype B (GTB) and GTC being the most prominent genotypes. Furthermore, Staph. aureus GTB was found to be contagious, whereas Staph. aureus GTC and all the remaining genotypes were involved in individual cow disease. In addition to RS-PCR, other methods for subtyping Staph. aureus are known, including spa typing and multilocus sequence typing (MLST). They are based on sequencing the spa and various housekeeping genes, respectively. The aim of the present study was to compare the 3 analytic methods using 456 strains of Staph. aureus isolated from milk of bovine intramammary infections and bulk tanks obtained from 12 European countries. Furthermore, the phylogeny of animal Staph. aureus was inferred and the zoonotic transfer of Staph. aureus between cattle and humans was studied. The analyzed strains could be grouped into 6 genotypic clusters, with CLB, CLC, and CLR being the most prominent ones. Comparing the 3 subtyping methods, RS-PCR showed the highest resolution, followed by spa typing and MLST. We found associations among the methods but in many cases they were unsatisfactory except for CLB and CLC. Cluster CLB was positive for clonal complex (CC)8 in 99% of the cases and typically positive for t2953; it is the cattle-adapted form of CC8. Cluster CLC was always positive for tbl 2645 and typically positive for CC705. For CLR and the remaining subtypes, links among the 3 methods were generally poor. Bovine Staph. aureus is highly clonal and a few clones predominate. Animal Staph. aureus always evolve from human strains, such that every human strain may be the ancestor of a novel animal-adapted strain. The zoonotic transfer of IMI- and milk-associated strains

  14. Prognostic impact of breast cancer subtypes in elderly patients.

    Science.gov (United States)

    Bergen, E S; Tichy, C; Berghoff, A S; Rudas, M; Dubsky, P; Bago-Horvath, Z; Mader, R M; Exner, R; Gnant, M; Zielinski, C C; Steger, G G; Preusser, M; Bartsch, R

    2016-05-01

    We aimed to analyse the impact of breast cancer (BC) subtypes on the clinical course of disease with special emphasis on the occurrence of brain metastases (BM) and outcome in an elderly BC population. A total number of 706 patients ≥65 years receiving treatment for BC from 2007 to 2011 were identified from a BC database. 62 patients diagnosed with DCIS and 73 patients with incomplete datasets were excluded, leaving 571 patients for this analysis. Patient characteristics, biological tumour subtypes, and clinical outcome including overall survival (OS) were obtained by retrospective chart review. 380/571 (66, 5 %) patients aged 65-74 years were grouped among the young-old, 182/571 (31.9 %) patients aged 75-84 years among the old-old, and 29/571 (5.1 %) patients aged ≥85 years among the oldest-old. 392/571 (68.8 %) patients presented with luminal BC, 119/571 (20.8 %) with HER2-positive, and 59/571 (10.3 %) with triple-negative BC (TNBC). At 38 months median follow-up, 115/571 (20.1 %) patients presented with distant recurrence. A higher recurrence rate was observed in the HER2-positive subtype (43/119 (36.1 %)), as compared to TNBC (15/59 (25.4 %)) and luminal BC (57/392 (14.5 %); p < 0.001). BM were detected at a significantly higher rate in HER2-positive BC patients (9/119 (7.6 %)), as compared to TNBC (2/59 (3.4 %)) and luminal BC patients (6/392 (1.5 %); p = 0.003). Diagnosis of metastatic disease (HR 7.7; 95 % CI 5.2-11.4; p < 0.001) as well as development of BM (HR 3.5; 95 % CI 1.9-6.4; p < 0.001) had a significantly negative impact on OS in a time-dependent covariate cox regression model. In contrast to younger BC patients, outcome in this large cohort of elderly patients suggests that HER2-positive disease-not TNBC-featured the most aggressive clinical course with the highest rates of metastatic spread and BM. In-depth analysis regarding a potentially distinct biology of TNBC in elderly is therefore warranted. PMID:27107570

  15. 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...

  16. A synthetic HIV-1 subtype C backbone generates comparable PR and RT resistance profiles to a subtype B backbone in a recombinant virus assay.

    Directory of Open Access Journals (Sweden)

    David Nauwelaers

    Full Text Available In order to determine phenotypic protease and reverse transcriptase inhibitor-associated resistance in HIV subtype C virus, we have synthetically constructed an HIV-1 subtype C (HIV-1-C viral backbone for use in a recombinant virus assay. The in silico designed viral genome was divided into 4 fragments, which were chemically synthesized and joined together by conventional subcloning. Subsequently, gag-protease-reverse-transcriptase (GPRT fragments from 8 HIV-1 subtype C-infected patient samples were RT-PCR-amplified and cloned into the HIV-1-C backbone (deleted for GPRT using In-Fusion reagents. Recombinant viruses (1 to 5 per patient sample were produced in MT4-eGFP cells where cyto-pathogenic effect (CPE, p24 and Viral Load (VL were monitored. The resulting HIV-1-C recombinant virus stocks (RVS were added to MT4-eGFP cells in the presence of serial dilutions of antiretroviral drugs (PI, NNRTI, NRTI to determine the fold-change in IC50 compared to the IC50 of wild-type HIV-1 virus. Additionally, viral RNA was extracted from the HIV-1-C RVS and the amplified GPRT products were used to generate recombinant virus in a subtype B backbone. Phenotypic resistance profiles in a subtype B and subtype C backbone were compared. The following observations were made: i functional, infectious HIV-1 subtype C viruses were generated, confirmed by VL and p24 measurements; ii their rate of infection was slower than viruses generated in the subtype B backbone; iii they did not produce clear CPE in MT4 cells; and iv drug resistance profiles generated in both backbones were very similar, including re-sensitizing effects like M184V on AZT.

  17. 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 ...

  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. Gene expression profiling reveals molecularly and clinically distinct subtypes of glioblastoma multiforme

    Science.gov (United States)

    Liang, Yu; Diehn, Maximilian; Watson, Nathan; Bollen, Andrew W.; Aldape, Ken D.; Nicholas, M. Kelly; Lamborn, Kathleen R.; Berger, Mitchel S.; Botstein, David; Brown, Patrick O.; Israel, Mark A.

    2005-01-01

    Glioblastoma multiforme (GBM) is the most common form of malignant glioma, characterized by genetic instability, intratumoral histopathological variability, and unpredictable clinical behavior. We investigated global gene expression in surgical samples of brain tumors. Gene expression profiling revealed large differences between normal brain samples and tumor tissues and between GBMs and lower-grade oligodendroglial tumors. Extensive differences in gene expression were found among GBMs, particularly in genes involved in angiogenesis, immune cell infiltration, and extracellular matrix remodeling. We found that the gene expression patterns in paired specimens from the same GBM invariably were more closely related to each other than to any other tumor, even when the paired specimens had strikingly divergent histologies. Survival analyses revealed a set of ≈70 genes more highly expressed in rapidly progressing tumors that stratified GBMs into two groups that differed by >4-fold in median duration of survival. We further investigated one gene from the group, FABP7, and confirmed its association with survival in two unrelated cohorts totaling 105 patients. Expression of FABP7 enhanced the motility of glioma-derived cells in vitro. Our analyses thus identify and validate a prognostic marker of both biologic and clinical significance and provide a series of putative markers for additional evaluation. PMID:15827123

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

    OpenAIRE

    Hurtado, Renata; Fabrizio, Thomas; Vanstreels, Ralph Eric Thijl; Krauss, Scott; Webby, Richard J.; Webster, Robert G.; Durigon, Edison Luiz

    2015-01-01

    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. Ther...

  1. 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...

  2. Analysis of Sequence Based Classifier Prediction for HIV Subtypes

    Directory of Open Access Journals (Sweden)

    S. Santhosh Kumar

    2012-10-01

    Full Text Available Human immunodeficiency virus (HIV is a lent virus that causes acquired immunodeficiency syndrome (AIDS. The main drawback in HIV treatment process is its sub type prediction. The sub type and group classification of HIV is based on its genetic variability and location. HIV can be divided into two major types, HIV type 1 (HIV-1 and HIV type 2 (HIV-2. Many classifier approaches have been used to classify HIV subtypes based on their group, but some of cases are having two groups in one; in such cases the classification becomes more complex. The methodology used is this paper based on the HIV sequences. For this work several classifier approaches are used to classify the HIV1 and HIV2. For implementation of the work a real time patient database is taken and the patient records are experimented and the final best classifier is identified with quick response time and least error rate.

  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. 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

  5. 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.

  6. 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

  7. 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

  8. 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.

  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. 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 of...... ovarian cancer....

  11. 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…

  12. Human immunodeficiency virus type- 1 subtypes of infected patients in Espírito Santo, Brazil

    Directory of Open Access Journals (Sweden)

    Valéria P Cabral

    2006-12-01

    Full Text Available Genetic variability of human immunodeficiency virus type - 1(HIV-1 is a potential threat for both diagnosis and treatment of HIV/AIDS, as well as the development of effective vaccines. Up to now, HIV subtypes circulating among HIV-positive patients in the state of Espírito Santo were not known. In the present study, blood samples from 100 therapy-naïve HIV-1 infected patients were collected and the HIV subtype was determined through the Heteroduplex Mobility Assay (HMA. Ninety-seven out of 100 studied samples were subtyped by HMA, 73 samples (75.2% were from subtype B, 9 (9.3% from subtype F, 3 (3.1% from subtype C, 6 (6.2% Benv/Fgag, and another 6 (6.2% Fenv/Bgag, what suggests that recombinant viruses were present in the studied samples. Twenty-eight percent of the subtype B samples were represented by the Brazilian B" subtype, which were identified by RFLP with Fok I. Data presented here demonstrate that the epidemiological characteristics of the HIV epidemic in the state of Espírito Santo are similar to those from the other Southeastern states and helped to better understand the genetic polymorphism of HIV in Brazil.

  13. 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.

  14. 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

  15. 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...

  16. HIV-1 subtypes and response to combination antiretroviral therapy in Europe

    DEFF Research Database (Denmark)

    Bannister, WP; Ruiz, L; Loveday, C; Vella, S; Zilmer, K; Kjær, Jesper; Knysz, B; Phillips, AN; Mocroft, A; Lundgren, Jens Dilling

    2006-01-01

    BACKGROUND: Combination antiretroviral therapy (cART) may vary in ability to suppress viral load and increase CD4+ T-cell count in people infected with different HIV-1 subtypes, possibly due to differences in resistance development. Antiretroviral drugs have predominantly been developed in Western...... Europe/North America on the basis of the most prevalent subtype, B. However, non-B subtypes are increasingly spreading worldwide. OBJECTIVE: To compare virological and immunological response to cART between patients infected with B and non-B subtypes across Europe. DESIGN: EuroSIDA prospective......, observational cohort with 11,928 HIV-1-infected patients. METHODS: Response to cART was analysed in patients with subtypes determined pre-cART, via multivariable logistic regression on the first measurements 6–12 months after starting cART. A virological response was defined as a viral load <500 copies/ml and...

  17. 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.

  18. 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

  19. 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

  20. 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

  1. 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

  2. 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.

  3. Muscarinic acetylcholine receptor subtypes which selectively couple to phospholipase C: Pharmacological and biochemical properties

    International Nuclear Information System (INIS)

    The pharmacological and biochemical properties of rat m1 and m3 muscarinic acetylcholine receptors (mAChR) stably transfected into Chinese hamster ovary-K1 (CHO) cells were characterized with ligand binding, affinity labeling and biochemical assays. Both mAChR subtypes display saturable, high affinity binding of [3H]-quinuclidinyl benzilate (QNB) and a rank order of antagonist potency of QNB greater than atropine greater than pirenzepine greater than AF-DX 116. Carbachol displacement of [3H]-QNB binding to the m3 mAChR revealed an approximate 17-fold higher affinity than observed with the m1 mAChR. [3H]-propylbenzilylcholine mustard (PrBCM) labeling of mAChR revealed that m1 and m3 mAChR migrated on SDS-polyacrylamide gels with apparent molecular masses of 80,000 and 94,000 daltons, respectively, consistent with the known differences in their molecular sizes. Both m1 and m3 mAChR elicited dose-dependent increases in the hydrolysis of phosphoinositides; however, the maximal increase in total inositol phosphates elicited with the m1 mAChR was approximately 2-fold greater than that observed in cells expressing similar densities of m3 mAChR. Agonist activation of the m1 mAChR also elicited increases in basal and forskolin-stimulated cAMP, whereas the m3 mAChR had no effect on intracellular cAMP levels. These data suggest that although m1 and m3 mAChR display a considerable degree of structural homology, they exhibit distinct pharmacological and biochemical properties

  4. Muscarinic acetylcholine receptor subtypes which selectively couple to phospholipase C: Pharmacological and biochemical properties

    Energy Technology Data Exchange (ETDEWEB)

    Buck, M.A.; Fraser, C.M. (National Institute on Alcohol Abuse and Alcoholism, Rockville, MD (USA))

    1990-12-14

    The pharmacological and biochemical properties of rat m1 and m3 muscarinic acetylcholine receptors (mAChR) stably transfected into Chinese hamster ovary-K1 (CHO) cells were characterized with ligand binding, affinity labeling and biochemical assays. Both mAChR subtypes display saturable, high affinity binding of (3H)-quinuclidinyl benzilate (QNB) and a rank order of antagonist potency of QNB greater than atropine greater than pirenzepine greater than AF-DX 116. Carbachol displacement of (3H)-QNB binding to the m3 mAChR revealed an approximate 17-fold higher affinity than observed with the m1 mAChR. (3H)-propylbenzilylcholine mustard (PrBCM) labeling of mAChR revealed that m1 and m3 mAChR migrated on SDS-polyacrylamide gels with apparent molecular masses of 80,000 and 94,000 daltons, respectively, consistent with the known differences in their molecular sizes. Both m1 and m3 mAChR elicited dose-dependent increases in the hydrolysis of phosphoinositides; however, the maximal increase in total inositol phosphates elicited with the m1 mAChR was approximately 2-fold greater than that observed in cells expressing similar densities of m3 mAChR. Agonist activation of the m1 mAChR also elicited increases in basal and forskolin-stimulated cAMP, whereas the m3 mAChR had no effect on intracellular cAMP levels. These data suggest that although m1 and m3 mAChR display a considerable degree of structural homology, they exhibit distinct pharmacological and biochemical properties.

  5. 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

  6. 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.

  7. 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.

  8. 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

  9. Expression profile analysis of long noncoding RNA in HER-2-enriched subtype breast cancer by next-generation sequencing and bioinformatics

    Directory of Open Access Journals (Sweden)

    Yang F

    2016-02-01

    useful information for exploring candidate therapeutic targets and new molecular biomarkers for HER-2-enriched subtype breast cancer. Keywords: ncRNA, breast cancer, gene ontology, pathway analysis, coexpression network

  10. 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

  11. 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

  12. 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.

  13. 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-...

  14. 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

  15. 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.

  16. Metabolic profiling distinguishes three subtypes of Alzheimer's disease.

    Science.gov (United States)

    Bredesen, Dale E

    2015-08-01

    The cause of Alzheimer's disease is incompletely defined, and no truly effective therapy exists. However, multiple studies have implicated metabolic abnormalities such as insulin resistance, hormonal deficiencies, and hyperhomocysteinemia. Optimizing metabolic parameters in a comprehensive way has yielded cognitive improvement, both in symptomatic and asymptomatic individuals. Therefore, expanding the standard laboratory evaluation in patients with dementia may be revealing. Here I report that metabolic profiling reveals three Alzheimer's disease subtypes. The first is inflammatory, in which markers such as hs-CRP and globulin:albumin ratio are increased. The second type is non-inflammatory, in which these markers are not increased, but other metabolic abnormalities are present. The third type is a very distinctive clinical entity that affects relatively young individuals, extends beyond the typical Alzheimer's disease initial distribution to affect the cortex widely, is characterized by early non-amnestic features such as dyscalculia and aphasia, is often misdiagnosed or labeled atypical Alzheimer's disease, typically affects ApoE4-negative individuals, and is associated with striking zinc deficiency. Given the involvement of zinc in multiple Alzheimer's-related metabolic processes, such as insulin resistance, chronic inflammation, ADAM10 proteolytic activity, and hormonal signaling, this syndrome of Alzheimer's-plus with low zinc (APLZ) warrants further metabolic, genetic, and epigenetic characterization. PMID:26343025

  17. Synchronous multicentric glioblastoma with PNET and O subtypes: Possible pathogenesis

    Directory of Open Access Journals (Sweden)

    Kai Rui Wan

    2014-01-01

    Full Text Available Background: Glioblastomas (GBM are highly infiltrative, cellular and mitotically active tumors with large histologic variations within and between tumours. Several subtypes have been described including the GBM with oligodendroglial differentiation (GBM-O and primitive neuroectodermal tumour components (GBM-PNET. We report the first described case of a patient with synchronous multi-centric GBM-O and GBM-PNET components. Case Description: A patient, who presented with a short history of progressive headache and difficulty with memory recall, was found on MRI imaging to have two intracranial lesions. These showed heterogeneous enhancement and were found in the left frontal and left temporal regions. The patient underwent gross total resection of these two lesions which were found to show GBM-O and GBM-PNET differentiations. Conclusion: Although tumour cell migration in the context of GBM is a well-recognized phenomenon, the traditional hypothesis is not able to satisfactorily explain this case of multicentric GBM whereby the two lesions demonstrate different cell origins. More current understanding of the migratory pathways from the subventricular zone provide an alternate and plausible pathway that fits our patient′s unusual diagnosis.

  18. Adrenergic receptor subtypes in the cerebral circulation of newborn piglets

    International Nuclear Information System (INIS)

    The purpose of this study was to identify the α-adrenergic receptor subtype mediating cerebral vasoconstriction during sympathetic nerve stimulation in the newborn piglet. The effect of α1- and α2-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. α1-Adrenergic receptor blockade with prazosin inhibited the sympathetic vasoconstriction in the cerebrum, hippocampus, and masseter muscle and abolished it in the choroid plexus. α/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 α1-adrenergic receptors mediate vasoconstriction to neuroadrenergic stimulation in cerebral resistance vessels in the newborn piglet

  19. 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.

  20. 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.

  1. 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

  2. Discrete Papular Mucinosis-A Rare Subtype of Lichen Myxoedematosus

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    Havva Kaya Akış

    2011-06-01

    Full Text Available Lichen myxoedematosus (synonym, papular mucinosis is an uncommon, chronic, idiopathic disorder characterized by lichenoid papules, nodules and/or plaques due to dermal mucin deposition and a variable degree of fibrosis in the absence of thyroid dysfunction. Actually, lichen myxoedematosus includes two clinicopathologic subsets: a generalized papular and sclerodermoid form (also called scleromyxedema with a monoclonal gammopathy and systemic, even lethal, manifestations and a localized papular form with non-disabling course. Discrete papular mucinosis is a rare subtype of the localized form and can be associated with hepatitis C virus and human immunodeficiency virus (HIV infection. Only 12 cases unrelated to HCV or HIV infection have been described in the literature to date. Herein, we report a 64-year-old woman who presented with asymptomatic, flat, flesh-coloured papules on her neck, upper trunk and proximal extremities. A skin biopsy from a papule on her neck demonstrated dermal mucin deposition after alcian blue staining. The number of fibroblasts was increased. Laboratory studies revealed normal thyroid function tests. Serum protein electrophoresis did not show any evidence of a monoclonal gammopathy. Serology tests for HCV and HIV were negative.

  3. 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

  4. 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.

  5. 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

  6. 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...

  7. 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

    -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...... subtypes that were also found in food as opposed to 31% of travel-associated infections. The results showed differences in the various Campylobacter populations, e.g. the Danish population as reflected in the domestically acquired infections and the Danish-produced food was more uniform than the isolates...

  8. Genome characterisation of the newly discovered avian influenza A H5N7 virus subtype combination

    DEFF Research Database (Denmark)

    Bragstad, K.; Jørgensen, Poul Henrik; Handberg, K.J.; Fomsgaard, A.

    2007-01-01

    In Denmark, in 2003, a previously unknown subtype combination of avian influenza A virus, H5N7 (A/Mallard/Denmark/64650/03), was isolated from a flock of 12,000 mallards. The H5N7 subtype combination might be a reassortant between recent European avian influenza A H5, H7, and a third subtype....../Duck/Hong Kong/3096/99 (H6N2) and A/WDk/ST/1737/2000 (H6N8), respectively. All genes of the H5N7 strain were of avian origin, and no further evidence of pathogenicity to humans has been found....

  9. 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

  10. 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

  11. CoINcIDE: A framework for discovery of patient subtypes across multiple datasets.

    Science.gov (United States)

    Planey, Catherine R; Gevaert, Olivier

    2016-01-01

    Patient disease subtypes have the potential to transform personalized medicine. However, many patient subtypes derived from unsupervised clustering analyses on high-dimensional datasets are not replicable across multiple datasets, limiting their clinical utility. We present CoINcIDE, a novel methodological framework for the discovery of patient subtypes across multiple datasets that requires no between-dataset transformations. We also present a high-quality database collection, curatedBreastData, with over 2,500 breast cancer gene expression samples. We use CoINcIDE to discover novel breast and ovarian cancer subtypes with prognostic significance and novel hypothesized ovarian therapeutic targets across multiple datasets. CoINcIDE and curatedBreastData are available as R packages. PMID:26961683

  12. Drugs selective for nicotinic receptor subtypes: a real possibility or a dream?

    Science.gov (United States)

    Gotti, C; Carbonnelle, E; Moretti, M; Zwart, R; Clementi, F

    2000-08-01

    Nicotine exerts a number of different effects on the nervous system by interacting with neuronal nicotinic acetylcholine receptors (nAChRs). These effects are mediated by its interaction with different nAChR subtypes, and this has led to the finding of subtype specific agonists and antagonists. In the search for subtype-selective drugs, we have synthesized some compounds derived from 4-oxystilbene, two of which (MG624 and F3) are selective ligands for the chick neuronal alphaBgtx receptors containing the alpha7 and/or alpha8 subunits. They have an antagonist action on oocyte-expressed chick and rat alpha7 subtypes. These compounds are selective toward the alpha7-containing receptors in chick, but, in mammals, although they still retain their potency toward alpha7-containing receptors, they are also active in non-alpha7-containing receptors. PMID:10942044

  13. PAM50 breast cancer intrinsic subtypes and effect of gemcitabine in advanced breast cancer patients

    DEFF Research Database (Denmark)

    Jørgensen, Charlotte Levin Tykjær; Nielsen, Torsten O; Bjerre, Karsten D;

    2014-01-01

    NanoString nCounter. Statistical analyses were prespecified as a formal prospective-retrospective clinical trial correlative study. Using time to progression (TTP) as primary endpoint, overall survival (OS) and response rate as secondary endpoints, relationships between subtypes and outcome after...... patients (31%) were classified as luminal A, 97 (36%) luminal B, 43 (16%) basal-like, and 46 (17%) as HER2-enriched. PAM50 intrinsic subtype was a significant independent prognostic factor for both TTP (p=0.014) and OS (p=0.0003). Response rate was not different by subtype, and PAM50 was not a predictor of...... TTP by treatment arm. PAM50 was however a highly significant predictor of OS following GD compared to D (pinteraction=0.0016). Patients with a basal-like subtype had a significant reduction in OS events [hazard ratio (HR)=0.29, 95% confidence interval (CI)=0.15-0.57; pinteraction=0.0006]. CONCLUSION...

  14. 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.

  15. Chest imaging of H7N9 subtype of human avian influenza

    Directory of Open Access Journals (Sweden)

    Xi-ming Wang

    2015-03-01

    Conclusions: The characteristic imaging demonstrations of H7N9 subtype of human avian influenza are segmental or lobar exudative lesions at lungs at the initial stage, which rapidly progress into bilateral distribution at lungs at the progressive stage.

  16. 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

  17. Social Likeability, Subtypes of Aggression, and the Attributional Style of Aggressive Youth

    OpenAIRE

    Blier, Heather K.

    2001-01-01

    Recent efforts to understand and predict the onset and maintenance of aggression have considered the heterogeneity of this behavior. Dodge (1980) and others, have suggested a distinction in aggression based on two primary subtypes: reactive and proactive aggression. The form, severity and persistence of these aggressive subtypes may depend on an on-going interaction between individual characteristics and environmental characteristics that elicit varying antecedents and consequences (Frick,...

  18. Prognostic Implication of Predominant Histologic Subtypes of Lymph Node Metastases in Surgically Resected Lung Adenocarcinoma

    OpenAIRE

    Kenichi Suda; Katsuaki Sato; Shigeki Shimizu; Kenji Tomizawa; Toshiki Takemoto; Takuya Iwasaki; Masahiro Sakaguchi; Tetsuya Mitsudomi

    2014-01-01

    The International Association for the Study of Lung Cancer, American Thoracic Society, and European Respiratory Society (IASLC/ATS/ERS) proposed a new classification for lung adenocarcinoma (AD) based on predominant histologic subtypes, such as lepidic, papillary, acinar, solid, and micropapillary; this system reportedly reflects well outcomes of patients with surgically resected lung AD. However, the prognostic implication of predominant histologic subtypes in lymph nodes metastases is uncle...

  19. SEROMONITORING OF AVIAN INFLUENZA H9 SUBTYPE IN BREEDERS AND COMMERCIAL LAYER FLOCKS

    Directory of Open Access Journals (Sweden)

    M. Numan, M. Siddique and M. S. Yousaf1

    2005-07-01

    Full Text Available A serological survey for detection of antibodies against avian influenza virus (AIV subtype H9 in vaccinated layer flocks was carried out. Serum samples were divided into age groups A, B, C, D (commercial layers and E, F, G, H (layer breeders. Haemagglutination inhibition (HI test was performed to determine serum antibodies against AIV-H9 subtype. Geometric mean titer (GMT values were calculated. Results showed the level of protection of vaccinated birds was satisfactory.

  20. Tracing the origin and northward dissemination dynamics of HIV-1 subtype C in Brazil.

    Directory of Open Access Journals (Sweden)

    Edson Delatorre

    Full Text Available Previous studies indicate that the HIV-1 subtype C epidemic in southern Brazil was initiated by the introduction of a single founder strain probably originating from east Africa. However, the exact country of origin of such a founder strain as well as the origin of the subtype C viruses detected outside the Brazilian southern region remains unknown. HIV-1 subtype C pol sequences isolated in the southern, southeastern and central-western Brazilian regions (n = 209 were compared with a large number (n ~ 2,000 of subtype C pol sequences of African origin. Maximum-likelihood analyses revealed that most HIV-1 subtype C Brazilian sequences branched in a single monophyletic clade (CBR-I, nested within a larger monophyletic lineage characteristic of east Africa. Bayesian analyses indicate that the CBR-I clade most probably originated in Burundi and was introduced into the Paraná state (southern region around the middle 1970s, after which it rapidly disseminated to neighboring regions. The states of Paraná and Santa Catarina have been the most important hubs of subtype C dissemination, and routine travel and spatial accessibility seems to have been the major driving forces of this process. Five additional introductions of HIV-1 subtype C strains probably originated in eastern (n = 2, southern (n = 2 and central (n = 1 African countries were detected in the Rio de Janeiro state (southeastern region. These results indicate a continuous influx of HIV-1 subtype C strains of African origin into Brazil and also unveil the existence of unrecognized transmission networks linking this country to east Africa.

  1. eMBI: Boosting Gene Expression-based Clustering for Cancer Subtypes

    OpenAIRE

    Chang, Zheng; Wang, Zhenjia; Ashby, Cody; Zhou, Chuan; Li, Guojun; Zhang, Shuzhong; Huang, Xiuzhen

    2014-01-01

    Identifying clinically relevant subtypes of a cancer using gene expression data is a challenging and important problem in medicine, and is a necessary premise to provide specific and efficient treatments for patients of different subtypes. Matrix factorization provides a solution by finding checker-board patterns in the matrices of gene expression data. In the context of gene expression profiles of cancer patients, these checkerboard patterns correspond to genes that are up- or down-regulated...

  2. Working memory deficits in adults with ADHD: is there evidence for subtype differences?

    OpenAIRE

    Medoff Deborah R; Hanford Russell B; Schweitzer Julie B

    2006-01-01

    Abstract Background Working memory performance is important for maintaining functioning in cognitive, academic and social activities. Previous research suggests there are prevalent working memory deficits in children with attention deficit hyperactivity disorder (ADHD). There is now a growing body of literature characterizing working memory functioning according to ADHD subtypes in children. The expression of working memory deficits in adults with ADHD and how they vary according to subtype, ...

  3. Social Skills and Social Phobia: An Investigation of DSM-IV Subtypes

    OpenAIRE

    Deborah C Beidel; Rao, Patricia A; Scharfstein, Lindsay; Wong, Nina; Alfano, Candice A.

    2010-01-01

    Social phobia is characterized as pervasive social timidity in social settings. Although much is known about this disorder, aspects of its clinical presentation remain unexplored, in particular characteristics that distinguish the generalized and non-generalized subtypes. For example, it remains unclear whether patients with the non-generalized subtype display social skills deficits in social interactions, and if so, are these deficits clinically, as well as statistically, significant? In thi...

  4. Temporomandibular Joint Disorder Complaints in Tinnitus: Further Hints for a Putative Tinnitus Subtype

    OpenAIRE

    Vielsmeier, Veronika; Sturtz, Jürgen; Kleinjung, Tobias; Schecklmann, Martin; Kreuzer, Peter M.; Landgrebe, Michael; Langguth, Berthold

    2012-01-01

    Objective Tinnitus is considered to be highly heterogeneous with respect to its etiology, its comorbidities and the response to specific interventions. Subtyping is recommended, but it remains to be determined which criteria are useful, since it has not yet been clearly demonstrated whether and to which extent etiologic factors, comorbid states and interventional response are related to each other and are thus applicable for subtyping tinnitus. Analyzing the Tinnitus Research Initiative Da...

  5. Nutrient dynamics in different sub-types of peat swamp forest in central Kalimantan, Indonesia

    OpenAIRE

    Sulistiyanto, Yustinus

    2005-01-01

    Nutrient dynamics of two sub-types of peat swamp forest, mixed swamp forest and low pole forest, in the upper catchment of the Sebangau River in Central Kalimantan, Indonesia were studied. Three permanent study plots, 50 x 50 m, were established in each forest sub-type to facilitate collection of throughfall, stemflow, litterfall, decomposition, above ground and below ground biomass, peat and water samples. Graphical presentation, Wilm's method, and analysis of variance were carried out for b...

  6. Distribution and clinical manifestations of Cryptosporidium species and subtypes in HIV/AIDS patients in Ethiopia.

    Directory of Open Access Journals (Sweden)

    Haileeyesus Adamu

    2014-04-01

    Full Text Available BACKGROUND: Cryptosporidiosis is an important cause for chronic diarrhea and death in HIV/AIDS patients. Among common Cryptosporidium species in humans, C. parvum is responsible for most zoonotic infections in industrialized nations. Nevertheless, the clinical significance of C. parvum and role of zoonotic transmission in cryptosporidiosis epidemiology in developing countries remain unclear. METHODOLOGY/PRINCIPAL FINDINGS: In this cross-sectional study, 520 HIV/AIDS patients were examined for Cryptosporidium presence in stool samples using genotyping and subtyping techniques. Altogether, 140 (26.9% patients were positive for Cryptosporidium spp. by PCR-RFLP analysis of the small subunit rRNA gene, belonging to C. parvum (92 patients, C. hominis (25 patients, C. viatorum (10 patients, C. felis (5 patients, C. meleagridis (3 patients, C. canis (2 patients, C. xiaoi (2 patients, and mixture of C. parvum and C. hominis (1 patient. Sequence analyses of the 60 kDa glycoprotein gene revealed a high genetic diversity within the 82 C. parvum and 19 C. hominis specimens subtyped, including C. parvum zoonotic subtype families IIa (71 and IId (5 and anthroponotic subtype families IIc (2, IIb (1, IIe (1 and If-like (2, and C. hominis subtype families Id (13, Ie (5, and Ib (1. Overall, Cryptosporidium infection was associated with the occurrence of diarrhea and vomiting. Diarrhea was attributable mostly to C. parvum subtype family IIa and C. hominis, whereas vomiting was largely attributable to C. hominis and rare Cryptosporidium species. Calf contact was identified as a significant risk factor for infection with Cryptosporidium spp., especially C. parvum subtype family IIa. CONCLUSIONS/SIGNIFICANCE: Results of the study indicate that C. parvum is a major cause of cryptosporidiosis in HIV-positive patients and zoonotic transmission is important in cryptosporidiosis epidemiology in Ethiopia. In addition, they confirm that different Cryptosporidium species and

  7. Temporomandibular joint disorder complaints in tinnitus: Further hints for a putative tinnitus subtype

    OpenAIRE

    Vielsmeier, V; Strutz, J; Kleinjung, T; Schecklmann, M; Kreuzer, P M; Landgrebe, M; Langguth, B

    2012-01-01

    OBJECTIVE: Tinnitus is considered to be highly heterogeneous with respect to its etiology, its comorbidities and the response to specific interventions. Subtyping is recommended, but it remains to be determined which criteria are useful, since it has not yet been clearly demonstrated whether and to which extent etiologic factors, comorbid states and interventional response are related to each other and are thus applicable for subtyping tinnitus. Analyzing the Tinnitus Research Initiative Data...

  8. Empirically Defined Subtypes of Alcohol Dependence in an Irish Family Sample

    OpenAIRE

    Sintov, Nicole D.; Kendler, Kenneth S; Young-Wolff, Kelly C.; Walsh, Dermot; Patterson, Diana G.; Prescott, Carol A.

    2010-01-01

    Alcohol dependence (AD) is clinically and etiologically heterogeneous. The goal of this study was to explore AD subtypes among a sample of 1, 221 participants in the Irish Affected Sib Pair Study of Alcohol Dependence, all of whom met DSM-IV criteria for AD. Variables used to identify the subtypes included major depressive disorder, antisocial personality disorder, illicit drug dependence (cannabis, sedatives, stimulants, cocaine, opioids, and hallucinogens), nicotine dependence, the personal...

  9. PROCESS EXAMINATION OF EXECUTIVE FUNCTION IN ADHD: SEX AND SUBTYPE EFFECTS

    OpenAIRE

    Wodka, Ericka L.; Mostofsky, Stewart H.; Prahme, Cristine; Larson, Jennifer C. Gidley; Loftis, Christopher; Denckla, Martha B.; MAHONE, E MARK

    2008-01-01

    To examine effects of group (Attention-Deficit/Hyperactivity Disorder [ADHD] versus Typically Developing [TD]), sex, and ADHD subtype on “process/optional” measures of executive functioning, children (n = 123; 54 ADHD, 69 TD) aged 8−16 completed subtests from the D-KEFS. No group, sex, or ADHD subtype effects were found on optional measures from the Trail Making, Color–Word Interference, and Tower tests. A significant interaction was found for Verbal Fluency Total Repetition Errors; boys with...

  10. Inhibitory Functioning across ADHD Subtypes: Recent Findings, Clinical Implications and Future Directions

    OpenAIRE

    Adams, Zachary W.; Derefinko, Karen J.; Milich, Richard; Fillmore, Mark T.

    2008-01-01

    Although growing consensus supports the role of deficient behavioral inhibition as a central feature of the combined subtype of ADHD (ADHD/C; Barkley, 2007; Nigg, 2001), little research has focused on how this finding generalizes to the primarily inattentive subtype (ADHD/I). This question holds particular relevance in light of recent work suggesting that ADHD/I might be better characterized as a disorder separate from ADHD/C (Diamond, 2005; Milich et al., 2001). The current paper describes m...

  11. The HIV-1 subtype C epidemic in South America is linked to the United Kingdom.

    Directory of Open Access Journals (Sweden)

    Tulio de Oliveira

    Full Text Available BACKGROUND: The global spread of HIV-1 has been accompanied by the emergence of genetically distinct viral strains. Over the past two decades subtype C viruses, which predominate in Southern and Eastern Africa, have spread rapidly throughout parts of South America. Phylogenetic studies indicate that subtype C viruses were introduced to South America through a single founder event that occurred in Southern Brazil. However, the external route via which subtype C viruses spread to the South American continent has remained unclear. METHODOLOGY/PRINCIPAL FINDINGS: We used automated genotyping to screen 8,309 HIV-1 subtype C pol gene sequences sampled within the UK for isolates genetically linked to the subtype C epidemic in South America. Maximum likelihood and Bayesian approaches were used to explore the phylogenetic relationships between 54 sequences identified in this screen, and a set of globally sampled subtype C reference sequences. Phylogenetic trees disclosed a robustly supported relationship between sequences from Brazil, the UK and East Africa. A monophyletic cluster comprised exclusively of sequences from the UK and Brazil was identified and dated to approximately the early 1980s using a Bayesian coalescent-based method. A sub-cluster of 27 sequences isolated from homosexual men of UK origin was also identified and dated to the early 1990s. CONCLUSIONS: Phylogenetic, demographic and temporal data support the conclusion that the UK was a crucial staging post in the spread of subtype C from East Africa to South America. This unexpected finding demonstrates the role of diffuse international networks in the global spread of HIV-1 infection, and the utility of globally sampled viral sequence data in revealing these networks. Additionally, we show that subtype C viruses are spreading within the UK amongst men who have sex with men.

  12. Determination of HLA-B27 Subtypes in Iranian Patients with Ankylosing Spondylitis

    Directory of Open Access Journals (Sweden)

    Mohamad Hossein Nicknam

    2008-03-01

    Full Text Available The human leukocyte antigen-B27 is one of the class I molecules of the major histocompatibility complex which is strongly associated with ankylosing spondylitis (AS. The strength of the disease association with B27 varies markedly among racial and ethnic populations. It is an allele family, which constitutes about 31 subtypes, with a considerable geographic and ethnic difference in distribution. It is important to know whether certain subtypes show any preferential association with AS. Because there is no report regarding HLA-B27 subtypes in Iranian patients with AS, the factthe main there are rarelystudies (if any; purpose of the present study was to assess the frequency of subtypes of human leukocyte antigen (HLA-B27 in patients with ankylosing spondylitis in Iranian populationOne hundred and nineteen AS patients (82 HLA-B27 positive and 37 HLA-B27 negative were selected for this study. HLA-B27 positive patients were selected screened for B*27 subtyping were performed by polymerase chain reaction amplification with sequence-specific primers (PCR-SSP for B*27 subtyping.. The results of present study revealed that onlythat only two subtypes were detected in Iranian patients, including: B*2705 (52 patients, 63.4% and B*2702 (30 patients, 36.6%. Our results showed a restricted number of HLA-B27 subtypes associated with AS in Iran and an elevated frequency of the B*2705 allele in these patients similar to other Euro-Caucasoid (Aryan groups in the world.

  13. Is There a High-Risk Subtype of Depression in Patients with Coronary Heart Disease?

    OpenAIRE

    Carney, Robert M.; Freedland, Kenneth E

    2012-01-01

    Depression is a risk factor for cardiac morbidity and mortality in patients with coronary heart disease, especially in those with a recent history of acute coronary syndrome. To improve risk stratification and treatment planning, it would be useful to identify the characteristics or subtypes of depression that are associated with the highest risk of cardiac events. This paper reviews the evidence concerning several putative depression subtypes and symptom patterns that may be associated with ...

  14. Eating disorder subtypes differ in their rates of psychosocial improvement over treatment

    OpenAIRE

    Kelly, Allison C; Carter, Jacqueline C.

    2014-01-01

    Background Individuals with Anorexia Nervosa (AN) are renowned for their poor short- and long-term treatment outcomes. To gain more insight into the reasons for these poor outcomes, the present study compared patients with AN-R (restrictive subtype), AN-BP (binge-purge subtype), bulimia nervosa (BN), and eating disorder not otherwise specified (EDNOS) over 12 weeks of specialized eating disorders treatment. Eighty-nine patients completed the Eating Disorder Examination- Questionnaire (EDE-Q) ...

  15. Sitaxentan for the Oral Treatment of Pulmonary Arterial Hypertension: Benefits from Endothelin Receptor Subtype Selectivity?

    OpenAIRE

    Hermann A.M. Mucke

    2009-01-01

    Pulmonary arterial hypertension (PAH) is a deadly and underdiagnosed disease which causes right heart failure secondary to pressure overload resulting from the thickening of the pulmonary artery endothelium, associated with elevated levels of circulating endothelin-1. Sitaxentan was the first endothelin antagonist with high selectivity for receptor subtype A (over subtype ET-B) to gain regulatory approval for the treatment of PAH in major pharmaceutical markets. This review traces the develop...

  16. Morphometric characteristics of basal cell carcinoma peritumoral stroma varies among basal cell carcinoma subtypes

    OpenAIRE

    Lesack Kyle; Naugler Christopher

    2012-01-01

    Abstract Background The role that the peritumoral stroma plays in the growth of tumours is currently poorly understood. In this manuscript the morphometric characteristics of basal cell carcinoma subtypes and their associated peritumoral stromas are presented. Methods Ninety eight digitized basal cell carcinoma histology slides were categorized as infiltrative, nodular, or superficial subtypes, and were analysed using a combination of manual and computer-assisted approaches. The morphometric ...

  17. Prevalence and origin of HIV-1 group M subtypes among patients attending a Belgian hospital in 1999.

    Science.gov (United States)

    Snoeck, Joke; Van Dooren, Sonia; Van Laethem, Kristel; Derdelinckx, Inge; Van Wijngaerden, Eric; De Clercq, Erik; Vandamme, Anne-Mieke

    2002-04-23

    HIV-1 group M strains are usually subtyped based on gag and/or env gene sequences. In our lab, part of the pol gene sequence was available in order to determine the genotypic anti-HIV drug resistance profile. To estimate the prevalence of the different HIV-1 subtypes in patients visiting the University Hospitals in Leuven in 1999 and for whom a genotypic drug resistance test was needed, we tried to use the pol sequence for subtyping. Recombination was investigated by similarity plots and bootscanning and subtyping was performed by phylogenetic analysis. The overall region spanning the entire protease and 747 nucleotides of the reverse transcriptase proved very suitable for subtyping, although there was a low phylogenetic signal at the beginning of the reverse transcriptase (nucleotides 0-250), as we demonstrated by likelihood mapping. Of the 41 samples analyzed, 21 belonged to subtype B. Of the other 20 non-B strains, 9 belonged to subtype C, 2 to subtype D and 1 to subtype A, G, H and J, respectively, 3 were CRF_02 (Circulating Recombinant Form), 1 was recombinant with a novel breakpoint and 1 sample was untypable. Although subtype B is still the most prevalent subtype in Belgium, it seems to be responsible for only half of the infections in this study. We could also document that the prevalence of subtype C is high in the Belgian native patients, especially among the heterosexually infected population. This could possibly be an indication for an epidemic spread of HIV-1 subtype C in Belgium, as for one third of these patients, no link to an endemic region could be found. The other non-B subtypes and the recombinants are mainly introduced by immigrants or by Belgian citizens traveling abroad. PMID:11955642

  18. Prognostic implication of predominant histologic subtypes of lymph node metastases in surgically resected lung adenocarcinoma.

    Science.gov (United States)

    Suda, Kenichi; Sato, Katsuaki; Shimizu, Shigeki; Tomizawa, Kenji; Takemoto, Toshiki; Iwasaki, Takuya; Sakaguchi, Masahiro; Mitsudomi, Tetsuya

    2014-01-01

    The International Association for the Study of Lung Cancer, American Thoracic Society, and European Respiratory Society (IASLC/ATS/ERS) proposed a new classification for lung adenocarcinoma (AD) based on predominant histologic subtypes, such as lepidic, papillary, acinar, solid, and micropapillary; this system reportedly reflects well outcomes of patients with surgically resected lung AD. However, the prognostic implication of predominant histologic subtypes in lymph nodes metastases is unclear so far. In this study, we compared predominant subtypes between primary lung tumors and lymph node metastatic lesions in 24 patients with surgically treated lung adenocarcinoma with lymph node metastases. Additionally, we analyzed prognostic implications of these predominant histologic subtypes. We observed several discordance patterns between predominant subtypes in primary lung tumors and lymph node metastases. Concordance rates were 22%, 64%, and 100%, respectively, in papillary-, acinar-, and solid-predominant primary lung tumors. We observed that the predominant subtype in the primary lung tumor (HR 12.7, P = 0.037), but not that in lymph node metastases (HR 0.18, P = 0.13), determines outcomes in patients with surgically resected lung AD with lymph node metastases. PMID:25371901

  19. Prognostic Implication of Predominant Histologic Subtypes of Lymph Node Metastases in Surgically Resected Lung Adenocarcinoma

    Directory of Open Access Journals (Sweden)

    Kenichi Suda

    2014-01-01

    Full Text Available The International Association for the Study of Lung Cancer, American Thoracic Society, and European Respiratory Society (IASLC/ATS/ERS proposed a new classification for lung adenocarcinoma (AD based on predominant histologic subtypes, such as lepidic, papillary, acinar, solid, and micropapillary; this system reportedly reflects well outcomes of patients with surgically resected lung AD. However, the prognostic implication of predominant histologic subtypes in lymph nodes metastases is unclear so far. In this study, we compared predominant subtypes between primary lung tumors and lymph node metastatic lesions in 24 patients with surgically treated lung adenocarcinoma with lymph node metastases. Additionally, we analyzed prognostic implications of these predominant histologic subtypes. We observed several discordance patterns between predominant subtypes in primary lung tumors and lymph node metastases. Concordance rates were 22%, 64%, and 100%, respectively, in papillary-, acinar-, and solid-predominant primary lung tumors. We observed that the predominant subtype in the primary lung tumor (HR 12.7, P = 0.037, but not that in lymph node metastases (HR 0.18, P = 0.13, determines outcomes in patients with surgically resected lung AD with lymph node metastases.

  20. Pediatric rhabdomyosarcoma at presentation: Can cross-sectional imaging findings predict pathologic tumor subtype?

    International Nuclear Information System (INIS)

    Objective: The purpose of the study is to determine whether there are cross-sectional imaging features of pediatric rhabdomyosarcoma that are specific to the different pathologic subtypes of the tumor. Materials and methods: Medical records of 14 pediatric patients who were diagnosed with rhabdomyosarcoma were reviewed retrospectively. Patient demographics, including age and sex, as well as final pathologic report were obtained. The initial CT, MRI, or both obtained at presentation, prior to the diagnosis being established, were reviewed by two radiologists. We recorded tumor features including site, size, margins, local extension, and presence of metastases. Presence of calcification, hemorrhage, or necrosis as well as attenuation and heterogeneity of the tumor were also recorded. Results: Ten of our fourteen patients were formally diagnosed with the embryonal subtype of rhabdomyosarcoma, while three were found to have the alveolar subtype, and one subtype was poorly differentiated. There was no significant difference in the attenuation and in the heterogeneity of the tumor between the embryonal and the alveolar subtype on CT. Conclusion: Imaging features at presentation, such as attenuation and heterogeneity, could not correlate to the pathologic subtype of pediatric rhabdomyosarcoma.

  1. Cerebral artery alpha-1 AR subtypes: high altitude long-term acclimatization responses.

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    Ravi Goyal

    Full Text Available In response to hypoxia and other stress, the sympathetic (adrenergic nervous system regulates arterial contractility and blood flow, partly through differential activities of the alpha1 (α1 - adrenergic receptor (AR subtypes (α1A-, α1B-, and α1D-AR. Thus, we tested the hypothesis that with acclimatization to long-term hypoxia (LTH, contractility of middle cerebral arteries (MCA is regulated by changes in expression and activation of the specific α1-AR subtypes. We conducted experiments in MCA from adult normoxic sheep maintained near sea level (300 m and those exposed to LTH (110 days at 3801 m. Following acclimatization to LTH, ovine MCA showed a 20% reduction (n = 5; P<0.05 in the maximum tension achieved by 10-5 M phenylephrine (PHE. LTH-acclimatized cerebral arteries also demonstrated a statistically significant (P<0.05 inhibition of PHE-induced contractility in the presence of specific α1-AR subtype antagonists. Importantly, compared to normoxic vessels, there was significantly greater (P<0.05 α1B-AR subtype mRNA and protein levels in LTH acclimatized MCA. Also, our results demonstrate that extracellular regulated kinase 1 and 2 (ERK1/2-mediated negative feedback regulation of PHE-induced contractility is modulated by α1B-AR subtype. Overall, in ovine MCA, LTH produces profound effects on α1-AR subtype expression and function.

  2. An integrated strategy for analyzing the unique developmental programs of different myoblast subtypes.

    Directory of Open Access Journals (Sweden)

    2006-02-01

    Full Text Available An important but largely unmet challenge in understanding the mechanisms that govern the formation of specific organs is to decipher the complex and dynamic genetic programs exhibited by the diversity of cell types within the tissue of interest. Here, we use an integrated genetic, genomic, and computational strategy to comprehensively determine the molecular identities of distinct myoblast subpopulations within the Drosophila embryonic mesoderm at the time that cell fates are initially specified. A compendium of gene expression profiles was generated for primary mesodermal cells purified by flow cytometry from appropriately staged wild-type embryos and from 12 genotypes in which myogenesis was selectively and predictably perturbed. A statistical meta-analysis of these pooled datasets--based on expected trends in gene expression and on the relative contribution of each genotype to the detection of known muscle genes--provisionally assigned hundreds of differentially expressed genes to particular myoblast subtypes. Whole embryo in situ hybridizations were then used to validate the majority of these predictions, thereby enabling true-positive detection rates to be estimated for the microarray data. This combined analysis reveals that myoblasts exhibit much greater gene expression heterogeneity and overall complexity than was previously appreciated. Moreover, it implicates the involvement of large numbers of uncharacterized, differentially expressed genes in myogenic specification and subsequent morphogenesis. These findings also underscore a requirement for considerable regulatory specificity for generating diverse myoblast identities. Finally, to illustrate how the developmental functions of newly identified myoblast genes can be efficiently surveyed, a rapid RNA interference assay that can be scored in living embryos was developed and applied to selected genes. This integrated strategy for examining embryonic gene expression and function provides

  3. Comparative functional expression of nAChR subtypes in rodent DRG neurons

    Directory of Open Access Journals (Sweden)

    J. Michael McIntosh

    2013-11-01

    Full Text Available We investigated the functional expression of nicotinic acetylcholine receptors (nAChRs in heterogeneous populations of dissociated rat and mouse lumbar dorsal root ganglion (DRG neurons by calcium imaging. By this experimental approach, it is possible to investigate the functional expression of multiple receptor and ion-channel subtypes across more than 100 neuronal and glial cells simultaneously. Based on nAChR expression, DRG neurons could be divided into four subclasses: 1 neurons that express predominantly alpha3beta4 and alpha6beta4 nAChRs; 2 neurons that express predominantly alpha7 nAChRs; 3 neurons that express a combination of alpha3beta4/alpha6beta4 and alpha7 nAChRs; and 4 neurons that do not express nAChRs. In this comparative study, the same four neuronal subclasses were observed in mouse and rat DRG. However, the expression frequency differed between species: substantially more rat DRG neurons were in the first three subclasses than mouse DRG neurons, at all developmental time points tested in our study. Approximately 70-80% of rat DRG neurons expressed functional nAChRs, in contrast to only ~15-30% of mouse DRG neurons. Our study also demonstrated functional coupling between nAChRs, voltage-gated calcium channels and mitochondrial Ca2+ transport in discrete subsets of DRG neurons. In contrast to the expression of nAChRs in DRG neurons, we demonstrated that a subset of non-neuronal DRG cells expressed muscarinic acetylcholine receptors (mAChRs and not nAChRs. The general approach to comparative cellular neurobiology outlined in this paper has the potential to better integrate molecular and systems neuroscience by uncovering the spectrum of neuronal subclasses present in a given cell population and the functionally integrated signaling components expressed in each subclass.

  4. Oxidative stress induces itch via activation of transient receptor potential subtype ankyrin 1 in mice

    Institute of Scientific and Technical Information of China (English)

    Tong Liu; Ru-Rong Ji

    2012-01-01

    Objective To investigate the role of oxidative stress in itch-indicative scratching behavior in mice,and furthermore,to define the cellular and molecular mechanisms underlying oxidative stress-mediated itch.Methods Scratching behavior was induced by intradermal injection of the oxidants hydrogen peroxide (H2O2) or tert-butylhydroperoxide (tBHP) into the nape of the neck in mice.The mice were observed for 30 min.Results Intradermal H2O2 (0.03%-1%) or tBHP (1-30 μmol) elicited robust scratching behavior,displaying an inverted U-shaped dose-response curve.Naloxone,an opioid receptor antagonist,but not morphine,largely suppressed the oxidant-induced scratching.Chlorpheniramine,a histamine H 1 receptor antagonist,blocked histamine-but not oxidant-induced scratching,indicating the involvement of a histamine-independent mechanism in oxidant-evoked itch.Further,resiniferatoxin treatment abolished oxidant-induced scratching,suggesting an essential role of C-fibers.Notably,blockade of transient receptor potential subtype ankyrin 1 (TRPA1) with the selective TRPA1 antagonist HC-030031,or genetic deletion of Trpal but not Trpvl (subfamily V,member 1) resulted in a profound reduction in H2O2-evoked scratching.Finally,systemic administration of the antioxidant Nacety1-L-cysteine or trolox (a water-soluble vitamin E analog) attenuated scratching induced by the oxidants.Conclusion Oxidative stress by different oxidants induces profound scratching behavior,which is largely histamine-and TRPV1-independent but TRPA1-dependent.Antioxidants and TRPA1 antagonists may be used to treat human itch conditions associated with oxidative stress.

  5. Negative Allosteric Modulators of Metabotropic Glutamate Receptors Subtype 5 in Addiction: a Therapeutic Window

    Science.gov (United States)

    2016-01-01

    Background: Abundant evidence at the anatomical, electrophysiological, and molecular levels implicates metabotropic glutamate receptor subtype 5 (mGluR5) in addiction. Consistently, the effects of a wide range of doses of different mGluR5 negative allosteric modulators (NAMs) have been tested in various animal models of addiction. Here, these studies were subjected to a systematic review to find out if mGluR5 NAMs have a therapeutic potential that can be translated to the clinic. Methods: Literature on consumption/self-administration and reinstatement of drug seeking as outcomes of interest published up to April 2015 was retrieved via PubMed. The review focused on the effects of systemic (i.p., i.v., s.c.) administration of the mGluR5 NAMs 3-((2-Methyl-4-thiazolyl)ethynyl)pyridine (MTEP) and 2-Methyl-6-(phenylethynyl)pyridine (MPEP) on paradigms with cocaine, ethanol, nicotine, and food in rats. Results: MTEP and MPEP were found to reduce self-administration of cocaine, ethanol, and nicotine at doses ≥1mg/kg and 2.5mg/kg, respectively. Dose-response relationship resembled a sigmoidal curve, with low doses not reaching statistical significance and high doses reliably inhibiting self-administration of drugs of abuse. Importantly, self-administration of cocaine, ethanol, and nicotine, but not food, was reduced by MTEP and MPEP in the dose range of 1 to 2mg/kg and 2.5 to 3.2mg/kg, respectively. This dose range corresponds to approximately 50% to 80% mGluR5 occupancy. Interestingly, the limited data found in mice and monkeys showed a similar therapeutic window. Conclusion: Altogether, this review suggests a therapeutic window for mGluR5 NAMs that can be translated to the treatment of substance-related and addictive disorders. PMID:26802568

  6. Molecular Typing of Treponema pallidum: A Systematic Review and Meta-Analysis

    Science.gov (United States)

    Peng, Rui-Rui; Wang, Alberta L.; Li, Jing; Tucker, Joseph D.; Yin, Yue-Ping; Chen, Xiang-Sheng

    2011-01-01

    Background Syphilis is resurgent in many regions of the world. Molecular typing is a robust tool for investigating strain diversity and epidemiology. This study aimed to review original research on molecular typing of Treponema pallidum (T. pallidum) with three objectives: (1) to determine specimen types most suitable for molecular typing; (2) to determine T. pallidum subtype distribution across geographic areas; and (3) to summarize available information on subtypes associated with neurosyphilis and macrolide resistance. Methodology/Principal Findings Two researchers independently searched five databases from 1998 through 2010, assessed for eligibility and study quality, and extracted data. Search terms included “Treponema pallidum,” or “syphilis,” combined with the subject headings “molecular,” “subtyping,” “typing,” “genotype,” and “epidemiology.” Sixteen eligible studies were included. Publication bias was not statistically significant by the Begg rank correlation test. Medians, inter-quartile ranges, and 95% confidence intervals were determined for DNA extraction and full typing efficiency. A random-effects model was used to perform subgroup analyses to reduce obvious between-study heterogeneity. Primary and secondary lesions and ear lobe blood specimens had an average higher yield of T. pallidum DNA (83.0% vs. 28.2%, χ2 = 247.6, p<0.001) and an average higher efficiency of full molecular typing (80.9% vs. 43.1%, χ2 = 102.3, p<0.001) compared to plasma, whole blood, and cerebrospinal fluid. A pooled analysis of subtype distribution based on country location showed that 14d was the most common subtype, and subtype distribution varied across geographic areas. Subtype data associated with macrolide resistance and neurosyphilis were limited. Conclusions/Significance Primary lesion was a better specimen for obtaining T. pallidum DNA than blood. There was wide geographic variation in T. pallidum subtypes. More research is needed

  7. Molecular typing of Treponema pallidum: a systematic review and meta-analysis.

    Directory of Open Access Journals (Sweden)

    Rui-Rui Peng

    2011-11-01

    Full Text Available BACKGROUND: Syphilis is resurgent in many regions of the world. Molecular typing is a robust tool for investigating strain diversity and epidemiology. This study aimed to review original research on molecular typing of Treponema pallidum (T. pallidum with three objectives: (1 to determine specimen types most suitable for molecular typing; (2 to determine T. pallidum subtype distribution across geographic areas; and (3 to summarize available information on subtypes associated with neurosyphilis and macrolide resistance. METHODOLOGY/PRINCIPAL FINDINGS: Two researchers independently searched five databases from 1998 through 2010, assessed for eligibility and study quality, and extracted data. Search terms included "Treponema pallidum," or "syphilis," combined with the subject headings "molecular," "subtyping," "typing," "genotype," and "epidemiology." Sixteen eligible studies were included. Publication bias was not statistically significant by the Begg rank correlation test. Medians, inter-quartile ranges, and 95% confidence intervals were determined for DNA extraction and full typing efficiency. A random-effects model was used to perform subgroup analyses to reduce obvious between-study heterogeneity. Primary and secondary lesions and ear lobe blood specimens had an average higher yield of T. pallidum DNA (83.0% vs. 28.2%, χ(2 = 247.6, p<0.001 and an average higher efficiency of full molecular typing (80.9% vs. 43.1%, χ(2 = 102.3, p<0.001 compared to plasma, whole blood, and cerebrospinal fluid. A pooled analysis of subtype distribution based on country location showed that 14d was the most common subtype, and subtype distribution varied across geographic areas. Subtype data associated with macrolide resistance and neurosyphilis were limited. CONCLUSIONS/SIGNIFICANCE: Primary lesion was a better specimen for obtaining T. pallidum DNA than blood. There was wide geographic variation in T. pallidum subtypes. More research is needed on the

  8. The Character of Influenza Virus the H7 Subtype and Alert to Novel Influenza Virus H7N9 Subtype Virus

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    NLP Indi Dharmayanti

    2013-08-01

    Full Text Available Influenza virus subtype H7 influenza viruses as well as other influenza virus geographically divided into two distinct genetic lineages, North American (H7N2, H7N3 or Eurasian (H7N7 and H7N3. Unlike the AI virus subtypes H5, since 1997 until now, all the infections caused by the H5 virus has Neuraminidase subtype 1 but H7 subtype of AI virus that transmitted successfully to humans have variety of Neuraminidase, so it seems compatible with H7 subtype. In poultry, the H7 subtype of AI virus typically causes mild symptoms, although there are also several outbreaks caused by this subtype virus, so it did not cause panic and active surveillance activities to identify this virus. It is very different from the H5N1 virus which caused many deaths and losses in poultry that infected with H5N1 virus so that it can be identified quickly. In April 2013, China reported a new AI virus is novel H7N9 which resulted in several people died. The world became aware of the H7N9 virus spreading to outside from China, it takes vigilance to be able to anticipate the disease, including Indonesia. Analysis of novel H7N9 virus showed that all genes of the virus is of avian origin, and the three other genes of the virus are reassorment from six internal genes of the AI virus A (H9N2 A/brambling/Beijing/16/2012, HA gene derived from A/duck/Zhejiang/12/2011 (H7N3, and NA genes thought to have come from A/wildbird/Korea/A14/2011 (H7N9. Epidemiological studies show that 77% of people infected by H7N9 have direct or indirect contact with animals including poultry when visiting or working in live poultry markets. Novel H7N9 virus was also found in pigeons, chickens, and environmental that have high genetic similarities with the novel H7N9 virus that infects humans. Until now (May 2013, a novel H7N9 virus has not been identified in Indonesia, so as a precaution and because the symptoms caused by the H7N9 virus is not visible (mild symptom in poultry so that the necessary actions

  9. Genetically Diverse Low Pathogenicity Avian Influenza A Virus Subtypes Co-Circulate among Poultry in Bangladesh

    Science.gov (United States)

    Gerloff, Nancy A.; Khan, Salah Uddin; Zanders, Natosha; Balish, Amanda; Haider, Najmul; Islam, Ausraful; Chowdhury, Sukanta; Rahman, Mahmudur Ziaur; Haque, Ainul; Hosseini, Parviez; Gurley, Emily S.; Luby, Stephen P.; Wentworth, David E.; Donis, Ruben O.; Sturm-Ramirez, Katharine; Davis, C. Todd

    2016-01-01

    Influenza virus surveillance, poultry outbreak investigations and genomic sequencing were assessed to understand the ecology and evolution of low pathogenicity avian influenza (LPAI) A viruses in Bangladesh from 2007 to 2013. We analyzed 506 avian specimens collected from poultry in live bird markets and backyard flocks to identify influenza A viruses. Virus isolation-positive specimens (n = 50) were subtyped and their coding-complete genomes were sequenced. The most frequently identified subtypes among LPAI isolates were H9N2, H11N3, H4N6, and H1N1. Less frequently detected subtypes included H1N3, H2N4, H3N2, H3N6, H3N8, H4N2, H5N2, H6N1, H6N7, and H7N9. Gene sequences were compared to publicly available sequences using phylogenetic inference approaches. Among the 14 subtypes identified, the majority of viral gene segments were most closely related to poultry or wild bird viruses commonly found in Southeast Asia, Europe, and/or northern Africa. LPAI subtypes were distributed over several geographic locations in Bangladesh, and surface and internal protein gene segments clustered phylogenetically with a diverse number of viral subtypes suggesting extensive reassortment among these LPAI viruses. H9N2 subtype viruses differed from other LPAI subtypes because genes from these viruses consistently clustered together, indicating this subtype is enzootic in Bangladesh. The H9N2 strains identified in Bangladesh were phylogenetically and antigenically related to previous human-derived H9N2 viruses detected in Bangladesh representing a potential source for human infection. In contrast, the circulating LPAI H5N2 and H7N9 viruses were both phylogenetically and antigenically unrelated to H5 viruses identified previously in humans in Bangladesh and H7N9 strains isolated from humans in China. In Bangladesh, domestic poultry sold in live bird markets carried a wide range of LPAI virus subtypes and a high diversity of genotypes. These findings, combined with the seven year

  10. Genetically Diverse Low Pathogenicity Avian Influenza A Virus Subtypes Co-Circulate among Poultry in Bangladesh.

    Directory of Open Access Journals (Sweden)

    Nancy A Gerloff

    Full Text Available Influenza virus surveillance, poultry outbreak investigations and genomic sequencing were assessed to understand the ecology and evolution of low pathogenicity avian influenza (LPAI A viruses in Bangladesh from 2007 to 2013. We analyzed 506 avian specimens collected from poultry in live bird markets and backyard flocks to identify influenza A viruses. Virus isolation-positive specimens (n = 50 were subtyped and their coding-complete genomes were sequenced. The most frequently identified subtypes among LPAI isolates were H9N2, H11N3, H4N6, and H1N1. Less frequently detected subtypes included H1N3, H2N4, H3N2, H3N6, H3N8, H4N2, H5N2, H6N1, H6N7, and H7N9. Gene sequences were compared to publicly available sequences using phylogenetic inference approaches. Among the 14 subtypes identified, the majority of viral gene segments were most closely related to poultry or wild bird viruses commonly found in Southeast Asia, Europe, and/or northern Africa. LPAI subtypes were distributed over several geographic locations in Bangladesh, and surface and internal protein gene segments clustered phylogenetically with a diverse number of viral subtypes suggesting extensive reassortment among these LPAI viruses. H9N2 subtype viruses differed from other LPAI subtypes because genes from these viruses consistently clustered together, indicating this subtype is enzootic in Bangladesh. The H9N2 strains identified in Bangladesh were phylogenetically and antigenically related to previous human-derived H9N2 viruses detected in Bangladesh representing a potential source for human infection. In contrast, the circulating LPAI H5N2 and H7N9 viruses were both phylogenetically and antigenically unrelated to H5 viruses identified previously in humans in Bangladesh and H7N9 strains isolated from humans in China. In Bangladesh, domestic poultry sold in live bird markets carried a wide range of LPAI virus subtypes and a high diversity of genotypes. These findings, combined with the

  11. Targeting the HA2 subunit of influenza A virus hemagglutinin via CD40L provides universal protection against diverse subtypes.

    Science.gov (United States)

    Fan, X; Hashem, A M; Chen, Z; Li, C; Doyle, T; Zhang, Y; Yi, Y; Farnsworth, A; Xu, K; Li, Z; He, R; Li, X; Wang, J

    2015-01-01

    The influenza viral hemagglutinin (HA) is comprised of two subunits. Current influenza vaccine predominantly induces neutralizing antibodies (Abs) against the HA1 subunit, which is constantly evolving in unpredictable fashion. The other subunit, HA2, however, is highly conserved but largely shielded by the HA head domain. Thus, enhancing immune response against HA2 could potentially elicit broadly inhibitory Abs. We generated a recombinant adenovirus (rAd) encoding secreted fusion protein, consisting of codon-optimized HA2 subunit of influenza A/California/7/2009(H1N1) virus fused to a trimerized form of murine CD40L, and determined its ability of inducing protective immunity upon intranasal administration. We found that mice immunized with this recombinant viral vaccine were completely protected against lethal challenge with divergent influenza A virus subtypes including H1N1, H3N2, and H9N2. Codon-optimization of HA2 as well as the use of CD40L as a targeting ligand/molecular adjuvant were indispensable to enhance HA2-specific mucosal IgA and serum IgG levels. Moreover, induction of HA2-specific T-cell responses was dependent on CD40L, as rAd secreting HA2 subunit without CD40L failed to induce any significant levels of T-cell cytokines. Finally, sera obtained from immunized mice were capable of inhibiting 13 subtypes of influenza A viruses in vitro. These results provide proof of concept for a prototype HA2-based universal influenza vaccine. PMID:25052763

  12. Controlling the Regional Identity of hPSC-Derived Neurons to Uncover Neuronal Subtype Specificity of Neurological Disease Phenotypes

    Directory of Open Access Journals (Sweden)

    Kent Imaizumi

    2015-12-01

    Full Text Available The CNS contains many diverse neuronal subtypes, and most neurological diseases target specific subtypes. However, the mechanism of neuronal subtype specificity of disease phenotypes remains elusive. Although in vitro disease models employing human pluripotent stem cells (PSCs have great potential to clarify the association of neuronal subtypes with disease, it is currently difficult to compare various PSC-derived subtypes. This is due to the limited number of subtypes whose induction is established, and different cultivation protocols for each subtype. Here, we report a culture system to control the regional identity of PSC-derived neurons along the anteroposterior (A-P and dorsoventral (D-V axes. This system was successfully used to obtain various neuronal subtypes based on the same protocol. Furthermore, we reproduced subtype-specific phenotypes of amyotrophic lateral sclerosis (ALS and Alzheimer’s disease (AD by comparing the obtained subtypes. Therefore, our culture system provides new opportunities for modeling neurological diseases with PSCs.

  13. Rapid semiautomated subtyping of influenza virus species during the 2009 swine origin influenza A H1N1 virus epidemic in Milwaukee, Wisconsin.

    Science.gov (United States)

    Bose, Michael E; Beck, Eric T; Ledeboer, Nate; Kehl, Sue C; Jurgens, Lisa A; Patitucci, Teresa; Witt, Lorraine; LaGue, Elizabeth; Darga, Patrick; He, Jie; Fan, Jiang; Kumar, Swati; Henrickson, Kelly J

    2009-09-01

    In the spring of 2009, a novel influenza A (H1N1) virus (swine origin influenza virus [S-OIV]) emerged and began causing a large outbreak of illness in Milwaukee, WI. Our group at the Midwest Respiratory Virus Program laboratory developed a semiautomated real-time multiplex reverse transcription-PCR assay (Seasonal), employing the NucliSENS easyMAG system (bioMérieux, Durham, NC) and a Raider thermocycler (HandyLab Inc., Ann Arbor, MI), that typed influenza A virus, influenza B virus, and respiratory syncytial virus (RSV) and subtyped influenza A virus into the currently circulating H1 and H3 subtypes, as well as a similar assay that identified H1 of S-OIV. The Seasonal and H1 S-OIV assays demonstrated analytical limits of detection of tissue culture infective doses/ml and 3 to 30 input copies, respectively. Testing of the analytical specificities revealed no cross-reactivity with 41 and 26 different common organisms and demonstrated outstanding reproducibility of results. Clinical testing showed 95% sensitivity for influenza A virus and influenza B virus and 95 and 97% specificity compared to tissue culture. Comparisons of results from other molecular tests showed levels of positive agreement with the Seasonal and H1 S-OIV assay results of 99 and 100% and levels of negative agreement of 98 and 100%. This study has demonstrated the use of a semiautomated system for sensitive, specific, and rapid detection of influenza A virus, influenza B virus, and RSV and subtyping of influenza A virus into human H1 and H3 and S-OIV strains. This assay/system performed well in clinical testing of regular seasonal influenza virus subtypes and was outstanding during the 2009 Milwaukee S-OIV infection outbreak. This recent outbreak of infection with a novel influenza A (H1N1) virus also demonstrates the importance of quickly distributing information on new agents and of having rapid influenza virus subtyping assays widely available for clinical and public health decisions. PMID

  14. Array-based DNA methylation profiling for breast cancer subtype discrimination.

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    Ilse Van der Auwera

    Full Text Available BACKGROUND: Abnormal DNA methylation is well established for breast cancer and contributes to its progression by silencing tumor suppressor genes. DNA methylation profiling platforms might provide an alternative approach to expression microarrays for accurate breast tumor subtyping. We sought to determine whether the distinction of the inflammatory breast cancer (IBC phenotype from the non-IBC phenotype by transcriptomics could be sustained by methylomics. METHODOLOGY/PRINCIPAL FINDINGS: We performed methylation profiling on a cohort of IBC (N = 19 and non-IBC (N = 43 samples using the Illumina Infinium Methylation Assay. These results were correlated with gene expression profiles. Methylation values allowed separation of breast tumor samples into high and low methylation groups. This separation was significantly related to DNMT3B mRNA levels. The high methylation group was enriched for breast tumor samples from patients with distant metastasis and poor prognosis, as predicted by the 70-gene prognostic signature. Furthermore, this tumor group tended to be enriched for IBC samples (54% vs. 24% and samples with a high genomic grade index (67% vs. 38%. A set of 16 CpG loci (14 genes correctly classified 97% of samples into the low or high methylation group. Differentially methylated genes appeared to be mainly related to focal adhesion, cytokine-cytokine receptor interactions, Wnt signaling pathway, chemokine signaling pathways and metabolic processes. Comparison of IBC with non-IBC led to the identification of only four differentially methylated genes (TJP3, MOGAT2, NTSR2 and AGT. A significant correlation between methylation values and gene expression was shown for 4,981 of 6,605 (75% genes. CONCLUSIONS/SIGNIFICANCE: A subset of clinical samples of breast cancer was characterized by high methylation levels, which coincided with increased DNMT3B expression. Furthermore, an association was observed with molecular signatures indicative of

  15. Association of adiposity, dysmetabolisms, and inflammation with aggressive breast cancer subtypes: a cross-sectional study.

    Science.gov (United States)

    Agresti, Roberto; Meneghini, Elisabetta; Baili, Paolo; Minicozzi, Pamela; Turco, Alberto; Cavallo, Ilaria; Funaro, Francesco; Amash, Hade; Berrino, Franco; Tagliabue, Elda; Sant, Milena

    2016-05-01

    Obesity and metabolic syndrome are risk and prognostic factors for breast cancer (BC) and are associated with chronic inflammation. We investigated the association between distinct BC subtypes and markers of adiposity, dysmetabolisms, and inflammation. We analyzed 1779 patients with primary invasive BC treated at a single institution, for whom anthropometric and clinical-pathological data were archived. BC subtypes were classified by immunohistochemical staining of ER, PR, HER2, and Ki67, and their relations with the study markers were assessed by multinomial logistic regression. Adjusted odds ratios (ORs) and 95 % confidence intervals (CIs) were calculated taking luminal A as reference. All subtypes more aggressive than luminal A were significantly more frequent in younger (<45 years) than older women. Before menopause, luminal B HER2-negative tumors were positively associated with large waist (OR 2.55, 95 % CI 1.53-4.24) and insulin resistance (OR 1.90, 95 % CI 1.05-3.41); luminal B HER2-positive tumors with large waist (OR 2.11, 95 % CI 1.03-4.35) and triple-negative tumors with overweight (OR 3.04, 95 % CI 1.43-6.43) and high C-reactive protein (p trend = 0.026). In postmenopausal women aged <65, luminal B HER2-negative (OR 1.94, 95 % CI 1.16-3.24) and luminal B HER2-positive tumors (OR 2.48, 95 % CI 1.16-5.27) were positively related with metabolic syndrome. Dysmetabolisms and inflammation may be related to different BC subtypes. Before menopause, triple-negative cancers were related to obesity and chronic inflammation, and aggressive luminal subtypes to abdominal adiposity. After menopause, in women aged <65 these latter subtypes were related to metabolic syndrome. Control of adiposity and dysmetabolism can reduce the risk of aggressive BC subtypes, improving the prognosis. PMID:27117160

  16. Stem cell-like gene expression in ovarian cancer predicts type II subtype and prognosis.

    Directory of Open Access Journals (Sweden)

    Matthew Schwede

    Full Text Available Although ovarian cancer is often initially chemotherapy-sensitive, the vast majority of tumors eventually relapse and patients die of increasingly aggressive disease. Cancer stem cells are believed to have properties that allow them to survive therapy and may drive recurrent tumor growth. Cancer stem cells or cancer-initiating cells are a rare cell population and difficult to isolate experimentally. Genes that are expressed by stem cells may characterize a subset of less differentiated tumors and aid in prognostic classification of ovarian cancer. The purpose of this study was the genomic identification and characterization of a subtype of ovarian cancer that has stem cell-like gene expression. Using human and mouse gene signatures of embryonic, adult, or cancer stem cells, we performed an unsupervised bipartition class discovery on expression profiles from 145 serous ovarian tumors to identify a stem-like and more differentiated subgroup. Subtypes were reproducible and were further characterized in four independent, heterogeneous ovarian cancer datasets. We identified a stem-like subtype characterized by a 51-gene signature, which is significantly enriched in tumors with properties of Type II ovarian cancer; high grade, serous tumors, and poor survival. Conversely, the differentiated tumors share properties with Type I, including lower grade and mixed histological subtypes. The stem cell-like signature was prognostic within high-stage serous ovarian cancer, classifying a small subset of high-stage tumors with better prognosis, in the differentiated subtype. In multivariate models that adjusted for common clinical factors (including grade, stage, age, the subtype classification was still a significant predictor of relapse. The prognostic stem-like gene signature yields new insights into prognostic differences in ovarian cancer, provides a genomic context for defining Type I/II subtypes, and potential gene targets which following further

  17. Validity of DSM-IV attention deficit/hyperactivity disorder symptom dimensions and subtypes.

    Science.gov (United States)

    Willcutt, Erik G; Nigg, Joel T; Pennington, Bruce F; Solanto, Mary V; Rohde, Luis A; Tannock, Rosemary; Loo, Sandra K; Carlson, Caryn L; McBurnett, Keith; Lahey, Benjamin B

    2012-11-01

    Diagnostic and Statistical Manual of Mental Disorders, 4th Edition (DSM-IV) criteria for attention deficit/hyperactivity disorder (ADHD) specify two dimensions of inattention and hyperactivity-impulsivity symptoms that are used to define three nominal subtypes: predominantly hyperactive-impulsive type (ADHD-H), predominantly inattentive type (ADHD-I), and combined type (ADHD-C). To aid decision making for DSM-5 and other future diagnostic systems, a comprehensive literature review and meta-analysis of 546 studies was completed to evaluate the validity of the DSM-IV model of ADHD. Results indicated that DSM-IV criteria identify individuals with significant and persistent impairment in social, academic, occupational, and adaptive functioning when intelligence, demographic factors, and concurrent psychopathology are controlled. Available data overwhelmingly support the concurrent, predictive, and discriminant validity of the distinction between inattention and hyperactivity-impulsivity symptoms, and indicate that nearly all differences among the nominal subtypes are consistent with the relative levels of inattention and hyperactivity-impulsivity symptoms that define the subtypes. In contrast, the DSM-IV subtype model is compromised by weak evidence for the validity of ADHD-H after first grade, minimal support for the distinction between ADHD-I and ADHD-C in studies of etiological influences, academic and cognitive functioning, and treatment response, and the marked longitudinal instability of all three subtypes. Overall, we conclude that the DSM-IV ADHD subtypes provide a convenient clinical shorthand to describe the functional and behavioral correlates of current levels of inattention and hyperactivity-impulsivity symptoms, but do not identify discrete subgroups with sufficient long-term stability to justify the classification of distinct forms of the disorder. Empirical support is stronger for an alternative model that would replace the subtypes with dimensional

  18. Combining miRNA and mRNA Expression Profiles in Wilms Tumor Subtypes

    Science.gov (United States)

    Ludwig, Nicole; Werner, Tamara V.; Backes, Christina; Trampert, Patrick; Gessler, Manfred; Keller, Andreas; Lenhof, Hans-Peter; Graf, Norbert; Meese, Eckart

    2016-01-01

    Wilms tumor (WT) is the most common childhood renal cancer. Recent findings of mutations in microRNA (miRNA) processing proteins suggest a pivotal role of miRNAs in WT genesis. We performed miRNA expression profiling of 36 WTs of different subtypes and four normal kidney tissues using microarrays. Additionally, we determined the gene expression profile of 28 of these tumors to identify potentially correlated target genes and affected pathways. We identified 85 miRNAs and 2107 messenger RNAs (mRNA) differentially expressed in blastemal WT, and 266 miRNAs and 1267 mRNAs differentially expressed in regressive subtype. The hierarchical clustering of the samples, using either the miRNA or mRNA profile, showed the clear separation of WT from normal kidney samples, but the miRNA pattern yielded better separation of WT subtypes. A correlation analysis of the deregulated miRNA and mRNAs identified 13,026 miRNA/mRNA pairs with inversely correlated expression, of which 2844 are potential interactions of miRNA and their predicted mRNA targets. We found significant upregulation of miRNAs-183, -301a/b and -335 for the blastemal subtype, and miRNAs-181b, -223 and -630 for the regressive subtype. We found marked deregulation of miRNAs regulating epithelial to mesenchymal transition, especially in the blastemal subtype, and miRNAs influencing chemosensitivity, especially in regressive subtypes. Further research is needed to assess the influence of preoperative chemotherapy and tumor infiltrating lymphocytes on the miRNA and mRNA patterns in WT. PMID:27043538

  19. [Real-time PCR Detection Method for the Reston Subtype of the Ebola Virus].

    Science.gov (United States)

    Xu, Lili; Bao, Linlin; Gu, Songzhi; Qin, Chuan

    2015-05-01

    We aimed to develop a real-time polymerase chain reaction (PCR) detection method for the Reston subtype of the Ebola virus. The NP gene of the Reston subtype of the Ebola virus was selected as the detection object. Sequences of different subtypes of Ebola viruses were aligned using Clustal W software. The most unique and conserved regions of the Reston subtype of the Ebola virus were recruited as candidate sequences for specific primers. Primer Express and Primer Premier 5. 0 software were used to filter the optimal pair of primers for detection. Real-time PCR was carried out using optimized parameters and positive DNA prepared by serial (tenfold) dilution of a recombinant plasmid and by plotting a standard curve. In addition, the reproducibility, accuracy, and specificity of the assay were tested. Results showed that the sensitivity of detection of the Reston subtype of the Ebola virus by real-time PCR could reached 10(2) copies/microL. The linear relationship (R2) reached 0.997, the slope of the standard curve was -0.3101, and amplification efficiency was 110.145%. A sharp and narrow melting peak appeared at 79.94 degrees C for all standards in different dilutions. In conclusion, a fast and sensitive real-time PCR detection system for the Reston subtype of the Ebola virus was developed. This system could be used as a supplementary diagnostic and monitoring approach for basic and clinical studies on the Reston subtype of the Ebola virus. The detection system does not require expensive technology or specialist operators. PMID:26470534

  20. Diversity of Group I and II Clostridium botulinum Strains from France Including Recently Identified Subtypes

    Science.gov (United States)

    Mazuet, Christelle; Legeay, Christine; Sautereau, Jean; Ma, Laurence; Bouchier, Christiane; Bouvet, Philippe; Popoff, Michel R.

    2016-01-01

    In France, human botulism is mainly food-borne intoxication, whereas infant botulism is rare. A total of 99 group I and II Clostridium botulinum strains including 59 type A (12 historical isolates [1947–1961], 43 from France [1986–2013], 3 from other countries, and 1 collection strain), 31 type B (3 historical, 23 recent isolates, 4 from other countries, and 1 collection strain), and 9 type E (5 historical, 3 isolates, and 1 collection strain) were investigated by botulinum locus gene sequencing and multilocus sequence typing analysis. Historical C. botulinum A strains mainly belonged to subtype A1 and sequence type (ST) 1, whereas recent strains exhibited a wide genetic diversity: subtype A1 in orfX or ha locus, A1(B), A1(F), A2, A2b2, A5(B2′) A5(B3′), as well as the recently identified A7 and A8 subtypes, and were distributed into 25 STs. Clostridium botulinum A1(B) was the most frequent subtype from food-borne botulism and food. Group I C. botulinum type B in France were mainly subtype B2 (14 out of 20 historical and recent strains) and were divided into 19 STs. Food-borne botulism resulting from ham consumption during the recent period was due to group II C. botulinum B4. Type E botulism is rare in France, 5 historical and 1 recent strains were subtype E3. A subtype E12 was recently identified from an unusual ham contamination. Clostridium botulinum strains from human botulism in France showed a wide genetic diversity and seems to result not from a single evolutionary lineage but from multiple and independent genetic rearrangements. PMID:27189984

  1. Magnetismo Molecular (Molecular Magentism)

    Energy Technology Data Exchange (ETDEWEB)

    Reis, Mario S [Universidade Federal Fluminense, Brasil; Moreira Dos Santos, Antonio F [ORNL

    2010-07-01

    The new synthesis processes in chemistry open a new world of research, new and surprising materials never before found in nature can now be synthesized and, as a wonderful result, observed a series of physical phenomena never before imagined. Among these are many new materials the molecular magnets, the subject of this book and magnetic properties that are often reflections of the quantum behavior of these materials. Aside from the wonderful experience of exploring something new, the theoretical models that describe the behavior these magnetic materials are, in most cases, soluble analytically, which allows us to know in detail the physical mechanisms governing these materials. Still, the academic interest in parallel this subject, these materials have a number of properties that are promising to be used in technological devices, such as in computers quantum magnetic recording, magnetocaloric effect, spintronics and many other devices. This volume will journey through the world of molecular magnets, from the structural description of these materials to state of the art research.

  2. eMBI: Boosting Gene Expression-based Clustering for Cancer Subtypes.

    Science.gov (United States)

    Chang, Zheng; Wang, Zhenjia; Ashby, Cody; Zhou, Chuan; Li, Guojun; Zhang, Shuzhong; Huang, Xiuzhen

    2014-01-01

    Identifying clinically relevant subtypes of a cancer using gene expression data is a challenging and important problem in medicine, and is a necessary premise to provide specific and efficient treatments for patients of different subtypes. Matrix factorization provides a solution by finding checker-board patterns in the matrices of gene expression data. In the context of gene expression profiles of cancer patients, these checkerboard patterns correspond to genes that are up- or down-regulated in patients with particular cancer subtypes. Recently, a new matrix factorization framework for biclustering called Maximum Block Improvement (MBI) is proposed; however, it still suffers several problems when applied to cancer gene expression data analysis. In this study, we developed many effective strategies to improve MBI and designed a new program called enhanced MBI (eMBI), which is more effective and efficient to identify cancer subtypes. Our tests on several gene expression profiling datasets of cancer patients consistently indicate that eMBI achieves significant improvements in comparison with MBI, in terms of cancer subtype prediction accuracy, robustness, and running time. In addition, the performance of eMBI is much better than another widely used matrix factorization method called nonnegative matrix factorization (NMF) and the method of hierarchical clustering, which is often the first choice of clinical analysts in practice. PMID:25374455

  3. Review of renal cell carcinoma and its common subtypes in radiology.

    Science.gov (United States)

    Low, Gavin; Huang, Guan; Fu, Winnie; Moloo, Zaahir; Girgis, Safwat

    2016-05-28

    Representing 2%-3% of adult cancers, renal cell carcinoma (RCC) accounts for 90% of renal malignancies and is the most lethal neoplasm of the urologic system. Over the last 65 years, the incidence of RCC has increased at a rate of 2% per year. The increased incidence is at least partly due to improved tumor detection secondary to greater availability of high-resolution cross-sectional imaging modalities over the last few decades. Most RCCs are asymptomatic at discovery and are detected as unexpected findings on imaging performed for unrelated clinical indications. The 2004 World Health Organization Classification of adult renal tumors stratifies RCC into several distinct histologic subtypes of which clear cell, papillary and chromophobe tumors account for 70%, 10%-15%, and 5%, respectively. Knowledge of the RCC subtype is important because the various subtypes are associated with different biologic behavior, prognosis and treatment options. Furthermore, the common RCC subtypes can often be discriminated non-invasively based on gross morphologic imaging appearances, signal intensity on T2-weighted magnetic resonance images, and the degree of tumor enhancement on dynamic contrast-enhanced computed tomography or magnetic resonance imaging examinations. In this article, we review the incidence and survival data, risk factors, clinical and biochemical findings, imaging findings, staging, differential diagnosis, management options and post-treatment follow-up of RCC, with attention focused on the common subtypes. PMID:27247714

  4. The identification of family subtype based on the assessment of subclinical levels of psychosis in relatives

    Directory of Open Access Journals (Sweden)

    Derks Eske M

    2012-07-01

    Full Text Available Abstract Background Schizophrenia is a complex psychiatric disorder characterized by high phenotypic heterogeneity. Previous studies have distinguished between familial and sporadic forms of schizophrenia and have suggested clinical differentiation between patients and relatives from sporadic and multiplex families. We will introduce a more refined method to distinguish between family subtypes based on psychosis dimension profiles in the relatives of schizophrenia patients. Methods Positive, negative, disorganization, mania, and depression scores were assessed in 1,392 relatives. Mixed Model Latent Class Analysis was used to identify family subtypes. A family subtype is a relatively homogeneous group of families with similar symptom profiles in the relatives in these families. Next, we investigated in 616 schizophrenia patients whether family subtype was associated with symptom profiles, IQ, cannabis dependence/abuse, or age of onset of psychosis. Results Based on the data of relatives, we identified two different family types: “healthy” and “at risk for psychiatric disorder”. Patients from at risk families obtained higher positive scores compared to patients from healthy families (Wald(1 = 6.6293, p = 0.010. No significant differences were found in any of the remaining variables. Conclusions Our findings confirm the existence of high-risk families and although we did not establish an etiological basis for the distinction between family types, genetic studies might reveal whether family subtype is associated with genetic heterogeneity.

  5. Adult neurogenesis and specific replacement of interneuron subtypes in the mouse main olfactory bulb

    Directory of Open Access Journals (Sweden)

    LaRocca Greg

    2007-11-01

    Full Text Available Abstract Background New neurons are generated in the adult brain from stem cells found in the subventricular zone (SVZ. These cells proliferate in the SVZ, generating neuroblasts which then migrate to the main olfactory bulb (MOB, ending their migration in the glomerular layer (GLL and the granule cell layer (GCL of the MOB. Neuronal populations in these layers undergo turnover throughout life, but whether all neuronal subtypes found in these areas are replaced and when neurons begin to express subtype-specific markers is not known. Results Here we use BrdU injections and immunohistochemistry against (calretinin, calbindin, N-copein, tyrosine hydroxylase and GABA and show that adult-generated neurons express markers of all major subtypes of neurons in the GLL and GCL. Moreover, the fractions of new neurons that express subtype-specific markers at 40 and 75 days post BrdU injection are very similar to the fractions of all neurons expressing these markers. We also show that many neurons in the glomerular layer do not express NeuN, but are readily and specifically labeled by the fluorescent nissl stain Neurotrace. Conclusion The expression of neuronal subtype-specific markers by new neurons in the GLL and GCL changes rapidly during the period from 14–40 days after BrdU injection before reaching adult levels. This period may represent a critical window for cell fate specification similar to that observed for neuronal survival.

  6. [Definition of inflammatory subtypes of chronic rhinosinusitis with nasal polyp and asthma].

    Science.gov (United States)

    Wu, Dawei; Zhang, Min; Song, Qian

    2015-08-01

    Chronic rhinosinusitis with nasal polyps (CRSwNP) and asthma is a common clinical refractory airway disease. Comprehensive treatment of nasal endoscopic surgery including nasal endoscopic surgery and medication, which can significantly improve nose-pulmonary symptoms and make sinusitis and asthma easier to be controlled by medication, has certain superiority. But the existence of disease heterogeneity of CRSwNP with asthma causes different reactions to the current treatment, which manifests as parts of polyps and asthma easy to recur and difficult to control. According to the research recently, the study of the heterogeneity of airway diseases, for example endotype, is a hot area of research. Endotype is a subtype of a condition, which is defined by a distinct functional or pathobiological mechanism. This is distinct from a phenotype, which is any observable characteristic or trait of a disease. Different Inflammatory subtypes often represent different pathophysiology and even different pathogenesis. The concept of inflammatory subtypes of airway diseases provides a new perspective for studies of airway diseases of endotype and the mechanism of combined airway diseases. This review summarizes recent advances in the clinical characterization and treatment of the CRSwNP with asthma. On this basis, we analyze and summarize the heterogeneity of CRSwNP and asthma separately from the perspective of inflammatory subtypes. Then according to the concept of the combined airway diseases and the common pathogenesis, we put forward the definition of inflammatory subtypes of the CRSwNP with asthma and preliminarily discuss the method of the definition. PMID:26665469

  7. Hodgkin lymphoma in Pakistan: an analysis of subtypes and their correlation with Epstein Barr virus.

    Science.gov (United States)

    Fatima, Samia; Ahmed, Rashida; Ahmed, Arsalan

    2011-01-01

    The epidemiology of Hodgkin lymphoma (HL) shows a wide geographic variation with regard to age, gender, histological subtypes and their association with Epstein-Barr virus. The proportion of EBV positive cases appears higher in developing than in developed countries. EBV is a common infection in Pakistan due to poor socioeconomic conditions, but reports regarding HL subtypes have been rather selective. Our aims were to establish the relative frequencies of the five subtypes of Hodgkin lymphoma, to determine their associations with Epstein-Barr virus, and finally to establish whether such association follows patterns seen in developing or developed countries. Among 100 cases, the male: female ratio was 4.5:1, with an age range of 4-82 years and an average of 26.6 years. Similar to the subtype distribution in developing countries, mixed cellularity was the commonest 57%, followed by nodular sclerosis 35%, lymphocyte rich 6% and nodular lymphocyte predominant 2%. EBV-LMP1 staining was demonstrated in 41/57 (71%) of the mixed cellularity and the 19/35 (54.2%) of nodular sclerosis subtypes. All 6 cases of lymphocyte rich and 2 cases of nodular lymphocyte predominant were negative for EBV-LMP 1. Speculation about prognostic effects of EBV infection on the course of HL are tempting. Thus the EBV-positive HL could in the future prove to be an excellent candidate for targeted cellular immunotherapy. PMID:22126469

  8. Phylogenetic analysis of Neuraminidase gene of avian influenza H5N1 subtype detected in Iran in 1390(2011)

    OpenAIRE

    E Kord; Shoushtari, A.; H Ghadakchi; MOHAMMADI, R.; A ,Hadinia

    2013-01-01

    Abstract Background & aim: Among the various subtypes of avian influenza viruses, an H5N1 subtype virus with high pathogenicity is of great importance. The aim of this study was to determine the Phylogenetic analysis of neuraminidase gene of avian influenza virus subtype of the H5N1 in Iran in 1390. Methods: In this experimental study, two swab samples from chickens with suspected symptoms of avian influenza were tested by the World Health Organization recommendation. The neuraminidase...

  9. Usefulness of KL-6 in the subtyping of intraductal papillary mucinous neoplasia of the pancreas, including carcinoma, dysplasia, and hyperplasia.

    Science.gov (United States)

    Ohtsuki, Yuji; Watanabe, Ryohei; Kimura, Masashi; Nomura, Katsuyoshi; Maeda, Tomoharu; Kito, Katsumi; Takeji, Miyuki; Lee, Gang-Hong; Furihata, Mutsuo

    2015-06-01

    KL-6 is known as a useful serum biomarker of the disease activity in interstitial pneumonias. We investigated its usefulness as a biomarker for subtyping intraductal papillary mucinous neoplasms (IPMNs) of the pancreas. IPMNs are generally divided into 4 subtypes, namely pancreatobiliary (PB), intestinal (INT), gastric (GS), and oncocytic (ONC). Aside from the KL-6 antibody, the MUC1, MUC2, MUC5AC, MUC6, and MIB-1 antibodies were also examined. Eighteen IPMN cases were examined, including 12 cases of intraductal papillary mucinous carcinomas (IPMCs) simultaneously associated with dysplasia (IPMDs) and hyperplasia (IPMHs) and 6 IPMD cases with IPMH. KL-6 antibody was positive in the 8 IPMC cases, corresponding to a MUC2-negative PB subtype, but negative in 4 IPMC cases, corresponding to the INT subtype, which is positive for MUC2. IPMD of moderate-to-severe degree positively stained for the KL-6 antibody in the IPMC cases of the PB subtype but not in those of the INT subtype. The IPMH cases were mostly negative for KL-6, similar to the mild IPMD cases. In the 6 cases of mild IPMD and/or IPMH, KL-6 and MUC2 expressions were mostly negative. In conclusion, the KL-6 antibody is immunohistochemically a good biomarker of the PB subtype of IPMC, but not the INT subtype. Identifying IPMN subtypes based on KL-6 stainability would be useful. Clinicopathological studies with more IPMC cases might be needed for further progress in this field of study. PMID:24908068

  10. Connectivity Analysis and Feature Classification in Attention Deficit Hyperactivity Disorder Sub-Types: A Task Functional Magnetic Resonance Imaging Study.

    Science.gov (United States)

    Park, Bo-Yong; Kim, Mansu; Seo, Jongbum; Lee, Jong-Min; Park, Hyunjin

    2016-05-01

    Attention deficit hyperactivity disorder (ADHD) is a pervasive neuropsychiatric disorder. Patients with different ADHD subtypes show different behaviors under different stimuli and thus might require differential approaches to treatment. This study explores connectivity differences between ADHD subtypes and attempts to classify these subtypes based on neuroimaging features. A total of 34 patients (13 ADHD-IA and 21 ADHD-C subtypes) underwent functional magnetic resonance imaging (fMRI) with six task paradigms. Connectivity differences between ADHD subtypes were assessed for the whole brain in each task paradigm. Connectivity measures of the identified regions were used as features for the support vector machine classifier to distinguish between ADHD subtypes. The effectiveness of connectivity measures of the regions were tested by predicting ADHD-related Diagnostic and Statistical Manual of Mental Disorders (DSM) scores. Significant connectivity differences between ADHD subtypes were identified mainly in the frontal, cingulate, and parietal cortices and partially in the temporal, occipital cortices and cerebellum. Classifier accuracy for distinguishing between ADHD subtypes was 91.18 % for both gambling punishment and emotion task paradigms. Linear prediction under the two task paradigms showed significant correlation with DSM hyperactive/impulsive score. Our study identified important brain regions from connectivity analysis based on an fMRI paradigm using gambling punishment and emotion task paradigms. The regions and associated connectivity measures could serve as features to distinguish between ADHD subtypes. PMID:26602102

  11. Prognostic Significance of Subtype Classification for Short- and Long-Term Survival in Breast Cancer: Survival Time Holds the Key

    OpenAIRE

    Ambs, Stefan

    2010-01-01

    Stefan Ambs provides a perspective on a recent research article by Paul Pharoah and colleagues that evaluated the prognostic significance of immunohistochemical subtype classification in early breast cancer.

  12. A research on the method of axillary osmidrosis treatment using minimally invasive resection of apocrine sweat gland and thick skin flap in armpit wrinkle%腋窝微创切除大汗腺及全厚皮瓣法治疗腋臭

    Institute of Scientific and Technical Information of China (English)

    张郑; 张汝敏

    2012-01-01

    Objective To study the curative effect of axillary osmidrosis,that incision in armpit wrinkle,orthoptic cut off the gland to thick skin flap.Methods Collected double-sided axillary osmidrosis 163 patients,all of them accepted armpit wrinkle incision,the scope of surgical operation super the armpit hair distribute 1 cm,swelling anaesthesia,orthoptic cut off the armpit organization 5 mm under skin included apocrine sweat gland,kept the operation scope to vessel net flap under skin.Hematischesis thoroughly used a double pole electricity hemostasis,kept drainage after operation,bandaged in pressure,took out sutures after 9 days.The foul smell standard referenced the Tung-Chain standard of axillary osmidrosis curative effect evaluation.Results Three hundred and twenty armpits (98.16%,320/326) were cure,6 armpits (1.84%,6/326) were excellence.The armpit hair variety:obvious reduce 322 armpits (98.77%,322/326),general reduce 4 armpits (1.23%,4/326).Perspire condition:obvious reduce 324 armpits (99.39%,324/326),improve but no obvious reduce 2 armpits ( 0.61%,2/326).The average surgical operation recovery time was about 9 days.Complication:necrosis on the edge of the skin was 8 armpits,scar formation on the incision was 3 armpits,hematoma was 1 armpit,shoulder joint limitation of activity was 0 armpit.Conclusion The method of axillary osmidrosis treatment useing thick skin flap in armpit wrinkle,which has extermination foundation of anatomy and pathology,which can cause axillary osmidrosis,this operation is simple,curative effect is credible,the wound is small,complication is little etc,utmost matching the principle of orthopedic surgery,worthy of clinical application.%目的 探讨腋窝皱襞小切口直视切除大汗腺及全厚皮瓣法治疗腋臭的疗效.方法 收集双侧腋臭患者163例,均采用腋窝皱襞切口,手术范围超腋毛分布1 cm,肿胀麻醉,直视下剪除包含大汗腺的腋部皮下组织5mm左右,直至腋窝手术范围皮肤

  13. Classification of Breast Cancer Subtypes by combining Gene Expression and DNA Methylation Data

    DEFF Research Database (Denmark)

    List, Markus; Hauschild, Anne-Christin; Tan, Qihua;

    2014-01-01

    Selecting the most promising treatment strategy for breast cancer crucially depends on determining the correct subtype. In recent years, gene expression profiling has been investigated as an alternative to histochemical methods. Since databases like TCGA provide easy and unrestricted access to gene......-20% and classification error of 1-50%, depending on breast cancer subtype and model. The gene expression model was clearly superior to the methylation model, which was also reflected in the combined model, which mainly selected features from gene expression data. However, the methylation model was able to identify...... unique features not considered as relevant by the gene expression model, which might provide deeper insights into breast cancer subtype differentiation on an epigenetic level....

  14. Glycosyltransferase Gene Expression Profiles Classify Cancer Types and Propose Prognostic Subtypes

    Science.gov (United States)

    Ashkani, Jahanshah; Naidoo, Kevin J.

    2016-05-01

    Aberrant glycosylation in tumours stem from altered glycosyltransferase (GT) gene expression but can the expression profiles of these signature genes be used to classify cancer types and lead to cancer subtype discovery? The differential structural changes to cellular glycan structures are predominantly regulated by the expression patterns of GT genes and are a hallmark of neoplastic cell metamorphoses. We found that the expression of 210 GT genes taken from 1893 cancer patient samples in The Cancer Genome Atlas (TCGA) microarray data are able to classify six cancers; breast, ovarian, glioblastoma, kidney, colon and lung. The GT gene expression profiles are used to develop cancer classifiers and propose subtypes. The subclassification of breast cancer solid tumour samples illustrates the discovery of subgroups from GT genes that match well against basal-like and HER2-enriched subtypes and correlates to clinical, mutation and survival data. This cancer type glycosyltransferase gene signature finding provides foundational evidence for the centrality of glycosylation in cancer.

  15. Phylodynamic and phylogeographic patterns of the HIV type 1 subtype F1 parenteral epidemic in Romania.

    Science.gov (United States)

    Mbisa, Jean L; Hué, Stéphane; Buckton, Andrew J; Myers, Richard E; Duiculescu, Dan; Ene, Luminita; Oprea, Cristiana; Tardei, Gratiela; Rugina, Sorin; Mardarescu, Mariana; Floch, Corinne; Notheis, Gundula; Zöhrer, Bettina; Cane, Patricia A; Pillay, Deenan

    2012-09-01

    In the late 1980s an HIV-1 epidemic emerged in Romania that was dominated by subtype F1. The main route of infection is believed to be parenteral transmission in children. We sequenced partial pol coding regions of 70 subtype F1 samples from children and adolescents from the PENTA-EPPICC network of which 67 were from Romania. Phylogenetic reconstruction using the sequences and other publically available global subtype F sequences showed that 79% of Romanian F1 sequences formed a statistically robust monophyletic cluster. The monophyletic cluster was epidemiologically linked to parenteral transmission in children. Coalescent-based analysis dated the origins of the parenteral epidemic to 1983 [1981-1987; 95% HPD]. The analysis also shows that the epidemic's effective population size has remained fairly constant since the early 1990s suggesting limited onward spread of the virus within the population. Furthermore, phylogeographic analysis suggests that the root location of the parenteral epidemic was Bucharest. PMID:22251065

  16. Subtype and sequence analysis of HIV-1 strains in Heilongjiang Province

    Institute of Scientific and Technical Information of China (English)

    WANG Fu-xiang; ZHOU Hui; LING Hong; ZHOU Hai-zhou; LIU Wei-hua; SHAO Yi-ming; ZHOU Jin

    2007-01-01

    Background Human immunodeficiency virus (HIV-1) is divided into two types, HIV-1 (groups M, N and O) and HIV-2.Heilongjiang Province located in the northeast of China, and the feature of the subtype distribution and sequence characteristics of HIV-1 strains prevalent in Heilongjiang Province is still uncertain. The aim of this study was to investigate the subtype distribution and genetic characteristics of HIV-1 strains in one hospital in Heilongjiang Province.Methods HIV-1 env gene was amplified by nested-PCR from peripheral blood mononuclear cells (PBMCs) obtained from 19 HIV-1 seropositive individuals in Heilongjiang Province. The C2-V3 region was sequenced. Aligned the nucleotide sequence of 19 samples with CLUSTAL W (BioEdit) software, results were acquired and used for phylogenetic tree analysis after artificial adjustment. Reference sequence, downloaded from Los Alamos HIV Sequence Database,was used to identify the subtype of obtained sequence. Genetic distance between sequences was assessed using the software MEGA 3.1 Kimura 2-parameter, and the Phylogenetic tree was reestablished with Neighbor-Joining method.Results Phylogenetic tree analysis showed that 19 Heilongjiang strains clustered closely to subtype B strain from Thailand and were far from other international subtype reference strains. Statistical test showed no significant discrepancy between the genetic distance of interclass and intra-class (P>0.05). The analysis of V3 loop amino sequence of 19 Heilongjiang B strains revealed that V3 tip motif of 10 samples (52.63%) was GPGQ, and of 4 samples (21.53%) was GPGR.Conclusions The subtype of 19 HIV-1 seropositive individuals in Heilongjiang Province is B', and it is introduced from He'nan Province. V3 tip motifs of the HIV-1 isolates are mainly GPGQ and GPGR.

  17. Working memory deficits in adults with ADHD: is there evidence for subtype differences?

    Directory of Open Access Journals (Sweden)

    Medoff Deborah R

    2006-12-01

    Full Text Available Abstract Background Working memory performance is important for maintaining functioning in cognitive, academic and social activities. Previous research suggests there are prevalent working memory deficits in children with attention deficit hyperactivity disorder (ADHD. There is now a growing body of literature characterizing working memory functioning according to ADHD subtypes in children. The expression of working memory deficits in adults with ADHD and how they vary according to subtype, however, remains to be more fully documented. Methods This study assessed differences in working memory functioning between Normal Control (NC adults (N = 18; patients with ADHD, Combined (ADHD-CT Type ADHD (N = 17; and ADHD, Inattentive (ADHD-IA Type (N = 16 using subtests from the Wechsler Adult Intelligence Scale-III and Wechsler Memory Scale-III and the Paced Auditory Serial Addition Task (PASAT. Results The ADHD groups displayed significant weaknesses in contrast to the NC group on working memory tests requiring rapid processing and active stimulus manipulation. This included the Letter-Number-Sequencing test of the Wechsler scales, PASAT omission errors and the longest sequence of consecutive correct answers on the PASAT. No overall ADHD group subtype differences emerged; however differences between the ADHD groups and the NC group varied depending on the measure and the gender of the participants. Gender differences in performance were evident on some measures of working memory, regardless of group, with males performing better than females. Conclusion In general, the data support a dimensional interpretation of working memory deficits experienced by the ADHD-CT and ADHD-IA subtypes, rather than an absolute difference between subtypes. Future studies should test the effects of processing speed and load on subtype performance and how those variables interact with gender in adults with ADHD.

  18. Frequency of telomerase reverse transcripter promoter mutations in desmoplastic melanoma subtypes: analyses of 76 cases.

    Science.gov (United States)

    Yang, Shi; Leone, Dominick; Frydenlund, Noah; Hoang, Mai; Deng, April; Hernandez-Perez, Marier; Biswas, Asok; Singh, Rajendra; Yaar, Ron; Mahalingam, Meera

    2016-08-01

    Estimates of the frequency of telomerase reverse transcripter (TERT) mutations in desmoplastic melanoma (DM) are limited. DM is categorized into subtypes, pure and mixed, differing in prognosis, suggesting genetic heterogeneity. Given this, our aims were to determine the incidence of TERT promoter mutations in DM subtypes and to evaluate its relationship with established histopathologic prognosticators, BRAF and RETp status, and neurofibromin protein expression. Of the archival annotated samples retrieved, 76 cases of DM (48 pure and 28 mixed) fulfilled the criteria for inclusion. PCR amplification of the TERT promoter region was performed on DNA extracted from formalin-fixed paraffin-embedded tissue using primers5'-GCCGATTCGACCTCTCTCC-3' (forward) and 5'-CAGCGCTGCCTGAAACTC-3' (reverse). For each case, appropriate C>T mutations were identified on the electropherograms. Univariate analysis using χ-test was carried out to identify potential confounders; a nested case-control study of demographic, clinical, histopathological, and genetic determinants was carried out using multiple logistic regression. Significant differences in TERT promoter mutation frequencies were noted in the subtypes (mixed vs. pure; 15/28, 54% vs. 11/48, 23%, respectively, P=0.0066). After adjusting for potential confounding, multivariate analyses indicated a three-fold increase in the odds of the TERT mutation for those with the mixed subtype compared with the pure subtype (P=0.04, adjusted odds ratio =3.32). No other significant associations were noted (sex/junctional component/Breslow depth/ulceration/mitoses/host response/RETp, BRAF status, and neurofibromin protein expression). Our findings, the largest to date investigating TERT promoter mutations in DM, support the hypothesis that the subtypes have distinct genetic drivers and underscore the relevance of telomere integrity in the etiopathogenesis of the mixed variant. PMID:27244099

  19. Molecular Electronics

    OpenAIRE

    Heath, James R.

    2009-01-01

    Molecular electronics describes the field in which molecules are utilized as the active (switching, sensing, etc.) or passive (current rectifiers, surface passivants) elements in electronic devices. This review focuses on experimental aspects of molecular electronics that researchers have elucidated over the past decade or so and that relate to the fabrication of molecular electronic devices in which the molecular components are readily distinguished within the electronic properties of the de...

  20. Evolutionary history of HIV-1 subtype B and CRF01_AE transmission clusters among men who have sex with men (MSM in Kuala Lumpur, Malaysia.

    Directory of Open Access Journals (Sweden)

    Kim Tien Ng

    Full Text Available HIV-1 epidemics among men who have sex with men (MSM continue to expand in developed and developing countries. Although HIV infection in MSM is amongst the highest of the key affected populations in many countries in Southeast Asia, comprehensive molecular epidemiological study of HIV-1 among MSM remains inadequate in the region including in Malaysia. Here, we reported the phylodynamic profiles of HIV-1 genotypes circulating among MSM population in Kuala Lumpur, Malaysia. A total of n = 459 newly-diagnosed treatment-naïve consenting subjects were recruited between March 2006 and August 2012, of whom 87 (18.9% were self-reported MSM. Transmitted drug resistance mutations were absent in these isolates. Cumulatively, phylogenetic reconstructions of the pro-rt gene (HXB2∶2253-3275 showed that HIV-1 subtype B and CRF01_AE were predominant and contributed to approximately 80% of the total HIV-1 infection among MSM. In addition to numerous unique transmission lineages within these genotypes, twelve monophyletic transmission clusters of different sizes (2-7 MSM sequences, supported by posterior probability value of 1 were identified in Malaysia. Bayesian coalescent analysis estimated that the divergence times for these clusters were mainly dated between 1995 and 2005 with four major transmission clusters radiating at least 12 years ago suggesting that active spread of multiple sub-epidemic clusters occurred during this period. The changes in effective population size of subtype B showed an exponential growth within 5 years between 1988 and 1993, while CRF01_AE lineage exhibited similar expansion between 1993 and 2003. Our study provides the first insight of the phylodynamic profile of HIV-1 subtype B and CRF01_AE circulating among MSM population in Kuala Lumpur, Malaysia, unravelling the importance of understanding transmission behaviours as well as evolutionary history of HIV-1 in assessing the risk of outbreak or epidemic expansion.